June 30, 2009
A modifiable factor in heart attacks and stroke, high blood pressure is a great candidate for natural products intervention, as many nutrients and herbs have been studied for management of pre-hypertension and hypertension.
Blood pressure management is about the numbers. Normal blood pressure, the force blood exerts on vessel walls, is less than 120 mmHg systolic (heart beating) and less than 80 mmHg diastolic (heart relaxing). Pre-hypertension is 120-129/80-89 (systolic/diastolic). Stage 1 hypertension begins above 140/90, with stage 2 hypertension starting above 160/100.
The numbers get scary when you consider the death rate from high blood pressure rose 25.2 percent from 1995 to 2005, with the actual number of deaths rising 56.4 percent during that time frame, according to the American Heart Association (AHA). Add to this about one in every three Americans has high blood pressure, according to the Centers for Disease Control and Prevention (CDC), which also reported an estimated 90 percent of middle-aged adults will develop high blood pressure in the remainder of their lifetime.
Even scarier? Public health officials have said as much as 20 percent of the population doesnt know they have hypertension. The confusion partially results from the fact that there are no major, recognizable symptoms of hypertension alone, although the condition can lead to greater cardiovascular problems and their associated symptoms. Even more troubling, CDC reported the cause of 90 to 95 percent of hypertension cases is not known.
The good news in all these daunting stats and facts is high blood pressure is easy to discover by a health care provider, and it is highly manageable via lifestyle and dietary changes, including dietary supplements.
Dietary strategies to blood pressure management are based on low-salt, low-fat diets proven successful in scientific research. The most popular such diet is the DASH (Dietary Approaches to Stop Hypertension) diet, which is based on National Institutes of Health (NIH) studies1 and is recommended by the AHA as well as the National Heart, Lung and Blood Institute. DASH focuses on a reduction of sodium intake while promoting an increased intake of fruits, vegetables, fish, poultry and whole grains instead of dairy and red meat.
More recently, the Mediterranean diet, which also favors fruits, vegetables and healthy fats, has demonstrated benefits to hypertension management.2 Involving a cohort of 8,594 participants aged 20 to 95, the 2009 Spanish study showed an inverse link between fruit/vegetable intake and risk of hypertension amongst those with low olive oil consumption (<15 g/d).
That plants form the heart of anti-hypertension diets is a credit to their content of nutrients and phytochemicals, especially antioxidants. Much of the research on lowering blood-pressure risk and managing hypertension levels focuses on these plant compounds, in addition to various botanicals.
For starters, fruits and vegetables contain numerous vitamins and minerals, some of which have been linked to benefits to blood pressure. For instance, mineral intake is important to controlling blood pressure. The International Study of Macro- and Micro-nutrients and Blood Pressure (INTERMAP) found an inverse link between blood pressure and increased intakes of dietary calcium, magnesium and phosphorus.3 University of Helsinki, Finland, researchers looked at potassium, calcium and magnesium, concluding greater intakes of these minerals result in a more than 10 mm Hg fall in the population average of systolic and diastolic blood pressure.4
Intake of magnesium alone may help regulate blood pressure and has been inversely associated with incidence of hypertension.5 In fact, animal studies have shown magnesium deficiency can have a long-term negative effect on arterial thickness and stiffness, arterial pressure and incidence of hypertension.6
University of Ottawa, Ontario, scientists have reported magnesium's effect on blood pressure is via vascular tone modulation and impact on vasodilation and inflammation.7 Magnesium's benefit may be narrowly targeted, according to Korean researchers, who found oral magnesium supplementation (as magnesium oxide) had no effect on blood pressure in healthy adults who were diabetes-free, normotensive and had normal magnesium levels; however, supplementation did lower blood pressure in a subgroup of people with hypertension and normal magnesium levels.8
Despite the lack of dairy in the DASH and Mediterranean diets, calcium is still a necessary nutrient for decreasing the risk of hypertension. French researchers investigating more than 900 middle-aged men found consumption of dairy products and dietary calcium were both significantly and independently associated with low levels of systolic blood pressure.9 The key to calcium-rich dairy may be keeping fat content low, as Harvard researchers studying 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.10
A late 2008 study report from Harvard Medical School, Boston, confirmed previous research conclusions of an inverse relationship between plasma 25-hydroxyvitamin D levels and risk of incident hypertension in young women.11 Specifically, young women with low levels of vitamin D had a substantially higher risk of hypertension than women with sufficient levels of the vitamin.
