Abstract
Hypertension is a global epidemic and a risk factor for many adverse outcomes, including cardiovascular disease, kidney disease, and death. Lifestyle plays a significant role in the development and maintenance of hypertension, and guidelines from several organizations recommend lifestyle modifications as first-line intervention for hypertensive patients. Data supporting the use of plant-based diets in the treatment of hypertension goes back almost a century. More recently, clinical trial data, including randomized controlled trials, have established plant-based diets as an effective lifestyle intervention for high blood pressure (BP). Plant-based diets differ from the standard American diet in a myriad of ways, with some substances being present in either substantially higher or lower amounts. Although the precise mechanism of a plant-based diet’s beneficial effects on BP is unknown, many of these differences may be responsible. Attributes of a plant-based diet that may lower BP include a lower energy content leading to weight loss, a lower sodium content, an increased potassium content, reduced oxidative stress, higher bioavailability of the vasodilator nitric oxide, and beneficial effects on the microbiome. The evidenced-based benefits of plant-based diets in treating hypertension should lead providers to advocate for this dietary pattern for their patients.
‘In 1930, it was reported that German monks who ate vegetarian diets had lower BPs than those eating meat.’
Introduction
Hypertension is one of the most common diseases worldwide, affecting nearly 1.4 billion people globally and is a significant risk factor for the development of cardiovascular disease, kidney disease, and death. 1 An elevated systolic blood pressure (BP) was the leading global risk factor for the development of death and disability-adjusted life years in the 2017 Global Burden of Disease Study. 2 In the United States, hypertension is extremely prevalent, affecting 46% of the adult population, or 103.3 million people, with a lifetime prevalence of the disease of greater than 80%.3,4 Lifestyle choices, particularly diet, play a significant role in the development and maintenance of hypertension. Research dating back almost a century has demonstrated benefits of plant-based foods on the development and management of hypertension. In this article, we discuss the multiple lines of evidence supporting the incorporation of plant-based foods for the prevention and treatment of hypertension.
Observational Evidence
Population Studies
Some of the earliest evidence documenting the lack of hypertension in older adults eating primarily plant-based foods comes from aboriginal societies in Kenya, Western China, the Solomon Islands, and Australia.5-8 Although these studies did not occur in modern societies, they were informative and hypothesis generating. In parallel, other types of observational studies, including cross-sectional, case-control, and cohort studies were eventually published.
Cross-sectional Data
With data showing lower BPs in rural societies, researchers subsequently sought to determine whether this relationship existed in industrialized societies. In 1930, it was reported that German monks who ate vegetarian diets had lower BPs than those eating meat. 9 Two later studies examining American populations of different religious practices with similar geographic and demographic characteristics provided further insight. The first study by Anholm 10 compared BPs of vegetarian Seventh Day Adventists with that of omnivorous Mormons (matched for age and sex) with similar lifestyles and found lower BPs in the Adventists consuming a vegetarian diet. Although no details regarding confounding factors (sodium intake, etc) were provided, the behaviors of the Mormons and Adventists are thought to be similar enough to serve as controls for one another while examining differences in diet. The second study by Rouse et al 11 compared vegetarian Adventists to omnivorous Adventists and Mormons and also showed lower rates of hypertension and lower BPs among those eating vegetarian diets. 11 After adjusting for age, height, and weight, mean BPs in Adventist vegetarian men (115.6 ± 9.5/68.7 ± 9.2 mm Hg) and women (109.1 ± 10.1/66.7 ± 9.3 mm Hg) were lower than in omnivorous Mormons (men 121.2 ± 9.8/72.3 ± 9.6 mm Hg; women 114.9 ± 10.5/72.6 ± 9.7 mm Hg). In addition, the prevalence of hypertension ranged from 8.5% to 10% for omnivores but only 1% to 2% for vegetarians.
Over the ensuing decades, dozens of cross-sectional studies were published. A meta-analysis of 32 of these studies involving 21 604 participants showed that consumption of vegetarian diets was associated with lower mean BP (−6.9/−4.7 mm Hg;
The Epic-Oxford study analyzed 11 004 British men and women with and without hypertension and found that those who were vegan had the lowest rates of hypertension and the lowest BPs.
