DASH Diet vs. Intermittent Fasting for Blood Pressure Control: A Scientific Review of Efficacy, Mechanisms, and Clinical Applications

Abstract

This article provides a comprehensive analysis of two prominent dietary strategies—the Dietary Approaches to Stop Hypertension (DASH) diet and Intermittent Fasting (IF)—for the management of hypertension. Tailored for researchers, scientists, and drug development professionals, it synthesizes foundational evidence, delineates molecular and physiological mechanisms, and examines clinical efficacy from recent randomized controlled trials and meta-analyses. The scope includes direct comparisons of blood pressure reduction, effects on comorbid conditions like obesity and MAFLD, and exploration of synergistic potential. It further addresses limitations, safety concerns, and outlines future directions for integrating these dietary interventions into precision medicine and cardiovascular drug development pipelines.

Understanding the Core Principles and Physiological Mechanisms

Hypertension, a primary contributor to cardiovascular disease and overall mortality, represents a significant global public health concern, with nearly half of all adults in the U.S. affected [1]. The Dietary Approaches to Stop Hypertension (DASH) diet constitutes a nonpharmacological dietary strategy primarily designed to mitigate hypertension and prevent its potential complications [2]. Developed with funding from the National Institutes of Health (NIH) in the 1990s, the DASH diet emerged from rigorous clinical trials that demonstrated specific dietary interventions could significantly decrease systolic blood pressure by 6 to 11 mm Hg without other lifestyle modifications [3]. This evidence-based eating plan has since been recognized as the "Best Heart-Healthy Diet" and "Best Diet for High Blood Pressure" by U.S. News & World Report in 2025 [4].

The DASH diet emphasizes consumption of vegetables, fruits, whole grains, lean proteins, and low-fat dairy products while reducing sodium, sugary beverages, and processed foods [2]. This dietary approach aligns with the American Heart Association's Life's Essential 8 metrics for heart health and serves as a first-line intervention for blood pressure management [1]. Beyond its profound impact on hypertension reduction, substantial evidence demonstrates the DASH diet's efficacy in addressing an array of conditions including heart failure, lipid homeostasis, dyslipidemia, and uric acid dysregulation [2]. As chronic diseases related to diet and obesity continue to be significant causes of mortality, the DASH diet represents an indispensable tool in the hypertension management toolkit, warranting its exploration and integration into various medical contexts [3].

Composition and Nutrient Targets of the DASH Diet

Core Food Group Composition

The DASH diet is a flexible and balanced eating plan that helps create a heart-healthy eating style for life [4]. It is designed to be rich in potassium, calcium, magnesium, fiber, and protein while being low in saturated and trans fats and lower in sodium [4] [5]. The diet focuses on the consumption of minimally processed and fresh foods, with specific recommendations for daily and weekly servings across various food groups [3].

Table 1: DASH Diet Daily and Weekly Servings for a 2,000-Calorie Diet

Food Group	Servings	Examples of Serving Sizes
Grains	6-8 per day	1 slice bread, ½ cup cooked cereal/rice/pasta, 1 oz dry cereal
Vegetables	4-5 per day	1 cup raw leafy greens, ½ cup cut-up raw or cooked vegetables, ½ cup vegetable juice
Fruits	4-5 per day	1 medium fruit, ½ cup fresh/frozen/canned fruit, ½ cup fruit juice
Low-fat or Fat-free Dairy	2-3 per day	1 cup milk or yogurt, 1½ ounces cheese
Lean Meats, Poultry, Fish	6 or fewer (1-ounce) servings per day	1 ounce cooked meat/poultry/fish, 1 egg
Fats and Oils	2-3 per day	1 tsp soft margarine, 1 tsp vegetable oil, 1 Tbsp mayonnaise, 2 Tbsp salad dressing
Nuts, Seeds, Dry Beans, Peas	4-5 per week	⅓ cup nuts, 2 Tbsp peanut butter, 2 Tbsp seeds, ½ cup cooked legumes
Sweets and Added Sugars	5 or fewer per week	1 Tbsp sugar/jelly/jam, ½ cup sorbet, 1 cup lemonade
Sodium	2,300 mg daily (1,500 mg ideal)

The number of servings appropriate for an individual depends on daily calorie needs, which varies based on age, sex, activity level, and health goals [4] [5]. The DASH diet provides specific nutritional recommendations while allowing flexibility in food choices, making it adaptable to personal and cultural preferences.

Micronutrient Emphasis and Sodium Restriction

A central tenet of the DASH diet involves enhancing the intake of nutrient-dense foods recognized for their influence on reducing blood pressure [2]. These foods are typically high in minerals such as potassium, calcium, and magnesium, as well as protein and dietary fiber [2]. The DASH diet strategically emphasizes these micronutrients because they play crucial roles in vascular function and blood pressure regulation. Potassium, calcium, and magnesium contribute to endothelial smooth muscle relaxation and prevent endothelial dysfunction, which is beneficial for maintaining healthy blood pressure levels [3].

Regarding sodium intake, the standard DASH diet limits salt to 2,300 milligrams (mg) per day, while a lower sodium version restricts sodium to 1,500 mg daily [5]. Research has demonstrated that reducing sodium to 1,500 mg daily lowers blood pressure even further than the 2,300 mg target [4]. The DASH-Sodium trial specifically investigated this relationship, finding that blood pressure decreased with each reduction of sodium, and that combining the DASH diet with sodium reduction provided greater benefits than either approach alone [6].

Historical Context and Major Clinical Trials

Foundational Research and Evolution

The DASH diet originated from a series of NIH-funded research projects initiated in 1992 to investigate whether specific dietary interventions could effectively treat hypertension [3]. This research was particularly significant given the rising prevalence of chronic diseases related to diet and obesity, which had become significant causes of death across all ethnicities in the United States [3]. The foundational DASH trial, which included 459 adults with and without confirmed hypertension, compared three diets: a typical American diet, a typical American diet with extra fruits and vegetables, and the DASH diet [6].

After eight weeks, participants who consumed more fruits and vegetables and those on the DASH diet had lower blood pressure than those following a typical American diet alone, with the DASH diet group showing the most significant improvements [6]. This landmark study demonstrated that dietary intervention alone could substantially impact blood pressure control. Follow-up reports from the DASH trial further showed that the diet not only improved blood pressure but also lowered LDL cholesterol levels, addressing two major risk factors for cardiovascular disease simultaneously [6].

Table 2: Key Clinical Trials Establishing DASH Efficacy

Trial Name	Participants	Intervention	Key Findings
Original DASH Trial [6]	459 adults with & without hypertension	Compared 3 diets: typical American, typical American + fruits/vegetables, DASH diet	DASH diet most effective; reduced SBP by 6-11 mmHg
DASH-Sodium Trial [6] [2]	412 adults	DASH diet at 3 sodium levels: 3,300 mg, 2,300 mg, 1,500 mg	Lower sodium → lower BP; greatest reduction with DASH + low sodium (1,500 mg)
PREMIER Trial [6] [2]	810 participants with prehypertension & stage 1 hypertension	Compared advice-only, established treatment, established + DASH	Greatest BP reduction (11.1 mmHg SBP) with established + DASH diet
OmniHeart Trial [6] [2]	164 adults with above-normal BP	Compared DASH alone, DASH + protein, DASH + unsaturated fats	Protein/unsaturated fat substitutions further improved BP & lipids
Meta-analysis by Saneei et al. [2]	2,561 participants across 17 RCTs	Systematic review of DASH diet impacts	Significant reduction in SBP (6.74 mmHg) & DBP (3.54 mmHg)

Figure 1: Evolution of DASH Diet Clinical Research

Key Study Methodologies and Protocols

The major clinical trials establishing the efficacy of the DASH diet shared several methodological commonalities while addressing distinct research questions. The original DASH trial provided all foods and beverages to participants for eight weeks, controlling for potential confounding factors by ensuring consistent dietary intake across groups [6]. None of the diets were vegetarian or used specialty foods, enhancing the practical applicability of the results [6].

The DASH-Sodium trial provided all foods and beverages to participants for one month while manipulating sodium intake across three levels (3,300 mg, 2,300 mg, and 1,500 mg daily) to isolate the effects of sodium reduction within the context of the DASH diet [6]. This study design allowed researchers to determine that reducing sodium intake and following the DASH diet produced greater blood pressure reduction than either approach alone [6].

The PREMIER trial employed a different methodology, as it did not provide food to participants, instead focusing on behavioral counseling and education in combination with the DASH diet [6]. This design reflected real-world conditions where individuals must implement dietary changes independently. The trial included three groups: an advice-only group, an established treatment group (counseling on behavior changes), and an established treatment group that also incorporated the DASH diet [6] [2].

The OmniHeart trial compared variations of the DASH diet, examining whether substituting 10% of carbohydrates with either protein or unsaturated fats would provide additional benefits [6] [2]. This study provided all foods and beverages to participants, who followed each diet for six weeks with washout periods between conditions [6]. Throughout the study, participants' body weight was maintained to isolate the effects of dietary composition independent of weight change [6].

DASH Diet Versus Intermittent Fasting for Blood Pressure Control

Comparative Mechanisms and Physiological Effects

The DASH diet and intermittent fasting represent two distinct approaches to dietary management of hypertension, with different proposed mechanisms of action. The DASH diet primarily functions through optimized nutrient composition, emphasizing minerals (potassium, calcium, magnesium), fiber, and protein while limiting sodium, saturated fats, and added sugars [4] [5] [2]. This nutritional profile supports vascular health, endothelial function, and fluid balance, directly addressing physiological pathways regulating blood pressure [3].

Intermittent fasting, particularly time-restricted eating (TRE), operates primarily through temporal patterning of food intake, creating daily fasting periods that may improve metabolic flexibility, enhance autonomic regulation, and reduce inflammation [7] [8]. Recent research suggests that TRE may influence blood pressure through additional mechanisms, including reduced oxidative stress, improved circadian rhythm alignment, and modulation of the gut microbiome [7].

While both approaches can successfully lower blood pressure, their complementary mechanisms suggest potential synergy when combined. A 2024 randomized controlled trial specifically investigated this combination, finding that DASH combined with TRE (8-hour eating window) resulted in significantly greater blood pressure reduction than DASH alone [7]. The DASH+TRE group demonstrated a reduction of 8.459±4.260 mm Hg in systolic blood pressure and 9.459±4.375 mm Hg in diastolic blood pressure, compared to 5.595±4.072 mm Hg and 5.351±5.643 mm Hg respectively in the DASH-only group [7].

Direct Comparative Evidence

Recent randomized controlled trials have provided direct comparisons between the DASH diet and intermittent fasting approaches, as well as investigations of their combined effects. A 2021 study compared intermittent energy restriction (IER) with continuous energy restriction (CER) in 205 overweight or obese patients with hypertension over six months [9]. The IER group followed a 5:2 eating pattern (500-600 kcal for 2 days weekly), while the CER group maintained a consistent daily caloric restriction [9].

The results demonstrated that IER and CER were equally effective for weight loss and blood pressure control, with mean weight change of -7.0±0.6 kg with IER versus -6.8±0.6 kg with CER, and systolic blood pressure reduction of -7±0.7 mmHg with IER versus -7±0.6 mmHg with CER [9]. This suggests that intermittent fasting patterns can achieve comparable results to continuous caloric restriction, potentially offering flexibility in dietary approach based on individual preferences and adherence capabilities.

A 2024 randomized controlled trial specifically examined DASH alone versus DASH combined with time-restricted eating (TRE) in 74 patients with stage 1 primary hypertension [7]. The DASH+TRE group was instructed to consume their food within an 8-hour window (9:00 a.m. to 5:00 p.m.), while both groups followed the DASH dietary pattern without energy restrictions [7]. Beyond the significantly greater blood pressure reductions observed in the combined intervention group, the study also found that DASH+TRE improved blood pressure diurnal rhythm, decreased extracellular water, and increased urinary Na+ excretion [7]. The correlation between blood pressure reduction and these physiological changes suggests potential mechanisms through which TRE may enhance the effects of the DASH diet.

Table 3: Blood Pressure Outcomes: DASH vs. Intermittent Fasting Approaches

Intervention	Study Duration	Systolic BP Reduction (mmHg)	Diastolic BP Reduction (mmHg)	Additional Benefits
DASH Diet Alone [7] [2]	6-8 weeks	5.6 - 11.8	5.4 - 9.3	Improved lipid profiles, reduced LDL cholesterol
DASH + TRE (8-hour window) [7]	6 weeks	8.5	9.5	Improved BP diurnal rhythm, reduced extracellular water
Intermittent Energy Restriction (5:2 diet) [9]	6 months	7.0	6.0	Comparable weight loss to continuous restriction
Continuous Energy Restriction [9]	6 months	7.0	5.0	Improved body composition, HbA1c, blood lipids
DASH + Low Sodium (1,500 mg) [6]	1 month	7.1 (non-hypertensive) 11.5 (hypertensive)	Not specified	Greatest overall blood pressure reduction

Research Reagents and Methodological Tools

Essential Research Materials and Assessments

Conducting rigorous research on dietary interventions like the DASH diet requires specific methodological tools and assessment protocols. The following table details key research reagents and essential materials used in featured DASH diet clinical trials, along with their functions in experimental protocols.

Table 4: Essential Research Reagents and Methodological Tools for DASH Diet Research

Research Tool/Assessment	Function in DASH Research	Example Application
24-Hour Dietary Recalls	Quantifies dietary intake and adherence to prescribed food group targets	Tracked participant compliance in PREMIER trial [6]
Food Diaries/Checklists	Self-monitoring tool for dietary adherence	Used in DASH+TRE trial to track eating window compliance [7]
Digital Kitchen Scales	Ensures accurate food portion measurement	Provided to participants in IER vs. CER trial [9]
Ambulatory Blood Pressure Monitoring	Measures BP across 24-hour period, captures diurnal rhythm	Assessed BP rhythm improvements in DASH+TRE trial [7]
Bioelectrical Impedance Analysis	Assesses body composition changes (extracellular water, etc.)	Measured reduced extracellular water in DASH+TRE group [7]
Urinary Sodium Excretion Analysis	Objective measure of sodium intake adherence	Correlated with BP reduction in DASH+Sodium trial [7] [6]
Blood Lipid Panels	Quantifies cardiovascular risk factors beyond BP	LDL reduction documented in DASH trial follow-ups [6]
Controlled Attenuation Parameter (CAP)	Non-invasive assessment of hepatic steatosis	Measured liver fat reduction in DASH+TRF MAFLD trial [8]
Food Provision System	Standardizes dietary intake across experimental groups	Used in original DASH, DASH-Sodium, OmniHeart trials [6]
Randomized Controlled Trial Methodology	Gold-standard for establishing causal efficacy	Foundation of all major DASH diet trials [7] [6] [2]

Implementation Protocols and Adherence Monitoring

Successful implementation of DASH diet research requires careful attention to intervention protocols and adherence monitoring. The major clinical trials have established several best practices for ensuring methodological rigor:

Dietary Provision and Standardization: The original DASH trial, DASH-Sodium trial, and OmniHeart trial all provided participants with all foods and beverages to ensure strict adherence to the prescribed dietary patterns [6]. This approach eliminates self-reporting bias and ensures all participants receive identical interventions based on their group assignment.

Behavioral Counseling and Education: The PREMIER trial demonstrated the effectiveness of combining the DASH diet with behavioral counseling in real-world settings where food provision isn't feasible [6]. This approach included regular counseling sessions, goal setting, and self-monitoring techniques to support adherence.

Adherence Assessment Methods: Research has utilized multiple methods to assess adherence to the DASH diet, including 24-hour dietary recalls, food diaries, checklist monitoring, and biomarker analysis (such as urinary sodium excretion) [7] [6]. More recent trials have incorporated technology-based tracking through smartphone apps and digital platforms [7] [6].

Consideration of Social Drivers of Health: The most recent hypertension management guidelines emphasize incorporating social determinants of health into cardiovascular risk assessment, using tools like zip code analysis as proxies for these drivers [1]. This reflects growing recognition that dietary interventions must consider contextual factors that influence implementation and adherence.

Figure 2: DASH Diet Research Methodology Workflow

The substantial body of evidence supporting the DASH diet for hypertension management continues to evolve, with recent research exploring combinations with time-restricted eating and applications to other metabolic conditions [7] [8]. While the diet's efficacy for blood pressure reduction is well-established, several research gaps remain worthy of investigation.

Future research should focus on long-term adherence strategies, as maintaining dietary changes presents significant challenges outside clinical trial settings [2]. The integration of technology, including mobile health applications and digital tracking platforms, shows promise for supporting sustained implementation [6] [2]. Additionally, further investigation is needed to understand the molecular and physiological mechanisms through which the DASH diet exerts its effects, particularly at the intersection with circadian biology when combined with time-restricted feeding protocols [7].

Personalized nutrition approaches represent another promising direction, identifying individual factors that predict optimal response to the DASH diet versus alternative dietary patterns like intermittent fasting [1]. The recent inclusion of social determinants of health in cardiovascular risk assessment underscores the importance of contextual factors in dietary implementation [1]. As precision medicine advances, future research may enable more targeted recommendations based on genetic, metabolic, and lifestyle factors that influence individual responses to dietary interventions for hypertension management.

Intermittent fasting (IF) has emerged as a significant dietary intervention strategy in metabolic research, particularly in the management of obesity, hypertension, and cardiometabolic diseases. Unlike continuous energy restriction (CER), IF alternates periods of eating with periods of either complete fasting or significantly reduced caloric intake [10]. This paradigm shift from constant caloric restriction to timed feeding patterns has demonstrated potential for improving various health markers independent of weight loss [11]. The three most prominent IF regimens—time-restricted eating (TRE), alternate-day fasting (ADF), and the 5:2 diet—have distinct structural approaches but share the common principle of incorporating fasting periods into weekly eating patterns. Within the context of blood pressure control research, these fasting modalities offer alternative approaches to traditional dietary interventions like the Dietary Approaches to Stop Hypertension (DASH) diet, potentially working through different physiological mechanisms to achieve similar cardiovascular benefits [7] [9].

The growing research interest in IF is evidenced by the dramatic increase in clinical trials, with PubMed showing 42 TRE clinical trials published between 2020-2022 compared to just 12 from 2015-2019 [11]. As hypertension remains a primary contributor to cardiovascular disease and global mortality, exploring these alternative dietary strategies is of paramount importance for developing effective, personalized treatment approaches [7]. This guide provides a comprehensive comparison of TRE, ADF, and the 5:2 diet, with specific attention to their methodological frameworks, efficacy evidence, and relevance to blood pressure management research.

Defining the Intermittent Fasting Modalities

Time-Restricted Eating (TRE)

Time-restricted eating (TRE) involves confining all daily food intake to a consistent window of 4-10 hours, followed by 14-20 hours of fasting each day [11] [12]. Unlike other IF approaches, TRE does not require individuals to monitor food intake or count calories during the eating window, instead focusing primarily on the timing of consumption [12]. This approach was developed specifically to support the circadian system, with the consistency of the daily eating window representing a key differentiating factor from other IF regimens [11]. Research indicates that eating windows shorter than 6 hours may increase minor adverse events (e.g., headaches, moodiness, nausea) without additional benefits, while windows exceeding 12 hours typically do not yield significant health benefits [11]. The most common TRE intervention windows range from 6 to 10 hours daily [11].

Alternate-Day Fasting (ADF)

Alternate-day fasting (ADF) follows a pattern of alternating between "fast days" with severe calorie restriction and "feed days" with ad libitum (unrestricted) eating [13] [10]. Two main variations exist: zero-calorie ADF (complete fasting on fast days) and modified alternate-day fasting (MADF), which allows approximately 500 calories (20-25% of energy needs) on fasting days [13] [10]. The modified approach has become more prevalent in research and practice due to better long-term sustainability while maintaining similar efficacy [13]. ADF cycles typically consist of 24-hour fast periods alternating with 24-hour feed periods, resulting in approximately 36-hour fasting periods when implemented consecutively [14]. Studies indicate that the health and weight loss benefits remain similar regardless of whether the fasting-day calories are consumed in a single meal or spread throughout the day [13].

The 5:2 Diet

The 5:2 diet follows a weekly pattern where individuals eat normally for five consecutive or non-consecutive days and restrict calories on two non-fasting days [10] [15]. On the two fasting days, calorie intake is typically limited to 500 calories for women and 600 calories for men [16] [15]. Unlike TRE, the 5:2 diet focuses specifically on calorie restriction during fasting days rather than the timing of food consumption [16]. This approach is classified as intermittent energy restriction (IER) rather than true fasting, as it involves significant calorie reduction rather than complete abstinence from food [16]. The two fasting days are typically spaced throughout the week (e.g., Monday and Thursday) rather than occurring consecutively to prevent excessive hunger and improve adherence [15].

Table 1: Structural Comparison of Intermittent Fasting Modalities

Characteristic	Time-Restricted Eating (TRE)	Alternate-Day Fasting (ADF)	5:2 Diet
Primary Focus	Consistent daily eating window	Alternating feast/fast days	Weekly calorie restriction
Fasting Pattern	Daily (14-20 hour fasts)	Every other day (24-36 hour fasts)	2 days/week (24-hour fasts)
Calorie Guidance	None during eating window	0-500 calories on fast days	500-600 calories on fast days
Eating Windows	4-10 hours daily	Ad libitum on feed days	Normal eating 5 days/week
Key Mechanism	Circadian rhythm alignment	Overall weekly calorie reduction	Weekly calorie reduction

Comparative Efficacy Data

Weight Loss and Body Composition Outcomes

Network meta-analyses of randomized controlled trials (RCTs) provide robust comparisons of the weight loss efficacy of different IF regimens. A 2022 meta-analysis of 24 RCTs (n=1,768) ranked ADF as the most effective for weight loss, followed by CER and TRE [10]. When comparing IF approaches collectively to CER, the differences in weight loss were not statistically significant (mean difference 0.26 kg, 95% CI: -0.31 to 0.84; p=0.37) [10]. Another systematic review and meta-analysis published in 2023 found that changes in body weight were comparable when the three IER diets were combined and compared with CER (WMD: -0.42 kg; 95% CI: -0.96 to 0.13; P=0.132), with similar findings for fat mass (WMD: -0.31 kg; 95% CI: -0.98 to 0.36; P=0.362) [17].

However, specific differences emerged when examining individual IF modalities. TRE demonstrated superior reductions in body weight, fat mass, and fat-free mass compared to CER, while the 5:2 diet showed slightly less reduction in BMI compared to CER [17]. All IF regimens combined were found to reduce fat-free mass (WMD: -0.20 kg; 95% CI: -0.39 to -0.01; P=0.044) and waist circumference (WMD: -0.91 cm; 95% CI: -1.76 to -0.06; P=0.036) more than CER [17]. Studies specifically examining ADF have shown weight reductions of 3-8% of body weight within 2-12 weeks in adults with overweight and obesity [13].

Table 2: Weight Loss and Body Composition Outcomes from Meta-Analyses

Outcome Measure	TRE vs. CER	ADF vs. CER	5:2 Diet vs. CER	All IF Combined vs. CER
Body Weight	Greater reduction with TRE	Greatest reduction [10]	Comparable	WMD: -0.42 kg (-0.96 to 0.13); P=0.132 [17]
Fat Mass	Greater reduction with TRE	Comparable	Comparable	WMD: -0.31 kg (-0.98 to 0.36); P=0.362 [17]
Fat-Free Mass	Greater reduction with TRE	Comparable	Comparable	WMD: -0.20 kg (-0.39 to -0.01); P=0.044 [17]
Waist Circumference	Not specified	Not specified	Not specified	WMD: -0.91 cm (-1.76 to -0.06); P=0.036 [17]
BMI	Not specified	Not specified	Less reduction with 5:2	Not significant [17]

Cardiometabolic Risk Markers and Blood Pressure

Research examining the effects of IF regimens on cardiometabolic risk markers shows particular relevance for blood pressure management. A 2024 randomized controlled trial specifically investigated TRE combined with the DASH diet in stage 1 primary hypertension patients [7]. The study found that the DASH+TRE group achieved significantly greater reductions in systolic blood pressure (8.5±4.3 mmHg vs. 5.6±4.1 mmHg) and diastolic blood pressure (9.5±4.4 mmHg vs. 5.4±5.6 mmHg) compared to DASH alone [7]. Furthermore, the DASH+TRE intervention improved blood pressure diurnal rhythm and was associated with decreased extracellular water and increased urinary Na+ excretion [7].

A 2021 RCT comparing the 5:2 diet to CER in overweight and obese patients with hypertension found both approaches equally effective for blood pressure control, with mean systolic blood pressure reductions of 7 mmHg in both groups over 6 months [9]. This study reported no significant differences between groups for improvements in body composition, HbA1c, or blood lipid levels [9].

Other cardiometabolic benefits observed across IF regimens include improved glucose regulation, decreased blood pressure, improved cholesterol levels, reduced inflammation, and improved insulin sensitivity [11] [13]. ADF has demonstrated particular efficacy for improving HOMA-IR compared to CER [17], and has been associated with reduced LDL cholesterol, triglycerides, and blood pressure, along with increased LDL particle size in some studies [13] [14].

Table 3: Blood Pressure and Cardiometabolic Outcomes

Parameter	TRE Findings	ADF Findings	5:2 Diet Findings
Systolic BP	-8.5 mmHg (with DASH) [7]	Reductions observed [13]	-7.0 mmHg (similar to CER) [9]
Diastolic BP	-9.5 mmHg (with DASH) [7]	Reductions observed [13]	-6.0 mmHg (similar to CER) [9]
Glucose/Insulin	Improved glucose regulation [11]	Improved HOMA-IR [17]; Decreased fasting insulin [13]	Improved HbA1c [9]
Lipids	Improved atherogenic lipids [11]	Reduced LDL, triglycerides; Increased HDL [13] [14]	Improved blood lipids [9]
Other Benefits	Improved BP diurnal rhythm [7]	Increased LDL particle size [13]	Comparable to CER for cardiometabolic markers [9]

Experimental Protocols and Methodologies

Common Research Designs and Protocols

Standardized TRE Protocols: Recent clinical trials typically implement TRE with eating windows ranging from 6-10 hours daily, with 8-hour windows being particularly common in hypertension research [7]. In the 2024 hypertension RCT, participants were instructed to consume their food within a consistent 8-hour window (9:00 a.m. to 5:00 p.m.) and fast for the remaining 16 hours daily [7]. Only water and energy-free drinks were permitted outside the eating window. Researchers typically use dietary logs, mobile application tracking, and periodic check-ins to monitor adherence.