As far as vitamins go, vitamin C is known in vascular health for its roles in collagen production and vascular flexibility. On hypertension specifically, low levels of vitamin C are concurrent with increased oxidative stress in hypertensive adults, indicating an oxidative factor in the development of hypertension.12 In fact, reducing oxidative stress appears to help manage blood pressure. Japanese researchers discovered systolic blood pressure and pulse pressure were significantly reduced in elderly patients being treated for hypertension who also took ascorbic acid (600 mg/d).13 Other research confirms this complementary pairing, as 1,000 mg/d of vitamin C added to antihypertensive therapy reduced systolic blood pressure and decreased parameters of oxidative stress in a trial out of India.14
The logical progression to combining antioxidant vitamins led researchers to the study of vitamins C and E together. In a University of Pisa, Italy, trial vitamin C (1 g/d) and vitamin E (400 IU/d) given to hypertensive men for eight weeks significantly improved flow-mediated dilation (FMD) and arterial flexibility, as well as vasodilation and oxidative stress parameters.15 Similarly, University of Chile, Santiago, research found hypertensive men taking vitamins C and E for eight weeks had significantly lower systolic and diastolic blood pressure, in addition to higher serum antioxidant capacity.16
Tocotrienol isomers of vitamin E may work on their own against hypertension. According to animal research, gamma-tocotrienol administration can reduce systolic blood pressure and improve nitric oxide synthase (NOS) activity, promoting production of the vasodilator nitric oxide (NO).17
NOS synthesizes NO from L-arginine, an amino acid that has proven its own potential to reduce arterial blood pressure along with auxiliary benefits to inter-media thickness and overall endothelial function.18,19 Incidentally, vitamin-like coenzyme Q10 can protect NO from oxidative stress and was shown to reduce elevated blood pressure in a 2008 Japanese animal study.20
Given the number of micronutrients with the potential to impact blood pressure, it was only a matter of time until researchers tested multivitamin and mineral (MVM) supplements against hypertension endpoints. A Harbin Medical University, China, trial compared a low-dose MVM, a high-dose MVM, a calcium supplement and a placebo for their effects on blood pressure in obese women with increased cardiovascular disease risk, including hypertension, hyperglycemia or hyperlipemia.21 After 26 weeks of intervention, the researchers found the high-dose MVM group had significantly decreased systolic and diastolic pressure, compared to the other groups.
However, the importance of fruits, vegetables and other plants in the anti-hypertension diets is due to more than just vitamins and minerals. Flavonoids are phytochemicals with antioxidant capabilities that have been proven useful to blood pressure management. In fact, one leading researcher argued flavonoids may be more important to heart health than vitamins C and E.22
United Kingdom scientists performed a review of research on several different types of flavonoids, including those from chocolate and soy, finding some positive effects on vascular health, including blood pressure.23 However, many flavonoid classes produced insufficient data; one exception was chocolate, which significantly lowered both systolic and diastolic blood pressure, in addition to increasing FMD after acute and chronic chocolate intake. They suggested future research in this area focus on flavonones and anthocyanins.
