Dr. Tori Hudson, N.D.

Fatigue is one of those experiences we all have had, at one time or another - either from too much work, too little sleep, stress, recovering from a trip, during a cold/flu, or what have you. This is not the kind of fatigue that really plagues some of us. Chronic fatigue syndrome or being persistently fatigued from a chronic and/or serious illness (ex/ hypothyroid, diabetes, hypoglycemia, depression, cancer) are the most debilitating kinds of fatigue. In between these short term bouts from relatively minor problems, and the more daily fatigue from something more serious, lies the episodic or recurring fatigue that can happen in relationship to different cycles and phases of a woman’s life - premenstrual, pregnancy and perimenopause.

Pregnancy is demanding in it’s own unique way: hormonal changes, increased nutritional demands, changes in sleep and eating patterns. Regular exercise, good healthy eating habits, a prenatal supplement, regular sleep, and moderating one’s work load, are usually enough to maintain energy throughout the pregnancy. Some women may become anemic during pregnancy and simple tests can detect this followed by simple nutrients as supplementation. At times, other health problems emerge during the pregnancy that can cause fatigue such as hypothyroid and diabetes. With good prenatal care, these can be detected and treated appropriately.

The cycles or phases of hormonal change such as the monthly premenstrual time, and the perimenopause transition can challenge what is called our stress adaptation mechanisms. There are three phases to this stress response which are regulated in large part, by our adrenal glands. The initial phase is the alarm reaction, or fight-or-flight response. This is triggered by reactions in the brain that cause the pituitary gland to produce a hormone, which causes the adrenals to secrete adrenaline as well as other stress related hormones. The alarm phase is usually very short lived. The next phase is the resistance reaction, which allows us to continue to deal with stress, after the fight-or-flight response has worn off. Hormones such as cortisol and other corticosteroids secreted by the adrenal cortex are in motion here and responsible for the resistance reaction. These hormones stimulate the conversion of protein to energy so that we have adequate fuel, after our glucose reservoirs have been used. The resistance reaction provides the energy and stabilizes our circulation under times of stress, as well as enabling us to deal with the emotional aspects of stress, fight infections and continue to perform our tasks. If the stress insult is prolonged and the resistance reaction is extended beyond our body’s capabilities to maintain balance, we become at risk for significant health care problems and end up in the final stage of general adaptation syndrome— exhaustion. In the exhaustion phase, our adrenal glands
have become depleted of hormones called glucocorticoids, and our body has a loss of potassium. In this phase, the body’s cells and tissues do not receive enough glucose or other nutrients to function properly.

As the exhaustion phase continues, our cells and organs in general feel the tremendous demand, and our metabolism is extremely challenged. Now we enter what we might call cellular fatigue and literally, our cells don’t get enough fuel to drive their function. This stress to our system takes a toll and nutritional status declines and disease status increases.

Premenstrual syndrome and perimenopause are their own kind of stress on the system. During these times, many women find their threshold of tolerating stress decreases. The complicated interaction of our hormones and our brain chemistry challenges our stress adaptation mechanisms, and fatigue can result. These fluctuating levels, both decreases and increases, in hormones such as estrogen, progesterone, cortisol and thyroid, interact with brain neurotransmitters such as serotonin, dopamine, GABA, and others, that affect our emotional and physical responses to life, to stressors in our environment, to insults, and even to infections.

Different circumstances call for different approaches, and if persistent fatigue is something that plagues you, it is important to consult with a licensed health care practitioner to determine the cause. A good medical history, physical exam, and selected laboratory tests can determine if the cause is low thyroid, anemia, an infectious agent, low or high blood sugar, or a serious illness. Licensed alternative practitioners will also have tools and perspectives to consider food sensitivities, toxicities, neurotransmitter imbalances, hormonal status and something we call adrenal fatigue syndrome.

A condition alternative medicine often calls “adrenal fatigue”, is a unique contribution to understanding a sometimes elusive problem such as fatigue.

Adrenal gland function and its production of hormones are vital performance tasks in our response to stress and our larger responses in our general adaptation syndrome. Nutritional and herbal support for a person who displays symptoms of intense or prolonged stress, and/or a fatiguing of the ability to adapt to the stress, can play a critical role in supporting our adrenal glands to adapt. An abnormal adrenal response, whether it is deficient or excessive hormone release, can be in large part addressed with key nutrients such as pantothene, B6, zinc, magnesium and vitamin C. These nutrients play a critical role in the optimal function of the adrenal glad and in the manufacture of adrenal hormones. Levels of these nutrients can be diminished during times of stress. Urinary excretion of vitamin C is increased during stress. Pantothene is also important during times of high stress or in individuals with adrenal fatigue. A deficiency of pantothenic acid results in fatigue, headaches, insomnia and more. Notable botanicals can also support adrenal function and enhance resistance to stress such as Siberian and Panax ginseng. These ginsengs are referred to as general tonics or adaptogens. Both Chinese and Siberian ginseng can be used to restore vitality in individuals who are chronically fatigued or who have decreased mental and physical performance and/or stamina. These ginseng species have been shown to act as tonics and anti-stress agents, enhancing the ability to cope with both physical and emotional stressors., , Individuals who take ginseng often report an increase in vitality, well being, increased mood, competence at work, mental and physical performance and reduced feelings of stress and anxiety. Rhodiola is well known amongst the Eastern Europeans for its ability to enhance energy, stamina and endurance. rhodiola appears to increase the chemicals that provide energy to the muscle of the heart and to prevent the depletion of adrenal hormones induced by acute stress.

Ashwagandha is also a significant adaptogen providing adrenal and immune support, , for increasing resistance to environmental stressors and as a general tonic. Ashwagandha contains several important active constituents including withanolides. Its mechanisms of action include pain relief, antioxidant effects, reducing inflammation, stimulating thyroid function, as well as respiratory and immune function. Some researchers have claimed that ashwagandha as an antistressor effect. It appears that it may suppress stress induced increases in dopamine receptors in the brain.

Astragalus has been used historically for strengthening and regulating the immune system, as a tonic, antioxidant, anti-inflammatory, antibacterial antiviral and to protect the liver. A lengthy list for sure. Although there is insufficient evidence to support the effectiveness of all of these uses, there is preliminary research that it is positive in some areas. Astragalus extracts seem to be able to restore or improve immune function in immune deficient cases. It may be able to restore suppressed T-cell function in cancer patients.7 Abnormal liver enzyme tests have improved in people chronic hepatitis when taking Astragalus. Astragalus is also thought to increase cardiac output and may be beneficial in individuals with congestive heart failure and compromised blood flow to the heart muscle. 8

We’re all familiar with our favorite spaghetti sauce that contains basil, but we may not know that this same plant, also known as Holy basil is a rich source of vitamin C, calcium, magnesium, potassium and iron. Holy basil has been gaining some attention due to experimental studies in humans on blood glucose. Elevated glucose levels were lowered by 21 mg/dl and lowering glucose after a meal, was also a positive effect of the basil. Many individuals with adrenal dysfunction, have increased glucose levels due to the increased cortisol as a result of stress.

