Natural Therapies

for

Hypertension

:

A

Research-Based Look into

Efficacy

by Chris D. Meletis, ND, and Rebecca Berzow, ND

Some of this material was previously published in Clinical Natural Medicine Handbook, by Drs. Chris Meletis, Nieske Zabriskie, and Robert Rountree.

Hypertension is one of the greatest health concerns of our time, costing an estimated $131 billion in medical expenses yearly and $25 billion in lost productivity.¹ According to the CDC, 1 in 3 Americans has high blood pressure, an estimated 68 million, less than half have their condition under control.² Alarmingly, another 1 in 5 US adults live with undiagnosed high blood pressure.³ High blood pressure is a known risk factor for heart attacks and strokes and is a leading cause of unexpected death.

Frustrating the development of treatment protocols is that the underlying cause is often unknown for each individual patient. This makes picking a therapy based on mechanism of action difficult, and it is rarely known what therapy will be most effective in which patients. This makes picking the best intervention for the patient as much luck as it is skill.

The first intervention should always be diet and lifestyle. Even the most resistant patients can be worked with to make minor changes that may benefit their condition. Lifestyle factors such as physical activity, incorporation of balanced minerals such as calcium, magnesium, potassium, and reducing sodium intake. Natural therapies can also be employed as either adjuncts or replacements for pharmaceutical therapies where appropriate. The goal should be to create as normotensive a patient as possible while minimizing side effects on a program that is sustainable for lifetime management.⁴ Our ratings for most efficacious to least efficacious natural therapies were developed from looking at the current research data, Aisle7 star-ratings system, the Natural Medicines Comprehensive database, the Natural Standard grading system, and our own clinical observations.

Diet

Despite compliance issues diet and lifestyle interventions need to be discussed because they can be extremely effective, reduce the need for medication and improve overall health. In a large randomized study from 2004, patients that increased physical activity, lost weight, decreased sodium and alcohol intake, had dramatic reductions in their base hypertension rates.⁵ Epidemiological studies have shown that among western populations, the most important risk factors for hypertension is lack of physical activity, followed by high sodium, low potassium and low magnesium intake. ⁶

It is clear from the evidence that dietary and lifestyle interventions can be extremely effective in reducing hypertension in a majority of patients. Sometimes, however these interventions may not be enough to return a patient to normal blood pressures; and in these cases pharmaceuticals, nutraceuticals, herbs, or a combination may need to be employed.

Best Evidence of Effective Natural Therapies

The following discussion is not ordered in of efficacy, this task is captured in Table 1. We have included in our discussion criteria that include other risk factors associated with hypertension such as inflammation and platelet aggregation. Blood pressure is a multimodal process; there is the presentation of elevated pressures, yet both the contributing factors and the associated risks that present with BP are ideally addressed simultaneously with what Dr. Meletis has termed “common thread prescribing,” which we both routinely use and that guides our prescribing practices.

INSERT TABLE 1

Fish Oil/Omega-3s

Fish oils from fatty fish such as salmon, mackerel, and herring are high in the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Omega-3 fatty acids from fish oils have anti-inflammatory and antithrombotic effects because they compete with arachidonic acid in the cyclooxygenase and lipoxygenase pathways. Omega-3 fatty acids suppress COX-2 expression and the inflammatory cytokines interleukin (IL)-1 alpha and tumor necrosis factor-alpha (TNF-α).⁷ A study showed highly purified EPA and DHA ethyl esters at a dose of 4 g per day to significantly decrease both systolic and diastolic blood pressure in mildly hypertensive individuals.⁸ Additional studies have shown that 4g per day of fish oil reduced systolic and diastolic blood pressure, as well as decreased triglycerides and very low density lipoprotein (VLDL) cholesterol.⁹ There is a dose-response effect of fish oil on blood pressure of −0.66/−0.35 mm Hg/g omega-3 fatty acids. The hypotensive effect may be strongest in hypertensive subjects and those with clinical atherosclerotic disease and/or hypercholesterolemia.¹⁰ Though modest in regard to lowering the total systolic and diastolic pressure, the side benefits of helping to control C-reactive protein and platelet adhesion are particularly significant for the hypertensive patient.

