In the war on cardiovascular disease, one battle is hypertension. Studies have shown that co-Q10 and omega-3 fatty acids can reduce blood pressure; other supplements, such as garlic, L-arginine and calcium, can offer support by affecting certain variables related to hypertension. Conrad Earnest, PhD, investigates
Cardiovascular disease risk is multi-factorial. A primary factor associated with CVD is the presence of hypertension, or high blood pressure (BP). Per classical pharmacotherapy, several medications are capable of lowering BP. Further, as with many of the co-morbidities associated with CVD, lifestyle interventions such as moderate exercise, weight loss and diet interventions can reduce its incidence.
Investigators using the DASH combination diet (Dietary Approaches to Stop Hypertension) have noted that the DASH programme — low in total fat, saturated fat and cholesterol, and rich in fruits, vegetables and low-fat dairy — significantly lowered both systolic BP and diastolic BP. The overall decrease was 11.4mm Hg and 5.5mm Hg, respectively, in 459 hypertensive individuals. 1
Another study, the phase II Trials of Hypertension Prevention, tested interventions to promote weight loss, dietary sodium reduction, and their combination for lowering diastolic BP, systolic BP and the incidence of hypertension. The four-year study assessed 2,382 men and women (age 30-54 years) not taking antihypertensive drugs. In this nine-centre trial, patients were counselled to reduce weight, reduce sodium intake, or reduce both weight and sodium intake.
Compared with a control group, systolic/diastolic BP decreased 3.7/2.7mm Hg in the weight-loss group, 2.9/1.6mm Hg in the sodium-reduction group and 4.0/2.8mm Hg in the combined group within six months. After 48 months, BP decreases remained greater in each intervention group than in the control group.2 A more recent randomised, controlled trial assessed the efficacy of simultaneously implementing diet, exercise and weight loss in a group of overweight, hypertensive adults.3 Forty-four hypertensive, overweight adults, taking a single blood pressure medication, were randomised to one of two groups. The lifestyle group ate a low-calorie, low-sodium diet based on the DASH diet and participated in moderate-intensity exercise three times weekly. The control group continued their previous lifestyle. The lifestyle group lost an average of 4.9kg in nine weeks. Reductions in daytime blood pressure readings were 12.1mm Hg systolic and 6.6mm Hg diastolic BP, while the control group showed no reduction.3 Beyond strict dietary measures, dietary supplements have evidence of efficacy in lowering BP. This article will review five supplements touted as having a profound influence on blood pressure measurements directly: co-Q10, omega-3 fatty acids, garlic, L-arginine and calcium.
Long theorised that patients with hypertension have a deficiency of co-Q10,4 recent evidence suggests that co-Q10 may lower blood pressure by correcting an endogenous provitamin deficiency. Provitamins are substances that are converted into a vitamin in animal tissues. In a recent review of eight trials, co-Q10 administration has shown a consistent reduction in blood pressure.4
Interestingly, these findings have been established using co-Q10 with hypertension medications as well as with co-Q10 alone. One such example is a randomised, double-blind trial using 60mg co-Q10 twice daily to 59 patients already receiving conventional antihypertensive medications.5 In this study, two treatment groups received either co-Q10 only or a B-vitamin complex for eight weeks, where the co-Q10 group showed a 16mm Hg reduction in systolic BP and a 9mm Hg reduction in diastolic BP.
In a larger study, 109 patients with essential hypertension (of unknown cause) were given an average oral dose of 225mg/day to their existing antihypertensive drug regimen. In a truly ?titrated-care? fashion, the dosage of co-Q10 was not fixed, but was adjusted according to clinical response and blood co-Q10 levels. In this study, a definite and gradual improvement in blood pressure status was observed with the concomitant need to gradually decrease antihypertensive drug therapy within the first one to six months. Half the patients were taken completely off of between one and three antihypertensive drugs at an average of 4.4 months after starting co-Q10.6
Coenzyme Q10 has also shown some benefit in treating isolated systolic hypertension. In one study, a cohort of 46 men and 37 women with isolated systolic hypertension were enrolled in a 12-week randomised, double-blind, placebo-controlled trial. The treatment group received 60mg co-Q10 twice daily. The reduction of systolic BP in the treatment group was about 17.8mm Hg. The reduction of systolic BP in the placebo group was only 1.7mm Hg.7
In a second study, 26 patients with essential arterial hypertension (hypertension in the pulmonary artery) were treated with oral co-Q10, 50mg twice daily for 10 weeks. At the end of the treatment, systolic BP decreased by 17.8mm Hg and diastolic BP decreased 12mm Hg.8 In a further demonstration of efficacy, plasma co-Q10 values significantly increased from 0.64 microgram/mL to 1.61 micrograms/mL. This is an interesting fact attesting to the pharmacokinetics associated with supplement ingestion echoed by a decline in a hard clinical end-point — in this case, blood pressure.8
Omega-3 fatty acids
The contribution and efficacy of omega-3 fatty acids, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been recognised by the US Food and Drug Administration as ameliorating cardiovascular health. So strong is the evidence that the American Heart Association recently issued recommendations for omega-3 fatty acids, while parenthetically failing to endorse the use of multivitamin/antioxidant therapies.9,10 Bolstered by a large degree of epidemiological evidence, several clinical trials attest to the antihypertensive benefits of fish oils.