The star of recent flavonoid research, chocolate has enjoyed positive results in various areas of heart health, including blood pressure. However, research reviewers from Athens Medical School, Greece, reported the blood-pressure lowering effect of dark chocolate and flavonoid-rich cocoa is attributed to the flavonoids impact on increased NO bioavailability.24 A JAMA study supported this hypothesis, finding intake of 6.3 g/d of dark chocolate (30 mg of polyphenols) for 18 weeks by adults with untreated pre-hypertension or stage 1 hypertension led to decreased mean systolic and diastolic blood pressure, improved NO formation and increased antioxidant measures.25
Punctuating chocolate's impact on blood pressure, an Italian trial noted flavanol-rich dark chocolate decreased blood pressure in hypertensive men and improved FMD.26
Grapes are also rich in polyphenols, and grape-based products have helped vascular health and blood pressure via some of the same mechanisms as micronutrient aids. Made from grapes, wine is rich in polyphenols and may improve endothelial function and decrease blood pressure by reducing oxidative stress.27 In vitro work also suggests red wine polyphenols may prevent expression of pro-inflammatory factors, resulting in limited development of angiotensin II-induced hypertension and endothelial dysfunction.28 Animal research supported these mechanisms, indicating wine polyphenols decreased blood pressure by improving endothelium-dependent dilation and antioxidant status.29
While drinking more wine may appeal to many people, others may find a simpler method of consuming these polyphenols by way of grape seed extract (GSE) supplements, which have undergone scientific inquiry into benefits to blood pressure. University of California, Davis, researchers conducted a few studies on GSE (as MegaNatural BP®, from Polyphenolics) and endothelial function an arterial blood pressure. An animal-based in vitro study found MegaNatural BP produced dose-dependent relaxation in aortic rings contacted with noradrenaline.30 The team's clinical work on the GSE showed adults with metabolic syndrome who took 150 mg/d or 300 mg/d of MegaNatural BP for one month had reductions in systolic and diastolic blood pressure.31 Their two-month follow-up study concluded pre-hypertensive subjects who received 300 mg/d of MegaNatural BP experienced a significant decrease in both systolic and diastolic blood pressure; the researchers theorized GSE polyphenols had a vasodilatory effect.32
A pair of Chinese studies on various diabetes-related endpoints in rats included results showing administration of GSE reduced systolic blood pressure.33 The researchers credited proanthocyanidins in GSE for this effect.
Oligomeric proanthocyanidins (OPCs) are a class of flavanols found in various botanicals, including maritime pine bark and green tea. OPCs and other flavonoids in pine bark extract have demonstrated an impact on cardiovascular health, including hypertension. In a joint study from University of Arizona, Tucson, and Westfalische Wilhelms University, Germany, men taking 200 mg/d pine park extract (as Pycnogenol®, from Horphag, supplied by Natural Health Science) had a significant decrease in systolic blood pressure, compared to placebo, but the effect on diastolic pressure failed to reach significance.34 More recently, a 2008 trial out of China examined the impact of 100 mg/d of Pycnogenol on patients with hypertension, finding the extract improved endothelial function, decreased endothelin-1 concentrations and increased NO levels in plasma.35
Another pine bark extract (as Enzogenol®, from ENZO Nutraceuticals, supplied by B&D Nutritional Ingredients) underwent a 12-week pilot study by New Zealand researchers, who paired it with vitamin C and measured various cardiac parameters.36 They reported 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.
Proanthocyanidins are closely related to fellow flavanol catechins, both of which are found in green tea. A University of Missouri, Columbia, research review discovered consumption of tea and its epigallocatechin-3-gallate (EGCG) appears to improve endothelial function and hypertension.37 Animal research has shown similar results, with green tea extract limiting induced hypertension in rats, by addressing oxidative damage.38 Most recently, a 2009 University of Florida, Gainesville, study involved healthy adults aged 21 to 70, who took a capsule of standardized green tea (Camilla sinesis) compounds twice daily and were tested for various cardiovascular parameters.39 After three weeks, systolic and diastolic pressures were decreased by 5 mmHg and 4 mmHG, respectively; systolic pressure remained low after three months.
Still more relief from high blood pressure may come from another class of flavonoids called anthocyanins, which are the dark pigments in many richly colored fruits and vegetables.
Chokeberry (Aronia melanocarpa) anthocyanins given to adults for two months significantly lowered both systolic and diastolic blood pressure in a Polish study.40
Similarly, Japanese researchers administered anthocyanins from purple corn, purple sweet potato and red radish to hypertensive rats, finding the flavonoids decreased blood pressure and heart rate.41
Tying into the Mediterranean diet on blood pressure, pomegranates are rich in anthocyanins and tannins and may help manage blood pressure. An Israeli trial found hypertensive patients taking pomegranate juice (50 mL) for just two weeks had significantly reduced systolic blood pressure and ACE activity.42 The same research team looked at long-term intervention, finding pomegranate juice consumption by hypertensive adults over a three-year period reduced systolic blood pressure by 21 percent after just one year.43 They noted there were no further reductions at three years, but pomegranate consumption did appear to improve vascular health by decreasing carotid intima-media thickness.
