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We get optimal vitamin D from solar UVB conversion of 7-dehydroxycholesterol in our skin.Foods, OTOH, typically contain only modest amounts of vitamin D, with only a few being truly rich sources of dietary vitamin D.So it's not that dietary vitamin D is poorly absorbed.Rather dietary vitamin D is sub-optimal in engendering sufficiency in vitamin D deficient individuals.To make matters worse, the well-substantiated link between sun exposure and skin cancer drive sun avoidance and widespread sunscreen usage. In combination with increasing indoor lifestyles, these have resulted in global vitamin D deficiency.Thus, overcoming vitamin D deficiency rather than maintaining sufficiency has become the problem du jour.Key difference? For vitamin D sufficient individuals, dietary vitamin D would perhaps suffice for maintenance.But for vitamin D deficient individuals, i.e. increasingly more and more people, vitamin D supplement intake rather than reliance on dietary intake alone becomes necessary.A few statistics help contextualize the gap between recommended and current average vitamin D levels.The US Institute of Medicine defines vitamin D deficiency as serum 25-hydroxyvitamin D3 [25(OH)D3] concentrations <20ng/ml (1).This requirement is based on the classic function of vitamin D to maintain bone homeostasis. However, recently, especially in the 21st century, many new functions of vitamin D have been discovered, ranging from immune system function to reduction in risk for cancer, hypertension, obesity and Type I diabetes (2).Official guidelines based on the decades-old vitamin D = bone health paradigm may thus be outdated (3).The current controversial definition for vitamin D sufficiency is >30ng/ml (1), assessed as circulating 25(OH)D3 levels. Controversial because no consensus yet across age groups and ethnicity nor does it encompass the changing concepts about vitamin D's link to overall health.The US National Health and Nutrition Examination Survey results for 1994 to 2004 (4, 5) showed that US vitamin D sufficiency levels (30 to 60ng/ml) fell from ~60% to ~30% in whites, from ~10% to ~5% in African Americans, and from ~24% to ~6% in Latinos.More than one study suggests that ~70% of adults and ~67% of children aged 1 to 11 years of age in the US have inadequate vitamin D levels (5, 6, 7).Thus, as an example of global trends, vitamin D insufficiency is common in the US population.What are problems associated with dietary vitamin D?Problem with Natural Foods as vitamin D sourcesDiet typically provides modest amounts of vitamin D. Why? Because few foods are natural vitamin D sources (8).Seafood is the relatively richest vitamin D source (9).Oily fish (salmon, mackerel, herring) and sun-dried mushrooms are rich vitamin D sources (8).Feeding on vitamin-D-rich plankton, ocean-raised fish are richer in vitamin D compared to farm-raised varieties (8).For example, farmed salmon fed pelleted food contain only ~10-25% of the vitamin D3 found in wild salmon (10).OTOH, farmed salmon in Norway are fed fish oil and thus contain similar vitamin D3 as wild salmon (11).Problems associated with Fortifying Foods with vitamin DMilk and orange juice sold in the US are fortified with 100IU of vitamin D per 8oz (8, 15).These levels (1IU = 25ng) are considered insufficient in providing circulating vitamin D levels of 30ng/ml.Milk is also a poor fortification choice for the ~50 million Americans, including ~75% of African Americans, who are lactose intolerant (12).Cod liver oil is rich in vitamin D but many commercial cod liver oil preparations also contain large amounts of vitamin A, which creates a two-fold problem.One, it can antagonize the action of vitamin D, at least in a rat model (13).Two, excess vitamin A can cause toxicity (14).An unfortunate legacy of past vitamin D fortificationAccording to Hector DeLuca, an eminent vitamin D researcher, a post-WW II outbreak of 'idiopathic hypercalcemia and related arterial supravascular stenosis' (3) was attributed to vitamin D fortification of food. As a result, such food fortification was stopped in many parts of the world, especially in Europe (16). Thus, while Finland and Sweden allow milk to be fortified with vitamin D3, most other European countries still forbid fortification of dairy products with vitamin D (11).One problem with synthetic vitamin D. Plant (vitamin D2) and Human (vitamin D3) vitamin D are differentCertain plant products such as sun-dried and shitaake mushrooms have abundant vitamin D but it's vitamin D2.vitamin D2 and D3 differencesDifferent side chains and metabolism.Different binding to vitamin D binding protein (DBP), which transports both vitamins through the circulation (2).Daily doses of 1000IU each of vitamin D2 and D3 are equally effective in maintaining serum [25(OH)D3] (17)However, vitamin D3 stayed longer in circulation after intermittent vitamin D supplementation (18, 19, 20).Bottomline? Vitamin D2 or D3 supplementation may not be equivalent for treating vitamin D insufficiency.Does vitamin supplementation help attain vitamin D sufficiency?Studies