November 2017 Issue

Integrative Nutrition: Holistic Cholesterol Management
By Carrie Dennett, MPH, RDN, CD
Today's Dietitian
Vol. 19, No. 11, P. 16

Nutraceuticals can boost and complement diet and lifestyle interventions.

"I don't want to go on a statin" is a common refrain among patients seeking nutrition counseling for rising cholesterol levels. While a smart diet and physical activity plan can help manage hyperlipidemia, it isn't always enough to budge the numbers to desired levels. One issue is that dietary components with potential cholesterol-lowering activity may be present in relatively small amounts in food. That's where nutraceuticals can be a valuable part of an integrative nutrition strategy. Nutraceuticals are fortified foods or dietary supplements that have benefits in addition to their nutritional value.

The Science
High blood cholesterol is one of the top 10 conditions for which people use complementary or integrative health practices such as dietary supplements,1 but Robin Foroutan, MS, RDN, HHC, a New York-based integrative dietitian and national spokesperson for the Academy of Nutrition and Dietetics, says it's important to remember that people have high cholesterol for different reasons.

"Some people are overproducing cholesterol, others are overabsorbing cholesterol—and some people are doing both," she says. "So when you're putting together your plan, it can be helpful to address both of these aspects. But the most important thing to keep in mind is to get chronic inflammation under control."2,3 To that end, the following are some nutraceuticals to consider.

Artichoke Leaf Extract
Artichoke (Cynara scolymus) leaf extract is marketed as an aid to lowering total and LDL cholesterol.4 It also may help raise HDL cholesterol and reduce inflammation thanks to its polyphenol content.5-7 It appears to increase cholesterol excretion while inhibiting cholesterol production in the liver.7 A 2013 Cochrane review found that artichoke leaf extract improved cholesterol levels modestly but the results weren't compelling enough to recommend it as a treatment option.8 Side effects are minimal, but the extract may cause an allergic reaction, especially in those with ragweed allergies.4

A bitter, intensely yellow substance from the bark, roots, and stems of plants in the genus Berberis, including the barberry plant, berberine has been shown to reduce total and LDL cholesterol and triglycerides, possibly reducing LDL by 20%.9 Berberine improves LDL uptake in the liver, similar to statins, and it may have a synergistic effect with statins, an idea that has been confirmed in cell culture, as well as in animal and a few human studies.10,11 The FDA hasn't released specific claims on berberine's safety and efficacy, and most clinical trials, which used 0.5 to 1.5 g/day, have been done only in Asian populations.9

Bergamot extract supplements have been shown in a clinical trial to significantly lower total cholesterol, triglycerides, and LDL, especially small, dense LDL particles.12 Bergamot may inhibit cholesterol production and improve LDL uptake from the bloodstream.12,13 It also may raise HDL.6 These effects likely are due to bergamot's high flavonoid content.6,12

A 2016 Cochrane review found that all types of dietary fiber may reduce total and LDL cholesterol,14 but notable sources are barley and oats, which are rich in beta-glucan and blond psyllium fiber.4,15 Remember that increasing fiber too quickly may cause digestive distress.

Flaxseed may lower total and LDL cholesterol even in patients who already are taking statins,16 although studies of various flaxseed preparations have shown mixed results. A 2009 review of the scientific research on flaxseed for lowering cholesterol found modest improvements in cholesterol, seen more often in postmenopausal women and in people with high initial cholesterol levels.17 A 2014 study found that 30 g/day of roasted flaxseed powder reduced total and LDL cholesterol as well as triglycerides.18 Flaxseed may interact with some blood-thinning medications, such as aspirin, clopidogrel, and warfarin.4

Allicin, the major bioactive compound in garlic, has anti-inflammatory effects and appears to inhibit cholesterol synthesis and intestinal absorption.10,19 In vitro and animal studies have supported garlic's cholesterol-lowering effects, but human studies have shown conflicting results.20 Overall, aged garlic extract and garlic powder supplements appear to have modest total cholesterol-lowering effects similar to those of diet modification alone.20 However, a study funded by the National Center for Complementary and Integrative Health on the safety and efficacy of three garlic preparations (fresh garlic, dried powdered garlic tablets, and aged garlic extract tablets) for lowering blood cholesterol levels found no effect.21 Although garlic supplements appear to be safe for most adults, they can thin the blood.1

Plant Sterols and Stanols
Phytosterols and their derivatives, stanols, are structurally similar to cholesterol and reduce absorption of dietary cholesterol in the intestines by competing with it.9 This leads to improved liver uptake of LDL from the bloodstream.10 Sterols are found in small amounts in fruits, vegetables, nuts, seeds, cereals, legumes, and vegetable oils,9 as well as oral supplements and certain foods including margarine, orange juice, and yogurt.4 The average dietary consumption is about 300 mg/day, although vegetarians may get double that.9 "If increasing dietary fiber or natural sources of plant sterols is not easy, 2 g of plant sterols in supplemental form has been shown to be an effective option as a strategy for reducing high LDL cholesterol," says Mary Purdy, MS, RDN, chair of Dietitians in Integrative and Functional Medicine, a dietetic practice group of the Academy of Nutrition and Dietetics.22