Shisandra is plant most familiar to those who use Chinese herbs. In traditional Chinese medicine, schisandra is used for many common problems, including physical fatigue. Schisandra is used for improving immune function, recovery after surgery, increasing physical performance and endurance, and for increasing resistance to disease and stress. Schisandra is also possibly effective for improving concentration. It is thought that the variety of lignans found in the fruit, are the active constituents in schisandra.

Maca, or Peruvian Ginseng, may be one of the most important plants having a diverse effect on the female reproductive system. Traditionally, it has been used for chronic fatigue syndrome, enhancing energy, stamina and overall energy. In the female reproductive system, its use for enhancing fertility, regulating the menstrual cycle, treating common menopause symptoms and to increase libido has been familiar to the traditional peoples of Peru and elsewhere, for many a generation. Studies soon to be published, will be able to document some of its specific effects for menopausal women.

This type of herbal/nutritional support is especially helpful for those who have been determined to have adrenal fatigue. Symptoms such as fatigue, low vitality, low libido, depression, anxiety, poor memory, low stamina, and difficulty handling the premenstrual phase and the perimenopausal transition are key indications of adrenal fatigue.

Some women who have premenstrual fatigue or perimenopausal fatigue, may need additional hormonal support as well. This may include actually using hormones as medicines, but also may involve improving the metabolisim of our hormones. These considerations can best be addressed utilizing a comprehensive approach with a licensed naturopathic physician who has both the alternative medicine perspective, as well as the ability to prescribe various hormones such as progesterone, estrogen, testosterone, cortisol and thyroid.

The best approach to fatigue is to find out the cause. Don’t just ignore your fatigue and “gut it out” and don’t make assumptions about the cause of your fatigue. With good health care team approach utilizing your insights, your reading and natural foods store resources, a naturopathic physician, and possibly medical doctor or other allied practitioners, you can be more assured of understanding the cause and therefore the best solutions.

References 

• Farnsworth N, et al. Siberian Ginseng: Current status as an adaptogen. Economic Medicinal Plant Research 1985;1: 156-215.
• Hikino H. Traditional remedies and modern assessment: The ase of Ginseng. In R.O.B. Wijeskera, ed. The Medicinal Plant Industry (Boca Raton, FL: CRC Press, 1991), 149-166.
• Shibata S, et al. Chemistry and Pharmacology of Panax. Econ Med Plant Research 1985;1:217-284.
• Hallstrom C, Fulder S, Carruthers. Effect of Ginseng on the performance of nurses on night duty. Comp Med East and West 1982;6:277-282.
• Maslova L, Kondrat’ev B, Maslov L, Lishmanov I. The cardioprotective and antiadrenergic activity of an extract of Rhodiola rosea in stress. Eksp Klin Farmakol 1994;57:61-63. (Article in Russian).
• Upton R, ed. Ashwagandha root (Withania somnifera): Analytical, quality control, and therapeutic monograph. American Herbal Pharmacopoeia 2000;April: 1-25.
• Sun Y, Hersh E, Talpaz M, et al. Immune restoration and/or augmentation of local graft versus host reaction by traditional Chinese medicinal herbs. Cancer 1983;52(1): 70-3.
• Upton R, Ed. Astragalus Root: analytical, quality control, and therapeutic monograph. Santa Cruz, CA: Am Herbal pharmacopoeia; 1999; 1-25.
• Agrawal P, Rai V, Singh R. Randomized placebo-controlled, single blind trial of holy basil leaves in patients with noninsulin-dependent diabetes mellitus. Int J Clin Pharmacol Ther. 1996;34(9): 406-409.
• Upton R, ed. Schisandra Berry: Analytical, Quality and Control, and Therapeutic Monograph. Santa Cruz, CA: American Herbal Pharmacopoeia 1999; 1-25.

The potential for soy protein or soy isoflavones to alter bone metabolism and bone loss is currently contradictory and inconclusive. Our two best measurements are bone density testing with DXA (an xray test) measures or bone metabolism markers. The lack of agreement in the literature is thought to be related to variations in study design using different soy products, (ie soy protein isolate, whole soy foods, or extracted soy isoflavones), different populations with sometimes perimenopausal women, other times early or even late postmenopause, and then of course different durations and dosage and bone marker assessments. All these different approaches make it very difficult to determine the effectiveness of soy, and therefore difficult to make clinical judgments.

Soybeans contain a class of compounds called phytoestrogens, comprising mostly genistein, daidzein and glycitein, all of which have a biochemical structure similar to 17 beta estradiol. The binding of isoflavones to estrogen receptors is preferential for the estrogen receptor beta and thus indicates that soy isoflavones act as selective estrogen modulators. Daidzein is similar in shape to a drug called Ipriflavone which is used in Europe to treat osteoporosis. In the U.S., Ipriflavone is available as a nutritional supplement.

Bone mineral density (BMD) is the gold standard for determining fracture risk due to nontraumatic events. Bone turnover is an independent predictor of fracture risk.

While the effects of soy on bone metabolism has been inconsistent, many positive studies do exist that suggest a role for soy in slowing bone turnover and bone density in women. Soy appears to have a pro estrogen effect on bone in some experimental evaluations. The bone density of ovariectomized rats was evaluated in which soy replaced casein in the diet, compared to another group that received estrogen. The addition of soy inhibited bone loss, although not to the same extent as was achieved with the estrogen treatment. Another study of ovariectomized rats also reported a positive effect of the soy phytoestrogen genistein in maintaining bone. These authors also reported that genistein suppresses the bone losing cells (osteoclasts), both in the test tube and in vivo. Arjmandi also did a double-blind, randomized, controlled trial using 40g of soy protein containing isoflavones over 3 months in postmenopausal women. Bone resorption was decreased, when compared to milk protein.

Several human studies have provided further insight and comfort in the possible role of soy in our bone health. A study conducted at the University of Illinois found that menopausal women had an increase in mineral levels and density in their lumbar spines after taking 55-90 mg of isoflavones for six months. The placebo group showed the lowest bone density and the greatest bone loss, while the estrogen group showed the highest bone density and the slowest bone loss. What was surprising was that the soybean diet was effective in preventing bone loss in the fourth lumbar vertebra and, although less so, in the right hip as well. Soybean seems to have more of an effect on trabecular bone (more predominant in the spine) than on cortical bone (more predominant in the hip). The soy did not show as great an ability in preventing bone loss as the estrogen group, but the positive effect it showed is encouraging.

