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NCCIH Clinical Digest

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High Cholesterol and Natural Products: What the Science Says

February 2024

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 U.S. 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?

  • 2022 network meta-analysis found that plant sterols supplementation can cause a modest reduction of low-density lipoprotein cholesterol (LDL-C) and total cholesterol with bergamot and red yeast rice being seemingly most effective.
  • 2023 single-center, prospective, randomized, single-blind clinical trial involving 190 participants compared the efficacy of a low-dose statin with placebo and six common supplements, including plant sterols, in impacting lipid and inflammatory biomarkers. The study found that none of the dietary supplements demonstrated a significant decrease in LDL-C compared with placebo.
  • 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 LDL-C levels. Further analysis showed no significant difference between the LDL-C lowering action of plant sterol/stanol 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. However, results from studies indicate that soy foods have more of a beneficial effect on cholesterol than soy protein supplements or isoflavones. 

What Does the Research Show?

  • 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.
  • 2022 systematic review and meta-analysis of various effects of phytoestrogens on lipid profiles in postmenopausal women found that soy protein supplementation led to a significant decrease in total cholesterol levels, as well as a significant increase in high-density lipoprotein cholesterol (HDL-C) levels.
  • Further, a 2023 review concluded that any beneficial effect of soy proteins is likely derived from a healthy diet in which soy proteins replace animal proteins rather than from the intrinsic properties of soy supplementation alone.

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.
  • 2022 systematic review and meta-analysis found that different flaxseed products showed different effects in postmenopausal women. Whole flaxseed supplementation significantly reduced total cholesterol, while supplementation with lignans significantly reduced total cholesterol, LDL-C, and HDL-C. Flaxseed oil supplements had no lowering effect on lipids.
  • 2015 randomized controlled trial of 110 participants with clinically significant cardiovascular disease found that milled flaxseed lowers total cholesterol and LDL-C in people with peripheral artery disease and may have additional LDL-C lowering capabilities when used in conjunction with cholesterol-lowering medications.

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 breastfeeding.
  • 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?

  • 2023 review found evidence that demonstrates mostly consistent total cholesterol reduction with garlic supplementation; however, its effect on LDL-C and HDL-C is variable.
  • 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 cholesterol and LDL-C by 10 percent if taken for more than 2 months by individuals with slightly elevated concentrations.

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?

  • 2023 review found evidence from several meta-analyses indicating that green tea is associated with small (2–5 percent) but significant reductions in total cholesterol and LDL-C; however, the effects on HDL-C are inconsistent.
  • 2020 meta-analysis of 31 trials involving a total of 3,321 participants found that green tea supplementation may lower LDL-C and total cholesterol, but not HDL-C or triglycerides in both normal weight subjects and those who were overweight or had obesity. However, the authors of the study noted the need for additional well-designed studies that include more diverse populations and longer duration.
  • 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.

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 LDL-C. 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.

Red Clover

Studies on the effects of red clover on cholesterol and other lipids have had inconsistent results.

What Does the Research Show?

  • 2020 systematic review and meta-analysis of 10 studies involving a total of 910 perimenopausal and postmenopausal women found that red clover extract was associated with a significant reduction in total cholesterol; however, its effects on HDL-C and LDL-C were not significant.
  • 2022 systematic review and meta-analysis found a significant reduction in total cholesterol levels after the use of red clover supplements and a significant increase in HDL-C levels.

Safety

  • Red clover extracts have been used in clinical studies for as long as 3 years with apparent safety.
  • Women should not take red clover supplements during pregnancy or while breastfeeding.

Bergamot

There is some limited evidence suggesting that bergamot and bergamot-derived polyphenols may have lipid-lowering properties.

What Does the Research Show?

  • 2022 systematic review and meta-analysis suggested that bergamot supplementation significantly decreased serum levels of total cholesterol, triglycerides, and LDL-C and increased HDL-C. The results, however, are uncertain, due to the small number of studies in the analyses and low level of evidence.

Safety

  • Oral use of bergamot extract at an appropriate dose appears safe over the short term.

References

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.

The National Center for Complementary and Integrative Health is dedicated to exploring complementary health products and practices in the context of rigorous science, training complementary health researchers, and disseminating authoritative information to the public and professionals. For additional information, call NCCIH’s Clearinghouse toll-free at 1-888-644-6226, or visit the NCCIH website at nccih.nih.gov. NCCIH is 1 of 27 institutes and centers at the National Institutes of Health, the Federal focal point for medical research in the United States.

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