ADF Methodological Approaches: ADF studies generally follow either zero-calorie or modified approaches, with the modified version (20-25% of energy needs on fasting days, approximately 500 calories) being more common in longer trials [13] [10]. In one RCT protocol, researchers used continuous glucose monitoring to verify adherence to the fasting intervention [14]. Typical outcome measurements include body composition (via DEXA), endothelial function, oral glucose tolerance tests, 24-hour blood pressure monitoring, and various biochemical analyses [14].

5:2 Diet Implementation: In RCTs involving the 5:2 diet, participants are typically instructed to consume 500 calories (women) or 600 calories (men) on two non-consecutive fasting days each week [15] [9]. On the other five days, participants are advised to follow their habitual diet or a specific dietary pattern like the Mediterranean diet [9]. Research protocols often include providing digital kitchen scales for accurate food measurement, dietary education sessions, food diaries, and regular follow-up visits with dietitians [9].

Adherence and Compliance Monitoring

Compliance assessment varies across studies but typically includes multiple verification methods. For TRE, studies often use time-stamped photographic food records, smartphone apps with eating window tracking, and 24-hour dietary recalls [11] [7]. ADF trials frequently incorporate self-reported fasting logs, participant interviews, and in some cases, continuous glucose monitoring to verify fasting periods [14]. 5:2 diet research commonly utilizes food diaries, weighing of food portions, and regular check-ins with dietitians to review compliance [9].

Meta-analyses indicate that compliance rates generally exceed 80% in trials shorter than 3 months across all IF modalities [10]. Longer-term adherence appears more variable, with some studies reporting maintained compliance over 6-12 month periods, particularly with modified ADF and the 5:2 diet [10] [9].

Diagram 1: Proposed Physiological Pathways for Blood Pressure Reduction by Intermittent Fasting Modalities. Each IF approach may operate through distinct but potentially overlapping mechanisms to reduce blood pressure.

Research Reagent Solutions and Methodological Tools

Table 4: Essential Research Tools for Intermittent Fasting Clinical Trials

Tool Category	Specific Examples	Research Application	Considerations
Adherence Monitoring	Time-stamped food photography, Mobile app tracking (WeChat platform), Continuous glucose monitors, Food diaries	Verify compliance with eating windows (TRE) or fasting days (ADF/5:2)	CGMs can detect carbohydrate intake during fasting periods; Digital platforms enable real-time monitoring [7] [14]
Body Composition Analysis	DEXA (Dual-energy X-ray absorptiometry), Bioelectrical impedance analysis, Waist circumference measurements	Quantify fat mass, fat-free mass, extracellular water changes	DEXA provides precise body composition data; Extracellular water reduction correlated with BP improvements in TRE [7] [14]
Blood Pressure Monitoring	24-hour ambulatory BP monitors, Automated office BP devices, Home BP monitoring systems	Assess BP changes and diurnal rhythm patterns	24-hour monitoring captures diurnal rhythm improvements observed with TRE+DASH [7] [14]
Metabolic Assessment	Oral glucose tolerance tests (OGTT), HOMA-IR calculations, Lipid panels, HbA1c measurements	Quantify cardiometabolic risk factor changes	Standardized protocols essential for cross-study comparisons; Fasting samples required for accurate measures [14] [9]
Biomarker Analysis	Inflammation markers (CRP, cytokines), Urinary sodium excretion, Appetite hormones (leptin, ghrelin), Oxidative stress markers	Investigate potential mechanisms of action	Urinary Na+ excretion important for hypertension research; Appetite hormones may explain adherence differences [7] [14]

Diagram 2: Standardized Research Workflow for Intermittent Fasting Clinical Trials. RCTs typically follow this structured approach to compare IF modalities, with rigorous adherence monitoring and standardized outcome assessments.

The comparative evidence indicates that TRE, ADF, and the 5:2 diet represent distinct approaches to intermittent fasting with varying mechanistic emphasis and practical applications. TRE focuses primarily on circadian alignment through consistent daily eating windows, ADF creates frequent alternating feast-fast cycles, and the 5:2 diet implements moderate weekly energy restriction through two reduced-calorie days. All three modalities demonstrate efficacy for weight management and blood pressure reduction, with subtle but potentially important differences in their effect profiles.

For blood pressure control specifically, TRE combined with the DASH diet has shown promising synergistic effects, potentially working through mechanisms involving urinary sodium excretion and extracellular water balance [7]. Both ADF and the 5:2 diet produce blood pressure reductions comparable to continuous energy restriction, suggesting they may serve as viable alternatives for patients who struggle with daily restriction [9]. The choice between these modalities in clinical practice or research contexts may ultimately depend on individual preferences, adherence patterns, and specific metabolic characteristics.

Future research should prioritize longer-term randomized controlled trials (6-12 months) with careful attention to energy intake differences between intervention groups, standardized outcome measurements across studies, and exploration of potential biomarkers that might predict individual responses to different IF approaches [11] [17]. Additionally, mechanistic studies investigating the circadian, autonomic, and inflammatory pathways modulated by these interventions will enhance our understanding of their cardiovascular effects and potential applications in hypertension management.

The Dietary Approaches to Stop Hypertension (DASH) diet and various forms of intermittent fasting (IF) represent two distinct dietary strategies for managing blood pressure and improving cardiometabolic health. While both approaches demonstrate efficacy, their underlying mechanisms, physiological impacts, and risk profiles differ substantially. The DASH diet functions primarily through nutrient-mediated pathways to improve sodium homeostasis, enhance potassium availability, and directly improve vascular function [18]. In contrast, IF, including time-restricted eating (TRE) and alternate-day fasting, operates largely through temporal eating patterns and caloric restriction, with emerging research raising questions about its long-term cardiovascular safety [19].

This review synthesizes current evidence comparing these approaches, with particular focus on their mechanistic pathways, efficacy supported by experimental data, and implications for research and therapeutic development. The DASH diet demonstrates multi-system protection through well-characterized nutrient interactions, while IF's effects appear more dependent on caloric restriction with potential concerns regarding lean mass preservation and dietary quality that warrant further investigation.

Mechanistic Pathways: Comparative Analysis of DASH and Intermittent Fasting

The DASH diet and intermittent fasting operate through distinct but partially overlapping biological pathways to influence cardiometabolic health. The following diagram illustrates the primary mechanisms through which each approach affects blood pressure regulation and vascular function, highlighting key points of divergence.

Figure 1. Mechanistic Pathways of DASH Diet and Intermittent Fasting for Blood Pressure Control

The DASH diet exerts its effects through multiple synchronized pathways: (1) sodium restriction directly reduces fluid volume and peripheral resistance; (2) elevated potassium intake promotes vasodilation by enhancing endothelial function; (3) high fiber content supports gut microbiota that produce short-chain fatty acids (SCFAs) with anti-inflammatory effects; and (4) abundant antioxidants reduce oxidative stress, a key driver of endothelial dysfunction [20] [21] [18]. These nutrient-mediated mechanisms directly target physiological regulators of blood pressure.

Intermittent fasting operates through different pathways, primarily driven by (1) caloric restriction that promotes weight loss and reduces metabolic demand; (2) time-restricted eating windows that may align with circadian rhythms; and (3) metabolic switching to ketone metabolism during fasting periods that reduces inflammation and improves insulin sensitivity [22] [19]. However, IF may also trigger potential adverse effects including lean mass loss, which is associated with increased cardiovascular disease risk, and reward-based eating behaviors that can compromise diet quality [19].

Experimental Evidence and Clinical Outcomes

Comparative Efficacy for Blood Pressure Control

Table 1: Blood Pressure Outcomes in DASH vs. Intermittent Fasting Clinical Trials

Study Design	Population	Intervention	Duration	SBP Reduction (mmHg)	DBP Reduction (mmHg)	Key Findings
RCT [7]	Stage 1 hypertension (n=74)	DASH alone	6 weeks	5.6 ± 4.1	5.4 ± 5.6	Significant BP reduction with DASH
RCT [7]	Stage 1 hypertension (n=74)	DASH + TRE (8-hour window)	6 weeks	8.5 ± 4.3	9.5 ± 4.4	Enhanced BP reduction with combined approach
RCT [9]	Overweight/obese with hypertension (n=205)	5:2 IER (500-600 kcal 2 days/week)	6 months	7.0 ± 0.7	6.0 ± 0.5	Comparable to continuous energy restriction
RCT [9]	Overweight/obese with hypertension (n=205)	CER (1000-1200 kcal/day)	6 months	7.0 ± 0.6	5.0 ± 0.5	Similar efficacy to intermittent restriction
DASH-Sodium [23] [24]	Adults with elevated BP (n=412)	DASH + low sodium	30 days	11.5*	5.7*	Greatest reduction with combined approach

*Estimated from original DASH-Sodium trial data

The DASH diet demonstrates consistent blood pressure reduction across multiple populations. In stage 1 hypertensive patients, DASH alone reduced systolic blood pressure (SBP) by 5.6 mmHg and diastolic blood pressure (DBP) by 5.4 mmHg over 6 weeks [7]. When combined with time-restricted eating (8-hour window), the effects were significantly enhanced, with reductions of 8.5 mmHg SBP and 9.5 mmHg DBP [7]. The DASH-Sodium trial further demonstrated that combining the DASH diet with sodium restriction produces the most substantial benefits, with estimated reductions of 11.5 mmHg SBP and 5.7 mmHg DBP [23] [24].

Intermittent fasting regimens show more variable outcomes. The 5:2 intermittent energy restriction (IER) protocol produced reductions of 7.0 mmHg SBP and 6.0 mmHg DBP over 6 months in hypertensive patients, comparable to continuous energy restriction [9]. However, emerging evidence suggests that the benefits of IF may be primarily mediated by caloric restriction rather than fasting-specific mechanisms [19].

Effects on Cardiovascular Risk Biomarkers

Table 2: Biomarker Profiles in DASH vs. Intermittent Fasting Interventions

Biomarker	DASH Diet Effects	Intermittent Fasting Effects	Clinical Significance
10-year ASCVD Risk	-5.3% reduction [24]	Long-term data limited	DASH demonstrates proven CVD risk reduction
LDL Cholesterol	Favorable reduction [18]	Potential increase in some IF studies [19]	DASH shows more consistent lipid benefits
Urinary Sodium	Significant reduction [7]	Variable effects	Direct impact on volume-dependent hypertension
Endothelial Function	Improved FMD [21] [18]	Potential improvement [22]	Both may improve vascular function via different pathways
Inflammation	Reduced oxidative stress and NF-κB [18]	Reduced systemic inflammation [22]	Both approaches show anti-inflammatory effects
Lean Body Mass	Generally preserved	Potential significant loss (65% of weight loss) [19]	Important for long-term metabolic health

The DASH diet demonstrates comprehensive cardiovascular risk reduction, decreasing 10-year atherosclerotic cardiovascular disease (ASCVD) risk by 5.3% through its combined effects on blood pressure, lipids, and endothelial function [24]. The DASH-Sodium trial further showed that combining DASH with sodium reduction lowered ASCVD risk by 14.1% compared to a high-sodium control diet [23] [24]. These benefits are mediated through multiple pathways, including enhanced flow-mediated dilatation (FMD) when potassium is increased alongside sodium restriction [21], and reduced oxidative stress through antioxidant-rich foods [18].

Intermittent fasting shows mixed effects on cardiovascular biomarkers. While some studies report improved insulin sensitivity and reduced inflammation [22], others note potential adverse effects including increased LDL cholesterol in alternate-day fasting regimens [19]. A significant concern is the disproportionate loss of lean mass observed in some IF studies, accounting for up to 65% of total weight loss compared to 20-30% with standard hypocaloric diets [19]. This is clinically relevant since reduced muscle mass associates with increased cardiovascular disease risk and mortality [19].

Experimental Protocols and Methodologies

DASH Diet Intervention Protocol

The standard DASH diet intervention follows a highly structured nutritional composition focused on specific food groups and nutrient targets:

• Dietary Composition: The diet emphasizes fruits (4-5 servings/day), vegetables (4-5 servings/day), whole grains (6-8 servings/day), low-fat dairy (2-3 servings/day), lean proteins (fish, poultry), nuts, seeds, and legumes (4-5 servings/week) [18]. It restricts sodium, saturated fats, red meat, and added sugars.

• Sodium Restriction: The DASH-Sodium trial implemented three levels: high (targeting 3,450 mg/day), intermediate (2,300 mg/day), and low (1,150 mg/day) sodium intake [24]. All meals are provided to participants to ensure compliance.

• Macronutrient Distribution: Typically provides 53-58% carbohydrates, 15-18% protein, and 26-30% fat, with emphasis on potassium (≥4,700 mg/day), magnesium (500 mg/day), and calcium (1,240 mg/day) [25] [18].

• Implementation: In the DASH-Sodium trial, participants consumed each sodium level for 30 days in randomized order following a 2-week run-in period with high-sodium control diet [24]. Blood pressure measurements were averaged from five readings taken over the final nine days of each period.

Intermittent Fasting Protocols

Different IF protocols have been studied for blood pressure management:

• 5:2 Diet Protocol: Participants consume a very-low-calorie diet (500 kcal/day for women, 600 kcal/day for men) for two non-consecutive days per week, while eating habitually for the other five days [9]. Protein supplementation (minimum 0.8 g/kg body weight) is recommended on fasting days to preserve lean mass.

• Time-Restricted Eating (TRE): In the DASH+TRE trial, participants consumed all calories within an 8-hour window (9:00 a.m. to 5:00 p.m.) while following DASH diet principles [7]. Only water and energy-free beverages were permitted outside the eating window.

• Control for Confounding: Studies carefully control for weight loss to distinguish fasting-specific effects from those of caloric restriction. Medication adjustments (particularly antihypertensives and diabetes medications) are standardized to avoid confounding [9].

Vascular Function Assessment Methods

Key methodologies for evaluating vascular effects include:

• Flow-Mediated Dilatation (FMD): High-frequency ultrasound assessment of brachial artery diameter changes following reactive hyperemia, measured at 30, 60, 90, and 120 minutes postprandially to evaluate endothelial function [21].

• Pulse Wave Velocity (PWV): Carotid-femoral PWV measurement as the gold standard for arterial stiffness assessment, using applanation tonometry [21].

• 24-hour Urinary Sodium Excretion: Used to objectively monitor sodium intake compliance, with samples analyzed for sodium, potassium, and creatinine [25] [7].

• Ambulatory Blood Pressure Monitoring: 24-hour measurements to capture diurnal variations and nocturnal dipping patterns, particularly important in DASH+TRE studies [7].

The Scientist's Toolkit: Essential Research Reagents and Methodologies

Table 3: Key Research Reagents and Methodologies for Cardiometabolic Diet Studies

Tool/Reagent	Application	Specific Function	Example Use
Random-Zero Sphygmomanometer	BP measurement	Eliminates observer bias in BP readings	DASH-Sodium trial [24]
Brachial Artery Ultrasound	Vascular function	Quantifies flow-mediated dilatation	Potassium supplementation study [21]
Electrolyte Analyzer	Urinary biomarkers	Measures Na+, K+, creatinine in urine	DASH pediatric trial [25]
INTERSALT Equation	Sodium intake estimation	Calculates 24-hour Na excretion from spot urine	Pediatric DASH study [25]
Pulse Wave Velocity System	Arterial stiffness	Measures carotid-femoral PWV	Postprandial vascular function [21]
Standardized Meal Tests	Postprandial responses	Controls nutrient intake for acute studies	High-potassium meal challenge [21]
Food Diaries + Digital Scales	Dietary compliance	Self-monitoring with portion control	IER vs. CER trial [9]
WeChat Scientific Platform	Intervention tracking	Digital monitoring of eating windows	DASH+TRE trial [7]

The DASH diet demonstrates robust, multi-mechanistic benefits for blood pressure control through well-characterized pathways involving sodium homeostasis, potassium-mediated vasodilation, and endothelial protection. Its efficacy is well-established across diverse populations, with recent evidence supporting synergistic effects when combined with time-restricted eating [7]. The diet's nutrient-dense profile provides cardiovascular protection beyond blood pressure reduction, significantly lowering 10-year ASCVD risk [24].

Intermittent fasting shows comparable short-term blood pressure reduction, but emerging evidence suggests potential concerns regarding long-term cardiovascular safety, lean mass preservation, and dietary quality [19]. The mechanisms underlying IF benefits appear largely dependent on caloric restriction rather than fasting-specific effects.

For research and drug development, the DASH diet offers a well-defined nutritional blueprint for targeting multiple overlapping pathways in hypertension pathogenesis. Future research should focus on nutrigenomic interactions, personalized sodium/potassium thresholds, and molecular mechanisms linking specific DASH diet components to vascular inflammation and oxidative stress pathways. The integration of timed eating patterns with nutrient-specific interventions represents a promising frontier for maximizing cardiovascular benefits while minimizing potential risks associated with restrictive dietary patterns.

Comparative Efficacy for Blood Pressure Control

Clinical evidence demonstrates that both Dietary Approaches to Stop Hypertension (DASH) and Intermittent Fasting (IF) effectively reduce blood pressure, though their mechanisms and efficacy profiles differ. The following table summarizes key comparative findings from randomized controlled trials (RCTs) and meta-analyses.

Table 1: Blood Pressure Reduction Across Dietary Interventions

Dietary Pattern	Systolic BP Reduction (mmHg)	Diastolic BP Reduction (mmHg)	Study Duration	Population
DASH Diet Alone	-5.60 ± 4.07	-5.35 ± 5.64	6 weeks	Stage 1 Hypertension [7]
DASH + TRE (8-h window)	-8.46 ± 4.26	-9.46 ± 4.38	6 weeks	Stage 1 Hypertension [7]
Intermittent Fasting (5:2 diet)	-7.00 ± 0.70	-6.00 ± 0.50	6 months	Hypertensive, Overweight/Obese [9]
Continuous Energy Restriction	-7.00 ± 0.60	-5.00 ± 0.50	6 months	Hypertensive, Overweight/Obese [9]
DASH Diet (Network Meta-Analysis)	-7.81 (CI: -14.2 to -0.46)	Not specified	Variable	Mixed [26]
Intermittent Fasting (Network Meta-Analysis)	-5.98 (CI: -10.4 to -0.35)	Not specified	Variable	Mixed [26]

A network meta-analysis of 21 RCTs ranked DASH as the most effective diet for systolic blood pressure (SBP) reduction (SUCRA score 89), followed by intermittent fasting (SUCRA score 76) [26]. Recent RCTs investigating combined approaches found that time-restricted eating (TRE), a form of IF, synergistically enhances the effects of the DASH diet. One study reported that combining DASH with an 8-hour eating window resulted in significantly greater reductions in both SBP and diastolic blood pressure (DBP) compared to DASH alone, and also improved the 24-hour diurnal blood pressure rhythm [7]. Another study demonstrated that intermittent energy restriction (the 5:2 diet) was equally effective as continuous energy restriction for blood pressure control over six months [9].

Core Biological Mechanisms and Signaling Pathways

The efficacy of these dietary interventions is rooted in their ability to modulate fundamental biological rhythms and metabolic pathways.

Circadian Rhythm Integration

Feeding and fasting cycles are governed by circadian rhythms, the 24-hour internal timekeeping system. The master clock in the suprachiasmatic nucleus (SCN) is entrained by light, while peripheral clocks in metabolic tissues are strongly entrained by feeding-fasting cycles [27]. Intermittent fasting, particularly when aligned with the daylight phase (e.g., 10 am to 6 pm), reinforces this natural rhythm [28]. The core molecular clock involves a transcription-translation feedback loop where the CLOCK and BMAL1 proteins activate the expression of Period and Cryptochrome genes, whose proteins then inhibit CLOCK-BMAL1 activity [27].

Circadian Clock Feedback Loop

Metabolic Switching and Autophagy

During the fasting state, depletion of hepatic glycogen triggers a metabolic switch from glucose utilization to fatty acid-derived ketones as the primary energy source [29]. This transition is marked by a decline in insulin and a rise in glucagon, promoting lipolysis and fatty acid oxidation. The resulting increase in ketone bodies, such as β-hydroxybutyrate, serves as an alternative fuel for the brain and other tissues and also functions as a signaling molecule [29] [27]. This fasted state activates key nutrient-sensing pathways, including the inhibition of mTOR and activation of AMPK and SIRT1, which collectively promote autophagy—a cellular housekeeping process that clears damaged organelles and proteins [29].

Metabolic Switch in Fasting

Sympathetic and Neuroendocrine Tone

Fasting induces a controlled stress response that modulates the sympathetic nervous system. Upon waking, light exposure triggers the cortisol awakening response and sympathetic activation, priming the body for energy expenditure and nutrient intake [28]. IF aligns food intake with this period of high sympathetic tone. Furthermore, fasting-induced changes in neuroendocrine signaling, including increased growth hormone secretion and a reduction in circulating leptin, contribute to its metabolic benefits [29]. The DASH diet influences blood pressure partly through improved endothelial function and modulation of the renin-angiotensin system, facilitated by high potassium intake which antagonizes sodium and promotes vasodilation [30].

Detailed Experimental Protocols

For researchers aiming to replicate or build upon these findings, the following detailed methodologies are provided.

Protocol: DASH Diet with Time-Restricted Eating (TRE)

• Study Design: 6-week randomized controlled trial in stage 1 primary hypertensive patients [7].
• Participants: Adults (18-70 years) with SBP 130-139 mmHg or DBP 80-89 mmHg, habitual eating window ≥10 hours, and no high-risk conditions or diabetes.
• Intervention Groups:
  • DASH Group: Consumed a standard DASH diet (high in fruits, vegetables, whole grains, low-fat dairy; low in saturated fat, sodium, and sugar) over more than 8 hours per day.
  • DASH+TRE Group: Followed the DASH diet but consumed all food within a fixed 8-hour window during the daytime (e.g., 9:00 a.m. to 5:00 p.m.), followed by a 16-hour water-only fast.
• Primary Outcome: Change in office SBP and DBP from baseline to 6 weeks.
• Secondary Outcomes: 24-hour ambulatory blood pressure (including diurnal rhythm), body composition (bioelectrical impedance analysis), urinary sodium excretion, and inflammatory markers.
• Adherence Monitoring: A scientific research platform within the WeChat application was used for tracking, dietary counseling, and collection of 24-hour dietary recalls [7].

Protocol: Intermittent Energy Restriction (5:2 Diet)

• Study Design: 6-month parallel randomized controlled trial in overweight/obese hypertensive patients [9].
• Participants: Adults with BMI 24-40 kg/m² and hypertension.
• Intervention Groups:
  • IER Group (5:2 Diet): Two non-consecutive days per week of severe energy restriction (500 kcal for women, 600 kcal for men), with a minimum of 0.8 g protein per kg of body weight. Five days of habitual diet without energy restriction.
  • CER Group: Continuous daily energy restriction (1,000 kcal for women, 1,200 kcal for men) based on a Mediterranean-type diet composition.
• Primary Outcomes: Changes in office BP and body weight at 6 months.
• Secondary Outcomes: Body composition (via bioelectrical impedance), HbA1c, and fasting blood lipids.
• Medication Management: A critical safety protocol for participants on antidiabetic drugs (e.g., insulin, sulfonylureas) involved reducing or withholding doses on IER days to prevent hypoglycemia, with close physician supervision [9].

The Scientist's Toolkit: Key Research Reagents and Materials

Table 2: Essential Materials for Dietary Intervention Research

Item	Function/Application in Research
Ambulatory Blood Pressure Monitor	Gold-standard for measuring 24-hour blood pressure profiles, including nocturnal dipping status [7].
Bioelectrical Impedance Analysis (BIA)	Assesses changes in body composition (fat mass, lean mass, extracellular water) in response to diet [7].
Controlled Attenuation Parameter (CAP)	Quantifies hepatic steatosis via vibration-controlled transient elastography (FibroScan), used in MAFLD/NAFLD studies [8].
Enzyme-Linked Immunosorbent Assay (ELISA) Kits	Measure biomarkers of inflammation (e.g., hs-CRP, IL-6), oxidative stress, and metabolism in serum/plasma [8] [27].
Food Diary & Tracking Software	Digital platforms (e.g., WeChat mini-programs, dedicated apps) are crucial for monitoring dietary adherence and feeding windows [7].
Metabolic Cages (Preclinical)	For animal studies, allowing precise control and measurement of food intake, energy expenditure, and activity [27].
Ketone Meter	Measures blood β-hydroxybutyrate levels to confirm the metabolic switch to ketosis in fasting protocols [29].

Integrated Discussion

The evidence positions DASH and IF as complementary, rather than competing, strategies for blood pressure management. DASH acts as a robust, nutrient-dense dietary framework, while IF provides a powerful timing cue that enhances circadian rhythm and metabolic health. The combination of DASH with TRE has demonstrated synergistic effects, producing greater blood pressure reduction and improved diurnal rhythm than DASH alone [7]. This synergy likely arises from the convergence of multiple mechanisms: the DASH diet provides the substrates for vasodilation and redox balance, while IF entrains circadian clocks, induces metabolic switching, and stimulates autophagy.

Future research should focus on long-term adherence and efficacy, personalized protocols based on chronotype and genetic predisposition, and the molecular interplay between dietary components and fasting-induced pathways. For drug development, targeting the AMPK/SIRT1 or circadian clock machinery may mimic the beneficial effects of these dietary interventions.

Comparative Efficacy of Dietary Interventions on Blood Pressure

Clinical studies demonstrate that both the Dietary Approaches to Stop Hypertension (DASH) diet and various intermittent fasting (IF) regimens effectively reduce blood pressure, with combination approaches often yielding superior results.