In an early study reported in the New England Journal of Medicine, BP and eicosanoid production were studied during supplementation for four weeks in 32 men with mild essential hypertension. In this small trial, four groups of eight subjects received either 10ml or 50ml fish oil (3g or 15g of n-3 fatty acids yielding 1.8 and 9.0g EPA and 1.2 and 6.0g DHA daily,) 50ml of safflower oil (39g of n-6 fatty acids), or 50ml of a mixture of oils that approximated the types of fat present in the American diet. 11 The findings showed that BP decreased in the men who received the high dose of fish oil (systolic BP 6.5mm Hg and diastolic BP pressure by 4.4mm Hg), but not in the other groups. An interesting finding is that the formation of vasodilatory prostacyclins (prostaglandins I2 and I3) increased initially; however, this increase was not maintained as blood pressure fell. 11
As with co-Q10, combination pharmaco and nutritive therapies appear to be efficacious as well. In one study, 47 male patients with mild essential hypertension were randomly allocated to three subgroups: propranolol (a beta blocker; 80mg/day) for 36 weeks followed by a placebo period of four weeks; encapsulated fish oil (9g/day) for 36 weeks with a subsequent four-week placebo period; propranolol (80mg/day) for 12 weeks, and then propranolol (80mg/day) plus fish oil capsules (9g/day equivalent to 1.8 g/day of EPA and 1.1 g/day of DHA) for 12 weeks; and propranolol plus fish oil placebo (same doses for 12 weeks) with a subsequent four-week propranolol placebo period. The results indicated that the BP-lowering effect of fish oil alone (-7mm Hg systolic BP) was comparable with that of propranolol (-12mm Hg systolic BP), yet the simultaneous intake of fish oil plus propranolol was actually more effective than propranolol or fish oil alone (-30mm Hg systolic BP).12 However, a similar trial involving the drug nephedepine did not echo these results.13
In 1996, researchers fed 20 hypertensive subjects Alsepa fish oil a combined 180mg EPA and 120mg DHA in three clinical trials of 13 days. During this study, plasma phospholipids showed an increase in EPA and DHA followed by a concomitant reduction in systolic BP and diastolic BP of 11mm Hg and 8mm Hg, respectively.
This was coupled with other CVD-friendly findings of a significant decrease in platelet adhesion and aggregation and TG.14 In a follow-up study, this same group reported similar findings in both the non-diabetic (-11mm Hg, systolic BP) and diabetic groups (-16mm Hg, systolic BP) as well as triglyceride concentrations (range, 25-30 per cent).15 Several other studies also confirm the aforementioned findings.16,17
For those unwilling or unable to consume fish and/or fish products, the results of plant-derived omega-3s — flax seed and walnut — are less impressive.18,19,20,21 However, in fairness, a well-constructed study examining BP and plant-derived omega-3 sources has not been performed. In the aforementioned studies, hypertension or blood pressure response was not a primary outcome measurement, but one reported in conjunction with the trial.
Therefore, studies looking specifically at hypertension may yield different responses. Furthermore, in several studies, the feeding of walnuts and flax seed appear to favourably alter vasoreactivity or the speed with which a blood vessel reacts to a period of occlusion. With the beneficial result being ?faster reactivity is better,? these trials do suggest a positive vascular response to flax seed and walnut consumption.20,22,23,24
Overall, a meta-analysis of trials evaluating the efficacy of garlic in the treatment of high blood pressure showed that garlic may decrease BP.25 To date, garlic is thought to be effective in treating hypertension by causing smooth muscle relaxation and vasodilatation. Included in this analysis were randomised controlled trials of garlic supplements for reducing blood pressure that lasted from four weeks to 10 months and ranged in dosage from 600-900mg/day.
