Trial Information

Macrobiotic Diet and Flax Seed: Effects on Estrogens, Phytoestrogens, & Fibrinolytic Factors

Broad health effects of endogenous and exogenous estrogens on diseases of aging, including
hormone-dependent cancers, cardiovascular disease, and osteoporosis, are generally
recognized. For example, estrogen replacement therapy (ERT) may increase the risk of
subsequent breast and endometrial cancer, but also decreases the risk of coronary disease
and fractures. Because of the increased cancer risk, many women seek out alternatives to
ERT. Phytoestrogens, plant compounds that have estrogenic effects, have been a focus of
interest as an alternative to ERT. The isoflavones and lignans are two major classes of
phytoestrogens that occur in the food supply. Among the former, soy foods have attracted
much interest, while among the latter, whole grains and seeds are sources in a typical diet.
More specifically, women consuming a macrobiotic diet have been observed to have extremely
high levels of phytoestrogen metabolites in their urine, perhaps 10 to 20 times that seen in
women consuming an omnivorous diet. Proponents of a macrobiotic diet have proposed that it
is beneficial in the context of cancer therapy, as well as for the prevention and treatment
of cardiovascular disease.

This study will investigate, in a randomized, three-arm study, the effects of two
interventions that are high in phytoestrogens on various parameters related to estrogen
metabolism and fibrinolysis. Approximately 120 women will be randomized to receive an
American Heart Association (AHA) Step 1 diet, an AHA Step 2 diet + 10 g/day flax seed, or a
macrobiotic dietary intervention. Blood and urine samples will be drawn at baseline, and at
three, six, nine, and twelve months, to examine both short and long-term effects of these
interventions. Outcomes include blood and urine levels of total estrogens and estradiol,
and related metabolites; antigens to plasminogen activator inhibitor-1 (PAI-1) and tissue
plasminogen activator (t-PA), fibrin D-dimer, and von Willebrand Factor; and endothelial
function as measured by high-resolution ultrasound. Blood levels of antioxidant vitamins
and retinoids will also be examined.

This study should provide information on whether these alternative, high phytoestrogen
dietary interventions result in favorable effects on these biological parameters that are
related to risk of major diseases of aging.