CoQ10

Coenzyme Q10 is one of the better-studied supplements with regard to hypertension, and also plays a crucial role in energy production and performance of the myocardium. Positive studies on the effects of CoQ10 on blood pressure date back to 1976.¹¹ A more recent study showed significant results from a dose of 50 mg b.i.d. for 10 weeks given to 26 participants. Participants systolic blood pressure dropped 18 points, diastolic 12 points, total cholesterol also dropped 10 mg/dL and HDL increased 2 mg/dl.¹² Despite the small study, these results suggest an added benefit to those patients suffering from both elevated blood pressure and cholesterol. An observational study found that of 109 patients already on high blood pressure medication who were supplemented with an average of 225 mg/day, over 50% could discontinue one or more of their high blood pressure medications after several months of supplementation.¹³ It is obvious from these results and the lack of risk to CoQ10 supplementation that this therapy may benefit a large number of patients living with hypertension and associated comorbidities. It is clear that while CoQ10 works well as an isolated therapy, it appears to have synergistic benefit when combined with certain allopathic treatments, though some interactions with blood-thinners and statins has also been noted.¹⁴

Green Coffee Extract

Green coffee has recently been getting a lot of press for its strong potential as a treatment for hypertension. A multicenter, randomized, double-blind, placebo-controlled, parallel group study evaluated green coffee extract effects on 117 male volunteers with mild hypertension. The study looked at results compared with the dosage of GCE given from 46 to 185 mg in four groups, observations and showed systolic blood pressure drops from −1.3 to −5.6 mmHg in a dose-dependent manner.¹⁵ Another study of 28 participants receiving 140 mg/day of chlorogenic acid from green coffee extract in the CGA group blood pressure decreased significantly during the ingestion period, there were no similar changes noted in the placebo group.¹⁶ There are other beneficial effects reported from the use of green coffee extract, including balancing blood sugar, weight loss, and antioxidant protection; this can protect vasculature, optimize body mass and hence peripheral resistance, and reduce oxidation of LDL. These effects are often needed in the hypertensive patient, and this supplement could be a great choice providing multiple benefits in one supplement.^17,18

Garlic

Garlic is another food botanical with mild antihypertensive effects. A meta-analysis of dried garlic powder studies suggests that garlic can have both systolic and diastolic lowering effects, though more studies are needed.¹⁹ In a placebo controlled trial the supine diastolic pressure dropped from 102 to 91 mmHg after 8 weeks and to 89 after 12 weeks. The serum cholesterol and triglycerides were also reduced after 8 and 12 weeks significantly. ²⁰ These results of course suggest longer-term studies are needed to fully understand garlic’s effectiveness. It is unclear how much more these numbers could be reduced over 6-12 months of therapy. Garlic has also been shown in studies to reduce platelet aggregation, and increase fibrinolytic activity.²¹ Studies regarding the cholesterol lowering effect of garlic have been mixed but several studies have shown a cholesterol lowering effect.²¹

Pycnogenol

In a study of hypertensive patients on ACE-inhibitor ramipril treatment, showing early renal function problems, Pycnogenol was shown to be protective against kidney damage and improved kidney cortical flow after 6 months of therapy.²² However an 8-week study conducted in 2012 showed improved endothelial function but no significant change in blood pressure was noted.²³ Yet another study however showed that supplementation with Pycnogenol for 12 weeks allowed for a reduction in the dosage of the calcium antagonist nifedipine.²⁴ The difference in outcome of these studies is unclear but, may be due to study design, length of the study, patient population or dosages supplied and more research could help clarify these issues. This clarification could then guide treatment in regards to dosages and patients likely to respond to therapy. It is clear from these studies that Pycnogenol supplementation requires monitoring of blood pressure and medication management for those hypertensive patients on pharmaceutical therapy concurrently. Pycnogenol has also been studied for its use as an antioxidant, and anti-inflammatory and may improve blood flow from encouraging NO production. Interactions have been noted with blood-thinning medications.²⁵

