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  • Mary works full time while raising three young children and has been suffering with insomnia and night sweats even though she is far from menopause; Joanne, a busy stockbroker, has such heavy periods that she is locked in her house for seven days every month; and Melinda, newly married with an exciting job, is losing her hair, gaining weight around the middle, and feeling exhausted. All three women are suffering from estrogen dominance, a common condition in women.

    Hormones Out of Balance
    We are bombarded by environmental estrogens, also called xenoestrogens or estrogen mimickers. These man-made chemicals act exactly like estrogen in the body. Estrogen-mimickers are found in everything from plastics, cosmetics and pesticides to dry cleaning chemicals, dairy products and more. Too much estrogen upsets the body’s delicate balance of hormones. Some of the most common female estrogen-dominant conditions are PMS, endometriosis, abnormal PAP tests, ovarian cysts, uterine fibroids, cystic breasts, heavy periods, low thyroid, hormonal acne, severe menopausal symptoms, breast cancer and the list goes on. Too much estrogen can block the uptake of thyroid hormone, promoting low thyroid. Over 23 percent of Canadians take thyroid medication for low thyroid and an estimated 30 percent have undiagnosed low thyroid with symptoms that include hair loss, weight gain, feeling cold, constipation, night sweats, recurring miscarriage, heavy periods, high cholesterol and so much more.

    Women need estrogen but not the toxic type found in the environment. Women are supplied with estrogen from their ovaries, adrenal glands and fat cells. When the ovaries take a much-needed rest at menopause, or if the ovaries are surgically removed during a hysterectomy, the adrenal glands become the main source of estrogen. The adrenal glands sit atop the kidneys and they also help us deal with stress and control water balance in the body. When our adrenal glands become exhausted from too much stress, hormone havoc ensues. Classic symptoms include insomnia where you fall asleep fine but wake up several hours later and can’t fall back to sleep, caffeine and salt cravings, no energy, difficulty handling stress, and weight gain around the middle. We must love our adrenals in order to have balanced hormones.

    The liver is the key organ for detoxifying excess hormones, breaks down and distributes estrogen and other hormones. Your liver decides if your estrogen is going to stay in the healthy form or be converted into cancer-causing estrogens. Our liver becomes sluggish due to a diet of too many bad fats (from lard, margarine and refined oils), sugars and artificial sweeteners, fried foods, and not enough vegetables and good protein. Regular alcohol consumption also negatively affects the liver’s ability to maintain hormone balance.

    Hormone Harmony
    The liver, thyroid and the adrenal glands must operate at peak performance to ensure hormone harmony. The basis of a healthy hormone program is a diet full of cruciferous vegetables and lean protein from wild, free-range sources. There are also key herbs and nutrients that been researched to support the adrenals, liver and thyroid.

    Adrenal Support
    Eight hours of deep restful sleep will reverse adrenal exhaustion quickly. At bedtime, take a natural sleep aid containing melatonin, chamomile, hops, valerian and passionflower to help with sleep. The following herbs should be taken in combination to nourish the adrenals and help reduce the effects of stress:

    Rhodiola increases the body’s resistance to all types of stress; enhances mental and physical performance; and regulates the heart by increasing oxygen utilization. Suma is called “para todo” which means “for everything.” It is considered a regenerative tonic for the nervous, reproductive and digestive systems and is used to treat hormonal disorders, sexual dysfunction, fatigue, and stress.

    Siberian ginseng, not a true ginseng, normalizes reactions to physical and mental stress, and increases the body’s ability to withstand adverse conditions such as heat, noise, increases in workload and physical endurance. It regulates blood sugar, protects the liver and supports optimal adrenal function.

    Schizandra berry is a general tonic that promotes liver health and counters the effects of stress and fatigue. It is also used for insomnia associated with changing hormones.

    Ashwagandha increases energy to improve overall health and longevity. Studies have proven powerful anti-stress effects as well as antioxidant, anti-inflammatory, anti-tumor and immune-modulating properties. Ashwagandha not only supports the adrenals but has also been found to improve thyroid function too.

    Support a Low Thyroid The adrenal glands and the thyroid are directly linked so once the adrenals become exhausted, the thyroid goes low. The following nutrients have been found to help support the thyroid. These nutrients can be safely taken along with thyroid medicines. Never stop your thyroid hormone drug without your doctor’s recommendation.

    Tyrosine is an amino acid necessary for the manufacture of thyroid hormones. Tyrosine assists a sluggish thyroid and can aid the loss of those unwanted pounds.

    Ashwagandha supports the thyroid gland. Studies show that it enhances thyroid function and produces a significant increase in T4 thyroid hormone.

    Guggal extract supports complete thyroid health while enhancing the conversion of T4 hormone to the more potent T3 hormone. Guggal extract and ashwagandha should be used together to support thyroid health.

    Potassium iodide is essential for the manufacture of thyroid hormones, and was initially added to salt to combat the epidemic of low thyroid in Canadians. Since many people now avoid salt for fear of high blood pressure, low thyroid and goitres are on the rise in Canada.

    Environmental Estrogen Protection
    We must avoid products containing environmental estrogens such as cosmetics containing parabens, plastics with BPA, synthetic hormones in dairy and meat, to name a few. Detoxification of these estrogens using saunas and dry brushing the skin will help to eliminate excess estrogens, as does eating organic broccoli, Brussels sprouts, cauliflower, cabbage and kale. Supplementing with the following nutrients can help protect you from the dangerous effects of environmental estrogens and balance hormones. If you have any of the estrogen-dominant conditions mentioned earlier, you need the following food-based nutrients every day. They can be purchased separately or in combo.

    Indole-3-carbinol (I-3-C) is a powerful plant nutrient from cruciferous vegetables. I-3-C prevents the conversion of good estrogens to cancer-causing estrogens. I-3-C maintains a healthy cervix, protects against HPV cervical lesions and controls abnormal cell growth found in those with uterine fibroids, breast lumps and endometriosis. It is very effective for heavy periods caused by a thickened uterine lining.

    D-glucarate is a powerful detoxifier of excess estrogens via the liver. It helps to maintain healthy hormone balance.

    Green tea extract contains polyphenols, catechins and flavonoids shown to be protective against estrogen-related cancers and it stops abnormal cell growth. (Note: Although uterine fibroids, ovarian cysts, endometriosis and breast lumps may not develop into cancers, they are cells growing out of control.)

    Curcuminis the yellow pigment of turmeric. This powerful anti-inflammatory agent works to inhibit all steps of cancer formation: initiation, promotion and progression. Curcumin also supports the liver.

    Rosemary extract, a potent antioxidant, protects cells from cancer-causing agents, inhibits the growth of cancer cells and helps to detoxify toxic estrogens.

    Sulforaphane, from Broccophane™ broccoli sprout extract, has been shown to stimulate the body’s production of detoxification enzymes that eliminate environmental estrogens. Sulforaphane is a powerful antioxidant and anticancer agent.

    Happy Conclusions
    Mary found relief from her insomnia and night sweats within a few days by using the adrenal support nutrients and a natural sleep aid. Joanne is relieved that, after only two months of taking indole-3-carbinol along with the other estrogen-balancing nutrients, her periods are now four days in length with normal flow. Since Melinda started taking the recommended thyroid nutrients, her hair stopped falling out and the added weight is now coming off effortlessly.

  • Many physicians routinely prescribe hormone replacement therapy (HRT) to postmenopausal or even perimenopausal women. As a matter of fact, about 17.5 million American women were taking HRT in 1998, according to a national survey. HRT, however, is not without its health risks. Before discussing HRT risks and alternatives, let's first examine the rationale for HRT in association with menopause.

    Menopause: Physiological Changes
    Menopause refers to the stopping of menstruation and the end of the reproductive capacity of a woman. This event usually occurs around age 50 but may happen prematurely in some individuals before age 45 or artificially by the removal of the ovaries during a hysterectomy. As many as ten years before menopause, the ovaries begin to cease normal function. During this time, many basic physiological changes occur, including failure to ovulate; a decreased number of developing follicles and oocytes; a decreased level of the hormones estrogen and progesterone; and a rapid rise in follicle stimulating hormone (FSH), a pituitary hormone, as well as a gradual rise in luteinizing hormone (LH). These ovarian changes eventually result in the cessation of menstruation (amenorrhea) and infertility. In the years before menopause a woman may have irregular uterine bleeding, heavy enough in some instances to produce anemia. Postmenopausal bleeding indicates a need for immediate medical attention, because the incidence of uterine or cervical cancer after menopause ranges from 15 to 30 percent of women.

    Menopause: Symptomology
    Most symptoms that occur during menopause result directly from the estrogen deficiency produced by the failing ovaries. It can be difficult to distinguish these symptoms from those caused by the normal aging process or from the social and domestic pressures faced by middle-aged women. Physical symptoms include hot flashes, night sweating, and tension or migraine headaches. These temporary symptoms contribute to the overall irritability and insomnia that normally occurs during this time. Osteoporosis, caused by severe or prolonged bone loss as a result of estrogen deficiency, affects 35 percent of women after a natural menopause. Psychological symptoms of menopause may include anxiety, depression, irritability, diminished energy, difficulty with concentration, and tension. Many women experience heightened libido after menopause because they know they can no longer get pregnant. However, emotional problems can cause a decline in sexual activity in some women.

    The Benefits of HRT
    Conventional medical treatment for menopause often involves HRT pharmaceutical hormones. It has been well documented for several decades that HRT can be an effective remedy for the hot flashes and sleep disturbances that often accompany menopause. Hormone replacement therapy has also consistently been shown to decrease vaginal discomfort by increasing the thickness, elasticity, and lubricating ability of vaginal tissue. Urinary tract tissue also becomes thicker and more elastic, which may reduce the incidence of stress incontinence and urinary tract infections. Furthermore, some physicians and medical agencies have advised that HRT may even decrease the risk for heart disease in postmenopausal women. These potential benefits of HRT are all well and good-and if this were the end of the story, I wouldn't have written this article. Unfortunately, there are health risks associated with HRT.

    The Risks of HRT
    Heretofore, the main concerns about HRT centered on the risk of endometrial cancer, ovarian cancer, and breast cancer, especially after long-term use (more than 10 years).1 For example, some studies suggest that HRT is associated with a one to 30 percent increase in the risk of breast cancer.2 Another study conducted by the American Cancer Society followed 211,581 postmenopausal women who had no history of cancer at the time of enrollment. Results of follow-up from 1982 through 1996 showed that women who used HRT for 10 or more years had an increased risk of dying from ovarian cancer, compared with women who had never used HRT or had used it for less than 10 years.3

    Recently, another potential risk issue regarding HRT and cardiovascular health has emerged. New recommendations by the American Heart Association, released on July 23, 2001, indicate that women who have had a heart attack or stroke do not benefit from HRT and may even increase their risk of suffering another attack.