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Meat eaters had the highest rates of hypertension and the highest BPs, whereas vegetarians and pescatarians had intermediate values. Omnivorous men were more than 2.5 times as likely as vegan men to have hypertension. The difference in BPs between meat eaters and vegans without hypertension was 4.2/2.8 mm Hg for men (
The findings of the Epic-Oxford study were confirmed in a North American population in a calibration substudy of the AHS-2. The substudy, originally designed to evaluate the collection and reporting of data in AHS-2, analyzed the BPs of 504 nonblack individuals randomly selected from the larger AHS-2 cohort of 96 000 Adventists living in the United States and Canada according to their dietary preference as vegan, ovolactovegetarian, or nonvegetarian.
14
The researchers found that vegetarians and vegans had lower BPs than meat eaters. After adjusting for gender and age, vegans had a mean lower systolic and diastolic BP of 6.8 mm Hg (
Prospective Cohort Data
Several prospective cohort studies have examined the effects of dietary patterns on BP, most notably a substudy of the Coronary Artery Risk Development in Young Adults (CARDIA) study and a combined analysis of the Nurses’ Health Study I (NHS I), Nurses’ Health Study II (NHS II), and the Health Professionals Follow-up Study (HPFS). In the CARDIA substudy, investigators followed 4304 young (18 to 30 years old) black and white men and women for more than 15 years and found a dose-dependent relationship between plant food intake (whole grains, refined grains, fruit, vegetables, nuts, or legumes) and a decreasing incidence of elevated BP (defined as a systolic BP ≥130 mm Hg, a diastolic BP ≥85 mm Hg, or the use of antihypertensive medications). 17 In contrast, red and processed meat intake was directly associated with a higher incidence of elevated BP. Those in the highest quintile of meat consumption had a higher risk (hazard ratio [HR] = 1.67; 95% CI = 1.21-2.30) of incident elevated BP compared with those in the lowest quintile.
Similarly, the combined analysis of the NHS I, NHS II, and HPFS showed an association between developing hypertension and the consumption of red meat, processed meat, poultry, and seafood. 18 The study included 188 518 participants with nearly 3 million person-years of follow-up, making it the largest prospective study to date on animal consumption and incidence of hypertension. Consumption of 1 serving/d of any animal flesh was positively associated with incident hypertension (pooled HR = 1.30; 95% CI = 1.16 to 1.47). Other smaller prospective studies have shown similar findings.18-23
Nonrandomized Experimental Evidence
Some of the earliest experimental evidence showing that plant-based diets reduced BP date back to nearly a century ago. In 1926, Arthur Donaldson published a case series of 5 vegetarian college students who had higher BPs after including meat in their diet. 24 Ten years later, Heun 25 reported an impressive average decline in BP of 60/28 mm Hg in 14 severely hypertensive patients who were treated with a fruit and vegetable diet.
In the 1940s, Walter Kempner, a physician at Duke University, gained attention for his ability to treat hypertension with a “rice diet” that excluded animal-based foods. 26 The carefully constructed diet included primarily white rice, fruits, and sugars; was designed to limit sodium to approximately 0.35 g of sodium chloride per day; and was calorie controlled according to the patients’ needs. Over several decades, Kempner treated thousands of patients with this diet. Although Kempner never performed a randomized controlled trial, he did publish data of a cohort of 777 patients treated on the diet for an average of 92 days, which resulted in an average decrease in BP from 196/116 to 150/96 mm Hg. Although his data were not adjusted for weight loss and his diet required close supervision, his results were still informative. 27
Randomized Experimental Evidence
In the mid-1980s, Australian researchers performed a pair of randomized controlled trials to test the effects of vegetarian diets on BP. In the first study (a 6-week crossover-design trial of 59 participants), consumption of a vegetarian diet lowered BP by 6.8 ± 8.8/2.7 ± 6.3 mm Hg (
The DASH trial was the first, major randomized controlled trial to evaluate the effects of a mostly plant-based diet on BP. The “DASH” diet was created to “have the blood pressure-lowering benefits of a vegetarian diet, yet contain enough animal products to make them palatable to nonvegetarians.”