suggest 1000 IU of vitamin D3/day or 50000 IU twice a month help maintain sufficient circulating [25(OH)D3] levels in individuals who present with vitamin D deficiency and are then treated for 8 weeks with 50000 IU of vitamin D2 per week (21).Vitamin D from food/supplements/skin exposure to UVB is biologically inactive.Needs to be modified to form [25(OH)D3], the storage form of vitamin D, usually in the liver.Small fraction of [25(OH)D3] is then converted to the physiologically active form, 1, 25-dihydroxyvitamin D (22).While various forms such as capsule versus tablets don't appear to have been widely compared in the literature, a compelling study (23) showed vitamin D3 capsule supplementation worked in preventing fractures in the elderly (>65 years of age). Compelling why? If vitamin D3 capsule works in such a vulnerable population, it's likely to work in others as well. US has two pharmaceutical formulations for vitamin D, liquid for pediatric and gelatin capsules for older children and adults (1). Capsules may provide better time-release and absorption compared to tablets.Different methods of vitamin D level assessment exist. This brings to the final wrinkle about vitamin D level levels, namely the tests.Tests for vitamin D levelsTests typically assess circulating levels of [25(OH)D3] for two reasonsIt has ~1000-fold higher circulating concentrations.It has a substantially longer circulating half-life compared to 1, 25-dihydroxyvitamin D.Easy to measure.Circulating levels of [25(OH)D3] thus reflect an intergrated measure of GI tract absorption plus skin synthesis.However, many drawbacks exist25(OH)D3 tests are expensive with problematic reimbursement.25(OH)D3 is measured using different methods.There is as yet no standardized approach for comparing results obtained from different methods (24, 25).How is vitamin D synthesized?vitamin D is not a vitamin.Instead it's a prohormone synthesized in the skin epidermis following exposure to solar UVB radiation (26, 27, 28).Skin cells contain 7-dehydrocholesterol, which absorbs UVB rays from sunlight.UVB absorption opens the B-ring of 7-dehydrocholesterol, converting it to pre-vitamin D3.Body temperature slowly converts pre-vitamin D3 to active vitamin D/cholecalciferol over several hours.The stable circulating form of vitamin D is 25-hydroxyvitamin D3 [25(OH)D3].The biologically active steroid hormone is 1, 25-dihydroxyvitamin D (29).A Caucasian adult in a bathing suit exposed to sun long enough for their skin to turn pink raises serum 25(OH)D to a level comparable to 10 to 20000 IU of vitamin D2 (30).5 to 30 minutes sun exposure of arms and legs between 10Am and 3PM is considered adequate (8).Factors that necessitate oral vitamin D supplementationAge, clothing, latitude, season, skin pigmentation, sunscreen use and time of day influence skin vitamin D synthesis (8).Skin exposure to UVB is much lower in Northern latitudes (25). This is because the zenith angle of the sun becomes more oblique at higher latitudes during fall and winter. As a result ozone efficiently absorbs most UVB radiation before it reaches the earth's surface (11).Thus, at latitudes >37oN, from about mid-October until mid-March, the solar angle is such that skin is unable to convert 7-dehydrocholesterol into vitamin D (11).Stored vitamin D synthesized using summer sunlight is often inadequate to cover the winter months (31).Aging reduces skin 7-dehydrocholesterol by ~50% between 20 and 80 years of age (32), a structural limitation on the amount of vitamin D3 that aging skin can synthesize.Sunscreen use and amount of melanin (brown pigment) in the skin impair the skin's ability to synthesize vitamin D (25, 33, 34).Greater skin pigmentation accounts for the higher prevalence of vitamin D-deficiency in darker-skinned people (35, 36, 37).As for sunscreen, SPF (sun protective factor) as low as 8 or 15 reportedly decrease skin vitamin D3 conversion by 95% (38).Sunscreen use brings us directly to the dilemma that sunlight now represents in our daily lives. On the one hand, judicious sun exposure is necessary to maintain vitamin D levels. OTOH, the well-substantiated link between sun exposure and skin cancer necessitates widespread sunscreen use and even sun avoidance, leading to inevitable vitamin D deficiency. Vitamin D supplements and food fortification thus become necessary to fill this obvious gap.BibliographyHolick, Michael F., et al. "Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline." The Journal of Clinical Endocrinology & Metabolism 96.7 (2011): 1911-1930. Page on endocrine.orgBikle, Daniel. "Nonclassic actions of vitamin D." The Journal of Clinical Endocrinology & Metabolism 94.1 (2009): 26-34. Page on endocrine.orgDeLuca, Hector F. "Evolution of our understanding of vitamin D." Nutrition reviews 66.suppl 2 (2008): S73-S87. Page on 164.208.4Kennel, Kurt A., Matthew T. Drake, and Daniel L. Hurley. "Vitamin D deficiency in adults: when to test and how to treat." 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The Journal of Clinical Endocrinology & Metabolism 64.6 (1987): 1165-1168.Thanks for the A2A, Jaquelyn McBain.