Calcium

The research on calcium has at times proved difficult to understand. In one study analysis of the entire group suggested that calcium supplementation had no significant effect on blood pressure. However when the results were separated by race and salt sensitivity it became clear that subjects identified as either black and/or salt-sensitive exhibited a significant blood pressure decrease with calcium supplementation.²⁶ It is also well known in scientific literature that there is a correlation with inadequate calcium intake and higher incidence of obesity and high blood pressure.²⁷ Clearly in light of these findings more research is needed to determine dosages as well as specific patient populations likely to derive the most benefit from calcium supplementation. From a clinical insight perspective, it would be intriguing to consider for those with dark pigment skin as to whether there might be a low vitamin D correlation. Vitamin D can increase calcium intestinal absorption by 40%, hence increasing calcium via supplementation though not correcting an inherent insufficiency of vitamin D, it may bypass the consequential suboptimal calcium levels.²⁸

Hibiscus

While research on hibiscus has proved interesting and hopeful as a hypotensive agent due to poor study design on some of the trials more research is needed before acceptance in the wider medical community. One controlled study showed that hibiscus tea had an 11.2% lowering to systolic blood pressure and a 10.7% reduction in diastolic blood pressure after just 12 days of starting treatment in the experimental group consisting of 31 participants. Three days after treatment cessation, systolic blood pressure rose 7.9% and diastolic 5.6%, suggesting that hibiscus does indeed have an observable hypotensive effect.²⁹ While a review of current Hibiscus studies on hypertension determined, “The four randomized controlled studies identified in this review do not provide reliable evidence to support recommending Hibiscus sabdariffa for the treatment of primary hypertension in adults,” interestingly, another randomized controlled trial study of captopril 50 mg/day and H. sabdariffa extract standardized to 9.6 mg anthocyanins showed no significant differences between hypotensive effects, antihypertensive effectiveness, or tolerability.^30,31 These starkly contrasting studies should be clarified by further investigations into the efficacy of hibiscus. However, clinically many a patient have reported benefits when using this botanical, realizing once again gleaning the unique dysregulation of a patient’s biochemistry that has led to the hypertensive state is varied indeed, and hence responsive to varying treatments.

Some

Evidence of Effectiveness

Hawthorn

Hawthorn has a long history of traditional use in the treatment of hypertension but is just now getting more research attention. One study of hawthorn on exercise capacity in congestive heart failure patients showed a meaningful increase in working capacity by 28 watts compared to a mere 5 watt in the placebo group. Though not the focus of the study, statistically significant drops in blood pressure and heart rate were also seen, and no adverse or side effects noted in the study.³²

Hawthorn appears to take 6 to 8 weeks of use before the effects are clinically observable therefore study design needs to reflect this. For example, one study failed to show results at 5 weeks but by 10 weeks reduction in blood pressure and anxiety were observed in the hawthorn group.³³ One of the challenges of studying botanicals is that optimal treatment timeframes are not always known, investigations should build this into studies whenever possible checking results at 1, 3, 6 months and longer could help to develop proper treatment protocols.

Melatonin

Melatonin has proved useful for those folks plagued with nighttime hypertension issues. Normally, blood pressure declines at night. People with hypertension who do not have this nighttime blood pressure decline are at increased risk of developing and dying from heart disease. Melatonin supplementation may therefore be beneficial for this subgroup of people with hypertension.³⁴ A double-blind study showed that treatment with 2 mg of sustained-release melatonin taken nightly for 4 weeks reduced nighttime systolic blood pressures.³⁴

Magnesium

Similar to calcium, the results on magnesium supplementation studies have not always shown a positive correlation to decreased blood pressures. One theory is that there may be a dose-dependent mechanism or only those with a deficiency of serum magnesium may react positively to supplementation. The effect observed has tended to be small and is most likely useful as a dietary consideration or adjunct therapy.³⁵ One factor seen in at least one study showed that magnesium supplementation was more effective in patients with a higher intraerythrocyte sodium concentration, suggesting that effectiveness may be higher in certain patient populations.³⁶

Clinically, measuring RBC magnesium levels, and optimizing them to the upper ¼ of the reference range is generally a good clinical goal.

