The most effective approaches to lowering cholesterol are lifestyle modifications to reduce weight, a heart-healthy diet and exercise, and the use of lipid-lowering medications.1
Herbal remedies and dietary supplements have been used to treat high cholesterol and some have been shown to be moderately effective in small trials.2 But they are not regulated with the same standards of effectiveness and safety as pharmacological treatments and, as such, should be used with caution.
While prescription and over-the-counter medication manufacturers must provide high-quality evidence to the Food and Drug Administration (FDA) that their products are safe and effective before they can be sold, the FDA does not review herbal remedies or dietary supplements for safety and effectiveness before they are marketed.2,3 For this reason, high-quality randomized controlled trials often do not exist for dietary supplements. In addition, although the FDA does provide guidance for good marketing practices to help ensure their identity, purity, strength, and composition, some supplements have been found to contain hidden prescription drugs or other compounds because the FDA has no regulatory oversight for the manufacturing process. There is no guarantee that the actual contents of any given bottle of herbs or supplements contain what it claims to contain. In addition, some supplements are known to interfere with the pharmacokinetics of other medications.
When evaluating the use of complementary and alternative lipid-lowering treatment, it is important to consider the quality and generalizability of the evidence supporting their efficacy, the lack of quality control in their production, limited information about side effects, their potential for harm, and the possible interactions between the alternative treatment and other medicines being taken.
Plant Stanols and Plant Sterols
Some foods and dietary supplements that contain added plant stanols or sterols are permitted to carry a health claim, approved by the FDA, saying that they may reduce the risk of heart disease when consumed in appropriate amounts.2,4 Plant sterols and plant stanols that are present in some foods reduce the intestinal absorption of cholesterol in much the same way as the lipid-lowering drug, ezetimibe.5 The main food sources of plant sterols are vegetable oils, spreads, margarines, bread, cereals, and vegetables. Wheat and rye cereals are the richest source of plant stanols. Because of the dramatic efficacy of ezetimibe in lowering low-density lipoprotein cholesterol (LDL-C), biologists and nutritionists have studied the effectiveness of plant sterols/stanols in lowering cholesterol.6–8 Muso-Veloso et al. conducted a meta-analysis of 130 randomized, placebo-controlled trials (study sample sizes varied from 7 to 201) and estimated that the consumption of foods with plant sterols/stanols (at the level of 2 mg/day) lowered LDL-C by 8.2% and 9.3%, respectively.7 Their data also suggest that higher levels of plant sterols do not further lower cholesterol levels, while higher doses of stanols produced LDL-C reductions as high as 16.4%. Gylling et al. compared the lipid-lowering effect of 8.8 g/day of plant stanol esters (as a spread or enriched drink) taken for 10 weeks with the effects of placebo.8 LDL-C levels were reduced by 17.3% in the people taking stanol esters. Similar results were found in a meta-analysis of 41 trials conducted by Katan et al.6 Sample sizes in individual studies have not been adequate to confirm the safety of adding sterols or stanols to the diet as a therapeutic measure. It is not yet known if increased levels of stanols would lower LDL-C enough to impact cardiovascular risk.
Although there are no randomized controlled trials that have demonstrated plant sterols or stanols reduce the risk of cardiovascular disease (CVD), the European Atherosclerosis Society has concluded that foods containing them may be recommended as lipid-lowering therapy for individuals with elevated cholesterol but low to intermediate cardiovascular risk who do not yet qualify for pharmacotherapy, or in addition to pharmacotherapy in individuals who fail to achieve LDL-C targets on medication.5
Soy Products
Soy protein can be obtained in the diet as soybeans or soy products or as a food supplement.9 Some studies have demonstrated a small lipid-lowering effect from soy.2 Possible mechanisms for the lipid-lowering effect of soy have been proposed including decreased cholesterol synthesis, increased bile acid synthesis, increased apolipoprotein B or E receptor activity, and decreased hepatic lipoprotein secretion.10 It is important to understand that some of the benefits of soy consumption in the diet may be attributable to the benefit of reduced consumption of saturated fats when soy is used as an alternative to meat proteins, and some of the benefits can be attributed to intrinsic components of the soy itself. It is estimated that intrinsic factors can lower LDL-C by 4.3%, and the displacement of saturated fats further reduces LDL-C by 3.6% to 6.0%.11 Observational studies have found a trend toward a decreased risk of CVD associated with higher self-reported intake of dietary soy protein in both men (n=3,885)12 and women (n=75,000).13 It is not clear, however, from these analyses how much of this effect can be directly attributed to intrinsic components of soy.
