GAMMA-ORYZANOL: An impressive yet under-appreciated natural agent for the treatment of hot flashes in menopause

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The Changing Face of Menopausal Management

Recent reports indicate that hormone replacement therapy  (a combination of estrogen plus progestin hormones) increases the risk of breast cancer by 26%, stroke by 41%, and heart attacks by 29%.  These alarming statistics that emerged from the American Women’s Health Initiative trial have prompted doctors and patients alike, to search for safer, alternative means by which to manage menopausal symptoms. (17) In Europe and Japan, alternative measures to combat menopausal symptoms have already been in use for more than 40 years, and well-designed clinical trials have shown that natural supplements such as black cohosh extract, soy isoflavones and gamma-oryzanol, are effective interventions in the management of a host of bothersome menopausal symptoms.  Active constituents from black cohosh extract (triterpene glycosides) and soy isoflavones appear to act as phytoestrogens, imparting their estrogenic influences on various tissues, to help compensate for the 90% decline in estrogen in a woman’s body that accompanies the menopausal years. (5,18,19) However, gamma-oryzanol, a less well-appreciated natural substance, is able to greatly reduce the number and severity of hot flashes during the early and most troublesome stage of menopause, through an entirely different mechanism of action.  Gamma-oryzanol (esters of ferulic acid) is a growth-promoting substance found in grains, and is isolated from rice bran oil for use as a supplement.  In 1970, gamma-oryzanol was approved as a medicinal treatment to lower cholesterol and triglycerides (Japan). (1) As far back as the 1960’s, gamma-oryzanol was also shown to be effective in the treatment of menopausal symptoms, including hot flashes, and subsequent studies have supported these findings. (1)

Orally administered gamma-oryzanol is converted in the body to free ferulic acid. (1)

Clinical Application and Mechanism of Action of Gamma-oryzanol

  1. Menopausal Symptoms - Supplementation with gamma-oryzanol (150mg, twice per day) has been shown to reduce the secretion of leutinizing hormone (LH) by the pituitary and promote endorphin release by the hypothalamus. (1) Hot flashes and other menopausal symptoms (profuse sweating, mood changes) result indirectly from the over-secretion of leutinizing hormone, which is attempting to initiate the start of another ovulatory cycle.  The lack of response by the immature egg cells in the ovaries in menopause results in an over-secretion of FSH and LH by the pituitary, contributing to the onset of hot flashes and related symptoms. (1)Clinical trials involving menopausal women and women who had their ovaries surgically removed, have revealed that 67-85 percent of women treated with gamma-oryzanol have experienced a significant reduction in menopausal symptoms. (1,2)

  2. Cholesterol and Triglyceride Lowering (hypolipidemic effects) - A number of clinical trials reveal that 300 mg per day of gamma-oryzanol supplementation can lower cholesterol by 8-12 percent and triglycerides by approximately 15 percent in subjects with elevated lipid levels. (1,2,3)

    Studies reveal that Gamma-oryzanol supplementation increases the conversion of cholesterol to bile acids, increases bile acid excretion, and inhibits the absorption of cholesterol from the intestinal tract to the bloodstream. (1,2)

    These are important considerations for postmenopausal women as heart disease is the most common cause of death in women over 50 years of age in North America.  The decline in circulating estrogen levels with menopause predisposes postmenopausal women to a rise in blood cholesterol and the development of atherosclerosis.  This is in part, due to the fact that estrogen increases the number of LDL-cholesterol receptors on body cells, enabling them to more efficiently remove cholesterol from the bloodstream. (1,2)

Dosage of Gamma-oryzanol

Menopausal Symptoms: 300 mg per day, taken in two divided doses (150 mg, twice per day)

Hypolipidemic Effects: 300 mg per day, taken in two divided doses (150 mg, twice per day) (1)