    This is based upon research where researchers randomly assigned women with known heart disease to take either hormones or a placebo. The researchers found no difference between the two groups in fatal or nonfatal heart attacks after four years. In the first year of the study, women taking hormones had 52 percent more heart-related illnesses than the placebo group. Then, a separate study testing estrogen in women with a previous stroke found that those who took the hormone suffered a higher incidence of fatal strokes than those who took a placebo.4

    This new AHA position removes one of the main reasons many women take hormones-to reduce their risk of heart disease, which kills more than 226,000 American women a year, making it the number one cause of death in U.S. women.

    Finally, a landmark study was published in the July 2002 issue of JAMA, which included 16608 postmenopausal women aged 50-79 who were using HRT as Estrogen plus progestin. The researchers found a significantly increased risk of a heart attack or stroke beginning in women's first year of HRT use. In addition, the risk of breast cancer jumped after four years of HRT use. The researchers concluded that overall health risks exceeded benefits from use of combined estrogen plus progestin, and that "the results indicate that this regimen should not be initiated or continued for primary prevention of CHD [coronary heart disease]." 5

    Does all this mean that women who are currently using HRT should discontinue their medication; or that women who are not yet using HRT should not do so? After the aforementioned JAMA study was published, the position of the National Institutes of Health (who sponsored the study) was to urge women who currently use HRT to talk with their doctors about what to do.6 Certainly this is a personal decision, which can only be made by a woman and her doctor. Nonetheless, some women who are concerned about conventional HRT have turned to natural HRT alternatives.

    Phytoestrogens: Natural Alternatives to HRT
    Natural alternatives to HRT include the use of phytoestrogens. Phytoestrogens are natural components from plants, which bind to estrogen receptors in the body. Make no mistake, phytoestrogens are not actually estrogen, but since they are capable of binding to estrogen receptors, they can "fool" the body into thinking and reacting as though there were more estrogen present. Furthermore, since they are not actually estrogen, phytoestrogens are not a risk factor in the development of breast or female reproductive system cancers. As a matter of fact, research suggests that certain phytoestrogens may even help to reduce the risk of these cancers, and promote a healthy cardiovascular system. Some of the most effective phytoestrogens can be found in Soy, Black Cohosh, Red Clover Leaf, Licorice Root, and Wild Yam. In addition, certain nutrients may also play a valuable role during menopause.

    In fact, The American College of Obstetricians and Gynecologists (ACOG) now recommends three botanicals for management of menopausal symptoms. These are Black Cohosh, Soybean (isoflavones) and St. John's Wort (SJW for symptoms of depression, not for any direct impact on female hormonal biochemistry).

    The protein fractions of soybeans contain an interesting group of substances called isoflavones. The ACOG suggests that short-term use of the phytoestrogens in soy may be helpful for relieving hot flashes and night sweats.8 In addition, research also indicates that these isoflavones may provide some very specific benefits, including cancer prevention, cholesterol reduction, and building bone density.

    Cancer prevention
    The isoflavones in soybeans have been shown to have anti-cancer effects. Apparently, the isoflavones have phytoestrogenic and antioxidant properties. One particular isoflavone called genistein (and possibly another called daidzein) has been proposed to contribute an important part of the anti-cancer effect of soy isoflavones. As a matter of fact, genistein in soy is considered by some researchers to be responsible for the lower rate of breast cancer observed in Asian women consuming soy.

    The effect of genistein was tested in one study in five human breast cancer cell lines. Genistein inhibited the growth of each of these cancer cells.9 Similar studies using genistein also showed significant inhibitory effects on breast cancer cells. It seems that genistein affects estrogen receptors in such a way as to prevent breast cancer growth.10 This estrogen altering response was also apparent in another study, which examined the influence of total soy isoflavones in six premenopausal women for one month. The result was that menstruation was delayed and cholesterol concentrations decreased 9.6 percent.11

    Furthermore, soy's anti-cancer effects are not limited to breast cancer. Researchers conducted test-tube research on human and animal bladder cancer cell lines, using pure soy isoflavones and soy phytochemical concentrate. The results were that both the pure soy isoflavones (genistein, genistin, daidzein, and biochanin A) and soy phytochemical concentrate inhibited growth of human and animal bladder cancer cell lines. Animal research also demonstrated that the ability of genistein, soy phytochemical concentrate, and soy protein isolate to inhibit the growth of bladder cancer in the animal (not in the test-tube). Genistein, dietary soy phytochemical concentrate, and dietary soy protein isolate reduced tumor size by 40, 48, and 37 percent, respectively, as compared with controls.12

    Cholesterol reduction
    Research indicates that substituting soy protein for animal protein may lead to reductions in plasma cholesterol. Three separate studies investigated the effect of soy products and isoflavones on the blood lipid levels of 74 postmenopausal women over a 6-month program. Forty grams of test protein were incorporated into the subjects' diets. The test protein was either isolated soy protein containing moderate amounts of isoflavones (ISP56), isolated soy protein containing higher amounts of isoflavones (ISP90), or casein and nonfat dry milk. The results were that both groups consuming the isolated soy protein diets had increased HDL levels (the "good" cholesterol). A significant lowering of non-HDL cholesterol (the "bad" cholesterol) was found in the groups consuming either of the isolated soy proteins in comparison to the group consuming casein dry milk protein. The results indicate that a low cholesterol, low saturated fat diet, combined with soy protein therapy may be effective in positively changing the ratio of HDL to non-HDL in postmenopausal women with high cholesterol levels.13 Although this research is very good, there is even more impressive research regarding soy and cholesterol reduction.

    A meta-analysis (an analysis of many studies that examine the same topic) published in The New England Journal of Medicine clearly demonstrated that soybean protein (which contain isoflavones) has significant cholesterol lowering properties.14 This meta-analysis examined 38 controlled clinical trials. The average soy protein intake was 47 grams per day. The following net changes were associated with the soy intake: total cholesterol decrease of 9.3 percent, LDL cholesterol decrease of 12.9 percent, and triglyceride decrease of 10.5 percent.

    Building bone density
    A review of interventional trials examining isoflavones and bone in animals and humans suggest that including them in the diet results in reduction in bone resorption caused by estrogen deficiency.15 For example, researchers at the University of Illinois at Urbana-Champaign decided to examine the effects of soy protein and its isoflavones on bone density in postmenopausal women. Sixty-six, postmenopausal women were randomly assigned to one of three dietary treatment groups for 24 weeks. One group consumed 40 grams of protein per day obtained from casein and nonfat dry milk. Another group obtained their 40 grams of protein from isolated soy protein containing 1.39 isoflavones per gram of protein (providing a total of 56 mg of isoflavones). The last group consumed their protein from isolated soy protein containing 2.25 mg isoflavones per gram of protein (providing a total of 90 mg of isoflavones). Bone density was measured twice during the study. The results showed that significant increases occurred in both bone mineral content and density in the soy group that received 90 mg of isoflavones. No other effects on bone density were seen in the other soy protein group or the casein group. This study successfully showed that soy protein providing 90 mg of isoflavones daily is effective in decreasing the risks of osteoporosis in postmenopausal women. The authors of this study pointed out that this discovery about the benefits of soy are important for postmenopausal women who cannot or choose not to undergo hormone replacement therapy, which is usually used for prevention and treatment of these two diseases.16

    Black Cohosh
    Black Cohosh has a long and successful history as a support herb used by menopausal women. An extract of Black Cohosh contains phytoestrogens that can reduce luteinizing hormone (LH) secretion.17,18 Surges of LH are associated with hot flashes in menopausal women.

    A newer, highly standardized extract of Black Cohosh has created a great deal of excitement internationally due to the results of a large open study employing 131 doctors and 629 patients. The type of extract used standardized for its triterpene glycosides, calculated as 27-deoxyacteine. Within six to eight weeks, over 80 percent of the patients experienced improvements in both physical and psychological symptoms. These symptoms included hot flashes, profuse perspiration, headache, vertigo, heart palpitation, ringing in the ears, nervousness/irritability, sleep disturbances, and depressive moods. Most patients reported noticeable benefits within four weeks. After six to eight weeks complete resolution of symptoms were achieved in a high number of patients.19

    Red Clover
    Finnish investigations of the phytoestrogen content of various plants revealed that Red Clover contained biologically active estrogenic isoflavones, especially biochanin.20 Furthermore, Red Clover has been shown to improve the elasticity of arteries in menopausal women, which is important given the increased cardiovascular risk associated with menopause.21 Ethnobotanist Steven Foster has described some research, which even shows that the phytoestrogens in Red Clover was found to inhibit the activation of cancer cells.22

    Licorice root
    Although often used for its gastrointestinal benefits / anti-ulcer benefits,23 Licorice root also contains phytoestrogens, which have been shown to induce ovulation in women with irregular periods.24 In addition, the journal Alternative and Complementary Therapies has indicated that Licorice root helps to balance estrogen and progesterone levels;25 clearly a benefit for the menopausal woman.

    Wild Yam
    Wild Yam contains diosgenin, which has phytoestrogenic properties.26 One of the reported uses of this botanical is in the treatment of menopausal symptoms.27

    Pantothenic acid
    Since menopause can be a very stressful state of being for many women, it can potentially affect the adrenal glands, which are often considered to be the "stress glands." This is somewhat problematic, since the adrenal glands produce the hormone DHEA, which can be converted into estrogen to help take over the production of estrogen when the ovaries cease to produce it. When the adrenals are stressed, however, this production of DHEA may be somewhat impaired. Pantothenic acid may be able to help. Pantothenic acid is intimately involved in adrenal function, and the production of adrenal hormones associated with stress.28 Administration of pantothenic acid has been shown to significantly increase the production of adrenal hormones in both animal and human studies.29,30

    Some researchers have suggested that women who are not using HRT should consider the use of certain natural substances as an alternative-including magnesium, which may prove to be effective in prevention and treatment of menopausal-related symptoms.31 Of course magnesium supplementation during menopause makes sense for other reasons as well. For example, research overwhelmingly supports the use of calcium supplementation, alone or in combination with other therapies for slowing or stopping the progression of osteoporosis32-a disease, which is common postmenopausal. One potential problem with calcium supplementation, however, is an increased risk of calcium stone formation. Concomitant supplementation with magnesium may reduce this risk and improve mineralization in the bone.33 This is really no surprise when you consider that magnesium regulates active calcium transport. In fact, at the end of a 2-year study on menopausal women, magnesium supplementation appeared to have prevented fractures and resulted in a significant increase in bone density.34

    Speaking of osteoporosis, research shows that chronically low intakes of the trace mineral boron may pre-dispose people to osteoporosis.35 Changes caused by boron deprivation include reduced blood levels of calcium, as well as in increase in urinary excretion of calcium. Boron deprivation causes changes similar to those seen in women with postmenopausal osteoporosis, and this mineral is needed to prevent the excessive bone loss, which often occurs in postmenopausal women and older men.36 In addition, studies have reported possible improvements in bone mineral density in women who were supplemented with boron.37 For example, research has found that supplementation with 3mg daily of the boron reduced urinary loss of both calcium and magnesium.38

    Given the recent and ongoing concerns about health risks associated with HRT, the use of phytoestrogen supplements and other key nutrients may be a wise alternative. I encourage women to discuss this option with their physicians.