Red Yeast Rice
Most forms of red yeast rice on the market contain various amounts of monacolin K, a substance that is chemically identical to the statin drug lovastatin, which explains its lipid-lowering potential.9 However, like lovastatin, it also carries the potential for side effects. For this reason, the FDA has determined it cannot be legally sold in the US as a dietary supplement.2 Any over-the-counter supplements sold in the US containing red yeast rice cannot contain lovastatin, thus do not have lipid-lowering effects. In a small (n= 62) randomized placebo-controlled trial, 1800 mg of red yeast rice that did contain monacolin K twice daily for 24 weeks reduced levels of LDL-C by 20% to 30% compared to low-dose statins and triglyceride levels by 10% to 20%, without increasing creatine phosphokinase levels (a measure of muscle damage).14 However, research has not shown that it improves muscle pain.14,15 Halbert et al. compared treatment discontinuation rates between 22 patients taking pravastatin 20 mg twice daily with 21 patients taking red yeast rice 2400 mg twice daily for 24 weeks.15 Those taking red yeast rice had previously discontinued statins due to intolerance. At the conclusion of the study, the groups did not differ significantly with respect to self-reported myalgia, treatment withdrawal rates, pain severity, or muscle strength.
Green Tea
There is some evidence that green tea, and less so black tea, consumption may lower cholesterol levels.2 Black tea differs from green tea because its leaves have been oxidized. Catechins are a class of flavanols that are found in tea and have been postulated to be responsible for its cholesterol-lowering properties.9 Catechins are powerful antioxidants that prevent the oxidation of LDL-C in humans. Catechins may also have an inhibitory effect on cholesterol synthesis and inhibit intestinal lipid absorption.
Several meta-analyses have been conducted examining the effects of tea consumption on lipid parameters and have consistently shown an LDL-C-lowering effect of green tea or green tea extracts.16–19 A Cochrane Systematic Review and meta-analysis (n=821 from 11 randomized controlled trials) was conducted to examine the effects of tea consumption on CVD.20 Seven studies examined the effects of green tea and four examined the effects of black tea. Unfortunately, none of the studies that met the analysis criteria reported cardiovascular events. Although dosages varied among the different studies, both black and green tea showed statistically significant reductions in LDL-C. Black tea consumption resulted in a mean difference (MD) of -16.63 mg/dL (95% confidence interval [CI] [-21.66 – -11.99]) compared to controls. Green tea resulted in a MD of -24.75 mg/dL (95% CI [-29.78 – -20.10]). The authors conclude that the small number of trials contributing to the analysis limits its interpretation and that further study is needed to assess the lipid-lowering effects of green tea on cardiovascular outcomes.
Observational studies have attempted to quantify the benefit of green tea consumption on cardiovascular risk.21 Tang et al. conducted a dose-response meta-analysis of 18 prospective cohort studies and using random effects models calculated pooled relative risks for CVD mortality. The dose-response analysis indicated that each one cup per day increment of green tea consumption was associated with a 5% lower risk of CVD mortality and with a 4% lower risk of all-cause mortality. Green tea consumption was significantly inversely associated with CVD and all-cause mortality. The explanation for the reduction in risk cannot be provided in an observational analysis. It is quite possible that frequent green tea drinkers possibly lead overall healthier lifestyles than non-tea drinkers, which might have contributed to the observed effect.
Garlic
Garlic supplements are available as garlic powder, aged garlic extract, garlic oil, and allicin, a product of crushed garlic. It has demonstrated cholesterol-lowering effects, but the mechanism is not known.9 Several meta-analyses have found that garlic supplement intake is associated with decreased levels of total cholesterol (TC),22–26 LDL-C,22,26 triglycerides,22,23 and increased high-density lipoprotein cholesterol (HDL-C) levels.22,23 The effect seems to be more robust in studies of longer duration and in patients with high lipid levels at baseline.22–24,26 A meta-analysis of 39 placebo-controlled trials (ranging in size from 19 to 221 participants) found garlic to be effective in reducing TC by 17 ± 6 mg/dL and LDL-C by 9 ± 6 mg/dL in individuals with elevated TC levels (>200 mg/dL), provided garlic is used for longer than two months.22 No studies yet provide evidence that the modest cholesterol-lowering effects have an impact on cardiovascular risk.
