Focus on Alternative and Complementary Therapies
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Focus Alternat Complement Ther©2005 Pharmaceutical Press
Focus Altern Complement Ther 2002; 7: 233–6
Coronary heart disease is a major cause of morbidity and mortality, accounting for approximately one-fifth of deaths in the UK in 2000.1 Hypercholesterolaemia is an important risk factor for coronary heart disease, and reductions in blood cholesterol levels have been associated with reductions in the risk of coronary events in large trials of coronary heart disease.2,3 Hypercholesterolaemia is a condition necessitating long-term treatment and for which patients are often required to modify lifestyle and dietary factors before pharmacological interventions are introduced. Many of these lifestyle and dietary approaches are common in, but not specific to, complementary medicine and will therefore not be discussed in this article. A large number of herbal medicinal products and food supplements are promoted for hypercholesterolaemia, including some of the top-selling products. There is also some evidence for yoga and relaxation techniques but no evidence from rigorous clinical trials for any other complementary therapy.
A systematic literature search in the databases Medline, Amed, Cinahl, CISCOM, Embase and the Cochrane Library revealed randomised clinical trials of the following 11 herbal medicinal products: guggul (Commiphora mukul), fenugreek (Trigonella foenum-graecum), garlic (Allium sativum), red yeast rice, artichoke (Cynara scolymus), Terminalia arjuna, holy basil (Ocimum sanctum), milk thistle (Silybum marianum), Solanum melongena, Achillea wilhelmsii and Panax ginseng.
There have been a large number of randomised clinical trials and several meta-analyses of the effect of garlic on elevated serum cholesterol levels.4–6 The most recent meta-analysis included 13 double-blind, placebo-controlled randomised clinical trials of 781 patients.6 On average, there was a significant reduction in total serum cholesterol of 0.41 mmol/l, or 4–6% of initial levels; however, the six most rigorous, diet-controlled trials showed only a non-significant trend. The authors concluded that while garlic was superior to placebo, the effect size was small and of debatable clinical significance.
Extracts from the resin of the mukul myrrh tree (C. mukul) have been used for centuries in Ayurvedic medicine and are widely used in the treatment of hypercholesterolaemia in India. Five randomised clinical trials of guggul, involving 305 patients with varying diagnoses, conducted in India, suggest reductions in total serum cholesterol ranging from 22% to 27% compared with baseline levels.7–11 The first randomised clinical trial conducted in a Western population was presented at the International Scientific Conference on Complementary, Alternative and Integrative Medical Research in Boston in April 2002. This placebo-controlled trial in 103 healthy subjects with mean baseline low-density lipoprotein (LDL) cholesterol approaching hypercholesterolaemic levels showed no significant reductions in LDL or total cholesterol levels after 8 weeks of treatment. Further well-designed studies are needed to further elucidate the true effects of guggul in hypercholesterolaemia.
Fenugreek is native to South-eastern and Western Asia. The seeds are commonly used for culinary purposes throughout India. Six randomised clinical trials, all but one of which were conducted in India, were identified, involving a total of 155 patients.12–16 Although the methodological quality of the trials was considered to be generally poor in four of the trials, statistically significant reductions in total serum cholesterol of between 15% and 33% compared with baseline were demonstrated.
Red yeast rice is produced by solid-state fermentation of washed and cooked rice using the fungus Monascus purpureus. It has been used in Asia as a food preservative and colorant and for its medicinal properties since the Tang Dynasty (800 AD) and is available in capsules, which contain a pulverised powder of fermented rice and yeast. Four randomised clinical trials of the lipid-lowering effects conducted in patients (n = 695) with hyperlipidaemia were identified.17–20 In all studies, statistically significant reductions (13–23%) in total serum cholesterol compared with placebo/control and/or baseline were seen.