Of the studies examined, seven were double-blind trials comparing garlic with placebo in 383 patients. Of the seven, only three showed a significant reduction in systolic BP from baseline compared to a placebo (average 7.7mm Hg). Four of the seven trials showed a significantly greater reduction of diastolic blood pressure from baseline with garlic compared with placebo, with an overall advantage of about 5mm Hg. Before jumping on the antihypertensive bandwagon, the authors also commented on the difficulty of the analysis due to poor study design, poor blood pressure measurement technique (See sidebar, below) and general lack of control in the studies? performance.
Another point that is not clear is the optimal dose required to elicit an antihypertensive effect. For example, in one pilot trial, a garlic preparation containing 1.3 per cent allicin at a large dose (2,400mg) was evaluated in an open-label study (that is, no control group) in nine patients with severe hypertension. This trial showed a reduction in systolic BP five hours after the dose and a persistent decrease in diastolic blood pressure from five to 14 hours after the dose. However, no multi-day effects were examined in this high-dose study.26
In an early study, researchers examined 47 non-hospitalised patients with mild hypertension in a randomised, placebo-controlled, double-blind trial. During this trial, patients were admitted into the trial if their diastolic BP was between 95 and 104mm Hg after a two-week acclimatisation phase. The patients then took either garlic powder or a placebo. After 12 weeks, significant differences between the placebo and the drug group were found during the course of therapy, whereby supine diastolic BP in the garlic group fell from 102 to 91mm Hg after eight weeks and to 89mm Hg after 12 weeks. The serum cholesterol and triglycerides were also significantly reduced after eight and 12 weeks of treatment. In the placebo group, on the other hand, no significant changes were observed.27
The use of L-arginine in hypertension is predicated on the concept that endothelial function and nitric oxide (NO)-mediated relaxing mechanism in the arterial walls are impaired in atherosclerotic and in hypertensive arteries. In essence, NO is an endothelium-derived relaxing factor that helps regulate vascular tone. By supplementing with L-arginine, more nitric oxide is produced, thereby inhibiting other vascular factors that impede vascular relaxation.28
Like many avenues of contemporary research, the groundwork for using L-arginine as a progenitor of NO release began (and continues) with the observation that rats fed and infused with L-arginine exhibited decreases in blood pressure. Furthermore, several trials using L-arginine have been shown to be effective when L-arginine is either infused or injected into the research subject directly.29,30,31,32 However, in humans, L-arginine has found success only in several small pilot studies, and falls into the general category of having some supportive evidence.
In an early single-blind, crossover trial, conducted in six healthy volunteers, the effect of arginine-rich diets on blood pressure was examined. Patients were separated into three groups. Group 1 served as the control group and received a diet relatively low in L-arginine. Group 2 received an L-arginine-rich diet based on natural foods such as dry legumes and nuts. Group 3 received a diet identical to that of the control group plus L-arginine supplementation. At the end of this study, the patients with higher L-arginine intake (Groups 2 and 3) showed a significant reduction in blood pressure, with a decrease in systolic BP of 6.2mm Hg more than the control group and a decrease in diastolic BP of 5.0mm Hg more than the control group.33 It should be noted that subject numbers this small should be viewed only as a pilot effort.
In another small pilot study, oral L-arginine had favourable effects on both systolic BP and diastolic BP in hypertensive kidney transplant and hemodialysis patients. Six normotensive individuals and 10 kidney transplant patients received 9g L-arginine daily for nine days, then 18g L-arginine daily for nine additional days. Six hemodialysis patients and four peritoneal dialysis patients received the same dose for 14 days. Five kidney transplant patients received 30mL canola oil daily in addition to L-arginine. In the hemodialysis patients, systolic BP decreased by approximately 28.7mm Hg, whereby the change in diastolic BP decreased to a lesser extent.34
In another pilot effort using crossover trial design, six patients with type 2 diabetes mellitus and mild hypertension received 3g arginine hourly for 10 hours on either day two or day three of the study.33 Blood pressure was measured between 5 a.m. and 4 p.m. Systolic BP and diastolic BP decreased by 12mm Hg and 6.2mm Hg, respectively.