Stevia

Stevia, often noted for its ability to lower blood glucose, has also shown hypotensive effects in studies. A Natural Standard review showed that two long-term studies (1–2 years) showed stevia to be effective in lowering blood pressure, however shorter studies(1–3 months) did not demonstrate a significant effect.³⁷ Another study of 106 participants showed a drop in systolic blood pressures from 166.0 +/−9.4 to 152.6+/−6.8 mmHg and diastolic blood pressures from 104.7+/−5.2 to 90.3+/−3.6 mmHG after three months of therapy, and no adverse effects were noted.³⁸ A study looking at mechanism of action determined that stevioside caused vasorelaxation by inhibiting CA2+ influx in to the blood vessel and was independent of NO.³⁹ These studies suggest that while stevia may have a blood-pressure lowering effect, it is likely due to long-term supplementation and results may not be seen clinically for several months. More research is welcomed to help develop a proper protocol including dosages and expected time frame for maximal effectiveness.

More Research

Needed

Olive Leaf

In rats, olive leaf extract showed blood pressure lowering effects, even when exposed to a hypertensive drug, in a dose-dependent manner. ⁴⁰

In an 8-week trial of olive vs. captopril, a significant reduction of triglyceride level was observed in the olive group, but not in the captopril group. The study authors concluded, “Olive (Olea europaea) leaf extract, at the dosage regimen of 500 mg twice daily, was similarly effective in lowering systolic and diastolic blood pressures in subjects with stage-1 hypertension as Captopril, given at its effective dose of 12.5-25 mg twice daily.”⁴¹ More human studies on safety, dosages and effectiveness are warranted to elucidate the power of olive leaf for treating hypertension.

Arginine and Citrulline

L-arginine is the precursor to endothelium-derived nitric oxide, which, as we know, relaxes the blood vessels and reduces blood pressure. One study injected various preparations of arginine into superficial hand veins. Dosages of 160 mumol/min caused a significant increase in forearm blood flow, indicating that arginine in high dosages is a vasodilator in vivo.⁴² Another study looked at 20 hypertensives currently treated with a combination of 20 mg enalapril and 12.5 mg hydrochlorothiazide. When 2 g t.i.d. oral L-arginine was added to their dual-drug regimen over 6 weeks, the arginine group had systolic drops in blood pressure from 155 +/−15 to 141 +/−18 and diastolic from 98 +/−11 to 90 +/−8, these results were statistically significant when compared with the placebo group.⁴³ In a small pilot study 9 adults were given 6 grams of L-citrulline/L-arginine from watermelon extract for 6 weeks. All subjects had improved arterial function and lowered aortic blood pressure.⁴⁴ Additional studies could help elucidate effective dosages and the use of L-arginine/L-citrulline as an adjunct to current drug therapies, potentially optimizing their effects, or as an alternative to drug therapy. More investigation is needed into watermelon as a food-based medicine, which is always preferable to supplements or drugs and tends to free of side effects or adverse effects. Food is our best preventative tool and interventional medicine.

MegaNatural-BP

MegaNatural-BP is a patent pending grapeseed product that reduces blood pressure through relaxing blood vessels by upgrading the reaction between ENOS and arginine to elevate nitric oxide. As a result, blood pressure is reduced. Human clinical trial #1 was performed at UC Davis; a randomized, double blind trial of 24 subjects with metabolic syndrome. The group was divided into three groups of 8; placebo, 150 mg and 300 mg GSE/day administered for 28 days. This trial showed that the 150 mg GSE group had a reduction in systolic pressures from 137 +/−4 to 125 +/−4, diastolic dropped from 84 +/−3.3 to 78 +/−1.9. The 300 mg GSE group dropped from 129 +/−4 to 117 +/−3 systolic and 79 +/−3 to 71 +/−3 diastolic.