Fans of the Mediterranean diet will often cite the prevalence of heart-healthy olive oil, but the leaves from the olive tree have been specifically studied for benefits to hypertension care. Olive leaf extract EFLA® 943 (as Benolea®, by Frutarom) showed hypotensive effects in hypertensive rats in a Cairo University, Egypt, study.44 Researchers attributed the benefit to the extract's ability to reverse adverse vascular changes. South African scientists were able to credit triterpenoids from Greek and African and olive leaf varieties to prevention of severe hypertension and atherosclerosis in experimental animals after a six-week intervention.45 In 2008, German and Swiss researchers conducted two experiments on olive leaf extract in identical human twins aged 18 to 60 with borderline hypertension, in an effort to generate consistent data free from genetic differences.46 First, they gave twins either 500 mg/d olive leaf extract for breakfast or a placebo. In the second study, they gave twins either 500 mg/d or 1,000 mg/d olive leaf extract, or placebo. Among those taking the highest amount of extract, systolic blood pressure fell by a significant amount, while those taking the lower amount of extract saw a five-point decline in systolic pressure, and those on placebo had a two-point increase in pressure.
Another leaf-based supplement, Ginkgo biloba, has had decent results on blood pressure, but mixed results on other vascular health parameters. Per animal research, ginkgo extract can decrease salt-related elevation of blood pressure and support vasodilation.47 Similarly, another animal study reveals standardized ginkgo extract (as EGb 761) can suppress age-related increases in blood pressure.48 However more recent Japanese research found while ginkgo extract reduces blood pressure, it can also impair peripheral circulation and increase liver weight in aged hypertensive rats.49
A plant-based hypotensive diet, especially Mediterranean, would be lacking without garlic, which has performed consistently well against rising blood pressure. A 2008 meta-analysis from the University of Adelaide, South Australia, summed up 11 studies with evidence of a significant decrease (4.6 +/- 2.8 mmHg) in systolic blood pressure among subjects taking garlic, while those in a hypertensive subgroup had even greater reductions in both systolic and diastolic blood pressure.50 However, a subsequent meta-analysis by Hartford Hospital, CT, researchers concluded garlic reduced blood pressure in subjects with elevated systolic pressure, but not those with normal systolic readings.51 Still, clinical study has suggested garlic lowers both systolic and diastolic blood pressure.52
The mechanism behind garlic's benefit to blood pressure management is the focus of many recent studies. Some point to antioxidant actions toward improved blood pressure,53,54 while others credit garlic's allicin content for improved endothelial function.55 Still other research indicates different preparations of garlic can affect its results on hypertension. In early 2009, Russian researchers reported time-released garlic powder tablets are more effective for the treatment of mild and moderate arterial hypertension than are regular garlic supplements, possibly due to the greater bioavailability of the powdered form.56
Other studies have focused on aged garlic extract (AGE), with one study finding both AGE and powdered garlic reversed rising blood pressure in the animals after 10 weeks of invtervention.57 Clinical research on hypercholesterolemic men revealed 7.2 g/d AGE supplementation for six months resulted in 5.5-percent decrease in systolic blood pressure and a modest reduction in diastolic blood pressure.58 Another clinical trial showed intervention with AGE plus vitamin B1 and ginseng extract effectively lowered blood pressure in hypertensive, but not normo-tensive patients.59
Tomatoes are another Mediterranean dietary staple, and their content of the carotenoid lycopene may be central to any blood pressure benefits associated with the vegetable. In fact, research out of Pennington Biomedical Research Center, Baton Rouge, LA, analyzed the phytochemical content of the DASH diet, using USDA food composition databases, and found DASH was much higher in lycopene and flavonols than control diets.60 Tomato extract itself was study by Israeli scientists, who reported the extract (as Lyc-O-Mato®, from Lycored) decreased both systolic and diastolic blood pressure in grade-1 hypertensive patients.61 Specifically, 250 mg/d of Lyc-O-Mato for eight-weeks decreased systolic blood pressure from 144 to 134 mmHg and diastolic blood pressure from 87.4 to 83.4 mmHg, compared to a placebo group.