However, the antihypertensive effect was only temporary. For example, BP dropped within two hours of initiating arginine and returned to the previous value within one hour of stopping arginine. This is an important consideration when one considers factors that affect the efficacy of any supplement — in this case, length of treatment effect. These results have been echoed in larger trials as well.
A larger, prospective, randomised, double-blind trial conducted in 35 people with essential hypertension showed less-promising results. Patients were randomised to receive either 6g L-arginine or placebo. Acute changes in blood pressure were noted, but long-term effects warrant further investigation.35 As the latter two studies demonstrate, L-arginine may be effective only in acute situations.
Early epidemiological evidence has provided some evidence to suggest that the intake of dietary calcium may have an influence on blood pressure. In one study, two communities were examined to determine the relationship of vitamin D and calcium as it relates to BP in 86 women, aged 20-35 years, and 222 women, aged 55-80 years, who were not using diuretics. (This is a very small sample size for epidemiology.) Based on a food frequency estimate of calcium intake, a 24-hour dietary recall and an extensive supplement-use history, the authors of this study found no overall significant relationship between estimated current dietary calcium consumption and blood pressure in either age group.
However, in younger women, there was a significant inverse relationship between estimated dietary intake of vitamin D and systolic blood pressure, which remained significant after adjusting for age, body mass index, alcohol consumption and calcium intake. Interestingly, older women whose consumption of both vitamin D and calcium was less than the RDA had a significantly higher systolic blood pressure.36 However, these findings were supported in a larger trial of 199 post-menopausal women.37
In a 1986 clinical trial, using a randomised, double-blind, placebo-controlled crossover design of oral calcium supplementation carried out in 18 patients with uncomplicated essential hypertension, 15 weeks of oral calcium supplementation (1g/day) showed a significantly reduced systolic BP (-8.6mm Hg).
Conrad Earnest, PhD, is director of the Center for Human Performance and Nutrition Research at The Cooper Institute Centers for Integrated Health Research in Dallas, Texas.
Respond: [email protected]
All correspondence will be forwarded to the author.
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; 336:1117-24.
2. The Trials of Hypertension Prevention Collaborative Research Group. Effects of weight loss and sodium reduction intervention on blood pressure and hypertension incidence in overweight people with high-normal blood pressure. The Trials of Hypertension Prevention, phase II. Arch Intern Med 1997; 157:657-67.
3. Miller ER, 3rd, et al. Results of the Diet, Exercise and Weight Loss Intervention Trial (DEW-IT). Hypertension 2002; 40:612-8.
4. Tran MT, et al. Role of coenzyme Q10 in chronic heart failure, angina and hypertension. Pharmacotherapy 2001; 21:797-806.
5. Singh RB, et al. Effect of hydrosoluble coenzyme Q10 on blood pressures and insulin resistance in hypertensive patients with coronary artery disease. J Hum Hypertens 1999; 13:203-8.
6. Langsjoen P, et al. Treatment of essential hypertension with coenzyme Q10. Mol Aspects Med 1994; 15 Suppl:S265-72.
7. Burke BE, et al. Randomized, double-blind, placebo-controlled trial of coenzyme Q10 in isolated systolic hypertension. South Med J 2001; 94:1112-7.
8. Digiesi V, et al. Coenzyme Q10 in essential hypertension. Mol Aspects Med 1994; 15 Suppl:s257-63.
9. Kris-Etherton PM, et al. Omega-3 fatty acids and cardiovascular disease: new recommendations from the American Heart Association. Arterioscler Thromb Vasc Biol 2003; 23:151-2.
10. Kris-Etherton PM, et al. Antioxidant vitamin supplements and cardiovascular disease. Circulation 2004; 110:637-41.
11. Knapp HR, FitzGerald GA. The antihypertensive effects of fish oil. A controlled study of polyunsaturated fatty acid supplements in essential hypertension. N Engl J Med 1989; 320:1037-43.
12. Singer P, et al. Fish oil amplifies the effect of propranolol in mild essential hypertension. Hypertension 1990; 16:682-91.
13. Landmark K, et al. Effects of fish oil, nifedipine and their combination on blood pressure and lipids in primary hypertension. J Hum Hypertens 1993; 7:25-32.
14. Yosefy C, et al. Repeated fasting and refeeding with 20:5, n-3 eicosapentaenoic acid (EPA): a novel approach for rapid fatty acid exchange and its effect on blood pressure, plasma lipids and hemostasis. J Hum Hypertens 1996; 10 Suppl 3:S135-9.
