Agents With Some Evidence of Benefit CoQ10
The Natural Medicines Comprehensive Database[3] has five potential categories of efficacy: effective, likely effective, possibly effective, possibly ineffective, or likely ineffective. The database uses evidence-based articles from Medline to classify each indication for each agent. CoQ10 falls into the category of possibly effective in the treatment of hypertension.
It has been theorized that most hypertensive patients have a significant deficiency of CoQ10. It is now understood that CoQ10 may lower blood pressure by correcting an endogenous provitamin deficiency.[11] Tran et al.[11] reviewed eight different trials that measured the decrease in blood pressure following differing doses of CoQ10. All eight trials showed some degree of reduction in blood pressure, although the amount of reduction was not consistent among the trials.[11]
A randomized, double-blind trial conducted by Singh et al.[12] suggested that administration of 60 mg CoQ10 twice daily to patients already receiving conventional antihypertensive medications provides protection to pancreatic ß cells, liver cells, arterial smooth muscle cells, and endothelial cells through its antioxidative action. Group A received CoQ10 at the previously defined dose. Group B received a B-vitamin complex. There were 30 patients in Group A and 29 patients in Group B. Patients were followed for 8 weeks. The CoQ10 group showed a 16 mm Hg reduction in SBP and a 9 mm Hg reduction in DBP. Reductions in the following indices were also noted in the CoQ10 group: fasting insulin and glucose levels, triglycerides, and lipid peroxides. In addition, increases in the following indices were noted: high-density lipoprotein cholesterol; vitamins A, C, and E; and beta carotene. Group B only benefited with an increase in vitamin C and beta carotene.
Coenzyme Q10 has also shown some benefit in the treatment of isolated systolic hypertension. A cohort of 46 men and 37 women with isolated systolic hypertension were enrolled in a 12-week randomized, double blind, placebo-controlled trial. The treatment group received 60 mg CoQ10 twice daily. The reduction of SBP in the treatment group was 17.8 ± 7.3 mm Hg. The reduction of SBP in the placebo group was only 1.7 mm Hg.[13]
The Natural Medicines Comprehensive Database gives fish oil a rating of possibly effective when used orally for hypertension. The omega-3 fatty acids (eicosapentoic acid and docosahexanoic acid) in fish oils potentially lower blood pressure by directly modulating the intracellular calcium ion, which signals vascular smooth muscles to dilate.[3]
Sixteen hypertensive men and 16 normotensive men were randomly assigned to receive either eicosapentoic acid and docosahexanoic acid or olive oil as a placebo for a period of 4 months. After 2 months, SBP decreased by 6 mm Hg and DBP decreased by 5 mm Hg in fish oil-treated hypertensives and normotensives.[14]
Yosefy et al.[15] examined the efficacy of dietary fish oil supplementation in obese patients with hypertension and dyslipidemia, with and without diabetes mellitus. Twenty nondiabetic patients who were obese, hypertensive, and dyslipidemic participated in a 13-day unblinded study. Participants fasted for four 20-hour periods on Days 1, 5, 9, and 13. Fish oil concentrate, in the form of a tablet containing 180 mg eicosapentaenoic acid and 120 mg docosahexanoic acid, was administered as 15 capsules daily for the 13 days (a high dose that often causes side effects). In addition, the patients were placed on the American Heart Association Step I diet, which includes cholesterol intake less than 300 mg with 50% of total daily energy intake coming from carbohydrates, 30% from fat, and 20% from protein. In the nondiabetic group, SBP decreased by 12.7 mm Hg and DBP decreased by 7.9 mm Hg. At a later time, 19 type 2 diabetic patients (controlled with sulfonylureas) who were obese, hypertensive, and dyslipidemic underwent the same study protocol. In the diabetic group, SBP decreased by 15.7 mm Hg and DBP decreased by 7.6 mm Hg.
