Mauro@MetabolicDiet.

com

Nutritional Supplements

www.MDPlusStore.com

DR. DS ELITE PERFORMANCE NEWSLETTER

Volume One, Issue One, December, 2009

Introduction to the Newsletter

This newsletter is for the elite athlete looking to maximize body composition and athletic performance. In it Ill present information that will help you accomplish that along with explaining how it all ties in with the MD+ line of nutritional supplements, which were formulated by listening to all of the relevant scientific and medical studies, and combining this information with my over four decades in the trenches experience dealing with athletic performance enhancement. I wont be writing this newsletter in my usual fashion. For example instead of writing as if I was doing a journal article, Ill be somewhat more colloquial with my writing, present some of the information in outline format, and limit the number of references to just the ones that I think youll find most useful. Ill list these references, including abstracts at the end of each section of the newsletter. As well, if it adds to the topic Im discussing, Ill also be listing a number of internet sites that have useful and relevant information. Im hoping to put out this newsletter every month but dont be surprised if its early or late as it will be done as time and energy permits, and as much time at my desk as my two young and physically demanding grandchildren will allow. This email will be exclusively sent to only a thousand or so individuals that Ive worked with either directly or indirectly. However, if anyone receiving this newsletter thinks that there are others that can benefit from it, please feel free to pass it on. As well, anyone who is not on the initial email list can contact me directly at Mauro@MetabolicDiet.com and ask to be put on the mailing list. Every month well be covering one or more topics that I hope elite athletes, their coaches, and sports orientated health professionals will find informative and useful. This month our main topic will be vitamin D as I feel that because of the rampant vitamin D deficiency in athletes its a topic that needs to be put front and center. In future newsletters well be covering a variety of topics including both macro and micro nutrients that are crucial for maximum athletic performance and body composition, drug testing, diets, and various aspects of supplements and the supplement industry, both good and bad.

Vitamin D and Athletic Performance

Vitamin D is More Than Just for Strong Bones
Not too many years ago vitamin D wasnt considered all that vital beyond helping calcium challenged people, especially women who were or had a tendency toward osteoporosis, and of course to prevent rickets, something rarely seen in industrialize countries since even minimal amounts of vitamin D prevents severe deficiency. As such, when most people hear about vitamin D they think of sunshine and bones. Thats because its common knowledge that exposure to the sun results in the formation of vitamin D and that vitamin D is important, along with calcium, for strong bones. While that aspect of vitamin D is important, theres a lot more to the vitamin D story. Vitamin D is really a group of fat soluble prohormones called secosteroids. Thus, unlike most other vitamins, vitamin D is really a steroid hormone that the body uses to manufacture calcitrol (1,25-Dihydroxycholecalciferol), which is the active form of vitamin D in our bodies. The two major forms of the vitamin obtained from sun exposure, food, and supplements are vitamin D2 (or ergocalciferol) and vitamin D3 (or cholecalciferol). Cholecalciferol is the vitamin D produced in humans by exposure to the sun, and is felt to be more effective than ergocalciferol for enhancing calcitrol levels in our bodies. Recent research however, show that vitamin D is crucial for many functions in the body, and is crucial for many internal cellular processes, insulin production, the immune system, depression, heart disease, pregnancy problems, birth defects, skin and other cancers, and other diseases, including inflammation in the body from various sources, including aging. For example recent studies have found that low serum vitamin D levels were associated with allcause mortality, cancer, and cardiovascular disease mortality. As a measure of just how important it is, its felt that possibly up to 2,000 different genes, which represents about one-sixth of the human genome, are affected by vitamin D.

Why Most of Us May Be Vitamin D Deficient

Vitamin D deficiency is increasingly being recognized as a worldwide epidemic. According to various reports experts believe that up to 3 out of every four adolescents and adults are vitamin D deficient, which is generally defined as having blood levels of less than 30 ng/mL. For your skin to make enough, you'd need direct midday summer sunlight on a large portion of your body for around 15 minutes a day. If you live north of Atlanta, it's impossible to get enough D from sunlight between October and March, no matter how exposed you are. And it's tougher for people of color to make vitamin D the melanin in dark skin decreases vitamin D production by up to 90 percent. 3

Although it seems logical to assume that people in high altitudes would not be deficient in vitamin D given that the ultraviolet light intensity is higher at high altitudes resulting in a greater vitamin D3 synthetic rate, the opposite is actually the case. The reason for this is likely that at higher altitudes the cooler weather involves using more clothing and less sunbathing. Declines in vitamin D occur over the winter, with the level of decline, without conscious efforts to expose yourself to adequate sunshine or tanning UVB rays and without supplementation, is dependant on the level of vitamin D at the beginning of winter. So the more youre able to maximize your vitamin D storage levels, the more youll be left with by the end of winter. However, if you rely on your summer acquired stores of vitamin D, and because winter can last several months, somewhere along the line youll develop vitamin D deficiency. Much of the decline during winter months, and for those who dont get a lot of sunlight during the summer, is due to the lack of vitamin D in the food we eat. Only certain kinds of fish and some fortified foods such as dairy and orange juice have significant amounts of vitamin D (see list below), and it would be hard to consume enough of these every day to get 1,000-plus IU. And its possible that even those who seem to get lots of sun, because of variable responsiveness to UVB radiation may be vitamin D deficient (see full paper and abstract below Low vitamin D status despite abundant sun exposure).

Vitamin D is Vital for Exercise Performance

The effects of vitamin D on performance have been known for decades. Back in the 1950s a number of German studies alluded to the beneficial effects of vitamin D on athletic performance (for example, Seidll E, Hettinger T. Influence of vitamin D3 on strength and efficiency of healthy adults. Int Z Angew Physiol. 1957;16(5):365-72.). As well, its well known that physical and athletic performance is seasonal in that it follows levels of vitamin D, peaking when it peaked and declining as vitamin D levels declined. Vitamin D also increases the size and number of Type II (fast twitch) muscle fibers. Most crosssectional studies show that 25(OH)D levels are directly associated with musculoskeletal and physical performance in older individuals. But its not just the performance of older people that are affected by vitamin D deficiency. A recent review concluded that Accumulating evidence supports the existence of a functional role for vitamin D in skeletal muscle with potentially significant impacts on both the performance and injury profiles of young, otherwise healthy athletes. Other studies have shown that low vitamin D is a contributory factor in stress fractures in athletes. Another recent review (Athletic performance and vitamin D. - Cannell JJ - Med Sci Sports Exerc - 01-MAY-2009; 41(5): 1102-10.) concluded "Most cross-sectional studies show that 25(OH)D levels are directly associated with musculoskeletal performance in older individuals. Most randomized controlled trials, again mostly in older individuals, show that vitamin D improves physical performance. CONCLUSIONS: Vitamin D may improve athletic performance in vitamin D-deficient athletes. Peak athletic performance may occur when 25(OH)D levels approach those 4

obtained by natural, full-body, summer sun exposure, which is at least 50 ng x mL(-1). Such 25(OH)D levels may also protect the athlete from several acute and chronic medical conditions."

How Much Vitamin D Can We Take?