15. Yosefy C, et al. The effect of fish oil on hypertension, plasma lipids and hemostasis in hypertensive, obese, dyslipidemic patients with and without diabetes mellitus. Prostaglandins Leukot Essent Fatty Acids 1999; 61:83-7.
16. Gray DR, et al. Fish oil as an adjuvant in the treatment of hypertension. Pharmacotherapy 1996; 16:295-300.
17. Sacks FM, et al. The effect of fish oil on blood pressure and high-density lipoprotein-cholesterol levels in phase I of the Trials of Hypertension Prevention. Trials of Hypertension Prevention Collaborative Research Group. J Hypertens Suppl 1994; 12:S23-31.
18. Sabate J, et al. Effects of walnuts on serum lipid levels and blood pressure in normal men. N Engl J Med 1993; 328:603-7.
19. Iwamoto M, et al. Walnuts lower serum cholesterol in Japanese men and women. J Nutr 2000; 130:171-6.
20. Rupp H, et al. Dietary linolenic acid-mediated increase in vascular prostacyclin formation. Mol Cell Biochem 1996; 162:59-64.
21. Nestel PJ, et al. Arterial compliance in obese subjects is improved with dietary plant n-3 fatty acid from flaxseed oil despite increased LDL oxidizability. Arterioscler Thromb Vasc Biol 1997;17:1163-70.
22. Ros E, et al. A walnut diet improves endothelial function in hypercholesterolemic subjects: a randomized crossover trial. Circulation 2004;109:1609-14.
23. Munoz S, et al. Walnut-enriched diet increases the association of LDL from hypercholesterolemic men with human HepG2 cells. J Lipid Res 2001; 42:2069-76.
24. West SG. Effect of diet on vascular reactivity: an emerging marker for vascular risk. Curr Atheroscler Rep 2001; 3:446-55.
25. Klepser TB, Klepser ME. Unsafe and potentially safe herbal therapies. Am J Health Syst Pharm 1999; 56:125-38; quiz 139-41.
26. McMahon FG, Vargas R. Can garlic lower blood pressure? A pilot study. Pharmacotherapy 1993; 13:406-7.
27. Auer W, et al. Hypertension and hyperlipidaemia: garlic helps in mild cases. Br J Clin Pract Suppl 1990; 69:3-6.
28. Wu G, Meininger CJ. Arginine nutrition and cardiovascular function. J Nutr 2000; 130:2626-9.
29. Campese VM, et al. Effect of L-arginine on systemic and renal haemodynamics in salt-sensitive patients with essential hypertension. J Hum Hypertens 1997; 11:527-32.
30. Herlitz H, et al. Effect of L-arginine infusion in normotensive subjects with and without a family history of hypertension. Kidney Int 1999; 56:1838-45.
31. Nelin LD, Hoffman GM. L-arginine infusion lowers blood pressure in children. J Pediatr 2001; 139:747-9.
32. Castejon AM, et al. Differential blood pressure effects of oral glucose and intravenous L-arginine in healthy lean normotensive and obese hypertensive subjects. J Hum Hypertens 2002; 16 Suppl 1:S133-6.
33. Siani A, et al. Blood pressure and metabolic changes during dietary L-arginine supplementation in humans. Am J Hypertens 2000; 13:547-51.
34. Kelly BS, et al. Oral arginine improves blood pressure in renal transplant and hemodialysis patients. JPEN J Parenter Enteral Nutr 2001;25:194-202.
35. Lekakis JP, et al. Oral L-arginine improves endothelial dysfunction in patients with essential hypertension. Int J Cardiol 2002; 86:317-23.
36. Sowers MR, et al. The association of intakes of vitamin D and calcium with blood pressure among women. Am J Clin Nutr 1985; 42:135-42.
37. Schramm MM, et al. Lack of an association between calcium intake and blood pressure in postmenopausal women. Am J Clin Nutr 1986; 44:505-11.
38. Strazzullo P, et al. Controlled trial of long-term oral calcium supplementation in essential hypertension. Hypertension 1986; 8:1084-8.
39. Lyle RM, et al. Metabolic differences between subjects whose blood pressure did or did not respond to oral calcium supplementation. Am J Clin Nutr 1988; 47:1030-5.
40. Lyle RM. Does baseline serum total calcium level influence the blood pressure response to calcium supplementation? A double-blind study. Neth J Med 1992; 41:48-55.