In each of the studies, women who consumed the highest dietary intake of soy had a lower risk for endometrial and ovarian cancers compared with the women who had the lowest intake.

Commentary: It is not surprising to see this report as we have seen previous observational studies with similar results, showing lack of endometrial proliferation, endometrial safety and/or reduced risk of endometrial cancer. Only one previous study that I’m aware of, did demonstrate that after 5 years, but not after one year or 3 years, who were given 150 mg per day of soy isoflavone tablets had an increased occurrence of endometrial hyperplasia (but no cases of atypical hyperplasia or endometrial cancer).[ii]

The mechanisms whereby soy appears to have an influence on lowering the risk of hormonal cancers, including breast, appear to be multiple. These include: through its ability to bind to certain estrogen receptors and actually have an estrogen blocking effect, raising sex hormone-binding globulin which decreases circulating estrogens, affecting selected enzyme pathways which result in anti-carcinogenic effects, direct tumor growth inhibition, and having antioxidant effects.

My advice: for most women, and for those who are not allergic to soy or have indigestion with soy products, I recommend 1-2 servings per day of the following soy foods: cooked soy beans, roasted soy nuts, soy milk, tofu, tempeh, edamame, tofu pate (my favorite).

[i] Myung S- K et al. Soy intake and risk of endocrine-related gynaecological cancer: A meta-analysis. BJOG 2009 Dec; 116:1697

[ii] Unfer V, et al. Endometrial effects of long-term treatment with phytoestrogens: a randomized, double-blind, placebo-controlled study. Fertility and Sterility 2004;82:145-148). 150 mg of soy isoflavones per day is above the average intake in an Asian diet (ranging from about 40-90 mg per day

Commentary: We know that elevated homocysteine levels are associated with the risk for AMD and B vitamins lower homocysteine levels. The current study suggests that supplementation with these three B vitamins can lower the risk for AMD, although it is not clear if this result is indeed related to homocysteine lowering or some other mechanism.

References

Christen W,et al. Folic acid, pyridoxine, and cyanocobalamin combination treatment and age-related macular degeneration in women: The women’s antioxidant and folic acid cardiovascular study. Arch Intern Med 2009. Feb 23;169:335

Individuals with CFS/FMS are found to have: 20% less energy in their muscles,, defective or inefficient mitochondria, nutrient deficiencies in cells and tissues needed to process food into energy, and thickened capillary walls slowing the rate of synthesizing energy.

As cellular energy is depleted, fatigue and muscle pain become more and more severe and the muscles require additional energy in their recovery efforts. Energy is used faster than fuel is made available to renew it, and the fatigue, soreness, pain and stiffness continue to progress. Energy depletion reaches a critical point and CFS/FMS becomes a state in which the mechanisms for recovery are overwhelmed.

D-Ribose is a naturally occurring five-carbon sugar found in all living cells. It is the D-isomer of ribose that has been shown to possess biological activity. The body naturally converts glucose into ribose. Ribose is then used to drive the pathways of energy metabolism. One of the problems faced when the body’s ribose stores have been depleted, is that tissues such as heart and muscle are unable to produce it quickly enough to restore this depleted energy store. It is this delay that slows cellular and tissue energy recovery.

D-ribose is a component of ATP, RNA, NADH, and coenzyme-A, all needed by the mitochondria to maintain cellular energy homeostasis. In the body, we form ribose through the pentose phosphate pathway (PPP) or through the hexose monophosphate shunt. In heart and muscle tissue, the PPP is fairly slow because these tissues lack the enzymes needed to shunt the glucose in the pathway of ribose synthesis. These tissues instead prefer to use glucose to fuel ATP. The enzymes glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase preserve glucose metabolism, at a cost to ribose synthesis. When ribose is needed to rebuild the ATP pools, the process is slow. This is the main rationale for providing supplemental ribose for heart and muscle tissue, the purpose being to speed up the rebuilding of depleted ATP pools, thereby promoting a quicker more efficient tissue recovery.

