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Circulating vitamin D3 and 25-hydroxyvitamin D in humans: An important tool to define adequate nutritional vitamin D status. Hollis BW, Wagner CL, Drezner MK, Binkley NC. J Steroid Biochem Mol Biol. 2007 Mar;103(3-5):631-4. Epub 2007 Jan 10. PMID: 17218096 In the present study, we sought to investigate what circulating 25(OH)D levels would result in populations exhibiting no substrate limitations to the vitamin D-25-hydroxylase. To perform this, we chose two distinct populations. The first were individuals from a year-found sunny environment who spent a good deal of time outdoors. The second were a group of lactating women receiving a substantial daily oral dose of vitamin D3. Surprisingly, a study such as this previously had not been undertaken. There are several reasons for this. First, finding a group of sun-exposed individuals is not an easy task; in fact, we had to go to Hawaii to find them. Secondly, very few studies have been performed where subjects actually received adequate vitamin D3 supplementation to make them replete. Finally, it is very difficult and costly to measure circulating vitamin D3 and relate it to circulating 25(OH)D. The results of our study are far-reaching. This study also demonstrates that individuals can be vitamin D deficient with significant sun exposure if the skin area exposed is limited as was suggested several years ago (19). Finally, whether one receives their vitamin D3 orally or through UV exposure, the vitamin D-25-hydroxylase appears to handle it in an equivalent fashion with respect to maintaining circulating 25(OH)D levels. Thus, we believe that the relationship between circulating vitamin D and 25(OH)D may define adequate nutritional vitamin D status.

Defining Adequate Vitamin D Intake : Cross-sectional and Intervention Studies Viljakainen, Heli Tuulikki University of Helsinki 2008-05-23 Doctoral dissertation (article-based) Vitamin D is required for normal bone growth and maintenance of the skeleton throughout life. In Finland, like in many other Western countries, the population suffers from inadequate or deficient vitamin D status, especially during winter, which is thought to increase the risk of osteoporosis. New strategies to prevent osteoporosis are actively being sought. The main objective of this thesis was to determine whether vitamin D is feasible in the primary prevention of osteoporosis; does it affect bone mineral accrual during the growth period? A second goal was to ascertain whether seasonal variation in calcitropic hormones affects bone remodelling, and to elucidate the vitamin D intake needed to overcome this variation in different age groups. In summary, vitamin D intake remains inadequate among the target groups of this thesis, as reflected by seasonal variation in calcitropic hormones and bone metabolism. Dietary intake of vitamin D should be increased to achieve at least an adequate vitamin D status (S-25-OHD>50 nmol/l) and possibly an optimal vitamin D status (S-25-OHD>80 nmol/l) throughout the year. This could be accomplished by introducing new vitamin D-fortified foods to the market."

Twice single doses of 100,000 IU of vitamin D in winter is adequate and safe for prevention of vitamin D deficiency in healthy children from Ushuaia, Tierra Del Fuego, Argentina. Tau C, Ciriani V, Scaiola E, Acuña M. J Steroid Biochem Mol Biol. 2007 Mar;103(3-5):651-4. Epub 2007 Jan 25. PMID: 17257830 doi:10.1016/j.jsbmb.2006.12.027 These results disclosed that to prevent vitamin D deficiency for children at zones of risk at the south of our country, double supplementation of 100,000 IU of vitamin D during autumn and winter, would be adequate and safe.

How much vitamin D3 do the elderly need? Viljakainen HT, Palssa A, Kärkkäinen M, Jakobsen J, Lamberg-Allardt C. J Am Coll Nutr. 2006 Oct;25(5):429-35. PMID: 17031013 Conclusions: A clear dose response was noted in S-25-OHD to different doses of vitamin D3. The recommended dietary intake of 15 µg is adequate to maintain the S-25-OHD concentration around 40-55 nmol/L during winter, but if the optimal S-25-OHD is higher than that even higher vitamin D intakes are needed. Interestingly, subjects with lower vitamin D status at baseline responded more efficiently to supplementation than those with more adequate status

Towards an adequate intake of vitamin D. An advisory report of the Health Council of the Netherlands R M Weggemans, G Schaafsma and D Kromhout Eur J Clin Nutr advance online publication, July 22, 2009; doi:10.1038/ejcn.2009.67