A study of the relation of soy isoflavone intake and bone mineral density was conducted within the Study of Women’s Health Across the Nation, a US cohort study of women aged 42-52 years. For African-American and Caucasian women, average intakes of genistein was too low to pursue analyses. For Chinese women, no association between genistein and bone mineral density was found. Pre-menopausal, but not peri-menopausal, Japanese women whose intakes were greater had a higher bone density of the spine and femoral neck. Mean spinal bone density of those women in the highest group was 7.7% greater than that of women in the lowest group. Bone density of the femoral neck was 12% greater in the highest intake group versus the lowest.

Other positive studies on soy and bone density also give some credence to the role of soy and bone health. In a study estimating the daily intakes of soy isoflavones in the diets of 478 postmenopausal Japanese women who reported soy consumption, high consumption of soy products was associated with increased bone mass.

A very recent analysis of nine studies further increases our optimism about using soy to inhibit bone resorption. Nine studies with a total of 432 menopausal women were evaluated for meta-analysis. Amount of soy intake varied amongst the nine studies from 37 mg of isoflavones per day to 118 mg of isoflavones per day. Testing for urinary peptides (deoxypyridinoline) of bone turnover demonstrated that when all nine study results are combined, those who consumed isoflavones had a decrease in these biomarkers of -2.08 nmol/mmol when compared to those who did not consume isoflavones. In five of the studies, isolated soy protein was used, as a group, there was no significant effect on urinary deoxypyridinoline. In the current analysis, significant reduction in urinary deoxypyridinoline did not occur in those studies with isoflavones of less than 90 mg/day. In a review of the research in 2003, the author concluded that 90mg of isoflavones per day is required to achieve benefits on bone health.

In contrast to the positive studies, several clinical trials using a variety of soy protein isolate formulations found no clinically important effects of soy on bone metabolism and bone turnover markers. Further inconsistent research can be seen with several clinical trials using soy protein or isoflavones demonstrating a positive effect on BMD, while others have not had positive findings.

I mentioned variations in dosing, duration, soy formulations used, and different study populations as possible reasons for inconsistent results on the effects of soy isoflavones on bone turnover and bone density. But, another significant consideration may be due to how the isoflavones are metabolized in the gut. In the recent study mentioned about analyzing nine studies 10 the significant effects on urinary peptides occurred in Asian women but not Caucasian women. This may be due to the conversion of isoflavones into its active metabolite equol in intestinal flora, and that only one-third of Caucasian women can metabolize isoflavones into equol, whereas more than half of Asian women possess this ability.

Soy isoflavones may also have more of an effect in post-menopausal women than in pre or perimenopausal women. In one study, 53.3 mg of isoflavones per day was associated with an increase in bone density in postmenopausal women, but not pre-menopausal women.

An area of soy foods that may be overlooked, is the amount of calcium in some soy foods. A diet that includes greater amounts of soy products can account for a meaningful amount of calcium, and some soy foods can offer as much or more calcium than a serving of dairy products.

With the inconsistent research, it is difficult to draw confident conclusions about the role of soy in bone health. My clinical advice is to increase soy foods as part of a regular diet in prevention strategies for all pre, peri and postmenopausal women. For all women who have significant risk factors for osteoporosis, I would in addition, recommend soy supplementation so that their total daily soy isoflavone intake would deliver approximately 90 mg of soy isoflavones per day. For treatment of peri and postmenopausal women who already have osteoporosis, I would not consider soy an adequate treatment alone. In addition to the 90 mg per day of soy isoflavones and typical supplementation including calcium, vitamin D and other potential nutrients (K, boron, magnesium, manganese, and more), dietary and exercise advice, for these women who already have osteoporosis, I am in favor of proven conventional therapies to reduce fracture risk.

References

• Weaver C, Cheong J. Soy isoflavones and bone health: the relationship is still unclear. J Nutr 2005; 135:1243-1247.
• Setchell K. Soy isoflavones-benefits and risk from nature’s selective estrogen receptor modulators (SERMS). J Am Coll Nutr 2001; 20: 354S-362S.
• Garnero P, Hausherr E, Chapuy M, et al. Markers of bone resorption predict hip fracture in elderly women: the EPIDOS Prospective Study. J Bone Miner Res 1996; 11:1531-1538.
• Arjmandi B, Alekel L, Hollis B, Amin D, Stacwicz-Sapuntzakis M, Guo , Kukreja S. Dietary soybean protein prevents bone loss in an ovariectomized rat model of osteoporosis. J Nutr 1996;126:161-167.
• Blair H, Jordan S, Peterson T, Barnes S. Variable effects of tyrosine kinase inhibitors on avian osteoclastic activity and reduction of bone loss in ovariectomized rats. J cell Biochem. 1996;61:629-637.
• Arjmandi B, Khalil D, Smith B, et al. Soy protein has a greater effect on bone in postmenopausal women not on hormone replacement therapy, as evidenced by reducing bone resorption and urinary calcium excretion. J Clin Endocrinol Metab 2003; 88: 1048-1054.
• Erdman J, Stillman R, Lee K, Potter S. Short-term effects of soybean isoflavones on bone in postmenopausal women. Program and Abstract Book, Second International symposium on the Role of Soy in Preventing and Treating Chronic Disease. Brussels, Belgium, 1996.
• Greendale G, FitzGerald G, Huang M, et al. Dietary soy isoflavones and bone mineral density: Results from the study of women’s health across the nation. Amer J Epidemiology 2002;155(8):746-754.
• Somekawa Y, Chiguchi M, Ishibashi T, Takeshi A. Soy intake related to menopausal symptoms, serum lipids, and bone mineral density in postmenopausal Japanese women. Obstet Gynecol 2001;97:109-115.
• Ma D-F, Qin L-Q, Want P-Y, Katoh R. Soy isoflavone intake inhibits bone resorption and stimulates bone formation in menopausal women: meta-analysis of randomized controlled trials. European J of Clinical Nutrition 2008; 62:155-161.
• Branca F. Dietary phyto-oestrogens and bone health. Proc Nutr Soc 2003; 62: 877-887.
• Wangen K, Duncan A, merz-Demlow B, et al. Effects of soy isoflavoens on markers of bone turnover in premenopausal and postmenopausal women. J Clin Endocrinol Metab 2000; 85:3043-3048.
• Knight D, Howes J, Eden J, Howes L. Effects of menopausal symptoms and acceptability of isoflavone-containing soy powder dietary supplementation. Climacteric 2001; 4:13-18.
• Dalais F, Ebeling P, Kotsopoulos D, McGrath B, Teede H. The effects of soy protein containing isoflavones on lipids and indices of bone resorption in postmenopausal women. Clin Endocrinol 2003; 58:704-709.
• Potter S, Baum J, Teng H, et al. Soy protein and isoflavones: their effects on blood lipids and bone density in postmenopausal women. Am J Clin Nutr 1998; 68:1375S-1379S.
• Alekel D, Germain A, Peterson C, et al. Isoflavone-rich soy protein attenuates bone loss in the lumbar spine of perimenopausal women. Am J Clin Nutr 2000; 72:844-852.
• Morabito N, Crisafulli A, Vergara C, et al. Effects of genistein and hormone-replacement therapy on bone loss in early postmenopausal women: a randomized double-blind placebo controlled study. J Bone Miner Res 2002; 17:1904-1912.
• Chen Y, Ho S, Lam S, Ho S, Woo J. Soy isoflavones have a favorable effect on bone loss in Chinese postmenopausal women with lower bone mass: a double-blind, randomized, controlled trial. J Clin Endocrinol Metab 2003;88:4740-4747.
• Lydeking-Olsen E, Beck-Jensen J, Setchell K, Holm-Jensen T. Soymilk or progesterone for prevention of bone loss: a 2 year randomized, placebo-controlled trial. Eur J Nutr 2004;43:246-257.
• Gallagher J, Satpathy R, Rafferty K, Haynatzka V. The effect of soy protein on bone metabolism. Menopause 2004; 11:290-298.
• Kreijkamp-Kaspers S, Kok L, et al. Effects of soy protein containing isoflavones on cognitive function, bone mineral density, and plasma lipids in postmenopausal women. JAMA 2004; 292:65-74.
• MeiJ, Yeung S, Kung A. High dietary phytoestrogen intake is associated with higher bone mineral density in postmenopausal but not premenopausal women. J Clin Endocrinol Metab 2001; 86:5217-5221