30
As a result, researchers created the DASH diet to include plant foods, like fruits, vegetables, and grains, but also low-fat dairy and limited amounts of lean meat. In all, the trial had 3 arms: a control diet to represent the “standard” American diet; the DASH diet; and finally, a “fruits and vegetables” diet that was an intermediate between the DASH and control diets. None of the diet types were completely vegetarian or vegan because they included varying proportions of red meat, fish, poultry, and dairy. Importantly, all food was provided over the 8-week study period to minimize dietary noncompliance, and weight and dietary sodium were kept stable to avoid confounding. In total, data from 459 adults were analyzed to show that the DASH diet reduced BP by a mean of 5.5/3.0 mm Hg (
The fruits and vegetables diet also lowered BP like the DASH diet but to a lesser extent. The smaller BP reduction can be explained by differences in dietary composition between the 2 groups. The fruits and vegetables group was similar to the control diet except for having more servings of fruits (5.2 vs 1.6) and vegetables (3.3 vs 2.0) per day. This amount of fruits and vegetables was similar to the DASH diet but did not exceed it. In fact, the DASH diet itself may have been more plant- based than the fruits and vegetables group because it had a higher number of daily servings of fruits (4.4 vs 3.3) and grains (7.5 vs 6.9) and fewer servings of beef, pork, and ham (0.5 vs 1.8). Despite these differences, both the DASH diet and fruit and vegetable group had the same amount of fiber of 31 g/d, which was more than the 9 g/d in the control diet. The DASH diet was also lower in fat (27% vs 37% of total calories) compared with the fruits and vegetables diet, which may have also helped with BP reduction. 33
Sodium restriction in conjunction with the DASH diet was not tested until several years later (DASH-sodium trial) and showed that limiting sodium consumption had additional effects on BP reduction when combined with the DASH diet.
34
A secondary analysis of the DASH-sodium trial showed that the magnitude of BP reductions increased with increasing baseline BP.
35
When compared with a high-sodium control diet (standard American diet), the DASH-sodium diet reduced BP by 20.8 mm Hg (95% CI = −30.88 to −10.69;
Ostensibly, the reduction in BP from the DASH-sodium diet might have been greater with the total elimination of animal-based foods from the diet. Further improvements could have been made by including a higher percentage of whole grains in the diets, which have been shown to lower BP and accounted for roughly 50% of grains consumed by weight for the DASH and fruits and vegetables diets in the study.30,36 Finally, fruit juices were the largest contributors, by weight, to the amount of fruit consumed in each of the 3 diets. 30 Replacing the fruit juices with actual fruit may further reduce BP because fruit juice has been associated with higher BPs and fruit itself with lower readings.37,38
Evidence from additional trials have confirmed the effect of plant-based foods on BP. In a meta-analysis of 7 clinical trials that excluded the DASH diet trials, Yokoyama et al
12
analyzed data from 311 participants to show that consumption of vegetarian diets reduced BP by 4.8 mm Hg (95% CI = −6.6 to −3.1;
Randomized Experimental Evidence: Chronic Kidney Disease
Metabolic acidosis, or a reduced serum bicarbonate level because of an inability to excrete endogenous acid, is a common complication of chronic kidney disease (CKD). Several randomized trials designed to test the efficacy of fruits and vegetables on metabolic acidosis in CKD provide evidence of a beneficial effect of increased consumption of plant-based foods on BP as well. In a trial of the effects of fruits and vegetables on metabolic acidosis in 199 participants with stage I or II CKD, researchers found that 2 to 4 cups of fruits and vegetables were able to significantly lower systolic BP by 2.4 ± 2.3 mm Hg (
Similar benefits have been seen in patients with CKD stages 3 and 4 as well.40,41 In 2 separate studies by Goraya et al, 39 participants were treated with either the addition of fruits and vegetables to their current diet or bicarbonate to treat the metabolic acidosis of CKD. The CKD stage 3 study also included a usual care group, which received neither fruits and vegetables nor supplemental bicarbonate.