Similarly, animal research has suggested fellow carotenoid astaxanthin may reduce blood pressure in hypertensive models, possibly by improving vascular elastin and arterial wall thickness, and modulating blood fluidity.62,63,64
The seasoning void in hypotensive diets that trim salt intake may well be filled by spices, which could additionally help manage blood pressure levels. The Nigella sativa seedwhich is often confused with black cumin, block onion and other similar black seedsis used as spice in many traditional Middle Eastern cultures and has been studied for hypotensive benefits. A study out of Shahrekord University of Medical Sciences, Iran, tested eight weeks of oral Nigella sativa (NS) seed extract supplement in patients with mild hypertension, finding doses of 100 or 200 mg/d of seed extract resulted in significant, dose-depent reductions in both systolic an diastolic blood pressure, compared to placebo, while also improving cholesterol profiles.65
Fat and Protein
Dietary intervention for hypertension requires low-fat foods, but the type of fat is the most important guiding factor, as even the Mediterranean diet is loaded with fish, a source of both protein and essential fatty acids (EFAs).
Higher consumption of fish, salad and cereals in adolescence has a positive effect on diastolic blood pressure and establishes a front against chronic disease, according to Australian researchers.66 Another Australian study found higher consumption of fish had vascular protective effects.67 Similarly, Italian research noted hypertensive adults who made a long-term dietary change to consume more fish and vegetables had better blood pressure management.68 A 2007 research review reported consumption of fish oil and its omega-3 EFAs can have a small but significant benefit to blood pressure, particularly among adults with hypertension.69 Epidemiological data from the aforementioned INTERMAP trial indicated an inverse relationship between total omega-3 intake from food and diastolic and systolic blood pressures, with the greatest impact from long-chain omega-3 intake from fish.70
Many hypotensive diets place tough limitations on meat intake, relative to American gastronomy. Offering flexibility on protein intake may help improve adherence to DASH, Mediterranean and similar diets, according to researchers at Brigham and Womens Hospital, Boston.71 They found slightly raising the level of healthy unsaturated fats and protein in these diets achieves similar blood pressure benefits, but make it easier to follow the diets long-term.
As in the case of calcium, dairy products may be limited in blood-pressure-lowering diets, but the peptides in milk and whey may help manage hypertension. Such peptides may inhibit vasoconstrictor enzymes such as angiotensin-1-convering enzyme (ACE), and positively impact vasodilation.72 Specifically, tetrapeptides from milk protein (alpha-lactorphin and beta-lactoglobulin) administered to spontaneously hypertensive rats improved vascular relaxation, influencing both endothelial function and endothelium-independent relaxation.73 A 2006 trial conducted at the University of Minnesota, Minneapolis concluded six weeks of whey-derived peptide supplementation in human subjects resulted in significant reductions in systolic and diastolic blood pressure, in addition to improvements in LDL cholesterol and inflammatory markers.74 Long-term intake of the ACE-inhibiting peptides isoleucine-proline-proline (IPP) and valine-proline-proline (VPP) slows the development of hypertension.75 A 2008 meta-analysis out of Norway confirmed peptides from such protein sources significantly lower both systolic and diastolic pressure, with the majority of studies using IPP and VPP.76 Then in 2009, DSM published safety research on its tensVida milk protein hydrolysate containing the lactotripeptide IPP, showing the ingredient is safe for use as intended after passing a 90-day repeated-dose oral toxicity study in rats, as well as several genotoxicity tests.77 Still other research suggests opioid receptors may be involved in the actions of tetrapeptides on diastolic and systolic blood pressure.78
Despite the potential for dairy-based peptides to manage hypertension, soy protein maintains the plant-focus of hypotensive diets and still offers improvement to blood pressure levels, in addition to its other well-known heart health benefits.