Vitamin D deficiency is a very common problem in the U.S., and especially in an aging population. Older individuals are at greater risk for deficiency because aging lowers the amount of 7-dehydrochlesterol in the skin and thus lowers the ability to produce vitamin D, as well as lower absorption. Most of our vitamin D comes from sun exposure, and only a small amount typically, obtained from food or supplements. Due to our decreasing exposure to sun—with spending so much time indoors, wearing clothing and/or sunscreen, the majority of us just don’t get enough vitamin D anymore, whether we live in Alaska or Arizona.

Vitamin D deficiency is associated with increased parathyroid secretion, increased bone turnover, osteoporosis, and increase risk of hip and other fractures. Lower levels of vitamin D as measured in the blood, is also associated with risks of cancers of the colon, breast and ovary in several observational studies. Vitamin D deficiency has other serious implications and has been associated with multiple sclerosis, type-1 diabetes, Chrohn’s disease , and even increases in the risk of hypertension and cardiovascular disease.
Causes of vitamin D deficiency include hereditary disorders, reduced skin synthesis and absorption of vitamin D, and acquired disorders of vitamin D absorption, metabolism and responsiveness.

We get our vitamin D from exposure to sunlight, from our diet and from supplementation. Vitamin D3 is produced in the skin on exposure to ultraviolet radiation, and vitamin D2 is derived from plants and enters our body only through the diet or supplementation. There are two major supplemental forms of vitamin D; vitamin D2 (ergocalciferol) and vitamin D3 (holecalciferol). Vitamin D2 is manufactured through the ultraviolet irradiation of ergosterol from yeast. Vitamin D3 is made through the ultraviolet irradiation of 7-dehydrocholesterol from lanolin. Vitamin D2 is considered to be vegetarian suitable, and vitamin D3 is animal derived, from the lanolin. Both forms are often added to foods such as milk, orange juices, infant formulas, cheeses and breakfast cereals. Natural food sources of vitamin D3 include salmon, sardines, mackerel, tuna, shiitake mushrooms, egg yolks, cod liver oil and exposure to sunlight. Both vitamin D2 and vitamin D3 are available in over the counter supplements, including low doses, and moderately higher doses, typically not more than 5,000 IU. High and higher doses of vitamin D2 are available by prescription.

The back story on whether or not vitamin D2 and vitamin D3 are equally effective, goes back to studies in the 1930s where they were assumed to be equally effective in humans. Over time, human studies comparing the increase in blood levels of vitamin D with the supplementation of vitamin D2 vs vitamin D3 have been inconsistent in their results and few in number. They have also been wrought with problems in small sample sizes, lack of vitamin D stability of the products used, wide variations in the seasons the blood was drawn (serum levels of vitamin D are naturally higher in the sunnier months), variable intestinal absorption amongst individuals, variable baseline serum levels of vitamin D, previous history of vitamin D supplementation and variations in age (older people have less vitamin D absorption). While common thought is that vitamin D2 is about 30% less potent than vitamin D3, these variables in the studies, make it extremely difficult to make comparisons and draw accurate conclusions. One small study done in 1998 did demonstrate that vitamin D3 yielded a small increase in serum 25-hydroxyvitamin D over the vitamin D2. A study of 30 men in 2004, between the ages of 20 and 61, demonstrated that the rise in blood levels within the first few days of receiving a single high dose was the same for both forms, indicating equivalent absorption. However, the vitamin D3 treated individuals had a continued rise over two weeks and peaked at 2 weeks, while the vitamin D2 treated men, had a decline to their baseline, by day 14. One might conclude from these two well designed studies, that the rise in serum levels with vitamin D3 might be only a very small amount, as in the first study. Or, rather than give one dose to last 2 or more weeks where there was a greater effect with vitamin D3, as in the second, this same study showed that within the first 3 days of either form, the rise in blood levels, was the same, indicating that a daily dose of either form of vitamin D would be equivalent.

The newest study addressing this question, challenges the long held belief that vitamin D2 is less potent or less effective than vitamin D3 in raising and maintaining blood levels. This was a randomized, placebo-controlled, double-blinded study of healthy individuals ages 18-84 years who received either placebo, 1,000 IU of vitamin D3, 1,000 IU of vitamin D2, or 500 IU of vitamin D2 plus 500 IU of vitamin D3 daily for 11 weeks at the end of the winter. Sixty percent of the study subjects were vitamin D deficient at the start of the study (< 20 ng/ml). This three month study of 68 individuals found that supplementation with both forms produced similar results. Neither 1,000 IU of vitamin D2 or vitamin D3 raised 25-hydroxyvitamin D levels in vitamin D deficient subjects to a level above 30 ng/ml. The authors concluded that vitamin D2 is equally as effective as vitamin D3 in maintaining 25-hydroxyvitamin D status.

My main point in this article is not to prove that the vegetarian supplementation of vitamin D2 is as potent as the non-vegetarian supplement vitamin D3, but rather, that we cannot state with reasonable certainty that D3 is 30% more potent, as is generally thought. Vegetarians may find some comfort in this article about vitamin D2 and vitamin D3 yielding similar results, at least when taken daily. If not, then the most we could assert, is that we may need a one third higher dose of vitamin D2 to yield the same results.