    1. National Cancer Institute: Cancer Facts "Menopausal Hormone Replacement Therapy"
    2. Anoymous, Am J Nat Med, (1996) 3(4) p 7-10.
    3. National Cancer Institute: Cancer Facts "Menopausal Hormone Replacement Therapy"
    4. Okie S. Study: Hormones Don't Protect Women From Heart Disease. Washington Post (2001) Tuesday, July 24. Page A1
    5. Rossouw JE, Anderson GL, Prentice RL, et al. Risks and Benefits of Estrogen Plus Progestin in Healthy Postmenopausal Women: Principal Results From the Women's Health Initiative Randomized Controlled Trial. JAMA. 2002;288(3):321-333.
    6. Study On Risks Of Estrogen-Progestin Combination To Treat Symptoms Of Menopause Prompts Many Questions. Associated Press. July 10, 2002.
    7. The American College of Obstetricians and Gynecologists. ACOG Practice bulletin: Use of botanicals for management of menopausal symptoms. 2001 June 20:
    8. National Cancer Institute: Cancer Facts "Menopausal Hormone Replacement Therapy"
    9. Pagliacci, M., et al, Eur J Cancer, (1994) 30A(11) p 1675-82.
    10. Wang, T., et al, Carcinogenesis, (1996) 17(2) p 271-5
    11. Cassidy, A., et al, Am J Clin Nutr, (1995) 62(1) p 151-3.
    12. Zhou JR, et al, Cancer Research (1998) 58:5231-5238.
    13. Baum J, et al, American Journal of Clinical Nutrition (1998) 68:545-551.
    14. Anderson, J., et al, New Eng J Med, (1995) 333, p 276-82.
    15. Scheiber MD, Rebar RW, Menopause (1999) 6(3):233-41.
    16. Potter SM, et al, Am J Clin Nutr (1998) 68(suppl):1375S -1379S
    17. Brinker, F., The Eclectic Medical Journals, (1996) 2(1) p 2-4.
    18. Duker, E., et al, Planta Med (1991) 57(5) p 420-7.
    19. Anoymous, ibid.
    20. Saloniemi, H., et al, Proc Soc Exp Biol Med (1995) 208(1) p 13-7.
    21. Nestel, PJ, et al, J Clin Endocrinol Metab (1999) 84(3):895-8.
    22. Foster, S., 101 Medicinal Herbs: An Illustrated Guide (1998), Interweave Press, Loveland, Colorado, pp. 168-9.
    23. Foster, S., pp. 132-3.
    24. Reichert, R., Quarterly Review of Natural Medicine (1994) Spring, p 27-33.
    25. Kelly, J. Alternative and Complementary Therapies (1996) November/December, pp. 348-353.
    26. Mirkin, G., JAMA (1991) 265(7) p 912.
    27. Fetrow C, Availa J, Professional's Handbook of Complementary & Alternative Medicines (1999) Springhouse Corp., Springhouse, Pennsylvania, p. 666-668.
    28. Kutsky R, Handbook of Vitamins and Hormones (1973) Van Nostrand Reinhold Company, New York. pp. 208.
    29. Tarasov IuA, Sheibak VM, Moiseenok AG, Vopr (1985) 4
    30. Fidanaza A, Floridi S, Lenti L, Boll Soc Ital Biol Sper (1981) 57(18):1869-72.
    31. Kass-Annese B. Alternative therapies for menopause. Clinical obstetrics and gynecology (2000) 43(1):162-83.
    32. Laulert L, et al, Revista brasileira de enfermagem (1995) 48(2):161-7.
    33. Celotti F; Bignamini A. Dietary calcium and mineral/vitamin supplementation: a controversial problem. Journal of international medical research (1999) 27(1):1-14.
    34. Sojka JE; Weaver CM. Magnesium supplementation and osteoporosis. Nutrition reviews (1995) 53(3):71-4.
    35. Bunker VW, British journal of biomedical science (1994) 51(3):228-40.
    36. Nielsen FH, Magnesium and trace elements (1990) 9(2):61-9.
    37. Volpe SL, Taper LJ, Meacham S, Magnesium research (1993) 6(3):291-6.
    38. Nielson FH, et al, FASEB J (1987) 1:394-97.
  • Menopause is the term used to describe the progressive cessation of menstruation in a woman over time. Menopause typically occurs after a woman’s child-bearing years, between the ages of 45 and 50. Some women, however, experience it as early as 35 and as late as 60 years old. The process of menopause can last for two to six years, during which time a woman’s hormone levels change due to the reduction in the production of estrogen and progesterone in the ovaries as they cease to produce eggs. Physiologically, menopause marks the end of a woman’s childbearing capacity and is a part of her natural aging process.

  • Women everywhere are talking about menopause and hormone replacement therapy (HRT). Is it safe or isn't it? Well, that depends on whom you ask, what studies you read and what media reports you're exposed to.

    Earlier this year, women—and even doctors—became more confused about HRT when the Society of Obstetricians and Gynaecologists of Canada (SOGC) issued a press release saying HRT is safe and effective if women start taking it early in menopause and for less than five years.

  • Menopause is a natural process that for some women brings on a myriad of uncomfortable symptoms. These symptoms usually come from imbalances your physiology that usually stem from poor choices in diet and lifestyle.

    Common perimenopausal complaints include:

    • Weight gain
    • Fatigue
    • Hot flashes
    • Headaches
    • Loss of libido
    • Dry skin
    • Vaginal dryness
    • Mood swings
    • Anxiety
    • Depression
    • Memory problems
    • Insomnia or sleep difficulties
    • Joint and muscle aches and pains

    After menopause, the risk of osteoporosis and heart disease also increase dramatically.

    The Western Approach to Menopause
    To combat perimenopausal symptoms, Western medicine developed synthetic feminine hormones. Hormone replacement therapy (HRT) was promoted as the fountain of youth. It was said to lower the risk of heart disease, strokes, Alzheimer’s, and osteoporosis. But several studies in the early 2000’s, including the Women’s Health Initiative, found mostly the opposite is true: women who take HRT have an increased risk of heart disease, strokes, blood clots, gall bladder disease and invasive breast and ovarian cancer. HRT does help osteoporosis, but not any more than a little weight bearing exercise and a diet high in calcium can.

    The Eastern Approach to Menopause
    Traditional systems of medicine, including Ayurveda and Traditional Chinese Medicine, say that menopause should be a time of gentle and easy transition. The hormonal changes at menopause are part of the natural progression of life. Symptoms only arise if you are out of balance—which usually develop from poor diet and lifestyle choices. Therefore, the best way to improve and control menopausal symptoms is to restore balance to the physiology through healthy diet and lifestyle choices. Then, if any symptoms are still present after you have made these changes, herbs and supplements may be added. If you don’t correct your habits that are creating the imbalances first, then herbs and supplements usually don’t work very well. It’s like trying to mop your floor dry, but forgetting to first turn off the faucet.

    The Natural Prescription
    Begin by cutting out the junk foods especially processed foods, sugar, red meat and excess alcohol. Instead favor organically grown fruits, vegetables, whole grains, nuts, seeds and omega- 3 fatty acids. Also, it is important to

    • Exercise regularly—even as little as 30 minutes of brisk walking every day can have profound benefits.
    • Get the most out of your sleep by going to bed by 10 p.m. and get up before 6 a.m.
    • Minimize stress by practicing an effective stress-reducing technique every day such as meditation, yoga, or deep breathing.

    Herbal Support
    In addition to these healthy diet and lifestyle changes, there are a variety of herbs that can help to alleviate uncomfortable symptoms. For example, research shows that a standardized herbal root extract, called EstroG-100, can effectively reduce many of the symptoms associated with menopause. This formula is composed of three different well-studied plants from China and Korea.

    • Cynanchum wilfordii is a key component of a famous Chinese herbal tonic that has been used for over a thousand years to enhance vitality. It is also been used in traditional Korean medicine to promote healthy aging.
    • Phlomis umbrosa root has been also been used in China for thousands of years to support liver health and detoxification. Because of its strong anti-inflammatory properties, it is useful for a variety of other health conditions including pain relief.
    • Angelica gigas root, also called Dang Gui, is an herb traditionally used in Korea to improve gynecological, cardiovascular and immune system health.

    There have been number of studies, both in-vitro as well as in-vivo, that have confirmed the safety and efficacy of EstroG-100.

    According to tests conducted by Chungbuk National University in South Korea, the herbs in EstroG-100 do not work through estrogen pathways.

    A 2005 prospective randomized, placebo-controlled clinical trial1 was conducted in South Korea with a total of 48 perimenopausal women who were followed for 12 months. At the end of 3 months, the women taking an herbal supplement containing EstroG-100 had significant improvements of their symptoms—in fact, five times better than the placebo group. At the end of 12 months, the herbal group also showed changes in bone markers, which are associated with improved bone density, as well as improvements in the levels of serum triglycerides and human growth hormone.

    In another randomized double-blind placebo-controlled trial2 conducted in California in 2012, 64 women pre-, periand post-menopausal women were assigned to either taking EstroG-100 (31 women) or a placebo (33 women). At the end of 12 weeks the Kuppermam menopausal index (KMI) score, which evaluates 11 symptoms, was significantly reduced in the EstroG-100 group compared to the placebo group. Improvements were seen in hot flashes, insomnia, nervousness, melancholia, dizziness, fatigue, and joint pain. There was also a statistically significant improvement in vaginal dryness in the EstroG-100 group.

    A third randomized, double-blind, placebo-controlled multi-center study of EstroG-100 has just completed with equally impressive results.3

    No Need to Suffer
    There’s no need to suffer with menopausal symptoms. This natural transition of life is meant to go smoothly. Making a few healthy diet and lifestyle changes can dramatically improve or resolve symptoms. There are also herbs that can bring some great relief. Be sure to choose an herbal supplement that has been proven by research to be effective, such as EstroG-100.