Flaxseed
Flaxseed contains three components with the potential to positively impact the cardiovascular system: a fatty acid, an antioxidant acid, and fiber.27 In small studies, flaxseed preparations have been shown to lower cholesterol at least in the short term, particularly in postmenopausal women and people with high initial levels of cholesterol.2,28 Edel et al. conducted a randomized double-blind placebo-controlled trial of 110 patients with peripheral artery disease.29 A total of 58 patients received a diet supplemented with 30 g of milled flaxseed and 52 patients received 30 g of whole wheat placebo for 12 months. Lipids were measured at baseline and one month, six months, and 12 months. The LDL-C was reduced by 15% in the flaxseed arm at one month (p=0.05 compared to placebo), but the reduction did not remain statistically significant at 6 months or 12 months. When cholesterol-lowering medications (statins) were added to a subgroup of statin-naïve patients in both arms, the LDL-C concentrations in the flaxseed + statin group were lowered by 8.5% ± 3.0% compared with baseline after 12 months; compared to LDL-C concentrations in the placebo + statin arm which increased by 3.0% ± 4.4% (p=0.03). The same study found flaxseed to have significant anti-hypertensive effects compared to placebo, but the actual number of cardiovascular events in each arm of the study was too low to achieve statistical significance.29,30
Of note, Wong et al. studied the effects of a diet enhanced with flaxseed compared to placebo in a population of 32 children aged 8 to 18 years with elevated LDL-C. (135 mg/dL to 193 mg/dL).31 Those taking flaxseed had no significant improvements in TC or LDL-C, but they did experience significant increases in triglycerides and reductions in HDL-C.
References
- Grundy S, Stone N, Beam C, Birtcher KK, Harm PD. 2018 AHA/ACC/AACVPR/AAPA/ ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol. J Am Coll Cardiol 2019; 73 (24): e285-e350.
- National Institutes of Health: National Center for Complementary and Integrative Health. Cholesterol Management at a Glance. https://nccih.nih.gov/. Accessed December 7, 2019.
- US Food and Drug Administration: Dietary supplements. https://www.fda.gov/food/dietarysupplements/. Accessed December 7, 2019.
- Food and Drug Administration (FDA). Authorized Health Claims That Meet the Significant Scientific Agreement (SSA) Standard. https://www.fda.gov/food/food-labeling-nutrition/authorized-health-claims-meet-significant-scientific-agreement-ssa-standard. Accessed December 7, 2019.
- Gylling H, Plat J, Turley S, et al. Plant sterols and plant stanols in the management of dyslipidaemia and prevention of cardiovascular disease. Atherosclerosis 2014; 232 (2): 346-360.
- Katan MB, Grundy SM, Jones P, Law M, Miettinen T, Paoletti R. Efficacy and safety of plant stanols and sterols in the management of blood cholesterol levels. Mayo Clin Proc 2003; 78 (8): 965-978.
- Musa-veloso K, Poon TH, Elliot JA, Chung C. A comparison of the LDL-cholesterol lowering efficacy of plant stanols and plant sterols over a continuous dose range : Results of a meta-analysis of. Prostaglandins Leukot Essent Fat Acids 2011; 85 (1): 9-28.
- Gylling H, Hallikainen M et al. Effect of very high plant stanol ester intake on serum lipids, carotenoids, and fat-soluble vitamins. Clin Nutr 2010; 29 (1): 112-118.
- Hunter PM, Hegele RA. Functional foods and dietary supplements for the management of dyslipidaemia. Nat Rev Endocrinol 2017; 13 (5): 278-288.
- Cicero AFG, Ferroni A, Ertek S. Tolerability and safety of commonly used dietary supplements and nutraceuticals with lipid-lowering effects. Exp Opin Drug Saf 2012; 11 (5): 753-766.
- Jenkins DJA, Mirrahimi A, Srichaikul K, et al. Soy protein reduces serum cholesterol by both intrinsic and food displacement mechanisms. J Nutr 2010; 140 (12): 2302S-2311S.
- Yu D, Zhang X, Xiang Y-B, et al. Association of soy food intake with risk and biomarkers of coronary heart disease in Chinese men. Int J Cardiol 2014; 172 (2): e285-7.