References

• MacLaughlin J, Holick M. Aging decreases the capacity of human skin to produce vitamin D3. J Clin Invest 1985; 76: 1536-1538.
• Parfitt A. Osteomalacia nd related disorders. In: Avioli L, Krane S, eds. Metabolic bone disease and clinically related disorders. 2nd ed. Philadelphia: WB Saunders; 329-396.
• Trivedi D, Doll R, Khaw K. Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomized double blind controlled trial. BMJ 2003; 326: 469- 474.
• Garland C, Garland F, Gorham E, et al. The role of vitamin D in cancer prevention. Am J Public Health. 2006; 96: 252-261.
• Cantorna M, Zhu Y, Froicu M, Wittke A. Vitamin D status, 1,25-dihydroxyvitamin D3, and the immune system. Am J Clin Nutr 2004; 80: Suppl 6: 1717S-1720S.
• Ponsonby A-L, McMichael A, van der Mei I. Ultraviolet radiation and autoimmune disease: insights from epidemiological reearch. Toxicology 2002; 181-182:71-78.
• Zittermann A. Vitamin D and disease prevention with special reference to cardiovascular disease. Prog Biophys Mol Biol 2006; 92: 39-48.
• Rostand S. Ultraviolet light may contribute to geographic and racial blood pressure differences. Hypertension 1997; 30: 150-6.
• Trang H, Cole D, Rubin L, et al. Evidence that vitamin D3 increases serum 25-hydroxyvitamin D more efficiently than does vitamin D2.
• Armas L, Hollis B, Heaney R. Vitamin D2 ismuch less effective than vitamin D3 in humans. J Clinical Endocrinology and Metabolism. 2004;89(11): 5387-5391.
• Holick M, Biancuzzo R, Chen T, et al. Vitamin D2 is as effective as vitamin D3 in maintaining circulating concentrations of 25-hydroxyvitamin D. J Clin Endocrinol Metab 2007; Dec 18.

In a population-based study, 1180 Caucasian women older than 55, were randomized to receive a calcium supplement , a calcium supplement plus 1100 IU of vitamin D (cholecalciferol), or a daily placebo. Health status and compliance to the regimen were assessed every 6 months over 4 years and serum vitamin D was measured at baseline and annually. 1024 women completed the study. The purpose of the analysis was to determine the efficacy of calcium by itself and calcium plus vitamin D in reducing the all-cancer risk in postmenopausal women.

Fifty women developed cancers other than skin cancer. The risk for cancer in the calcium-plus vitamin-D group was less than half that in the placebo group (RR 0.4; P=0.013). The calcium only group had no statistically significant risk reduction. Researchers adjusted for the possibility that cancers detected during the first year of the study, had been present but silent at baseline, and analyzed these separately. Relative risk for cancer in the calcium/vitamin D group was lower than in the placebo control subjects 0.2 (P< 0.005), and the risk reduction for the calcium only group was not statistically significant.

Women in the calcium plus vitamin D group had higher serum vitamin D levels that correlated with lower cancer risk, both at baseline and at one year. Adherence to the study doses was 86%.

Lappe JM, et al. Vitamin D and calcium supplementation reduces cancer risk: Results of a randomized trial. Am J Clin Nut 2007; Jun;85(6):1586-1591

Commentary: The only other randomized trial of vitamin D and cancer was the Women’s Health Initiative, which used a lower dose of vitamin D (400 IU) and women with a lower baseline vitamin D status. The WHI reported no significant effect of the vitamin D intervention on colorectal cancer incidence but did observe a significant inverse relation between baseline vitamin D levels and cancer risk, as in this study. It’s reassuring to see that the benefits of higher than recommended dosing of vitamin D is catching on. It is estimated that about 60% of women in the U.S. are vitamin D deficient, no what part of the country they live in. The current adult daily recommendations for vitamin D in women 51 to 70 is
400 IU -800 IU per day. Supplement doses up to 2000 IU are considered safe and to be without significant risk for adverse events. Many practitioners are advising even higher doses, but I would recommend this only after assessment for medical need, serum testing, and evaluation for risk of side effects.

Calcium and Vitamin D Intake and Risk for Breast Cancer

The relationship between vitamin D and breast cancer was prospectively assessed among 10,000 premenopausal and 20,000 postmenopausal women who were enrolled in the Women’s Health Study. Intake of calcium and vitamin D was determined from self-reported questionnaires about diet and vitamin use.

During an average follow-up of 10 years, the overall incidence of invasive breast cancer was 2.6% among premenopausal women and 3.6% among postmenopausal women. Among premenopausal women, the hazard ratio for developing breast cancer was 0.61 for women in the highest versus lowest quintiles of calcium use and 0.65 for vitamin D intake. No benefit was seen for these nutrient intakes and breast cancer risk in postmenopausal women.

Lin J et al. Intakes of calcium and vitamin D and breast cancer risk in women. Arch Intern Med 2007, May 28; 167(10):1050-1059.


Commentary: This is a very large, prospective study, which once again demonstrates important findings for vitamin D, at least for premenopausal women. A higher intake of calcium and vitamin D was associated with a lower risk for breast cancer among premenopausal women, but not for postmenopausal women. While the hazard ratio was large, the absolute reduction in risk was small. Being a population based study using only self-reported questionnaires, the usefulness of the findings in this study are limited, especially since the amount of vitamin D and calcium was recorded only once at baseline. In addition, there could easily be other variables that explain the findings. Nonetheless, it supports the trend to advise women about adequate intakes of calcium and vitamin D, both in the diet and in supplement form.

Chances are, many of you have not ever heard of polycystic ovarian syndrome (PCOS). Hopefully, that will mean you have no health problems indicative of PCOS. For other women, it may mean you have this commonly under recognized, under diagnosed condition.

PCOS is not really classified as a disease, because it is not a specific and constant set of symptoms and physical characteristics. Rather, it is better described as a syndrome, with a collection of symptoms, physical and laboratory findings. There are two consistent aspects of PCOS: hyper-androgenism (or an increase in male hormones) and a lack of or infrequent ovulation. The most common characteristics of PCOS are obesity, excess body hair (hirsutism), and irregular/infrequent/lack of ovulation and thus irregular menses and poor fertility. Over 95% of women who have all three of the classic signs of obesity, hirsutism and infertility and/or irregular menses, have PCOS. One of the problems with PCOS, is that many women have this syndrome, but don’t have all three of the classic signs. So, not all women with PCOS are obese, in fact not even 50%. Many PCOS women are of normal weight or even underweight, have no excess hair growth on the face of chest or legs, and may even have pretty regular menses.

