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NCCIH Clinical Digest

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High Cholesterol and Natural Products: What the Science Says

February 2019

Clinical Guidelines, Scientific Literature, Info for Patients: 
High Cholesterol and Natural Products

Cholesterol Label
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Natural Products

Stanols and Sterols

The use of foods containing added plant stanols or sterols is an option in conventional treatment for high cholesterol levels. Stanols and sterols are also available in dietary supplements. The evidence for the effectiveness of the supplements is less extensive than the evidence for foods containing stanols or sterols, but in general, studies show that stanol or sterol supplements, taken with meals, can reduce cholesterol levels. Some foods and dietary supplements that contain stanols or sterols are permitted to carry a health claim, approved by the Food and Drug Administration (FDA), saying that they may reduce the risk of heart disease when consumed in appropriate amounts.
What Does the Research Show?

  • A 2013 systematic review and meta-analysis of eight studies found that supplementation of plant sterols/stanols (in tablets and capsules) was associated with clinically significant reductions in low-density lipoprotein cholesterol levels. Further analysis showed no significant difference between the LDL-cholesterol−lowering action of plant sterols/stanols supplements compared with foods enriched with plant sterols/stanols.

Safety

  • Plant sterols/stanols are generally safe for most healthy people. Side effects include diarrhea or fat in the stool.
  • In people with sitosterolemia, high plant sterol levels have been associated with increased risk of premature atherosclerosis.

Soy

Some soy products can have a small cholesterol-lowering effect. A 2015 meta-analysis of 35 studies indicated that soy foods were more effective in lowering cholesterol than soy protein supplements and that isoflavones did not lower cholesterol. The effect of soy is much smaller than that of cholesterol-lowering drugs.

What Does the Research Show?

  • A 2018 randomized controlled trial of 32 healthy and non-obese postmenopausal women without hormone therapy examined the effect of isoflavone supplementation in addition to combined exercise training on plasma lipid levels, inflammatory markers, and oxidative stress. The study found that the supplementation of isoflavones when combined with exercise training was effective in reducing total cholesterol and increasing interleukin-8 levels.
  • A 2011 meta-analysis of 20 parallel-design studies and 23 crossover studies found that soy protein consumption (a median of 30 g/day) was associated with a significant improvement in lipoprotein risk factors for coronary heart disease.

Safety

  • Except for people with soy allergies, soy is believed to be safe when consumed in normal dietary amounts. However, the safety of long-term use of high doses of soy extracts has not been established.
  • The most common side effects of soy are digestive upsets, such as stomach pain and diarrhea.
  • Long-term use of soy isoflavone supplements might increase the risk of endometrial hyperplasia. Soy foods do not appear to increase the risk of endometrial hyperplasia.
  • Current evidence indicates that it’s safe for women who have had breast cancer or who are at risk for breast cancer to eat soy foods. However, it’s uncertain whether soy isoflavone supplements are safe for these women.

Flaxseed

Studies of flaxseed preparations to lower cholesterol levels suggest possible beneficial effects for some types of flaxseed supplements, including whole flaxseed and flaxseed lignans but not flaxseed oil. The effects were stronger for women (especially postmenopausal women) than men and for people with higher initial cholesterol levels.

What Does the Research Show?

  • Studies of flaxseed and flaxseed oil to lower cholesterol levels have had mixed results.
  • A 2015 randomized controlled trial of 110 participants with clinically significant cardiovascular disease found that milled flaxseed lowers total and low-density lipoprotein cholesterol in people with peripheral artery disease and may have additional low-density lipoprotein-cholesterol-lowering capabilities when used in conjunction with cholesterol-lowering medications.
  • A 2009 meta-analysis of 28 studies found that flaxseed lowered cholesterol only in people with relatively high initial cholesterol levels.

