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Lignans and Heart Disease

Important Scientific Research Regarding Lignans and Coronary Heart Disease

Clinical review 97: Potential health benefits of dietary phytoestrogens: a review of the clinical, epidemiological, and mechanistic evidence.
 
Journal of Clinical Endocrinology and Metabolism - July, 1998

Tham DM, Gardner CD, Haskell WL.

Stanford Center for Research in Disease Prevention, Stanford University Medical School, California 94304, USA. doris.tham@forsythe.stanford.edu

Phytoestrogens represent a family of plant compounds that have been shown to have both estrogenic and antiestrogenic properties. A variety of these plant compounds and their mammalian metabolic products have been identified in various human body fluids and fall under two main categories: isoflavones and lignans. A wide range of commonly consumed foods contain appreciable amounts of these different phytoestrogens. For example, soy and flax products are particularly good sources of isoflavones and lignans, respectively. Accumulating evidence from molecular and cellular biology experiments, animal studies, and, to a limited extent, human clinical trials suggests that phytoestrogens may potentially confer health benefits related to cardiovascular diseases, cancer, osteoporosis, and menopausal symptoms. These potential health benefits are consistent with the epidemiological evidence that rates of heart disease, various cancers, osteoporotic fractures, and menopausal symptoms are more favorable among populations that consume plant-based diets, particularly among cultures with diets that are traditionally high in soy products. The evidence reviewed here will facilitate the identification of what is known in this area, the gaps that exist, and the future research that holds the most potential and promise.

Phyto-oestrogens and Western diseases.

Annals of Medicine - April, 1997

Adlercreutz H, Mazur W.

Department of Clinical Chemistry, University of Helsinki, Meilahti Hospital, Finland. herman.adlercreutz@helsinki.fi

Incidences of breast, colorectal and prostate cancer are high in the Western world compared to countries in Asia. We have postulated that the Western diet compared to the semivegetarian diet in some Asian countries may alter hormone production, metabolism or action at the cellular level by some biochemical mechanisms. Our interest has been focused on two groups of hormone-like diphenolic phyto-oestrogens of dietary origin, the lignans and isoflavonoids abundant in plasma of subjects living in areas with low cancer incidence. The precursors of the biologically active compounds detected in man are found in soybean products, whole-grain cereal food, seeds, and berries. The plant lignan and isoflavonoid glycosides are converted by intestinal bacteria to hormone-like compounds. The weakly oestrogenic diphenols formed influence sex-hormone production, metabolism and biological activity, intracellular enzymes, protein synthesis, growth factor action, malignant cell proliferation, differentiation, cell adhesion and angiogenesis in such a way as to make them strong candidates for a role as natural cancer-protective compounds. Their effect on some of the most important steroid biosynthetic enzymes may result in beneficial modulation of hormone concentrations and action in the cells preventing development of cancer. Owing to their oestrogenic activity they reduce hot flushes and vaginal dryness in postmenopausal women and may to some degree inhibit osteoporosis, but alone they may be insufficient for complete protection. Soy intake prevents oxidation of the low-density lipoproteins in vitro when isolated from soy-treated individuals and affect favourably plasma lipid concentrations. Animal experiments provide evidence suggesting that both lignans and isoflavonoids may prevent the development of cancer as well as atherosclerosis. However, in some of these experiments it has not been possible to separate the phyto-oestrogen effect from the effect of other components in the food. The isoflavonoids and lignans may play a significant inhibitory role in cancer development particularly in the promotional phase of the disease, but recent evidence points also to a role in the initiation stage of carcinogenesis. At present, however, no definite recommendations can be made as to the dietary amounts needed for prevention of disease. This review deals with all the above-mentioned aspects of phyto-oestrogens.

Dietary flax seed in prevention of hypercholesterolemic atherosclerosis.
 
Atherosclerosis - July,1997 

Prasad K.