So many variables exist with this syndrome, that it’s no wonder it can be hard to come up with a definitive diagnosis. There can be other manifestations of hyper-androgenism in women including hair thinning or acne. And, not all PCOS women are infertile, yet PCOS is likely the single most common cause of a lack of ovulation, leading to abnormal menstrual cycles and infertility

An important feature of PCOS is that there are some kind of changes in hormones- for sure, elevated levels of the male hormones, although this is often not detected by the poor sensitivity of laboratory testing. The underlying cause of PCOS is varied and still evolving. What we currently know is the following:

1. elevated secretions of male hormones from the ovaries and/or adrenal glands that overwhelm the body’s ability to convert these male hormones to estrogen
2. abnormal ratios of the pituitary hormones, leutinizing hormone (LH) to follicle stimulating hormone (FSH)
3. failure of the monthly maturing of a follicle in the ovaries
4. a resistance to insulin
5. and likely a genetically driven defect in the action of insulin

Metabolic dysfunctions including abnormalities in blood fat(lipid) levels, insulin and blood sugar levels, and high blood pressure are significant medical problems, that can be related to the underlying syndrome of PCOS.

Besides the potential changes in one’s appearance of weight gain, acne, facial hair, or hair thinning, the irregular menstrual cycles and potential of infertility, there are significant diseases that can result from the underlying syndrome, including and increased risk of cardiovascular disease, type II diabetes and uterine cancer.

With all this going on, you might wonder how could it possibly be underdiagnosed? The answers lie in more than one area. Women with PCOS often have a similar story to tell: they went to their dermatologist for acne- then were given topical treatments or antibiotics. Or, they went to their gynecologist for irregular menses and were put on birth control pills. These two common stories are the result of compartmentalization in medicine, and not enough health care providers understanding this syndrome and all the body systems it can affect. Things are changing though, and this multiple system syndrome, is now better understood, with more common accurate diagnoses being made, and better treatments both natural and conventional.

The metabolic goals of a holistic natural medicine approach are to…

1. lower androgens
2. inhibit the conversion of testosterone to the more potent dihydrotestosterone
3. to induce regular ovulation
4. to modify insulin resistance and lower the hyper-secretion of insulin.

Diet and exercise are common to both conventional and alternative treatments of PCOS - to promote weight loss, increase insulin sensitivity, decrease male hormone levels, and thus restoring ovulation. Dietary changes that may improve insulin resistance are the primary emphasis with a reduction of refined carbohydrates and total calories, while increasing the high fiber foods of vegetables, legumes and whole grains. Many individuals with PCOS will respond to a diet that is not more than 80 gm/day of carbohydrates, and 60-80 gm per day of protein

There are several natural substances that bind to and stimulate sex hormone binding glogulin (SHBG), which then binds some of the testosterone in our blood stream, which in turn reduces the hyperandrogenism of PCOS. The root of the nettles plant contains many lignans and these compounds have an affinity to SHBG in humans. , Nettles root can also affect aromatase inhibition which could inhibit the conversion of the weaker testosterone to dihydrotestosterone.

Caffeine containing beverages (coffee, green tea, black teak, oolong tea and even colas), were seen to have a relationship between intake and increases in SHBG. This then, had a favorable effect on hormone levels,. As caffeine intake and SHBG increases, estrogen level decreases. This is just one of the mechanisms by which green tea may have breast health implications and favorably influencing the risk of breast cancer.

Flax seeds and soy, are two important foods groups relevant in a PCOS diet. The flax seeds again, containing lignans, which increases SHBG, lowering blood testosterone levels and perhaps reducing the hyperandrogenic effects1 I recommend 1-2 tbsp per day of flax seeds or ground flax meal.

One of the potential significant aspects of PCOS is a buildup of the lining of the uterus. This occurs because the ovaries still produce adequate estrogen, but not enough progesterone, due to a lack of ovulation. The uterus then receives what is called unopposed estrogen stimulation. This thickening is called hyperplasia, and the cells over time can become atypical or even malignant. The potential role of soy foods in the diets of women with PCOS may have some contradictions but basically, it is thought that soy can reduce blood estrogen levels and increase SHBG and that women with higher soy diets excrete more than twice the amount of estrogen in their stool in one study, and increased the excretion of estrogens in the urine in another. There are indeed, other soy studies that do not show the same results. I recommend one serving of a soy food per day, or something equivalent to 50mg-100 mg of soy isoflavones daily.

Saw palmetto inhibits the activity of an enzyme, 5-alpha reductase, thereby reducing the conversion of testosterone to dihydrotestosterone, the more potent form. This may have implications in reducing acne, excess facial and body hair, as well as hair loss from the scalp. Saw palmettos was recently studied as part of a formula and was able to initiate a reduction in hair loss and an improvement in hair density in patients with testosterone related hair loss.

Calcium and vitamin D are two of the most reaching nutrients our body needs affecting muscles, bones, thyroid, brain, heart, hormones, colon, breast and more. Calcium and vitamin D regulation may also contribute to the development of faulty ovarian follicle development in women with PCOS, resulting in reproductive and menstrual dysfunction. Vitamin D also plays a role in glucose metabolism and is commonly deficient in individuals with type 2 diabetes. Supplementing with vitamin D has been shown to improve glucose tolerance, insulin secretion and insulin sensitivity in those with DM., A deficiency of vitamin D may be more frequent in women with PCOS and in a small study, five of thirteen women had an overt vitamin D deficiency. Seven of the nine women with no menses or infrequent menses, had a return to a normal menstrual cycle within two months of being given 50,000 IU once or twice per week of vitamin D and 1,500 mg per day of calcium.10

Chromium is a trace mineral that enhances the action of insulin. Supplementing with chromium has been shown in some studies to improve the blood sugar control in those with type 2 DM. Giving PCOS women 1,000 mcg per day of chromium for as little as two months was able to improve insulin sensitivity by 30% and by 38% in obese women with PCOS.

A little known supplement, D-chiro-inositol is not commercially available, but pinitol, a compound similar to D-chiro-inositol, is available. Pinitol appears to mediate insulin activity. In an important study about this nutrient, 600 mg of pinitol twice per day for three months lowered blood glucose levels by 19%, lowered average glucose levels by 12% and significantly improved insulin resistance.

Conventional treatment of PCOS includes diet and exercise, and a drug, Metformin, used to improve insulin resistance. This can lead to normal ovulation. Other medications are used to induce ovulation such as clomiphene citrate, spironolactone to decrease testosterone on the hair follicle, and oral contraceptives to address irregular menstrual cycles and excess body hair. A newer drug, Vaniqa, is used topically, to reduce facial hair.

Working with a licensed alternative medicine provider with knowledge of this condition, the ability to run laboratory tests and to assess for complications of the syndrome and an understanding of the mechanism of the natural ingredients, would be optimal. It’s a complicated condition, requiring long term attention and regular medical care. But, don’t despair if you have this syndrome. We finally have lots of options to address the symptoms and the metabolic dysregulation, and natural medicines play a big part.

