Addressing Hypertension via Nutrition

Known as the “silent killer,” hypertension is the medical term for high blood pressure. The American Heart Association (AHA) estimates approximately 73 million American adults age 20 and over have high blood pressure, although only 70 percent are aware of it. Further, only 60 percent of adults who have hypertension are being treated for it, and two-thirds of those don’t have it under control.

Blood pressure (BP) itself results from two forces. The top number—systolic—represents the pressure created by the heart as it contracts to pump blood into the arteries and through the circulatory system. The lower number—diastolic—is the pressure when the heart relaxes between beats as the arteries resist the blood flow. AHA defines hypertension as a systolic blood pressure of 140 mmHg or higher, or a diastolic blood pressure of 90 mmHg or higher. Almost 30 percent of adults have prehypertension, with systolic BP between 120 and 139, or diastolic BP of 80 to 89.

Prehypertension and hypertension can be at work in the body for years, damaging the heart, kidneys and blood vessels. By making the heart work harder than is optimal, hypertension contributes to atherosclerosis and increases the risk for heart disease and stroke. Further, it can exacerbate development of conditions such as congestive heart failure, kidney disease and blindness.

Unfortunately, the cause of up to 95 percent of hypertension cases is unknown. MayoClinic.com outlined a number of risk factors, including older age, race (the condition is more common among blacks), family history, excess weight, inactivity, tobacco use and stress. It further noted an imbalance of sodium and potassium intake can raise blood pressure. Excess sodium can lead to fluid retention, which increases pressure in the arteries; potassium balances the levels of sodium in the body’s cells.

Because of the uncertain etiology, diet is considered a front-line approach to avoiding high blood pressure and helping to manage it if and when it is diagnosed. In fact, AHA released a statement in 2006¹ that noted, in part: “A substantial body of evidence strongly supports the concept that multiple dietary factors affect blood pressure (BP). Well-established dietary modifications that lower BP are reduced salt intake, weight loss, and moderation of alcohol consumption (among those who drink). Over the past decade, increased potassium intake and consumption of dietary patterns based on the ‘DASH diet’ have emerged as effective strategies that also lower BP.”

The original Dietary Approaches to Stop Hypertension (DASH) clinical study, funded by the National Institutes of Health (NIH), was conducted at Johns Hopkins University, Baltimore, with results published in 1997 in the New England Journal of Medicine.² That study showed the DASH combination diet could help lower BP and control hypertension. The DASH diet emphasizes consuming fruits, vegetables and low-fat dairy products; is low in saturated fat, total fat and cholesterol; and has high levels of dietary fiber, potassium, calcium and magnesium.

While initial interest in and adherence to the DASH diet was positive, the message has lost some of its initial impact. Researchers from the Hypertension Center of the Hattiesburg Clinic, Hattiesburg, Miss., analyzed data from the National Health and Nutrition Examination Survey (NHANES) from the 1988 to 1994 and 1999 to 2004 periods to determine DASH accordance among adults with hypertension.³ They found accordance with the DASH diet was 7.3-percent lower in the more recent NHANES survey than the previous one, suggesting the impact of the initial message is being lost. However, researchers from Duke University, Durham, N.C., conducted an intervention using the DASH diet plus behavioral counseling, and found adding enhancements could increase adherence and inclusion of nutrient-dense foods.⁴ Another possibility was tested in the OmniHeart trial at Brigham and Women’s Hospital, Boston, which found using the DASH diet as a starting point and offering some level of flexibility in macronutrient intake, such as increasing protein levels slightly or raising the level of healthy unsaturated fats, could achieve similar results in relation to high blood pressure while making it easier to follow the diet in the long-term.⁵

The type of protein in the diet may also impact blood pressure. Soy, for example, has a heart healthy profile and approved health claim. Data from the Shanghai Women’s Health Study indicated long-term consumption of soy protein was inversely related to both systolic and diastolic BP, with the association growing stronger with age.⁶ And intervention work out of Beth Israel Deaconess Medical Center, Boston, showed substituting soy nuts for non-soy protein could significantly reduce blood pressure in both normotensive and hypertensive women.⁷ The researchers suggested the impact may be due to improved endothelial function and reduction in inflammation.

