Nutrition and Estrogen Metabolism

Epidemiological and animal studies have identified estrogen exposure as a risk factor for cancer of breast, endometrium, ovary, testis, prostate and thyroid, increasing risk associated with increased exposure

Many nutritional factors influence how estrogens and other hormones act on the body tissues, how they are metabolized (broken down for excretion from the body), and how the metabolites (breakdown products) affect human health.

Dr. Douglas C. Hall, M.D., wrote an article in Applied Nutritional Science Reports, January 2001, entitled, "Nutritional Influences on Estrogen Metabolism," in which he documents many of these nutritional influences on the very complex interplay of hormones. He cites 81 references in this very thorough coverage of this topic, and I will attempt to summarize some of the most important areas. This paper focuses mainly on estrogens. However, this is not to say that other hormones like progesterone are not also important in modifying the results of estrogen effects on tissues.

It is well known that excessive estrogen exposure, both from inside and from outside the body, is one of the most prominent causes of breast cancer and many other health problems in men and women. Estrogens (estradiol, estrone and estriol) and their metabolites affect a variety of tissues throughout the body in both men and women, and not just in the reproductive organs.

The estrogens are changed in molecular structure in the liver so they can be excreted through the bile, feces and urine. Dr. Hall details the numerous metabolic pathways of estrogens that result in a variety of end products. Each one of these metabolites of estrogens has a different biological effect on the body tissues, some beneficial and some not so beneficial.

In Phase I detoxification, estrone and estradiol can be transformed into 2-hydroxyestrone (2- OH), a safer metabolite with weaker estrogenic activity, or into 16 alpha hydroxyestrone (16 alpha-OH) and 4 hydroxy estrone (4-OH), both of which promote tissue proliferation, breast cancer and estrogen dominance (imbalance with other hormones).

Phase II detoxification further modifies estrogen metabolites. The 2-OH and 4-OH metabolites could be oxidized into quinines, which can cause DNA damage and cancer, were it not for a methylation process that renders the (4-OH) less harmful and makes the (2OH), now 2 methoxyestrone, actually an inhibitor of breast cancer.

Vitamins A, E and C, N-acetylcysteine, turmeric, green tea, lycopene, alpha lipic acid and flavonoids reduce the oxidation of the estrogen metabolites. Folic acid, Vitamins B2, B6 and B12, and magnesium promote the methylation reactions. The overall detoxification of estrogens in Phase I and Phase II is promoted by turmeric and the aforementioned B-vitamins, flavonoids and magnesium, and D-limonene, the oil in citrus fruits.

The other important Phase II reaction is glucuronidation, where glucuronic acid is conjugated, (attached) to the estrogen molecule to help it to pass through the bile and out the intestinal tract. However, an enzyme in the intestinal tract -- beta glucuronidase -- which is promoted by a high fat and meat diet, can split the glucuronic acid off the estrogen molecule and allow the estrogen to re-enter the circulation and further increase estrogen activity in the body. Things that inhibit beta glucuronidase are probiotics (acidophilus and bifidobacteria, found in yogurt and food supplements), high fiber, low fat foods and calcium d-glucarate.

What are the hazards of too much estrogen? One of the major areas of concern is that of carcinogenesis (promotion of cancer). Epidemiological and animal studies have identified estrogen exposure as a risk factor for cancer of breast, endometrium, ovary, testis, prostate and thyroid, increasing risk associated with increased exposure.

The 16 alpha-OH and the 4-OH metabolites are implicated in toxic effects on DNA and on altering gene expression toward proliferation of cells, while the 2-OH metabolite may inhibit cell proliferation and thus prevent cancer.

Dr. Hall cites a five-year prospective study (Epidemiology, 2000; 11 (6) 635-40) of 10,786 women, which found that a high 2-OH:16 alpha-OH ratio predicted 40 percent lower incidence of breast cancer. Two other studies also confirmed this relationship.

This 2-OH:16 alpha-OH ratio is decreased by pesticides, obesity and certain drugs (including Tagamet). This same ratio is increased by intake of cruciferous vegetables (cabbage, broccoli, cauliflour, etc.), Indole-3 carbinols (found in the cruciferous vegetables), soy products, flax seeds and isoflavones from soy and kudzu.

Some sources of increased total estrogens are obesity, high insulin levels (Syndrome X), alcohol intake (even in moderation), oral contraceptives, hormone replacement therapy, hormones from meat and mild products from agriculturally added hormones. Environmental toxins can cause harm by mimicking estrogens. Some of these are in pesticides, herbicides, plastics and plasticizers, and solvents.

Isoflavones, fiber and the lignans in flaxseed can increase SHBG (sex hormone binding globulin), thus decreasing the amount of unbound or free circulating estrogens.

The isoflavones and lignans and Indole-3 carbinols also modify estrogen receptor activity to decrease some of the harmful effects of the already present estrogens on the cells and tissues.

Low vitamin E levels are associated with elevated estrogen levels. Too low dietary protein can result in decreased Phase I detoxification of estrogens.

These are some of the nutritional factors that affect the metabolism of the estrogens, and there is much more yet to be discovered. It is important to pay attention to them because we may be able to affect hormone balance with beneficial results, without always having to supplement with hormones or hormone-blocking drugs.

The research supporting Dr. Hall's article is cited in 81 references, some of which include the New England Journal of Medicine; the Lancet; the Journal of Endocrinology; Epidemiology; British Journal of Cancer; Cancer Research; Nutrition and Cancer; Journal of the National Cancer Institute; Gynecology and Oncology; International Journal of Cancer; Biochemistry and Pharmacology; and Carcinogenesis.