In contrast to the benefits attributed to fish oil supplementation in the treatment of hypertension and dyslipidemia in obese patients, no benefit could be observed in the prevention of pregnancy-induced hypertension. In six multicenter trials, women with high-risk pregnancies were randomly assigned to receive fish oil or olive oil in identical capsules from 20-33 weeks until delivery. Fish oil had no effect on the occurrence of pregnancy-induced hypertension.[16]
The Natural Medicines Comprehensive Database rates garlic as possibly effective when taken orally for hypertension. Fresh, intact garlic cells contain the amino acid alliin, which is considered to be the most active constituent. When the intact cells are broken, alliin is converted to allicin by the enzyme allinase. Garlic is thought to be effective in the treatment of hypertension by causing smooth muscle relaxation and vasodilation.[3]
A meta-analysis of trials evaluating the efficacy of garlic in the treatment of high blood pressure showed that garlic decreases SBP by 7.7 mm Hg and DBP by 5.0 mm Hg when compared with placebo. The optimum dosage of garlic for the treatment of hypertension has yet to be established and the use of garlic in the treatment of hypertension remains controversial.[17] Several studies have alluded to the fact that garlic is effective in the treatment of hyper-tension[18,19] whereas a placebo-controlled study reported that it has no effect on blood pressure.[20] These contradictions are probably due to variations in treatment protocols, duration of therapy, and formulation utilized; however, a recent study argued that the results warrant using standardized formulations of garlic.[21] Although garlic does fit the working definition of some evidence of benefit, the studies that allude to its efficacy include humans in small, uncontrolled studies. Before recommending garlic in the treatment of hypertension, more well developed studies showing positive outcomes on blood pressure are needed.
Vitamin C (ascorbic acid) is listed as possibly effective in the treatment of hypertension in the Natural Medicines Comprehensive Database.[3] The probable mechanism of action for vitamin C is that it functions as an antioxidant to enhance the synthesis or prevent the breakdown of nitric oxide.[14]
A study conducted by Duffy et al. [22] noted that vitamin C added to conventional medication lowered SBP effectively, but had no effect on DBP.
A randomized, placebo-controlled study conducted in 39 patients concluded that vitamin C is effective in the treatment of hypertension. Patients were randomized to receive either placebo or ascorbic acid in a one-time loading dose of 2 g, then 500 mg daily for 30 days. SBP decreased by approximately 13 mm Hg in the ascorbic acid group after 30 days. However, the reduction in DBP was not statistically significant. There was no change in the placebo group.[14]
According to the Natural Medicines Comprehensive Database, L-arginine receives a rating of likely ineffective in the treatment of hypertension.[3] It has however, been found to have potential in the treatment of hypertension in several small pilot studies, and thus fits the working definition of having some evidence of benefit.[23,24,25]
The amino acid L-arginine serves as the substrate for nitric oxide synthesis in the body. Nitric oxide is an endothelium-derived relaxing factor that is essential for regulating vascular tone. By supplementing L-arginine, more nitric oxide is produced. Nitric oxide then stimulates angiogenesis and inhibits endothelin-1 release, leukocyte adhesion, platelet aggregation, and superoxide generation.[26]
A single-blind, crossover trial, conducted in six healthy volunteers, measured the effect of argi-nine-rich diets on blood pressure. 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. The patients receiving L-arginine-rich diets (Groups 2 and 3) showed a significant reduction in blood pressure, with a decrease in SBP of 6.2 mm Hg more than the control group and a decrease in DBP of 5.0 mm Hg more than the control group.[24]
A pilot study conducted by Kelly et al.[27] showed that oral L-arginine had favorable effects on both SBP and DBP in hypertensive kidney transplant and hemodialysis patients. Six normotensive individuals and 10 kidney transplant patients received 9 g L-arginine daily for 9 days, then 18 g L-arginine daily for 9 additional days. Six hemodialysis patients and four peritoneal dialysis patients received the same dose for 14 days. Five kidney transplant patients received 30 mL canola oil daily in addition to L-arginine. Blood pressure, creatinine clearance, and serum creatinine level were measured at baseline, 9 days, and 18 days. Hemodialysis patients were noted to have a decrease in SBP of approximately 28.7 mm Hg.[27] DBP also decreased, but to a lesser extent. Renal function remained the same in all groups. Canola oil had no effect on blood pressure.
A larger, prospective, randomized, double blind trial conducted in 35 people with essential hypertension showed less promising results. Patients were randomized to receive either 6 g L-arginine or placebo. Acute changes in blood pressure were noted, but long-term effects warrant further investigation.[28]
A prospective, crossover trial was conducted in six patients with type 2 diabetes mellitus and mild hypertension. The patients received 3 g arginine hourly for 10 hours on either day 2 or day 3 of the study. Blood pressure was measured between 5 a.m. and 4 p.m. SBP and DBP decreased by 12 mm Hg and 6.2 mm Hg, respectively. The antihypertensive effect was temporary, however. Blood pressure dropped within 2 hours of initiating arginine and returned to the previous value within 1 hour of stopping arginine. According to this study, arginine may be useful for temporarily decreasing blood pressure in type 2 diabetics.[23]
As the latter two studies demonstrate, arginine is only effective in acute situations. For example, intravenous arginine has been used to lower pulmonary vascular resistance and cardiac output in infants with pulmonary hypertension.[27]
© 2004 Le Jacq Communications, Inc.
Cite this: The Natural Treatment of Hypertension - Medscape - May 01, 2004.
Comments