Vitamin D is fat-soluble, which means it stays in the body for longer periods of time as opposed to the water soluble vitamins such as vitamin C. This is good because it takes a longer period of time to become deficient if you start off with healthy levels in your body. For example if you build up vitamin D over the summer then theres less chance youll be come deficient over the winter as long as you take in some vitamin D by eating foods high in vitamin D, take vitamin D supplements or expose your skin to artificial ultraviolet light. Its also bad in that if you take too much it can accumulate in the body and can cause toxicity. However, this aspect of vitamin D has been overemphasized in the past as it was thought that vitamin D accumulated and stayed in the body much more than it actually does. Vitamin D doesnt stay in the body forever as it is broken down continually by the body and disposed of. Vitamin D stored in the body has a half life of only three or four weeks, and this half life shortens with higher vitamin D levels. Exposure of skin to direct sunlight can produce up to 25,000 IU of vitamin D. However, when vitamin D gets to a certain level, any further vitamin D that is produced is degraded. That means that the body can degrade and lower vitamin D levels in the body if it has to and thus can handle a lot more vitamin D than was previously thought. That doesnt mean that our bodies can handle a lot more than previously understood, and that you cant overdose on vitamin D and develop some counter productive and health damaging toxicity. However, in my opinion it would take over 10,000 IU per day for several months before you would overwhelm the bodys ability to degrade excess vitamin D and produce more than physiological levels.

How Much Vitamin D do Athletes Need?

With sun exposure, pre-vitamin D3 is rapidly converted in the dermis to vitamin D3 (cholecalciferol), before its subsequent conversion to 25-hydroxy vitamin D [25(OH)D] in the liver. Further hydroxylation of 25-hydroxy vitamin D to its active form, 1,25 hydroxy vitamin D (1,25(OH)2D), occurs in the kidney However, while the active form of vitamin D may be normal in the blood, the lack of reserves in the form of 25(OH)D is the actual measure of vitamin D reserves in the body and is used as a measure of vitamin D deficiency. Besides being a better marker of overall D status, it is the marker that translates best with the overall beneficial effects of vitamin D. 5

The basis for figuring out how much vitamin D that any one individual needs can be casually stated (such as a suggested range of vitamin D intake) or can be more precise depending on the tools we use. For precise determinations we need to know just what the present state of any individual is by getting a serum 25(OH)D level. From this level we can figure out just how much vitamin D is needed on a daily basis in order to achieve a desired vitamin D level in the body. For example, if your 25(OH)D level is OK, and for optimal levels it should be between 50 and 70 ng/mL (for nnmol/L multiply by 2.5 so 50 ng/mL would be 125 nmol/L see http://www.globalrph.com/conv_si.htm#top), then youre in the right range and to stay there you should get between 1,000 and 2,000 IU of vitamin D per day. If youre below 50 ng/mL then you need to top up first and that might require 5,000 to 10,000 IU for several days to weeks depending on how low your levels are. If for example theyre below 20 ng/mL then I would suggest you take 10,000 IU for at least a month and then your levels checked again to see if you should continue at that level or go to maintenance levels of between 1,000 to 2,000 IU per day. As a guide, Ive put my recommendations for maximum health, body composition and performance in the following table. 25(OH)D level in ng/mL Less than 20 Between 20-30 Between 30-40 Between 40-50 Above 50 Amount of Daily Vitamin D to take 10,000 IU per day 10,000 IU per day 5,000 IU per day 5,000 IU per day 1,000 to 2,000 IU Length of Time For at least 4 weeks For at least 2 weeks For at least 4 weeks For at least 2 weeks Daily

How you get the required amounts of vitamin D is up to the individual and his or her circumstances. For those with access to full UV-B sunshine, a half hour a day of near full body exposure (be careful to build up slowly and not get sunburned) will go a long way to giving you the necessary amount of vitamin D. As well, eating food high in vitamin D is also an option although to get enough (unless youre unbelievably fond of fatty fish and liver oils, and even if you are fond of cod and other fish liver oil you have to make sure you dont overdo the vitamin A that these oils also contain), you will likely have to combine the dietary intake with sun exposure and/or vitamin D supplements. If you feel that you cant meet your requirements through a combination of sun exposure and food, then the use of vitamin D in the form of supplements, ideally as cholecalciferol or vitamin D3, is the easiest, cheapest, and safest way to make sure you're covered. To make sure that they stay in the optimal vitamin D zone I recommend that athletes take in between 1,000 IU up to 2,000 IU, a day in the form of supplements. This amount will insure that 6

your vitamin D levels stay where they should be and also insure that you dont run into any toxicity, no matter how long you take that level of vitamin D.

Conclusions and Recommendations

First of all its important to get your 25(OH)D blood level measured to see just where you are as far as your long term vitamin D intake. Once you have the initial measurement and make any changes that need to be made as far as daily vitamin D intake, you should have your 25(OH)D level check as needed until youre above 50 ng/mL, and then once its relatively stabilized get it done at least once a year just to make sure youre not developing a deficiency. Although this process takes some effort its important for all athletes who want to maximize natural performance. At the same time a number of other blood tests can be done that will point out other problems and deficiencies. Ive copied below the screening protocol I suggest athletes have done. If money is tight then the bolded tests are the ones that are absolutely necessary, while the others can be done as finances permit. Dont hesitate to get some full sun exposure every day. The sensationalistic naysayers and purveyors of skin cancer with any amount of sun exposure should be ignored. Reasonable, and controlled levels of daily sun exposure to your body is not something to avoid but something to be sought as it has significant health benefits as long as sunburn is avoided and there are no medical contraindications such as the presence or predisposition to skin cancer and interactions with some medications. Regardless of sun exposure and foods eaten, take between 1,000 and 2,000 IU of supplemental vitamin D every day. If your vitamin D levels are low then take more until youre at a level that you feel comfortable with, at least above 50 ng/mL, and then maintain by talking supplemental vitamin D as above. The bottom line is that regardless of whom you are or what sport youre into, without enough vitamin D, youre not reaching your health, body composition, and performance potential.

Some of the best natural sources of vitamin D

Fish Liver Oil amount depends on the fish.
Cod liver oil 1 tablespoon 1383 IU

Fish
Herring 3 oz 1383 IU Sardines 3.5 oz 500 IU Salmon 3.5 oz 360 IU Mackerel 3.5 oz 345 IU Tuna 3 oz 200 IU Eel 3.5 oz 200 IU

Other Foods
Orange Juice 1 cup 100 IU Milk 1 cup 98 IU Margarine 1 tbsp 60 IU Whole Egg 1 20 IU Beef Liver 3 oz 15 IU

Vitamin D in my MD+ supplements:

When buying supplements or fortified foods, make sure the label reads vitamin D3 (cholecalciferol). This is the more biologically active form of vitamin D and is what I use in all of my supplements. For more information on the supplements listed below, as well as the rest of nutritional supplement line up go to www.MDPlusStore.com. If you go to https://www.mdplusstore.com/listCategoriesAndProducts.asp?idParentCategory=40 you can view all of the supplements on one page. By clicking on the Product PDF button under each of the supplements you can view the complete information piece on that supplement.

Supplement MVM Amino Joint Support MRP LoCarb Metabolic InsideOut LipoFlush EFA+

Amount of vitamin D 800 IU 200 IU 200 IU 200 IU 200 IU 200 IU 100 IU 100 IU

Total vitamin D intake if all supplements were used daily as directed would be a minimum of 2,000 IU a day. MVM along with EFA+, part of my Foundation supplements along with Antiox, meant to provide an optimal foundation for maximizing body composition and performance, contains 900 IU units of vitamin D at one dose of each daily. Its common for athletes in hard training to take a half to full dose extra of each and that would provide 1350 to 1800 IU of vitamin D. Amino and MRP LoCarb, which make up two of the three supplements that I recommend all athletes use after training and competition, provide an additional 400 IU. And if any of the other supplements are used, as they are by many of my athlete, and are often included in their nutritional supplement regimens, there is an additional 200 to 400 IU per day. Overall, its easy to fall within my suggested 1,000 to 2,000 IU of vitamin D daily with the use of my supplements. Its important to realize that vitamin D is only a small part of my multi-ingredient, targeted formulations and that my supplements, used in concert, cover all the nutritional bases for optimizing body composition and athletic performance.