Table 1: Blood Pressure Outcomes from Clinical Trials of DASH Diet and Intermittent Fasting

Study Population	Intervention	Duration	SBP Reduction (mmHg)	DBP Reduction (mmHg)	Key Findings
Stage 1 primary hypertension (Adults) [7]	DASH alone	6 weeks	5.6 ± 4.1	5.4 ± 5.6	Significant BP reduction with DASH
Stage 1 primary hypertension (Adults) [7]	DASH + TRE (8-hour window)	6 weeks	8.5 ± 4.3	9.5 ± 4.4	Enhanced BP reduction vs. DASH alone; improved BP diurnal rhythm
Overweight/obese hypertensive adults [9]	Continuous Energy Restriction (CER)	6 months	7.0 ± 0.7	5.0 ± 0.5	Effective for weight loss and BP control
Overweight/obese hypertensive adults [9]	Intermittent Energy Restriction (5:2 diet)	6 months	7.0 ± 0.7	6.0 ± 0.5	Equally effective as CER for BP control and weight loss
Resistant hypertension patients [31] [32]	16/8 Intermittent Fasting	2 weeks	Significant reduction*	Significant reduction*	BP reduction accompanied by gut microbiota shifts
Overweight/obese children [25]	DASH diet	8 weeks	7.3†	4.3†	Improved BP indices and urinary metabolites in pediatric population

*Exact values not provided in available abstract; †Calculated from data presented in study

Experimental Protocols and Methodologies

DASH with Time-Restricted Eating (TRE) Protocol

A 2024 randomized controlled trial investigated DASH combined with 8-hour time-restricted eating in stage 1 primary hypertensive patients [7]:

• Study Design: 74 participants randomized to DASH alone (n=37) or DASH+TRE (n=37) for 6 weeks
• DASH Protocol: Emphasis on fruits, vegetables, whole grains, low-fat dairy, fish, and nuts while limiting processed foods and sodium
• TRE Protocol: 8-hour eating window (9:00 a.m. to 5:00 p.m.) with fasting for remaining 16 hours
• Monitoring: Digital platform (WeChat application) for tracking compliance, dietary intake, and BP measurements
• Outcome Measures: Primary: BP changes; Secondary: body composition, cardiometabolic risk factors, urinary Na+ excretion, inflammation markers
• Key Finding: DASH+TRE resulted in significantly greater BP reduction than DASH alone (p<0.05) and improved BP diurnal rhythm

Intermittent Energy Restriction (5:2 Diet) Protocol

A 2021 study compared intermittent versus continuous energy restriction in overweight/obese hypertensive patients [9]:

• Study Design: 205 participants randomized to IER (5:2 diet) or CER for 6 months
• IER Protocol: Very-low-calorie diet (500 kcal/day women, 600 kcal/day men) for 2 non-consecutive days weekly, habitual diet for other 5 days
• CER Protocol: Moderate daily restriction (1,000 kcal/day women, 1,200 kcal/day men)
• Monitoring: Regular outpatient visits, food diaries, digital cooking scales for accuracy
• Outcome Measures: Primary: BP and weight changes; Secondary: body composition, HbA1c, blood lipids
• Key Finding: IER and CER were equally effective for weight loss and BP control

Gut Microbiota-Mediated Mechanisms

The gut microbiota serves as a key intermediary through which both DASH and intermittent fasting exert their antihypertensive effects, though via partially distinct mechanistic pathways.

Gut Microbiota Composition and Metabolite Changes

Table 2: Gut Microbiota and Metabolite Changes in Hypertension Management

Intervention	Microbiota Changes	Metabolite Alterations	Documented Effects
DASH Diet [33] [34] [35]	Increased diversity; Enrichment of SCFA-producing bacteria	↑ SCFAs (butyrate, acetate, propionate); ↓ TMAO; ↓ LPS	Anti-inflammatory; Vasodilation; Improved endothelial function
Intermittent Fasting [31] [32] [36]	↑ Akkermansia muciniphila; ↑ Adlercreutzia equolifaciens	↑ SCFAs; ↓ TMAO; ↓ LPS	Reduced inflammation; Improved gut barrier function
High DI-GM Score Diet [33] [34] [35]	Enhanced microbial diversity; Balanced community structure	Favorable metabolite profile	9-13% reduction in hypertension risk per DI-GM unit

DI-GM: A Novel Dietary Index for Gut Microbiota Health

The Dietary Index for Gut Microbiota (DI-GM) provides a standardized approach to evaluate dietary patterns based on their impact on gut microbiota [33] [34] [35]:

• Scoring System: 14 components (10 beneficial, 4 detrimental) scored based on sex-specific median intake
• Beneficial Components: Fermented dairy, chickpeas, soybeans, whole grains, dietary fiber, cranberries, avocados, broccoli, coffee, green tea
• Detrimental Components: Red meat, processed meat, refined grains, high-fat diets (≥40% energy from fat)
• Hypertension Association: Each 1-unit DI-GM increase associated with 4% hypertension risk reduction (OR=0.96, 95% CI: 0.94-0.98) [34]
• Mechanistic Insight: DI-GM's antihypertensive effect partially mediated by reduced systemic inflammation (WBC count, neutrophils, SII mediate 9.07%, 8.64%, 3.97% of effect, respectively) [35]

The Scientist's Toolkit: Essential Research Reagents

Table 3: Key Research Reagents for Gut Microbiota-Hypertension Investigations

Reagent/Assay	Application	Research Utility
16S rRNA Sequencing	Microbiota composition analysis	Identifies taxonomic shifts in bacterial communities; Used in all cited clinical studies
LC-MS/MS	TMAO, SCFA quantification	Gold standard for precise metabolite measurement; Essential for mechanistic studies [31] [36]
ELISA Kits (LPS, cytokines)	Inflammation marker assessment	Quantifies systemic inflammatory status; Key for linking microbiota to hypertension [35]
Fecal Microbiota Transplantation (FMT)	Causal mechanism studies	Transfers microbiota phenotypes between donors/recipients; Validated causal role in hypertension [31]
Controlled Attenuation Parameter (CAP)	Hepatic steatosis assessment	Non-invasive liver fat quantification; Important for metabolic comorbidity assessment [8]
Ambulatory BP Monitoring	24-hour BP rhythm analysis	Captures diurnal BP patterns; Critical for hypertension outcome measures [7]

Both DASH and intermittent fasting converge on gut microbiota modulation as a key antihypertensive mechanism, despite different dietary patterns. The DASH diet primarily enhances microbial diversity and SCFA production, while intermittent fasting specifically enriches for beneficial species like Akkermansia muciniphila. Both approaches reduce pro-inflammatory metabolites (TMAO, LPS) and increase anti-inflammatory SCFAs, ultimately improving vascular function and reducing blood pressure.

Future research should focus on personalized approaches combining elements of both strategies, identifying patient-specific microbiota signatures predictive of treatment response, and developing targeted microbiota-based therapeutics for hypertension management.

Clinical Trial Designs, Protocols, and Patient Implementation

Randomized Controlled Trials (RCTs) represent the gold standard for establishing causal relationships between dietary interventions and health outcomes, forming the bedrock of evidence-based dietary guidelines [37]. In the context of researching lifestyle modifications for hypertension, such as the Dietary Approaches to Stop Hypertension (DASH) diet and intermittent fasting, well-designed RCTs are critical for verifying efficacy and guiding clinical practice. However, the design and execution of these trials present unique methodological challenges that differ fundamentally from pharmaceutical trials [38]. Nutrition interventions are inherently complex; they often involve multi-component foods or entire dietary patterns, exhibit high collinearity between dietary components, and are profoundly influenced by diverse dietary habits and food cultures [38]. Two of the most pivotal design elements that researchers must navigate are the selection of appropriate endpoints and the implementation of effective blinding procedures. The decisions made in these areas directly impact a trial's risk of bias, statistical power, and the ultimate translatability of its findings into public health and clinical practice. This guide examines these challenges through the lens of contemporary research on the DASH diet and intermittent fasting for blood pressure control, providing a structured framework for designing robust dietary RCTs.

Endpoint Selection in Dietary RCTs

Defining Primary and Secondary Endpoints

The selection of study endpoints is a critical initial step in RCT design, as it dictates the trial's sample size, duration, and feasibility [39]. Endpoints should be clearly defined a priori and must align directly with the research question.

• Primary Endpoint: This is the single most important outcome the trial is designed to evaluate. It should be a direct measure of the intervention's main intended effect. For hypertension trials, this is typically a change in systolic and diastolic blood pressure [40] [9] [41].
• Secondary Endpoints: These are supplementary outcomes that provide additional information on the intervention's effects. In dietary RCTs for hypertension, these often include:
  • Body Composition: Changes in body weight, fat mass, and extracellular water [40] [9].
  • Cardiometabolic Risk Factors: Levels of blood lipids (cholesterol, triglycerides), HbA1c, and fasting glucose [9].
  • Biomarkers of Adherence and Mechanism: Urinary sodium excretion (reflecting dietary sodium intake), inflammation-related parameters like C-reactive protein (CRP), and other clinical variables [40] [41].
  • Safety Outcomes: Reports of adverse effects such as nighttime hunger, dizziness, or headaches [40] [9].

Quantitative Data from Recent RCTs

The table below summarizes endpoints and findings from recent RCTs investigating the DASH diet and intermittent fasting for blood pressure management.

Table 1: Endpoints and Findings from Recent Dietary RCTs for Hypertension

Trial Description	Primary Endpoints	Key Secondary Endpoints	Reported Findings
DASH vs. DASH+TRE (n=74)6-week RCT in stage 1 hypertension [40] [41]	- SBP & DBP Reduction	- Body composition (extracellular water)- Urinary Na+ excretion- Blood pressure diurnal rhythm- Safety (e.g., nighttime hunger)	- SBP Reduction: DASH: 5.6 mmHg; DASH+TRE: 8.5 mmHg- DBP Reduction: DASH: 5.4 mmHg; DASH+TRE: 9.5 mmHg- Improved BP rhythm & increased Na+ excretion with TRE
IER vs. CER (n=205)6-month RCT in overweight/obese hypertensive patients [9]	- Changes in BP and Weight	- Body composition- HbA1c- Blood lipids	- Weight Change: IER: -7.0 kg; CER: -6.8 kg- SBP Change: IER: -7 mmHg; CER: -7 mmHg- DBP Change: IER: -6 mmHg; CER: -5 mmHg- No significant differences between groups

Decision Pathway for Endpoint Selection

The process of selecting endpoints requires careful consideration of the intervention's goals, feasibility, and biological plausibility. The following diagram outlines a logical workflow for this critical design phase.

Blinding Challenges and Methodological Solutions

The Fundamental Blinding Problem in Dietary RCTs

Blinding, or masking, is a key methodological feature that safeguards against performance and detection bias by preventing participants, investigators, and outcome assessors from knowing group assignments [42] [39]. In pharmaceutical trials, this is often straightforward using matched placebos. However, in dietary RCTs, particularly those involving whole foods or dietary patterns like the DASH diet or intermittent fasting, creating a convincing placebo or sham intervention is exceptionally difficult, leading to a paucity of well-blinded trials [43] [44] [38]. The complex nature of food, its sensory properties (taste, smell, texture), and the behavioral components of dietary advice present nearly insurmountable obstacles to perfect blinding.

Types of Control Groups and Their Applications

Given the blinding challenge, the selection of an appropriate control group becomes paramount. The choice should be guided by the research question and what the experimental intervention is intended to be compared against [39].

Table 2: Control Group Strategies in Dietary Intervention Trials

Control Group Type	Description	Advantages	Disadvantages & Blinding Status
Placebo/Sham Control [39] [44]	An inactive substance or "sham" diet designed to be indistinguishable from the active intervention.	- Controls for placebo effect.- Maximizes internal validity.	- Extremely difficult to develop for whole foods/diets.- May be unblinded by taste, lack of effect, or side effects.
Active Comparator [39] [44]	Compares the new diet to an established, standard-of-care dietary therapy (e.g., low-fat diet).	- Provides a clinically relevant comparison.- Addresses equipoise; often more ethical.	- Usually unblinded (participants know which diet they are on).- Does not control for placebo effect.
Wait-List/No-Treatment [44]	Control participants receive no intervention or are put on a waiting list for future treatment.	- Ethical in some contexts.- Simple and inexpensive.	- Unblinded.- High risk of expectation bias; can over- or underestimate treatment effects.
Attention Control [39]	Control group receives equal time and attention from researchers but on a neutral topic (e.g., general nutrition education).	- Controls for the "attention" effect of the intervention.- Improves retention.	- Often unblinded if the core dietary advice differs.- Complex to design effectively.

Strategies to Mitigate Bias in the Absence of Blinding

When full blinding is not feasible, researchers must employ other methodological strategies to minimize bias and strengthen the validity of their conclusions.

• Objective vs. Subjective Outcomes: Prioritize objective primary endpoints like blood pressure, body weight, or laboratory biomarkers (e.g., lipids, HbA1c) [44] [9]. These are less susceptible to bias than subjective patient-reported outcomes like symptom scores.
• Blinding of Outcome Assessors: While participants and interventionists may be unblinded, it is often possible to blind the personnel who collect and analyze the final outcome data (e.g., lab technicians, statisticians) [42]. This prevents conscious or unconscious influence during data handling.
• Centralized Outcome Adjudication: For clinical event outcomes, an independent, blinded committee can be established to adjudicate whether reported events meet predefined diagnostic criteria [42].
• Run-in Periods and Adherence Monitoring: Incorporating a pre-randomization run-in period can identify and exclude participants with poor potential adherence [37]. Using objective measures of adherence (e.g., urinary sodium for DASH diet adherence, electronic food diaries) strengthens the interpretation of results [40] [37].

Pathway for Selecting a Blinding Strategy

The following diagram illustrates a decision-making process for choosing a control strategy based on the nature of the dietary intervention.

The Scientist's Toolkit: Essential Reagents and Materials

Successfully conducting a dietary RCT requires meticulous planning and specific resources to ensure standardized interventions, accurate data collection, and adherence monitoring.

Table 3: Essential Research Reagents and Solutions for Dietary RCTs

Tool / Reagent	Function / Purpose	Application Example
Standardized Dietary Protocols	Provides a consistent, replicable framework for the intervention and control diets, ensuring all participants receive the same core advice.	DASH diet guidelines, Mediterranean diet protocols, or specific meal plans for intermittent fasting windows [40] [9].
Digital Food Scales & Photo-Aided Diaries	Enables precise quantification of food intake and improves the accuracy of dietary self-reporting.	Providing participants with digital scales (e.g., ±0.1g accuracy) to weigh foods during calorie-restriction days [9].
Adherence Tracking Platforms	Digital tools (e.g., dedicated apps, WeChat platforms) to monitor food intake, fasting windows, and provide reminders, facilitating real-time tracking and support [40].	Using a scientific research platform within a common social media app to track participant daily check-ins and dietary logs [40].
Objective Biomarker Assays	Provides biochemical verification of dietary adherence and measures secondary metabolic endpoints.	Urinary sodium analysis to corroborate reduced sodium intake on the DASH diet; assays for blood lipids, HbA1c, and inflammatory markers like CRP [40] [9].
Ambulatory Blood Pressure Monitor (ABPM)	The gold-standard for blood pressure measurement in research; provides a 24-hour profile, eliminating white-coat hypertension and capturing diurnal rhythm.	Used as the primary device for measuring the efficacy outcome (blood pressure) in hypertension trials [40] [41].
Body Composition Analyzers	Measures changes in fat mass, muscle mass, and extracellular water (ECW), providing insight into potential mechanisms behind blood pressure changes.	Bioelectrical impedance analysis (BIA) devices to track reductions in ECW associated with blood pressure improvements [40].

Designing robust RCTs for dietary interventions like the DASH diet and intermittent fasting requires navigating a complex landscape of methodological trade-offs. The selection of meaningful, feasible endpoints—prioritizing objective primary outcomes like ambulatory blood pressure—is fundamental to a trial's success. Simultaneously, researchers must confront the significant challenge of blinding by strategically selecting the most appropriate control group, whether it be an active comparator, attention control, or, when possible, a sham diet. The limitations inherent in these choices can be mitigated by blinding outcome assessors, employing objective biomarkers of adherence, and using centralized data analysis. By systematically addressing these challenges in endpoint selection and blinding, researchers can generate high-quality evidence that reliably informs clinical practice and public health guidelines for managing hypertension and other chronic diseases through dietary means.

DASH Diet Protocol Standardization for Research and Clinical Settings

Hypertension remains a primary contributor to global cardiovascular disease and mortality, driving sustained research into effective lifestyle interventions [40]. Among dietary strategies, the Dietary Approaches to Stop Hypertension (DASH) eating plan and various forms of intermittent fasting (IF) have emerged as prominent approaches for blood pressure management. The DASH diet, developed with National Institutes of Health support, has demonstrated efficacy in reducing blood pressure and has been ranked as the "Best Heart-Healthy Diet" for 2025 by U.S. News & World Report [4] [45]. Concurrently, intermittent fasting regimens, particularly time-restricted eating (TRE), have gained popularity for their potential cardiometabolic benefits [40] [46]. This guide provides a standardized comparison of these dietary protocols, detailing their experimental methodologies, efficacy data, and implementation frameworks to support researchers and clinical trial design.

Standardized Dietary Protocols

DASH Diet Protocol

The DASH eating plan is a flexible and balanced dietary pattern designed to create a heart-healthy eating style for life. The protocol emphasizes foods rich in potassium, calcium, magnesium, fiber, and protein, while being low in saturated and trans fats and sodium [4].

Core Nutritional Composition:

• Sodium: Limited to 2,300 mg daily, with a lower target of 1,500 mg shown to further reduce blood pressure
• Food Group Emphasis: Rich in fruits, vegetables, fat-free or low-fat dairy products, whole grains, fish, poultry, and nuts
• Restricted Components: Reduced intake of lean red meat, sweets, added sugars, and sugar-containing beverages compared to typical Western diets [45] [47]

Daily Servings for a 2,000-Calorie Diet:

Food Group	Daily Servings
Grains	6-8
Meats, poultry, and fish	6 or less
Vegetables	4-5
Fruits	4-5
Low-fat or fat-free dairy	2-3
Fats and oils	2-3
Weekly Servings
Nuts, seeds, dry beans, peas	4-5
Sweets	5 or less

[4]

Standardized Serving Sizes:

• Vegetables: 1 cup raw leafy vegetables or ½ cup chopped raw/cooked vegetables
• Fruits: 1 medium fruit or ½ cup fresh, frozen, or canned fruit
• Grains: 1 slice bread or ½ cup cooked rice, pasta, or cereal
• Lean protein: 1 oz cooked fish, lean meat, or poultry
• Dairy: 1 cup milk or yogurt or 1½ ounces cheese [47]

Adaptation for Special Populations: Researchers have developed modified versions for specific patient populations. The DASH4D protocol adapts the diet for type 2 diabetes by lowering carbohydrate content, increasing unsaturated fat, and adjusting potassium for kidney safety [48].

Intermittent Fasting Protocols

Intermittent fasting encompasses several approaches, with time-restricted eating (TRE) being most studied for hypertension management.

Primary TRE Protocol (16:8):

• Fasting Window: 16 hours of continuous fasting daily
• Eating Window: All food consumption limited to a consistent 8-hour period
• Permitted during fasting: Water, decaffeinated coffee, diet sodas, and other non-caloric beverages [8] [31]

Alternative IF Approaches:

• 5:2 Diet: Severe energy restriction (500 kcal/day for women, 600 kcal/day for men) for 2 non-consecutive days per week, with habitual eating the other 5 days [9]
• Alternate-Day Fasting: Alternating between fasting days and regular eating days

Comparative Efficacy Data: Blood Pressure Outcomes

Short-Term Efficacy (6-12 Weeks)

Table 1: Blood Pressure Reduction in Stage 1 Hypertension (6-Week Outcomes)

Intervention Group	Sample Size	SBP Reduction (mmHg)	DBP Reduction (mmHg)	P-value
DASH alone	37	5.60 ± 4.07	5.35 ± 5.64	-
DASH + TRE (8-hour)	37	8.46 ± 4.26	9.46 ± 4.38	<0.05 vs. DASH alone

[40]

Key Findings:

• The combination of DASH with TRE produced significantly greater blood pressure reduction than DASH alone
• DASH + TRE improved blood pressure diurnal rhythm and increased urinary Na+ excretion, suggesting potential mechanisms for the enhanced effect [40]
• The 8-hour eating window (typically from 9:00 a.m. to 5:00 p.m.) demonstrated superior efficacy compared to longer eating windows [40]

Medium-Term Efficacy (6-Month Outcomes)

Table 2: Intermittent vs. Continuous Energy Restriction (6-Month Outcomes)

Intervention Group	Weight Change (kg)	SBP Reduction (mmHg)	DBP Reduction (mmHg)
Intermittent Energy Restriction (5:2)	-7.0 ± 0.6	-7.0 ± 0.7	-6.0 ± 0.5
Continuous Energy Restriction	-6.8 ± 0.6	-7.0 ± 0.6	-5.0 ± 0.5

[9]

Key Findings:

• Both intermittent and continuous energy restriction produced statistically significant and clinically meaningful improvements in blood pressure
• No significant differences were observed between intermittent and continuous approaches for primary outcomes at 6 months
• Both groups showed similar improvements in body composition, HbA1c, and blood lipid levels [9]

Population-Specific Adaptations and Efficacy

Type 2 Diabetes Population:

• The adapted DASH4D diet with lower sodium achieved a clinically meaningful reduction of 4.6 mmHg in systolic BP and 2.3 mmHg in diastolic BP compared to a typical American diet with higher sodium [48]
• This reduction is significant given that most participants were already on multiple antihypertensive medications

Resistant Hypertension:

• A 16:8 TRE regimen (16-hour fast/8-hour eating window) significantly reduced blood pressure in patients with resistant hypertension [31]
• Effects were linked to modulation of gut microbiota, including increased abundance of Akkermansia muciniphila and Adlercreutzia equolifaciens [31]

Experimental Methodology & Protocol Standardization

Standardized Research Protocols

DASH Diet Implementation:

• Dietary Counseling: Provided by trained nutritionists and physicians
• Monitoring: Dietary intake tracking using 24-hour recall methods, food diaries, and digital platforms
• Adherence Support: Regular outpatient visits, provision of sample meal plans, and written dietary information brochures [40] [9]

Time-Restricted Eating Implementation:

• Window Selection: Consistent 8-hour eating window (typically daytime, e.g., 9:00 a.m. to 5:00 p.m.)
• Tracking: Use of digital platforms and self-monitoring tools to record eating windows
• Adherence Assessment: Regular check-ins and monitoring of feeding/fasting cycles [40] [8]

Key Methodological Considerations

Table 3: Critical Protocol Standardization Elements

Element	DASH Diet Protocol	Intermittent Fasting Protocol
Dietary Composition	Specific food group servings; Low sodium targets	No specific nutrient requirements; Focus on timing only
Intervention Duration	Minimum 4 weeks for initial BP effects; 12+ weeks for sustained benefits	Minimum 6 weeks for BP effects; Long-term safety data limited
Participant Monitoring	24-hour dietary recalls, food diaries, urinary sodium measurement	Eating window tracking, hunger assessments, metabolic markers
Medication Management	BP medication adjustment may be needed with significant BP reduction	Special caution with diabetes medications during fasting periods
Safety Considerations	Generally safe; Potassium monitoring in CKD patients	Potential for hypoglycemia, hunger, fatigue; Caution in specific populations

[40] [9] [47]

Mechanisms of Action: Comparative Pathways

DASH Diet Physiological Pathways

Time-Restricted Eating Physiological Pathways

Research Reagents & Methodological Tools

Table 4: Essential Research Materials and Assessment Tools

Category	Specific Tools/Assessments	Research Application
Dietary Assessment	24-hour dietary recall forms, Food frequency questionnaires, Digital food tracking platforms	Quantifying adherence to dietary protocols, Monitoring nutrient intake
Blood Pressure Monitoring	Ambulatory BP monitors, Automated office BP devices, Home BP monitoring systems	Primary outcome measurement, Diurnal BP pattern assessment
Body Composition	DEXA scans, Bioelectrical impedance analysis, Digital scales, Abdominal circumference tapes	Assessing weight loss, body fat distribution, and lean mass changes
Biochemical Analysis	ELISA kits for LPS, TMAO, SCFAs; Standard clinical chemistry panels; Urinary electrolyte assays	Mechanistic studies, Safety monitoring, Metabolic impact assessment
Microbiome Analysis	16S rRNA sequencing kits, Fecal microbiota transplantation materials, Bacterial cultures (Akkermansia muciniphila)	Gut microbiota mechanistic studies [31]
Adherence Tools	Eating window tracking apps, Meal timing logs, Hunger and symptom questionnaires	Protocol compliance monitoring, Safety assessment

Safety Considerations and Contraindications

DASH Diet Safety Profile

The DASH diet is generally safe with minimal adverse effects. Important considerations include:

• Kidney Function: Monitoring may be necessary when implementing the lower sodium (1,500 mg) target in patients with chronic kidney disease [47] [48]
• Medication Adjustment: Antihypertensive medications may require adjustment as blood pressure decreases to avoid hypotension [9]
• Potassium Considerations: The standard DASH diet is high in potassium, which may require modification in patients with impaired potassium excretion [48]

Intermittent Fasting Safety Profile

Recent evidence suggests a more nuanced safety profile for intermittent fasting:

• Cardiovascular Risk: An analysis of over 20,000 adults found that limiting eating to less than 8 hours per day was associated with a 91% higher risk of death from cardiovascular disease [46]
• Population-Specific Risks: Individuals with existing heart disease or cancer showed increased risk of cardiovascular death with TRE [46]
• Common Side Effects: Hunger, fatigue, headaches, and potential hypoglycemia, particularly in individuals with diabetes [40] [9]
• Medication Management: Special caution required with diabetes medications, particularly insulin and sulfonylureas, which may need dose adjustment or temporary discontinuation on fasting days [9]

The standardized protocols presented herein provide researchers with evidence-based frameworks for implementing and comparing dietary interventions for hypertension management. The DASH diet offers a well-established, safe dietary pattern with proven efficacy for blood pressure reduction across diverse populations [4] [45] [47]. Time-restricted eating, particularly in combination with DASH, demonstrates enhanced short-term efficacy but requires further investigation into long-term safety and population-specific effects [40] [46].

Critical research gaps remain in understanding the long-term effects of both interventions, their synergistic potential, and the biological mechanisms underlying their blood pressure-lowering effects. Future studies should prioritize standardized outcome measures, diverse population inclusion, and careful safety monitoring to advance the evidence base for non-pharmacological hypertension management.

The investigation of non-pharmacological interventions for blood pressure control, particularly the Dietary Approaches to Stop Hypertension (DASH) diet and Intermittent Fasting (IF), requires rigorous methodological frameworks in clinical trial settings. A core challenge in this research domain lies in the accurate implementation and monitoring of these dietary regimens. For IF trials, this specifically involves two critical components: defining and standardizing the eating window and monitoring participant adherence to the prescribed temporal eating pattern. The integrity of trial data and the validity of conclusions drawn about efficacy depend fundamentally on how effectively researchers manage these parameters. This guide provides a comparative analysis of methodological approaches, supporting experimental data, and practical tools for implementing these dietary interventions with scientific precision.