Most body tissues cannot make enough ribose to restore energy levels to normal once they have been depleted. When cells suffer metabolic stress or mitochondrial dysfunction, ATP is catabolized and metabolic recovery is compromised. These mechanisms may be similar to what occurs in individuals with CFS. Under these conditions, adenosine diphosphate (ADP) accumulates and the cells try to balance the ratios of ATP with ADP to maintain energy. These reactions lead to catabolic end products that are washed out of the cell with a subsequent loss in purines and adenine nucleotides. One therapeutic option is to try to restore these energy substrates in order to recover the function of the cell, including muscle cells. By providing supplementation in the form of ribose, it is possible to enhance the nucleotide recovery, and preserve or even rebuild cellular energy stores.

D-ribose research in CFS/FMS was initiated with a case study in 2004 of a veterinary surgeon with fibromyalgia. After 3 weeks of ribose she was back to full time work, with her profound fatigue and muscle pain having disappeared. An important study was also done involving high-intensity athletes. Post exercise, muscle energy levels were reduced by almost 30%. Supplementing with 10 g of ribose per day for 3 days following the exercise restored muscle levels to normal while those treated with placebo received no effect.

An open-label uncontrolled pilot study was done to evaluate the effect of D-ribose on symptoms in forty-one CFS and FMS patients D-ribose was given at a dose of 5 grams t.i.d. for an average of three weeks. Questionnaires pre and post D-ribose intervention were compared and showed a significant improvement in five categories: energy, sleep, mental clarity, pain intensity and well being. At the end of the study, approximately 66% of patients experienced significant improvement while using D-ribose. These patients had a 45% average increase in energy and a 30% overall improvement in well-being.

Many individual nutrients and botanicals are utilized in the treatment of CFS/FMS: magnesium, CoQ10, malic acid, vitamin D, rhodiola, licorice, ginseng, resveratrol, carnitine and more. While most alternative minded practitioners embrace a whole system, mind/body, functional approach in working with these challenging clinical situations, I have found D-ribose to be the single most important nutrient in the search for alleviation of symptoms and a path towards health. I thank Jacob Teitelbaum, M.D. and other D-ribose researchers for pointing us in the right direction.