Dr. Tissa Kappagoda is the primary researcher. Human clinical trial #2 also at UC Davis a randomized, double-blind trial of prehypertensive subjects divided into two groups, placebo and 300 mg GSE/day. Results showed an 8 mmHg drop in systolic pressure in the experimental group and 5 mmHg drop in diastolic pressure versus no change and an increase of 2 mmHg in placebo group respectively. Kappagoda, discussing human trials of MegaNatural at UC-Davis stated, “On average, patients were seeing a drop in blood pressure of 12 mmHg and 8 mmHg (systolic/diastolic) with a dose (daily) of only 150 mg, within a week.”

This product looks very promising as a possible treatment for hypertension, and a possible preventative measure for those with prehypertension.⁴⁵

Pomegranate

The seeds and the juice have been used traditionally as a heart tonic for many years. Recently researchers have been discovering that these early herbalists were using a scientifically sound therapy. One study administered 50 ml of pomegranate juice daily (equivalent to about 1.5 mmol total polyphenols) for 2 weeks to a group of hypertensive patients. Results showed a decrease in ACE activity by 36% and a 5% drop in systolic blood pressure.⁴⁶ Pomegranate juice consumption from 1 to 3 years was observed in atherosclerotic patients with carotid artery stenosis. The results showed a decrease in systolic blood pressure by 21% after 1 year.⁴⁷

Coleus

Coleus has traditionally been used in India for hypertension. The herb contains diterpenes that may contribute to the antihypertensive effect. Forskolin, one of these diterpenes, directly acts on adenyl cyclase and leads to increased intracellular levels of the second messenger cAMP.⁴⁸ This may lead to vasodilation and decreased blood pressure, more studies are needed. A study done on a small sample size showed statistically significant though minor drops in blood pressure in an elderly population.⁴⁹ Larger-scale studies conducted in a double-blind, placebo-controlled fashion are needed to fully understand coleus and its potential as a treatment for hypertension.

Conclusion

Just as various prescriptions medicine work or don’t for a given patient, whether it be a ACE inhibitor I or II, calcium channel blocker, diuretic, beta blocker or similar, and so on, finding the correct nutraceutical that best meets the patient’s overall needs is essential. It is becoming increasingly clear that there is a place for herbal medicine, nutraceuticals and diet, and lifestyle modification in modern medicine. Research done to a quality that the greater medical community can accept is now being done on a larger scale and is demonstrating that there is validity to some of these traditionally used therapies. Due to the varied biochemical makeup of patients it is clear that we need many options for treatment. Using botanicals, pharmaceuticals, and lifestyle changes can offer that variety. More research is needed on interactions and how to safely implement integrative therapies to the best benefit to our patients. Due to the dangerous adverse effects and side effects of some pharmaceutical medications for hypertension and the wide prevalence of the condition in the US, this area deserves our attention as clinicians and researchers.

Notes

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2. CDC. Vital signs: prevalence, treatment, and control of hypertension – United States, 1999-2002 and 2005-2008. MMWR. 2011;60(4):103–108.

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4. Meletis CD, Zabriskie N, Rountree R. Taming high blood pressure naturally. In: Clinical Natural Medicine Handbook. New Rochelle, NY: Mary Anne Liebert Inc.; 2008:221–228.

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7. Curtis CL, Hughes CE, Flannery CR, Little CB, Harwood JL, Caterson B. n-3 fatty acids specifically modulate catabolic factors involved in articular cartilage degradation. J Biol Chem. 2000 Jan 14;275(2):721–724.