Certain compounds found in soy may also have an effect on blood pressure. Isoflavones, phenolic compounds found in soy, have been an area of focus. In one Korean study using hypertensive rats, adding 10 g/kg/d of soy powder, with 31-percent isoflavones, to a high-fat diet decreased oxidative damage, prevented incremental increases in blood pressure and augmented the production of nitric oxide (NO), which positively affects endothelial function.⁸ Another animal trial focused specifically on the isoflavone genistein, and found supplementation could improve aortic endothelial-derived NO, alleviating hypertension in the rats.⁹

Another soy-related compound is nattokinase, an enzyme originally isolated from the fermented soy food natto. The enzyme has the ability to break up blood fibrin, a protein involved in clotting. Japanese research has found consumption of 30 g of lyophilized natto extract could reduce both systolic and diastolic blood pressure in human volunteers. In fact, unpublished research on nattokinase (as NSK-SD®, from Japan Bio-Science Laboratories) has found the compound had significant effects on blood coagulation, improving blood flow, and also aids in reducing hypertension in adults with untreated high blood pressure.

Soy is not the only positive protein source when looking at blood pressure regulation. Milk proteins, both casein and whey, are rich sources of peptides that can inhibit vasoconstrictor enzymes such as angiotensin-1-convering enzyme (ACE), and positively impact vasodilation.¹⁰ Researchers from the University of Helsinki, Finland, evaluated the anti-hypertensive mechanisms and vascular effects of tetrapeptides from milk protein in spontaneously hypertensive rats (SHR).¹¹ The tetrapeptides from alpha-lactorphin and beta-lactoglobulin improved vascular relaxation, with the former affecting endothelial function and the latter enhancing endothelium-independent relaxation.

The Finnish researchers also reported long-term intake of the peptides isoleucine-proline-proline (IPP) and valine-proline-proline (VPP) in SHR attenuates the development of hypertension by inhibiting angiotension converting enzyme (ACE), a key regulator for the production of the vasoconstricting hormone Angiotensin 2.12 Further, there is evidence from animal trials that the opioid receptors may be involved in the ability of tetrapeptides to lower diastolic and systolic blood pressure.13

In one clinical trial out of the University of Minnesota, Minneapolis, researchers randomized 30 prehypertensive adults to receive 20 g/d of hydrolyzed whey protein or an unmodified whey control for six weeks.¹⁴ After intervention, the patients taking the whey-derived peptides had significant reductions in systolic and diastolic blood pressure, and improvements in LDL cholesterol and inflammatory markers.

Another beneficial protein source when looking at blood pressure control is fish. Australian researchers recently reported following a dietary pattern with higher consumption of fish, salad and cereals in adolescence positively impacts diastolic blood pressure and sets the stage for preventing chronic disease.¹⁵ In another study from Australia, researchers examined the association between fish consumption and microvascular structure from a 12-year cohort, and found higher consumption of fish had vascular protective effects.¹⁶ And Italian researchers reported hypertensive adults who made a long-term dietary change to consume more fish and vegetables had greater control of blood pressure.¹⁷

A review from the University of Connecticut Health Center, Farmington, noted studies on fish oil and its omega-3 essential fatty acids have shown consuming fish oil can produce a small but significant decline in blood pressure, particularly among adults with hypertension.¹⁸ The International Study of Macro- and Micro-nutrients and Blood Pressure (INTERMAP), an international cross-sectional epidemiologic study of 4,680 adults from population-based samples in China, Japan, the United Kingdom and United States, has looked at the impact of omega-3s on blood pressure parameters.¹⁹ There does appear to be an inverse relationship between total omega-3 intake from food and diastolic and systolic blood pressures, with greater impact related to long-chain omega-3 intake from fish.

As mentioned earlier, balancing mineral intake is another important dietary adjustment to controlling blood pressure. Data from the INTERMAP trial, for example, found greater intakes of dietary calcium, magnesium and phosphorus were inversely associated with blood pressure.²⁰ And researchers from the University of Helsinki, Finland, said the country’s salt reduction efforts, combined with greater intakes of potassium, calcium and magnesium, have contributed to a more than 10 mm Hg fall in the population average of systolic and diastolic blood pressure.²¹

Dairy products are one of the leading sources of calcium in the diet, and studies have shown an inverse association between dietary consumption of dairy products and calcium and blood pressure. For example, Harvard researchers looking at the relationship between hypertension and dairy products in a cohort of 28,886 U.S. women found intakes of low-fat dairy products, calcium and vitamin D were each inversely associated with hypertension.²² Similarly, French researchers reported consumption of dairy products and dietary calcium were both significantly and independently associated with low levels of systolic blood pressure in a sample of more than 900 middle-aged men.