Although both fruits and vegetables and supplemental bicarbonate were successful in increasing serum bicarbonate, the fruits and vegetables group had lower BPs on follow-up. For patients with CKD stage 3, systolic BP after 3 years of intervention was 128 mm Hg versus 136 mm Hg for the supplemental bicarbonate group and 135 mm Hg for the usual care group (both comparisons
Mechanisms of Blood Pressure Reduction
The tendency for plant-based foods to lower BP and animal-based foods to raise BP may be related to several mechanisms, which are described below.
Weight
Plant-based diets can help facilitate weight loss by being high in fiber, low in fat, and having a reduced energy density. 43 Losing weight and having a lower body weight are associated with lower BPs, whereas weight gain and obesity are associated with higher measurements. 44 Obesity can facilitate a rise in BP through several mechanisms, including increased tubular sodium reabsorption impairing pressure natriuresis, activation of the renin-angiotensin-aldosterone system, and increased sympathetic nervous system activity. 45
Although vegetarians and vegans do have lower BMIs, differences in BP persist after adjusting for weight in multiple studies.13,18 In a population of Israeli adults, Ophir et al 46 also found that the BP of vegetarians was lower than that of nonvegetarians of a similar body weight.
Sodium
A surfeit of total body sodium has long been thought to contribute to hypertension.47,48 Because vegans consuming a plant-based diet (including fruits, vegetables, legumes, and whole grains) typically consume less sodium than nonvegans, this has been proffered as a potential mechanism explaining its antihypertensive effect.49,50 However, it is important to note that a vegan diet can be altered to be high in sodium and that any benefit of eating foods without sodium can be negated by adding sodium, especially in the context of processed foods.
The Intersalt study examined the relationship between 24-hour urinary sodium excretion and blood electrolytes in more than 10 000 participants from more than 30 countries and found a significant relationship between sodium excretion and BP. 51 A recent meta-analysis found that decreasing sodium intake from an average of 201 to 66 mmol/d led to a significant reduction in both systolic and diastolic BP in those with hypertension, irrespective of race. 52 A separate meta-analysis found a strong linear dose-response relationship between sodium intake and BP. Each reduction of 2.3 g of sodium per day was associated with a reduction in systolic BP of 3.82 mm Hg. 53
Potassium
It has been well recognized for almost a century that higher potassium intake improves BP. Addison published a case report in 1928 showing that BP could be lowered by the administration of potassium salts. 54 In recent decades, most55-60 but not all 61 meta-analyses have confirmed this finding, demonstrating that potassium supplementation leads to significant BP reduction. The current animal-heavy Western diet contains less potassium than diets traditionally consumed by humans. The Institute of Medicine sets the level of adequate intake of potassium at 4700 mg/d, 62 yet most Americans fall far short of this value. Data from the National Health and Nutrition Examination Survey for the period 2009-2010 show that for men and women >20 years of age, the mean potassium intake was 2992 and 2296 mg, respectively, and that less than 25% of men and 1% of women are meeting the 4700-mg recommendation. 63 This is in stark contrast to our prehistoric ancestors whose potassium intake is estimated to have been up to 15 000 mg/d. 64 The potassium content does differ between dietary patterns. An Australian cross-sectional study found that among men 20 to 59 years of age, vegans consumed more potassium daily (5959 ± 1580 mg) compared with ovolactovegetarians (5014 ± 1411 mg) and moderate meat eaters (4126 ± 1038 mg), although high meat eaters also had a high daily potassium intake (5855 ± 1529 mg). 65 In addition to the amount of potassium, the sodium to potassium ratio has also been shown to positively correlate with BP.66,67 In the Australian study cited above, despite having similar levels of potassium excretion, vegans had much less sodium in their urine, manifesting a lower urinary sodium to potassium ratio compared with heavy meat eaters (0.46 ± 0.17 vs 0.78 ± 0.20). 65