Analysis of data from the Shanghai Womens Health Study concluded long-term consumption of soy protein was inversely related to both systolic and diastolic pressure, with the association growing stronger with age.79 Also, substituting soy nuts for non-soy protein could significantly reduce blood pressure in both normotensive and hypertensive women, according to research from Beth Israel Deaconess Medical Center, Boston, which attributed the benefit to improved endothelial function and reduction in inflammation.80 Likewise, adding 10 g/kg/d of soy powder (31-percent isoflavones) to a high-fat diet can decrease oxidative damage, inhibit increases in blood pressure and influence NO production for endothelial benefit.81 Of soy isoflavones, genistein has improved aortic endothelial-derived NO, alleviating hypertension in the rats.82
Fermented soy, called natto, contains ACE-inhibiting substances that have antihypertensive effects.83 Natto has also been shown to suppress intimal thickening in the arteries. Nattokinase, may contribute to blood pressure management by breaking up blood fibrin, a protein involved in clotting. Proprietary research from Japan Bio-Science Laboratories on its NSK-SD® nattokinase ingredient attributed vascular benefits to the enzyme's effects on blood coagulation, blood flow, and hypertension in adults with untreated high blood pressure. In a 2008 study from Yonsei University, Seoul, Korea, untreated hypertensive adults (systolic=130-159 mmHg) who took nattokinase (2,000 fibrin-degrading units/capsule) for eight weeks had significant reduction in systolic (-5.5 mmHg) and diastolic (-2.8 mmHg) blood pressure.84
Dubbed a "silent killer," high blood pressure does not have to exact its cruel cardiovascular consequences, as numerous dietary and lifestyle modifications have proven useful in limiting development and progression of hypertension. Further, dietary ingredients, such as vitamins, minerals, fats, protein and plants, can boost these hypotensive efforts.
References on the next page...
"Blood Pressure" References
1. 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.
2. Nuñez-Cordoba JM et al. "Role of vegetables and fruits in Mediterranean diets to prevent hypertension." Euro J Clin Nutr. 2009;63:605612.
3. 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.
4. Karppanen H, Mervaala E. Sodium intake and hypertension. Prog Cardiovasc Dis. 2006 Sep-Oct;49(2):59-75.
5. 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.
6. 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.
7. Sontia B, TouyzRM. Magnesium transport in hypertension. Pathophysiology. 2007 Dec;14(3-4):205-11.
8. Lee S et al. "Effects of oral magnesium supplementation on insulin sensitivity and blood pressure in normo-magnesemic nondiabetic overweight Korean adults." Nutr Metab Cardio Dis. Epub ahead of print.
9. 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.
10. 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.
11. Forman JP et al. "Plasma 25-hydroxyvitamin D levels and risk of incident hypertension among young women." Hypertension. 2008 Nov;52(5):828-32.
12. Rodrigo R et al. Relationship between oxidative stress and essential hypertension. Hypertens Res. 2007 Dec;30(12):1159-67.
13. Sato K et al. Effects of ascorbic acid on ambulatory blood pressure in elderly patients with refractory hypertension. Arzneimittelforschung. 2006;56(7):535-40.
14. 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.
15. 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.
16. 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.
17. 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.
18. Gornik HL, Creager MA. Arginine and Endothelial and Vascular Health. J Nutr. 2004;134:2880S-2887S.
19. Lin PH et al. Rheolytic pharmacomechanical thrombectomy in experimental chronic deep vein thrombosis: effect of L-arginine on thrombogenicity and endothelial vasomotor function. World J Surg. 2007 Apr;31(4):664-75.
20. Kunitomo M et al. "Beneficial effect of coenzyme Q10 on increased oxidative and nitrative stress and inflammation and individual metabolic components developing in a rat model of metabolic syndrome." J Pharmacol Sci. 2008 Jun;107(2):128-37.
21. Wang C et al. "Effects of supplementation with multivitamin and mineral on blood pressure and C-reactive protein in obese Chinese women with increased cardiovascular disease risk." Asia Pac J Clin Nutr. 2009;18(1):121-30.
22. Doheny K. Finding Out How Flavonoids Protect the Heart. HealthDay News. July 10, 2008. www.medicinenet.com/script/main/art.asp?articlekey=90956
23. 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.
24. 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.
25. 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.
26. 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.
27. 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.
28. 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.
29. 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.
30. 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.
31. Kappagoda CT et al. Presented at SupplySide West, Las Vegas, Nev., Nov. 2006.
32. Kappagoda CT et al. Presented at Experimental Biology Conference, WashingtonDC, April 30, 2007.
33. Li X et al. "Grape seed proanthocyanidins ameliorate diabetic nephropathy via modulation of levels of AGE, RAGE and CTGF." Nephron Exp Nephrol. 2009;111(2):e31-41. Li X et al. "Effects of grape seed proanthocyanidins extracts on AGEs and expression of bone morphogenetic protein-7 in diabetic rats." J Nephrol. 2008 Sep-Oct;21(5):722-33.
34. Hosseini S et al. "A randomized, double-blind, placebo-controlled, prospective, 16 week crossover study to determine the role of Pycnogenol in modifying blood pressure in mildly hypertensive patients." 2001; 21(9): 1251-1260.