Balancing intake of calcium with magnesium is important, as magnesium helps to regulate blood pressure and an inverse relationship has been seen between intake of this mineral and incidence of hypertension.²³ Researchers from the University of Ottawa, Ontario, note magnesium influences blood pressure by modulating vascular tone, impacting vasodilation, and helping control inflammation.²⁴ Animal trials have further found that a diet even moderately deficient in magnesium can have long-term adverse effects on arterial thickness and stiffness, increasing arterial pressure and increasing incidence of hypertension.²⁵

Another nutritional compound that supports vascular health is vitamin C, which enhances collagen production and vascular flexibility. Further, hypertensive adults appear to have higher levels of oxidative stress and lower plasma levels of vitamin C, suggesting oxidative stress may play a role in the pathology of hypertension.²⁶ Clinical trials have found a benefit to reducing oxidative stress. A study out of Japan found providing ascorbic acid (600 mg/d) to elderly patients being treated for hypertension could markedly reduce systolic blood pressure and pulse pressure.²⁷ Another study conducted in India reported similar results, as 1,000 mg/d of vitamin C added to antihypertensive therapy reduced systolic blood pressure and decreased parameters of oxidative stress.²⁸

Combined antioxidant supplementation—vitamin C plus the fat-soluble vitamin E—may have even better results. Researchers from the University of Pisa, Italy, evaluated the effect of vitamin C (1 g/d) and vitamin E (400 IU/d) versus placebo in hypertensive men (n=30) for eight weeks.²⁹ Intervention significantly improved flow-mediated dilation (FMD) and arterial flexibility, as well as vasodilation and oxidative stress parameters. A similar intervention netted like results in a trial from the University of Chile, Santiago, in which men with hypertension (n=110) who took vitamins C+E for eight weeks had significantly lower systolic and diastolic blood pressure and higher serum antioxidant capacity.³⁰

Vitamin E’s tocotrienol isomers also appear to play a role in reducing hypertension. In one study, hypertensive rats were treated with gamma-tocotrienol for three months; plasma and blood vessel lipid peroxides were reduced, and total antioxidant status was improved.³¹ In follow-up work, the same team found gamma-tocotrienol could reduce systolic blood pressure significantly, and improve nitric oxide synthase (NOS) activity, impacting the pathogenesis of hypertension.³²

The fruits and vegetables emphasized in the AHA-recommended dietary interventions don’t only deliver more basic vitamins and minerals; they’re also rich sources of flavonoids, water-soluble antioxidant compounds with positive health effects. A recent review out of the University of Anglia, Norwich, England, examined the efficacy of different flavonoid subclasses and flavonoid-rich foods on different parameters of heart health, including blood pressure.³³ Leading the review was chocolate, which increased FMD and reduced systolic and diastolic blood pressure and soy protein isolate, and reduced diastolic blood pressure and LDL cholesterol. The team noted future studies should look at commonly-consumed flavonoid classes such as anthocyanins and flavanones to provide greater evidence of health effects. Johanna Geleijnse, Wageningen University, Netherlands, who authored an editorial accompanying the report, noted: “Evidence is accumulating that these substances are more important to cardiovascular health than vitamin C and vitamin E.”³⁴

Chocolate, which topped the review, has garnered great media attention, as studies have shown its positive effects on heart health. A review from Athens Medical School, Greece, noted dark chocolate and flavonoid-rich cocoa have a blood-pressure lowering effect that can be attributed to the flavonoids’ impact on increased NO bioavailability.³⁵ Their theory was supported by a study published in the Journal of the American Medical Association (JAMA), which found providing adults with untreated prehypertension or stage 1 hypertension with 6.3 g/d of dark chocolate with 30 mg of polyphenols for 18 weeks decreased mean systolic and diastolic blood pressure, improved NO formation and increased antioxidant measures.³⁶ Similarly, a trial in Italy found flavanol-rich dark chocolate could decrease blood pressure in hypertensive men, while also improving FMD and cholesterol parameters.³⁷

As mentioned in the flavonoid review, anthocyanins are an up-and-coming area of interest in hypertension research. Polish researchers recently reported providing adults with metabolic syndrome with anthocyanins (3 x 100 mg/d) from Aronia melanocarpa (chokeberry) for two months significantly lowered both systolic and diastolic blood pressure, as well as levels of inflammatory markers.³⁸ Similarly, when Japanese researchers provided anthocyanins from purple corn, purple sweet potato and red radish to hypertensive rats, the flavonoids helped decrease blood pressure and heart rate.³⁹

Pomegranate juice, which is rich in anthocyanins and tannins, may also impact blood pressure. One study out of Israel found providing pomegranate juice (50 mL) to hypertensive patients for just two weeks significantly reduced systolic blood pressure and ACE activity.⁴⁰ Longer-term intervention may have even greater effects, as the same team investigated the effects of pomegranate juice consumption by hypertensive adults over a three-year period.⁴¹ Consumption of pomegranate juice reduced systolic blood pressure by 21 percent after just one year; no further reductions were seen by three years. Intervention also decreased carotid intima-media thickness.