In summary, a comprehensive plan for PCOS would include:

Weight loss in those who are overweight
Daily aerobic exercise one hour per day
Low simple carbohydrates
Up to 80 gm/day of carbohydrates
60-80 gm per day of protein
Flax seeds 1-2 tbsp per day
Soy food 1 serving per day
Vitamin D 2,000 i.u. per day (or more under doctor’s supervision)
Calcium 1,000mg-1,500 mg per day
Chromium 1,000 mcg per day
Green tea (90% polyphenols, 80% catechins, 45% EGCG) 300mg-500 mg per day or 3 cups of tea per day
Nettles root 600 mg per day
Saw Palmetto extract 400 mg per day
Pinitol 600 mg twice per day

Important resources:

Women’s Encyclopedia of Natural Medicine. Tori Hudson, N.D., McGraw/Hill publishing

PCOS, A Woman’s Guide to Dealing with Polycystic Ovary Syndrome. Colette Harris with Dr. Adam Carey. Thorson’s publishing

PCOS, The Hidden Epidemic. Samuel Thatcher, M.D., PhD. Perspectives Press

The Natural Diet Solution for PCOS and Infertility. Nan Dunne, N.D. (paperback and e-book) 
PCOS Health Review- free newsletter; Nan Dunne, N.D. and Bill Slater

Schottner M, Gansser D, Spiteller G. Lignans from the roots of Urtica dioica and their metabolites bind to human sex hormone binding globulin. Planta Med 1997; 63(6): 529-532

Gansser D, Spiteller G. Plant constituents interfering with human sex hormone-binding globulin. Evaluation of a test method and its application to Urtica dioica root extracts. Z Naturforsch 1995;50(1-2):98-104.

Gansser D, Spiteller G. Aromatase inhibitors from Urtica dioica roots. Planta Med. 1995;61(2): 138-140.

Nagata C, Kabuto M, Shimizu H. Association of coffee, green tea, and caffeine intakes with serum concentrations of estradiol and sex hormone-binding globulin in premenopausal Japanese Women. Nutrition and Cncer 1998; 30(1): 21-24.

Kumar N, Cantor A, Allen K, et al. The specific role of isoflavones on estrogen metabolism in premenopausal women. Cancer 2002;94:1166-1174.

Goldin B, Adlercreutz H, Gorbach S, et al. The relationship between estrogen levels and diets of Caucasian American and Oriental immigrant women. Am J Clin Nutr 1986;44:945-953

Xu X, Duncan A, Wangen K, Kurzer M. Soy consumption alters endogenous estrogen metabolism in postmenopausal women. Cancer Epidemiology, Biomarkers and Prevention 2000;9:781-786.

Martini M, Dancisak B, Haggans C, Thomas W, Slavin J. Nutrition and Cancer 1999;34(2): 133-139.

Prager N, Bicket K, French N, Marovici G. A randomized, double-blind, placebo-controlled trial to determine the effectiveness of botanically derived inhibitors of 5-alpha-reductase in the treatment of androgenetic alopecia. JAH and Comple Med 2002;8(2): 143-152.

Thys-Jacobs S, Donovan D, Papadopoulos A, et al. Vitamin D and calcium dysregulation in the polycystic ovarian syndrome. Steroids 1999;64:430-435.

Raghuramulu N, Raghunath M, Chandra S, et al. Vitamin D improves oral glucose tolerance and insulin secretion in human diabetes. J Clin Biochem Butr 1992;13:45-51.

Borissova A, Tankova T, Kirilov G, et al. The effect of vitamin D3 on insulin secretion and peripheral insulin sensitivity in type 2 diabetic patients, Int J Clin Pract 2003;57:258-261.

Gaby A. Chromium. Integrative Med 2006;5(4):22-26.

Lydic L, McNurlan M, Komaroff E, et al. Effects of chromium supplementation on insulin sensitivity and reproductive function in polycystic ovarian syndrome: a pilot study. Fertil Steril 2003;80 (Suppl 3): S45-S46.

Lydic M, McNurlan M, Bembo S, Mitchell L, Komaroff E, Gelato M. Chromium picolinate improves insulin sensitivity in obese subjects with polycystic ovary syndrome. Fertil Steril 2006;86:243-246.

Davis A, Christiansen M, Horowitz J, et al. Effect of pinitol treatment on insulin action in subjects with insulin resistance. Diabetes Care 2000;23:1000-1005.

Kim J, Kim J, Kang M, et al. Effects of pinitol isolated from soybeans on glycaemic control and cardiovascular risk factors in Korean patients with type II diabetes mellitus: a randomized contolled study. Eur J Clin Nutr 2005;59:456-458.

This randomized, double-blind, controlled 3-month study in China enrolled 244 menopausal women aged 40-60. Women were assigned to either an isopropanolic extract of Black Cohosh containing 40 mg/day or one 2.5 mg tibolone tablet per day, a drug known to reduce hot flashes.

Results: There was a significant trend (57.8%) that women given Black Cohosh respond better than they do to tibolone in terms of efficacy-risk balance and that Black Cohosh was clearly superior to tibolone regarding the safety profile, looking at issues such as abnormal bleeding, endometrial thickening, breast pain, vaginal discharge and edema. The total Kupperman Menopause Index ( measuring hot flashes, profuse sweating, insomnia, nervousness, depressive mood, vertigo, weakness and fatigue, joint pain, headaches and palpitations) declined from 24.7 + 6.1 at baseline to 11.2 + 6.2 and 7.7 + 5.8 after Black Cohosh for 4 and 12 weeks to 11.2 + 7.2 and 7.5 + 6.8 after tibolone treatment.

Bai W, Henneicke-von Zepelin H, Wang S, et al. Efficacy and tolerability of a medicinal product containing an isopropanolic black cohosh extract in Chinese women with menopausal symptoms: A randomized, double blind, parallel-controlled study versus tibolone. Maturitas, Volume 58, Issue 1, Pages 31-41

Comments: These results show that Black Cohsoh had significant benefit in reducing the total score and the individual items of the Kupperman Menopause Index (KMI). This success in treating moderate to severe menopause symptoms in this case was as good as the tibolone drug. The study also concluded that the efficacy-safety balance, a composite of the KMI and the frequency of adverse events was definitely in favor of Black Cohosh and superior to tibolone.

Tibolone is a selective tissue estrogenic activity regulator (STEAR), which expresses estrogenic, progestogenic and androgenic activity. It has not available in the U.S. and in fact, was recently denied approval by the FDA. In Europe and other countries, it is considered to be an effective alternative to HT in treating menopause symptoms.

This is the first study of Black Cohosh in Chinese women. It might interest us to know that psychological symptoms are frequent in Chinese peri- and post-menopausal women. The most common of these are nervousness, depressive mood swings, sleep problems and vertigo. In the current study, these types of symptoms were mild or moderate, at baseline and were significantly reduced at 12 weeks, both in the Black Cohosh group and in the tibolone group.