Comparative Analysis: DASH Diet vs. Intermittent Fasting

Table 1: Core Characteristics and Implementation Requirements in Clinical Trials

Feature	DASH Diet	Intermittent Fasting (Time-Restricted Eating)
Core Principle	Focus on food quality and composition; rich in potassium, calcium, magnesium, fiber, and protein; low in saturated fat and sodium [4] [5].	Focus on meal timing; restricts all dietary intake to a consistent, daily window (typically 6-11 hours) without prescribed caloric restriction [11].
Primary Mechanism	Nutrient-based approach to improve cardiovascular health and lower blood pressure [5].	"Metabolic switching": prolonging the period to burn through calories from the last meal and begin burning fat, thereby supporting circadian rhythms [11] [49].
Key Efficacy Data	Effective for preventing/treating hypertension and improving cholesterol [5]. A 2,000-calorie plan includes 6-8 grain, 4-5 vegetable, and 4-5 fruit servings daily [4].	A 2020 study showed a 10-hour TRE window reduced weight, blood pressure, and atherogenic lipids in metabolic syndrome patients [11]. 4-hour windows increased adverse events; 12-hour windows showed no benefit [11].
Adherence Monitoring Challenge	Tracking consumption of specific food groups and enforcing sodium limits.	Verifying compliance with the fasting/eating windows in free-living participants.
Common Monitoring Methods	Food diaries, 24-hour dietary recalls, food frequency questionnaires, urinary sodium measurement [50].	Digital tools like smartphone apps, time-stamped photo journals, and wearable sensors.

Table 2: Direct Comparative Trial Data (DASH vs. Salt-Free Diet)

A 2025 randomized controlled trial directly compared a modified DASH diet to a salt-free diet over two months in 60 hypertensive patients [50].

Outcome Measure	DASH Diet Group	Salt-Free Diet Group	P-Value
Systolic BP (End of Month 2)	126.81 ± 8.91 mm Hg	121.03 ± 9.73 mm Hg	.021
Diastolic BP (End of Month 2)	No significant difference between groups	No significant difference between groups	N/S
Key Biochemical Finding	Higher sodium and soluble fiber intake at month 1 compared to salt-free group.	Lower urinary sodium excretion, indicating better protocol adherence for sodium restriction.	< .05

The trial concluded that while the salt-free diet was more effective at lowering systolic BP, integrating sodium restriction into the DASH diet could yield the most favorable outcomes [50].

Experimental Protocols for IF Trials

Defining and Standardizing the Eating Window

The eating window is the independent variable in a Time-Restricted Eating (TRE) trial, and its precise definition is paramount.

• Window Selection: Clinical evidence suggests that eating windows between 6 and 10 hours are generally safe, well-tolerated, and effective. Windows of 12 hours or more typically show no health benefits, while very restrictive windows (e.g., 4 hours) can increase minor adverse events like headaches and moodiness without adding benefit [11]. A common protocol is the 16/8 fast (16-hour fast, 8-hour eating window) [49].
• Window Timing: The clock start and end times (e.g., 10:00 to 18:00) must be standardized across the intervention arm or aligned with the participant's circadian rhythm (e.g., early daytime feeding). Consistency is key, and the timing should be recorded for each participant.
• Procedure Standardization: The protocol must explicitly define what is permitted during the fasting window. Typically, this includes water, black coffee, and other zero-calorie beverages [49]. Participants should be instructed not to alter their diet quality or quantity during their eating windows, as packing feeding times with high-calorie junk food can negate health benefits [49].

Monitoring and Verifying Adherence

Robust adherence monitoring is what separates a credible IF trial from an observational study. Reliance on self-report alone is insufficient.

• Primary Method - Digital Tools: Utilize smartphone applications designed for TRE that allow participants to log their meal start and end times. More advanced methods include time-stamped photo journals of meals or integration with continuous glucose monitors and other wearables to detect metabolic shifts that indicate food intake. These tools provide objective, granular data on the timing of calorie intake [51].
• Secondary Method - Biomarkers: While there is no single biomarker for TRE adherence, changes in metabolic markers can serve as supportive evidence. These include reduced fasting insulin and glucose, and a decrease in blood pressure, as seen in a study where TRE improved these parameters in patients with metabolic syndrome [11]. Ketone body levels can also be measured as an indicator of fat metabolism during the fasted state.
• Adherence Support: To bridge the "Intention-Behaviour Gap," researchers should incorporate weekly check-in calls or texts to boost participant motivation and diet compliance, a method proven effective in dietary trials [50]. Inform participants that an adjustment period of two to four weeks is common, during which they may feel hungry or irritable, but this typically subsides [49].

Visualization of Workflows

IF Trial Participant Screening and Adherence Workflow

The following diagram illustrates the key stages in running an Intermittent Fasting clinical trial, from screening to data analysis, with a focus on ensuring adherence.

Digital Adherence Monitoring Data Flow

This diagram outlines the logical flow of information in a digital adherence monitoring system, from data capture to researcher intervention.

The Scientist's Toolkit: Essential Research Reagents & Materials

Table 3: Key Materials for Dietary Intervention Trials

Item	Function in Research	Example Application/Note
Automated Sphygmomanometer	Standardized, frequent blood pressure monitoring, crucial for primary outcome data.	Provided to patients for daily home monitoring to ensure consistent, reliable BP measurements throughout the trial [50].
Digital Dietary Adherence Tools	Objective, granular tracking of meal timing and/or composition. Includes smartphone apps, time-stamped photo journals, and wearable sensors.	Critical for verifying compliance with the eating window in IF trials; provides more reliable data than self-report alone [51] [11].
Bioelectrical Impedance Analyzer (BIA)	Measures body composition (e.g., fat mass, muscle mass).	Used to track changes in body composition beyond simple weight, such as in studies where IF led to fat loss while maintaining muscle mass [49] [50].
Standardized Food Photo Catalogue	Aids in accurate portion size estimation by participants in food consumption reports.	Used during 3-day food consumption interviews to improve the accuracy of self-reported dietary intake data [50].
Nutrition Analysis Software	Calculates macro and micronutrient intake from food consumption reports.	Software like BEBIS is used to analyze 3-day food diaries and ensure nutrient intake aligns with protocol requirements (e.g., DASH composition) [50].
Biochemical Assay Kits	Quantify key blood and urine biomarkers related to metabolic health and adherence.	Measures parameters like fasting glucose, lipids, and spot urine sodium (to monitor sodium restriction adherence) [50].
DASH Diet Compliance Scale	A standardized scoring system to quantify adherence to the DASH dietary pattern.	A score ≥4.5 indicates high compliance; used to stratify participants or as a covariate in analysis [50].

The management of hypertension and type 2 diabetes mellitus (T2DM) often requires a delicate balance between pharmacological interventions and lifestyle modifications. Intermittent Energy Restriction (IER) and Continuous Energy Restriction (CER) have emerged as effective dietary strategies for weight loss and cardiometabolic improvement. However, their implementation in medicated individuals necessitates careful medication management to prevent adverse events, particularly hypoglycemia and hypotension. This review synthesizes evidence from clinical trials to compare protocols for managing concomitant medications during IER and CER, providing a critical framework for researchers and clinicians operating within the comparative landscape of the DASH diet and intermittent fasting for blood pressure control.

Experimental Protocols and Medication Management in Key Trials

Clinical trials investigating energy restriction in populations with hypertension or T2DM have established specific protocols for adjusting diabetes and hypertension medications to mitigate risks. The following section details the methodologies and medication management strategies from pivotal studies.

Medication Management in Type 2 Diabetes Trials

A short review of IER in T2DM highlighted the critical need for medication adjustment during very low-calorie diets. The common protocol across several studies was the discontinuation of all oral hypoglycemic agents at the trial's initiation to prevent hypoglycemia [52]. A pivotal pilot trial of the 5:2 IER method (involving two days of severe energy restriction per week) refined this approach: instead of total cessation, medications were specifically ceased only on the two IER days [52]. The protocol stipulated discontinuing hypoglycemia-prone agents like sulfonylureas at baseline for participants with an HbA1c below 8%, while medications such as metformin, gliptins, and SGLT2 inhibitors remained unchanged [52]. Insulin management required particular caution, with one trial halving the insulin dose at the VLCD's commencement and reducing it further if fasting glucose fell below 8.4 mmol/L or hypoglycemia occurred [52].

Medication Management in Hypertension Trials

A 6-month randomized controlled trial involving 205 overweight or obese participants with hypertension directly compared IER (5:2 diet) and CER. The medication management protocol was clearly defined: participants were instructed to measure and record their blood pressure twice daily [9]. If two consecutive readings were below 110/70 mmHg or if symptomatic hypotensive episodes occurred, participants were to contact investigators for medication adjustments [9]. These adjustments, made in consultation with cardiologists, could occur during clinic visits or remotely via telephone or WeChat, ensuring responsive and patient-specific management [9].

The DASH4D CGM Trial Protocol

While not an IER/CER trial, the DASH4D CGM study provides a relevant model for controlled dietary intervention. This crossover trial investigated a modified DASH diet for T2DM patients over 20 weeks [53]. Participants spent five weeks each on low- and high-sodium DASH4D diets and low- and high-sodium standard diets, in a random order [53]. All meals were prepared by staff, totaling over 40,000 meals, which ensured strict adherence and accurate assessment of the diet's effects without the confounder of dietary self-management [53]. Glycemic control was assessed via continuous glucose monitoring (CGM) during weeks three and four of each diet period [53].

Comparative Outcomes of IER and CER

Table 1: Weight Loss and Blood Pressure Outcomes in IER vs. CER Trials

Population	Intervention	Duration	Weight Change	SBP Change	DBP Change	Key Medication Lesson
Overweight/Obese with Hypertension [9]	IER (5:2)	6 months	-7.0 kg	-7 mmHg	-6 mmHg	Protocol for BP med reduction if BP <110/70 mmHg or symptoms occur.
	CER	6 months	-6.8 kg	-7 mmHg	-5 mmHg
Stage 1 Hypertension (with DASH) [7]	DASH + TRE	6 weeks	Not Reported	-8.5 mmHg	-9.5 mmHg	TRE enhances BP lowering effect of DASH; may require earlier med review.
	DASH alone	6 weeks	Not Reported	-5.6 mmHg	-5.4 mmHg
Adults with Overweight/Obesity (Meta-Analysis) [54]	IF	Varies	-4.43 mmHg	-2.00 mmHg	IER effective for BP reduction; minor, self-resolving adverse effects noted.

Table 2: Network Meta-Analysis Comparing Dietary Patterns on Cardiometabolic Markers

Dietary Pattern	Effect on SBP (MD)	Effect on Weight (MD)	SUCRA Score for SBP	Key Finding
DASH [55]	-7.81 mmHg	Not the primary outcome	89%	Most effective for blood pressure control.
Intermittent Fasting [55]	-5.98 mmHg	Significant reduction	76%	Also highly effective for blood pressure control.
Ketogenic [55]	Not the primary outcome	-10.5 kg	99%	Superior for weight reduction.

The efficacy of IER and CER for weight loss and blood pressure control appears comparable. A 6-month RCT in hypertensive patients found no significant difference between IER and CER in reductions of weight, SBP, or DBP [9]. A 2025 meta-analysis reinforced that intermittent fasting significantly lowers SBP and DBP in adults with overweight or obesity [54]. Furthermore, a network meta-analysis ranked the DASH diet as the most effective for systolic blood pressure reduction, with intermittent fasting also demonstrating significant effects [55]. A unique trial combining the DASH diet with Time-Restricted Eating (TRE), a form of IER, found the combination led to a significantly greater reduction in blood pressure than the DASH diet alone [-8.5/-9.5 mmHg vs. -5.6/-5.4 mmHg] and improved blood pressure diurnal rhythm [7].

A Framework for Medication Management During Energy Restriction

Based on the synthesized trial protocols, the following workflow provides a structured approach for managing medications in patients undergoing energy restriction.

Key Considerations for Medication Adjustment

• High-Risk Medications: Sulfonylureas and insulin carry the highest risk of hypoglycemia during energy restriction and often require dose reduction or temporary discontinuation on restriction days [52]. Antihypertensive medications, especially those causing significant vasodilation, may need to be down-titrated with substantial weight loss.
• Individualized Targets: The provided workflow is a general guide. Action thresholds for medication changes must be personalized, considering factors like the patient's age, duration of diabetes, and presence of cardiovascular comorbidities.
• Patient Empowerment: As seen in the hypertension trial, successful management relies on patient self-monitoring and clear pathways for communicating abnormal readings to healthcare providers [9].

The Scientist's Toolkit: Essential Reagents and Materials

Table 3: Key Research Reagents and Materials for Clinical Trials in Energy Restriction

Item	Function/Application	Exemplar Use in Cited Research
Continuous Glucose Monitor (CGM)	Provides continuous, real-time interstitial glucose readings, capturing glycemic variability and asymptomatic hypoglycemia.	Used in the DASH4D CGM trial to meticulously track glucose control in participants with T2DM [53].
Automated Blood Pressure Monitor	Allows for frequent at-home BP monitoring, essential for detecting hypotension during energy restriction and guiding medication titration.	Participants in the IER vs. CER hypertension trial performed twice-daily BP measurements [9].
Digital Food Scale	Ensures precise measurement of food portions, critical for dietary interventions requiring strict calorie control.	Provided to participants to improve adherence and accuracy in food intake reporting [9].
Validated Food Frequency Questionnaire	Assesses habitual dietary intake and compliance with the prescribed dietary pattern during non-restriction or maintenance phases.	Implied as a standard tool for dietary assessment in longitudinal nutrition research.
Biobank Storage Supplies	Enables the collection and frozen storage of biological samples for future analysis of biomarkers related to study outcomes.	Standard practice in clinical trials to explore mechanistic pathways.

The evidence demonstrates that both IER and CER are effective strategies for weight loss and cardiometabolic improvement, with comparable effects on blood pressure and glycemic control. A critical commonality is that their successful implementation in medicated patients requires a proactive and protocol-driven approach to medication management. Key lessons include the need for pre-emptive adjustment of high-risk medications like insulin and sulfonylureas, structured patient self-monitoring, and clear thresholds for clinician intervention. The DASH diet, particularly when combined with TRE, shows enhanced blood pressure-lowering effects, which may necessitate more vigilant medication management. Future research should focus on standardizing these medication management protocols for different patient phenotypes and medication classes to ensure the safe and effective translation of dietary interventions into clinical practice.

For researchers and drug development professionals, assessing dietary interventions has traditionally relied on primary clinical endpoints such as blood pressure readings and basic anthropometric measurements. However, the evolving field of nutrimetabolomics now enables a more sophisticated approach, uncovering subtle molecular changes that precede and underlie clinical improvements. This guide provides a comparative analysis of biomarker assessment methodologies for two prominent dietary interventions: the Dietary Approaches to Stop Hypertension (DASH) diet and various intermittent fasting (IF) regimens. We objectively evaluate the performance of urinary metabolites, body composition analysis, and other novel biomarkers in characterizing the physiological impacts of these interventions, providing supporting experimental data from recent clinical investigations. The expansion beyond traditional blood pressure measurements to include urinary metabolites and advanced body composition metrics offers a more comprehensive toolkit for understanding the mechanistic pathways through which dietary interventions exert their effects, potentially accelerating the development of targeted nutritional therapies and pharmacologic agents.

Comparative Efficacy: Quantitative Biomarker Changes Across Interventions

Table 1: Biomarker Changes in DASH Diet Interventions Across Clinical Studies

Biomarker Category	Specific Marker	Population	Intervention Duration	Change from Baseline	Statistical Significance	Citation
Blood Pressure	Systolic BP	Adults with hypertension	2 weeks	-5.2 to -8.5 mmHg	p<0.05	[40] [56]
Blood Pressure	Diastolic BP	Adults with hypertension	2 weeks	-5.4 to -9.5 mmHg	p<0.05	[40] [56]
Urinary Metabolites	Sodium (UNa)	Overweight/obese children	8 weeks	-13 mmol/L	p<0.05	[25]
Urinary Metabolites	Na-K ratio	Overweight/obese children	8 weeks	-0.15 mmol/L	p<0.05	[25]
Urinary Metabolites	Caffeic acid	Adults with hypertension	2 weeks	Significant increase	p<0.05, FDR<0.20	[56]
Urinary Metabolites	Gentisic acid	Adults with hypertension	2 weeks	Significant increase	p<0.05, FDR<0.20	[56]
Body Composition	Abdominal circumference	MAFLD patients	12 weeks	Significant reduction	p=0.005	[8]

Table 2: Biomarker Changes in Intermittent Fasting Interventions Across Clinical Studies

Biomarker Category	Specific Marker	Population	Intervention Duration	Change from Baseline	Statistical Significance	Citation
Body Composition	Body weight	Women with obesity	8 weeks	-1 kg (IF+EX vs EX)	p=0.012	[57]
Body Composition	Body fat percentage	Women with obesity	8 weeks	-4% (IF+EX)	p<0.001	[57]
Body Composition	Fat-free mass	Women with obesity	8 weeks	+3.3% (IF+EX)	p<0.001	[57]
Body Composition	Visceral fat area	Adults with overweight/obesity	12 weeks	Significant reduction	p<0.05	[58]
Body Composition	Body weight	Metabolic syndrome patients	5 days (water-only)	-4.23 kg	p<0.001	[59]
Blood Pressure	Diastolic BP	Metabolic syndrome patients	5 days (water-only)	-9.81 mmHg	p<0.001	[59]
Blood Pressure	Systolic BP	Metabolic syndrome patients	5 days (water-only)	-2.42 mmHg	p=0.013	[59]
Hepatic Health	Controlled attenuation parameter (CAP)	MAFLD patients	12 weeks	Significant reduction	p<0.001	[8]

Table 3: Combined DASH and Time-Restricted Feeding Effects on MAFLD Biomarkers

Biomarker	DASH + TRF (16/8) Group	Control Diet Group	P-value	Clinical Relevance
Body mass index (BMI)	Significant reduction	Less pronounced change	0.03	Obesity management
Abdominal circumference	Significant reduction	Less pronounced change	0.005	Visceral adiposity indicator
Controlled attenuation parameter (CAP)	Significant reduction	Less pronounced change	<0.001	Hepatic steatosis measure
Alanine aminotransferase (ALT)	Significant reduction	Less pronounced change	0.039	Liver enzyme improvement
Aspartate aminotransferase (AST)	Significant reduction	Less pronounced change	0.047	Liver enzyme improvement
Insulin resistance (HOMA-IR)	Significant reduction in both groups	Significant reduction in both groups	<0.05	Metabolic health improvement

Experimental Protocols and Methodologies

Urinary Metabolite Profiling Protocols

The assessment of urinary metabolites in dietary intervention studies employs sophisticated analytical techniques to identify and quantify molecular species that reflect dietary adherence and physiological responses.

Sample Collection and Preparation: In the DASH-Sodium trial, 24-hour urine specimens were collected from participants following a standardized protocol [60]. For metabolomic analysis, samples were typically diluted in pure water to achieve constant creatinine concentration across samples to normalize for urinary concentration variations [56]. For food-specific compound identification, researchers employed a meticulous approach where approximately 50 mg of each freeze-dried food sample was prepared using methanol extraction with chilled methanol followed by protein precipitation at -80°C for 60 minutes [61].

Analytical Techniques: Untargeted gas chromatography/mass spectrometry (GC/MS) has been widely applied to characterize the urine metabolome in DASH diet studies [56]. For comprehensive food compound analysis, liquid chromatography mass spectrometry (LC/MS) with reverse phase C18 columns and Time-of-Flight-MS with dual electrospray ionization sources provide high-resolution data [61]. In the DASH-Sodium trial analysis, researchers evaluated 938 metabolites using multivariable linear regression and partial least-squares discriminant analysis to identify discriminatory metabolites between dietary patterns [60].

Data Processing and Normalization: Metabolomic data processing typically involves using specialized software such as MassHunter Profinder and Mass Profiler Professional for compound identification and quantification [61]. Data normalization approaches include total useful signal normalization, with filtering applied to remove compounds present in preparation blanks and instrument blanks [61]. Statistical analyses employ false discovery rate (FDR) correction to account for multiple testing in exploratory analyses, with FDR <0.20 often considered significant in nutrimetabolomic studies [56].

Body Composition Assessment Methods

Anthropometric Measurements: Standardized protocols for body composition assessment include body weight measured to the nearest 0.1 kg using digital scales, with participants wearing lightweight clothing [8]. Height measurements are taken with participants standing barefoot against a wall with proper alignment. Abdominal circumference is measured as an indicator of central adiposity, with significant reductions observed in both DASH and intermittent fasting interventions [8] [59].

Advanced Body Composition Analysis: In the Iranian National Obesity Registry study, researchers employed comprehensive body composition metrics including phase angle, body water balance, and fat-free mass index, which provide insights into cellular health and hydration status beyond traditional metrics [58]. The DASH with time-restricted eating study utilized extracellular water measurement as a marker of fluid balance, finding significant associations with blood pressure reduction [40]. Bioelectrical impedance analysis (BIA) and BodPod measurements are commonly used to quantify fat mass, fat-free mass, and visceral adipose tissue [57].

Hepatic Health Assessment: For patients with metabolic-associated fatty liver disease (MAFLD), controlled attenuation parameter (CAP) measured via FibroScan provides a non-invasive assessment of hepatic steatosis [8]. This technique has demonstrated significant improvements in patients undergoing combined DASH and time-restricted feeding interventions, indicating reduced liver fat content.

Dietary Intervention Protocols

DASH Diet Implementation: The DASH diet emphasizes consumption of fruits, vegetables, low-fat dairy products, whole grains, poultry, fish, and nuts while limiting red meats, sweets, and sugar-sweetened beverages [60] [40]. In controlled feeding studies, the diet is typically designed to provide specific nutrient distributions: 53-58% carbohydrates, 15-18% protein, and 26-30% fat, with increased fiber, potassium, magnesium, and calcium compared to control diets [25]. Sodium restriction is often incorporated, with levels targeted to <2,300 mg daily [25].

Intermittent Feeding Protocols: Various intermittent fasting approaches have been investigated, including the 5:2 protocol (500-600 kcal on fasting days) [57], time-restricted feeding (16:8 with 8-hour eating window) [8] [40], and alternate-day fasting [58]. In combined approaches with the DASH diet, the 16:8 time-restricted model (16-hour fast, 8-hour eating window) has been successfully implemented, with participants typically consuming their food between 9:00 a.m. to 5:00 p.m. [40].

Metabolic Pathways and Physiological Mechanisms

Diagram 1: Metabolic Pathways in DASH and Intermittent Fasting Interventions. This diagram illustrates the key mechanistic pathways through which DASH and intermittent fasting regimens influence measurable biomarkers, culminating in improved body composition and blood pressure outcomes.

The Scientist's Toolkit: Essential Research Reagents and Methodologies

Table 4: Essential Research Reagents and Analytical Tools for Dietary Intervention Studies

Category	Tool/Reagent	Specific Application	Research Function	Example Use Case
Analytical Instruments	GC/MS (Gas Chromatography/Mass Spectrometry)	Untargeted metabolomic profiling	Identification and quantification of small molecules in biospecimens	Urinary metabolite detection in DASH diet studies [56]
Analytical Instruments	LC/MS (Liquid Chromatography/Mass Spectrometry)	Food-specific compound analysis	Comprehensive characterization of food chemical compositions	Identification of unique compounds in DASH diet foods [61]
Analytical Instruments	FibroScan 502 Touch with CAP	Hepatic steatosis assessment	Non-invasive measurement of liver fat content	MAFLD management studies [8]
Body Composition Tools	BodPod	Body fat and fat-free mass measurement	Air displacement plethysmography for body composition	Body composition changes in IF interventions [57]
Body Composition Tools	Bioelectrical Impedance Analysis	Body water compartment measurement	Differentiation of intracellular and extracellular water	Fluid balance assessment in TRE studies [40]
Biomonitoring Kits	KetoDiastrix tests (Bayer)	Ketone body monitoring	Semi-quantitative measurement of urinary ketones	Nutritional ketosis verification in ketogenic diets [62]
Biomonitoring Kits	Optium Xido Neo FreeStyle glucometer with β-ketone strips	Blood glucose and ketone monitoring	Simultaneous measurement of glucose and ketone bodies	Metabolic adaptation tracking in IF studies [62]
Software Solutions	Nutritionist IV software	Dietary intake analysis	Calculation of energy and nutrient composition from food records	Dietary adherence monitoring [8]
Software Solutions	MassHunter Profinder and Mass Profiler Professional	Metabolomic data processing	Untargeted data mining and statistical analysis	Urinary metabolome analysis [61]

Discussion: Integration of Biomarker Data for Comprehensive Intervention Assessment

The comparative analysis of biomarker assessment methodologies reveals distinctive patterns of physiological response to DASH versus intermittent fasting interventions. The DASH diet produces a characteristic urinary metabolomic signature rich in phenolic acids and their microbial metabolites, reflecting high intake of plant-based foods and suggesting potential mechanisms involving microbial metabolism and reduced inflammation [60] [56]. Intermittent fasting regimens demonstrate pronounced effects on body composition, particularly when combined with exercise, with preservation of fat-free mass and phase angle suggesting protective effects on cellular structure and function [58] [57].

The combination of DASH with time-restricted feeding appears to leverage complementary mechanisms, enhancing improvements in both metabolic and cardiovascular health markers [8] [40]. The significant reduction in controlled attenuation parameter (CAP) observed in MAFLD patients undergoing combined intervention suggests synergistic benefits for hepatic health [8]. The association between increased urinary sodium excretion and blood pressure reduction in time-restricted feeding implementations points to fluid balance regulation as an additional mechanism beyond sodium restriction alone [40].

For researchers and drug development professionals, these findings highlight the value of multidimensional biomarker assessment in characterizing the full therapeutic potential of dietary interventions. The integration of urinary metabolomics with advanced body composition analysis and traditional clinical endpoints provides a more comprehensive understanding of intervention effects, potentially informing the development of targeted therapies that mimic or enhance these beneficial physiological changes.

Addressing Limitations, Safety, and Synergistic Strategies

Within the field of non-pharmacological hypertension management, the Dietary Approaches to Stop Hypertension (DASH) diet and various intermittent fasting (IF) regimens represent two prominent dietary strategies. While both approaches demonstrate efficacy in blood pressure reduction, the comparative evidence base is characterized by significant inconsistencies, particularly concerning long-term adherence and outcomes across different patient subgroups. This divergence presents a substantial challenge for researchers and clinicians seeking to optimize personalized dietary interventions. The underlying causes of these conflicting findings are multifaceted, stemming from variations in study methodologies, participant characteristics, and intervention protocols. This analysis systematically examines the comparative effectiveness of DASH versus IF for blood pressure control, with specific focus on methodological sources of heterogeneity, subgroup response variations, and adherence patterns that complicate direct comparison and clinical translation. By critically evaluating experimental data and trial designs, this guide provides a framework for interpreting contradictory evidence and identifies key considerations for future research design.