Polyphenols are also found in wine, and may work to improve endothelial function and decrease blood pressure by reducing oxidative stress levels.⁴² In vitro work suggests red wine polyphenols may prevent angiotensin II-induced hypertension and endothelial dysfunction by also preventing expression of pro-inflammatory factors.⁴³ French researchers reported providing hypertensive rats with red wine polyphenols (100 mg/kg/d in drinking water) could improve endothelium-dependent dilation and benefit antioxidant status, helping to decrease blood pressure.⁴⁴

Grape seed extract is another source of beneficial polyphenols. Studies from the University of California, Davis, have sought to examine the effects of a specific grape seed extract on endothelial function and arterial pressure. In an in vitro study, researchers applied GSE (as MegaNatural BP®, from Polyphenolics) to rabbit aortic rings, and found the extract could produce a dose-dependent relaxation when the rings were contacted with noradrenaline.⁴⁵ Relaxation was inhibited by removal of the endothelium, underscoring the role of eNOS in the response; the extract was also found to activate the P13K/Akt signally pathway, resulting in phosphorylation of eNOS.

Clinical work by the team supports the efficacy of MegaNatural BP. In a 2006 study, 24 adults diagnosed with metabolic syndrome received a placebo, or 150 mg/d or 300 mg/d of the patented GSE.⁴⁶ After one month, the participants taking GSE had reductions in systolic and diastolic blood pressure. A two-month follow-up study involved pre-hypertensive subjects who received 300 mg/d of MegaNatural BP or placebo.(REF) Those on the intervention had a significant decrease in systolic and diastolic blood pressure, which the researchers attributed to the vasodilation effects of the GSE polyphenols.

One of the most consumed beverages in the world, tea, also offers benefits to blood pressure. A recent review out of the University of Missouri-Columbia noted consumption of tea, and its abundant polyphenol epigallocatechin-3-gallate (EGCG), may improve endothelial function and hypertension.⁴⁷ In fact, animal research has shown green tea extract has the ability to prevent induced hypertension in rats, which was attributed to prevention of oxidative damage, supporting vascular health.⁴⁸

Polyphenols found in pine bark extract have been investigated for their impact on vascular health. One placebo-controlled, double blind study out of China examined the impact of 100 mg/d of pine bark extract (as Pycnogenol®, from Horphag, supplied by Natural Health Science) on patients with hypertension.⁴⁹ The intervention improved endothelial function, decreasing endothelin-1 concentrations and increasing NO levels in plasma, although there were no significant changes in heart rate. A 12-week pilot study from New Zealand examined the impact of pine bark extract (as Enzogenol®, from ENZO Nutraceuticals, supplied by B&D Nutritional Ingredients) plus vitamin C on blood pressure and other cardiac parameters.⁵⁰ Intervention at a dose of 480 mg/d pine bark extract and 240 mg/d vitamin C was associated with a significant reduction in systolic blood pressure.

The majority of research to date on Ginkgo biloba has focused on its possible benefit to cognitive function; however, studies are investigating its possible effect on blood pressure, though results have been mixed. Japanese researchers reported ginkgo extract could decrease salt-related elevation of blood pressure and support vasodilation in rats;⁵¹ another Japanese rat trial found a standardized ginkgo extract (as EGb 761) could suppress age-related increases in blood pressure.⁵² However, additional work from Japan found ginkgo extract worked to reduce blood pressure in younger animals, but impaired peripheral circulation and increased liver weight in aged hypertensive rats, suggesting a need for further investigation on its effects.⁵³

