This study was a double blind clinical trial in 150 women in Iran. Two groups of 75 women each were evaluated for severity and duration of breast pain which was measured according to a breast pain chart and something called a Visual Analog Scale.

Chewable tablets of either vitamin E 200 mg tablets or a placebo were given twice a day for 4 months, and again, the severity and duration of breast pain was evaluated at the end of the second and fourth month. The results at two months for vitamin E were dramatically better than placebo in severity and duration, and appear to be achievable in about 70% of the women. The improvement was seen as soon as two months, and no continued improvement after 4 months.

Commentary: Other studies have been conducted in vitamin E and breast pain. In 1997, Khanna et al compared vitamin E with a drug called Danazol. Vitamin E reduced pain in 41% of the women in the studies and Danazol had similar pain reduction in 72% of the women. Clearly the drug helped more women, but the side effects of that drug are significant and one third of the women developed other side effects. Meyer et al did a study in 1990 but did not show any benefit from Vitamin E. Ernester in 1985 studied 201 women with mastalgia as it relates to fibrocystic breast disease. He concluded that vitamin E was not effective, but he was not evaluating breast pain as a distinct issue. In 2004, Bespalov et al studied 66 women with a combination of beta-carotene, vitamin E, vitamin C and garlic powder. There was a reduction in the severity of mastalgia, premenstrual syndrome, infrequent menses and menstrual cramping as well as a reduction in symptoms of fibromatosis in 75% of the women compared with 45% of women on placebo.

If vitamin E alone is not sufficiently helpful in reducing mastalgia, evening primrose or borage oil should be considered, as well as carotenoids, iodine, eliminating caffeine, lowering saturated fats in the diet and increasing fiber.

References

Parsay S, Olfati F, Nahidi S. Therapeutic effects of vitamin E on cyclic mastalgia. The Breast Journal 2009;15(5):510-514.

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

It has been known for a considerable amount of time, that folic acid when given to women planning for pregnancy and during pregnancy, can lower the risk for neural tube defects. Based on the research up to that time, the US Preventive Services Task Force (USPSTF) first published their recommendations in 1996. This has recently been updated and the USPSTF has issued a new statement in May, 2009. Based on the observational evidence and randomized controlled trials published since 1996, the USPSTF found convincing evidence that supplements containing 0.4 to 0.8 mg of folic acid during the preconception period lowers the risk for neural tube defects.[1]

There now appears to be additional benefits for folic acid before conception and during pregnancy, possibly the prevention of cleft lip (BMJ 2007;334:464) and most recently, lowering the rates of severe congenital heart defects. In a Quebec study, investigators observed a drop in the prevalence of severe congenital heart defects after mandatory folic acid fortification of grains. The average prevalence of severe congenital heart defects at birth was 1.64 per 1000 births during the 9 years before the folic acid food fortification began and the rate fell by 6.2% yearly during the seven years studied, after the mandatory fortification.[2]

Following the recommendation that all women of child bearing age should take a daily supplement containing 0.4 mg to 0.8 mg per day of folic acid is good, safe medicine and perhaps even more beneficial than previously thought.

References

[1] Woffe T, Takacs-Witkop C, Miller T, Syed S. Folic acid supplementation for the prevention of neural tube defects: An update of the evidence for the U.S. Preventive Services Task Force. May 2009.150; (9): 632-639

[2] Ionescu-Ittu R, et al. Prevalence of severe congenital heart disease after folic acid fortification of grain products: Time trend analysis in Quebec, Canada. BMJ 2009;338:b1673

St John’s wort was compared with a placebo in a double-blind, randomized clinical trial on symptoms and quality of life issues in perimenopausal women. Forty-seven 40 to 65 y.o. perimenopausal women who experienced three or more hot flashes per day were randomized to receive either 900 mg three times daily of a St. John’s wort extract or placebo for 3-months. Hot flash severity and frequency were evaluated and the Menopause-Specific Quality of Life questionnaire was used to evaluate menopause related quality of life.

After 12 weeks, only a small difference was seen favoring St. John’s wort in the frequency of hot flashes. A 30% improvement in 50% of the women was seen in the St. John’s wort group and only 23% in the placebo group. A significant reduction in sleep problems and depression was seen with St. John’s wort and the St. John’s wort group scored significantly better menopause related quality of life.

References

Al-Akoum M, Maunsell E, Verreault R, et al. Effects of Hypericum perforatum (St. John’s wort) on hot flashes and quality of life in perimenopausal women: a randomized pilot trial. Menopause 2009; 16(2):307-314

Folic acid updates for pregnant women

It has been known for a considerable amount of time, that folic acid when given to women planning for pregnancy and during pregnancy, can lower the risk for neural tube defects. Based on the research up to that time, the US Preventive Services Task Force (USPSTF) first published their recommendations in 1996. This has recently been updated and the USPSTF has issued a new statement in May, 2009. Based on the observational evidence and randomized controlled trials published since 1996, the USPSTF found convincing evidence that supplements containing 0.4 to 0.8 mg of folic acid during the preconception period lowers the risk for neural tube defects.[i]

There now appears to be additional benefits for folic acid before conception and during pregnancy, possibly the prevention of cleft lip (BMJ 2007;334:464) and most recently, lowering the rates of severe congenital heart defects. In a Quebec study, investigators observed a drop in the prevalence of severe congenital heart defects after mandatory folic acid fortification of grains. The average prevalence of severe congenital heart defects at birth was 1.64 per 1000 births during the 9 years before the folic acid food fortification began and the rate fell by 6.2% yearly during the seven years studied, after the mandatory fortification.[ii]

Following the recommendation that all women of child bearing age should take a daily supplement containing 0.4 mg to 0.8 mg per day of folic acid is good, safe medicine and perhaps even more beneficial than previously thought.

References

[i] (Woffe T, Takacs-Witkop C, Miller T, Syed S. Folic acid supplementation for the prevention of neural tube defects: An update of the evidence for the U.S. Preventive Services Task Force. May 2009.150; (9): 632-639)

[ii] (Ionescu-Ittu R, et al. Prevalence of severe congenital heart disease after folic acid fortification of grain products: Time trend analysis in Quebec, Canada. BMJ 2009;338:b1673.)

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.