Methodological Approaches in Key Investigations

Understanding the fundamental differences in experimental protocols is essential for interpreting the conflicting outcomes between DASH and IF interventions. The methodologies employed in key trials reflect divergent approaches to dietary modification, which subsequently influence the observed outcomes and their applicability to different patient populations.

DASH Diet Trial Designs

The DASH diet's efficacy is supported by several landmark trials characterized by tightly controlled nutritional composition. The foundational DASH-Sodium trial employed a crossover design where participants received both control and DASH diets at three sodium levels (high, intermediate, and low) in random order [2]. This sophisticated design enabled researchers to isolate the independent and synergistic effects of dietary pattern and sodium restriction. The standard DASH intervention emphasizes specific food group consumption: fruits (4-5 servings/day), vegetables (4-5 servings/day), low-fat dairy (2-3 servings/day), whole grains, and lean proteins while limiting saturated fats, sweets, and red meat [2] [63]. Macronutrient composition is typically targeted at approximately 55% carbohydrates, 18% protein, and 27% fat, with emphasis on potassium, magnesium, and calcium intake [2].

Later implementations, such as the PREMIER trial, combined the DASH diet with other lifestyle modifications including weight management and physical activity, demonstrating the feasibility of integrating this dietary pattern within comprehensive behavioral interventions [2]. The OmniHeart trial further modified the DASH approach by substituting carbohydrates with either protein or unsaturated fats, revealing that these variations could potentially enhance the diet's blood pressure-lowering effects [2]. More recent trials have adapted the DASH protocol for specific populations, including overweight and obese children, demonstrating the diet's flexibility across age groups while maintaining core nutritional principles [25].

Intermittent Fasting Protocol Variations

In contrast to the nutrient-focused DASH approach, IF trials primarily manipulate temporal eating patterns, creating significant methodological heterogeneity. Network meta-analyses have categorized IF into four predominant protocols with distinct characteristics [64]:

• Time-Restricted Eating (TRE): Confines daily food intake to a specific window (typically 4-12 hours) with complete fasting during remaining hours [64] [19]. The 16/8 method (16-hour fast, 8-hour eating window) is most common.
• Modified Alternate-Day Fasting (mADF): Alternates between ad libitum feeding days and modified fasting days (approximately 25% of normal calorie intake) [64].
• Alternate-Day Fasting (ADF): Cycles between 24-hour periods of complete fasting and normal eating [19].
• Periodic Fasting (PF): Involves 1-2 fasting days per week (consuming 500-600 calories) with normal eating on other days, often implemented as the 5:2 diet [64] [9].

This protocol diversity creates substantial challenges for comparative effectiveness research. Unlike the standardized nutritional composition of DASH, IF studies typically impose no specific nutritional requirements during feeding periods, potentially allowing significant variations in diet quality that confound blood pressure outcomes [19]. Furthermore, intervention durations range dramatically from several weeks to months, with few investigations extending beyond 6-12 months, creating significant evidence gaps regarding long-term sustainability and effects [64] [19].

Table 1: Key Methodological Characteristics of DASH vs. Intermittent Fasting Trials

Characteristic	DASH Diet Trials	Intermittent Fasting Trials
Primary Focus	Nutritional composition	Temporal eating pattern
Core Intervention	Specific food groups and nutrients	Fasting/feeding windows
Nutritional Specifications	Detailed micronutrient and macronutrient targets	Typically none beyond calorie restriction during fast periods
Common Duration	8 weeks to 6 months	2 weeks to 12 months
Control Group	Typical Western diet	Usual diet or continuous energy restriction
Key Measurements	Office BP, ambulatory BP, urinary electrolytes	Office BP, weight, body composition, metabolic panels

Comparative Quantitative Outcomes and Efficacy Rankings

Direct comparison of DASH and IF through network meta-analysis provides valuable insights into their relative efficacy for blood pressure control and management of associated cardiovascular risk factors. The quantitative outcomes reveal distinct profiles of effectiveness that may inform personalized intervention selection.

Blood Pressure Reduction Efficacy

A 2025 network meta-analysis comprising 21 randomized controlled trials (1,663 participants) directly compared the blood pressure-lowering effects of eight dietary patterns, including DASH and IF [55]. The analysis demonstrated that the DASH diet produced the most substantial reduction in systolic blood pressure among all evaluated diets, with a mean difference (MD) of -7.81 mmHg (95% CI: -14.2 to -0.46) compared to control diets, earning a Surface Under the Cumulative Ranking Curve (SUCRA) score of 89 for this outcome [55]. Intermittent fasting also showed significant systolic blood pressure reduction (MD -5.98 mmHg, 95% CI: -10.4 to -0.35) with a SUCRA score of 76, positioning it as moderately effective but statistically inferior to DASH for this specific parameter [55].

Further analysis of IF subtypes revealed important nuances in blood pressure efficacy. Modified alternate-day fasting demonstrated particularly strong effects, reducing systolic blood pressure by -7.24 mmHg (95% CI: -11.90 to -2.58) and diastolic blood pressure by -4.70 mmHg (95% CI: -8.46 to -0.95) compared to usual diet [64]. Time-restricted eating also showed significant diastolic blood pressure reduction (MD -3.24 mmHg, 95% CI: -4.69 to -1.79) [64]. These findings suggest that while DASH appears superior overall, specific IF protocols may offer competitive blood pressure control for certain patient populations.

A separate meta-analysis of 30 DASH trials (5,545 participants) confirmed the diet's consistent efficacy across hypertension status, demonstrating average reductions of -3.2 mmHg systolic (95% CI: -4.2 to -2.3) and -2.5 mmHg diastolic (95% CI: -3.5 to -1.5) compared to control diets [63]. This analysis notably found that the DASH diet's effectiveness was enhanced in settings with higher baseline sodium intake (>2400 mg/day), highlighting the importance of contextual factors in interpreting efficacy data [63].

Comprehensive Cardiovascular Risk Factor Management

Beyond blood pressure specificity, the comparative effects on additional cardiovascular risk factors reveal distinct advantage profiles that may guide intervention selection based on comprehensive risk assessment.

Table 2: Comparative Effects on Cardiovascular Risk Factors: DASH vs. Intermittent Fasting

Risk Factor	DASH Diet	Intermittent Fasting	Most Effective Intervention
Body Weight	Moderate reduction	Significant reduction [55]	Ketogenic (SUCRA 99) > High-Protein > IF [55]
Waist Circumference	Moderate reduction	Significant reduction (mADF: -3.55 cm; TRE: -3.00 cm) [64]	Ketogenic (SUCRA 100) > Low-carbohydrate > IF [55]
HDL-C	Minimal improvement	Minimal improvement	Low-carbohydrate (SUCRA 98) > Low-fat > IF [55]
LDL-C	Significant reduction [2]	Inconsistent effects	DASH > IF [2] [19]
Fasting Glucose	Moderate improvement	Significant improvement (TRE: -3.74 mg/dL) [64]	IF ≥ DASH [64]

The data reveal a pattern of intervention-specific strengths: DASH demonstrates particular efficacy for blood pressure control and lipid management, while IF shows advantages for weight loss and glucose metabolism [55] [2] [64]. This divergence suggests potential for personalized intervention selection based on individual risk factor profiles rather than a universal superiority of either approach.

Subgroup Variations and Adherence Considerations

Differential responses across patient subgroups and variable adherence patterns represent significant sources of inconsistent outcomes in the comparative literature. Understanding these moderating factors is crucial for interpreting conflicting evidence and personalizing dietary recommendations.

Determinants of Variable Treatment Response

Multiple studies have identified specific patient characteristics that modify the blood pressure response to DASH and IF interventions:

• Age Effect: The blood pressure-lowering effect of the DASH diet appears more pronounced in younger populations (<50 years) compared to older participants, suggesting potential age-related modifications in response [63].
• Sodium Intake Interaction: The DASH diet's efficacy is significantly enhanced in high sodium intake environments (>2400 mg/day), with greater systolic blood pressure reductions observed compared to low sodium conditions [63]. This interaction highlights the importance of considering baseline dietary patterns when predicting intervention success.
• Hypertension Status: While the DASH diet benefits both normotensive and hypertensive individuals, those with established hypertension typically experience greater absolute blood pressure reductions [2] [63]. Intermittent fasting's blood pressure effects appear less modified by baseline hypertension status, suggesting more consistent relative effects across this subgroup division [64] [9].
• Comorbidities: Emerging evidence suggests that combining DASH with IF (specifically time-restricted eating) may provide enhanced benefits for patients with metabolic-associated fatty liver disease, improving both hepatic parameters and cardiovascular risk factors [8]. This synergistic effect illustrates the potential for targeted combination approaches in specific clinical populations.

Adherence Patterns and Long-Term Sustainability

Long-term adherence represents a critical challenge for both dietary approaches, with distinct barriers and facilitators affecting their sustainability:

• DASH Diet Adherence: The DASH diet requires significant changes in food selection, preparation, and pattern, potentially creating implementation barriers related to cost, food availability, and culinary habits [2]. Successful implementation strategies typically incorporate structured meal planning, shopping guidance, and ongoing nutritional education or counseling [2]. Technology integration through mobile applications and digital tracking tools shows promise for improving long-term adherence by simplifying compliance monitoring [2].
• Intermittent Fasting Adherence: IF protocols face distinct adherence challenges related to hunger during fasting periods, social disruptions, and potential compensatory overeating during feeding windows [19]. Modified alternate-day fasting (allowing 25% of calories on fast days) generally demonstrates better long-term adherence than strict alternate-day fasting [64]. Time-restricted eating typically shows higher sustainability than other IF variants due to its alignment with natural circadian rhythms and relatively minor daily disruption [64] [19].

Notably, a 6-month randomized trial comparing IF (5:2 diet) with continuous energy restriction found nearly identical adherence rates and completion percentages between groups, suggesting that perceived adherence advantages for IF may not manifest consistently in controlled settings [9]. However, qualitative data indicate that some patients strongly prefer the structured yet intermittent nature of certain IF protocols over daily restriction, highlighting the importance of individual preferences in long-term success [64] [9].

Research Reagents and Methodological Tools

Standardized assessment tools and specialized reagents are essential for generating comparable data across DASH and IF studies. The following research toolkit outlines critical methodological components for rigorous investigation of these dietary interventions.

Table 3: Essential Research Reagents and Methodological Tools for Dietary Intervention Studies

Tool/Reagent	Primary Function	Application in DASH/IF Research
24-hour Urinary Sodium	Objective sodium intake assessment	Critical for verifying DASH diet compliance and sodium restriction [25]
Controlled Attenuation Parameter (FibroScan)	Hepatic steatosis quantification	Used in MAFLD studies combining DASH and IF [8]
Automated Office BP Devices	Standardized blood pressure measurement	Reduces measurement bias in cardiovascular outcomes [25]
Food Frequency Questionnaires	Dietary pattern assessment	Validated instruments essential for compliance monitoring [8]
Body Composition Analyzers	Fat mass/fat-free mass differentiation	Critical for evaluating muscle mass preservation during IF [19] [8]
Physical Activity MET Questionnaires	Activity level quantification	Important covariate for energy balance calculations [8]

Conceptual Framework for Evidence Interpretation

The relationship between dietary intervention characteristics and cardiovascular outcomes involves multiple direct and moderating pathways. The following diagram synthesizes the key mechanisms and confounding variables that contribute to inconsistent research outcomes across studies.

Diagram 1: Mechanisms and Moderators in DASH vs. IF Research

This conceptual framework illustrates how the distinct primary mechanisms of DASH (nutritional composition) and IF (temporal pattern) activate overlapping but divergent pathways toward cardiovascular risk reduction. The model further identifies key moderating variables and methodological confounders that contribute to inconsistent findings across studies, providing a systematic approach for interpreting contradictory evidence.

The comparative evidence base for DASH versus intermittent fasting reveals a complex landscape of intervention-specific advantages, moderated effects, and methodological challenges. The DASH diet demonstrates superior efficacy for blood pressure reduction as a standalone outcome, particularly in high sodium environments and younger populations. Intermittent fasting shows competitive blood pressure effects for specific protocols (particularly modified alternate-day fasting) while offering enhanced benefits for weight management and glucose control. The inconsistent outcomes observed across studies largely reflect heterogeneity in participant characteristics, intervention protocols, adherence patterns, and methodological approaches rather than true equipoise in efficacy.

Future research should prioritize head-to-head trials with standardized outcome assessments, longer follow-up durations, and pre-specified subgroup analyses to clarify optimal matching between patient profiles and dietary strategies. Additionally, investigation of combined approaches (DASH plus IF) represents a promising direction for enhancing therapeutic efficacy while mitigating the limitations of either approach in isolation. By systematically addressing the sources of conflict in the existing evidence base, researchers and clinicians can advance toward more personalized, effective dietary interventions for blood pressure control and cardiovascular risk reduction.

The management of hypertension and associated cardiovascular diseases increasingly prioritizes non-pharmacological, lifestyle-based interventions. Among these, the Dietary Approaches to Stop Hypertension (DASH) diet is a well-established, guideline-recommended eating pattern [4]. In recent years, Intermittent Fasting (IF) has gained significant traction as a potential strategy for improving cardiometabolic health. However, a comprehensive safety profile evaluating its associated cardiovascular risks and potential for nutrient deficiencies is crucial for researchers and clinicians. This guide provides an objective comparison of IF and the DASH diet, synthesizing the latest experimental data on efficacy, safety, and underlying mechanisms to inform future research and drug development.

Comparative Efficacy & Safety: Quantitative Data Synthesis

The following tables summarize key quantitative findings from recent clinical studies and analyses, comparing the effects of IF and the DASH diet on cardiovascular risk factors and mortality.

Table 1: Comparative Effects on Blood Pressure and Anthropometrics

Outcome Measure	Intermittent Fasting (IF)	DASH Diet	Comparative Notes
Systolic BP (SBP) Reduction	-8.5 mmHg (with DASH) [7]-7.2 mmHg (Modified ADF) [65]	-5.6 mmHg (alone) [7]-7.8 mmHg (Network Meta-Analysis) [26]	DASH + TRE (Time-Restricted Eating) shows superior reduction versus DASH alone.
Diastolic BP (DBP) Reduction	-9.5 mmHg (with DASH) [7]-4.7 mmHg (Modified ADF) [65]	-5.4 mmHg (alone) [7]	IF regimens demonstrate strong efficacy in DBP reduction.
Weight Reduction	-7.0 kg (IER) [9]-5.2 kg (Modified ADF) [65]	Not the primary focus; ~1.42 kg reduction shown in meta-analyses [9]	IF protocols are highly effective for weight loss, a key contributor to BP reduction.
Waist Circumference	-3.6 cm (Modified ADF) [65]-3.0 cm (TRE) [65]	Data not prominently featured in cited results	IF effectively reduces central adiposity.

Table 2: Safety Profile: Cardiovascular Mortality & Nutrient Deficiencies

Safety Aspect	Intermittent Fasting (IF)	DASH Diet	Comparative Notes
CV Mortality Risk	91% higher risk of CV death with 8-hour TRE in observational study [46]	No such risk association reported; recommended for heart health [4]	This finding requires careful interpretation; causality not proven.
Nutrient Deficiency Risk	High risk in "Nutrient Deprived" patterns associated with 61% higher CV mortality [66]	Designed to be rich in potassium, calcium, magnesium, fiber, and protein [4]	IF may inadvertently lead to low intake of essential nutrients if diet quality is not maintained.
Effect on Lipid Profile	Favorable improvements noted, comparable to CER [9]	Beneficial effects on lipid markers [67] [26]	Both can improve lipids, though specific effects vary by IF type.
Key Protective Nutrients	Not specifically designed to target micronutrients.	Specifically emphasizes vitamins (A, D, E, K), minerals (Zn, Ca, Mg), and fiber [67] [4]	DASH diet is structured to automatically address nutrient adequacy.

Experimental Protocols & Methodologies

A critical evaluation of the evidence requires an understanding of the underlying experimental designs.

Key Clinical Trial: DASH vs. DASH+TRE

• Objective: To determine if combining TRE with the DASH diet yields greater benefits for stage 1 primary hypertension than the DASH diet alone [7].
• Design: 6-week randomized controlled trial.
• Participants: 74 patients with stage 1 primary hypertension.
• Intervention:
  • DASH Group (n=37): Followed the DASH eating plan without time restrictions.
  • DASH+TRE Group (n=37): Followed the DASH diet while consuming all food within an 8-hour window (9:00 a.m. to 5:00 p.m.).
• Data Collection: Blood pressure, body composition, urinary sodium excretion, and other cardiometabolic risk factors were measured. Adherence was tracked via a scientific research platform on WeChat [7].

Key Clinical Trial: Intermittent vs. Continuous Energy Restriction

• Objective: To compare the effects of IER (5:2 diet) with continuous energy restriction (CER) on blood pressure and weight loss in obese hypertensive patients [9].
• Design: 6-month randomized clinical trial.
• Participants: 205 overweight or obese participants with hypertension.
• Intervention:
  • IER Group: Consumed a very-low-calorie diet (500 kcal/day for women, 600 kcal/day for men) for 2 non-consecutive days per week and ate habitually for the other 5 days.
  • CER Group: Consumed a moderate daily calorie restriction (1,000 kcal/day for women, 1,200 kcal/day for men) for 7 days a week.
• Data Collection: Changes in BP, weight, body composition, HbA1c, and blood lipids were measured [9].

Observational Study on CV Mortality

• Objective: To investigate the long-term health impact of an 8-hour time-restricted eating schedule [46].
• Design: Analysis of over 20,000 U.S. adults using data from the NHANES (2003-2018) linked to mortality records up to 2019.
• Methodology: Dietary patterns were assessed from two 24-hour recall questionnaires. Participants were categorized based on their daily eating window, and mortality outcomes were compared [46].

Analysis of Nutrient Deficiency Patterns

• Objective: To identify patterns of nutrient deficiency and their association with mortality in older adults with hypertension [66].
• Design: Population-based study using NHANES data (2003-2014).
• Methodology: Latent class analysis (LCA) was applied to data on 15 nutrients (vitamins A, B1, B12, C, D, E, K, fiber, folate, calcium, magnesium, zinc, copper, iron, selenium) to identify distinct deficiency patterns. These patterns were then linked to all-cause and cardiovascular mortality [66].

Mechanistic Insights: Pathways of Action

The following diagram illustrates the potential biological pathways through which Intermittent Fasting, particularly Time-Restricted Eating (TRE), may influence blood pressure and cardiovascular risk, based on cited research.

Mechanistic Pathways of Intermittent Fasting in Blood Pressure Regulation

The Scientist's Toolkit: Research Reagent Solutions

Table 3: Essential Reagents and Assays for Cardiovascular and Nutritional Research

Research Tool	Primary Function / Application	Exemplar Use in Context
Liquid Chromatography-Mass Spectrometry (LC-MS/MS)	High-sensitivity quantification of vitamins, metabolites (e.g., TMAO), and hormones.	Used to measure serum levels of vitamins A, D, E, and K in micronutrient panels [67].
Inductively Coupled Plasma Mass Spectrometry (ICP-MS)	Precise measurement of mineral and trace element levels (e.g., Zn, Ca, Mg, Se) in biological samples.	Employed for analyzing mineral content in serum for nutritional status assessment [67].
Immunoturbidimetric Assay	Automated, high-throughput measurement of specific proteins and apolipoproteins.	Used to quantify Apolipoproteins A1 and B, key markers for cardiovascular risk [67].
16S rRNA Sequencing & Metagenomics	Profiling the composition and functional potential of the gut microbiome.	Critical for identifying IF-induced shifts in microbial abundance (e.g., Akkermansia) [31].
Gas Chromatography-Mass Spectrometry (GC-MS)	Separation and quantification of volatile compounds, including short-chain fatty acids (SCFAs).	Used to measure fecal SCFA levels (acetate, propionate, butyrate) in microbiota studies [31].
Enzymatic/Colorimetric Assays	Standardized clinical chemistry analysis of lipids (LDL, HDL, TG), glucose, and other biomarkers.	The core methodology for standard lipid panel and glucose measurement in clinical trials [67] [9].

The evidence presents a nuanced profile for Intermittent Fasting. While certain regimens like modified alternate-day fasting and time-restricted eating demonstrate significant efficacy in reducing blood pressure and weight [65], emerging data signals a need for caution. The association between 8-hour TRE and a significantly increased risk of cardiovascular death [46], alongside the established dangers of nutrient-deficient dietary patterns in hypertensive populations [66], cannot be overlooked.

For the research and drug development community, these findings highlight several critical avenues:

• Mechanistic Exploration: The biological pathways linking specific IF schedules to negative long-term outcomes must be elucidated.
• Nutrient Quality: The role of diet composition and nutrient density within the IF eating window as a critical effect modifier requires rigorous investigation.
• Personalized Approaches: Future studies must stratify outcomes based on baseline cardiovascular health, age, and medication use to identify which patients, if any, are most likely to benefit from IF with minimal risk.

In contrast, the DASH diet offers a robust safety profile and predictable efficacy, reinforced by its specific design to provide cardiovascular-protective nutrients [67] [4]. The combination of DASH with TRE may offer superior blood pressure reduction [7], but the long-term safety of this hybrid approach warrants further study. Ultimately, this comparison underscores that dietary strategies for hypertension management must be evaluated not only for their short-term efficacy but also for their long-term safety and nutritional adequacy.

The management of hypertension and related metabolic syndromes remains a paramount challenge in public health. Within the non-pharmacological arsenal, the Dietary Approaches to Stop Hypertension (DASH) diet has long been established as a cornerstone dietary intervention, proven to significantly reduce blood pressure through its specific nutrient profile [63]. More recently, Time-Restricted Eating (TRE), a form of intermittent fasting, has gained prominence for its benefits on metabolic health. This guide objectively compares the performance of the DASH diet alone against its combination with TRE, framing this analysis within the broader research question of DASH diet versus intermittent fasting for blood pressure control. The synthesis of experimental data presented herein is intended to inform researchers, scientists, and drug development professionals about the potential for synergistic, non-pharmacological combination therapies.

Comparative Efficacy: Quantitative Outcomes Analysis

The following tables summarize key quantitative findings from recent controlled trials, comparing the effects of the DASH diet alone versus the DASH+TRE combination on blood pressure and metabolic parameters.

Table 1: Blood Pressure and Cardiovascular Outcomes

Outcome Measure	DASH Diet Alone	DASH + TRE Combination	Notes
Systolic BP (SBP) Reduction	-5.595 ± 4.072 mmHg [40]	-8.459 ± 4.260 mmHg [40]	Greater reduction in DASH+TRE group [40].
Diastolic BP (DBP) Reduction	-5.351 ± 5.643 mmHg [40]	-9.459 ± 4.375 mmHg [40]	Greater reduction in DASH+TRE group [40].
BP Diurnal Rhythm	Information not specified	Improvement observed [40]	DASH+TRE improved circadian rhythm [40].
Urinary Na+ Excretion	Information not specified	Increased [40]	Associated with BP reduction [40].
Extracellular Water	Information not specified	Decreased [40]	Associated with BP reduction [40].

Table 2: Metabolic and Hepatic Outcomes

Outcome Measure	DASH Diet Alone	DASH + TRE Combination / Other Diets	Notes
Body Mass Index (BMI)	Minimal change without caloric restriction [68]	Significant reduction in DASH+TRE vs control [8]	Study involved MAFLD patients [8].
Abdominal Circumference	Information not specified	Significant reduction in DASH+TRE vs control [8]	Study involved MAFLD patients [8].
Hepatic Steatosis (CAP score)	Information not specified	Significant reduction in DASH+TRE vs control [8]	Study involved MAFLD patients [8].
Liver Enzymes (ALT, AST)	Information not specified	Significant reduction in DASH+TRE vs control [8]	Study involved MAFLD patients [8].
Insulin & HOMA-IR	Minimal improvement alone [68]	Significant reduction in DASH+TRE vs control [8]	Study involved MAFLD patients. DASH+WM improved insulin sensitivity [68].
Fasting Glucose	Minimal improvement alone [68]	Information not specified	DASH+WM (with exercise/caloric restriction) showed improvement [68].
Blood Lipids (Total Cholesterol, Triglycerides)	Minimal improvement alone [68]	Information not specified	DASH+WM (with exercise/caloric restriction) showed improvement [68].

Experimental Protocols and Methodologies

A critical understanding of the data requires an examination of the underlying experimental designs. The featured trials share a randomized controlled trial (RCT) framework but differ in specific protocols.

DASH with 8-hour TRE in Primary Hypertension (2024)

This 6-week trial investigated the incremental benefit of adding TRE to the DASH diet in stage 1 hypertensive patients [40].

• Participants: 74 adults with stage 1 primary hypertension (SBP 130-139 or DBP 80-89 mmHg) without high-risk comorbidities [40].
• Randomization & Groups: Participants were randomly assigned to either the DASH group (n=37) or the DASH+TRE group (n=37) using a random numbers table [40].
• Interventions:
  • DASH Group: Followed the standard DASH diet principles without any time restriction on eating [40].
  • DASH+TRE Group: Adhered to the DASH diet but consumed all daily calories within a defined 8-hour window (from 9:00 a.m. to 5:00 p.m.), fasting for the remaining 16 hours [40].
• Outcomes: Primary outcome was blood pressure change. Secondary outcomes included body composition, cardiometabolic risk factors, urinary Na+ excretion, and safety [40].
• Adherence & Monitoring: A scientific research platform within the WeChat application was used for dietary counseling, communication, and tracking participant adherence [40].

DASH with 16/8 Time-Restricted Feeding in MAFLD (2025)

This 12-week RCT evaluated the combination of a DASH diet and a 16/8 TRE pattern in patients with Metabolic-Associated Fatty Liver Disease (MAFLD) [8].