The Women’s Healthy Eating and Living (WHEL) study is a multi-center, randomized controlled trial studying a total of 3088 women diagnosed with early stage breast cancers –stage I-IIIa who were diagnosed within the previous four years. Subjects in the WHEL study were randomized into either a treatment group, who’s diet consisted of; a daily dose of 5 servings of vegetables, 16 oz of vegetable juice, 3 servings of fruit, 30 g of fiber and 15% to 20% of energy intake from fat and a control group which consumed a regular diet of 5 servings of vegetables and fruit, more than 20 g of fiber and less than 30% total energy intake from fat.

The main outcome was a recurrence of breast cancer, a new primary breast cancer, or death from any cause. After an average follow-up of a 7.3 years , there were no differences in breast cancer events or all-cause mortality between women in the two dietary groups despite the treatment group eating 65% more vegetables, 25% more fruit, 30% more fiber and 13% less fat.

16.7% of the women in the dietary intervention group developed an invasive breast cancer event and 10.1% died vs. 16.9% in the regular diet group with 10.3% having died.

Pierce J, et al. Influence of a diet very high in vegetables, fruits, and fiber and low in fat on prognosis following treatment for breast cancer. JAMA 2007;298(3):289-298.

Commentary: This is a discouraging bit of news from those of us who work with breast cancer survivors advising them on dietary changes. It can be noted that in the WHEL study, women who had undergone chemotherapy were not included. It may be that we would see better results in women receiving chemotherapy undergoing dietary changes vs. those that don’t. In addition, with a one on one clinical practice, we would often achieve better compliance with more success in eating more vegetables, fruit, fiber and less fat. Other reports on dietary fat show that those studies that reduce fat intake to 15% -20% of total calories consumed, may not achieve results, while studies that reduce fat intake to 10%of calories and focus on fish, seeds, nuts and olive oil as a source of fats, do in fact bode well for future breast health. The current WHEL study also failed to achieve two important results in the dietary intervention group — there was no reduction in total calories and no difference in weight loss, two important influences on breast health.

While many dietary factors have been shown to have influence on risks of breast cancer in observational studies, these relatively small changes in vegetable, fruit and fat intake in the WHEL study, did not make much difference. The message here: we need to eat even more vegetables and fruits, lower fat to 10% and focus on the good fats, eat less in general and do a better job of managing our weight. Sigh…..

This randomized, double-blind, placebo-controlled trial was conducted at three medical centers in Italy. The trial studied the effects of 54mg/day of pure soy genestein on bone metabolism in postmenopausal women with osteopenia. Bone density at the femoral neck and lumbar spine was tested after 24 months along with serum levels of bone-specific alkaline phosphatase, markers of bone turnover (urinary excretion of pyridinoline and deoxypyridinoline), insulin-like growth factor 1 (IFG-1) and endometrial thickness.

389 postmenopausal women aged 49 to 67 with a femoral neck bone mineral density (BMD) of less than 0.795 g/cm2 received either genistein or placebo. All women received calcium and vitamin D. After 2 years, BMD at the femoral neck increased in the group that received the genistein and declined in the women who received placebo. A mean change of 0.035 gm/cm2 for genistein vs – 0.037 gm/cm2 for placebo. A smaller positive change was seen at the lumbar spine for genistein and a smaller loss in the placebo group.

Bone turnover decreased significantly in the women who received genistein, and bone-specific alkaline phosphatase and IGF-1 also significantly increased. None of these markers changed in the placebo group. Genistein did not significantly change the endometrial thickness but did reduce the mean number of hot flashes. Side effects included gastrointestinal symptoms and the withdrawal rate from the study due to these side effects was 19% in the genistein group vs 8% in the placebo group.

Marini H, Minutoli L, Polito F, et al. Effects of phytoestrogen genistein on bone metabolism in osteoenic postmenopausal women: a randomized trial. Ann Intern Med 2007;146:839-847.

Comments: Previous studies have reported that women with high soy diets had a lower risk for osteoporosis. The current report provides additional compelling evidence that 54 mg of genistein per day, along with 500 mg of calcium and vitamin D 400 IU for 2 years can increase the BMD of the lumbar spine and femoral neck. Further evidence is provided by the decreased urinary markers for bone resorption and the increase in circulating levels of the bone formation markers.

More than twice as many women had side effects in the genistein group and discontinued treatment because of these symptoms. That said, these side effects are considerably less than those reported for many women who utilize bisphosphanates for bone loss. Although I would not consider genistein an adequate treatment for women with osteoporosis, I would consider genistein an important treatment in women with osteopenia, especially up to the age of 65, prior to higher age related risks for fracture.

In a population-based study, 1180 Caucasian women older than 55, were randomized to receive a daily placebo, calcium or calcium plus 1000 IU of vitamin D (cholecalciferol).  Health status and compliance to the regimen were assessed every 6 months over 4 years and serum vitamin D was measured at baseline and annually. 1024 women actually completed the study.  

Lappe J, et al.  Vitamin D and calcium supplementation reduces cancer risk: Results of a randomized trial.  Am J Clin Nut 2007; une 85: 1586-1591

Lin J et al.  Intakes of calcium and vitamin D and breast cancer risk in women. Arch Intern Med 2007, May 28; 167:1050-1059.

Sixty postmenopausal women were randomized in a crossover trail to either a therapeutic lifestyle changes (TLC) diet alone consisting of 30% total fat (< 7% saturated fat, 15% protein, 55% carbohydrates, and < 200 mg of cholesterol). or a similar TLC diet which included one-half cup soy nuts containing 25 grams of soy protein and 101 mg of isoflavones, divided into 3-4 doses throughout the day. For each 8-week time period, study subjects recorded the number of hot flashes.

The TLC diet plus soy nuts was associated with a 45% decrease in hot flashes, when compared to the TLC diet alone, in women with > 4.5 hot flashes per day. With treatment, there were 4.1 hot flashes per day in the TLC plus soy nut group vs 7.5 hot flashes per day in the TLC diet alone group. Soy nuts were also associated with a significant improvement in other menopausal symptom quality of life issues including psychosocial scores.

Welty F, Lee K, Lew N, et al. The association between soy nut consumption and decreased menopausal symptoms. J Women’s Health 2007;16(3): 361-369

Commentary: Numerous previous studies have shown inconsistent reductions in menopausal symptoms with soy preparations, whether it be soy foods, soy beverage, soy powders or soy isoflavone capsules/tablets. In this study, it may be that the complex of a whole soy bean with a significant amount of soy protein and isoflavones were responsible for greater relief relative to most other studies. This study was not blinded, so a placebo response must be considered.