Department of Physiology, College of Medicine, University of Saskatchewan, Saskatoon, Canada.

Oxygen free radicals (OFRs) have been implicated in the development of hypercholesterolemic atherosclerosis. Flax seed is the richest source of omega-3 fatty acid and lignans. omega-3 Fatty acid suppresses the production of interleukin-1 (IL-1), tumor necrosis factor (TNF) and leukotriene B4 (LTB4), and of OFRs by polymorphonuclear leukocytes (PMNLs) and monocytes. Lignans possess anti-platelet activating factor (PAF) activity and are antioxidant. PAF, IL-1, TNF and LTB4 are known to stimulate PMNLs to produce OFRs. Flaxseed would, therefore, reduce the levels of OFRs and hence would prevent the development of hypercholesterolemic atherosclerosis. The effects of dietary flax seed on a high cholesterol diet induced atherosclerosis, lipid profile and OFR-producing activity of PMNLs (PMNL-CL) were investigated in rabbits. The rabbits were divided into 4 groups: group I, control; group II, flax seed diet (7.5 g/kg daily, orally); group III, 1% cholesterol diet; and group IV, same as group III but received flax seed (7.5 g/kg daily, orally). Blood samples were collected before and after 4 and 8 weeks on their respective diets for biochemical measurements and aortae were removed at the end of 8 weeks for estimation of atherosclerotic changes. The high cholesterol diet increased the serum level of total cholesterol (TC) and PMNL-CL without altering the levels of serum triglycerides (TG). These changes were associated with a marked development of atherosclerosis in the aorta. Flax seed reduced the development of aortic atherosclerosis by 46% and reduced the PMNL-CL without significantly lowering the serum cholesterol. Flax seed in normocholesterolemic rabbits increased serum total cholesterol and decreased PMNL-CL without significantly affecting the serum TG. Modest dietary flax seed supplementation is effective in reducing hypercholesterolemic atherosclerosis markedly without lowering serum cholesterol. Its effectiveness against hypercholesterolemic atherosclerosis could be due to suppression of enhanced production of OFRs by PMNLs in hypercholesterolemia. Dietary flax seed supplementation could, therefore, prevent hypercholesterolemia-related heart attack and strokes.

Risk of acute coronary events according to serum concentrations of enterolactone: a prospective population-based case-control study.
 
Lancet - December, 1999

Vanharanta M, Voutilainen S, Lakka TA, van der Lee M, Adlercreutz H, Salonen JT.

Research Institute of Public Health, University of Kuopio, Finland.

BACKGROUND: The lignan enterolactone, produced by the intestinal microflora from dietary precursors, has been implicated in protection against cancer. We investigated the association of serum enterolactone concentration with the risk of acute coronary events in a prospective nested case-control study in middle-aged men from eastern Finland. METHODS: Enterolactone was measured by time-resolved fluoroimmunoassay in serum from 167 men who had an average 7.7 years of follow-up to an acute coronary event and from 167 control men. Both cases and controls were from a cohort of 2005 men who had no clinical coronary heart disease (CHD) at baseline. The controls were matched for age, examination year, and residence. Acute coronary events were registered prospectively. FINDINGS: The mean baseline serum enterolactone concentration was lower among the cases than the controls (18.2 [SD 21.1] vs 23.5 [18.2] nmol/L, p=0.001). The men in the highest quarter of the enterolactone distribution (>30.1 nmol/L) had a 58.8% (95% CI 24.1-77.6, p=0.005) lower risk of acute coronary events than men in the lowest quarter. After adjustment for the nine most strongly predictive risk factors, men in the highest enterolactone quarter had a 65.3% (11.9-86.3, p=0.03) lower risk than men in the lowest quarter. INTERPRETATION: Healthy men with high serum concentrations of enterolactone had a lower risk of acute coronary events than men with lower concentrations. These findings support the hypothesis that plant-dominated fibre-rich food lowers the risk of CHD.