On Line Information and Papers for Vitamin D

http://en.wikipedia.org/wiki/Vitamin_D http://www.merck.com/mmpe/sec01/ch004/ch004k.html?qt=vitamin D&alt=sh#tb004_6 http://ods.od.nih.gov/factsheets/vitamind.asp http://www.nlm.nih.gov/medlineplus/ency/article/003569.htm http://www.boomnc.com/archive/2009_05/articles_live-well_200905_vitamind.html http://www3.interscience.wiley.com/cgi-bin/fulltext/122616574/PDFSTART http://jcem.endojournals.org/cgi/reprint/92/6/2130 http://www.ajcn.org/cgi/reprint/88/2/570S http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2629072/pdf/nihms82607.pdf http://www.ajcn.org/cgi/reprint/86/5/1399 http://www.ajcn.org/cgi/reprint/88/6/1535 http://www.ajcn.org/cgi/reprint/88/2/483S ----------------------------------------

International Units of Vitamin D

The vitamin-D content of a food is sometimes cited in micrograms of cholecalciferol, while at other times it is reported in International Units. There is an exact relationship between the two: one IU is equal to 0.025 micrograms of cholecalciferol. Hence: To convert IUs of vitamin D into micrograms: multiply the number of IUs by 0.025. The result is the number of micrograms in the food. To convert micrograms to IUs: multiply the number of micrograms by 40. The result is the number of IUs in the food.

10

Recommended Screening Blood Work

Blood work should be done at least two times in the yearly training plan to ensure optimal health status during training and leading into key competitions. Tests can also be ordered after an athlete presents with symptoms and requires subsequent treatment. Any abnormalities would trigger additional tests and possible follow up testing. Samples should normally be obtained in the morning, prior to coffee, breakfast or exercise. Avoid high intensity exercise for 24 hrs prior to sample collection ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ACTH Albumin Apolipoprotein (b) Blood group and Rh Factor Complete Blood Count Cortisol serum AM and PM C-reactive Protein Creatine Kinase DHEA and DHEAS Electrolytes/minerals etc. - Calcium, CO2, Chloride, Magnesium, Phosphorus, Potassium, Sodium, Zinc. Erythrocyte Sedimentation Rate (ESR) Estradiol Fibrinogen Free, bioavailable, and Total Testosterone Glucose Fasting Glycosylated Hemoglobin (HB A1C) HDL/LDL, Total Cholesterol Heavy Metal Profile (mercury, nickel, lead, arsenic and cadmium) Homocysteine Insulin-like growth factor-I (IGF-I) Lipoprotein (a) Liver Function Tests (serum total bilirubin, alkaline phosphatase, aminotransferase (AST and ALT)), GGT. Luteinizing Hormone (LH) Melatonin Prolactin RBC Folate Renal Function Tests Creatinine, Bun, Bun/Creatinine Ratio Serum Hormone Binding Protein (SHBG) Serum Iron Status Iron, Ferritin, Transferrin, Percentage Transferrin Saturation Thyroid Profile TSH, T4, T3, rT3 Serum Protein - Total Protein, Albumin, Globulin Albumin/Globulin Ratio. Triglycerides Uric Acid Vitamin B12 Vitamin D - 25-hydroxy vitamin D [25(OH)D] 11

Vitamin D References and Further Reading Table of Contents for References:

Use Ctrl + Click on any line to go to the specific reference. Vitamin D and Human Skeletal Muscle. ................................................................................................13! Vitamin D and its role in skeletal muscle...............................................................................................13! The level of vitamin D in the serum correlates with fatty degeneration of the muscles of the rotator cuff. ..............................................................................................................................................................14! Vitamin D: what is an adequate vitamin D level and how much supplementation is necessary? ..........15! Vitamin D Production after UVB Exposure Depends on Baseline Vitamin D and Total Cholesterol but Not on Skin Pigmentation......................................................................................................................16! Is vitamin D the fountain of youth? ........................................................................................................16! Vitamin D: current status and perspectives...........................................................................................17! Vitamin D level in summer and winter related to measured UVR exposure and behavior. ...................18! Vitamin D and skeletal muscle tissue and function. ..............................................................................19! Relationship between vitamin D status, body composition and physical exercise of adolescent girls in Beijing. ..................................................................................................................................................19! [Stress fracture in female athlete runner carrying weights] ...................................................................20! The vitamin D deficiency pandemic and consequences for nonskeletal health: mechanisms of action.21! Associations of diet, supplement use, and ultraviolet B radiation exposure with vitamin D status in Swedish women during winter. .............................................................................................................22! Estimation of the dietary requirement for vitamin D in healthy adults....................................................23! Low vitamin D status despite abundant sun exposure. .........................................................................24! Vitamin D physiology.............................................................................................................................25! Vitamin D and muscle function..............................................................................................................26! The vitamin D deficiency pandemic and consequences for nonskeletal health: mechanisms of action.27! Athletic performance and vitamin D. .....................................................................................................28! Should we be concerned about the vitamin D status of athletes?.........................................................29! The effect of conventional vitamin D(2) supplementation on serum 25(OH)D concentration is weak among peripubertal Finnish girls: a 3-y prospective study. ...................................................................29!

12

Scand J Med Sci Sports. 2009 Oct 5. [Epub ahead of print] Vitamin D and Human Skeletal Muscle. Hamilton B. ASPETAR, Qatar Orthopaedic and Sports Medicine Hospital, Doha, Qatar. Vitamin D deficiency is an increasingly described phenomenon worldwide, with well-known impacts on calcium metabolism and bone health. Vitamin D has also been associated with chronic health problems such as bowel and colonic cancer, arthritis, diabetes and cardiovascular disease. In recent decades, there has been increased awareness of the impact of vitamin D on muscle morphology and function, but this is not well recognized in the Sports Medicine literature. In the early 20th century, athletes and coaches felt that ultraviolet rays had a positive impact on athletic performance, and increasingly, evidence is accumulating to support this view. Both cross-sectional and longitudinal studies allude to a functional role for vitamin D in muscle and more recently the discovery of the vitamin D receptor in muscle tissue provides a mechanistic understanding of the function of vitamin D within muscle. The identification of broad genomic and non-genomic roles for vitamin D within skeletal muscle has highlighted the potential impact vitamin D deficiency may have on both underperformance and the risk of injury in athletes. This review describes the current understanding of the role vitamin D plays within skeletal muscle tissue. PMID: 19807897 [PubMed - as supplied by publisher] ----------------------------------------Curr Opin Clin Nutr Metab Care. 2009 Nov;12(6):628-33. Vitamin D and its role in skeletal muscle. Ceglia L. Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111, USA. lisa.ceglia@tufts.edu