Another botanical, olive leaf extract (as EFLA® 943, sold as Benolea® by Frutarom), was found in a rat model to exert hypotensive effects in hypertensive rats, which may be attributed to reversing adverse vascular changes.⁵⁴ A clinical trial presented at the Phytopharmaka and Phytotherapy 2005 Congress in Berlin also found olive leaf extract could dose-dependently reduce blood pressure. In this study, 20 monozygotic twins were randomly divided into two groups. Group 1 took 500 mg/d olive leaf extract (as EFLA 943) and group 2 took 1,000 mg/d olive leaf extract. Blood pressure was recorded at baseline and after one, two, four, six and eight weeks; the mean value of these readings was used for data analysis. In Group 1, systolic blood pressure decreased by six mmHg and diastolic blood pressure decreased by 13 mmHg. Greater reductions in blood pressure were observed in Group 2 (19 mmHg and 10 mmHg, respectively). Both groups experienced significant reductions in low-density lipoprotein (LDL) cholesterol. The researchers concluded the results of the study support the beneficial effect of EFLA 943 as a dietary supplement in the control of a non-pharmacological approach for the treatment of mild hypertensive states.

Garlic also has a good quantity of research supporting its benefits to cardiovascular health, including blood pressure. A 2008 meta-analysis from the University of Adelaide, South Australia, included 11 studies from a systematic review and reported the studies showed a mean decrease of 4.6 +/- 2.8 mm Hg for systolic blood pressure in the garlic group compared to placebo, while the mean decrease in the hypertensive subgroup was 8.4 +/- 2.8 mm Hg for systolic blood pressure, and 7.3 +/- 1.5 mm Hg for diastolic blood pressure.⁵⁵ Studies suggest garlic may exert its positive effects on blood pressure via antioxidant properties,⁵⁶ or due to its allicin content benefiting endothelial function.⁵⁷ Clinical work in men with hypertension has shown supplementation with garlic lowers both systolic and diastolic blood pressure.⁵⁸

Aged garlic extract (AGE) may have a greater beneficial effect than fresh. Japanese researchers compared AGE to raw garlic powder in spontaneously hypertensive rats in a 10 week intervention, and found both reduced the increase of blood pressure in the animals; however, AGE also reduced pulse pressure and supported blood vessel health.⁵⁹ Clinical work with AGE has also shown positive results. A double blind crossover trial in which hypercholesterolemic men (n=41) took 7.2 g/d AGE for six months found the intervention produced a 5.5 percent decrease in systolic blood pressure and a modest reduction in diastolic blood pressure.⁶⁰ And in an open clinical trial, intervention with AGE plus vitamin B1 and ginseng extract was effective in lowering blood pressure in patients with high blood pressure, but not in those with normal blood pressure.⁶¹

In the diet, garlic often comes accompanied by tomatoes, themselves a source of beneficial compounds, such as the antioxidant carotenoid lycopene. A team from the Pennington Biomedical Research Center, Baton Rouge, La., used USDA food composition databases to analyze phytochemical content of the DASH diet and found it was much higher in lycopene and flavonols than control diets.⁶² Tomato extract itself was the subject of a study out of University of the Negev, Beer Sheva, Israel, in which researchers investigated the effect of tomato extract (as Lyc-O-Mato®, from Lycored) on systolic and diastolic blood pressure in grade-1 hypertension.⁶³ Researchers treated the 31 subjects with 250 mg/d of Lyc-O-Mato for eight-weeks, followed by a four-week placebo intervention. After active treatment, systolic blood pressure decreased from 144 to 134 mm Hg, and diastolic blood pressure declined to 83.4 mm Hg from 87.4 mm Hg. No changes to blood pressure were seen on the placebo.

The carotenoid astaxanthin also may impact hypertensive markers. Japanese researchers found oral administration of astaxanthin (50 mg/kg/d) in hypertensive rats could induce a significant reduction in arterial blood pressure, while also modulating levels of circulating lipids.⁶⁴ Further animal research suggests astaxanthin may exert its positive effects on blood pressure by improving vascular elastin and arterial wall thickness,⁶⁵ and modulating blood fluidity.⁶⁶

In a condition such as hypertension, where the etiology behind the majority of cases is unknown, dietary interventions and lifestyle modifications have a significant role to play in optimizing health and avoiding steps toward this chronic disease. Offering multi-faceted nutritional products that can help consumers take charge of the range of cardiovascular risk factors means not staying silent, but sounding the charge for positive heart health.

References are on the next page...

References for "Addressing Hypertension via Nutrition"

1. Appel LJ et al. “Dietary Approaches to Prevent and Treat Hypertension: A Scientific Statement From the American Heart Association.” Hypertension. 2006;47:296.