    1. Ki Ho Lee, Duck Ju Lee, Sang Man Kim, Sang Hyeun Je, Eun Ki Kim, Hae Seung Han, In Kwon Han, “Evaluation of Effectiveness and Safety of Natural Plants Extract(Estromon®) on Perimenopausal Women for 1Year,” J. Korea Soc. Menopause 2005: 11(1). 16–26
    2. Albert Chang, Bo-Yeon Kwak, Kwontaek Yi, Jae Soo Kim, “The Effect of Herbal Extract (EstroG-100) on Pre-Peri- and Post- Menopausal Women: A Randomized Double-blind, Placebocontrolled Study,” Phytother. Res. 2012(26): 510–6
    3. Duck Joo Lee, Tak Kim, Seok-Kyo Seo, “The Evaluation of the Efficacy and Safety of Herbal Extract (PAC-EX01: EstroG-100) on Menopausal Symptoms: 12 weeks, Multi Center, A randomized, Double-Blind Placebo-Controlled Clinical Study.” Submitted for publication.
  • At best of times, understanding the ebb and flow of women’s hormones through the various stages of their life can seem like a daunting task. To make matters even more challenging, the Allopathic medicine perspective tends to medicalize and pathologize women’s hormonal issues. All too often, the first approach is prescribing hormones either as bio-identical hormones or HRT, both options come with risks.

  • Which supplements should people take to help promote good health, and at what doses? Vitamins? Minerals? Herbs? Nutraceuticals? Perhaps the best answer is before experimenting with exotic dietary supplement ingredients, it first makes sense to start out with the three dietary supplements that everyone should be taking. This includes a multivitamin, vitamin D and omega- fatty acids.


    There is a good case for the daily use of a multivitamin, as a nutrition insurance policy that helps to fill in the gaps for those nutrients people may not be getting in their diet. Furthermore, in a study1 of 90,771 men and women, the regular use of a multivitamin was found to significantly improve adequate intake of nutrients compared to non-users. Also, research2 found that multivitamin supplements are generally well tolerated, do not increase the risk of mortality, cerebrovascular disease, or heart failure, and their use likely outweighs any risk in the general population (and may be particularly beneficial for older people). So, the bottom line is that multivitamins really do work as a nutrition insurance policy.

    Other multivitamin benefits
    In addition to functioning as a nutrition insurance policy, the daily use of a multivitamin may offer other benefits as well.

    Cardiovascular Disease
    A 12-week, randomized, placebo-controlled study3 of 182 men and women (24 to 79 years) found that a multivitamin was able to lower homocysteine levels and the oxidation of LDLcholesterol—both of which are highly beneficial in reducing the risk for cardiovascular disease. Other multivitamin research4 has also demonstrated effectiveness in lowering homocysteine levels.

    A 6-month, randomized, double-blind, placebo-controlled study5 of 87 men and women (30 to 70 years) found that multivitamin use was associated with lower levels of C-reactive protein, a measurement of inflammation associated with cardiovascular disease and other degenerative diseases. Other multivitamin research6 in women has shown similar results.

    A Swedish, population-based, case-control study7 of 1296 men and women (45 to 70 years) who previously had a heart attack and 1685 healthy men and women as controls, found those using a multivitamin were less likely to have a heart attack. Other multivitamin research8 in Swedish women has shown similar results.

    A large-scale, randomized, double-blind, placebo-controlled study9 was conducted with 14,641 male U.S. physicians initially 50 years or older, including 1312 men with a history of cancer, to determine the long-term effects of multivitamin supplementation on the incidence of various types of cancers. Results showed that during a median follow-up of 11.2 years, men with a history of cancer who took a daily multivitamin had a statistically significant reduction in the incidence of total cancer compared to those taking a placebo.

    A human clinical study10 with 96 healthy men (18 to 46 years) examined the effect of multivitamin supplementation in relation to plasma interleukin-6 (IL-6, a pro-inflammatory chemical produced by the body) and anger, hostility, and severity of depressive symptoms. The results showed that plasma IL-6 was associated with anger, hostility, and severity of depressive symptoms, and that multivitamin use was associated with lower plasma IL-6 levels.

    A review11 of the scientific literature indicated that patients complaining of fatigue, tiredness, and low energy levels may have low levels of vitamins and minerals. Certain risk groups like the elderly and pregnant women were identified, as was the role of B-vitamins in energy metabolism. Results found that supplementation with nutrients including B-vitamins (e.g., a multivitamin) can alleviate deficiencies, but supplements must be taken for an adequate period of time.

    A meta-analysis12 of eight randomized and placebo-controlled studies evaluated the influence of diet supplementation on stress and mood. Results showed that supplementation reduced the levels of perceived stress, mild psychiatric symptoms, anxiety, fatigue, and confusion. Supplements containing high doses of B-vitamins (e.g., multivitamins) may be more effective in improving mood states.

    At the ends of our chromosomes are stretches of DNA called telomeres. These telomeres protect our genetic data, making it possible for cells to divide. Each time a cell divides, telomeres get shorter. When they get too short, the cell can no longer divide and becomes inactive or "senescent" or dies. This process is associated with aging. In a cross-sectional analysis of data from 586 women (35 to 74 years), multivitamin use was assessed, and relative telomere length was measured. The results were that multivitamin use was significantly associated with longer telomeres. Compared with nonusers, the relative telomere length was on average 5.1 percent longer among daily multivitamin users. It is possible, therefore, that multivitamins may help us live longer.


    Vitamin D is the "sunshine vitamin," so coined because exposure to the sun's ultraviolet light will convert a form of cholesterol under the skin into vitamin D. This nutrient is best known for its role in helping to facilitate the absorption of calcium and phosphorus (as well as magnesium), and so helping to promote bone health.13 Over the past decade, however, research on vitamin D has identified numerous other roles it plays in human health and wellness, which includes:

    • Inhibiting the uncontrolled proliferation of cells (as in the case of cancer) and stimulating the differentiation of cells (specialization of cells for specific functions).14
    • Helping prevent cancers of the prostate and colon.15,16
    • Functioning as a potent immune system modulator.17,18
    • Helping prevent autoimmune reactions.19,20,21
    • Helping improve insulin secretion.22,23,24
    • Decreasing the risk of high blood pressure via the reninangiotensin system's regulation of blood pressure.25
    • Reducing osteoporotic fractures.26,27,28
    • Reducing the incidence of falls in older adults.29,30
    • Reducing the risk of developing premenstrual syndrome (PMS).31
    • Reducing the prevalence of depression, especially in the elderly.32
    • Reducing the prevalence of urinary infections and lower urinary tract symptoms (e.g., benign prostatic hyperplasia or BPH).33

    Vitamin D deficiency and insufficiency
    Outright vitamin D deficiency is present in 41.6 percent of the U.S. population,34 while vitamin D insufficiency (i.e., lacking sufficient vitamin D) is present in 77 percent of the world's population.35 If you are deficient in vitamin D you will not be able to absorb enough calcium to satisfy your body's calcium needs.36 It has long been known that severe vitamin D deficiency has serious consequences for bone health, but other research indicates that lesser degrees of vitamin D deficiency are common and increase the risk of osteoporosis and other health problems.37,38

    Vitamin D sufficiency is measured by serum 25-hydroxyvitamin D levels in the body.39 Laboratory reference ranges for serum 25-hydroxyvitamin D levels are based upon average values from healthy populations. However, recent research examining the prevention of secondary hyperparathyroidism and bone loss suggest that the range for healthy 25-hydroxyvitamin D levels should be considerably higher. Based upon the most current research, here are the ranges for serum 25-hydroxyvitamin D values:

    • Less than 20–25 nmol/L: Indicates severe deficiency associated with rickets and osteomalacia.40,41
    • 50–80 nmol/L: Previously suggested as normal range.42
    • 75–125 nmol/L: More recent research suggests that parathyroid hormone43,44 and calcium absorption45 are optimized at this level; this is a healthy range.46

    Based upon the 75–125 nmol/L range, it is estimated that one billion people in the world are currently vitamin D deficient.47 Furthermore, research indicates that supplementation with at least 800–1,000 IU daily are required to achieve serum 25-hydroxyvitamin D levels of at least 80 nmol/L.48,49 Furthermore, there are many groups of individuals who currently are at risk for vitamin D deficiency. These include:

    • Exclusively breast-fed infants: Especially if they do not receive vitamin D supplementation and if they have dark skin and/or receive little sun exposure.50
    • Dark skin: People with dark-colored skin synthesize less vitamin D from sunlight than those with light-colored skin.51 In a U.S. study, 42 percent of African American women were vitamin D deficient compared to four percent of white women.52
    • The Elderly: When exposed to sunlight have reduced capacity to synthesize vitamin D.53
    • Those using sunscreen: Applying sunscreen with an SPF factor of eight reduces production of vitamin D by 95 percent.54
    • Those with fat malabsorption syndromes: The absorption of dietary vitamin D is reduced in Cystic fibrosis and cholestatic liver disease.55
    • Those with inflammatory bowel disease: An increased risk of vitamin D deficiency occurs in those with inflammatory bowel disease like Crohn's disease.56
    • Obese individuals: Obesity increases the risk of vitamin D deficiency.57

    Vitamin D2 and D3
    There are two forms of vitamin D available as a dietary supplement: cholecalciferol (vitamin D3) and ergocalciferol (vitamin D2). Cholecalciferol is the form made in the human body, and it is more active than ergocalciferol. In fact, Vitamin D2 potency is less than one third that of vitamin D3.58

    Commercially, ergocalciferol is derived from yeast, and so is considered vegetarian, while cholecalciferol is commonly derived from lanolin (from sheep) or fish oil—although a vegetarian D3 derived from lichen is available.

    Ideal dosing for vitamin D
    The Linus Pauling Institute recommends that generally healthy adults take 2,000 IU of supplemental vitamin D daily.59 The Vitamin D Council states that if well adults and adolescents regularly avoid sunlight exposure, then it is necessary to supplement with at least 5,000 IU of vitamin D daily.60 The Council for Responsible Nutrition recommends 2,000 IU daily for adults.61 Taking a conservative position, at least 2,000 IU of vitamin makes sense for adults.