13

PURPOSE OF REVIEW: Vitamin D is best known for its role in regulating calcium homeostasis and in strengthening bone. However, it has become increasingly clear that it also has important beneficial effects beyond the skeleton, including muscle. This review summarizes current knowledge about the role of vitamin D in skeletal muscle tissue and physical performance. RECENT FINDINGS: Molecular mechanisms of vitamin D action in muscle tissue include genomic and nongenomic effects via a receptor present in muscle cells. Knockout mouse models of the vitamin D receptor provide insight into understanding the direct effects of vitamin D on muscle tissue. Vitamin D status is positively associated with physical performance and inversely associated with risk of falling. Vitamin D supplementation has been shown to improve tests of muscle performance, reduce falls, and possibly impact on muscle fiber composition and morphology in vitamin D deficient older adults. SUMMARY: Further studies are needed to fully characterize the underlying mechanisms of vitamin D action in human muscle tissue, to understand how these actions translate into changes in muscle cell morphology and improvements in physical performance, and to define the 25-hydroxyvitamin D level at which to achieve these beneficial effects in muscle. -------------------------------------------J Bone Joint Surg Br. 2009 Dec;91(12):1587-93. The level of vitamin D in the serum correlates with fatty degeneration of the muscles of the rotator cuff. Oh JH, Kim SH, Kim JH, Shin YH, Yoon JP, Oh CH. Department of Orthopaedic Surgery, Seoul National University, College of Medicine, Seoul National University Bundang Hospital, Bundang-gu, Seongnam, Korea. This study examined the role of vitamin D as a factor accounting for fatty degeneration and muscle function in the rotator cuff. There were 366 patients with disorders of the shoulder. A total of 228 patients had a full-thickness tear (group 1) and 138 patients had no tear (group 2). All underwent magnetic resonance arthrography and an isokinetic muscle performance test. The serum concentrations of vitamin D (25(OH)D(3)) were measured. In general, a lower serum level of vitamin D was related to higher fatty degeneration in the muscles of the cuff. Spearman's correlation coefficients were 0.173 (p = 0.001), -0.181 (p = 0.001), and -0.117 (p = 0.026) for supraspinatus, infraspinatus and subscapularis, respectively. In group 1, multivariate linear regression analysis revealed that the serum 14

level of vitamin D was an independent variable for fatty degeneration of the supraspinatus and infraspinatus. The serum vitamin D level has a significant negative correlation with the fatty degeneration of the cuff muscle and a positive correlation with isokinetic muscle torque. ---------------------------------------------Best Pract Res Clin Rheumatol. 2009 Dec;23(6):789-95. Vitamin D: what is an adequate vitamin D level and how much supplementation is necessary? Bischoff-Ferrari H. Centre on Aging and Mobility, University of Zurich, Department of Rheumatology and Institute of Physical Medicine, Zurich, Switzerland. heike.bischoff@usz.ch Strong evidence indicates that many or most adults in the United States and Europe would benefit from vitamin D supplements with respect to fracture and fall prevention, and possibly other public health targets, such as cardiovascular health, diabetes and cancer. This review discusses the amount of vitamin D supplementation needed and a desirable 25-hydroxyvitamin D level to be achieved for optimal musculoskeletal health. Vitamin D modulates fracture risk in two ways: by decreasing falls and increasing bone density. Two most recent meta-analyses of double-blind randomised controlled trials came to the conclusion that vitamin D reduces the risk of falls by 19%, the risk of hip fracture by 18% and the risk of any non-vertebral fracture by 20%; however, this benefit was dose dependent. Fall prevention was only observed in a trial of at least 700 IU vitamin D per day, and fracture prevention required a received dose (treatment dose*adherence) of more than 400 IU vitamin D per day. Anti-fall efficacy started with achieved 25-hydroxyvitamin D levels of at least 60 nmol l(-1) (24 ng ml(-1)) and anti-fracture efficacy started with achieved 25-hydroxyvitamin D levels of at least 75 nmol l(-1) (30 ng ml(-1)) and both endpoints improved further with higher achieved 25-hydroxyvitamin D levels. Founded on these evidence-based data derived from the general older population, vitamin D supplementation should be at least 700-1000 IU per day and taken with good adherence to cover the needs for both fall and fracture prevention. Ideally, the target range for 25-hydroxyvitamin D should be at least 75 nmol l(1), which may need more than 700-1000 IU vitamin D in individuals with severe vitamin D deficiency or those overweight. ------------------------------------15

J Invest Dermatol. 2009 Oct 8. [Epub ahead of print] Vitamin D Production after UVB Exposure Depends on Baseline Vitamin D and Total Cholesterol but Not on Skin Pigmentation. Bogh MK, Schmedes AV, Philipsen PA, Thieden E, Wulf HC. Department of Dermatology, Copenhagen University Hospital, Bispebjerg, Copenhagen NV Vejle, Denmark. UVB radiation increases serum vitamin D level expressed as 25-hydroxyvitamin-D(3) (25(OH)D), but the influence of skin pigmentation, baseline 25(OH)D level, and total cholesterol has not been well characterized. To determine the importance of skin pigmentation, baseline 25(OH)D level, and total cholesterol on 25(OH)D production after UVB exposure, 182 persons were screened for 25(OH)D level. A total of 50 participants with a wide range in baseline 25(OH)D levels were selected to define the importance of baseline 25(OH)D level. Of these, 28 non-sun worshippers with limited past sun exposure were used to investigate the influence of skin pigmentation and baseline total cholesterol. The participants had 24% of their skin exposed to UVB (3 standard erythema doses) four times every second or third day. Skin pigmentation and 25(OH)D levels were measured before and after the irradiations. Total cholesterol was measured at baseline. The increase in 25(OH)D level after UVB exposure was negatively correlated with baseline 25(OH)D level (P<0.001) and positively correlated with baseline total cholesterol level (P=0.005), but no significant correlations were found with constitutive or facultative skin pigmentation. In addition, we paired a dark-skinned group with a fairskinned group according to baseline 25(OH)D levels and found no differences in 25(OH)D increase after identical UVB exposure.Journal of Investigative Dermatology advance online publication, 8 October 2009; doi:10.1038/jid.2009.323. -----------------------------------------Endocr Pract. 2009 Sep-Oct;15(6):590-6. Is vitamin D the fountain of youth? Binkley N.

16

University of Wisconsin Osteoporosis Research, 2870 University Avenue, Suite 100, Madison, WI 53705, USA. nbinkley@wisc.edu OBJECTIVE: To review the role of vitamin D deficiency for both classic and "nonclassic" effects and raise the caution that association does not prove causation. METHODS: The pertinent literature regarding vitamin D and its effects on bone, muscle function, immune function, glucose tolerance, cancer risk, and development of cardiovascular disease and other conditions is reviewed. In addition, the limitations of observational studies are discussed. RESULTS: Vitamin D inadequacy is common worldwide and classically causes osteomalacia and rickets. More recently, the contribution of low vitamin D status to increased falls and fracture risk has become appreciated. Additionally, nonclassic effects of vitamin D inadequacy are being recognized, and low vitamin D status is being potentially associated with a multitude of conditions (including Alzheimer disease, osteoarthritis, multiple sclerosis, and hypertension) and higher overall mortality. It is important to recognize that associations in observational studies can be due to chance, bias, or confounders or may be indicative of causality. CONCLUSION: Because vitamin D deficiency has been established to have adverse musculoskeletal consequences, optimization of vitamin D status, for both the individual patient and the overall population, is indicated. ----------------------------------------------Clin Chem Lab Med. 2009;47(2):120-7. Vitamin D: current status and perspectives. Cavalier E, Delanaye P, Chapelle JP, Souberbielle JC. Department of Clinical Chemistry, University Hospital of Liege, University of Liege, Belgium. Etienne.cavalier@chu.ulg.ac.be The role of vitamin D in maintaining bone health has been known for decades. Recently, however, the discovery that many tissues expressed the vitamin D receptor and were able to transform the 25-OH vitamin D into its most active metabolite, 1,25-(OH)(2) vitamin D, has led to a very promising future for this "old" molecule. Indeed, observational studies, and more and more interventional studies, are raising the importance of a significant vitamin D supplementation for not-only skeletal benefits. Among them, 25-OH vitamin D has been found to play an important role in prevention of cancers, auto17