Several mechanisms have been proposed to explain how potassium achieves its BP-lowering effect. Experimental work shows that potassium can inhibit sodium reabsorption in many areas of the kidney, and it is postulated that this natriuresis contributes to the BP-lowering effect. 68 In addition, by virtue of its stimulatory effects on the sodium-potassium ATPase, potassium leads to cellular hyperpolarization with enhanced net positivity of its interior. This, in turn, leads to a decreased cytosolic calcium concentration with resultant vasodilation. Other possible mechanisms include inhibition of the sympathetic nervous system and increased endothelial nitric oxide (NO) production. 69
Animal Protein
Much of the information described previously suggests that animal-based foods may directly raise BP. Further evidence for this hypothesis comes from a secondary analysis of amino acid intake within an observational cohort study of participants consuming either low-fat or Mediterranean style diets. 70 Tuttle et al 70 found that intake of methionine and alanine, which are seen in higher proportions in animal-based foods, were associated with higher BP, whereas intake of threonine and histidine, which are found in higher proportions in plant-based foods, had the opposite association. There are several putative mechanisms to explain this association. First, methionine is a homocysteine precursor that may increase BP by raising concentrations of asymmetric dimethylarginine, a competitive inhibitor of NO, which lowers BP. Another explanation is the formation of advanced glycation end products (AGEs) when animal protein (red meat, pork, high-fat cheese, poultry, and eggs) is cooked under high heat to cause browning, or a Maillard reaction, which occurs as a nonenzymatic reaction between reducing sugars and free amino moieties. 71 AGEs then induce vasoconstriction and anti-natriuresis by stimulating the release of angiotensin II. 70 AGEs also promote oxidative stress through the production of reactive oxygen species (ROS), which cause NO quenching, impairing vasodilation to ultimately raise BP.
Plant Protein: Redox Signaling
Redox signaling, or signal transduction by electron transfer, is another potential mechanism through which plant-based diets may affect BP.
72
The main effectors of redox signaling are ROS, which are generated by endothelial cells and other vascular constituents. Among other actions, these ROS play an important role in vascular tone.
72
NO, a gas synthesized by vascular endothelial cells, has a critical signaling role in vascular biology. NO leads to vasodilation and lowering of BP, and decreased bioavailability of NO is associated with arterial hypertension.
73
ROS play an important role in NO-based cell signaling via actions on endothelial nitric oxide synthase (eNOS). eNOS produces NO via the oxidation of
When oxidative stress is increased, eNOS can lose this physiological function and, instead of producing NO, result in the generation of superoxide (O2-). 74 This is known as eNOS uncoupling. Many compounds exert beneficial effects on redox signaling, ultimately resulting in increased NO generation. 74 Examples of such compounds, collectively known as polyphenols, include flavonoids, stilbenoids, curcuminoids, and phenylethanoids. Data show that these compounds act on NO signaling and metabolism, augment eNOS expression, and reduce eNOS uncoupling. Because plant-based foods contain polyphenols, the enhanced availability of NO via these effects on redox signaling is another potential mechanism of their antihypertensive effect. In addition to their antioxidant properties, certain vegetables, such as leafy greens and beets, are rich in natural nitrates, and data suggest that high-nitrate foods are associated with lower BP, with the postulated mechanism being increased bioavailability of NO. 75 These nitrates may serve as an eNOS-independent source of NO; however, to become bioactive, dietary nitrate requires an initial reduction to nitrite. 76 Humans lack the requisite gene for this reduction, but this reaction can be carried out by commensal bacteria within the oral flora. The nitrite produced can act as a storage pool of NO or act as a NO independent signal.
Microbiome
The microbiome refers to the endogenous population of microbes that line our body surfaces, including the skin and the gut. Experimental animal studies indicate an altered microbiome in hypertension and that transplanting the cecal microbiota of hypertensive animals can induce hypertension in previously normotensive recipients.77,78 Although human data are scarce, there is some information to guide understanding of the effects of plant-based diets on the microbiome and BP. An analysis of 10 patients with a normal SBP (119 ± 2 mm Hg) and 7 patients with an elevated SBP (144 ± 9 mm Hg) showed changes in the gut microbiome, including decreased bacterial diversity and composition.