2. Appel LJ et al. “A clinical trial of the effects of dietary patterns on blood pressure. DASH Collaborative Research Group.” N Engl J Med. 1997 Apr 17;336(16):1117-24.

3. Mellen PB et al. “Deteriorating dietary habits among adults with hypertension: DASH dietary accordance, NHANES 1988-1994 and 1999-2004.” Arch Intern Med. 2008 Feb 11;168(3):308-14.

4. Lin PH et al. “The PREMIER intervention helps participants follow the Dietary Approaches to Stop Hypertension dietary pattern and the current Dietary Reference Intakes recommendations.” J Am Diet Assoc. 2007 Sep;107(9):1541-51.

5. Swain JF et al. “Characteristics of the diet patterns tested in the optimal macronutrient intake trial to prevent heart disease (OmniHeart): options for a heart-healthy diet.” J Am Diet Assoc. 2008 Feb;108(2):257-65.

6. Yang G et al. “Longitudinal study of soy food intake and blood pressure among middle-aged and elderly Chinese women.” Am J Clin Nutr. 2005 May;81(5):1012-7.

7. Nasca MM, Zhou JR, Welty FK. “Effect of soy nuts on adhesion molecules and markers of inflammation in hypertensive and normotensive postmenopausal women.” Am J Cardiol. 2008 Jul 1;102(1):84-6. Epub 2008 Apr 16.

8. Park E et al. “Soy isoflavone supplementation alleviates oxidative stress and improves systolic blood pressure in male spontaneously hypertensive rats.” J Nutr Sci Vitaminol (Tokyo). 2005 Aug;51(4):254-9.

9. Si H, Liu D. “Genistein, a soy phytoestrogen, upregulates the expression of human endothelial nitric oxide synthase and lowers blood pressure in spontaneously hypertensive rats.” J Nutr. 2008 Feb;138(2):297-304.

