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Vitamin D: New Information about an Essential Nutrient • At the end of this workshop, participants will be able to – Understand the current concepts of the role Vitamin D plays in human health, the rational for Vitamin D supplements, and not be afraid to claim their place in the sun. Resources and references • Galland, Leo. Power Healing. 1997. Random House. New York, NY • Holick, Michael. The UV Advantage. 2003 Ibooks. New York, NY • Kuhn,Thomas. The Structure of Scientific Revolutions. 1970 University of Chicago Press. Chicago, IL • Vasquez A et al The Clinical Importance of Vitamin D (Cholecalciferol): A Paradigm Shift with Implications for All Healthcare Providers. Alternative Therapies in Health and Disease. Sept/Oct 2004. Vol. 10 No 5 • Willett, Walter Eat Drink and Be Healthy. 2001 Simon and Shuster. New York, NY Vitamin D is the most common nutritional deficiency in the US • What percent of the following groups are Vitamin D deficient? • Free-living and institutionalized elders__ • Boston medical students and residents at the end of winter__ • African American women of childbearing age at the end of winter__ The Answers • What percent of the following groups are Vitamin D deficient? • Free-living and institutionalized elders__>50% • Boston medical students and residents at the end of winter__32% • African American women of childbearing age at the end of winter__41% Forms of Vitamin D Cholecalciferol (D3) is the naturally occurring form of Vitamin D in the skin and in food. It is converted in the liver to: Calcidiol (25-hydroxy Vitamin D), which is considered a “prehormone.” The calcidiol blood level is measured to assess Vitamin D stores in the body. Calcidiol is converted in the kidneys, breast, prostate, ovary, pituitary, brain, etc to: Calcitriol 1,25 hydroxy Vitamin D, which maintains calcium in the blood and has an array of effects in the body’s organs. Ergocalciferol (D2) is a synthetic form of Vitamin D used as a supplement. Calcitriol, the most biologically active form of vitamin D does the following: Controls bone metabolism Modulates neurotransmitter and neurological function Has immunoregulatory function and can decrease inflammation (Autoimmune disease such as multiple sclerosis) Modulates transcription of several genes, particularly those effecting differentiation and proliferation (Cancer mortality) Controls Bone Metabolism, cont. – Increases calcium and phosphorous absorption in the gut – Induces osteoclast maturation for bone remodeling – Promotes calcium deposition in bone (osteoblasts) – Causes reduction in parathyroid hormone (lower PTH levels correlate with reduced risk of HTN, MI and stroke) How much Vitamin D do we need? RDA (Recommended Daily Allowance) vs. DRI’s (Optimal Intake) • “The advent of the new dietary reference intakes (DRIs) has redefined the role of recommended micronutrient intakes and shifted the focus from prevention of nutrient deficiency to reduction of disease risk. A key component of this new approach is establishing reliable functional indicators of nutrient status that may predict disease risk before a severe nutrient deficiency ensues. The identification and use of functional indicators is also important in the determination of nutrient intakes adequate to support key metabolic functions” • Reference: Rampersaud G et al Genomic DNA methylation decreases in response to moderate folate depletion in elderly women American Journal of Clinical Nutrition, Vol. 72, No. 4, 998-1003, Vitamin D and Cancer Research scientists in the 1980's had already discovered that calcitriol had profound anti-cancer effects, both in the test tube and in animals, through the following mechanisms. Check which apply. • __reduced the unregulated growth of cancer cells by promoting normal cell death (apoptosis); • __prevented new cells from becoming cancerous (promoted differentiation). • __helped prevent cancer cells from spreading (metastasis) • __inhibited cancer cells from developing new blood supply (angiogenesis). In short, calcitriol seemed like the perfect anticancer drug • Answer: All are true Sun exposure, Vitamin D and cancer Increased sun exposure is associated with what change in risk of the following cancers: (increase /decrease/no effect) __Breast cancer __Squamous cell cancer (1,500 deaths/year) __Prostate Cancer (40,000 deaths/year) __Lung Cancer __Breast Cancer (50,000 deaths