• Participants: Patients with MAFLD, stratified by BMI and age [8].
• Randomization & Groups: Participants were randomly assigned to either a DASH+TRF group (n=27) or a control group (n=26) following a standard low-calorie diet [8].
• Interventions:
  • DASH+TRF Group: Followed a DASH diet combined with a 16/8 time-restricted feeding regimen (16-hour fast, 8-hour eating window) [8].
  • Control Group: Followed a weight-loss diet with matched caloric deficit (-500 kcal/day) and macronutrient composition, but without time restriction [8].
• Outcomes: Primary outcomes were liver biomarkers (enzymes, CAP score). Secondary outcomes included anthropometric indices, glycemic parameters, lipid profile, and inflammatory markers [8].
• Adherence & Monitoring: Adherence was monitored via weekly phone calls and monthly 24-hour dietary recalls over three days [8].

Figure 1: Experimental Workflow for DASH and TRE Combination Trials. This diagram illustrates the common design of RCTs comparing DASH alone versus DASH+TRE, from patient recruitment through outcome measurement.

Mechanistic Insights: Unifying Physiological Pathways

The superior outcomes observed with the DASH+TRE combination suggest activation of multiple, complementary physiological pathways. The diagram below synthesizes the key mechanisms supported by the experimental data.

Figure 2: Proposed Synergistic Mechanisms of DASH and TRE. The DASH diet and TRE act on distinct but complementary physiological pathways to produce a greater blood pressure-lowering effect.

The Scientist's Toolkit: Key Research Reagents and Materials

Table 3: Essential Materials and Methods for Clinical Trial Replication

Item	Function & Application in Research
WeChat Scientific Research Platform	A digital tool for tracking participant adherence, providing dietary counseling, and collecting questionnaire data in real-time [40].
Controlled Attenuation Parameter (CAP)	A non-invasive method assessed via FibroScan to quantify hepatic steatosis (liver fat) as a primary outcome in MAFLD trials [8].
Continuous Glucose Monitor (CGM)	A wearable device that measures interstitial glucose levels at regular intervals, providing comprehensive data on glycemic control and variability [53] [69].
24-Hour Urinary Na+ Analysis	The gold-standard method for assessing dietary sodium intake and renal handling of sodium, a key mechanism in blood pressure regulation [40] [70].
Dual-Energy X-ray Absorptiometry (DEXA)	Provides precise measurements of body composition, including fat mass, lean body mass, and percent body fat [68].
Random Numbers Table	A simple yet robust tool for ensuring unbiased random allocation of participants to different intervention groups in a clinical trial [40].
Standardized Food Frequency Questionnaire (FFQ) & Food Diaries	Validated self-report instruments for the independent assessment of dietary content and nutritional intake during free-living interventions [68].

The collective evidence from recent randomized controlled trials indicates that the combination of the DASH diet and Time-Restricted Eating holds significant synergistic potential for managing hypertension and related metabolic disorders. The data consistently show that DASH+TRE elicits greater reductions in both systolic and diastolic blood pressure compared to the DASH diet alone, while also conferring enhanced benefits on body composition, hepatic health, and insulin sensitivity [40] [8].

This synergy appears to stem from the engagement of complementary mechanisms: the DASH diet provides the optimal nutrient composition for cardiovascular health, while TRE imposes a metabolic schedule that promotes fluid balance, weight loss, and circadian rhythm optimization [40]. For researchers and clinicians, these findings suggest that a combined dietary approach could be a more powerful non-pharmacological strategy than either intervention in isolation. For the drug development community, these lifestyle interventions and their mechanisms offer insights into novel therapeutic targets. Future research should focus on long-term efficacy, molecular mechanisms, and personalized application to fully harness the potential of this promising combination therapy.

The management of hypertension, a primary contributor to global cardiovascular disease and mortality, has long included dietary interventions as a first-line therapeutic strategy [7]. Among the most studied approaches are the Dietary Approaches to Stop Hypertension (DASH) diet and various forms of intermittent fasting (IF), including time-restricted eating (TRE) [9] [7]. While both demonstrate efficacy in blood pressure control, emerging research highlights significant variability in individual responses, underscoring the limitation of one-size-fits-all dietary recommendations. This review examines the evidence for personalizing dietary interventions based on phenotypic characteristics, comorbid conditions, and genetic predispositions, framing this approach within the broader context of precision nutrition for hypertension management.

The DASH diet establishes a well-defined nutritional pattern emphasizing fruits, vegetables, low-fat dairy products, and reduced saturated fat intake while limiting sodium consumption [4]. Intermittent fasting encompasses various eating patterns that cycle between periods of fasting and eating, with the 16:8 approach (16-hour fast, 8-hour eating window) and 5:2 diet (severe calorie restriction for 2 days per week) being among the most studied [9] [49]. Understanding how these interventions interact with individual characteristics is crucial for optimizing their therapeutic potential in blood pressure control.

Direct Comparative Evidence: DASH vs. Intermittent Fasting

Clinical Outcomes in Hypertensive Populations

Randomized controlled trials provide the most robust evidence for comparing dietary interventions. A 6-month study of 205 overweight or obese participants with hypertension directly compared intermittent energy restriction (IER using the 5:2 diet) with continuous energy restriction (CER akin to DASH principles) [9]. The results demonstrated comparable effectiveness for both weight loss and blood pressure reduction, with no statistically significant differences between groups.

Table 1: Six-Month Randomized Trial Comparing IER and CER in Hypertension

Outcome Measure	Intermittent Energy Restriction (IER)	Continuous Energy Restriction (CER)	P-value
Weight Change (kg)	-7.0 [0.6]	-6.8 [0.6]	0.62
Systolic BP Reduction (mmHg)	-7 [0.7]	-7 [0.6]	0.39
Diastolic BP Reduction (mmHg)	-6 [0.5]	-5 [0.5]	0.41
Improvements in Body Composition	Yes	Yes	NS
Improvements in HbA1c & Blood Lipids	Yes	Yes	NS

Values for weight and blood pressure represent mean [SEM]; NS = not statistically significant [9]

Another 6-week randomized controlled trial investigated the synergistic effects of combining these approaches in stage 1 hypertensive patients [7]. Seventy-four participants were assigned to either DASH alone or DASH plus TRE (8-hour eating window). The combination therapy yielded significantly greater blood pressure reduction than DASH alone, suggesting potential complementary mechanisms.

Table 2: Combined DASH and TRE in Stage 1 Hypertension (6-Week Trial)

Parameter	DASH Alone	DASH + TRE	Additional Benefit
Systolic BP Reduction (mmHg)	5.6 ± 4.1	8.5 ± 4.3	+2.9 mmHg
Diastolic BP Reduction (mmHg)	5.4 ± 5.6	9.5 ± 4.4	+4.1 mmHg
Blood Pressure Diurnal Rhythm	No significant improvement	Significant improvement	Enhanced circadian regulation
Urinary Na+ Excretion	No significant change	Significant increase	Improved sodium handling
Extracellular Water	No significant change	Significant decrease	Reduced fluid retention

All values expressed as mean ± SD [7]

Mechanistic Insights: Divergent Pathways to Blood Pressure Control

The differential effects observed in these studies suggest distinct but complementary biological mechanisms through which DASH and intermittent fasting exert their antihypertensive effects.

Biological Pathways for Blood Pressure Reduction

The DASH diet primarily functions through nutrient-mediated mechanisms, providing adequate potassium to counteract sodium effects, dietary nitrates that convert to vasodilatory nitric oxide, and antioxidants that reduce vascular oxidative stress [4] [71]. In contrast, intermittent fasting operates through fasting-activated pathways including metabolic switching from glucose to ketone metabolism, activation of cellular repair processes like autophagy, and optimization of circadian rhythms that influence blood pressure regulation [72] [49].

Personalization Based on Comorbidities and Phenotypes

Diabetes and Metabolic Comorbidities

The presence of diabetes significantly alters dietary recommendations and expected outcomes. Research indicates that while intermittent fasting can improve insulin sensitivity and glycemic control, it requires careful monitoring in patients using insulin or sulfonylureas due to hypoglycemia risk [9] [49]. The DASH diet has demonstrated particular benefit for diabetic populations, with a recent Johns Hopkins Medicine study showing that a modified "DASH for Diabetes" (DASH4D) diet lowered systolic blood pressure by approximately 4.6 mmHg in adults with type 2 diabetes, most of whom were taking multiple antihypertensive medications [48].

Table 3: Dietary Protocol Modifications for Comorbid Conditions

Comorbidity	Recommended Approach	Protocol Modifications	Safety Considerations
Type 2 Diabetes	DASH4D (Modified DASH)	Lower carbohydrates, increased unsaturated fat, adjusted potassium for renal function	Monitor hypoglycemia risk with medications; avoid in type 1 diabetes [49]
Cardiovascular Disease	DASH diet	Standard protocol with emphasis on sodium restriction (<1500 mg/day)	Caution with TRE: associated with 91% higher CVD mortality in one observational study [46]
Obesity (without CVD)	Either approach	IER: 500-600 kcal 2 days/week; TRE: 16/8 method	Both effective for weight loss; IER may offer compliance advantages [9]
Chronic Kidney Disease	Adapted DASH	Reduced potassium and phosphorus content; moderate protein	Contraindicated: prolonged fasting (>16 hours) due to electrolyte disturbance risk [48]
History of Eating Disorders	DASH diet	Standard protocol with regular meal pattern	Intermittent fasting contraindicated due to potential for triggering disordered eating [49]

Age, Sex, and Lifestyle Considerations

Personalization must also account for demographic and lifestyle factors. Intermittent fasting is not recommended for children, teens under 18, or pregnant and breastfeeding women [49]. Shift workers and those with irregular schedules may struggle with consistent TRE windows, making DASH a more feasible option [72]. A person's ability to adhere to specific dietary protocols is influenced by socioeconomic factors, cultural food preferences, and practical constraints, highlighting the need for individualized implementation strategies.

Genetic and Molecular Considerations

Epigenetic Modulation by Dietary Patterns

Emerging evidence suggests that both DASH and intermittent fasting influence gene expression through epigenetic mechanisms, particularly DNA methylation [73]. The DASH diet, rich in folate and polyphenols, provides methyl donors and cofactors that influence DNA methylation patterns in genes regulating blood pressure, vascular function, and inflammation [73] [74]. Intermittent fasting has been shown to impact circadian clock gene methylation, potentially enhancing the amplitude of blood pressure circadian rhythms, which aligns with clinical observations of improved diurnal blood pressure patterns in the DASH+TRE trial [7].

Epigenetic Regulation by Dietary Interventions

Pharmacogenomic Interactions

The interplay between diet and antihypertensive medications represents another dimension of personalization. Dietary sodium restriction enhances the effectiveness of most antihypertensive agents, while very low-carbohydrate approaches during fasting periods may potentiate the effects of certain medications, requiring dose adjustments [9] [48]. Future research should explore specific gene-diet interactions, such as how sodium-sensitive genotypes respond differently to various dietary approaches, enabling truly personalized hypertension management.

Methodological Considerations for Research

Experimental Protocols and Outcome Measures

Standardized methodologies are essential for comparing outcomes across studies. Key trials in this field share common elements in their experimental designs:

Intermittent Fasting Protocols: The 5:2 IER protocol typically involves 2 non-consecutive days per week with severe calorie restriction (500 kcal/day for women, 600 kcal/day for men), with habitual eating the other 5 days [9]. TRE protocols generally enforce a consistent daily eating window (typically 6-10 hours) with complete fasting outside this window, allowing only water, black coffee, or other non-caloric beverages [7].

DASH Diet Implementation: Standard DASH provides specific serving recommendations based on calorie levels (e.g., 6-8 servings of grains, 4-5 servings of fruits and vegetables for 2000 kcal/day) with sodium restriction to 2300 mg or 1500 mg daily [4]. The modified DASH4D for diabetes features lower carbohydrates, increased unsaturated fats, and adjusted mineral content for renal safety [48].

Table 4: Core Outcome Measures in Hypertension Diet Trials

Domain	Primary Outcomes	Secondary Outcomes	Novel/Specialized Measures
Blood Pressure	Office SBP/DBP; 24-hour ambulatory BP	BP variability; Nocturnal dipping; Morning surge	Central aortic pressure; Pulse wave velocity
Metabolic Parameters	Body weight; BMI; Fasting glucose	HbA1c; Insulin sensitivity (HOMA-IR); Lipid profile	Oxidative stress markers; Inflammatory cytokines
Fluid/Electrolyte Balance	-	Urinary sodium excretion; Serum electrolytes	Extracellular water (bioimpedance); RAAS activation
Adherence Metrics	Food diaries; 24-hour dietary recall	Biomarkers (urinary potassium, serum selenium)	Digital tracking (app-based); Metabolomic profiling

Research Reagent Solutions and Methodological Tools

Table 5: Essential Research Materials and Methods for Dietary Intervention Studies

Category	Specific Tools/Assays	Research Application
Dietary Assessment	24-hour dietary recall interviews; Food frequency questionnaires; Digital food photography	Quantifying adherence to prescribed dietary protocols; Measuring micronutrient intake
Blood Pressure Monitoring	Automated office BP devices; 24-hour ambulatory BP monitors; Central BP tonometry	Capturing different BP phenotypes; Assessing circadian patterns
Body Composition Analysis	DEXA (Dual-energy X-ray absorptiometry); Bioelectrical impedance analysis; MRI/CT	Differentiating fat mass vs. lean mass changes; Measuring ectopic fat depots
Molecular Analysis	ELISA for inflammatory markers (CRP, IL-6); HPLC for metabolomics; Pyrosequencing for DNA methylation	Uncovering mechanistic pathways; Identifying epigenetic modifications
Data Collection & Management	Electronic data capture systems; Mobile health platforms; Wearable activity trackers	Enhancing protocol compliance; Real-time data collection

The evidence reviewed demonstrates that both DASH and intermittent fasting represent effective dietary strategies for blood pressure control, with similar overall efficacy but potentially different optimal applications based on individual characteristics. Personalization strategies that account for phenotypic traits, comorbid conditions, and genetic predispositions promise to enhance the effectiveness of dietary interventions for hypertension.

Future research should prioritize several key areas: first, exploring gene-diet interactions to identify genetic markers that predict response to specific dietary approaches; second, conducting longer-term studies to establish the sustainability and lasting benefits of personalized nutrition; and third, developing more sophisticated biomarkers of adherence and response beyond traditional clinical measures. The integration of continuous glucose monitoring, wearable technology, and metabolomic profiling may provide the multidimensional data needed to advance truly personalized dietary recommendations for hypertension management.

As precision medicine evolves, dietary recommendations for blood pressure control will increasingly move beyond generic advice to embrace tailored strategies that maximize therapeutic benefits while minimizing burdens and risks for individual patients.

Mitigating Attrition in Long-Term Dietary Intervention Studies

Long-term adherence is a pivotal challenge in nutritional science, determining the real-world efficacy and translational potential of dietary interventions. Within the specific context of evaluating the Dietary Approaches to Stop Hypertension (DASH) diet against various intermittent fasting (IF) regimens for blood pressure control, mitigating participant attrition is not merely a methodological concern but a core determinant of data validity and clinical relevance. Attrition rates directly influence the statistical power, internal validity, and generalizability of findings, making retention strategies a critical component of robust trial design. This guide objectively compares the performance of these two dietary strategies, with a focused lens on the experimental data and protocols that illuminate their associated adherence and attrition challenges.

Quantitative Comparison of Attrition and Efficacy

A synthesis of recent clinical trials reveals distinct patterns in attrition rates and cardiometabolic outcomes between DASH and IF interventions. The data underscores the critical balance between efficacy and adherence.

Table 1: Attrition and Blood Pressure Outcomes in DASH Diet Trials

Trial Name	Duration	Attrition Rate	Systolic BP Reduction	Diastolic BP Reduction	Key Adherence Strategies
PREMIER [2]	6 months	Not Specified	-11.1 mmHg (Established + DASH)	Not Specified	Behavioral counseling, weight management
DASH-Sodium [2]	4-12 weeks	Not Specified	-11.5 mmHg (Hypertensive)	Not Specified	Provision of meals, controlled feeding
ENCORE [2]	4 months	Not Specified	-16.1 mmHg (DASH + Weight Mgmt)	Not Specified	Combined diet and exercise sessions
Saneei et al. Meta-Analysis [2]	Varies	Not Specified	-6.74 mmHg (Overall)	-3.54 mmHg (Overall)	Energy restriction in some studies

Table 2: Attrition and Cardiometabolic Outcomes in Intermittent Fasting Trials

Study (Protocol)	Duration	Attrition Rate	Weight Loss	Systolic BP Reduction	Key Adherence Findings
4:3 IMF (Catenacci et al.) [75]	12 months	19% (IMF) vs. 30% (DCR)	Greater than DCR	More favorable vs. DCR	Superior adherence measured by doubly labeled water
TRE for Metabolic Syndrome [76]	12 weeks	Not Specified	-3.3 kg	-5.1 mmHg	Self-selected 10-hour window for flexibility
ADF vs. CR (Gabel et al.) [77]	12 months	Not Specified	Equivalent to CR	No significant change	More challenging adherence for ADF vs. CR
Rynders et al. Review [78]	≥8 weeks	Generally Equivalent to CER	Equivalent to CER	Varies	9 of 11 studies showed no difference in weight loss vs. CER

Detailed Experimental Protocols and Methodologies

DASH Diet Intervention Protocols

The efficacy of the DASH diet is rooted in rigorous, highly controlled feeding studies. The original DASH and subsequent DASH-Sodium trials employed a standardized controlled feeding design [2]. This protocol involves preparing and providing all meals and snacks to participants according to a fixed menu, ensuring strict adherence to nutrient targets. The core DASH diet emphasizes high intake of fruits, vegetables, and low-fat dairy products, providing specific serving guides based on calorie levels (e.g., 6-8 servings of grains, 4-5 servings each of vegetables and fruits daily for a 2,000-calorie diet) [4]. The DASH-Sodium trial extended this by systematically varying sodium levels across three phases (low, medium, high) while maintaining the DASH dietary pattern, which required even more precise meal preparation and monitoring [2]. To translate these findings into practical settings, later trials like PREMIER and ENCORE utilized behavioral intervention protocols [2]. These involved multi-component strategies including group educational sessions, individual counseling, self-monitoring with food diaries, and motivational interviewing to encourage adoption of the DASH diet and other lifestyle changes such as weight loss and physical activity.

Intermittent Fasting Intervention Protocols

IF trials employ distinct protocols centered on the timing of energy intake. Two predominant models are Alternate Day Fasting (ADF) and Time-Restricted Eating (TRE).

• ADF Protocol (e.g., 4:3 IMF): The protocol from Catenacci et al. is a prime example [75]. This 3-day-per-week fasting regimen involves a weekly cycle where participants drastically reduce calorie intake (to 400-700 calories, based on body size) on three non-consecutive "fast days." On the remaining four "feast days," participants are instructed to eat a normal, healthy diet without calorie counting. The caloric prescription is individualized, based on measured resting energy expenditure to create a target 34% weekly energy deficit, matching the deficit in the comparator daily calorie restriction (DCR) group [75].

• TRE Protocol: Studies, such as the one on metabolic syndrome by Wilkinson et al., use a consistent daily eating window [76]. In this protocol, participants with a baseline eating window of ≥14 hours are instructed to consume all calorie-containing foods and beverages within a self-selected 10-hour window each day for 12 weeks. Food intake is typically ad libitum within this window, with no explicit calorie counting. Adherence is often monitored using mobile apps or digital platforms that allow participants to log their first and last food intake daily [76].

Visualizing Intervention Pathways and Attrition Risks

The following diagram illustrates the structural differences and potential attrition points in DASH versus Intermittent Fasting protocols.

The diagram highlights fundamental differences: DASH's structure derives from its specific nutrient composition and required behavioral changes, whereas IF's structure is primarily temporal. These differences give rise to distinct attrition risks—diet complexity for DASH and social conflict/rigidity for IF—which must be addressed through tailored retention strategies.

The Scientist's Toolkit: Essential Research Reagents & Materials

Successful execution and monitoring of long-term dietary trials require a suite of specialized tools and materials to ensure data accuracy, protocol adherence, and participant safety.

Table 3: Essential Research Materials for Dietary Intervention Trials

Tool/Reagent	Primary Function	Application in DASH vs. IF Trials
Doubly Labeled Water (DLW)	Objective measurement of total energy expenditure and free-living calorie intake.	Gold-standard for verifying adherence to calorie restriction in IF and DCR arms [75].
24-Hour Dietary Recall	Detailed, structured assessment of all foods/beverages consumed in the past 24 hours.	Standard for monitoring nutrient composition in DASH and energy intake patterns in IF [2].
Continuous Glucose Monitor (CGM)	Captures interstitial glucose levels continuously throughout day and night.	Key for assessing glycemic control in IF studies, particularly TRE's impact on 24-hr glucose rhythms [77].
Actigraphy Devices	Objective measurement of physical activity and sleep-wake cycles.	Controls for confounding from activity changes; monitors circadian rhythms in TRE studies [76].
Standardized BP Monitors	Automated, office and ambulatory blood pressure measurement.	Primary efficacy outcome for both DASH and IF interventions [2] [31].
Bioelectrical Impedance Analysis (BIA)	Estimates body composition (fat mass, lean mass, body water).	Tracks changes in body composition beyond simple weight measurement in both diets [77] [76].
Fecal Sample Collection Kits	Standardized collection and stabilization of stool samples for microbiome analysis.	Enables investigation of gut microbiota as a mechanism, e.g., in IF and blood pressure reduction [31].
Biobank Storage Solutions	Long-term, stable storage of biological samples (serum, plasma, feces) at -80°C.	Allows for batch analysis of biomarkers (e.g., LPS, TMAO, SCFAs) and future exploratory research [31].

Direct head-to-head comparisons of the DASH diet and intermittent fasting focusing specifically on long-term attrition are still needed. However, extant data suggests that the choice between these interventions involves a trade-off. The DASH diet, with its strong, guideline-endorsed efficacy for hypertension and potential for flexible implementation through behavioral counseling, offers a proven path [2]. In contrast, certain IF regimens, particularly the 4:3 model, demonstrate a promising capacity to enhance adherence and reduce attrition over 12 months, which is a significant advantage in long-term trial design and potential clinical translation [75]. Future research should prioritize direct comparisons that are powered for attrition as a primary endpoint, incorporate the objective adherence measures outlined in the "Scientist's Toolkit," and explore hybrid models that combine the circadian benefits of IF with the nutrient-density of DASH to maximize both retention and cardiometabolic efficacy.

Efficacy Meta-Analysis, Comparative Effectiveness, and Broader Health Impacts

Hypertension remains a critical modifiable risk factor for cardiovascular disease, the leading cause of mortality worldwide. Non-pharmacological interventions, particularly dietary modifications, play an essential role in blood pressure management. The Dietary Approaches to Stop Hypertension (DASH) and various forms of intermittent fasting represent two distinct dietary strategies with demonstrated efficacy. However, their comparative effectiveness against other dietary patterns remains unclear. This network meta-analysis (NMA) synthesizes evidence from randomized controlled trials (RCTs) to rank dietary patterns based on their efficacy for blood pressure reduction using the Surface Under the Cumulative Ranking Curve (SUCRA) metric, providing clinicians and researchers with evidence-based guidance for selecting optimal dietary interventions.

Comparative Efficacy of Dietary Patterns

Recent high-quality network meta-analyses have directly compared the effects of multiple dietary patterns on cardiovascular risk factors, enabling statistical ranking of their relative efficacy. The key findings demonstrate diet-specific cardioprotective effects, with different patterns excelling across various cardiovascular risk parameters [79].

For systolic blood pressure (SBP) reduction, the DASH diet consistently demonstrates superior efficacy. A 2025 NMA by Sun et al. analyzing 21 RCTs with 1,663 participants found the DASH diet achieved the highest SUCRA value (89) for SBP reduction, with a mean difference (MD) of -7.81 mmHg (95% CI -14.2 to -0.46) compared to control diets [79]. Intermittent fasting also showed significant blood pressure-lowering effects (MD -5.98 mmHg, 95% CI -10.4 to -0.35; SUCRA 76) [79]. These findings were corroborated by a 2025 NMA focusing specifically on metabolic syndrome, which confirmed the DASH diet's efficacy (MD -5.99 mmHg, 95% CI -10.32 to -1.65) while also identifying the ketogenic diet as highly effective for both systolic (MD -11.00 mmHg, 95% CI -17.56 to -4.44) and diastolic blood pressure (MD -9.40 mmHg, 95% CI -13.98 to -4.82) reduction [80] [81].

Table 1: SUCRA Rankings and Efficacy of Dietary Patterns for Blood Pressure Reduction

Dietary Pattern	Systolic BP Reduction (MD, mmHg)	SUCRA Value (SBP)	Diastolic BP Reduction (MD, mmHg)	SUCRA Value (DBP)	Primary Cardiovascular Benefit
DASH	-7.81 (-14.2 to -0.46) [79]	89 [79]	-2.3 (DASH4D study) [48]	Not reported	Blood pressure control [79]
Intermittent Fasting	-5.98 (-10.4 to -0.35) [79]	76 [79]	-6.0 [9]	Not reported	Blood pressure control [79]
Ketogenic	-11.00 (-17.56 to -4.44) [80]	Not reported	-9.40 (-13.98 to -4.82) [80]	Not reported	Blood pressure, triglycerides [80]
Mediterranean	Not reported	Not reported	Not reported	Not reported	Fasting blood glucose [80]
Vegan	Not reported	Not reported	Not reported	Not reported	Waist circumference, HDL-C [80]
Low-carbohydrate	Not reported	Not reported	Not reported	Not reported	Lipid modulation [79]

For other cardiovascular risk factors, ketogenic (MD -10.5 kg, 95% CI -18.0 to -3.05; SUCRA 99) and high-protein diets (MD -4.49 kg, 95% CI -9.55 to 0.35; SUCRA 71) showed superior efficacy for weight reduction, while ketogenic (MD -11.0 cm, 95% CI -17.5 to -4.54; SUCRA 100) and low-carbohydrate diets (MD -5.13 cm, 95% CI -8.83 to -1.44; SUCRA 77) achieved the greatest reductions in waist circumference [79]. Low-carbohydrate (MD 4.26 mg/dL, 95% CI 2.46-6.49; SUCRA 98) and low-fat diets (MD 2.35 mg/dL, 95% CI 0.21-4.40; SUCRA 78) optimally increased HDL-C levels [79].

Synergistic Effects of Combined Interventions

Emerging evidence suggests that combining dietary approaches may yield synergistic benefits. A 2024 randomized controlled trial demonstrated that combining time-restricted eating (TRE) with the DASH diet produced significantly greater blood pressure reductions than the DASH diet alone in stage 1 hypertensive patients [40]. The DASH+TRE group achieved reductions of 8.46/9.46 mmHg in systolic/diastolic blood pressure compared to 5.60/5.35 mmHg in the DASH-only group [40]. The combined intervention also improved blood pressure diurnal rhythm, decreased extracellular water, and increased urinary Na+ excretion, suggesting multiple mechanisms for its enhanced efficacy [40].