10. FitzGerald RJ, Murray BA, Walsh DJ. “Hypotensive peptides from milk proteins.” J Nutr. 2004 Apr;134(4):980S-8S.11. Sipola M et al. “Alpha-lactorphin and beta-lactorphin improve arterial function in spontaneously hypertensive rats.” Life Sci. 2002 Aug 2;71(11):1245-53.12. Sipola M et al. “Long-term intake of milk peptides attenuates development of hypertension in spontaneously hypertensive rats.” J Physiol Pharmacol. 2001 Dec;52(4 Pt 2):745-54.13. Nurminen ML et al. “Alpha-lactorphin lowers blood pressure measured by radiotelemetry in normotensive and spontaneously hypertensive rats.” Life Sci. 2000;66(16):1535-43.14. Pins JJ, Keenan JM. “Effects of whey peptides on cardiovascular disease risk factors.” J Clin Hypertens (Greenwich). 2006 Nov;8(11):775-82.15. McNaughton SA et al. “Dietary patterns of adolescents and risk of obesity and hypertension.” J Nutr. 2008 Feb;138(2):364-70.16. Kaushik S et al. “Frequency of fish consumption, retinal microvascular signs and vascular mortality.” Microcirculation. 2008 Jan;15(1):27-36.17. FerraraLA et al. “Dietary pattern and blood pressure control in a hypertension outpatient clinic.” Hypertens Res. 2007 Nov;30(11):1043-50.18. Yang H, Kenny A. “The role of fish oil in hypertension.” Conn Med. 2007 Oct;71(9):533-8.19. Ueshima H et al. “Food omega-3 fatty acid intake of individuals (total, linolenic acid, long-chain) and their blood pressure: INTERMAP study.” Hypertension. 2007 Aug;50(2):313-9. Epub 2007 Jun 4.20. Elliott P et al. “Dietary phosphorus and blood pressure: international study of macro- and micro-nutrients and blood pressure.” Hypertension. 2008 Mar;51(3):669-75. Epub 2008 Feb 4.21. Karppanen H, Mervaala E. “Sodium intake and hypertension.” Prog Cardiovasc Dis. 2006 Sep-Oct;49(2):59-75.22. Wang L et al. “Dietary intake of dairy products, calcium, and vitamin D and the risk of hypertension in middle-aged and older women.” Hypertension. 2008 Apr;51(4):1073-9. Epub 2008 Feb 7.23. Ruidavets JB et al. “Independent contribution of dairy products and calcium intake to blood pressure variations at a population level.” J Hypertens. 2006 Apr;24(4):671-81.24. Sontia B, TouyzRM. “Magnesium transport in hypertension.” Pathophysiology. 2007 Dec;14(3-4):205-11. Epub 2007 Oct 29.25. Adrian M et al. “A long-term moderate magnesium-deficient diet aggravates cardiovascular risks associated with aging and increases mortality in rats.” J Hypertens. 2008 Jan;26(1):44-52.26. Rodrigo R et al. “Relationship between oxidative stress and essential hypertension.” Hypertens Res. 2007 Dec;30(12):1159-67.27. Sato K et al. “Effects of ascorbic acid on ambulatory blood pressure in elderly patients with refractory hypertension.” Arzneimittelforschung. 2006;56(7):535-40.28. Mahajan AS et al. “Antihypertensive and antioxidant action of amlodipine and vitamin C in patients of essential hypertension.” J Clin Biochem Nutr. 2007 Mar;40(2):141-7.29. Plantinga Y et al. “Supplementation with vitamins C and E improves arterial stiffness and endothelial function in essential hypertensive patients.” Am J Hypertens. 2007 Apr;20(4):392-7.30. Rodrigo R et al. “Decrease in oxidative stress through supplementation of vitamins C and E is associated with a reduction in blood pressure in patients with essential hypertension.” Clin Sci (Lond). 2008 May;114(10):625-34.31. Newaz MA, Nawal NN. “Effect of gamma-tocotrienol on blood pressure, lipid peroxidation and total antioxidant status in spontaneously hypertensive rats (SHR).” Clin Exp Hypertens. 1999;21:1297-313.32. Newaz MA et al. “Nitric oxide synthase activity in blood vessels of spontaneously hypertensive rats: antioxidant protection by gamma-tocotrienol.” J Physiol Pharmacol. 2003;54:319-27.33. Hooper L et al. “Flavonoids, flavonoid-rich foods, and cardiovascular risk: a meta-analysis of randomized controlled trials.” Am J Clin Nutr. 2008 Jul;88(1):38-50.34. Doheny K. “Finding Out How Flavonoids Protect the Heart.” HealthDay News. July 10, 2008. www.medicinenet.com/script/main/art.asp?articlekey=9095635. Vlachopoulos C, Alexopoulos N, Stefanadis C. “Effect of dark chocolate on arterial function in healthy individuals: cocoa instead of ambrosia?” Curr Hypertens Rep. 2006 Jun;8(3):205-11.36. Taubert D et al. “Effects of low habitual cocoa intake on blood pressure and bioactive nitric oxide: a randomized controlled trial.” JAMA. 2007 Jul 4;298(1):49-60.37. Grassi D et al. “Cocoa reduces blood pressure and insulin resistance and improves endothelium-dependent vasodilation in hypertensives.” Hypertension. 2005 Aug;46(2):398-405. Epub 2005 Jul 18.38. Broncel M et al. “[Effect of anthocyanins from Aronia melanocarpa on blood pressure, concentration of endothelin-1 and lipids in patients with metabolic syndrome.][Article in Polish]” Pol Merkur Lekarski. 2007 Aug;23(134):116-9.39. Shindo M et al. “Effects of dietary administration of plant-derived anthocyanin-rich colors to spontaneously hypertensive rats.” J Nutr Sci Vitaminol (Tokyo). 