    Chemically, a fatty acid is an organic acid that has an acid group at one end of its molecule, and a methyl group at the other end.62 Fatty acids are typically categorized in the omega groups 3, 6 and 9 according to the location of their first double bond (there's also an omega 7 group, but these are less important to human health).63 The body uses fatty acids for the formation of healthy cell membranes, the proper development and functioning of the brain and nervous system, and for the production of hormone-like substances called eicosanoids (thromboxanes, leukotrienes, and prostaglandins). These chemicals regulate numerous body functions including blood pressure, blood viscosity, vasoconstriction, immune and inflammatory responses.64

    Deficiency of omega-3 fatty acids
    While omega-3, 6 and 9 fatty acids are all important for different reasons, it is the omega-3 fatty acids (O3FA) that are currently particularly critical—and specifically the O3FA known as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The reason for this current importance is that Western diets are deficient in O3FA, and have excessive amounts of omega-6 fatty acids. While human beings evolved on a diet with approximately a 1:1 ratio of omega-6 to omega-3 fatty acids (EFA), the current Western diet provides about a 16:1 ratio.65 As a matter of fact, a recent Harvard School of Public Health study indicates that Omega-3 deficiency causes 96,000 U.S. deaths per year.66 Other research has clearly shown that excessive amounts of omega-6 fatty acids and a very high omega-6 to omega-3 ratio, as is found in today's Western diets, promote many diseases, including cardiovascular disease, cancer, and inflammatory and autoimmune diseases, whereas increased levels of omega-3 (a low omega-6 to omega-3 ratio) exert protective effects.67

    Benefits of omega-3 fatty acids

    O3FA offer a broad range of benefits in human health. These benefits are listed below categorically:

    Cardiovascular Health
    In several studies O3FA have been shown to help lower triglyceride levels.68 In fact, the FDA has even approved an O3FA product for this purpose.69 Individually, EPA and DHA also have triglyceride-lowering properties. Consuming 1 gram/day of fish oils from fish (about 3 ounces of fatty fish such as salmon) or fish oil supplements has a cardioprotective effect.70

    Evidence suggests increased consumption of O3FA from fish or fish-oil supplements, but not of alpha-linolenic acid, reduces the rates of all-cause mortality, cardiac and sudden death, and possibly stroke.71 Higher consumption of fish and O3FA has been associated with a lower risk of coronary heart disease.72,73 Clinical research shows that DHA supplementation helps increase HDL cholesterol levels (the "good cholesterol").74,75 Supplementation with fish oil produces modest, but significant reductions in systolic and diastolic blood pressure in patients with mild hypertension.76,77,78

    O3FA have been shown to help relieve inflammation caused by a variety of factors.79,80


    Research81 has demonstrated that fish oil supplementation is effective in the treatment of rheumatoid arthritis.

    Clinical research shows that taking supplements with 500 mg EPA, three times daily, modestly but significantly reduces the frequency of hot flashes compared to placebo in menopausal women.82

    Research has shown children with attention deficit/hyperactive disorder (ADHD) may have low plasma levels of EPA and DHA.83,84 Clinical research suggests that supplementation with DHA might improve aggression and social relationships in ADHD children.85

    Macular degeneration
    Increased dietary consumption of DHA is associated with reducing the risk of macular degeneration.86

    Alzheimer's Disease
    Participants who consumed fish once per week or more had 60 percent less risk of Alzheimer's disease compared with those who rarely or never ate fish, and this was attributed to the DHA content of the fish.87

    The sources of omega-3 fatty acids

    To begin with, the overwhelming majority of research on the health benefits of supplementation with O3FA has been conducted using fish oil products. Consequently, a strong argument can be made that fish oil supplements are the preferred source of O3FA. Amongst these, the primary fish used commercially as the source from which O3FA are derived include mackerel, herring, tuna, halibut, salmon and cod liver.88 Although some fish are touted as superior over others as sources for supplemental fish oil, it is the opinion of this author that they all provide acceptable sources of omega-3s. Still, there are other sources of O3FA besides fish oil. This includes squid, krill, flax seed oil and algae oil.

    Squid-derived O3FA are derived from by-products of squid that are usually discarded when squid are commercially fished, and provides a much higher concentration of DHA (up to 50 percent) than do fish oil. However, there is a lack of human clinical data on squid-source O3FA, although they likely will have similar effects as fish oil.

    Krill oil derived from the shrimp-like crustacean know as krill contain significant amounts of the EPA and DHA omega-3 fatty acids, as well as phospholipids (e.g., phosphatidylcholine),89 vitamin A, vitamin E and astaxanthin, a powerful carotenoid antioxidant.90,91 Human clinical research92 has shown that krill oil has greater absorption than fish oil—although krill provides significantly less EPA/DHA per gram than fish oil.

    Flaxseed oil contains about 52–55 percent omega-3s, but as alpha-linolenic acid (ALA), not EPA/DHA.93 This is significant since ALA has to be converted to EPA and DHA before it will provide the much-touted health benefits attributed to O3FA. This is problematic since studies indicate that in men approximately eight percent of ALA is converted to EPA and 0–4 percent is converted to DHA.94 In women, approximately 21 percent of dietary ALA is converted to EPA and nine percent is converted to DHA.95 This is not to say that flaxseed oil has no value. It does, but just not as significant a value as fish oil.

    Algae oil
    Certain algae extracts provide a vegetarian source of O3FA—but in this case the O3FA are EPA and DHA, not ALA. Consequently, for vegetarians, algae oil is a viable substitute for fish oil. That being said, human clinical research on algae oil sources of O3FA is limited, and the cost is far more than fish oil.