Red Yeast Rice
A Chinese herbal supplement produced by fermenting rice with the yeast Monascus purpureus, red yeast rice contains substances called monacolins. One of these, monacolin K, is virtually identical to the cholesterol-lowering drug lovastatin,9 with both inhibiting cholesterol synthesis in the liver.23 The FDA doesn't allow red yeast rice products with more than trace amounts of monacolin K to be sold as dietary supplements,24 because monacolin K can have the same side effects and drug interactions as lovastatin.25

Formulations with monacolin K have been shown to be effective in lowering total and LDL cholesterol,26-28 but other monacolins may lower cholesterol too.24 Red yeast rice also contains phytosterols, which inhibit cholesterol absorption, and fiber and niacin, which have their own cholesterol-lowering effects.9 Because there's no way to know how much monacolin K is in a particular red yeast rice product—despite FDA regulations, it may show up in products in the United States—many experts believe more regulation is needed before recommending any formulation.29

Whole soyfoods such as edamame, soymilk, tofu, and tempeh may inhibit cholesterol production and increase uptake from the bloodstream, reducing LDL by 4% to 13%.9,11,30 This is due to a variety of compounds in whole soy, including proteins, isoflavones, phytosterols, and beta-glucan.9,30,31 Soy also has anti-inflammatory effects.31 The FDA allows the health claim that diets low in saturated fat and cholesterol and include soy protein may reduce heart disease risk. The daily dietary intake of soy protein associated with reduced heart disease risk is 25 g or more.32

Integrating Nutraceuticals Into Practice
Who might benefit most from nutraceuticals? For patients who have low to moderate cardiovascular risk and need to reduce LDL only slightly, using nutraceuticals in addition to dietary therapy might make it easier to reach and sustain target goals.10,11 They also may present an alternative for patients who can't take statins due to side effects.10,11 Occupying the middle ground is combination therapy: Using nutraceuticals such as berberine or phytosterols that have a mode of action different from statins may increase the statin's effectiveness, possibly allowing patients to reduce their dose.10,13

When it comes to dietary interventions, it's important to focus on more than just dietary fat. "Fats usually get most of the attention when it comes to serum cholesterol and for good reason—obviously, avoiding trans fats completely and limiting saturated fats are important," Foroutan says. "But research also has linked heart disease and high cholesterol with diets high in added sugars and processed carbohydrates."

Smart strategies include helping patients emphasize healthful sources of polyunsaturated and monounsaturated fats, including nuts and avocados, which have been shown to help reduce LDL. Purdy says the polyphenols in olive oil have been shown to specifically reduce levels of oxidized LDL, a key contributor to arterial plaque.33 Helping patients incorporate more high-fiber foods such as oatmeal, oat bran, beans and lentils, fruits, and vegetables may reduce reliance on commercial baked goods and snack foods. This has the dual benefit of reducing unhealthful fats and refined carbohydrates, two major contributors to chronic inflammation.

"As with other chronic conditions, addressing inflammation is critical," Foroutan says. "Best strategies include supplementing with omega-3 fatty acids, following a phytonutrient-rich anti-inflammatory diet, exercising regularly to raise HDL levels, and balancing blood sugar. All these things work together to support cardiovascular health."

— Carrie Dennett, MPH, RDN, CD, is the nutrition columnist for The Seattle Times and speaks frequently on nutrition-related topics. She also provides nutrition counseling via the Menu for Change program in Seattle.

1. 5 tips: what you should know about high blood cholesterol. National Institutes of Health, National Center for Complementary and Integrative Health website. Updated September 24, 2015. Accessed August 22, 2017.

2. Ridker PM, Everett BM, Thuren T, et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med. 2017;377(12):1119-1131.

3. Libby P, Ridker PM, Hansson GK; Leducq Transatlantic Network on Atherothrombosis. Inflammation in atherosclerosis: from pathophysiology to practice. J Am Coll Cardiol. 2009;54(23):2129-2138.

4. Cholesterol-lowering supplements may be helpful. Mayo Clinic website. Updated October 3, 2015. Accessed August 22, 2017.

5. Rondanelli M, Giacosa A, Opizzi A, et al. Beneficial effects of artichoke leaf extract supplementation on increasing HDL-cholesterol in subjects with primary mild hypercholesterolaemia: a double-blind, randomized, placebo-controlled trial. Int J Food Sci Nutr. 2013;64(1):7-15.

6. Rondanelli M, Giacosa A, Morazzoni P, et al. MediterrAsian diet products that could raise HDL-cholesterol: a systematic review. Biomed Res Int. 2016;2016:2025687.