2007 Feb;53(1):90-3.40. Aviram M, Dornfeld L. “Pomegranate juice consumption inhibits serum angiotensin converting enzyme activity and reduces systolic blood pressure.” Atherosclerosis. 2001 Sep;158(1):195-8.41. Aviram M et al. “Pomegranate juice consumption for 3 years by patients with carotid artery stenosis reduces common carotid intima-media thickness, blood pressure and LDL oxidation.” Clin Nutr. 2004 Jun;23(3):423-33.42. López-Sepúlveda R et al. “Wine polyphenols improve endothelial function in large vessels of female spontaneously hypertensive rats.” Hypertension. 2008 Apr;51(4):1088-95. Epub 2008 Feb 7.43. Walter A et al. “Angiotensin II induces the vascular expression of VEGF and MMP-2 in vivo: preventive effect of red wine polyphenols.” J Vasc Res. 2008;45(5):386-94. Epub 2008 Mar 20.44. Chan SL et al. “Impact of chronic treatment with red wine polyphenols (RWP) on cerebral arterioles in the spontaneous hypertensive rat.” J Cardiovasc Pharmacol. 2008 Mar;51(3):304-10.45. Edirisinghe I, Burton-Freeman B, Kappagoda CT. “Mechanism of the endothelium-dependent relaxation evoked by a grape seed extract.” Clin Sci. 2008;114:331-7.46. Kappagoda CT et al. Experimental Biology Conference, April 30, 2007.47. Kim JA. “Mechanisms underlying beneficial health effects of tea catechins to improve insulin resistance and endothelial dysfunction.” Endocr Metab Immune Disord Drug Targets. 2008 Jun;8(2):82-8.48. Antonello M et al. “Prevention of hypertension, cardiovascular damage and endothelial dysfunction with green tea extracts.” Am J Hypertens. 2007 Dec;20(12):1321-8.49. Liu X et al. “Pycnogenol, French maritime pine bark extract, improves endothelial function of hypertensive patients.” Life Sci. 2004 Jan 2;74(7):855-62.50. Shand B et al. “Pilot study on the clinical effects of dietary supplementation with Enzogenol, a flavonoid extract of pine bark and vitamin C.” Phytother Res. 2003 May;17(5):490-4.51. Kubota Y et al. “Effects of Ginkgo biloba extract feeding on salt-induced hypertensive Dahl rats.” Biol Pharm Bull. 2006 Feb;29(2):266-9.52. Sasaki Y et al. “Effects of Ginkgo biloba extract (EGb 761) on cerebral thrombosis and blood pressure in stroke-prone spontaneously hypertensive rats.” Clin Exp Pharmacol Physiol. 2002 Nov;29(11):963-7.53. Tada Y et al. “Long-term feeding of Ginkgo biloba extract impairs peripheral circulation and hepatic function in aged spontaneously hypertensive rats.” Biol Pharm Bull. 2008 Jan;31(1):68-72.54. Khayyal MT et al. “Blood pressure lowering effect of an olive leaf extract (Olea europaea) in L-NAME induced hypertension in rats.” Arzneimittelforschung. 2002;52(11):797-802.55. Ried K et al. “Effect of garlic on blood pressure: a systematic review and meta-analysis.” BMC Cardiovasc Disord. 2008 Jun 16;8:13.56. Cruz C et al. “Renoprotective and antihypertensive effects of S-allylcysteine in 5/6 nephrectomized rats.” Am J Physiol Renal Physiol. 2007 Nov;293(5):F1691-8. Epub 2007 Aug 8.57. Sun X, Ku DD. “Allicin in garlic protects against coronary endothelial dysfunction and right heart hypertrophy in pulmonary hypertensive rats.” Am J Physiol Heart Circ Physiol. 2006 Nov;291(5):H2431-8. Epub 2006 May 26.58. Dhawan V, Jain S. “Effect of garlic supplementation on oxidized low density lipoproteins and lipid peroxidation in patients of essential hypertension.” Mol Cell Biochem. 2004 Nov;266(1-2):109-15.59. Harauma A, Moriguchi T. “Aged garlic extract improves blood pressure in spontaneously hypertensive rats more safely than raw garlic.” J Nutr. 2006 Mar;136(3 Suppl):769S-773S.60. Steiner M et al. “A double-blind crossover study in moderately hypercholesterolemic men that compared the effect of aged garlic extract and placebo administration on blood lipids.” Am J Clin Nutr. 1996;64(6):866-70.61. Tokunaga A, Hayashi T. “Effect of LE-5 on Blood Pressure. Shinyaku to Rinsho.” J New Remedies Clinics. 1996;45(10):2015-20.62. Most MM. “Estimated phytochemical content of the dietary approaches to stop hypertension (DASH) diet is higher than in the Control Study Diet.” J Am Diet Assoc. 2004 Nov;104(11):1725-7.63. Engelhard YN, Gazer B, Paran E. “Natural antioxidants from tomato extract reduce blood pressure in patients with grade-1 hypertension: a double-blind, placebo-controlled pilot study.” Am Heart J. 2006 Jan;151(1):100.64. Hussein G et al. “Astaxanthin ameliorates features of metabolic syndrome in SHR/NDmcr-cp.” Life Sci. 2007 Jan 16;80(6):522-9. Epub 2006 Oct 12.65. Hussein G et al. “Antihypertensive potential and mechanism of action of astaxanthin: III. Antioxidant and histopathological effects in spontaneously hypertensive rats.” Biol Pharm Bull. 2006 Apr;29(4):684-8.66. Hussein G et al. “Antihypertensive potential and mechanism of action of astaxanthin: II. Vascular reactivity and hemorheology in spontaneously hypertensive rats.” Biol Pharm Bull. 2005 Jun;28(6):967-71.