    1. Murphy SP, White KK, Park SY, Sharma S. Multivitamin-multimineral supplements' effect on total nutrient intake. Am J Clin Nutr. 2007 Jan;85 (1):280S–4S.
    2. Ward E. Addressing nutritional gaps with multivitamin and mineral supplements. Nutr J.2014 Jul 15;13(1):72. 43 Earnest CP, Wood KA, Church TS.
    3. Complex Multivitamin Supplementation Improves Homocysteine and Resistance to LDL-C Oxidation. J Am Coll Nutr. 2003;22(5):400–7.
    4. den Heijer M, Brouwer IA, Bos GM, et al. Vitamin supplementation reduces blood homocysteine levels: a controlled trial in patients with venous thrombosis and healthy volunteers. Arterioscler Thromb Vasc Biol. 1998 Mar;18(3):356–61.
    5. Church TS, Earnest CP, Wood KA. James B. Kampert. Reduction of C-Reactive Protein Levels Through Use of a Multivitamin. Am J Med. 2003;115:702–7.
    6. Wang C, Li Y, Zhu K, Dong YM, Sun CH. Effects of supplementation with multivitamin and mineral on blood pressure and C-reactive protein in obese Chinese women with increased cardiovascular disease risk. Asia Pac J Clin Nutr. 2009;18(1):121–30.
    7. Holmquist C, Larsson S, Wolk A, de Faire U. Multivitamin Supplements Are Inversely Associated with Risk of Myocardial Infarction in Men and Women— Stockholm Heart. Epidemiology Program (SHEEP). J Nutr.2003;133: 2650–4.
    8. Rautiainen S, Akesson A, Levitan EB, Morgenstern R, Mittleman MA, Wolk A. Multivitamin use and the risk of myocardial infarction: a population-based cohort of Swedish women. Am J Clin Nutr. 2010 Nov;92(5):1251–6.
    9. Gaziano JM, Sesso HD, Christen WG, Bubes V, Smith JP, MacFadyen J, Schvartz M, Manson JE, Glynn RJ, Buring JE. Multivitamins in the prevention of cancer in men: the Physicians' Health Study II randomized controlled trial. JAMA. 2012 Nov 14;308(18):1871–80.
    10. Suarez EC. Plasma interleukin-6 is associated with psychological coronary risk factors: moderation by use of multivitamin supplements. Brain Behav Immun. 2003 Aug;17(4):296–303.
    11. Huskisson E, Maggini S, Ruf M. The role of vitamins and minerals in energy metabolism and well-being. J Int Med Res. 2007 May–Jun;35(3):277–89.
    12. Long SJ, Benton D. Effects of vitamin and mineral supplementation on stress, mild psychiatric symptoms, and mood in nonclinical samples: a metaanalysis. Psychosom Med. 2013 Feb;75(2):144–53.
    13. Holick MF. Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis. Am J Clin Nutr. 2004;79(3):362–71.
    14. Ibid.
    15. Lin R, White JH. The pleiotropic actions of vitamin D. Bioessays. 2004; 26(1):21–8.
    16. Gorham ED, Garland CF, Garland FC, et al. Vitamin D and prevention of colorectal cancer. J Steroid Biochem Mol Biol. 2005;97(1-2):179–94.
    17. Griffin MD, Xing N, Kumar R. Vitamin D and its analogs as regulators of immune activation and antigen presentation. Annu Rev Nutr. 2003;23:117–45.
    18. Hayes CE, Nashold FE, Spach KM, Pedersen LB. The immunological functions of the vitamin D endocrine system. Cell Mol Biol. 2003;49(2):277–300.
    19. Ibid.
    20. Munger KL, Zhang SM, O'Reilly E, et al. Vitamin D intake and incidence of multiple sclerosis. Neurology 2004;62:60–5.
    21. Merlino LA, Curtis J, Mikuls TR, et al. Vitamin D intake is inversely associated with rheumatoid arthritis. Arthritis Rheum 2004;50:72–7.
    22. Zeitz U, Weber K, Soegiarto DW, Wolf E, Balling R, Erben RG. Impaired insulin secretory capacity in mice lacking a functional vitamin D receptor. FASEB J. 2003;17(3):509–11.
    23. Borissova AM, Tankova T, Kirilov G, Dakovska L, Kovacheva R. The effect of vitamin D3 on insulin secretion and peripheral insulin sensitivity in type 2 diabetic patients. Int J Clin Pract. 2003;57(4):258–61.
    24. Inomata S, Kadowaki S, Yamatani T, Fukase M, Fujita T. Effect of 1 alpha (OH)-vitamin D3 on insulin secretion in diabetes mellitus. Bone Miner. 1986;1(3):187–192.
    25. Li YC, Kong J, Wei M, Chen ZF, Liu SQ, Cao LP. 1,25-Dihydroxyvitamin D(3) is a negative endocrine regulator of the renin-angiotensin system. J Clin Invest. 2002;110(2):229–38.
    26. Feskanich D, Willett WC, Colditz GA. Calcium, vitamin D, milk consumption, and hip fractures: a prospective study among postmenopausal women. Am J Clin Nutr. 2003;77(2):504–511.
    27. Bischoff-Ferrari HA, Willett WC, Wong JB, Giovannucci E, Dietrich T, Dawson-Hughes B. Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials. JAMA. 2005;293(18):2257–64.
    28. Bischoff-Ferrari HA, Giovannucci E, Willett WC, Dietrich T, Dawson-Hughes B. Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes. Am J Clin Nutr. 2006;84(1):18–28.
    29. Bischoff-Ferrari HA, Dawson-Hughes B, Willett WC, et al. Effect of Vitamin D on falls: a meta-analysis. JAMA 2004;291:1999–2006.
    30. Bischoff HA, Stahelin HB, Dick W, et al. Effects of vitamin D and calcium supplementation on falls: a randomized controlled trial. J Bone Miner Res 2003;18:343–51.
    31. Bertone-Johnson ER, Hankinson SE, Bendich A, et al. Calcium and vitamin D intake and risk of incident premenstrual syndrome. Arch Intern Med 2005;165:1246–52.
    32. Hoogendijk WJG, Lips P, Dik MG, Deeg DJH, Beekman ATF, Penninx BWJH. Depression Is Associated With Decreased 25-Hydroxyvitamin D and Increased Parathyroid Hormone Levels in Older Adults. Archives of General Psychiatry 2008; 65(5):495.
    33. Vaughan CP, Johnson TM 2nd, Goode PS, Redden DT, Burgio KL, Markland AD. Vitamin D and lower urinary tract symptoms among US men: results from the 2005–2006 National Health and Nutrition Examination Survey. Urology. 2011 Dec;78(6):1292–7.
    34. Forrest KY, Stuhldreher WL. Prevalence and correlates of vitamin D deficiency in US adults. Nutr Res. 2011;31(1):48–54.
    35. Ginde AA, Liu MC, Camargo CA Jr. Demographic differences and trends of vitamin D insufficiency in the US population, 1988-2004. Arch Intern Med. 2009;169:626–32.
    36. Holick MF. Vitamin D: A millenium perspective. J Cell Biochem. 2003;88(2):296–307.
    37. Heaney RP. Long-latency deficiency disease: insights from calcium and vitamin D. Am J Clin Nutr. 2003;78(5):912–9.
    38. Zittermann A. Vitamin D in preventive medicine: are we ignoring the evidence? Br J Nutr. 2003;89(5):552–72.
    39. Wharton B, Bishop N. Rickets. Lancet. 2003;362(9393):1389–1400. 40 Heaney RP. Long-latency deficiency disease: insights from calcium and vitamin D. Am J Clin Nutr. 2003;78(5):912–919.
    40. Ibid. 79
    41. Malabanan A, Veronikis IE, Holick MF. Redefining vitamin D insufficiency. Lancet. 1998;351(9105):805–6.
    42. Chapuy MC, Preziosi P, Maamer M, et al. Prevalence of vitamin D insufficiency in an adult normal population. Osteoporos Int. 1997;7(5):439–43.
    43. Thomas MK, Lloyd-Jones DM, Thadhani RI, et al. Hypovitaminosis D in medical inpatients. N Engl J Med. 1998;338(12):777–83.
    44. Heaney RP, Dowell MS, Hale CA, Bendich A. Calcium absorption varies within the reference range for serum 25-hydroxyvitamin D. J Am Coll Nutr. 2003;22(2):142–6.
    45. Holick MF. Vitamin D deficiency: what a pain it is. Mayo Clin Proc. 2003;78(12):1457–9.
    46. Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357(3):266–281.
    47. Vieth R. Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety. Am J Clin Nutr. 1999;69(5):842–56.
    48. Tangpricha V, Koutkia P, Rieke SM, Chen TC, Perez AA, Holick MF. Fortification of orange juice with vitamin D: a novel approach for enhancing vitamin D nutritional health. Am J Clin Nutr. 2003;77(6):1478–83.
    49. Wagner CL, Greer FR, and the Section on Breastfeeding and Committee on Nutrition. Prevention of rickets and vitamin D deficiency in infants, children, and adolescents. American Academy of Pediatrics. 2008;122(5):1142–52.
    50. Ibid. 53
    51. Nesby-O'Dell S, Scanlon KS, Cogswell ME, et al. Hypovitaminosis D prevalence and determinants among African American and white women of reproductive age: third National Health and Nutrition Examination Survey, 1988-1994. Am J Clin Nutr. 2002;76(1):187–92.
    52. Harris SS, Soteriades E, Coolidge JA, Mudgal S, Dawson-Hughes B. Vitamin D insufficiency and hyperparathyroidism in a low income, multiracial, elderly population. J Clin Endocrinol Metab. 2000;85(11):4125–30.
    53. Ibid. 53
    54. Food and Nutrition Board, Institute of Medicine. Vitamin D. Dietary Reference Intakes: Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. Washington D.C.: National Academies Press; 1999:250–87.
    55. Jahnsen J, Falch JA, Mowinckel P, Aadland E. Vitamin D status, parathyroid hormone and bone mineral density in patients with inflammatory bowel disease. Scand J Gastroenterol. 2002;37(2):192–9.
    56. Arunabh S, Pollack S, Yeh J, Aloia JF. Body fat content and 25-hydroxyvitamin D levels in healthy women. J Clin Endocrinol Metab. 2003;88(1):157–161.
    57. Armas LA, Hollis BW, Heaney RP. Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab. 2004;89(11):5387–91.
    58. Higdon J, Drake VJ, DeLuca HF.Vitamin D. The Linus Pauling Institute Micronutrient Information Center 2000–2010; Last updated 11/30/10. Retrieved December 6, 2010 from
    59. Understanding Vitamin D Cholecalciferol. The Vitamin D Council, n.d., Retrieved December 6, 2010 from
    60. CRN Reacts to Institute of Medicine DRI Recommendations for Vitamin D. November 30, 2010. Retrieved December 6, 2010 from
    61. Whitney EN, Cataldo CB, Rolfes SR. Understanding Normal and Clinical Nutrition, 5th ed. Belmont, CA:West/Wadsworth; 1998:141–75.
    62. Jones PJH, Papamandjaris AA. "Chapter 10 - Lipids: Cellular Metabolism" IN Present Knowledge in Nutrition, 8th ed. Bowman BA, Russell RM (eds). Washington, DC: ILSI Press; 2001:104–14
    63. Davis B. Essential Fatty Acids in Vegetarian Nutrition. Andrews University Nutrition Department. Accessed August 18, 2005 from
    64. Simopoulos AP. The importance of the ratio of omega-6/omega-3 essential fatty acids. Biomed Pharmacother. 2002;56(8):365–79.
    65. Danaei G, Ding EL, Mozaffarian D, et al. The Preventable Causes of Death in the United States: Comparative Risk Assessment of Dietary, Lifestyle, and Metabolic Risk Factors. PLoS Med. 2009 Apr 28;6(4):e1000058.
    66. Ibid. 105
    67. Harris WS. n-3 fatty acids and serum lipoproteins: human studies. Am J Clin Nutr. 1997;65(5 Suppl):1645S–54S.
    68. Lovaza: Omega-3 Acid Ethyl Esters. Retrieved August 6, 2009 from
    69. Kris-Etherton PM, Harris WS, Appel LJ. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation. 2002;106(21):2747–57.
    70. Wang C, Harris WS, Chung M, et al. n-3 Fatty acids from fish or fish-oil supplements, but not alpha-linolenic acid, benefit cardiovascular disease outcomes in primary- and secondary-prevention studies: a systematic review. Am J Clin Nutr. 2006;84(1):5–17.
    71. Hu FB, Bronner L, Willett WC, et al. Fish and omega-3 fatty acid intake and risk of coronary heart disease in women. JAMA. 2002;287(14):1815–21.
    72. Jarvinen R, Knekt P, Rissanen H, Reunanen A. Intake of fish and long-chain n-3 fatty acids and the risk of coronary heart mortality in men and women. Br J Nutr. 2006;95(4):824–9.
    73. Agren JJ, Hanninen O, Julkunen A, et al. Fish diet, fish oil and docosahexaenoic acid rich oil lower fasting and postprandial plasma lipid levels. Eur J Clin Nutr 1996;50:765–71.
    74. Mori TA, Burke V, Puddey IB, et al. Purified eicosapentaenoic and docosahexaenoic acids have differential effects on serum lipids and lipoproteins, LDL particle size, glucose, and insulin in mildly hyperlipidemic men. Am J Clin Nutr 2000;71:1085–94.
    75. Prisco D, Paniccia R, Bandinelli B, et al. Effect of medium-term supplementation with a moderate dose of n-3 polyunsaturated fatty acids on blood pressure in mild hypertensive patients. Thromb Res 1998;1:105–12.
    76. Toft I, Bonaa KH, Ingebretsen OC, et al. Effects of n-3 polyunsaturated fatty acids on glucose homeostasis and blood pressure in essential hypertension. A randomized, controlled trial. Ann Intern Med 1995;123:911–8.
    77. Yosefy C, Viskoper JR, Laszt A, et al. The effect of fish oil on hypertension, plasma lipids and hemostasis in hypertensive, obese, dyslipidemic patients with and without diabetes mellitus. Prostaglandins Leukot Essent Fatty Acids 1999;61:83–7.
    78. Wall R, Ross RP, Fitzgerald GF, Stanton C. Fatty acids from fish: the anti-inflammatory potential of long-chain omega-3 fatty acids. Nutr Rev. 2010;68(5):280–9.
    79. Calder PC. n-3 polyunsaturated fatty acids, inflammation, and inflammatory diseases. Am J Clin Nutr. 2006;83:1505S–19S.
    80. Fortin PR, Lew RA, Liang MH, et al. Validation of a meta-analysis: the effects of fish oil in rheumatoid arthritis. J Clin Epidemiol. 1995;48(11):1379–90.
    81. Lucas M, Asselin G, Merette C, et al. Effects of ethyl-eicosapentaenoic acid omega-3 fatty acid supplementation on hot flashes and quality of life among middle-aged women: a double-blind, placebo-controlled, randomized clinical trial. Menopause. 2009;16:357–66.
    82. Stevens LJ, Zentall SS, Deck JL, et al. Essential fatty acid metabolism in boys with attention-deficit hyperactivity disorder. Am J Clin Nutr. 1995;62:761–8.
    83. Voigt RG, Llorente AM, Jensen CL, et al. A randomized, double-blind, placebo-controlled trial of docosahexaenoic acid supplementation in children with attention-deficit/hyperactivity disorder. J Pediatr. 2001;139:189–6.
    84. Hamazaki T, Hirayama S. The effect of docosahexaenoic acid-containing food administration on symptoms of attention-deficit/hyperactivity disorder-a placebo-controlled double-blind study. Eur J Clin Nutr. 2004;58:838.
    85. Cho E, Hung S, Willet W, et al. Prospective study of dietary fat and the risk of age-related macular degeneration. Am J Clin Nutr. 2001;73:209–18.
    86. Morris MC, Evans DA, Bienias JL, et al. Consumption of fish and n-3 fatty acids and risk of incident Alzheimer disease. Arch Neurol. 2003;60:940–6.
    87. MedlinePlus. Fish Oil. U.S. National Library of Medicine. Last reviewed–12/10/2011.
    88. Bottino NR. Lipid composition of two species of Antarctic krill: Euphausia superba and E. crystallorophias. Comp Biochem Physiol B 1975;50:479–84.
    89. Ibid.
    90. Dunlap WC, Fujisawa A, Yamamoto Y, et al. Notothenioid fish, krill and phytoplankton from Antarctica contain a vitamin E constituent (alphatocomonoenol) functionally associated with cold-water adaptation. Comp Biochem Physiol B Biochem Mol Biol 2002;133:299–305.
    91. Ulven SM, Kirkhus B, Lamglait A, Basu S, Elind E, Haider T, Berge K, Vik H, Pedersen JI. Metabolic effects of krill oil are essentially similar to those of fish oil but at lower dose of EPA and DHA, in healthy volunteers. Lipids 2011;46(1):37–46.
    92. Vereshagin AG and Novitskaya GV. The triglyceride composition of linseed oil. Journal of the American Oil Chemists' Society 1965;42:970–4.
    93. Burdge GC, Jones AE, Wootton SA. Eicosapentaenoic and docosapentaenoic acids are the principal products of alpha-linolenic acid metabolism in young men. Br J Nutr. 2002;88(4):355–64.
    94. Burdge GC, Wootton SA. Conversion of alpha-linolenic acid to eicosapentaenoic, docosapentaenoic and docosahexaenoic acids in young women. Br J Nutr. 2002;88(4):411–20.
  • Dehydroepiandrosterone (DHEA) is an important hormone produced in the adrenal glands and liver1, and in men, the testes. DHEA and its sulfate ester, dehydroepiandrosterone sulfate (DHEA-S), are interconvertible. DHEA-S is the storage form of DHEA.2,3 DHEA can then be metabolized to androstenedione, the major human precursor to androgens and estrogens4,5—although DHEA doesn’t have direct estrogenic or androgenic activity.6 In most individuals, the production of DHEA normally peaks during the mid-’20s and then begins a steady, progressive decrease of up to 90 percent with aging.7 This decrease is associated with a host of age-related syndromes and conditions, including a concurrent reduction in protein formation, a decrease in muscle mass, and an increase in body fat.8 There are no good dietary sources of DHEA other than by way of supplementation.