immune diseases, cardiovascular diseases, diabetes, and infections. Vitamin D deficiency, defined as serum 25-OH vitamin D levels <30 ng/mL, is very common in our population. The cost/benefit ratio and some recently published studies are clearly now in favor of a controlled and efficient vitamin D supplementation in these patients presenting a 25-OH vitamin D level <30 ng/mL. More attention should also be focused on pregnant and lactating women, as well as children and adolescents. ----------------------------------------------Photochem Photobiol. 2009 Nov-Dec;85(6):1480-4. Vitamin D level in summer and winter related to measured UVR exposure and behavior. Thieden E, Philipsen PA, Heydenreich J, Wulf HC. Department of Dermatology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark. et01@bbh.regionh.dk The influence of the summer UVR exposure on serum-25-hydroxyvitamin D (25(OH)D) in late summer and winter was investigated in an open study on 25 healthy, adult volunteers. The UVR exposure dose in standard erythema dose (SED) was monitored continuously during a summer season with personal, electronic wristwatch UVR dosimeters and sun exposure diaries. Constitutive and facultative skin pigmentation was measured in September. 25(OH)D was measured in September and February and was in mean 82 nmol/L +/- 25 (mean +/- SD) in September and 56 nmol/L +/- 19 (mean +/- SD) in February. The received cumulative UVR dose measured during a mean of 121 days was 156 SED +/159 (mean +/- SD). The following UVR exposure parameters correlated with 25(OH)D in September and February, respectively: (1) The cumulative UVR dose (r = 0.53; P < 0.01) and (r = 0.43; P = 0.03); (2) Mean daily hours with UVR measurements monitored by the dosimeter (r = 0.64, P = 0.001) and (r = 0.53; P = 0.007); (3) Days "with sun-exposed upper body" (r = 0.58, P = 0.003) and (r = 0.50; P = 0.01); (4) Facultative pigmentation (r = 0.47; P < 0.02) and (r = 0.7; P < 0.001); (5) Constitutive pigmentation (r = 0.06, n.s.) and (r = 0.43, P = 0.03). Neither days "sunbathing" nor days with "sunscreen applied" correlated with 25(OH)D. The fall in 25(OH)D during winter was dependent on the entry value. --------------------------------------------------------18

Mol Aspects Med. 2008 Dec;29(6):407-14. Epub 2008 Aug 8. Vitamin D and skeletal muscle tissue and function. Ceglia L. Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Bone Metabolism Laboratory, 711 Washington Street, Boston, MA 02111, USA. lisa.ceglia@tufts.edu This review aims to summarize current knowledge on the role of vitamin D in skeletal muscle tissue and function. Vitamin D deficiency can cause a myopathy of varying severity. Clinical studies have indicated that vitamin D status is positively associated with muscle strength and physical performance and inversely associated with risk of falling. Vitamin D supplementation has shown to improve tests of muscle function, reduce falls, and possibly impact on muscle fiber composition and morphology in vitamin D deficient older adults. Molecular mechanisms of vitamin D action on muscle tissue include genomic and non-genomic effects via a receptor present in muscle cells. Genomic effects are initiated by binding of 1,25-dihydroxyvitamin D [1,25(OH)(2)D] to its nuclear receptor, which results in changes in gene transcription of mRNA and subsequent protein synthesis. Non-genomic effects of vitamin D are rapid and mediated through a cell surface receptor. Knockout mouse models of the vitamin D receptor provide insight into understanding the direct effects of vitamin D on muscle tissue. Recently, VDR polymorphisms have been described to affect muscle function. Parathyroid hormone which is strongly linked with vitamin D status also may play a role in muscle function; however, distinguishing its role from that of vitamin D has yet to be fully clarified. Despite the enormous advances in recent decades, further research is needed to fully characterize the exact underlying mechanisms of vitamin D action on muscle tissue and to understand how these cellular changes translate into clinical improvements in physical performance. --------------------------------------Osteoporos Int. 2009 Mar;20(3):417-25. Epub 2008 Jul 16. Relationship between vitamin D status, body composition and physical exercise of adolescent girls in Beijing. Foo LH, Zhang Q, Zhu K, Ma G, Trube A, Greenfield H, Fraser DR. 19

Faculty of Veterinary Science, University of Sydney, Sydney, NSW, Australia. lhfoo@kb.usm.my Little is known about the prevalence of actual vitamin D deficiency in healthy school-aged adolescents, particularly in China. The aim of this study was to examine the prevalence of hypovitaminosis D and to identify whether there was any association between vitamin D status, body composition and physical exercise in 323 Chinese adolescent girls in Beijing, China (40 degrees N). INTRODUCTION: It is well recognized that persistent severe vitamin D deficiency is associated with the bone abnormalities of rickets and osteomalacia. However, there is now evidence suggesting that low vitamin D status, not previously considered to be a state of deficiency is associated with secondary hyperparathyroidism, increased bone remodelling and other clinical signs thought only to be found in severe vitamin D deficiency. Hypovitaminosis D in healthy children and adolescents has been reported frequently in many countries, especially in winter. METHODS: We performed a cross-sectional analysis of 323 Chinese adolescent girls in Beijing in winter. Mean age of the subjects was 15.0 (+/-0.4) years. About 32.8%, 68.4% and 89.2% of the subjects were at risk of vitamin D deficiency when defined as plasma concentrations of 25OHD of 25, 37.5 or 50 nmol/L, respectively. RESULTS: This cross-sectional analysis of 323 Chinese adolescent girls in Beijing in winter showed that hypovitaminosis D was common in these subjects. In addition, body mass index, milk intake, participation in organized sports and total physical activity were all significant independent determinants of vitamin D status. An inverse association was found between plasma 25OHD and intact-parathyroid hormone (iPTH) concentration. Body mass index (BMI), milk intake, participation in organized sports and total physical activity all emerged as major independent determinants of vitamin D status as assessed by plasma 25OHD concentration. Vitamin D status was positively associated with lean body mass (LBM), but there was no association with the degree of body adiposity. Regardless of the concentration of 25OHD in blood used to define vitamin D deficiency, hypovitaminosis D was common in these subjects. CONCLUSION: It is recommended that policies be developed to prevent vitamin D deficiency in adolescent girls. Further studies are needed to identify the mechanisms whereby vitamin D status is related to exercise and to body composition during growth. -----------------------------------------Ugeskr Laeger. 2008 Sep 29;170(40):3138-9. [Stress fracture in female athlete runner carrying weights] 20

[Article in Danish] Olesen UK, Lauritzen JB. Ortopaedkirurgisk Afdeling M, Bispebjerg Hospital, DK-2400 Kbenhavn NV. ulrik@instruksen.dk Comment in:
!