35. Liu X et al. "Antidiabetic effect of Pycnogenol French maritime pine bark extract in patients with diabetes type II." Life Sci. 2004 Oct 8;75(21):2505-13.
36. 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.
37. 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.
38. 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.
39. Nantz MP et al. "Standardized capsule of Camellia sinensis lowers cardiovascular risk factors in a randomized, double-blind, placebo-controlled study." Nutrition. 2009 Feb;25(2):147-54.
40. 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.
41. 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.
42. 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.
43. 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.
44. 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.
45. Somova LI et al. "Antihypertensive, antiatherosclerotic and antioxidant activity of triterpenoids isolated from Olea europaea, subspecies africana leaves." J Ethnopharmacol. 2003 Feb;84(2-3):299-305.
46. Perrinjaquet-Moccetti T et al. "Food supplementation with an olive (Olea europaea L.) leaf extract reduces blood pressure in borderline hypertensive monozygotic twins." Phytother Res. 2008 Sep;22(9):1239-42.
47. 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.
48. 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.
49. 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.
50. Ried K et al. Effect of garlic on blood pressure: a systematic review and meta-analysis. BMC Cardiovasc Disord. 2008 Jun 16;8:13.
51. Reinhart KM et al. "Effects of garlic on blood pressure in patients with and without systolic hypertension: a meta-analysis." Ann Pharmacother. 2008 Dec;42(12):1766-71.
52. 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
53. 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.
54. Drobiova H et al. "Garlic Increases Antioxidant Levels in Diabetic and Hypertensive Rats Determined by a Modified Peroxidase Method." Evid Based Complement Alternat Med. 2009 Feb 20. Epub ahead of print.
55. 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.
56. Sobenin IA et al. "Time-released garlic powder tablets lower systolic and diastolic blood pressure in men with mild and moderate arterial hypertension." Hypertens Res. 2009 Jun;32(6):433-7.
57. 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.
58. 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.
59. Tokunaga A, Hayashi T. Effect of LE-5 on Blood Pressure. Shinyaku to Rinsho. J New Remedies Clinics. 1996;45(10):2015-20.
60. 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.
61. 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.
62. 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.
63. 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.
64. 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.
65. Dehkordi FR and Kamkhah AF. "Antihypertensive effect of Nigella sativa seed extract in patients with mild hypertension." Fundam Clin Pharmacol. 2008 Aug;22(4):447-52.
66. McNaughton SA et al. Dietary patterns of adolescents and risk of obesity and hypertension. J Nutr. 2008 Feb;138(2):364-70.
67. Kaushik S et al. Frequency of fish consumption, retinal microvascular signs and vascular mortality. Microcirculation. 2008 Jan;15(1):27-36.
68. FerraraLA et al. Dietary pattern and blood pressure control in a hypertension outpatient clinic. Hypertens Res. 2007 Nov;30(11):1043-50.
69. Yang H, Kenny A. The role of fish oil in hypertension. Conn Med. 2007 Oct;71(9):533-8.
70. 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.
71. 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.
72. FitzGerald RJ, Murray BA, Walsh DJ. Hypotensive peptides from milk proteins. J Nutr. 2004 Apr;134(4):980S-8S.
73. 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.
74. Pins JJ, Keenan JM. Effects of whey peptides on cardiovascular disease risk factors. J Clin Hypertens (Greenwich). 2006 Nov;8(11):775-82.
75. 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.
76. Pripp AH. "Effect of peptides derived from food proteins on blood pressure: a meta-analysis of randomized controlled trials." Food Nutr Res. 2008;52. Epub ahead of print.
77. Ponstein-Simarro Doorten AY et al. "Safety evaluation of an IPP tripeptide-containing milk protein hydrolysate." Food Chem Toxicol. 2009 Jan;47(1):55-61.
78. 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.
79. 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.
80. 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.
81. 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.
82. 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.
83. Okamoto A et al. "Anti-hypertensive substances in fermented soybean, natto." Plant Foods Hum Nutr. 1995 Jan;47(1):39-47.
84. Kim JY et al. "Effects of nattokinase on blood pressure: a randomized, controlled trial." Hypertens Res. 2008 Aug;31(8):1583-8.
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