per year) __Colon Cancer __Malignant Melanoma (7,000 deaths per year) __Ovarian Cancer The Answers Increased sun exposure is associated with what change in risk of the following cancers: (increase /decrease/no effect) Decrease__Breast cancer Increase__Squamous cell cancer (1,500 deaths/year) Decrease__Prostate Cancer (40,000 deaths/year) No Change__Lung Cancer Decrease__Breast Cancer (50,000 deaths per year) Decrease__Colon Cancer Increase__Malignant Melanoma (7,000 deaths/year) Decrease__Ovarian Cancer Higher Vitamin D levels provide protection against what other diseases? (Check all that are true) • • • • • • • • _Diabetes mellitus type 1 _osteoporosis _osteoarthritis _hypertension _cardiovascular disease _metabolic syndrome and type 2 diabetes _depression (especially SAD) _certain autoimmune diseases (esp. MS) Higher Vitamin D levels provide protection against what other diseases? • • • • x_Diabetes mellitus and metabolic syndrome – Hypovitaminosis D is associated with increased insulin resistance in diabetics and healthy adults – Vitamin D supplementation was more effective than metformin in improving insulin sensitivity in Type II diabetics – Vitamin D supplementation in infants and children reduced the incidence of Type I diabetes by 80% x_osteoarthritis – Progression of knee and hip arthritis is slowed by adequate levels of Vitamin D (Framingham Study) x_cardiovascular disease – Cardiovascular deaths are more common in the winter, at higher latitudes, and lower altitudes. – Heart attack risk is higher for those with lower Vitamin D blood levels – Vitamin D deficiency can contribute to congestive heart failure and hypertension x_depression (especially seasonal affective disorder (SAD) Sunlight and Multiple Sclerosis An estimated 330,000 Americans have Multiple sclerosis, a chronic debilitating disease that affects the brain and spinal cord. Which of the following statements are true: • There is a genetic component to MS risk, with Northern Europeans being at higher risk. • You are 2 times more likely to get MS if you live in Europe or North America than in the tropics • The prevalence rate for MS is twice as high in the US above the 37th parallel, then below. • Exposure to the sun at any age decreases the likelihood of developing MS • Norwegians who live along the coast have a lower risk of MS than those who live inland, and Eskimos who eat a traditional diet (bear liver whale, seal blubber, oily fish) have almost no MS. Sunlight and Multiple Sclerosis • There is a genetic component to MS risk, with Northern Europeans being at higher risk. TRUE • You are 2 times more likely to get MS if you live in Europe or North America than in the tropics. FALSE. Your are actually at a 5 times higher risk. • The prevalence rate for MS is twice as high in the US above the 37th parallel, then below. TRUE. (The 37th parallel runs through Virginia) • Exposure to the sun at any age decreases the likelihood of developing MS. FALSE. Exposure to the sun before age 15 reduces the risk of MS. • Norwegians who live along the coast have a lower risk of MS than those who live inland. TRUE. Coastal inhabitants eat more fish, • Eskimos who eat a traditional diet (bear liver whale, seal blubber, oily fish) have almost no MS. TRUE Sources of Vitamin D TRUE OR FALSE You can get adequate Vitamin D by: __Exposure to UV rays for ¼ the time it would take your skin to redden __Walking in the moonlight during a full moon __Studying under bright fluorescent lights __Spending Spring and Winter breaks snorkelling in the Bahamas __Taking 1000 units (25 mg) of cholecalciferol (Vitamin D3) daily __Taking the RDA (400 units per day) of ergocalciferol Vitamin D3) daily __Drinking 10 glasses of milk per day __Taking 2 tsp of Cod Liver Oil daily __Taking one tsp of Concentrated Fish Oil (Omega 3 Fatty Acids) daily __Eating a 3 ½ oz serving of salmon per day __Visiting a tanning salon regularly The Answers • TRUE OR FALSE You can get adequate Vitamin D by: • T Exposure to UV rays for ¼ the time it would take your skin to redden (4000-10000 IU) • __Walking in the moonlight during a full moon • __Studying under fluorescent lights • T Spending Spring and winter breaks in the Bahamas • T Taking 1000 units (25 mg) of cholecalciferol (Vitamin D3) daily • __Taking the RDA (400 units per day) of ergocalciferol Vitamin D2) daily • T Drinking 10 glasses of milk per day (100 u Vitamin D/glass) • T Taking 2 tsp of Cod Liver