Phytoestrogen-Rich Diet for Lowering Serum Cholesterol
April 1998; Volume 1: 41-42
By Joshua J. Ofman MD, MSHS, and Jay K. Udani, MD
Most patients with elevated serum choles- terol levels are given a trial of dietary modification with a lower total fat diet as the first step in therapy. Because these efforts suffer from poor adherence and limited cholesterol effect, many physicians ultimately resort to pharmacologic therapy. There is an alternative dietary modification, however, that may supplement or even replace conventional step 1 and step 2 dietary therapy-a phytoestrogen-rich diet.
Phytoestrogens are a diverse group of plant-derived compounds that exhibit estrogen-like biological activity, including lowering serum cholesterol. There is now a large body of literature that indicates that protein from soybeans lowers blood cholesterol levels.1,2 Lowering cholesterol is the critical step in the primary prevention of death from coronary heart disease among middle-aged men and in the secondary prevention of death from coronary heart disease in men and women 45-70 years of age.
Pharmacology
The three main classes of phytoestrogens include isoflavones, lignans, and coumestans. The major isoflavones are genistein and daidzein, which are converted from inactive precursors by intestinal glucosidases. In humans, plant lignans and isoflavones are converted into heterocyclic phenols similar in structure to estrogen.
Mechanism of Action
The biologic importance of the phytoestrogens became apparent in the 1940s, when it was discovered that sheep grazing in western Australian pastures rich in clover had become infertile. Identified in human blood and urine in the 1980s, phytoestrogens are characterized by their ability to bind estrogen receptors and elicit response in estrogen-sensitive tissue. The mechanism of the hypocholesterolemic effect is unclear, but many hypotheses exist, including impaired cholesterol absorption and/or bile acid reabsorption, endocrine effects, increased apolipoprotein receptor activity, and increased hepatic cholesterol clearance.3 Recent primate studies suggest that the isoflavones may be responsible.4 Additional anti-atherogenic effects of soy protein include a decrease in LDL and increase in HDL cholesterol.5 The antioxidant properties of isoflavones protect LDL cholesterol from oxidation and arteries from atherosclerotic plaque formation.6
Clinical Studies
There are no known clinical trials in humans that isolate the hypocholesterolemic effect of phytoestrogens; rather the trials evaluate soy protein in general. A recent meta-analysis of 38 controlled trials in humans found soy protein consumption is significantly associated with a 9.3% reduction in total cholesterol, a 12.9% reduction in LDL cholesterol and a 10.5% reduction in triglyceride levels.5 There was a trend toward a (2.4%) rise in HDL cholesterol. The soy protein intake averaged 47 g/d (range, 17-124 g), and 40% of the studies used 31 g/d or less. The higher the pretreatment cholesterol level, the greater the effect of soy protein.
Studies in nonhuman primates suggest that soy isoflavones account for 60-70% of the effects of soy protein.5 A recent randomized trial in rats suggests that low-dose simvastatin may potentiate the hypocholesterolemic effect of soy protein.7
Diet/Formulation
The isoflavones with estrogenic activity occur mostly in legumes and beans such as soybeans, soy milk, tofu, green split peas, lentils, chick peas, flaxseed, and clover and alfalfa sprouts.
Lignans are found in whole grain cereals (oats, barley, hops, bran, wheat germ, rice), fruits (cherries, apples, pears), vegetables (onion, garlic, carrots, and vegetable oil), seeds (fennel and sunflower), and alcoholic beverages made from hops and/or corn. Coumestans occur predominantly in bean sprouts, such as soy, and fodder crops, such as clover.
Dietary supplements rich in phytoestrogens include black cohosh root (e.g., Remifemin, Menobalance), dong quoi (an herb that is added to some Chinese teas), red clover, and licorice. Plants vary greatly in the quantity of phytoestrogens they contain, and processed soy products (especially powdered soy flour and milk) are practically devoid of phytoestrogens.
Dose
The traditional diet in the Far East contains 20-150 mg/d of isoflavones from soy found in miso, tofu, and soy noodles. The dose of soy protein required to achieve a hypocholesterolemic effect is uncertain, but most experts agree that two servings of soy-based protein or 17-25 g/d would have an effect.8 This could include a soy beverage containing 8 g of soy protein and an entree providing 15-20 g of soy protein. Tofu products are a rich source of phytoestrogens and are available as soft and silken (for dressings, desserts, sauces, and spreads), and firm and extra firm (for soups, stir-fries, and for the broiler, smoker and even the grill). Good quality reduced fat versions are now available: Mori-Nu is a reliable producer. Soybeans, and tempeh are rich in isoflavones.9 Soy sauce reportedly has none.
Adverse Effects
The major potential toxicity of phytoestrogens in the diet relates to their estrogenic effects. High doses of soy protein have resulted in infertility, menstrual cycle abnormalities, and developmental problems. Soy allergy is reported to be a potential problem. There is concern about the carcinogenic effect of intrinsic protease inhibitors like soy, but since commercial soy products are heat treated, the potential is limited.
Conclusion
Lipid abnormalities are a major contributor to the morbidity and mortality associated with coronary heart disease. The mechanisms of action and the results of clinical studies suggest that soy protein, and perhaps the phytoestrogen content of soy protein, lowers serum cholesterol and improves the lipid profile.
Nonpharmacologic therapy with soy protein is safe, effective, and readily available in many formulations. Use of soy protein as an adjunct to the diet offers the potential to provide primary prevention and decrease medication requirements in patients with more severe hypercholesterolemia. We recommend that patients with hypercholesterolemia increase their intake of soy protein to 25 g/d in a nondesiccated form in addition to other recommended therapies such as exercise and anti-hypercholesterolemic medications.
References
1. Potter SM. Soy protein and serum lipids. Curr Opin Lipidol 1996;7:260-264.
2. Carroll K., Kurowska EM. Soy consumption and cholesterol reduction: Review of animal and human studies. J Nutrition 1995;125:594S-597S.
3. Potter SM. Overview of proposed mechanisms for the hypocholesterolemic effect of soy. J Nutrition 1995;125:606S-611S.
4. Cruz ML, Wong WW, Mimouni F, et al. Effects of infant nutrition on cholesterol synthesis rates. Pediatr Res 1994;35:135-140.
5. Anderson JW, Johnstone BM, Cook-Newell ME. Meta-analysis of the effects of soy protein intake on serum lipids. N Engl J Med 1995;333:276-282.
6. Wei H, Bowen R, Cal Q, et al. Antioxidant and antipromotional effects of the soybean isoflavone Genistein. Proc Soc Exper Biol Med 1995;208:124-130.
7. Giroux I, Lavigne C, Moorjani S, et al. Simvastatin further enhances the hypocholesterolemic effect of soy protein in rabbits. J Am Coll Nutr 1997;16:166-174.
8. Anderson JJB, Garner SC. Phytoestrogens and human Function. Nutrition Today 1997;32:232-239.
9. Bakhit RM, Klein BP, Essex-Sorlie D, et al. Intake of 25 g of soybean protein with or without soybean fiber alters plasma lipids in men with elevated cholesterol concentrations. J Nutrition 1994;124:213-222.
April 1998; Volume 1: 41-42You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content