Safety

  • Raw or unripe flaxseeds may contain potentially toxic compounds.
  • Flaxseed and flaxseed oil supplements seem to be well tolerated in limited amounts. Few side effects have been reported.
  • Flaxseed and flaxseed oil should be avoided during pregnancy as they may have mild hormonal effects. There’s little reliable information on whether it’s safe to use flaxseed when nursing.
  • Flaxseed, like any fiber supplement, should be taken with plenty of water, as it could worsen constipation or, in rare cases, cause an intestinal blockage. Both flaxseed and flaxseed oil can cause diarrhea.

Garlic

A recent review of the research on garlic supplements concluded that they can lower cholesterol if taken for more than 2 months, but their effect is modest in comparison with the effects of cholesterol-lowering drugs.

What Does the Research Show?

  • A 2016 meta-analysis and review of 39 randomized controlled trials involving 2,300 participants treated for a minimum of 2 weeks found garlic to be effective in reducing total and low-density lipoprotein cholesterol by 10 percent if taken for more than 2 months by individuals with slightly elevated concentrations.
  • A 2009 systematic review and meta-analysis of 29 trials found that garlic may reduce total cholesterol to a modest extent, but had no significant effect on low-density lipoprotein or high-density lipoprotein cholesterol levels.

Safety

  • Garlic is probably safe for most people in the amounts usually eaten in foods.
  • Side effects include breath and body odor, heartburn, and upset stomach. These side effects can be more noticeable with raw garlic. Some people have allergic reactions to garlic.
  • Taking garlic may increase the risk of bleeding.
  • Garlic has been found to interfere with the effectiveness of some drugs, including saquinavir, a drug used to treat HIV infection.

Green Tea

There is some limited evidence that suggests green tea may have a modest cholesterol-lowering effect.

What Does the Research Show?

  • A 2018 meta-analysis of 21 randomized controlled trials involving 1,704 overweight or obese participants found that green tea significantly decreased plasma total cholesterol and low-density lipoprotein cholesterol levels. The study found that green tea had no effect on high-density lipoprotein cholesterol levels.
  • A 2014 systematic review and meta-analysis of 20 randomized controlled trials involving 1,536 participants found significant reductions in total cholesterol and low-density lipoprotein cholesterol.
  • A 2011 meta-analysis of 14 randomized controlled trials involving 1,136 participants found significant reductions in serum total cholesterol and low-density lipoprotein concentrations, but observed no effect on high-density lipoprotein cholesterol levels.

Safety

  • Green tea, when consumed as a beverage, is believed to be safe when used in moderate amounts.
  • Liver problems have been reported in a small number of people who took concentrated green tea extracts. Although the evidence that the green tea products caused the liver problems is not conclusive, experts suggest that concentrated green tea extracts be taken with food and that people discontinue use and consult a health care provider if they have a liver disorder or develop symptoms of liver trouble, such as abdominal pain, dark urine, or jaundice.
  • Except for decaffeinated green tea products, green tea and green tea extracts contain substantial amounts of caffeine.
  • Green tea has been shown to reduce blood levels of the drug nadolol, a beta-blocker used for high blood pressure and heart problems. It may also interact with other medicines.

Red Yeast Rice

The FDA has determined that red yeast rice that contains more than trace amounts of a substance called monacolin K is an unapproved new drug and cannot be sold legally as a dietary supplement. Monacolin K is chemically identical to the cholesterol-lowering drug lovastatin, and some red yeast rice contains substantial amounts of this substance. Red yeast rice that contains monacolin K may lower blood cholesterol levels, but it can also cause the same types of side effects and drug interactions as lovastatin.

Researchers have not reported results of any studies of red yeast rice products that contain little or no monacolin K, so whether these products have any effect on blood cholesterol is unknown.

What Does the Research Show?

  • In clinical trials of red yeast rice products that contained substantial amounts of monacolin K, the products lowered blood levels of total cholesterol and low-density lipoprotein (LDL) cholesterol. It is important to emphasize that all of these clinical trials used products that contained substantial amounts of monacolin K.
  • A 2010 analysis showed that some of the red yeast rice products on the market contain very little monacolin K. These products may have little or no effect on blood cholesterol levels.

