Shining a light on the Sunshine Vitamin Lin A. Brown,MD Dartmouth and DHMC Vitamin D What do surfers have in abundance and maybe most of the rest of us lack? Vit D - a vitamin primarily obtained by man in nature from exposure to sunlight. 1
Why is it called the Sunshine Vitamin? Sun (UV B) converts a component of skin cell membranes (7-dehydrocholesterol) to cholecalciferol which is Vit D3. Ergocalciferol, (Vit D2) is produced in plants the same way from ergosterol. Dark skin reduces vit D production by the sun.?sunblock High latitudes reduce the amount of vit D that can be made - folk in north become vit D deficient in winter. 2
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Facts and figures Reported in ng/ml or nmol/l Frank deficiency <10 ng/ml (25nmol/L) Insufficiency 10-30 ng/ml (25-75nmol/L) Many methods of measurement 10+ ng/ml change with seasons Lower level defined by increase in PTH level or maximum calcium absorption. Where else can humans get vitamin D? Nutritional sources are few Deep salt water, fatty fish like salmon, bluefish, sardines Egg yolk Liver Fortified foods like milk, yogurt, cereal, bread, some juices 4
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Why not just rely on the sun? 6
We start with the grapes under the sun, turn them to raisins one by one. Cholecalciferol is transported to the liver where it is converted to 25-(OH) Vit D which is the main depot form of Vit D 25(OH)D is then transported to the kidney where it is transformed to 1,25-(OH)2 the active vitamin This steroid compound is then available to enter cells and cause genes to be transcribed. 7
People with kidney or liver disease can have trouble making vit D. Obese people have low blood levels. People with mal-absorption syndromes have low Vit D (like celiac disease) So we turn to supplements OTC supplements are numerous. Cod liver oil 1,360 IU/Tbsp Tuna 3 oz 200 Mackerel 345 3.5 oz Sardines 250 1.75 oz 8 oz fortified OJ 100 8 oz fortified milk 100 MVI 400-800 Viactiv 400 Fosamx plus D 5600/wk Os-cal 500 plus D 200; extra-d 400 8
Vit D2 vs D3 Vit D2 is ergocalciferol Vit D3 is cholecalciferol One IU is contained in 0.025 mg cholecalciferol (i.e. 1 mg vitamin D contains 40 IU). Is there a preference No. data Handling in the body is slightly different for D2 and D3 but the effect on calcium and parathyroid hormone is the same. 9
What does vitamin D do for bones Vit D acts on the gut to increase calcium absorption and phosphorous absorption. This is needed for optimal bone mineralization. Inadequate Vit D in children = ricketts Inadequate Vit D in adults = osteomalacia ( soft, poor bones) What is the optimal level of Vitamin D for bone health? Inadequate calcium absorption results in an elevation in PTH hormone - this hormone defends the body s blood calcium concentration. When the body has adequate calcium levels, the PTH level is low. Vit D drives calcium absorption so when Vit D level reaches some point, the PTH level is unchanged by more Vit D. 30 ng/ ml is where PTH levels do not change 10
Are there other beneficial effects of Vit D? Many observational studies suggest that there is a relationship between Vit D level and many conditions including cancer, multiple sclerosis, rheumatoid arthritis, dementia and others. However, observational studies are notorious for finding associations rather than causes - think Womens Health Study and Estrogen. What is the rationale for believing that there is a connection? Vit D receptors exist on most cell types suggesting that they plan a role in more than bone physiology. The enzyme to convert 25OH Vit D to 1,25 Vit D is found in many tissues including colon, prostate and breast. 1,25 Vit D acts to activate the transcription of many genes that can regulate growth of cells and possibly cancer. 11
Lupus Study showed lower disease activity level with higher levels of Vit D Diabetes Children supplemented with 2000 IU/d through age 1 decreased the development of DM by 80% over the next 20 years. In the observational Nurses Health Study, vit D and calcium supplementation were associated with lower rates of Type 2 diabetes 12
Multiple sclerosis Risk increases with latitude But no evidence that treatment with Vit D helps MS symptoms. Allergy and asthma Interestingly,higher vit D levels correlate with worse allergies and asthma. 13
Infection Vit D is required for function of an enzyme in macrophages that participate in killing bacteria. Despite the finding that higher levels of vit D correlated with reduced risk of TB infection, treatment with Vit D did not improve outcomes in patient with TB infection. (baseline mean level of 31 ng/ml). Rheumatoid arthritis Iowa health study showed reduction in risk of RA with greater vit D intake in older women. 14