Ugeskr Laeger. 2008 Oct 20;170(43):3447; author reply 3448. A 32-year old female athlete was referred with a femoral neck fracture. She practiced intensive cycling and running while carrying weights. The fracture had been overlooked on multiple occasions. She suffered from underweight, Vitamin D deficiency, ammenorhea and osteopenia. -----------------------------------------------------------Mol Aspects Med. 2008 Dec;29(6):361-8. Epub 2008 Sep 2. The vitamin D deficiency pandemic and consequences for nonskeletal health: mechanisms of action. Holick MF. Department of Medicine, Section of Endocrinology, Nutrition, and Diabetes, Vitamin D, Skin and Bone Research Laboratory, Boston University Medical Center, Boston, MA, USA. mfholick@bu.edu Vitamin D, the sunshine vitamin, is important for childhood bone health. Over the past two decades, it is now recognized that vitamin D not only is important for calcium metabolism and maintenance of bone health throughout life, but also plays an important role in reducing risk of many chronic diseases including type I diabetes, multiple sclerosis, rheumatoid arthritis, deadly cancers, heart disease and infectious diseases. How vitamin D is able to play such an important role in health is based on observation that all tissues and cells in the body have a vitamin D receptor, and, thus, respond to its active form 1,25-dihydroxyvitamin D. However, this did not explain how living at higher latitudes and being at risk of vitamin D deficiency increased risk of these deadly diseases since it was also known that the 1,25-dihydroxyvitamin D levels are normal or even elevated when a person is vitamin D insufficient. Moreover, increased intake of vitamin D or exposure to more sunlight will not induce the kidneys to produce more 1,25-dihydroxyvitamin D. The revelation that the colon, breast, prostate, 21

macrophages and skin among other organs have the enzymatic machinery to produce 1,25dihydroxyvitamin D provides further insight as to how vitamin D plays such an essential role for overall health and well being. This review will put into perspective many of the new biologic actions of vitamin D and on how 1,25-dihydroxyvitamin D is able to regulate directly or indirectly more than 200 different genes that are responsible for a wide variety of biologic processes. --------------------------------------------------------Am J Clin Nutr. 2007 Nov;86(5):1399-404. Associations of diet, supplement use, and ultraviolet B radiation exposure with vitamin D status in Swedish women during winter. Burgaz A, Akesson A, Oster A, Michalsson K, Wolk A. Division of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden. BACKGROUND: Vitamin D is produced endogenously after sun exposure but can also be obtained from natural food sources, food fortification, and dietary supplements. OBJECTIVE: We aimed to determine the vitamin D status of women (61-86 y old) living in central Sweden (latitude 60 degrees ) during winter and its relation with vitamin D intake and exposure to ultraviolet B radiation. DESIGN: In a cross-sectional study, we assessed the vitamin D status (serum 25-hydroxyvitamin D [25(OH)D]) of 116 women by using an enzyme immunoassay. The women completed questionnaires covering food habits, use of dietary supplements, and sun-related behavior. RESULTS: In a multiple linear regression model, the main determinants of serum 25(OH)D concentrations (x +/- SD: 69 +/- 23 mmol/L) were dietary vitamin D (6.0 +/- 1.8 mug/d), travel to a sunny location during winter within the previous 6 mo (26%), and the use of dietary supplements (16%). There was no association between serum 25(OH)D status during the winter and age, time spent outdoors, the use of sunscreen, or skin type. Serum 25(OH)D concentrations increased by 25.5 nmol/L with 2-3 servings (130 g/wk) fatty fish/wk, by 6.2 nmol/L with the daily intake of 300 g vitamin D-fortified reduced-fat dairy products, by 11.0 nmol/L with regular use of vitamin D supplements, and by 14.5 nmol/L with a sun vacation during winter. Among nonsupplement users without a wintertime sun vacation, 2-3 servings fatty fish/wk increased serum vitamin D concentrations by 45%. CONCLUSION: Fatty fish, vitamin D-fortified reduced-fat dairy 22

products, regular supplement use, and taking a sun vacation are important predictors for serum concentrations of 25(OH)D during winter at a latitude of 60 degrees . ---------------------------------------Am J Clin Nutr. 2008 Dec;88(6):1535-42. Estimation of the dietary requirement for vitamin D in healthy adults. Cashman KD, Hill TR, Lucey AJ, Taylor N, Seamans KM, Muldowney S, Fitzgerald AP, Flynn A, Barnes MS, Horigan G, Bonham MP, Duffy EM, Strain JJ, Wallace JM, Kiely M. Department of Food and Nutritional Sciences, University College, Cork, Ireland. k.cashman@ucc.ie Comment in:
!

Am J Clin Nutr. 2009 Oct;90(4):1114-5; author reply 1115-6. BACKGROUND: Knowledge gaps have contributed to considerable variation among international dietary recommendations for vitamin D. OBJECTIVE: We aimed to establish the distribution of dietary vitamin D required to maintain serum 25-hydroxyvitamin D [25(OH)D] concentrations above several proposed cutoffs (ie, 25, 37.5, 50, and 80 nmol/L) during wintertime after adjustment for the effect of summer sunshine exposure and diet. DESIGN: A randomized, placebo-controlled, double-blind 22-wk intervention study was conducted in men and women aged 20-40 y (n = 238) by using different supplemental doses (0, 5, 10, and 15 microg/d) of vitamin D(3) throughout the winter. Serum 25(OH)D concentrations were measured by using enzyme-linked immunoassay at baseline (October 2006) and endpoint (March 2007). RESULTS: There were clear dose-related increments (P < 0.0001) in serum 25(OH)D with increasing supplemental vitamin D(3). The slope of the relation between vitamin D intake and serum 25(OH)D was 1.96 nmol x L(-1) x microg(-1) intake. The vitamin D intake that maintained serum 25(OH)D concentrations of >25 nmol/L in 97.5% of the sample was 8.7 microg/d. This intake ranged from 7.2 microg/d in those who enjoyed sunshine exposure, 8.8 microg/d in those who sometimes had sun exposure, and 12.3 microg/d in those who avoided sunshine. Vitamin D intakes required to maintain serum 25(OH)D concentrations of >37.5, >50, and >80 nmol/L in 97.5% of the sample were 19.9, 28.0, and 41.1 microg/d, respectively. CONCLUSION: The range of vitamin D intakes required to ensure maintenance of wintertime vitamin D status [as defined by incremental 23

cutoffs of serum 25(OH)D] in the vast majority (>97.5%) of 20-40-y-old adults, considering a variety of sun exposure preferences, is between 7.2 and 41.1 microg/d. ---------------------------------------J Clin Endocrinol Metab. 2007 Jun;92(6):2130-5. Epub 2007 Apr 10. Low vitamin D status despite abundant sun exposure. Binkley N, Novotny R, Krueger D, Kawahara T, Daida YG, Lensmeyer G, Hollis BW, Drezner MK. University of Wisconsin Osteoporosis Research Program, Madison, WI 53705, USA. nbinkley@wisc.edu CONTEXT: Lack of sun exposure is widely accepted as the primary cause of epidemic low vitamin D status worldwide. However, some individuals with seemingly adequate UV exposure have been reported to have low serum 25-hydroxyvitamin D [25(OH)D] concentration, results that might have been confounded by imprecision of the assays used. OBJECTIVE: The aim was to document the 25(OH)D status of healthy individuals with habitually high sun exposure. SETTING: This study was conducted in a convenience sample of adults in Honolulu, Hawaii (latitude 21 degrees ). PARTICIPANTS: The study population consisted of 93 adults (30 women and 63 men) with a mean (sem) age and body mass index of 24.0 yr (0.7) and 23.6 kg/m(2) (0.4), respectively. Their selfreported sun exposure was 28.9 (1.5) h/wk, yielding a calculated sun exposure index of 11.1 (0.7). MAIN OUTCOME MEASURES: Serum 25(OH)D concentration was measured using a precise HPLC assay. Low vitamin D status was defined as a circulating 25(OH)D concentration less than 30 ng/ml. RESULTS: Mean serum 25(OH)D concentration was 31.6 ng/ml. Using a cutpoint of 30 ng/ml, 51% of this population had low vitamin D status. The highest 25(OH)D concentration was 62 ng/ml. CONCLUSIONS: These data suggest that variable responsiveness to UVB radiation is evident among individuals, causing some to have low vitamin D status despite abundant sun exposure. In addition, because the maximal 25(OH)D concentration produced by natural UV exposure appears to be approximately 60 ng/ml, it seems prudent to use this value as an upper limit when prescribing vitamin D supplementation. -----------------------------------------24