Oil daily (453 u Vitamin D/tsp) • __Taking one tsp of Concentrated Fish Oil (Omega 3 Fatty Acids) daily • __Eating a 3 ½ oz serving of salmon/day (360 u Vitamin D) • T Visiting a tanning salon regularly (4000-10000 IU) What is a toxic level of Vitamin D? • • • • A. 1,000 units per day B. 2,000 units per day C. 10,000 units per day D. Greater than 10,000 units per day What is a toxic intake of Vitamin D • A. 1,000 units per day is at the lower end of a realistic therapeutic intake for someone with limited sun exposure • B. 2,000 units per day. This is the Food and Nutrition Board’s previously defined upper limit which most, if not all Vitamin D experts feel is far too low • C. 10,000 units per day. Total-body sun exposure easily provides the equivalent of 250 microg (10000 IU) vitamin D per day/d, suggesting that this is a physiologic limit. • D. More than 10,000 units/day, over a period of 2-3 months • Reference: Vieth R, Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety. Am J Clin Nutr. 1999 May;69(5):842-56. What is a toxic intake of Vitamin D • The assembled data from many vitamin D supplementation studies reveal a curve for vitamin D dose versus serum 25-hydroxyvitamin D [25(OH)D] response that is surprisingly flat up to 250 microg (10000 IU) vitamin D/d. • Except in those with conditions causing hypersensitivity, there is no evidence of adverse effects with serum 25(OH)D concentrations <140 nmol/L, which require a total vitamin D supply of 250 microg (10000 IU)/d to attain • Published cases of vitamin D toxicity with hypercalcemia, for which the 25(OH)D concentration and vitamin D dose are known, all involve intake of > or = 1000 microg (40000 IU)/d. • Because vitamin D is potentially toxic, intake of >25 microg (1000 IU)/d has been avoided even though the weight of evidence shows that the currently accepted, “no observed adverse effect” limit of 50 microg (2000 IU)/d is too low by at least 5-fold. Vitamin D from sun exposure • Judiciously expose as much skin as possible to direct midday sunlight for 1/4 the time it takes for the skin to turn red, during those months when the proper ultraviolet light occurs at their latitude (usually late spring, summer and early fall). • Do not get sunburned. Vitamin D production is already maximized before your skin turns pink and further exposure does not increase levels of vitamin D but may increase your risk of skin cancer. • Black persons may need five to ten times longer in the sun than whites, depending on skin type. • Topical application of an SPF of 8 will reduce the cutaneous production of Vitamin D3 by 97.5% Laboratory values of Vitamin D Vitamin D 25Hydroxy is the important level for nutritional adequacy (not Vitamin D1,25) • Deficiency – UVA norm 10-100 ng/ml – MJH norm 20-100 ng/ml – generally <20 ng/ml or <30ng/ml (Holick) • Insufficiency <40 ng/ml – Below level of 40-50 tissue levels are depleted and PTH hormone levels begin to increase • Optimal Vitamin D status 40-65 ng/ml (100-160 nmol/L) – Some experts propose 80-100ng/ml as upper range • Vitamin D excess – May occur with levels >125 ng/ml Vitamin D Supplementation • Use D3 (cholecalciferol) rather than D2 (ergocalciferol) – D3 is more efficient than D2 in raising and sustaining Vitamin D levels. • For correcting deficiency: Dosages should reflect physiologic requirements and natural endogenous production and should be in the range of 2,000-10,000 units per day • Supplementation should be continued for 3-9 months • Vitamin D levels do not plateau until 3-4 months. • Most studies of Vitamin D supplementation have been flawed due to insufficient therapeutic intervention • Vitamin D levels should be monitored to assess effectiveness of therapy, by measuring Vitamin D 25-hydroxy • Vitamin D 1,25 levels do no reflect body stores of Vitamin D • Supplements should be used that have been tested for potency Vitamin D Supplementation • For Maintenance (Persons with adequate Vitamin D levels) – Adults without sun exposure should receive 1000 units of Vitamin D daily, possibly more – Pregnant women without sun exposure should receive 1000 units of Vitamin D daily, possibly more – Present recommendations of 200-600 units are woefully inadequate – Apart from fish and milk, there is very little Vitamin D in food. Cheese, yogurt, ice cream, butter, etc. do not contain significant amounts of Vitamin D, – and 1/3 of milk samples contains none or less than stated on the label.