8. Prisco D, Paniccia R, Bardinelli B, et al. Effect of medium-term supplementation with a moderate dose of n-3 polyunsaturated fatty acids on blood pressure in mild hypertensive patients. Thromb Res. 1998 Aug 1;91(3):105–112.

9. Toft I, Bonaa KH, Ingrebretsen OC, Nordoy A, Jenssen T. Effects on n-3 polyunsaturated fatty acids on glucose homeostasis and blood pressure in essential hypertension. A randomized, controlled trial. Ann Intern Med. 1995 Dec 15;123(12):911–918.

10. Morris MC, Sacks F, Rosner B. Does fish oil lower blood pressure? A meta-analysis of controlled trials. Circulation. 1993 Aug;88(2):523–533.

11. Yamagami T, Shibata N, Folkers K. Bioenergetics in clinical medicine: VIII. Administration of coenzyme Q10 to patients with essential hypertension. Res Commun Chem Pathol Pharmacol. 1976;721–727.

12. Digiesi V, Cantini F, Oradei A, et al. Coenzyme Q10 in essential hypertension. Mol Aspects Med. 1994;15(suppl.):S257–263.

13. Langsjoen P, Langsjoen P, Willis R, Folkers K. Treatment of essential hypertension with coenzyme Q10. Mol Aspects Med. 1994;15(suppl):S265–S272.

14. University of Maryland Medical Center: Possible interaction with Coenzyme Q10 [online article]. http://www.umm.edu/altmed/articles/coenzyme-q10-000950.htm. Accessed February 24, 2013.

15. Kozuma K, Tsuchiva S, Kohori J, Hase T, Tokimitsu I. Antihypertensive effect of green coffee bean extract on mildly hypertensive subjects. Hypertens Res. 2005 Sep;28(9):711–718

16. Watanabe T, Arai Y, Mitsui Y, et al. The blood pressure-lowering effect and safety of chlorogenic acid from green coffee bean extract in essential hypertension. Clin Exp Hypertens. 2006;28:439–449.

17. Jockers D. Coffee bean extract is a powerful antioxidant [online article]. Natural News. May 18, 2012. http://www.naturalnews.com/035903_coffee_bean_extract_antioxidants.html. Accessed February 23, 2013.

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20. Auer W, Eiber A, Hertkorn E, et al. Hypertension and hyperlipidaemia: garlic helps in mild cases. Br J Clin Pract Suppl. 1990 Aug;69:3–6.

21. Banerjee S, Maulik S. Effect of garlic on cardiovascular disorders: a review. Nutr J. 2002;1:4. Available at http://www.nutritionj.com/content/1/1/4. Accessed February 23, 2013.

22. Cesarone MR, Belcaro G, Stuard S, et al. Kidney flow and function in hypertension: protective effects of pycnogenol in hypertensive participants – a controlled study. J Cardiovasc Pharmacol Ther. 2010 Mar;15(1):41–46.

23. Enseleit F, Sudano I, Périat D, et al. Effects of Pycnogenol on endothelial function in patients with stable coronary artery disease: a double-blind, randomized, placebo-controlled, cross-over study. Eur Heart J. 2012 Jul;33(13):1589–1597

24. Liu X, Wei J, Tan F, Zhou S, Wurthwein G, Rohdewald P. Pycnogenol, French maritime pine bark extract, improves endothelial function of hypertensive patients. Life Sci. 2004 Jan 2;74(7):855–862.

25. Pycnogenol benefits and side effects and Tinnitus [online article]. Superfoods Scientific Research. March 28, 2012. http://www.superfoods-scientific-research.com/natural-remedies/pycnogenol-benefits.htm. Accessed February 24, 2013.

26. Weinberger MH, Wagner UL, Fineberg NS The blood pressure effects of calcium supplementation in humans of known sodium responsiveness. Am J Hypertens. 1993 Sep;6(9):799–805

27. Zemel MB. Calcium modulation of hypertension and obesity: mechanisms and implications. J Am Coll Nutr. 2001 Oct;20(5 Suppl):428S–435S; discussion 440S–442S.

28. Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357:266–281.

29. Haji FM, Haji TA. The effect of sour tea (Hibiscus sabdariffa) on essential hypertension. J Ethnopharmacol. 1999 Jun;65(3):231–236.

30. Wahabi HA, Alansary LA, Al-Sabban AH, Glasziuo P. The effectiveness of Hibiscus Sabdariffa in the treatment of hypertension: a systemic review. Phytomedicine. 2010 Feb;17(2):83–86

31. Herrera-Arellano A, Flores-Romero S, Chavez-Soto MA, Tortoriello J. Effectiveness and tolerability of a standardized extract from Hibiscus sabdariffa in patients with mild to moderate hypertension: a controlled and randomized clinical trial. Phytomedicine. 2004 Jul;11(5):375–382.

32. Schmidt U, Kuhn U, Ploch M, Hubner WD. Efficacy of the Hawthorne (Crataegus) preparation LI 132 in 78 patients with chronic congestive heart failure defined as NYHA functional class II. Phytomedicine. 1994 Jun;1(1):17–24.

33. Walker AF, Marakis G, Morris AP, Robinson PA. Promising hypotensive effect of hawthorn extract: a randomized double-blind pilot study of mild, essential hypertension. Phytother Res. 2002 Feb;16(1):48–54.

34. Grossman E, Laudon M, Yalcin R, et al. Melatonin reduces night blood pressure in patients with nocturnal hypertension. Am J Med. 2006;119:898–902.

35. Kawano Y, Matsuoka H, Takishita S, Omae T. Effects of magnesium supplementation in hypertensive patients : assessment by office, home, and ambulatory blood pressures. Hypertension. 1998;32:260–265

36. Motoyama T, Sano H, Fukazaki H. Oral magnesium supplementation in patients with essential hypertension. Hypertension.1989; 13: 227–232.

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41. Susalit E, Agus N, Effendi I, et al. Olive (Olea europaea) leaf extract effective in patients with stage-1 hypertension: comparison with Captopril. Phytomedicine 2011 Feb 15;18(4):251–258 Epub 2010 Oct 30.

42. Calver A, Collier J, Vallance P. Dilator actions of arginine in human peripheral vasculature. Clin Sci (Lond). 1991 Nov;81(5):695–700.

43. Pezza V, Bernardini F, Pezza E, et al. Study of supplemental oral l-arginine in hypertensives treated with enalapril + hydrochlorothiazide. Am J Hypertens. 1998;11:1267–1270 [letter].

44. Figueroa A, Sanchez-Gonzalez MA, Perkins-Veazie PM, Arjmandi BH. Effects of watermelon supplementation on aortic blood pressure and wave reflection in individuals with prehypertension: a pilot study. Am J Hypertens. 2011 Jan;24(1):40–44;doi:10.1038/ajh.2010.142. Epub 2010 Jul 8.

• Original research on MegaNatural^®-BP [Web page]. Polyphenolics. http://www.polyphenolics.com/original-research-on-meganatural-bp. Accessed February 23, 2013.

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46. Aviram M, Rosenblat M, Gaitini D, et al. Pomegranate consumption for three years by patients with carotid artery stenosis reduces common carotid intima-media thickness, blood pressure and LDL oxidation. Clin Nutr. 2004 Jun;23(3):423–433

47. Ishikawa Y. Isoform-targeted regulation of cardiac adenylyl cyclase. J Cardiovasc Pharmacol. 2003;41(suppl.1):S1–S4.

48. Jagtap M, Chandola HM, Ravishankar B. Clinical efficacy of Coleus forskholii (Willd.) Brig. (Makandi) in hypertension of geriatric population. Ayu. 2011 Jan–Mar;32(1):59–65.