References

• No authors listed. Symptoms of mitochondrial cytopathies. United Mitochondrial Disease Foundation. Avalable at http://www.umdf.org/site/c.dnJEKLNqFoG/b.3042207/. Accessed March 4, 2008.
• Mignot E, Taheri S, Nishino S. Sleeping with the hypothalamus: emerging therapeutic targets for sleep disorders. Nat Neurosci 2002; Nov;5 Suppl: 1071-1075.
• Palkovits M. Interconnections between the neuroendocrine hypothalamus and the central autonomic system. Geoffrey Harris Memorial Lecture, Kitakyushu, Japan, October 1998. Front Neuroendocrinol. 1999;20(4):270-295.
• Demitrack M, Dale K, Straus S, et al. Evidence for impaired activation of the hypothalamic-pituitary-adrenal axis in patients with chronic fatigue syndrome. J Clin Endocrinol Metab. 1991: 73(6); 1223-1234.
• Bengtsson A, Henriksson K. The muscle in fibromyalgia-a review of Swedish studies. J Rheumatol Suppl. 1989 Nov; 19:144-149.
• Lund N, Bengtsson A, Thjorborg P. Muscle tissue oxygen pressure in primary fibromyalgia. Scand J Rheumatol. 1986; 15(2):165-173.
• Strobel E, Krapf M, Suckfull M, et al. Tissue oxygen measurement and 31P magnetic resonance spectroscopy in patients with muscle tension and fibromyalgia. Rheumatol Int. 1997; 16(5)175-180.
• Douche-Aourik F, Berlier W, Feasson L, et al. Detection of enterovirus in human skeletal muscle from patients with inflammatory muscle disease or fibromyalgia and healthy subjects. J Med Virol. 2003;71(4):540-547.
• Park J, Phothimat P, Oates C, Hernanz-Schulman M, Olson N. Use of P-31 magnetic resonance spectroscopy to detect metabolic abnormalities in muscles of patients with fibromyalgia. Arthritis Rheum. 1998; 41(3):406-413.
• Kushmerick M. Muscle energy metabolism, nuclear magnetic resonance spectroscopy and their potential in the study of fibromyalgia. J Rheumatol Suppl. 1989 Nov; 19:40-46.
• Bengtsson A, Henriksson K, Larsson J. Reduced high-energy phosphate levels in the painful muscles of patients with primary fibromyalgia. Arthritis Rheum. 1986;29(7):817-821.
• Lund E, Kendall S, Janerot-Sjoberg B, Bengtsson A. Muscle metabolism in fibromyalgia studied by P-31 magnetic resonance spectroscopy during aerobic and anaerobic exercise. Scand J Rheumatol. 2003;32(3):138-145.
• Eisinger J, Bagneres D, Arroyo P, Plantamura A, Ayavou T. Effects of magnesium, high-energy phosphates, piracetam and thiamin on erythrocyte transketolase. Magnes Res. 1994;7(1):59-61.
• Pouleur H. Diastolic dysfunction and myocardial energetics. Eur Heart J 1990; 11(Supp): 30-34.
• Pasque M, Wechsler A. Metabolic intervention to affect myocardial recovery following ischemia. Ann Surg 1984;200:1-10.
• Perlmutter N, Wilson R, Angello D, et al. Ribose facilitates thallium-201 redistribution in patients with coronary artery disease. J Nucl Med 1991; 32:193-200.
• Gebhart B, Jorgenson J. Benefit of ribose in a patient with fibromyalgia. Pharmacotherapy. 2004;24(11):1646-1648.
• Hellsten Y, Skadhauge L, Bangsbo J. Effect of ribose supplementation on resynthesis of adenine nucleotides after intense intermittent training in humans. Am J Physiol Regul Integr Comp Physiol. 2004;286(1):R182-R188.
• Teitelbaum J, Johnson C, St Cyr J. The use of D-ribose in chronic fatigue syndrome and fibromyalgia: a pilot study. J Altern Complement Med 2006 Nov; 12(9):857-862.

1. ingredients
2. potency
3. quality
4. manufacturing process

In general, however, basic mass-market multiples are often sold at a lower price because they are inferior in one or more of those four basic ways. Typically, they omit mixed carotenoids, bioflavonoids and smaller minerals and nutrients such as vitamin K, boron and iodine. Because they contain fewer ingredients, and often not some of the premier more costly ingredients such as CoQ10, they are less expensive. One of the most striking differences is the amount of individual ingredients. For instance, vitamin D may range from 100 IU to 400 IU; calcium may vary from 200 mg to 500 mg. Taking one capsule/tablet per day may be what is written on the label, but serving sizes may be 2 or 3 capsules in order to get the total on the label. The point is, read the label carefully so you are taking the number of capsules you need to take, in order to get the dose on the label. Many of the vitamins and minerals are available in more than one form and some are more bioavailable than others. Bioavailability is determined by absorption or more efficient use by the body. For instance, calcium carbonate is usually less expensive, but for some people it is constipating and they do better with calcium citrate - this is not necessarily more expensive, but it is a bulkier form of calcium with less elemental calcium per pill, so you have to take more pills to get the dose you have targeted. Many vitamins are synthetic and aren’t available in natural forms. Beta carotene for example comes in a natural or synthetic form and better yet, some multiples contain natural mixed carotenoids and the natural form of other vitamins, which provide additional more potent antioxidant effects. Processing methods also vary, and some of those methods expose the nutrients to greater heat less stable conditions, and use additives and dyes which can render them with less nutritional value.

One capsule/tablet per day mass market multis are usually very low potency, contain the less desired form of the nutrient, omit some important ingredients that would be optimal for a daily vitamin, and contain unnecessary additives. Look for multis where the serving size is 2 or 3 capsules per day, have mixed natural carotenoids, have some of the extras such as bioflavonoids, vitamin K, boron, iodine and then you have to be a bit studious in order to learn about the more bio-available forms of nutrients. The book, Encyclopedia of Nutritional Supplements by Michael Murray, N.D. is an excellent resource for this.