1,25(OH)2 and cancer Decreases the growth of cells and promotes cell death Inhibits the growth of blood vessels Inhibits telomerase expression (tails on chromosomes gets longer which is correlated with cell longevity) These properties would be useful in preventing or treating cancer Improves mood Cognition May delay alzheimer s disease Low levels associated with schizophrenia and maybe depression 15
Neuromuscular function Improves balance, muscles strength and prevents falls Shown definitively in women What is the evidence? One meta-analysis of Vit D levels in less frequent falls A cross-sectional study of older adults looking at lower extremity function and vit D level. 16
Bischoff-Ferrari et al 204 Looked at ambulatory person older than 60 from the NHANES data base (4100) Correlated lower extremity function with serum vit D levels looking at 8-foot walk time and repeated sit-to-stand time. Found that levels between 22.5 and 40 showed the greatest improvement but levels between 40 and 90 were best. This effect was present regardless of activity level. Chilean study Randomized control studies of vit D supplementation following the Tufts study were done to see if increasing Vit D levels would help prevent falls. 400 IU daily improved gait speed and reduced body sway although it did not reduce the incidence of falls. 17
Bischoff-Ferrari et al 2004 Did a meta-analysis of RCT of Vit D levels and falls. Found 5 RCT of Vit D supplementation in person older than 60. 1237 pt were included. Vit D reduced the incidence of falls by 22% with a NNT of 15. The inclusion of less homogeneous studies with increased number of pts reduced the incidence by 13% which remained statistically significant. The majority of review studies agree that Vit D decreases falls 18
Cardiovascular risk Low levels of Vit D are associated with increased CV risk. A prospective study noted a correlation between vit D levels <20 and increased risk of CV disease. Dobnig H Arch Int Med 2008 These however are all observational studies and recent concern has focused on Vit D accelerating vascular calcification. Mortality and Vit D level NHANES III, an observational study of adults >65 years the risk of death was 45% lower in those with 25(OH) vit D >40 ng/mlc/w <10 ng/ml. Also in NHANES, levels <21 were associated with ht, DM and obesity. In a meta-analysis of 18 RCT of supplementation in postmenopausal women with dosage ranging from 300-2000 IU/d reported a 7% reduction that was statically significant. 19
What is the bottom line? A very recent (May 2011) NEJM opinion piece noted that the evidence that Vit D effects systems or diseases other than bones was unwarranted at this time based on an extensive review of the literature conducted by the IOM. Should you check the vit D level? Maybe not! Assume insufficiency Testing is expensive and possibly misleading due to lab variability. 20
Obese individuals Who is at risk? Those who are housebound Those at risk for falls Those with low bone mass Pregnant women Those with muscle weakness Anyone above the 37 latitude. Who is at risk? Malabsorption of Vit D - celiac disease, GI bypass, IBD, biliary disease, bacterial overgrowth Anti-seizure medicines Glucocorticoids (prednisone). 21
Treatment in 2009 IOM recommends children to adults get 200 IU, 50-70 yo get 400 IU and age greater than 70 get 600 IU per day. This is likely too little - 700-800 IU per day were needed to reduce fx in elderly by 23% Who needs more? Obese, malabsorption, those with low vit D levels who needs more to replete than to maintain. 2010 IOM recommendations Exhaustive review of calcium and vitamin D in health. Concluded that both were essential for bone health, But no evidence for use of Vit D in any other condition. 22
CALCIUM AND VIT D age RDA ULI RDA ULI 19-1000 2500 600 4000 30 301-1000 2500 600 4000 50 51-1000 2000 600 4000 70 M 51-1200 2000 600 4000 70 F >70 1200 2000 800 4000 Repletion/treatment vs maintaining bone mass 1000 IU per day inceases serum vit D level by 10ng/ml increase over 3-4 months. 2600 IU is estimated to meet the needs of 97% of the population Deficiency can be treated with 50,000 IU twice a week for 5 weeks or a single intramuscular dose of 500,000 IU of vit D2 although this dose actually increased the rate of falls. 23
Surfers Can you get too much? Institutionalized folks Oral supplements What are signs and symptoms of toxicity from Vit D Elevated vitamin D leads to increased blood calcium levels. Symptoms: nausea, vomiting, loss of appetite, weakness, itching, thirst, frequent urination, kidney damage or failure. 24
In summary Vit D is clearly needed for bone health Vit D levels are frequently insufficient for optimal PTH levels Vit D is not readily available in foods Vit D is made through sun exposure of the skin, and the risk remains unclear - but above the 37 parallel no one can make enough. Vit D probably effect strength. Vit D may have other beneficial effect on immunity and aging, but the data is currently not of high quality. 25