78
In another study, researchers fed various molecular weights of β-glucan, a major soluble fiber found in oat and barley, to participants to examine changes in the microbiome and cardiovascular risk.
79
Consumption of high-molecular-weight β-glucan produced a favorable shift in the
Proposed mechanisms linking dysbiosis of the microbiome and hypertension include, among others, increased short-chain fatty acid (SCFA) production, changes in gene expression, inflammation and increased sympathetic nervous system activity, an induction of salt sensitivity and modulation of endothelium-derived NO. 80 Of these, the role of SCFAs in hypertension may be the best understood. Consumption of dietary fiber leads to colonic fermentation and, ultimately, the production of SCFAs, which have been shown to have vasodilatory properties.81-83
Epigenetics
Epigenetics refers to changes in phenotype caused by alteration in gene expression rather than changes to the genetic code itself. The mechanisms of epigenetic regulation include DNA methylation, histone modification, and RNA mechanisms.84,85 Bioactive substances in food may modulate BP in an epigenetic fashion. Human data linking plants or plant bioactives to improved BP via epigenetic mechanisms are lacking; however, animal data support this theory. Experiments in salt-sensitive rats show worse hypertension and renal damage in rats fed a diet high in animal protein versus those fed a diet high in plant-based protein. 86 In addition, DNA methylation and histone modification are associated with modification in expression of many genes associated with hypertension, including angiotensinogen, the α unit of the electroneutral sodium channel (ENaC), glucocorticoid receptor, and angiotensin-converting enzyme 1. 87 Many plant-derived compounds do show activity either in inhibiting DNA methylation or in histone modification, making epigenetic mechanisms a plausible contributor to the antihypertensive mechanism of a plant-based diet. 88
Other putative mechanisms explaining the beneficial effects of a plant-based diet on BP in adults include (but are not limited to) increased fiber, a decreased amount of high-fructose corn syrup present (such as those found in sugar-sweetened beverages), and downregulation of the renin angiotensin and the sympathetic nervous systems.89-92
Hypertension in Children
Hypertension affects children, and longitudinal studies show that high BP in childhood tracks with high BP as an adult and also increases the risk of end-stage renal disease.93,94 Because hypertension causes end-organ damage over time, early treatment may mitigate long-term consequences. The prevalence of hypertension is estimated at approximately 3.5% of the general pediatric population. 95 The prevalence is higher in those with obesity; systolic BP increases as BMI and waist circumference increase.96-98
Although research is limited, plant-based diets have been shown to be beneficial in children. In a small 4-week randomized trial comparing a plant-based diet with the American Heart Association diet in obese children with hypercholesterolemia, the former group demonstrated a significant mean decrease in their systolic BP of 6.43 mm Hg from baseline. 99 Although larger and longer duration studies are needed, this result demonstrates the ability of a plant-based diet to lower BP in children.
In 2017, the American Academy of Pediatrics updated its
Conclusion
Plant-based diets have long been used in the management of hypertension. Studies in the future, including longer duration of randomized trials, may help elucidate the long-term effects. At this time, however, the preponderance of the evidence suggests that plant-based diets are a safe and effective way to manage high BP without the side effects of antihypertensive medications. There are many potential mechanisms explaining how plant-based diets exert their beneficial effects on BP, and future research will likely clarify these. In the interim, we support the use of a predominantly (or completely) plant-based diet as first-line therapy for the management of hypertensive patients.
Footnotes
Authors’ Note
The authors of this article have participated in all stages of manuscript production, declare no conflicts of interest, and agree to publish the article.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.
Ethical Approval
Not applicable, because this article does not contain any studies with human or animal subjects.
Informed Consent
Not applicable, because this article does not contain any studies with human or animal subjects.
Trial Registration
Not applicable, because this article does not contain any clinical trials.