    7-keto DHEA is a metabolite of DHEA and may prove to be a safer alternative. Unlike DHEA, 7-keto-DHEA is not converted to androgens and estrogens.9,10,11 Oral or topical administration of 7-keto-DHEA does not affect plasma levels of steroid hormones.12,13Similarly to DHEA, 7-keto-DHEA is rapidly converted to the sulfated form, known as 7-keto-DHEAS14.

    Areas Of Benefit
    Clinical studies have been conducted on supplementation with both DHEA and 7-keto-DHEA. Based upon that research, DHEA offers potential benefits for adrenal support, youthful skin, sexual support, bone mineral density, mood support/ mental function, healthy inflammatory response in body tissues, fatigue reduction, menopause, weight loss, and insulin sensitivity. Clinical studies on 7-keto DHEA have identified three major areas of potential benefit, including weight loss, cognitive function, and immune function. Following is an overview of the research on each of these dietary supplement ingredients.

    DHEA: Adrenal Support
    In individuals with suboptimal adrenal function, daily supplementation with 20–50 mg DHEA seems to improve feelings of well-being, skin and hair, and sexuality responsiveness.15,16 DHEA also helps support healthy maturation of the adrenal glands in children with suboptimal adrenal function.17

    DHEA: Youthful Skin
    As previously discussed. DHEA levels decline with age. In research with individuals 60–79 years old, taking 50 mg DHEA daily helped reverse certain parameters of aging skin. Subjects experienced an increase in epidermal thickness, sebum production, skin hydration, and decrease facial skin pigmentation.18

    DHEA: Sexual Support
    Aging males supplemented with 50 mg DHEA daily for six months experienced improvements in parameters of male performance, including erection, orgasmic function, sexual desire, and overall sexual satisfaction. DHEA helped improve male performance in men with suboptimal blood pressure balance or whose performance was suboptimal for unknown reasons, but did not improve performance in individuals with diabetes or neurological disorders.19,20

    In postmenopausal women, clinical evidence has demonstrated that a single 300 mg dose of DHEA improved sexual response, including significantly greater mental and physical sexual arousal.21 Furthermore, vaginal application of DHEA was found to be effective in reducing vaginal atrophy in elderly postmenopausal women.22

    DHEA: Bone Mineral Density
    Loss of bone mineral density (BMD) is common with aging. Daily supplementation with 50–100 mg DHEA has been shown to improve BMD in older women and men with suboptimal BMD.23,24 It also helps improve BMD in younger women with eating disorders.25

    DHEA: Mood Support / Mental Function
    Experiencing moodiness or “the blues” is common during the lifecycle but can increase with age.26Some clinical research suggests that taking DHEA orally might improve symptoms of moodiness in elderly subjects.27,28,29 Taking DHEA orally seems to improve healthy mental function in individuals with suboptimal perception or expression of reality.30

    DHEA: Healthy Inflammatory Response In Body Tissues
    Some individuals experience acute and chronic inflammation of various tissues of the body resulting from an attack by their body’s own immune system. Taking DHEA orally in conjunction with conventional treatment may help support a healthy inflammatory response in various tissues.31,32,33,34,35,36,37 It may also help promote the normalization of symptoms such as muscle ache.38 In addition, DHEA also seems to improve bone mineral density in such individuals whose conventional medications adversely affect bone mineral density.39,40,41

    DHEA: Fatigue Reduction
    Some individuals, who experience a period of high physical and/or emotional stress, also experience the onset of fatigue of a chronic nature. DHEA may be able to help. In a clinical study, supplementation with DHEA led to a significant reduction in associated pain, fatigue, limitations in activities of daily living, helplessness, anxiety, difficulty thinking, poor memory, and sexual problems over the period of the study.42

    DHEA: Menopause
    In a clinical study, 25 mg of DHEA daily increased the levels of all the hormones that derive from DHEA metabolism. It also increased neurosteroids and endorphin levels. The results were an improvement of vasomotor symptoms such as hot flashes, as well as psychological symptoms throughout 12 months of therapy.43

    DHEA: Weight Loss & Insulin Sensitivity
    In a randomized, double-blind, placebo-controlled study, fiftysix elderly subjects took 50 mg DHEA daily for six months. Subjects taking the DHEA experienced a significant decrease in abdominal fat, and improvements in insulin sensitivity compared to those using the placebo.44

    7-keto: Weight Loss
    7-keto-DHEA is thought to be beneficial in weight loss by increasing metabolism and thermogenesis. Early evidence in animals suggests 7-keto-DHEA can increase thermogenesis, possibly by stimulation of thermogenic enzymes in the liver45 ; however this effect has not yet been reported in humans. Clinical evidence suggests 7-keto-DHEA might increase basal metabolism.

    In obese patients, 7-keto-DHEA can significantly increase the thyroid hormone triiodothyronine (T3) when used over four weeks.46 This effect on thyroid function may positively influence metabolism47, helping patients reduce body weight and body fat. In fact, one clinical study seems to support the hypothesis that the supplement can enhance weight loss.

    Thirty overweight adults were randomized into a prospective, double-blind, placebo controlled eight-week study.48 Fifteen subjects received 100 mg 7-Keto DHEA twice per day whereas the other 15 subjects received a matching placebo. All subjects exercised three times per week, 60 minutes per session of cross-training (aerobic and anaerobic) under the supervision of an exercise physiologist. The exercise plus 7-Keto DHEA group lost a significant amount of body weight as compared with the exercise plus placebo group.

    When analyzed per a four-week interval, the 7-Keto DHEA group lost 3.17 lbs per interval, whereas placebo lost 1.09 lbs. In terms of actual body composition changes, the exercise plus 7-Keto DHEA group lost 1.8 percent body fat as compared to 0.57 percent for the placebo group. When viewed as a change in body fat per four-week interval, the 7-Keto DHEA group lost 0.89 percent body fat per interval as compared to 0.29 percent for the placebo.

    In a later randomized, double-blind, placebo-controlled, crossover trial49, 7-Keto DHEA was tested in overweight adults maintained on a calorie-restricted diet to determine efficacy in increasing the resting metabolic rate (RMR). The results were that RMR increased significantly by 1.4 percent in the 7-Keto DHEA group, whereas RMR decreased by 3.9 percent in the placebo group. In this study, 7-Keto reversed the decrease in RMR normally associated with dieting and was generally well tolerated with no serious adverse events.

    7-Keto: Cognitive Function
    Research has indicated that that DHEA administration might be beneficial in terms of neuroprotection against agerelated loss of brain functions like learning and memory.50 Furthermore, DHEA showed insignificant effects on both learning/memory ability in aging rats.51 Higher DHEAS levels are also independently and favorably associated with executive function, concentration, and working memory in humans.52 In addition, other research suggests that 7-keto-DHEA improves chemically-induced and age-related memory impairment.53

    7-Keto: Immune Function
    7-keto DHEA has also been studied for its potential immuneboosting properties. This includes immunomodulatory effects by stimulating interleukin-2 production by human lymphocytes in-vitro.54 Researchers think that it may also stimulate the activity and effectiveness of T-lymphocytes. These T-lymphocytes may in turn stimulate additional immune system functions.55 Studies based on these observations suggest that 7-keto DHEA may have a future as an important immune system enhancer.56,57 Thus, 7-keto DHEA could prove to be therapeutically useful in a wide range of conditions. Studies suggest that DHEA may reduce the replication of certain types of viruses.58