49. Mori TA, Bao DQ, Burke V, et al. Docosahexaenoic acid but not eicosapentaenoic acid lowers ambulatory blood pressure and heart rate in humans. Hypertension. 1999;34:253–260.

51. Holm T, Andreassen AK, Aukrust P, et al. Omega-3 fatty acids improve blood pressure control and preserve renal function in hypertensive heart transplant recipients. Eur Heart J. 2001 Mar;22(5):428–436.

52. Toft I, Bonaa KH, Ingebretsen OC, Nordoy A, Jenssen T. Fibrinolytic function after dietary supplementation with omega3 polyunsaturated fatty acids. Arterioscler Thromb Vasc Biol. 1997;17(5):814–819.

53. Gray DR, Gozzip CG, Eastham JH, Kashyap ML. Fish oil as an adjuvant in the treatment of hypertension. Pharmacotherapy. 1996;16(2):295–300.

54. Folkers K, Drzewoski J, Richardson PC, et al. Bioenergetics in clinical medicine. XVI. Reduction of hypertension in patients by therapy with coenzyme Q10. Res Commun Chem Pathol Pharmacol. 1981;31:129–40.

55. Digiesi V, Cantini F, Brodbeck B. Effect of coenzyme Q10 on essential arterial hypertension. Curr Ther Res. 1990;47:841–845.

56. Singh RB, Niaz MA, Rastogi SS, et al. Effect of hydrosoluble coenzyme Q10 on blood pressures and insulin resistance in hypertensive patients with coronary artery disease. J Hum Hypertens. 1999;13:203–208.

57. Hypertension [Web page]. Aisle7. http://aisle7.com/index.php/demos/aisle7-online1. Accessed February 18, 2012.

58. Foods, Herbs & Supplements [Web page]. Natural Standard. http://www.naturalstandard.com/databases/herbssupplements/all/a. Accessed February 18, 2012.

59. Noordzij M, Uiterwaal CS, Arends LR, et al. Blood pressure response to chronic intake of coffee and caffeine: a meta-analysis of randomized controlled trials. J Hypertens 2005;23:921–928 [review].

60. Ibid.

61. Yamaguchi T, Chikama A, Mori K, et al. Hydroxyhydroquinone-free coffee: a double-blind, randomized controlled dose-response study of blood pressure. Nutr Metab Cardiovasc Dis. 2008;18:408–414.

62. Ochiai R, Jokura H, Suzuki A, et al. Green coffee bean extract improves human vasoreactivity. Hypertens Res 2004;27:731–737.

63. Holzgartner H, Schmidt U, Kuhn U. Comparison of the efficacy and tolerance of a garlic preparation vs. bezafibrate. Arzneimittelforschung. 1992;42(12):1473–1477.

64. Isaacsohn JL, Moser M, Stein EA, et al. Garlic powder and plasma lipids and lipoproteins: a multicenter, randomized, placebo-controlled trial. Arch Intern Med. June 8, 1998;158(11):1189–1194.

65. McCrindle BW, Helden E, Conner WT. Garlic extract therapy in children with hypercholesterolemia. Arch Pediatr Adolesc Med. 1998;152(11):1089–1094.

66. Saradeth T, Seidl S, Resch KL, and et al. Does garlic alter the lipid pattern in normal volunteers? Phytomedicine. 1994;1:183–185.

67. Hosseini S, Lee J, Sepulveda RT, Fagan T, et al. A randomized, double blind, placebo-controlled, prospective 16 week crossover study to determine the role of Pycnogenol(R) in modifying blood pressure in mildly hypertensive patients. Nutr Res. 2001;21:67–76.

Table 1

Note

: These ratings are a reflection of these remedies in relationship to hypertension only. Other conditions may yield different ratings for the same supplements.

Our Ratings:

4: likely effective for condition, solid scientific evidence

3: possible effective for condition, some strong positive evidence

2: possibly effective for condition, some pertinent negative studies or undesirable effects

1: likely ineffective for condition due to extensive negative studies or lack of evidence of efficacy