Similarly, a 2025 study on metabolic-associated fatty liver disease found that combining time-restricted feeding (16/8) with a DASH diet significantly improved obesity indices, hepatic steatosis, and fibrosis compared to a control diet [8]. This suggests that the benefits of combined dietary approaches may extend across multiple metabolic parameters.

Methodological Approaches in Key Studies

Network Meta-Analysis Methodology

The NMAs cited in this review employed rigorous methodology following PRISMA-NMA guidelines [80] [82]. The 2025 NMA by Sun et al. utilized a random-effects model to analyze mean differences in cardiovascular risk factors and ranked dietary efficacy via SUCRA scores [79]. SUCRA values range from 0% to 100%, with higher values indicating greater probability of being the most effective intervention [79].

Bayesian network meta-analyses were conducted using Markov Chain Monte Carlo methods with multiple chains running for tens of thousands of iterations to ensure statistical robustness [83] [82]. Consistency between direct and indirect evidence was assessed using node-splitting methods, and heterogeneity was examined using I² statistics [82]. These sophisticated statistical approaches allow for simultaneous comparison of multiple interventions while preserving randomisation characteristics of the original trials.

Randomized Controlled Trial Designs

Recent RCTs investigating dietary patterns for blood pressure control have implemented sophisticated feeding and monitoring protocols:

DASH for Diabetes Study (2025): This crossover feeding study provided all meals to participants, eliminating non-adherence concerns [48]. The study compared four diets in random sequence: 1) DASH4D diet with lower sodium, 2) DASH4D diet with higher sodium, 3) typical American diet with lower sodium, and 4) typical American diet with higher sodium [48]. Each diet period lasted five weeks with weight maintenance calories. The modified DASH4D diet featured reduced carbohydrates and potassium alongside increased unsaturated fats to enhance safety for diabetic patients with chronic kidney disease [48].

Time-Restricted Eating + DASH Trial (2024): This 6-week RCT recruited stage 1 hypertensive patients without high-risk factors [40]. The intervention group consumed food within an 8-hour window (9:00 a.m. to 5:00 p.m.) while following DASH diet principles, while the control group followed DASH alone without time restrictions [40]. The study utilized a scientific research platform within the WeChat application to track participant adherence and collected extensive data including body composition, cardiometabolic risk factors, inflammation-related parameters, and urinary sodium excretion [40].

Intermittent vs. Continuous Energy Restriction Trial (2021): This 6-month RCT compared intermittent energy restriction (IER) using the 5:2 diet (500-600 kcal for 2 days/week) with continuous energy restriction (CER) (1,000-1,200 kcal/day) in overweight and obese hypertensive patients [9]. Participants received dietary education from qualified dietitians, kept food diaries, used digital kitchen scales, and attended regular outpatient visits for monitoring [9]. The study included detailed medication management protocols to prevent hypotension and hypoglycemia [9].

Diagram 1: Methodological Framework for Dietary Pattern Network Meta-Analyses. This diagram illustrates the systematic approach from study design through outcome assessment and statistical analysis used in recent NMAs evaluating dietary interventions for blood pressure control.

The Researcher's Toolkit: Essential Methodological Components

Table 2: Essential Research Reagents and Methodological Components for Dietary Intervention Studies

Component	Function/Application	Example Implementation
SUCRA Analysis	Ranks interventions by probability of being best for specific outcomes	Statistical ranking of dietary patterns for blood pressure reduction [79]
Bayesian NMA	Enables simultaneous comparison of multiple interventions	Markov Chain Monte Carlo simulation with multiple chains [82]
Controlled Feeding	Eliminates adherence variability in efficacy assessment	Providing all meals to participants in DASH4D study [48]
Time-Restriction Monitoring	Tracks adherence to intermittent fasting protocols	WeChat application tracking of 8-hour eating window [40]
Ambulatory BP Monitoring	Provides comprehensive blood pressure assessment	24-hour monitoring to detect diurnal rhythm changes [40]
Biomarker Analysis	Objective metabolic outcome assessment	Urinary sodium excretion, lipid profiles, inflammatory markers [40] [8]

Discussion

Clinical Implications and Applications

The SUCRA rankings derived from recent network meta-analyses provide evidence-based guidance for personalizing dietary approaches to hypertension management. The DASH diet's superior performance for blood pressure reduction (SUCRA 89) supports its continued recommendation as a first-line dietary intervention for hypertensive patients [79]. However, the significant efficacy of intermittent fasting (SUCRA 76) offers an alternative for patients who may struggle with the specific food restrictions of the DASH diet [79].

The synergistic effect observed when combining time-restricted eating with the DASH diet suggests that multi-component dietary interventions may maximize blood pressure reduction [40]. This combination approach addresses both dietary quality and meal timing, potentially leveraging multiple physiological mechanisms including enhanced natriuresis, improved insulin sensitivity, and circadian rhythm alignment [40].

For patients with specific metabolic comorbidities, different dietary patterns may offer complementary benefits. The ketogenic diet's strong performance for both blood pressure reduction and triglyceride lowering may be particularly beneficial for patients with combined hypertension and hypertriglyceridemia [80]. Similarly, the Mediterranean diet's efficacy for glycemic control makes it suitable for hypertensive patients with impaired glucose metabolism [80].

Limitations and Research Gaps

Despite robust methodology, several limitations persist in the current evidence base. Most dietary intervention trials face challenges with blinding, potentially introducing performance bias. Long-term adherence to restrictive dietary patterns remains a concern, as 12-month effects tend to attenuate compared to 6-month outcomes [84]. Additionally, many studies lack sufficient representation of diverse demographic groups, limiting generalizability.

Future research should prioritize longer-term interventions with innovative adherence support strategies, head-to-head comparisons of combined dietary approaches, and personalized nutrition studies identifying individual factors predictive of response to specific dietary patterns. Mechanistic studies elucidating the physiological pathways through which different dietary patterns influence blood pressure will further refine intervention strategies.

This network meta-analysis demonstrates that while multiple dietary patterns effectively reduce blood pressure, the DASH diet remains the most evidence-based approach for hypertension management based on SUCRA rankings. Intermittent fasting represents a viable alternative with significant efficacy, particularly when combined with DASH principles. The emerging paradigm supports personalized dietary recommendations based on individual patient characteristics, preferences, and comorbidity profiles, with combined approaches potentially offering synergistic benefits. Future research should focus on long-term adherence strategies and mechanistic studies to further optimize dietary interventions for blood pressure control.

Hypertension remains a critical global health challenge, driving the need for effective non-pharmacological interventions. Among dietary strategies, the Dietary Approaches to Stop Hypertension (DASH) diet and various forms of intermittent fasting (IF) have emerged as prominent approaches for blood pressure management. While the DASH diet is well-established in clinical guidelines, intermittent fasting, particularly time-restricted eating (TRE), has gained recent attention for its potential cardiometabolic benefits. This guide provides a quantitative, data-driven comparison of the systolic and diastolic blood pressure (SBP/DBP) lowering efficacy of these interventions, synthesizing evidence from recent clinical trials to inform researchers and drug development professionals.

The following table summarizes the blood pressure-lowering effects of DASH and intermittent fasting interventions as reported in key clinical studies.

Table 1: Quantitative Blood Pressure Reduction from Clinical Trials

Intervention	Study Population	Duration	SBP Reduction (mmHg)	DBP Reduction (mmHg)	Citation
DASH Diet Alone	Stage 1 Hypertension	6 weeks	-5.60 ± 4.07	-5.35 ± 5.64	[7]
DASH + TRE (8-hour window)	Stage 1 Hypertension	6 weeks	-8.46 ± 4.26	-9.46 ± 4.38	[7]
DASH Diet	Hypertensive & Prehypertensive Adults	Variable (Meta-analysis)	-6.74	-3.54	[2]
IER (5:2 diet)	Overweight/Obese Hypertensive Patients	6 months	-7.00 ± 0.70	-6.00 ± 0.50	[9]
CER	Overweight/Obese Hypertensive Patients	6 months	-7.00 ± 0.60	-5.00 ± 0.50	[9]
Modified ADF	Adults with Cardiovascular Risk Factors	Variable (Network Meta-analysis)	-7.24	-4.70	[65]
TRE	Adults with Cardiovascular Risk Factors	Variable (Network Meta-analysis)	*	-3.24	[65]
DASH-Sodium (Low Sodium)	Hypertensive Patients	Variable	-11.50	*	[2]

Specific systolic blood pressure data not reported in the network meta-analysis for TRE.

DASH Diet Intervention Protocols

Core Dietary Composition

The DASH dietary pattern emphasizes increased consumption of fruits, vegetables, whole grains, lean proteins, and low-fat dairy products while reducing intake of saturated fats, cholesterol, and sodium. The standard DASH eating plan for a 2,000-calorie diet includes: 6-8 daily servings of grains; 4-5 daily servings of both vegetables and fruits; 2-3 daily servings of low-fat or fat-free dairy products; and 6 or fewer daily servings of lean meats, poultry, and fish. Weekly, it recommends 4-5 servings of nuts, seeds, and legumes, and limits sweets to 5 or fewer servings [4].

Key Clinical Trial Methodologies

The DASH-Sodium Trial(as described in [2]) employed a controlled feeding study design to investigate the combined effects of the DASH diet with varying sodium intake levels. Participants were provided with all meals and snacks prepared in a metabolic kitchen. The trial compared a typical American diet (control) to the DASH diet across three sodium levels (high, intermediate, and low). The low-sodium DASH diet (targeting 1,500 mg/day) produced the most substantial blood pressure reductions, highlighting the synergistic effect of combining the DASH dietary pattern with sodium restriction [2].

The PREMIER Trial(as detailed in [2]) examined the integration of the DASH diet into broader lifestyle modifications. This multi-center randomized trial assigned 810 participants with prehypertension or stage 1 hypertension to one of three groups: an "advice-only" group receiving a single educational session; an "established" intervention group implementing weight loss, physical activity, and sodium reduction; and an "established plus DASH" group that combined all established interventions with adherence to the DASH diet. Blood pressure measurements were conducted using standardized clinic-based protocols [2].

Figure 1: DASH Diet Efficacy Workflow

Intermittent Fasting Intervention Protocols

Major IF Variants and Definitions

Intermittent fasting encompasses several distinct timing approaches:

• Time-Restricted Eating (TRE): Confines all daily calorie consumption to a specific window, typically 6-10 hours, followed by a 14-18 hour fast [7] [19].
• Alternate-Day Fasting (ADF): Alternates between ad libitum feeding days and days featuring significant calorie restriction (approximately 75% reduction) or complete fasting [65] [19].
• 5:2 Diet: Involves five days of habitual eating per week interspersed with two non-consecutive days of severe calorie restriction (500-600 kcal/day) [9] [19].

Key Clinical Trial Methodologies

The DASH plus TRE Trial(detailed in [7]) was a 6-week randomized controlled trial involving 74 patients with stage 1 primary hypertension. Participants were randomized to either a DASH diet alone group or a DASH plus TRE group. The TRE component required participants to consume all daily calories within an 8-hour window (9:00 a.m. to 5:00 p.m.). Compliance was monitored via a scientific research platform embedded within the WeChat application. Beyond blood pressure, researchers assessed body composition, cardiometabolic risk factors, inflammation markers, urinary sodium excretion, and blood pressure diurnal rhythm [7].

The Intermittent vs. Continuous Energy Restriction Trial(from [9]) compared the 5:2 intermittent fasting pattern to continuous energy restriction in 205 overweight or obese hypertensive patients over 6 months. The IER group followed a 5:2 protocol (500-600 calories on two non-consecutive days per week), while the CER group maintained a consistent daily caloric deficit (1,000 kcal/day for women; 1,200 kcal/day for men). Both groups received dietary education and digital cooking scales. Blood pressure was measured as a primary outcome, alongside weight, body composition, HbA1c, and blood lipids [9].

Figure 2: Intermittent Fasting Experimental Protocol

Mechanisms of Action and Physiological Pathways

DASH Diet Mechanisms

The DASH diet exerts its antihypertensive effects through multiple complementary physiological pathways:

• Electrolyte Balance: Increased intake of potassium, calcium, and magnesium helps counteract the hypertensive effects of sodium and regulates vascular tone [2].
• Vascular Function: The diet's rich array of phytochemicals and reduced saturated fat content improve endothelial function and reduce oxidative stress [53].
• Volume Regulation: When combined with sodium restriction, the DASH diet enhances renal handling of sodium and water, reducing extracellular fluid volume [7] [48].

Intermittent Fasting Mechanisms

Intermittent fasting influences blood pressure through both weight-dependent and weight-independent pathways:

• Weight and Insulin Sensitivity: Fasting periods deplete glycogen stores, enhance insulin sensitivity, and promote lipolysis, leading to weight loss and reduced sympathetic nervous system activity [9] [19].
• Circadian Rhythm Alignment: TRE synchronizes food intake with circadian biology, optimizing metabolic processes and hormone regulation [7] [19].
• Gut Microbiota Modulation: Recent evidence suggests IF alters gut microbiota composition, increasing beneficial species like Akkermansia muciniphila that produce short-chain fatty acids with antihypertensive properties [31].
• Autonomic Nervous System: IF may enhance parasympathetic tone and reduce sympathetic activation, contributing to blood pressure reduction and improved diurnal rhythm [7].

Figure 3: Blood Pressure Regulation Pathways of DASH vs. Intermittent Fasting

Research Reagents and Methodological Toolkit

Table 2: Essential Research Materials and Methods for Hypertension Dietary Studies

Category	Specific Tool/Reagent	Research Application	Exemplary Use
Blood Pressure Measurement	24-hour Ambulatory BP Monitor	Gold-standard for BP assessment and diurnal rhythm	Detected improved BP diurnal rhythm in DASH+TRE group [7]
Body Composition Analysis	Bioelectrical Impedance Analysis (BIA)	Measures extracellular water and body composition	Identified reduced extracellular water correlating with BP reduction [7]
Dietary Compliance Tools	Digital Food Weighing Scale	Ensures accurate dietary adherence in feeding studies	Provided to participants for meal portion control [9]
Metabolic Biomarkers	ELISA Kits for LPS, TMAO, SCFAs	Quantifies gut-derived metabolites	Used to demonstrate IF-induced reduction in pro-hypertensive metabolites [31]
Mobile Health Platforms	WeChat Scientific Research Module	Enables real-time dietary tracking and compliance	Facilitated participant monitoring and data collection [7]
Glucose Monitoring	Continuous Glucose Monitor (CGM)	Assesses glycemic variability	Employed in DASH4D study to measure glucose improvements [53]

Comparative Analysis and Research Implications

The quantitative data reveals a compelling efficacy profile for both interventions. The standard DASH diet demonstrates consistent SBP reductions of approximately 5-7 mmHg and DBP reductions of 3-5 mmHg across multiple studies [7] [2]. When enhanced with sodium restriction, these effects magnify substantially, with SBP reductions exceeding 11 mmHg in hypertensive individuals [2].

The intermittent fasting approaches show variable efficacy depending on the specific protocol. The 5:2 diet produces substantial reductions of approximately 7/6 mmHg in SBP/DBP [9], while modified alternate-day fasting demonstrates even greater efficacy with 7.24/4.70 mmHg reductions according to network meta-analysis [65].

Notably, the combination of DASH with TRE appears particularly potent, achieving 8.46/9.46 mmHg reductions in SBP/DBP - significantly greater than DASH alone [7]. This synergistic effect suggests complementary mechanisms of action, with DASH addressing nutritional composition and TRE leveraging timing-based metabolic regulation.

For research applications, these findings indicate that combined intervention approaches may yield superior efficacy compared to either strategy alone. The gut microbiota modulation observed with IF [31] presents a promising avenue for mechanistic studies, while the differential effects on lipid profiles between standard and higher-fat DASH variants [85] highlight the potential for personalized dietary approaches based on patient-specific risk factors.

Future research should prioritize direct head-to-head trials with careful mechanistic substudies, longer-term follow-up to assess sustainability, and exploration of genetic factors that might predict individual response to these dietary interventions.

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Impact Beyond Hypertension: Effects on Liver Enzymes, Lipid Profiles, and Glycemic Control

The Dietary Approaches to Stop Hypertension (DASH) diet and intermittent fasting (IF) are established dietary strategies primarily recognized for their efficacy in blood pressure control. However, their therapeutic influence extends far beyond hypertension management to encompass critical metabolic parameters including liver enzymes, lipid profiles, and glycemic control. This comparative analysis examines the multidimensional effects of these dietary interventions through the lens of recent clinical evidence, providing researchers and drug development professionals with a systematic evaluation of their pleiotropic benefits. As metabolic diseases continue to present growing global health challenges, understanding the full spectrum of action of these non-pharmacological approaches informs both clinical practice and the development of targeted therapeutic agents.

Comparative Efficacy Analysis: Quantitative Outcomes Across Metabolic Parameters

Table 1: Effects on Liver Enzymes and Hepatic Health

Parameter	DASH Diet Alone	Intermittent Fasting	DASH + TRE Combination	Study Details
ALT (IU/L)	-3.305 IU/L (weighted mean difference) [89]	Small effect size (SMD: -0.44) [88]	Significant reduction (p=0.039) [8]	6-study meta-analysis [89]; MAFLD patients [8]
AST (IU/L)	Significant reduction (p<0.001) [89]	Small effect size (SMD: -0.30) [88]	Significant reduction (p=0.047) [8]	6-study meta-analysis [89]; MAFLD patients [8]
Liver Steatosis	Improved in NAFLD patients [90]	Medium effect size (SMD: -0.73) [88]	CAP score reduction (p<0.001) [8]	MAFLD patients, 12-week RCT [8]
Liver Fibrosis	Not reported	No significant effect (SMD: -0.28, p=0.07) [88]	Significant improvement [8]	MAFLD patients, 12-week RCT [8]
Mechanism	Reduced TLR-4, MCP-1, LPS [90]	Enhanced autophagy, reduced oxidative stress [88]	Synergistic reduction in inflammation and fat accumulation [8]

Table 2: Effects on Glycemic Control and Lipid Metabolism

Parameter	DASH Diet Alone	Intermittent Fasting	DASH + TRE Combination	Study Details
Fasting Glucose	Decreased in both DASH and control [90]	Improves with LCD comparably [86]	Not significantly different from control [8]	8-week RCT in obese NAFLD patients [90]
HbA1c	Significant decrease [90]	Not reported	Not significantly different from control [8]	8-week RCT in obese NAFLD patients [90]
Insulin/HOMA-IR	Not reported	Not significantly different from LCD [86]	Significant reduction in both groups (p<0.05) [8]	MAFLD patients, 12-week RCT [8]
Triglycerides	Not reported	No significant change (11.22 mg/dL) [86]	Not significantly different from control [8]	10-month RCT in MAFLD [86]
LDL Cholesterol	Not reported	Significant reduction [86]	Not significantly different from control [8]	10-month RCT in MAFLD [86]

Table 3: Effects on Blood Pressure and Body Composition

Parameter	DASH Diet Alone	Intermittent Fasting	DASH + TRE Combination	Study Details
Systolic BP	-5.595 mmHg [40]	-7 mmHg (comparable to CER) [9]	-8.459 mmHg [40]	6-week RCT in stage 1 hypertension [40]; 6-month RCT [9]
Diastolic BP	-5.351 mmHg [40]	-6 mmHg (comparable to CER) [9]	-9.459 mmHg [40]	6-week RCT in stage 1 hypertension [40]; 6-month RCT [9]
Body Weight	Significant reduction in obesity indices [90]	-7.0 kg (comparable to CER) [9]	BMI reduction (p=0.03) [8]	8-week RCT in obese NAFLD [90]; 6-month RCT [9]
Abdominal Circumference	Greater reduction vs. control [90]	Not reported	Significant reduction (p=0.005) [8]	8-week RCT in obese NAFLD [90]; MAFLD patients [8]

Experimental Protocols: Methodological Approaches in Key Studies

DASH with Time-Restricted Eating in Hypertension

A 6-week randomized controlled trial investigated the combined effects of DASH and time-restricted eating (TRE) in 74 patients with stage 1 primary hypertension [40]. Participants were randomized to DASH alone (n=37) or DASH+TRE (n=37), with the latter group consuming food within an 8-hour window (9:00 a.m. to 5:00 p.m.) and fasting for the remaining 16 hours [40]. The DASH diet emphasized fruits, vegetables, low-fat dairy products, whole grains, poultry, fish, nuts, seeds, and legumes while reducing fats, red meat, sweets, and sugar-containing drinks [90]. Primary outcomes included blood pressure measurements, while secondary outcomes encompassed body composition, cardiometabolic risk factors, inflammation-related parameters, urinary Na+ excretion, and safety outcomes [40]. Researchers utilized a scientific research platform within the WeChat application to track participant adherence and compliance throughout the study period [40].

DASH with Time-Restricted Feeding in MAFLD

A 12-week randomized controlled trial examined the efficacy of DASH combined with time-restricted feeding (TRF 16/8) in patients with metabolic-associated fatty liver disease (MAFLD) [8]. The intervention group (n=27) followed an 8-hour eating window with 16 hours of fasting daily while adhering to DASH dietary principles, compared to a control group (n=26) following a standard low-calorie diet [8]. The DASH diet was characterized by low content of processed and red meats and sugar-sweetened beverages, and high content of fruits, vegetables, low-fat dairy, and diverse protein sources including fish, chicken, legumes, and nuts [8]. Energy intake was set at 500 kcal less than maintenance needs for both groups, with macronutrient distribution at 30% fat, 18% protein, and 52% carbohydrates [8]. Primary outcomes focused on liver biomarkers, including enzyme levels and imaging tests, while secondary outcomes included lipid, glycemic, and inflammatory indicators, as well as body composition [8].

Intermittent Fasting Versus Low-Calorie Diet in MAFLD

A 10-month, parallel, single-blind randomized controlled trial compared the effects of a 16:8 intermittent fasting diet with a low-calorie diet in 52 patients with MAFLD [86]. The IF group followed a time-restricted feeding protocol with an 8-hour eating window and 16-hour fasting period daily, while the LCD group maintained a consistent daily caloric restriction [86]. Researchers assessed anthropometric, biochemical, liver enzyme, steatosis, fibrosis, inflammatory, and oxidative status parameters before and after the interventions [86]. This longer-term study provided insights into the sustained effects of these dietary interventions on liver health and metabolic parameters.

Mechanistic Insights: Pathways Underpinning Metabolic Benefits

Figure 1: Molecular and Metabolic Pathways of DASH and Intermittent Fasting

The mechanistic pathways through which DASH and intermittent fasting exert their metabolic benefits involve complex physiological adaptations. The DASH diet primarily functions through its high fiber and antioxidant components, which reduce oxidative stress and inflammation, particularly through downregulation of TLR-4, MCP-1, and LPS signaling pathways [90]. This anti-inflammatory effect is complemented by improved insulin sensitivity resulting from the diet's favorable micronutrient profile and low saturated fat content [90].

Intermittent fasting operates through distinct mechanisms centered around metabolic switching and cellular stress resistance. During fasting periods, depletion of hepatic glycogen stores triggers a metabolic shift toward fatty acid oxidation and ketone body production [88]. This transition enhances metabolic flexibility and reduces hepatic fat content. Additionally, the fasting state activates autophagy, a cellular self-cleaning process that promotes the removal of damaged organelles and proteins, thereby reducing hepatic inflammation and improving liver function [88].

When combined, DASH and time-restricted eating create synergistic effects that amplify their individual benefits. The time-restricted feeding component enhances natriuresis, as evidenced by increased urinary sodium excretion, which contributes to blood pressure reduction [40]. Furthermore, aligning food intake with circadian rhythms optimizes metabolic efficiency and glucose homeostasis [8]. The anti-inflammatory components of the DASH diet complement the autophagy-mediated inflammation reduction from fasting, creating a multi-targeted approach to metabolic health.

The Scientist's Toolkit: Essential Research Reagents and Methodologies

Table 4: Essential Research Reagents and Assessment Methodologies

Reagent/Instrument	Primary Application	Research Function	Representative Use
FibroScan 502 Touch	Hepatic steatosis and fibrosis assessment	Quantifies liver fat content (CAP score) and stiffness (kPa)	MAFLD patient screening and intervention monitoring [8]
ELISA Kits (TLR-4, MCP-1, LPS)	Inflammation biomarker quantification	Measures meta-inflammation and gut permeability markers	Evaluating DASH diet effects on inflammatory pathways [90]
Automated Biochemistry Analyzers	Liver enzyme and lipid profile measurement	Quantifies ALT, AST, triglycerides, LDL cholesterol	Primary outcome assessment in dietary interventions [86] [8]
Bioelectrical Impedance Analysis	Body composition assessment	Measures extracellular water, fat mass, lean mass	Monitoring fluid shifts and body composition changes [40]
Continuous Glucose Monitors	Glycemic variability assessment	Tracks interstitial glucose levels continuously	Evaluating glucose homeostasis in fasting interventions [8]
24-Hour Dietary Recall Software	Dietary adherence monitoring	Quantifies nutrient intake and eating window compliance	Ensuring protocol adherence in DASH and TRE interventions [8]
Ambulatory Blood Pressure Monitors	Blood pressure rhythm assessment	Tracks 24-hour blood pressure patterns	Evaluating diurnal blood pressure changes [40]

Research Implications and Future Directions

The accumulating evidence on DASH and intermittent fasting reveals their substantial potential as non-pharmacological approaches for managing multifaceted metabolic disorders. For researchers and drug development professionals, these dietary interventions represent both complementary approaches to pharmacotherapy and models for understanding the integrated physiology of metabolic regulation. The synergistic effects observed when combining DASH with time-restricted eating suggest potential for developing multi-component lifestyle interventions that target multiple pathological pathways simultaneously [40] [8].

Future research should prioritize elucidating the molecular mechanisms underlying the observed benefits, particularly the interplay between nutrient quality and feeding-fasting cycles. The differential effects on various metabolic parameters – with DASH demonstrating particular efficacy for inflammation reduction and intermittent fasting showing promise for enhancing metabolic flexibility – suggest that personalized approaches based on individual metabolic phenotypes may yield optimal outcomes [86] [90]. Long-term studies are needed to establish the sustainability of these dietary interventions and their durability in maintaining metabolic improvements.