Prog Biophys Mol Biol. 2006 Sep;92(1):4-8. Epub 2006 Feb 28. Vitamin D physiology. Lips P. Department of Endocrinology, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, Netherlands. p.lips@vumc.nl Vitamin D3 is synthesized in the skin during summer under the influence of ultraviolet light of the sun, or it is obtained from food, especially fatty fish. After hydroxylation in the liver into 25-hydroxyvitamin D (25(OH)D) and kidney into 1,25-dihydroxyvitamin D (1,25(OH)2D), the active metabolite can enter the cell, bind to the vitamin D-receptor and subsequently to a responsive gene such as that of calcium binding protein. After transcription and translation the protein is formed, e.g. osteocalcin or calcium binding protein. The calcium binding protein mediates calcium absorption from the gut. The production of 1,25(OH)2D is stimulated by parathyroid hormone (PTH) and decreased by calcium. Risk factors for vitamin D deficiency are premature birth, skin pigmentation, low sunshine exposure, obesity, malabsorption and advanced age. Risk groups are immigrants and the elderly. Vitamin D status is dependent upon sunshine exposure but within Europe, serum 25(OH)D levels are higher in Northern than in Southern European countries. Severe vitamin D deficiency causes rickets or osteomalacia, where the new bone, the osteoid, is not mineralized. Less severe vitamin D deficiency causes an increase of serum PTH leading to bone resorption, osteoporosis and fractures. A negative relationship exists between serum 25(OH)D and serum PTH. The threshold of serum 25(OH)D, where serum PTH starts to rise is about 75nmol/l according to most surveys. Vitamin D supplementation to vitamin Ddeficient elderly suppresses serum PTH, increases bone mineral density and may decrease fracture incidence especially in nursing home residents. The effects of 1,25(OH)2D and the vitamin D receptor have been investigated in patients with genetic defects of vitamin D metabolism and in knock-out mouse models. These experiments have demonstrated that for active calcium absorption, longitudinal bone growth and the activity of osteoblasts and osteoclasts both 1,25(OH)2D and the vitamin D receptor are essential. On the other side, bone mineralization can occur by high ambient calcium concentration, so by high doses of oral calcium or calcium infusion. The active metabolite 1,25(OH)2D has its effects through the vitamin D receptor leading to gene expression, e.g. the calcium binding protein or osteocalcin or through a plasma membrane receptor and second messengers such as cyclic AMP. The latter responses are very rapid and include the effects on the pancreas, vascular smooth 25

muscle and monocytes. Muscle cells contain vitamin D receptor and several studies have demonstrated that serum 25(OH)D is related to physical performance. The active metabolite 1,25(OH)2D has an antiproliferative effect and downregulates inflammatory markers. Extrarenal synthesis of 1,25(OH)2D occurs under the influence of cytokines and is important for the paracrine regulation of cell differentiation and function. This may explain that vitamin D deficiency can play a role in the pathogenesis of auto-immune diseases such as multiple sclerosis and diabetes type 1, and cancer. In conclusion, the active metabolite 1,25(OH)2D has pleiotropic effects through the vitamin D receptor and vitamin D responsive elements of many genes and on the other side rapid non-genomic effects through a membrane receptor and second messengers. Active calcium absorption from the gut depends on adequate formation of 1,25(OH)2D and an intact vitamin D receptor. Bone mineralization mainly depends on ambient calcium concentration. Vitamin D metabolites may play a role in the prevention of auto-immune disease and cancer. ------------------------------------------Osteoporos Int. 2002 Mar;13(3):187-94. Vitamin D and muscle function. Pfeifer M, Begerow B, Minne HW. Institute of Clinical Osteology Gustav Pommer and Clinic Der Firstenhof, Bad Pyrmont, Germany. iko_pyrmont@t-online.de The aim of this review is to summarize current knowledge on the relation between vitamin D and muscle function. Molecular mechanisms of vitamin D action on muscle tissue have been known for many years and include genomic and non-genomic effects. Genomic effects are initiated by binding of 1,25-dihydroxyvitamin D3 (1,25(OH)2D) to its nuclear receptor, which results in changes in gene transcription of messenger RNA and subsequent protein synthesis. Non-genomic effects of vitamin D are rapid and mediated through a membrane-bound vitamin D receptor (VDR). Genetic variations in the VDR and the importance of VDR polymorphisms in the development of osteoporosis are still a matter of controversy and debate. Most recently, VDR polymorphisms have been described to affect muscle function. The skin has an enormous capacity for vitamin D production and supplies the body with 80-100% of its requirements of vitamin D. Age, latitude, time of day, season of the year and 26

pigmentation can dramatically affect the production of vitamin D in the skin. Hypovitaminosis D is a common feature in elderly people living in northern latitudes and skin coverage has been established as an important factor leading to vitamin D deficiency. A serum 25-hydroxyvitamin D level below 50 nmol/l has been associated with increased body sway and a level below 30 nmol/l with decreased muscle strength. Changes in gait, difficulties in rising from a chair, inability to ascend stairs and diffuse muscle pain are the main clinical symptoms in osteomalacic myopathy. Calcium and vitamin D supplements together might improve neuromuscular function in elderly persons who are deficient in calcium and vitamin D. Thus 800 IU of cholecalciferol in combination with mg of elemental calcium reduces hip fractures and other non-vertebral fractures and should generally be recommended in individuals who are deficient in calcium and vitamin D. Given the strong interdependency of vitamin D deficiency, low serum calcium and high levels of parathyroid hormone, however, it is difficult to identify exact mechanisms of action. ----------------------------------------Mol Aspects Med. 2008 Dec;29(6):361-8. Epub 2008 Sep 2. The vitamin D deficiency pandemic and consequences for nonskeletal health: mechanisms of action. Holick MF. Department of Medicine, Section of Endocrinology, Nutrition, and Diabetes, Vitamin D, Skin and Bone Research Laboratory, Boston University Medical Center, Boston, MA, USA. mfholick@bu.edu Vitamin D, the sunshine vitamin, is important for childhood bone health. Over the past two decades, it is now recognized that vitamin D not only is important for calcium metabolism and maintenance of bone health throughout life, but also plays an important role in reducing risk of many chronic diseases including type I diabetes, multiple sclerosis, rheumatoid arthritis, deadly cancers, heart disease and infectious diseases. How vitamin D is able to play such an important role in health is based on observation that all tissues and cells in the body have a vitamin D receptor, and, thus, respond to its active form 1,25-dihydroxyvitamin D. However, this did not explain how living at higher latitudes and being at risk of vitamin D deficiency increased risk of these deadly diseases since it was also known that the 1,25-dihydroxyvitamin D levels are normal or even elevated when a person is vitamin D insufficient. Moreover, increased intake of vitamin D or exposure to more sunlight will not induce the 27