The chloretic effect of the leaf extract of C. scolymus has been widely studied; however, only two randomised clinical trials of its hypocholesterolaemic effects are available.21,22 The larger and more rigorous of the two studies involved 143 patients with baseline total serum cholesterol levels of 7.7 mmol/l; following 6 weeks’ treatment with either artichoke leaf extract or placebo, reductions in total cholesterol were 18.5% in the artichoke group and 8.6% in the placebo group (P = 0.0001).22
One randomised clinical trial was identified for each of the remaining six herbs. No change in lipid levels was seen in trials of S. melongena, P. ginseng and S. marianum.23–25 Modest reductions in total serum cholesterol (10% and 6.5%, respectively) compared with baseline were seen in trials of Terminalia arjuna (n = 105 patients with coronary artery disease)26 and O. sanctum (n = 60 patients with hyperlipidaemia),27 while in the trial of A. wilhelmsii (n = 60 patients with hyperlipidaemia) a reduction in total serum cholesterol of 39% was seen compared with baseline.28 The methodological quality of all these studies was considered to be poor.
Several food supplements are promoted for treatment of hypercholesterolaemia, including chitosan and coenzyme Q10, for which the evidence from randomised clinical trials is limited, and dietary fibre.
Despite promising results in animal studies, in the absence of simultaneous dietary intervention, chitosan supplementation has produced no statistically significant changes in total serum cholesterol levels in three randomised clinical trials (n = 175) of patients with hypercholesterolaemia.29–31 One trial of poor methodological quality, in which patients were restricted to 1000 kcal/day in addition to receiving chitosan treatment, showed reductions of 23.9% and 10.4% following treatment with chitosan and placebo, respectively.32
Coenzyme Q10 is synthesised in large quantities for the food supplement market and promoted for a wide range of indications from heart failure to a general tonic. It is present in most cells of the body, with highest concentrations found in the heart, liver, kidneys and pancreas. In a randomised, double-blind, placebo-controlled trial of 47 patients with acute coronary disease, 28 days’ treatment with coenzyme Q10 (120 mg/day) resulted in increases in high-density lipoprotein (HDL) cholesterol (7.5%; P < 0.05) but no changes in total cholesterol levels.33
Several water-soluble dietary fibres, e.g. guar gum, psyllium and oat fibres, are used either alone or in combination in the treatment of hypercholesterolaemia. Clinical trials have shown varying effects on blood lipids ranging from no change to decreases of 20% in total serum cholesterol.34,35 The differences in results may be attributable to differences in methodological quality, sample sizes, type of patient included and concurrent factors such as diet. The US Food and Drug Administration (FDA) has approved health claims for two dietary fibres, β-glucan (0.75 g/serving), found in oat products, and psyllium (1.78 g/serving), obtained from Plantago ovata, on the assumption that four servings per day would reduce cardiovascular disease risk. A randomised clinical trial of 68 hyperlipidaemic patients designed to assess the effectiveness of this regime compared a high-fibre diet that included four servings per day of foods containing β-glucan or psyllium with a control low-fat, low cholesterol diet for 1 month. Compared with the control diet, the high-fibre diet reduced total cholesterol by 2.1% (P = 0.003).36
Several randomised clinical trials of yoga and/or relaxation techniques for serum cholesterol reduction have been reported. The most recent trial was performed in India and involved 42 men with angiographically proven coronary artery disease, randomised to receive either management with risk factor control and diet (control group) or yoga, risk factor control, diet and moderate aerobic exercise (yoga group) for 12 months. Compared with the control group, a greater reduction in total serum cholesterol was seen in the group receiving the yoga programme. Reductions in the number of anginal episodes and revascularisation procedures required were also noted.37
There is evidence from randomised clinical trials for a wide range of herbal medicinal products and food supplements which may be of use in serum lipid reduction as adjuncts to the lifestyle and dietary changes often required of patients with hypercholesterolaemia. Compelling evidence exists for garlic and dietary fibres, but the effect sizes are modest and considerably less than that of synthetic lipid-lowering drugs. Yoga may also be a useful addition to management, although further research is needed. While several of the other products, such as fenugreek, guggul and red yeast rice, have demonstrated useful effects in some trials, the methodological quality of these on the whole is poor, and more data are required to fully elucidate their potential value.