For the pharmaceutical industry, these findings highlight the importance of considering dietary patterns as potential modulators of drug efficacy, particularly for medications targeting metabolic pathways. Additionally, the identified mechanisms of action provide novel targets for drug development that mimic or enhance the beneficial effects of these dietary interventions. As precision medicine advances, integrating genetic, metabolic, and microbiome profiling with dietary intervention response data may enable truly personalized nutritional approaches for metabolic disease prevention and management.

The management of hypertension through non-pharmacological means is a cornerstone of cardiovascular disease prevention. Among the most prominent dietary interventions are the Dietary Approaches to Stop Hypertension (DASH) diet and various forms of intermittent fasting (IF), including time-restricted eating (TRE). While both approaches have demonstrated efficacy in blood pressure control, their effectiveness varies significantly across different patient populations. This review synthesizes current evidence to objectively compare the performance of the DASH diet and intermittent fasting protocols across three distinct populations: pediatric patients, individuals with obesity, and those with resistant hypertension. Understanding these population-specific outcomes is crucial for clinicians and researchers aiming to personalize lifestyle interventions for optimal blood pressure management.

Comparative Efficacy Across Populations

Pediatric Population

Hypertension in children and adolescents represents a growing public health concern, with a global pooled prevalence of approximately 4.0%, though rates vary significantly by region [91]. The biological and behavioral considerations for dietary interventions in this demographic are distinct from adults, necessitating specialized evidence.

DASH Diet Efficacy: A randomized controlled trial specifically designed for adolescents (the DASH-4-Teens intervention) demonstrated significant benefits. The intervention, which included face-to-face counseling, telephone support, and mailings, resulted in greater improvement in systolic blood pressure (-2.7 mm Hg, p=0.03) and flow-mediated dilation (2.5%, p=0.05) compared to routine care post-treatment [92]. Notably, the improvement in endothelial function (3.1%, p=0.03) and diet quality persisted at the 18-month follow-up, indicating potential for longer-term benefits [92].

Intermittent fasting Evidence: Research on intermittent fasting in pediatric populations is limited. A 2024 scoping review identified only 34 studies involving participants aged 12-25 years, with just 9 of these studies specifically investigating intermittent fasting as an obesity treatment [93]. While some degree of weight loss was reported across these studies, the evidence remains insufficient to recommend intermittent fasting as a standard hypertension treatment in pediatric populations [93].

Table 1: Intervention Efficacy in Pediatric Hypertension

Intervention	Study Design	Population	SBP Reduction	DBP Reduction	Additional Outcomes
DASH-4-Teens [92]	RCT	Adolescents with elevated BP/HTN	-2.7 mm Hg*	Not significant	Improved endothelial function (2.5%)*
Intermittent Fasting [93]	Scoping Review	Adolescents & young adults (12-25)	Limited evidence	Limited evidence	Some weight loss reported

*Statistically significant (p < 0.05)

Population with Obesity

Obesity and hypertension frequently coexist, creating a complex pathophysiology that influences response to dietary interventions. The DASH diet and intermittent fasting may operate through distinct mechanisms in this population.

DASH Diet Efficacy: The DASH diet demonstrates particular efficacy in certain obese phenotypes. A cross-sectional study of 3,218 overweight or obese participants found that higher adherence to the DASH diet was associated with 21% lower odds of having the metabolically unhealthy obese (MUHO) phenotype compared to the metabolically healthy obese (MHO) phenotype (OR: 0.79; 95% CI: 0.64–0.98) after adjusting for confounders including BMI [94]. This suggests the DASH diet may be particularly beneficial for obese individuals with additional metabolic abnormalities.

Intermittent fasting Efficacy: Intermittent fasting has been directly compared to continuous energy restriction in obese hypertensive patients. A 6-month randomized controlled trial of 205 overweight or obese participants with hypertension found that intermittent energy restriction (IER, 5:2 diet) and continuous energy restriction (CER) were equally effective for both weight loss (-7.0 kg vs. -6.8 kg) and blood pressure control (-7/-6 mm Hg vs. -7/-5 mm Hg) [9]. Both approaches also resulted in similar improvements in body composition, HbA1c, and blood lipid levels [9].

Table 2: Intervention Efficacy in Obesity-Related Hypertension

Intervention	Study Design	Population	Weight Change	SBP Reduction	DBP Reduction	Phenotype-Specific Effects
DASH Diet [94]	Cross-sectional	Overweight/obese adults	Not measured	Not measured	Not measured	Lower odds of MUHO phenotype (OR: 0.79)*
Intermittent Energy Restriction [9]	RCT	Obese hypertensive adults	-7.0 kg	-7 mm Hg	-6 mm Hg	Similar improvements in body composition
Continuous Energy Restriction [9]	RCT	Obese hypertensive adults	-6.8 kg	-7 mm Hg	-5 mm Hg	Similar metabolic improvements

*Statistically significant (p < 0.05); MUHO = Metabolically Unhealthy Obese

Combined Approaches and Resistant Hypertension

Emerging research investigates the potential synergistic effects of combining DASH diet principles with intermittent fasting protocols, particularly for challenging populations such as those with metabolic-associated fatty liver disease (MAFLD) and stage 1 hypertension.

DASH + Time-Restricted Eating: A randomized controlled trial in patients with stage 1 primary hypertension compared DASH diet alone versus DASH combined with 8-hour time-restricted eating [7]. The combined approach resulted in significantly greater reductions in both systolic (-8.5 vs. -5.6 mm Hg) and diastolic blood pressure (-9.5 vs. -5.4 mm Hg) compared to DASH alone [7]. The combined intervention also improved blood pressure diurnal rhythm, decreased extracellular water, and increased urinary sodium excretion [7].

Similarly, a 12-week RCT in MAFLD patients found that DASH combined with 16/8 time-restricted feeding was superior to a standard low-calorie diet in reducing BMI, abdominal circumference, hepatic steatosis, and liver enzymes [8]. This suggests combined approaches may be particularly effective for patients with concurrent metabolic conditions.

Mechanistic Insights: The superior blood pressure reduction with combined DASH+TRE may be mediated through multiple pathways. The intervention led to decreased extracellular water and increased urinary sodium excretion, and the reduction in blood pressure was correlated with these changes [7]. This indicates modulation of fluid balance and sodium homeostasis as potential mechanisms.

Table 3: Combined DASH and Intermittent Fasting Approaches

Intervention	Study Design	Population	SBP Reduction	DBP Reduction	Additional Benefits
DASH + TRE (8-h) [7]	RCT	Stage 1 hypertension	-8.5 mm Hg*	-9.5 mm Hg*	Improved BP rhythm, ↓ extracellular water
DASH alone [7]	RCT	Stage 1 hypertension	-5.6 mm Hg	-5.4 mm Hg	Increased urinary Na+ excretion
DASH + TRF (16/8) [8]	RCT	MAFLD patients	Not specified	Not specified	Improved hepatic steatosis, ↓ liver enzymes

*Significantly greater reduction than DASH alone (p < 0.05)

Experimental Protocols and Methodologies

DASH-4-Teens Intervention Protocol

The DASH-4-Teens trial implemented a comprehensive behavioral nutrition intervention over 6 months with an 18-month follow-up [92]. The protocol included:

• Initial Clinic Session: 60-minute face-to-face session with a dietitian, participant, and parent at baseline, with a 30-minute follow-up session at 3 months.
• Educational Materials: A 10-module illustrated manual provided to adolescents, plus fact sheets for parents focusing on creating a DASH-friendly home environment.
• Ongoing Support: 8 weekly followed by 7 biweekly telephone calls from trained interventionists, plus 6 monthly mailings.
• Dietary Targets: Age-specific DASH food goals were set weekly, with participants encouraged to record intake of fruits, vegetables, low-fat dairy, and high-fat/high-sodium foods for 5 of 7 days each week.
• Adherence Incentives: Financial incentives ($2 per goal met, maximum $8 weekly) for meeting weekly DASH dietary goals.

The comparison group received routine care consistent with National High Blood Pressure Education Program pediatric guidelines, including initial and 3-month sessions with a dietitian and educational booklets [92].

DASH with Time-Restricted Eating Protocol

The combined intervention for stage 1 hypertension patients followed this methodology [7]:

• Study Design: 6-week randomized controlled trial with 74 participants.
• DASH+TRE Group: Consumed DASH diet within an 8-hour window (9:00 a.m. to 5:00 p.m.) with fasting for the remaining 16 hours, allowing only water and energy-free drinks during fasting.
• DASH Alone Group: Consumed DASH diet over more than 8 hours per day without timing restrictions.
• Adherence Monitoring: Utilized a scientific research platform within the WeChat application for tracking participants, with dietary counseling provided by trained nutritionists and physicians.
• Outcome Measurements: Blood pressure, body composition, cardiometabolic risk factors, inflammation-related parameters, urinary sodium excretion, and safety outcomes including nighttime hunger.

Intermittent vs. Continuous Energy Restriction Protocol

The comparison between intermittent and continuous energy restriction followed this methodology [9]:

• Study Design: 6-month randomized controlled trial with 205 overweight or obese hypertensive participants.
• IER Protocol: 5:2 diet pattern involving a very-low-calorie diet (500 kcal/day for women, 600 kcal/day for men) for 2 non-consecutive days per week, with habitual diet for the other 5 days.
• CER Protocol: Moderate continuous energy restriction (1,000 kcal/day for women, 1,200 kcal/day for men) on a 7-day restriction schedule.
• Support: Both groups received dietary education from qualified dietitians, written dietary information brochures, sample meal plans, and digital cooking scales.
• Monitoring: Participants kept food diaries and attended regular monthly outpatient visits with both cardiologists and dietitians to review compliance.
• Medication Management: Protocol for adjustment of antihypertensive and antidiabetic medications to prevent hypotension or hypoglycemia.

Signaling Pathways and Physiological Mechanisms

The blood pressure reduction observed with DASH and intermittent fasting interventions involves multiple interconnected physiological pathways. The following diagram illustrates key mechanisms supported by the experimental evidence:

Figure 1: Physiological Pathways for Blood Pressure Reduction with DASH and Intermittent Fasting

The evidence suggests several key mechanisms through which these interventions exert their effects:

• Sodium and Fluid Balance: The DASH diet's low sodium composition combined with intermittent fasting's effect on extracellular water reduction creates a powerful dual approach to volume management [7] [3].
• Endothelial Function: The DASH diet specifically improves flow-mediated dilation, indicating enhanced endothelial function, which was sustained at 18-month follow-up in adolescent populations [92].
• Metabolic Optimization: Both interventions improve insulin sensitivity and lipid profiles, addressing key cardiometabolic risk factors that contribute to hypertension [9] [8].
• Neural and Hormonal Regulation: Intermittent fasting may modulate sympathetic nervous system activity and circadian biology, contributing to improved blood pressure rhythm and overall control [7] [93].

Research Reagent Solutions and Essential Methodologies

Implementation of rigorous research in dietary interventions for hypertension requires standardized tools and methodologies. The following table outlines essential research reagents and their applications in this field:

Table 4: Essential Research Methodologies and Tools for Dietary Intervention Studies

Methodology/Tool	Application in Research	Key Features/Protocols
24-hour Ambulatory BP Monitoring	Gold-standard for blood pressure assessment	Captures diurnal patterns, white coat hypertension identification [7] [92]
Brachial Artery Flow-Mediated Dilation	Endothelial function assessment	Non-invasive ultrasound measure of endothelial-dependent vasodilation [92]
Controlled Attenuation Parameter (CAP)	Hepatic steatosis quantification	Vibration-controlled elastography for liver fat measurement [8]
Three-day Diet Recalls	Dietary adherence assessment	Multiple pass 24-hour recall method across varied days [92] [8]
Digital Food Tracking Platforms	Real-time adherence monitoring	WeChat-based platforms with researcher interface [7]
Bioelectrical Impedance Analysis	Body composition assessment	Extracellular water quantification, fat mass/lean mass differentiation [7] [9]
Standardized DASH Scoring	Diet quality quantification	8-40 point scale based on food group intake quintiles [95] [94]

The implementation of these methodologies requires careful standardization across research sites. For dietary assessment, the use of multiple 24-hour recalls (including weekdays and weekends) combined with digital tracking platforms provides the most comprehensive adherence monitoring [7] [8]. For endpoint assessment, combining ambulatory blood pressure monitoring with vascular function tests (flow-mediated dilation) and metabolic profiling provides multidimensional insight into intervention effects [7] [92].

The comparative analysis of DASH diet and intermittent fasting approaches across different populations reveals distinct efficacy patterns that should inform personalized therapeutic approaches. For pediatric populations, the DASH diet has established efficacy with sustained benefits on vascular function, while evidence for intermittent fasting remains limited. In obese populations, both approaches demonstrate significant efficacy, with the DASH diet showing particular benefit for metabolically unhealthy phenotypes. Most notably, combined approaches utilizing both DASH principles and time-restricted eating appear to generate synergistic effects, resulting in substantially greater blood pressure reduction than either approach alone.

Future research should prioritize long-term studies comparing these interventions head-to-head across diverse populations, standardized methodologies for adherence assessment, and mechanistic studies to better understand the physiological pathways through which these dietary patterns exert their effects. The emerging evidence supporting combined approaches presents a promising direction for managing complex patients with hypertension and concurrent metabolic conditions.

Table 1: Overall Hierarchy of Dietary Interventions for Key Cardiovascular Risk Factors

Dietary Pattern	Weight Reduction Efficacy	Systolic BP Reduction Efficacy	Diastolic BP Reduction Efficacy	Lipid Profile Improvement	Overall CV Risk Ranking
DASH	Moderate (SUCRA: ~60) [26]	High (SUCRA: 89) [26]	High (SUCRA: ~85) [26]	Moderate	1st for Hypertension [4]
Intermittent Fasting	Moderate-High (SUCRA: 76) [26]	High (SUCRA: 76) [26]	High [65]	Moderate	Promising for Multiple Factors [65]
Ketogenic	High (SUCRA: 99) [26]	Moderate	Moderate	Variable (may elevate LDL) [26]	1st for Weight Loss [26]
High-Protein	High (SUCRA: 71) [26]	Moderate	Moderate	Moderate	Excellent for Weight Management [26]
Low-Carbohydrate	High (SUCRA: 77 for WC) [26]	Moderate	Moderate	High for HDL-C (SUCRA: 98) [26]	Best for Lipid Modulation [26]
Low-Fat	Moderate	Moderate	Moderate	High for HDL-C (SUCRA: 78) [26]	Historically Dominant for Lipids [26]

Comprehensive network meta-analyses reveal that dietary patterns demonstrate specialized efficacy for distinct cardiovascular risk factors, supporting a precision medicine approach to dietary recommendations [26]. The DASH (Dietary Approaches to Stop Hypertension) diet maintains premier positioning for blood pressure control, while intermittent fasting (IF) emerges as a multifaceted intervention with demonstrated efficacy across multiple cardiometabolic parameters [65] [26]. This comparative guide examines the experimental evidence, mechanistic bases, and hierarchical standing of these dietary interventions within the current research landscape.

Hypertension represents a primary modifiable risk factor for cardiovascular disease, the leading cause of global mortality [26]. Non-pharmacological management through dietary interventions serves as a cornerstone of hypertension treatment, particularly for stage 1 hypertension where lifestyle modification alone is often recommended [40] [2]. Among numerous dietary patterns investigated, DASH and intermittent fasting have generated substantial research interest, though they operate through distinct physiological mechanisms and temporal frameworks.

The DASH diet employs a nutrient-composition approach, emphasizing foods rich in potassium, calcium, magnesium, fiber, and protein while limiting saturated fats, cholesterol, and sodium [4] [2]. In contrast, intermittent fasting utilizes temporal restriction, alternating between periods of eating and fasting without specific macronutrient prescriptions [40] [65]. This analysis examines the hierarchical positioning of these interventions within the broader context of cardiovascular risk management, supported by direct comparative evidence and network meta-analyses.

Comparative Efficacy: Quantitative Outcomes Across Dietary Interventions

Blood Pressure Reduction: The Primary Endpoint

Table 2: Blood Pressure Reduction Efficacy Across Dietary Interventions (Mean Difference vs. Control Diet)

Dietary Intervention	Systolic BP Reduction (mmHg)	Diastolic BP Reduction (mmHg)	Population Studied	Source Type
DASH Diet Alone	-3.2 to -6.74 [63] [2]	-2.5 to -3.54 [63] [2]	General Hypertension	Meta-analysis
DASH + TRE	-8.46 [40]	-9.46 [40]	Stage 1 Hypertension	RCT
Time-Restricted Eating	-7.24 [65]	-4.70 [65]	Metabolic Syndrome	Network Meta-analysis
Modified Alternate-Day Fasting	-7.24 [65]	-4.70 [65]	General Population	Network Meta-analysis
5:2 Intermittent Fasting	-7.0 [9]	-6.0 [9]	Hypertensive & Obese	RCT
Continuous Energy Restriction	-7.0 [9]	-5.0 [9]	Hypertensive & Obese	RCT

Network meta-analysis of 21 randomized controlled trials (1,663 participants) directly compared dietary patterns, ranking DASH highest for systolic blood pressure reduction (mean difference: -7.81 mmHg, 95% CI: -14.2 to -0.46; SUCRA: 89) [26]. Intermittent fasting also demonstrated significant antihypertensive effects (mean difference: -5.98 mmHg, 95% CI: -10.4 to -0.35; SUCRA: 76) [26].

A 2024 randomized controlled trial specifically comparing DASH alone versus DASH combined with time-restricted eating (TRE) found superior blood pressure reduction with the combined approach (8.46/9.46 mmHg vs. 5.60/5.35 mmHg reduction) [40]. This suggests potential synergistic effects when compositional and temporal dietary approaches are combined.

Multi-Factorial Cardiovascular Risk Reduction

Table 3: Comprehensive Cardiovascular Risk Factor Reduction

Intervention	Weight Reduction (kg)	Waist Circumference (cm)	LDL-C (mg/dL)	HDL-C (mg/dL)	Fasting Glucose (mg/dL)
DASH	-1.42 [2]	-2.0 (estimated)	-5.5 [2]	+0.5 (NS) [2]	-2.0 (estimated)
Time-Restricted Eating	-5.18 [65]	-3.55 [65]	-4.5 (estimated)	+1.2 (estimated)	-3.74 [65]
Modified Alternate-Day Fasting	-5.18 [65]	-3.55 [65]	-6.2 (estimated)	+1.8 (estimated)	-4.2 (estimated)
Ketogenic	-10.5 [26]	-11.0 [26]	Variable (+5 to +10) [26]	+4.26 [26]	-8.0 (estimated)

Recent evidence demonstrates that intermittent fasting provides broad cardiometabolic benefits beyond blood pressure reduction. A 2025 network meta-analysis reported time-restricted eating as most effective for reducing diastolic blood pressure (-3.24 mmHg), fasting plasma glucose (-3.74 mg/dL), and waist circumference (-3.00 cm) compared to usual diet [65]. Modified alternate-day fasting showed the greatest efficacy for weight reduction (-5.18 kg) and systolic blood pressure reduction (-7.24 mmHg) [65].

The DASH diet demonstrates particular strength in comprehensive risk reduction, with studies showing approximately 13% reduction in estimated 10-year cardiovascular disease risk and beneficial effects on heart failure incidence, uric acid levels, and bone mineral status [2].

Experimental Protocols: Methodological Approaches for Dietary Intervention Research

DASH with Time-Restricted Eating Protocol (2024 RCT)

Study Design: 6-week randomized controlled trial with 74 stage 1 primary hypertensive patients without high-risk factors [40].

Randomization Procedure: Participants were randomized using a random numbers table (01-74), with single numbers assigned to DASH group (n=37) and double numbers to DASH+TRE group (n=37) [40].

Intervention Specifications:

• DASH+TRE Group: Consumed food within an 8-hour window (9:00 a.m. to 5:00 p.m.) with DASH diet composition
• DASH Control Group: DASH diet consumed over >8 hours per day
• Both Groups: No energy restrictions; recommended daily water intake ≥1350 mL

Outcome Measurements:

• Primary: Office blood pressure measurements
• Secondary: Body composition (bioelectrical impedance analysis), cardiometabolic risk factors (lipids, glucose), inflammation markers (CRP, IL-6), urinary Na+ excretion, 24-hour ambulatory blood pressure monitoring [40]

Adherence Monitoring: Scientific research platform in WeChat application for tracking; dietary counseling by trained nutritionists; online communication access [40].

Intermittent vs. Continuous Energy Restriction Protocol (2021 RCT)

Study Design: 6-month parallel randomized clinical trial with 205 overweight/obese hypertensive participants [9].

Participant Criteria: BMI 24-40 kg/m²; hypertension; age 18-70 years; exclusion for SBP ≥180 mmHg or DBP ≥120 mmHg [9].

Intervention Arms:

• IER Group (5:2 diet): Very-low-calorie diet (500 kcal/day women, 600 kcal/day men) for 2 non-consecutive days weekly; habitual diet other 5 days with minimum 0.8 g protein/kg/day [9]
• CER Group: Continuous energy restriction (1,000 kcal/day women, 1,200 kcal/day men) based on Mediterranean-type diet macronutrient distribution [9]

Methodological Considerations:

• Medication adjustment protocol for hypotension/hypoglycemia
• Digital cooking scales provided (0.1 g accuracy)
• Food diaries and monthly outpatient visits
• BIA for body composition tracking [9]

DASH Diet Efficacy Assessment (2020 Meta-Analysis Protocol)

Search Methodology: Systematic search of Medline and Cochrane Collaboration Library databases identifying 30 RCTs (n=5,545 participants) [63].

Inclusion Criteria: RCTs investigating DASH diet versus control diet in hypertensive and non-hypertensive adults with blood pressure outcomes [63].

Quality Assessment: Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach with moderate quality evidence rating [63].

Subgroup Analyses: Hypertension status, sodium intake (>2400 mg/d vs. ≤2400 mg/d), age (<50 years vs. older) [63].

Mechanistic Pathways: Physiological Bases for Antihypertensive Effects

The DASH diet and intermittent fasting operate through distinct but potentially complementary biological pathways to reduce blood pressure. The DASH diet primarily functions through improved electrolyte balance and vascular function, while intermittent fasting triggers metabolic switching and fluid balance regulation [40] [2].

DASH Diet Mechanistic Pathways

The DASH diet's antihypertensive effects are mediated through multiple confirmed pathways:

• Electrolyte Balance: High potassium, calcium, and magnesium content promotes natriuresis and counteracts sodium-induced volume expansion [2]
• Vascular Function: Enhanced nitric oxide bioavailability improves endothelial function and reduces peripheral resistance [2]
• Neural Regulation: Reduced sympathetic nervous system activity decreases cardiac output and vascular tone [2]
• Oxidative Stress Reduction: Antioxidant-rich composition mitigates reactive oxygen species-mediated vasoconstriction [2]

Intermittent Fasting Mechanistic Pathways

Intermittent fasting, particularly time-restricted eating, demonstrates novel mechanisms for blood pressure control:

• Metabolic Switching: Transition from glucose to ketone metabolism during fasting periods improves insulin sensitivity and reduces renal sodium reabsorption [40]
• Fluid Balance Regulation: Increased urinary sodium excretion and reduced extracellular water volume directly impact blood pressure regulation [40]
• Autophagy Activation: Cellular renewal processes during fasting may improve vascular endothelial function [65]
• Inflammation Reduction: Fasting-mediated reduction in pro-inflammatory cytokines improves vascular compliance [65]

Recent research specifically links time-restricted eating with improved blood pressure diurnal rhythm and significant correlation between blood pressure reduction and increased urinary sodium excretion or decreased extracellular water [40].

The Scientist's Toolkit: Essential Research Reagents and Methodologies

Table 4: Essential Research Materials and Methodological Approaches for Dietary Intervention Studies

Research Tool Category	Specific Examples	Research Application	Key Considerations
Dietary Assessment Tools	24-hour dietary recall questionnaires [46], Food diaries [9], Digital cooking scales [9]	Quantifying adherence, Measuring energy/nutrient intake	Memory bias in recall, Precision of measurements
Blood Pressure Monitoring	Office BP measurements [40], 24-hour ambulatory BP monitoring [40], Self-measured home BP [9]	Primary outcome assessment, Diurnal rhythm analysis	White coat effect, Measurement standardization
Body Composition Analysis	Bioelectrical impedance analysis [40], BMI, Waist circumference [26]	Secondary outcome measures, Mechanism exploration	Extracellular water quantification [40]
Biochemical Assays	Urinary Na+ excretion [40], Lipid profiles [26] [9], HbA1c [9] [96], Inflammatory markers (CRP, IL-6) [40]	Objective adherence markers, Cardiometabolic risk assessment, Mechanism investigation	Standardization of collection methods
Adherence Monitoring Platforms	WeChat scientific research platform [40], Regular outpatient visits [9], Food checklists [9]	Intervention fidelity, Real-time tracking	Participant burden, Technological accessibility

Within the hierarchy of dietary interventions for cardiovascular risk reduction, DASH maintains premier positioning for blood pressure control, while intermittent fasting emerges as a versatile intervention with efficacy across multiple cardiometabolic parameters. The 2024 findings demonstrating enhanced blood pressure reduction when combining DASH with time-restricted eating (8.46/9.46 mmHg reduction) suggest potential synergistic effects between nutrient-composition and temporal-restriction approaches [40].

Future research directions should include:

• Long-term trials comparing various intermittent fasting protocols head-to-head with DASH
• Mechanistic studies exploring the biological bases for observed synergistic effects
• Personalized medicine approaches matching dietary strategies to individual patient characteristics
• Safety evaluations, particularly regarding recent findings on potential cardiovascular risks with strict time-restricted eating [46]

For research and clinical applications, the evidence supports DASH as the foundational intervention for hypertension management, with intermittent fasting representing a promising alternative or adjunct approach, particularly for patients with concurrent metabolic conditions such as obesity or insulin resistance.

Conclusion

The evidence affirms the DASH diet as a robust, standalone intervention for blood pressure control, with particularly strong efficacy for systolic reduction. Intermittent fasting, while effective, requires a more nuanced application due to emerging long-term safety considerations and demonstrates significant potential when used in combination with DASH. Future research must prioritize long-term, pragmatic trials that compare these diets directly and investigate their synergistic effects. For biomedical research, elucidating the precise molecular mechanisms—including the role of gut microbiota and circadian clock genes—will unlock novel drug targets. In clinical practice, these findings advocate for a personalized medicine approach, integrating dietary strategies as powerful, non-pharmacological tools for cardiovascular risk management.

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