Safety

  • Some red yeast rice products contain substantial amounts of monacolin K, which is chemically identical to the active ingredient in the cholesterol-lowering drug lovastatin. These products may lower blood cholesterol levels and can cause the same types of side effects and drug interactions as lovastatin.
  • Red yeast rice products may be contaminated with citrinin, a substance that may cause kidney damage.

Oats and Oat Bran

Long-term dietary intake of oats or oat bran can have a beneficial effect on blood cholesterol. Studies suggest that there is a beneficial effect of oat consumption on reducing the risk of cardio vascular disease (CVD) by lowering total and LDL-cholesterol.

What Does the Research Show?

  • A 2014 systematic review provided evidence that increased oat consumption has a beneficial effect on serum cholesterol concentration, particularly in individuals with hypercholesterolemia. This finding is consistent with a 1992 meta-analysis that concluded that about 3 g/d of soluble fiber from oat products can lower total cholesterol, with a greater reduction in individuals with higher initial cholesterol concentrations.

Safety

  • Oats are probably safe for most people in the amounts usually eaten.
  • Oats can cause intestinal gas and bloating.

References

  • Anderson JW, Bush HM. Soy protein effects on serum lipoproteins: a quality assessment and meta-analysis of randomized, controlled studies. J Am Coll Nutr. 2011;30(2):79-91.

  • 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. 145(4):749-757.

  • Giolo JS, Costa JG, da Cunha-Junior JP, et al. The effects of isoflavone supplementation plus combined exercise on lipid levels, and inflammatory and oxidative stress markers in postmenopausal women. Nutrients. 2018;10(4):424.

  • Gordon RY, Cooperman T, Obermeyer W, et al. Marked variability of monacolin levels in commercial red yeast rice products: buyer beware! Arch Intern Med. 2010;170(19):1722-1727.

  • Onakpoya I, Spencer E, Heneghan C, et al. 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.

  • Pan A, Yu D, Demark-Wahnefried W, et al. Meta-analysis of the effects of flaxseed interventions on blood lipids. Am J Clin Nutr. 2009;90(2):288-297.

  • Reinhart KM, Talati R, White CM, et al. The impact of garlic on lipid parameters: a systematic review and meta-analysis. Nutr Res Rev. 2009;22(1):39-48.

  • Ried K. Garlic lowers blood pressure in hypertensive individuals, regulated serum cholesterol, and stimulates immunity: an updated meta-analysis and review. J Nutr. 146(2):389S-396S.

  • Ripsin CM, Keenan JM, Jacobs DRJ, et al. Oat products and lipid lowering. A meta-analysis. JAMA. 1992;267:3317–3325.

  • Shaghaghi A, Abumweis SS, Jones PJ. Cholesterol-lowering efficacy of plant sterols/stanols provided in capsule and tablet formats: results of a systematic review and meta-analysis. J Acad Nutr Diet. 2013;113(11):1494-1503.

  • Thies F, Masson LF, Boffetta P, Kris-Etherton P. Oats and CVD risk markers: a systematic literature review. Br J Nutr. 2014;112 Suppl 2:S19-30.

  • Tokede OA, Onabanjo TA, Yansane A, et al. Soya products and serum lipids: a meta-analysis of randomised controlled trials. Br J Nutr. 2015;114(6):831-843.

  • Yuan F, Dong H, Fang K, et al. Effects of green tea on lipid metabolism in overweight or obese people: a meta-analysis of randomized controlled trials. Mol Ntr Food Res. 2018;62(1).

  • Zheng XX, Xu YL, Li SH, et al. Green tea intake lowers fasting serum total and LDL cholesterol in adults: a meta-analysis of 14 randomized controlled trials. 2011;94(2):601-610.

NCCIH Clinical Digest is a service of the National Center for Complementary and Integrative Health, NIH, DHHS. NCCIH Clinical Digest, a monthly e-newsletter, offers evidence-based information on complementary health approaches, including scientific literature searches, summaries of NCCIH-funded research, fact sheets for patients, and more.

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