Adverse Side Effects and Toxicity

Toxicity studies on animals demonstrate that gamma-oryzanol is a very safe compound.  No significant side effects have been reported in human trials at the above noted recommended dosage. (1,2,16)

Drug Nutrient Interactions

There are no reported drug-nutrient interactions for Gamma-Oryzanol. (1)

Conclusion

Health practitioners are being called upon to recommend safe and effective alternatives to HRT and estrogen replacement therapy.  A detailed review of the world-wide evidence suggests that black cohosh extract, soy isoflavones and gamma-oryzanol, are the most thoroughly researched and most widely recognized natural agents that alone, or in combination, are able to significantly reduce menopausal symptoms and help reduce risk of other conditions, such as osteoporosis, heart disease and breast cancer, that are common problems in the postmenopausal years. Of these natural agents, gamma-oryzanol is the least well known, but health practitioners should be made aware of its proven abilities to contain menopausal symptoms, reduce cholesterol and triglyceride levels, and be assured that it has a long history of use and an impressive safety profile.  As such, gamma-oryzanol deserves strong consideration, as part of an overall nutrition and supplementation program, in a wellness program designed for the postmenopausal patient.

References

  1. Encyclopedia of Nutritional Supplements Prima Publishing 1996;Murray M:332-335
  2. Fujiwara S et al. Mass fragmentographic determination of ferulic acid in plasma after oral administration of gamma-oryzanol. Chem Parm Bull 1982;30:973-979.
  3. Yamauchi J et al. Inhibition of LH secretion by gamma-oryzanol in rat. Horm Metabol Res 1981;13:185.
  4. The Merk Manual (16th edition) Merck & Co. 1992;1767-1768.
  5. Murase Y and Iishima H. Clinical studies of oral administration of gamma-oryzanol on climateric complaints and its syndrome. Obstet Gynecol Prac 1963;12:147-149.
  6. Ishihara M. Effect of gamma-oryzanol on serum lipid peroxide levels and climateric disturbances. Asia Oceania J Obstet Gynecol 1984;10:317.
  7. Yoshino G, Kazumi T, Amano M et al. Effects of gamma-oryzanol on hyperlipidemic subjects. Curr Ther Res 1989;45:543-552.
  8. Yoshino G et al. Effects of gamma-oryzanol and probucol on hyperlipidemia. Durr Ther Res 1989;45,975-982.
  9. Sasaki J et al. Effect of gamma-oryzanol on serum lipids and apolipoproteins in dyslipidemic schizophrenics receiving major tranquilizers. Clin Ther 1990;12:263-268.
  10. Seetharamaiah GS and Chandrasekhara N. Effect of oryzanol on cholesterol absorption and biliary & fecal bile acids in rats. Ind J Med Res 1990;92:471-475.
  11. Sakamoto K et al. Effects of gamma-oryzanol and cycloartenol ferulic acid ester on cholesterol diet induced hyperlipidemia in rats. Jap J Pharmacol 1987;45:559-565.
  12. Gura T estrogen: key player in heart disease among women. Science 1995;269:771-773.
  13. Colditz G et al. Menopause and the risk of coronary heart disease in women. New Engl J Med 1987;316:1105-1110.
  14. Tamagawa M et al. Carcinogenicity study of gamma-oryzanol in B6C3F1 mice. Food Chem Toxicol 1992;30:49-56.
  15. Tamagawa M et al. Carcinogenicity study of gamma-oryzanol in F344 rats. Food Chem Toxicol 1992;30:41-48.
  16. Healthnotes, Inc.2001 www.healthnotes.com: Gamma Oryzanol
  17. Use of combination hormone replacement therapy is light of recent data from the Women’s Health Initiative.  Form Medscape Women’s Health eJournal. Posted 07/12/2002.
  18. Alternatives to estrogen. The Wholistic News Magazine; 10/31/1998; 62: 19
  19. Herbal alternatives to hormones.  Colgan Chronicles. 1998; 2,3: 8-9.

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