7. Ben Salem M, Affes H, Ksouda K, et al. Pharmacological studies of artichoke leaf extract and their health benefits. Plant Foods Hum Nutr. 2015;70(4):441-453.

8. Wider B, Pittler MH, Thompson-Coon J, Ernst E. Artichoke leaf extract for treating hypercholesterolaemia. Cochrane Database Syst Rev. 2013;(3):CD003335.

9. Pirro M, Vetrani C, Bianchi C, Mannarino MR, Bernini F, Rivellese AA. Joint position statement on "nutraceuticals for the treatment of hypercholesterolemia" of the Italian Society of Diabetology (SID) and of the Italian Society for the Study of Arteriosclerosis (SISA). Nutr Metab Cardiovasc Dis. 2017;27(1):2-17.

10. Barbagallo CM, Cefalù AB, Noto D, Averna MR. Role of nutraceuticals in hypolipidemic therapy. Front Cardiovasc Med. 2015;2:22.

11. Cicero AF, Colletti A. Combinations of phytomedicines with different lipid lowering activity for dyslipidemia management: the available clinical data. Phytomedicine. 2016;23(11):1113-1118.

12. Toth PP, Patti AM, Nikolic D, et al. Bergamot reduces plasma lipids, atherogenic small dense LDL, and subclinical atherosclerosis in subjects with moderate hypercholesterolemia: a 6 months prospective study. Front Pharmacol. 2016;6:299.

13. Patti AM, Toth PP, Giglio RV, et al. Nutraceuticals as an important part of combination therapy in dyslipidaemia. Curr Pharm Des. 2017;23(17):2496-2503.

14. Hartley L, May MD, Loveman E, Colquitt JL, Rees K. Dietary fibre for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2016;(1):CD011472.

15. Zhu X, Sun X, Wang M, et al. Quantitative assessment of the effects of beta-glucan consumption on serum lipid profile and glucose level in hypercholesterolemic subjects. Nutr Metab Cardiovasc Dis. 2015;25(8):714-723.

16. 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.

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

18. Saxena S, Katare C. Evaluation of flaxseed formulation as a potential therapeutic agent in mitigation of dyslipidemia. Biomed J. 2014;37(6):386-390.

19. Ried K. Garlic lowers blood pressure in hypertensive individuals, regulates serum cholesterol, and stimulates immunity: an updated meta-analysis and review. J Nutr. 2016;146(2):389S-396S.

20. Varshney R, Budoff MJ. Garlic and heart disease. J Nutr. 2016;146(2):416S-421S.

21. Gardner CD, Lawson LD, Block E, et al. Effect of raw garlic vs commercial garlic supplements on plasma lipid concentrations in adults with moderate hypercholesterolemia: a randomized clinical trial. Arch Intern Med. 2007;167(4):346-353.

22. Han S, Jiao J, Xu J, et al. Effects of plant stanol or sterol-enriched diets on lipid profiles in patients treated with statins: systematic review and meta-analysis. Sci Rep. 2016;6:31337.

23. Burke FM. Red yeast rice for the treatment of dyslipidemia. Curr Atheroscler Rep. 2015;17(4):495.

24. Red yeast rice. National Institutes of Health, National Center for Complementary and Integrative Health website. Updated July 2013. Accessed August 22, 2017.

25. Gerards MC, Terlou RJ, Yu H, Koks CH, Gerdes VE. Traditional Chinese lipid-lowering agent red yeast rice results in significant LDL reduction but safety is uncertain — a systematic review and meta-analysis. Atherosclerosis. 2015;240(2):415-423.

26. Verhoeven V, Lopez Hartmann M, Remmen R, Wens J, Apers S, Van Royen P. Red yeast rice lowers cholesterol in physicians — a double blind, placebo controlled randomized trial. BMC Complement Altern Med. 2013;13:178.

27. Peng D, Fong A, Pelt AV. Original research: the effects of red yeast rice supplementation on cholesterol levels in adults. Am J Nurs. 2017;117(8):46-54.

28. Li Y, Jiang L, Jia Z, et al. A meta-analysis of red yeast rice: an effective and relatively safe alternative approach for dyslipidemia. PLoS One. 2014;9(6):e98611.

29. Nguyen T, Karl M, Santini A. Red yeast rice. Foods. 2017;6(3):19.

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

31. Ramdath DD, Padhi EM, Sarfaraz S, Renwick S, Duncan AM. Beyond the cholesterol-lowering effect of soy protein: a review of the effects of dietary soy and its constituents on risk factors for cardiovascular disease. Nutrients. 2017;9(4):E324.

32. Electronic Code of Federal Regulations, 101.82: health claims: soy protein and risk of coronary heart disease (CHD). US Government Publishing Office website. Updated September 12, 2017.

33. Hernáez Á, Remaley AT, Farràs M, et al. Olive oil polyphenols decrease LDL concentrations and LDL atherogenicity in men in a randomized controlled trial. J Nutr. 2015;145(8):1692-1697.