    1. Lardy H, Partridge B, Kneer N, Wei Y. Ergosteroids: induction of thermogenic enzymes in liver of rats treated with steroids derived from dehydroepiandrosterone. Proc Natl Acad Sci U S A 1995;92:6617–9.
    2. Moffat SD, Zonderman AB, Harman M, et al. The relationship between longitudinal declines in dehydroepiandrosterone sulfate concentrations and cognitive performance in older men. Arch Int Med 2000;160:2193–8.
    3. Pepping J. DHEA: dehydroepiandrosterone. Am J Health Syst Pharm 2000;57:2048-50, 2053– 4, 2056.
    4. Oelkers W. Dehydroepiandosterone for adrenal insufficiency (editorial). N Engl J Med 1999;341:1073– 4.
    5. van Vollenhoven RF. Dehydroepiandrosterone in systemic lupus erythematosus. Rheum Dis Clin North Am 2000;26:349- 62.
    6. Tchernof A, Labrie F. Dehydroepiandrosterone, obesity and cardiovascular disease risk: a review of human studies. Eur J Endocrinol 2004;151:1– 14.
    7. Mortola J, Yen SSC. The Effects of Oral Dehydroepiandrosterone on Endocrine-Metabolic Parameters in Postmenopausal Women. J Clin Endocrin 1990;71(3): 696–704.
    8. Morales AJ, Nolan JJ, Nelson JC, Yen SS. Effects of replacement dose of dehydroepiandrosterone in men and women of advancing age. J Clin Endocrin 1994;78(6):1360– 7.
    9. Lardy H, Partridge B, Kneer N, Wei Y. Ergosteroids: induction of thermogenic enzymes in liver of rats treated with steroids derived from dehydroepiandrosterone. Proc Natl Acad Sci U S A 1995;92:6617–9.
    10. Davidson MH, Weeks C, Lardy H, et al. Clinical Safety and Endocrine Effects of 7-KETO-DHEA. Abstract presented at: Experimental Biology 98, April 19-22, 1998, San Francisco, CA. Abstract obtained from Humanetics Corporation website.
    11. Colker CM, Torina GC, Swain MA, Kalman DS. Double-Blind Study Evaluating the Effects of Exercise Plus 3-Acetyl-7-oxodehydroepiandrosterone on Body Composition and the Endocrine System in Overweight Adults. Journal of Exercise Physiology Online 1999;2(4):Abstract #30.
    12. Davidson M, Marwah A, Sawchuk RJ, et al. Safety and pharmacokinetic study with escalating doses of 3-acetyl-7-oxo-dehydroepiandrosterone in healthy male volunteers. Clin Invest Med 2000;23:300–10.
    13. Sulcova J, Hill M, Masek Z, et al. Effects of transdermal application of 7-oxo-DHEA on the levels of steroid hormones, gonadotropins and lipids in healthy men. Physiol Res 2001;50:9– 18.
    14. Davidson M, Marwah A, Sawchuk RJ, et al. Safety and pharmacokinetic study with escalating doses of 3-acetyl-7-oxo-dehydroepiandrosterone in healthy male volunteers. Clin Invest Med 2000;23:300–10.
    15. Arlt W, Callies F, van Vlijmen JC, et al. Dehydroepiandosterone replacement in women with adrenal insufficiency. N Engl J Med 1999;341:1013–20.
    16. Johannsson G, Burman P, Wiren L, et al. Low dose dehydroepiandrosterone affects behavior in hypopituitary androgen-deficient women: a placebo-controlled trial. J Clin Endocrinol Metab 2002;87:2046– 52.
    17. Kim SS, Brody KH. Dehydroepiandrosterone replacement in Addison’s disease. Eur J Obstet Gynecol Reprod Biol 2001;97:96– 7.
    18. Baulieu EE, Thomas G, Legrain S, et al. Dehydroepiandrosterone (DHEA), DHEA sulfate, and aging. Contribution of the DHEAge study to a sociobiomedical issue. Proc Natl Acad Sci U S A 2000;97:4279- 84.
    19. Reiter WJ, Pycha A, Schatzl G, et al. Dehydroepiandosterone in the treatment of erectile dysfunction: A prospective, double-blind, randomized, placebo-controlled study. Urol 1999;53:590– 5.
    20. Reiter WJ, Schatzl G, Mark I, et al. Dehydroepiandrosterone in the treatment of erectile dysfunction in patients with different organic etiologies. Urol Res 2001;29:278–81.
    21. Hackbert L, Heiman JR. Acute dehydroepiandrosterone (DHEA) effects on sexual arousal in postmenopausal women. J Womens Health Gend Based Med 2002;11:155– 62.
    22. Labrie F, Diamond P, Cusan L, et al. Effect of 12 month dehydroepiandrosterone replacement therapy on bone, vagina, and endometrium in postmenopausal women. J Clin Endocrinol Metab 1997;82:3498–505.
    23. Sun Y, Mao M, Sun L, et al. Treatment of osteoporosis in men using dehydroepiandrosterone sulfate. Chin Med J (Engl) 2002;115:402–4.
    24. Villareal DT, Holloszy JO, Kohrt WM. Effects of DHEA replacement on bone mineral density and body composition in elderly women and men. Clin Endocrinol (Oxf) 2000;53:561– 8.
    25. Gordon CM, Grace E, Emans SJ, et al. Effects of oral dehydroepiandrosterone on bone density in young women with anorexia nervosa: a randomized trial. J Clin Endocrinol Metab 2002;87:4935– 41.
    26. Hybels CF and Blazer DG. Epidemiology of late-life mental disorders. Clinics in Geriatric Medicine 2003; 19:663– 696.
    27. Wolkowitz OM, Reus VI, Keebler A, et al. Double-blind treatment of major depression with dehydroepiandosterone. Am J Psychiatry 1999;156:646–9.
    28. Bloch M, Schmidt PJ, Danaceau MA, et al. Dehydroepiandrosterone treatment of midlife dysthymia. Biol Psychiatry 1999;45:1533–41.
    29. Wolkowitz OM, Reus VI, Manfredi F, et al. Dehydroepiandrosterone (DHEA) treatment of depression. [Abstract] Biol Psychiatry 1997;41:311–8.
    30. Strous RD, Maayan R, Lapidus R, et al. Dehydroepiandrosterone augmentation in the management of negative, depressive, and anxiety symptoms in schizophrenia. Arch Gen Psychiatry 2003;60:133– 41.
    31. van Vollenhoven RF, Morabito LM, Engleman EG, et al. Treatment of systemic lupus erythematosus with dehydroepiandrosterone: 50 patients treated up to 12 months. J Rheumatol 1998;25:285– 9.
    32. van Vollenhoven RF, Engleman EG, McGurie JL. Dehydroepiandrosterone in Systemic Lupus Erythematosus. Arth Rheum 1995;38:1826– 31.
    33. van Vollenhoven RF, Engleman EG, McGuire JL. Dehydroepiandrosterone in systemic lupus erythematosus. Arthritis Rheum1994;37:1305–10.
    34. an Vollenhoven RF, Park JL, Genovese MC, et al. A double-blind, placebo-controlled, clinical trial of dehydroepiandrosterone in severe lupus erythematosus. Lupus 1999;8:181–7.
    35. Mease PJ, Merrill JT, Lahita RG, et al. GL701 (prasterone, dehydroepiandrosterone) improves systemic lupus erythematosus. 2000 American College of Rheumatology Meeting. Philadelphia, PA. October 29–November 2. Abstract 1230.
    36. Petri MA, Mease PJ, Merrill JT, et al. Effects of prasterone on disease activity and symptoms in women with active systemic lupus erythematosus. Arthritis Rheum 2004;50:2858–68.
    37. Petri MA, Lahita RG, Van Vollenhoven RF, et al. Effects of prasterone on corticosteroid requirements of women with systemic lupus erythematosus: a double-blind, randomized, placebo-controlled trial. Arthritis Rheum 2002;46:1820–9.
    38. Petri MA, Mease PJ, Merrill JT, et al. Effects of prasterone on disease activity and symptoms in women with active systemic lupus erythematosus. Arthritis Rheum 2004;50:2858–68.
    39. Mease PJ, Merrill JT, Lahita RG, et al. GL701 (prasterone, dehydroepiandrosterone) improves systemic lupus erythematosus. 2000 American College of Rheumatology Meeting. Philadelphia, PA. October 29-November 2. Abstract 1230.
    40. Mease PJ, Ginzler EM, Gluck OS, et al. Improvement in bone mineral density in steroid-treated SLE patients during treatment with GL701 (prasterone, dehydroepiandrosterone). 2000 American College of Rheumatology Meeting. Philadelphia, PA. October 29-November 2. abstract 835.
    41. van Vollenhoven RF, Park JL, Genovese MC, et al. A double-blind, placebo-controlled, clinical trial of dehydroepiandrosterone in severe lupus erythematosus. Lupus 1999;8:181–7. 42. Himmel PB, Seligman TM. A Pilot Study Employing Dehydroepiandrosterone (DHEA) in the Treatment of Chronic Fatigue Syndrome. [Abstract] J Clin Rheumatol 1999:5:56–9.
    42. Genazzani AD, Stomati M, Bernardi F, et al. Long-term low-dose dehydroepiandrosterone oral supplementation in early and late postmenopausal women modulates endocrine parameters and synthesis of neuroactive steroids. Fertil Steril 2003;80:1495–501.
    43. Villareal DT, Holloszy JO. Effect of DHEA on abdominal fat and insulin action in elderly women and men. JAMA 2004;292:2243–8.
    44. Lardy H, Partridge B, Kneer N, Wei Y. Ergosteroids: induction of thermogenic enzymes in liver of rats treated with steroids derived from dehydroepiandrosterone. Proc Natl Acad Sci U S A 1995;92:6617–9.
    45. Colker CM, Torina GC, Swain MA, Kalman DS. Double-Blind Study Evaluating the Effects of Exercise Plus 3-Acetyl-7-oxodehydroepiandrosterone on Body Composition and the Endocrine System in Overweight Adults. Journal of Exercise Physiology Online 1999;2(4):Abstract #30.
    46. Lardy H, Partridge B, Kneer N, Wei Y. Ergosteroids: induction of thermogenic enzymes in liver of rats treated with steroids derived from dehydroepiandrosterone. Proc Natl Acad Sci USA 1995;92(14):6617–9.
    47. Colker CM, Torina GC, Swain MA, Kalman DS. Double-Blind Study Evaluating the Effects of Exercise Plus 3-Acetyl-7-oxodehydroepiandrosterone on Body Composition and the Endocrine System in Overweight Adults. Journal of Exercise Physiology Online 1999;2(4):Abstract #30.
    48. Zenk JL, Frestedt JL, Kuskowski MA. HUM5007, a novel combination of thermogenic compounds, and 3-acetyl-7-oxodehydroepiandrosterone: each increases the resting metabolic rate of overweight adults. J Nutr Biochem. 2007;18(9):629–34.
    49. Taha A, Mishra M, Baquer NZ, Sharma D. Na+ K(+)-ATPase activity in response to exogenous dehydroepiandrosterone administration in aging rat brain. Indian J Exp Biol. 2008;46(12):852–4.
    50. Chen C, Lang S, Zuo P, Yang N, Wang X. Treatment with dehydroepiandrosterone increases peripheral benzodiazepine receptors of mitochondria from cerebral cortex in D-galactose-induced aged rats. Basic Clin Pharmacol Toxicol 2008;103(6):493–501.
    51. Davis SR, Shah SM, McKenzie DP, Kulkarni J, Davison SL, Bell RJ. Dehydroepiandrosterone sulfate levels are associated with more favorable cognitive function in women. J Clin Endocrinol Metab 2008;93(3):801–8.
    52. Shi J, Schulze S, Lardy HA. The effect of 7-oxo-DHEA acetate on memory in young and old C57BL/6 mice. Steroids 2000;65:124–9.
    53. Nelson R, Herron M, Weeks C, Lardy H. Dehydroepiandrosterone and 7-KETO-DHEA augment Interleukin 2 (IL2) Production by Human Lymphocytes In Vitro. Abstract presented at: The 5th Conference on Retroviruses and Opportunistic Infections, February 1–5, 1998, Chicago, IL. Abstract obtained from Humanetics Corporation.
    54. Whittington R, Faulds D. Interleukin-2. A review of its pharmacological properties and therapeutic use in patients with cancer. Drugs 1993;46(3):446–514.
    55. Nelson R, Herron M, Weeks C, Lardy H. Dehydroepiandrosterone and 7-keto DHEA Augment Interleukin 2 (IL2) Production by Human Lymphocytes in Vitro. The 5th Conference on Retroviruses and Opportunistic Infections. Chicago, IL. Feb 1998;598:49.
    56. Hampl R. 7-Hydroxydehydroepiandrosterone--a natural antiglucocorticoid and a candidate for steroid replacement therapy? Physiol Res 2000;49 Suppl 1:S107–12.
    57. Henderson E, Yang JY, Schwartz A. Dehydroepiandrosterone (DHEA) and synthetic DHEA analogs are modest inhibitors of HIV-1 IIIB replication. AIDS Res Hum Retroviruses1992;8(5):625–31.