kidneys to produce more 1,25-dihydroxyvitamin D. The revelation that the colon, breast, prostate, macrophages and skin among other organs have the enzymatic machinery to produce 1,25dihydroxyvitamin D provides further insight as to how vitamin D plays such an essential role for overall health and well being. This review will put into perspective many of the new biologic actions of vitamin D and on how 1,25-dihydroxyvitamin D is able to regulate directly or indirectly more than 200 different genes that are responsible for a wide variety of biologic processes. ------------------------------------------------Med Sci Sports Exerc. 2009 May;41(5):1102-10. Athletic performance and vitamin D. Cannell JJ, Hollis BW, Sorenson MB, Taft TN, Anderson JJ. Atascadero State Hospital, Atascadero, CA 93422, USA. jcannell@dmhash.state.ca.us PURPOSE: Activated vitamin D (calcitriol) is a pluripotent pleiotropic secosteroid hormone. As a steroid hormone, which regulates more than 1000 vitamin D-responsive human genes, calcitriol may influence athletic performance. Recent research indicates that intracellular calcitriol levels in numerous human tissues, including nerve and muscle tissue, are increased when inputs of its substrate, the prehormone vitamin D, are increased. METHODS: We reviewed the world's literature for evidence that vitamin D affects physical and athletic performance. RESULTS: Numerous studies, particularly in the German literature in the 1950s, show vitamin D-producing ultraviolet light improves athletic performance. Furthermore, a consistent literature indicates physical and athletic performance is seasonal; it peaks when 25-hydroxy-vitamin D [25(OH)D] levels peak, declines as they decline, and reaches its nadir when 25(OH)D levels are at their lowest. Vitamin D also increases the size and number of Type II (fast twitch) muscle fibers. Most cross-sectional studies show that 25(OH)D levels are directly associated with musculoskeletal performance in older individuals. Most randomized controlled trials, again mostly in older individuals, show that vitamin D improves physical performance. CONCLUSIONS: Vitamin D may improve athletic performance in vitamin D-deficient athletes. Peak athletic performance may occur when 25(OH)D levels approach those obtained by natural, full-body, summer sun exposure, which is at least 50 ng x mL(-1). Such 25(OH)D levels may also protect the athlete from several acute and chronic medical conditions. 28

----------------------------------------------Int J Sport Nutr Exerc Metab. 2008 Apr;18(2):204-24. Should we be concerned about the vitamin D status of athletes? Willis KS, Peterson NJ, Larson-Meyer DE. Department of Family and Consumer Sciences, University of Wyoming, Laramie, WY 82071, USA. A surprisingly high prevalence of vitamin D insufficiency and deficiency has recently been reported worldwide. Although very little is known about vitamin D status among athletes, a few studies suggest that poor vitamin D status is also a problem in athletic populations. It is well recognized that vitamin D is necessary for optimal bone health, but emerging evidence is finding that vitamin D deficiency increases the risk of autoimmune diseases and nonskeletal chronic diseases and can also have a profound effect on human immunity, inflammation, and muscle function (in the elderly). Thus, it is likely that compromised vitamin D status can affect an athlete's overall health and ability to train (i.e., by affecting bone health, innate immunity, and exercise-related immunity and inflammation). Although further research in this area is needed, it is important that sports nutritionists assess vitamin D (as well as calcium) intake and make appropriate recommendations that will help athletes achieve adequate vitamin D status: serum 25(OH)D of at least 75 or 80 nmol/L. These recommendations can include regular safe sun exposure (twice a week between the hours of 10 a.m. and 3 p.m. on the arms and legs for 5-30 min, depending on season, latitude, and skin pigmentation) or dietary supplementation with 1,000-2,000 IU vitamin D3 per day. Although this is significantly higher than what is currently considered the adequate intake, recent research demonstrates these levels to be safe and possibly necessary to maintain adequate 25(OH)D concentrations. ----------------------------------------Eur J Clin Nutr. 2002 May;56(5):431-7. The effect of conventional vitamin D(2) supplementation on serum 25(OH)D concentration is weak among peripubertal Finnish girls: a 3-y prospective study. Lehtonen-Veromaa M, Mttnen T, Nuotio I, Irjala K, Viikari J.

29

Paavo Nurmi Centre, Sport and Exercise Medicine Unit, Department of Physiology, University of Turku, Turku, Finland. OBJECTIVES: To study the effect of vitamin D supplementation and the impact of summer season on serum 25-hydroxyvitamin D (S-25(OH)D) in Finnish 9-15-y-old girls. DESIGN: Three-year follow-up study with vitamin D(2) supplementation using D(2) 10 microg daily from October to January for the first and from October to February for the second winter as well as 20 microg daily from October to March for the third winter. SETTING: Paavo Nurmi Centre, University of Turku, Turku, Finland. SUBJECTS: A total of 171 female volunteers aged 9-15 y. METHODS: Vitamin D and calcium intakes were estimated by a semi-quantitative food frequency questionnaire (FFQ). S-25(OH)D was measured by radioimmunoassay. RESULTS: The median daily dietary intakes of vitamin D and calcium were 3.8 microg (interquartile range (IQR) 2.7-5.0) and 1451 mg (IQR 1196-1812), respectively, over 3 y. The prevalence of severe hypovitaminosis D (S-25(OH)D<20 nmol/l) was 14% and of moderate hypovitaminosis D (20 nmol/l < or = S-25(OH)D < or = 37.5 nmol/l) 75% at baseline in winter. None of the participants had severe hypovitaminosis D in summer. The effect of 10 microg of D(2) daily was insufficient to raise S-25(OH)D from baseline. The daily supplementation of 20 microg of D(2) increased S-25(OH)D significantly in wintertime compared with the non-supplement users (to 45.5 vs 31.8 nmol/l; P<0.001). None of the subjects with vitamin D(2) supplementation approximately 20 microg daily had severe hypovitaminosis D; however, 38% of those participants had moderate hypovitaminosis D at 36 months. Sun exposure in summer raised mean S-25(OH)D to 62.0 nmol/l. Both the daily supplementation of approximately 20 microg of D(2) and summer sunlight exposure had more effect on those who had severe hypovitaminosis than those who had a normal vitamin D status (increase of 24.2 vs 0.9 nmol/l (P<0.001), and 38.8 vs 18.2 nmol/l (P<0.001), respectively). CONCLUSION: Vitamin D supplementation daily with 20 microg is needed to prevent hypovitaminosis D in peripubertal Finnish girls in winter. Sunlight exposure in summer is more effective than approximately 20 microg of D(2) supplementation daily in winter to raise S-25(OH)D. Both the daily supplementation with 20 microg of D(2) and summertime sunlight exposure had more effect on those who had severe hypovitaminosis D than those who had a normal vitamin D status. SPONSORSHIP: Supported by the Yrj Jahnsson Foundation and the Medical Research Foundation of the Turku University Central Hospital. Note: 20 microg equals 800 IU. This is the amount of vitamin D in MVM, although MVM contains the more effective vitamin D3. See conversion information above. - Mauro 30