Armanini D, Castello R. Scaroni C, et al. Treatment of polycystic ovary syndrome with spironolactone plus licorice. Eur J Obstet Gynecol 2007;131:61-67.

Commentary: It’s very useful to find a second study on licorice and it’s role in PCOS. Glycyrrhetinic acid has been shown to reduce serum testosterone and induce regular ovulation. (Yaginuma T, Izumi R, Yasui H, et al. Effect of traditional herbal medicine on serum testosterone levels and its inductions of regular ovulation in hyperandrogenic and oligomenorrheic women. Nippon Sanka Fujinka Gakkai Zasshi 1982;34:939-944) ( Takahashi K, Yoshino K, Shirai T, et al. Effect of a traditional herbal medicine on testosterone secretion in patients with polycystic ovary syndrome detected by ultrasound. Nippon Sanka Fujinka Gakkai Zasshi 1988;789-92.)

Spironolactone is often used as part of a treatment plan in PCOS women with bothersome hirsutism. While Spironolactone can be helpful, fatigue and polyuria are a frequent side effect. It may be that licorice and glycyrrhetinic acid have a potential synergistic effect on the androgen receptors, reduce the side effects associated with Spironolactone, as well as reducing serum testosterone and inducing regular ovulation. Licorice extract along with a lower carbohydrate/higher protein diet, therapies that increase SHBG such as nettles root, green tea, flax seeds and soy and insulin sensitizing strategies such as daily aerobic exercise, fenugreek powder, cinnamon extract, d-pinitol, chromium (and possibly glucophage) offer a comprehensive approach for women with PCOS.

According the Hamilton Depression Rating Scale, 15 of 25 women in the saffron group responded to treatment vs only 1 of 25 in the placebo group. (P< 0.0001). Again, a significant difference was seen between cycles 3 and 4 with a statistically significant difference by the study end (P< 0.0001).

Crocus sativus L. (saffron) in the treatment of premenstrual syndrome: a double-blind, randomised and placebo-controlled trial. Agha-Hosseini M, Kashani L, Aleyaseen A, et al. BJOG 2008;115:515-519.

Commentary: Improvements in the Total Premenstrual Daily Symptoms and the Hamilton Depression Rating Scale with saffron should give us definite motivation to try this simple treatment. Saffron has been previously shown to have an antidepressant effect in women with mild to moderate depression, through a serotonergic mechanism, so it’s not surprising that it would work in PMS. Research on PMS in the last several years has pointed strongly to the etiology being the dysregulation of the serotonergic system. This is why we have seen conventional medical practitioners focus on the use of SSRIs in treatment.

This is the first clinical trial I’ve seen in the use of saffron for the treatment of PMS. While only a small study and short follow-up, the positive results warrant further study, and in the meantime, accumulating some clinical experience.

The National Institutes of Health has one of the most well-accepted guidelines for women’s calcium intake:

Most people need to supplement to get enough calcium because we have reduced our dairy intake. Estimating dietary sources of calcium is an important first step, before deciding how much to augment in a pill. Not counting dairy or calcium-fortified foods, you get about 250 mg of calcium per day from our grains, seeds and vegetables. If you drink milk, calcium-fortified soy milk or OJ, you rack up an additional 300 mg per 1 cup serving. That’s 250 mg + 300 mg = 550 mg per day. Let’s say you’re 51, postmenopausal and not using estrogen. You’ll need an additional 950 mg to reach the goal of 1,500 mg per day. More is not better. Taking too much may not be good for your heart or other soft tissue and may inhibit mineral absorption.

But bone is not nourished by calcium alone. Vitamin D, is probably even more important than calcium. Other nutrients that can affect bone health include magnesium, manganese, boron, zinc, folic acid, vitamin B6 and vitamin K. These different nutrients are important in one or more of the following: bone density, bone architecture and/or bone strength.

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 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.
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• Garland C, Garland F, Gorham E, et al. The role of vitamin D in cancer prevention. Am J Public Health. 2006; 96: 252-261.
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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…..