- Zhang X, Shu XO, Gao Y-T, et al. Soy food consumption is associated with lower risk of coronary heart disease in Chinese women. J Nutr 2003; 133 (9): 2874-2878.
- Becker DJ, Gordon RY, Halbert SC, French B, Morris PB, Rader DJ. Red yeast rice for dyslipidemia in statin-intolerant patients: a randomized trial. Ann Intern Med 2009; 150 (12): 830-839, W147-9.
- Halbert SC, French B, Gordon RY, et al. Tolerability of red yeast rice (2,400 mg twice daily) versus pravastatin (20 mg twice daily) in patients with previous statin intolerance. Am J Cardiol 2010; 105 (2): 198-204.
- Onakpoya I, Spencer E, Heneghan C, Thompson M. The effect of green tea on blood pressure and lipid profile: a systematic review and meta-analysis of randomized clinical trials. Nutr Metab Cardiovasc Dis 2014; 24 (8): 823-836.
- Kim A, Chiu A, Barone MK, et al. Green tea catechins decrease total and low-density lipoprotein cholesterol: a systematic review and meta-analysis. J Am Diet Assoc 2011; 111 (11): 1720-1729.
- Hooper L, Kroon PA, Rimm EB, et al. Flavonoids, flavonoid-rich foods, and cardiovascular risk: a meta-analysis of randomized controlled trials. Am J Clin Nutr 2008; 88 (1): 38-50.
- Zheng X-X, Xu Y-L, Li S-H, Liu X-X, Hui R, Huang X-H. Green tea intake lowers fasting serum total and LDL cholesterol in adults: a meta-analysis of 14 randomized controlled trials. Am J Clin Nutr 2011; 94 (2): 601-610.
- Hartley L, Flowers N, Holmes J, et al. Green and black tea for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev 2013;(6): CD009934.
- Tang J, Zheng J-S, Fang L, Jin Y, Cai W, Li D. Tea consumption and mortality of all cancers, CVD and all causes: a meta-analysis of eighteen prospective cohort studies. Br J Nutr 2015; 114 (5): 673-683.
- Ried K, Toben C, Fakler P. Effect of garlic on serum lipids: an updated meta-analysis. Nutr Rev 2013; 71 (5): 282-299.
- Zeng T, Guo F-F, Zhang C-L, Song F-Y, Zhao X-L, Xie K-Q. A meta-analysis of randomized, double-blind, placebo-controlled trials for the effects of garlic on serum lipid profiles. J Sci Food Agric 2012; 92 (9): 1892-1902.
- Reinhart KM, Talati R, White CM, Coleman CI. The impact of garlic on lipid parameters: a systematic review and meta-analysis. Nutr Res Rev 2009; 22 (1): 39-48.
- Stevinson C, Pittler MH, Ernst E. Garlic for treating hypercholesterolemia. A meta-analysis of randomized clinical trials. Ann Intern Med 2000; 133 (6): 420-429.
- Kwak JS, Kim JY, Paek JE, et al. Garlic powder intake and cardiovascular risk factors: a meta-analysis of randomized controlled clinical trials. Nutr Res Pr 2014; 8 (6): 644-654.
- Parikh M, Netticadan T, Pierce GN. Flaxseed: its bioactive components and their cardiovascular benefits. Am J Physiol Hear Circ Physiol 2018; 314 (2): H146-H159.
- Patade A, Devareddy L, Lucas EA, Korlagunta K, Daggy BP, Arjmandi BH. Flaxseed reduces total and LDL cholesterol concentrations in Native American postmenopausal women. J Womens Heal 2008; 17 (3): 355-366.
- Edel AL, Rodriguez-Leyva D, Maddaford TG, et al. Dietary flaxseed independently lowers circulating cholesterol and lowers it beyond the effects of cholesterol-lowering medications alone in patients with peripheral artery disease. J Nutr 2015; 145 (4): 749-757.
- Parikh M, Pierce GN. Dietary flaxseed : what we know and don ’ t know about its effects on cardiovascular disease. Can J Physiol Pharmacol 2019; 81 (December 2018): 75-81.
- Wong H, Chahal N, Manlhiot C. Flaxseed in pediatric hyperlipidemi: a placebo-controlled, blinded, randomized clinical trial of dietary flaxseed supplementation for children and adolescents with hypercholesterolemia. JAMA Peditr 2013; 167 (8): 708-713.