Cod liver oil, vitamin A toxicity, frequent respiratory infections, and the vitamin D deficiency epidemic. Cannell JJ, Vieth R, Willett W, Zasloff M, Hathcock JN, White JH, Tanumihardjo SA, Larson-Meyer DE, Bischoff-Ferrari HA, Lamberg-Allardt CJ, Lappe JM, Norman AW, Zittermann A, Whiting SJ, Grant WB, Hollis BW, Giovannucci E. Ann Otol Rhinol Laryngol. 2008 Nov;117(11):864-70. Review. PMID: 19102134 Until we have better information on doses of vitamin D that will reliably provide adequate blood levels of 25(OH)D without toxicity, treatment of vitamin D deficiency in otherwise healthy children should be individualized according to the numerous factors that affect 25(OH)D levels, such as body weight, percent body fat, skin melanin, latitude, season of the year, and sun exposure.2 The doses of sunshine or oral vitamin D3 used in healthy children should be designed to maintain 25(OH)D levels above 50 ng/mL. As a rule, in the absence of significant sun exposure, we believe that most healthy children need about 1,000 IU of vitamin D3 daily per 11 kg (25 lb) of body weight to obtain levels greater than 50 ng/mL. Some will need more, and others less. In our opinion, children with chronic illnesses such as autism, diabetes, and/or frequent infections should be supplemented with higher doses of sunshine or vitamin D3, doses adequate to maintain their 25(OH)D levels in the mid-normal of the reference range (65 ng/mL) - and should be so supplemented year round. Otolaryngologists treating children are in a good position to both diagnose and treat vitamin D deficiency.

Use of vitamin D in clinical practice. Cannell JJ, Hollis BW. Altern Med Rev. 2008 Mar;13(1):6-20. PMID: 18377099 The recent discovery--from a meta-analysis of 18 randomized controlled trials--that supplemental cholecalciferol (vitamin D) significantly reduces all-cause mortality emphasizes the medical, ethical, and legal implications of promptly diagnosing and adequately treating vitamin D deficiency. Not only are such deficiencies common, and probably the rule, vitamin D deficiency is implicated in most of the diseases of civilization. Vitamin D's final metabolic product is a potent, pleiotropic, repair and maintenance, seco-steroid hormone that targets more than 200 human genes in a wide variety of tissues, meaning it has as many mechanisms of action as genes it targets. One of the most important genes vitamin D up-regulates is for cathelicidin, a naturally occurring broad-spectrum antibiotic. Natural vitamin D levels, those found in humans living in a sun-rich environment, are between 40-70 ng per ml, levels obtained by few modern humans. Assessing serum 25-hydroxy-vitamin D (25(OH)D) is the only way to make the diagnosis and to assure treatment is adequate and safe. Three treatment modalities exist for vitamin D deficiency: sunlight, artificial ultraviolet B (UVB) radiation, and vitamin D3 supplementation. Treatment of vitamin D deficiency in otherwise healthy patients with 2,000-7,000 IU vitamin D per day should be sufficient to maintain year-round 25(OH)D levels between 40-70 ng per mL. In those with serious illnesses associated with vitamin D deficiency, such as cancer, heart disease, multiple sclerosis, diabetes, autism, and a host of other illnesses, doses should be sufficient to maintain year-round 25(OH)D levels between 55 -70 ng per mL. Vitamin D-deficient patients with serious illness should not only be supplemented more aggressively than the well, they should have more frequent monitoring of serum 25(OH)D and serum calcium. Vitamin D should always be

Vitamin D is a fat-soluble vitamin that is essential for maintaining normal calcium metabolism (1). Vitamin D3 (cholecalciferol) can be synthesized by humans in the skin upon exposure to ultraviolet-B (UVB) radiation from sunlight, or it can be obtained from the diet. Plants synthesize ergosterol, which is converted to vitamin D2 (ergocalciferol) by ultraviolet light. Vitamin D2 is less active in birds than vitamin D3 and may also be less active in humans (2). When exposure to UVB radiation is insufficient for the synthesis of adequate amounts of vitamin D3 in the skin, adequate intake of vitamin D from the diet is essential for health.

Benefits of Vitamin D Supplementation Joel M. Kauffman, Ph.D. Journal of American Physicians and Surgeons Volume 14 Number 2 - Summer 2009 Clinical trials show that vitamin D supplementation at higher levels than previously recommended is beneficial for many conditions. It decreases the frequency of falls and fractures, helps prevent cardiovascular disease, and reduces symptoms of colds or influenza. Benefits are also seen in diabetes mellitus, multiple sclerosis, Crohn disease, pain, depression, and possibly autism. Sunlight does not cause an overdose of vitamin D production, and toxicity from supplementation is rare. Dose recommendations are increasing, but appear to be lagging the favorable trial results. A number of common drugs deplete vitamin D levels, and others may limit its biosynthesis from sunlight. People with adequate levels from sun exposure will not benefit from supplementation. While dietary intake is helpful, supplementation is better able to raise serum 25-hydroxyvitamin D , the major circulating metabolite, to the level now thought adequate, 30-50 ng/mL. Where there is inadequate daily sun exposure, oral doses of 1,000-2,000 IU/d are now considered routine, with much higher doses (up to 50,000 IU) for rapid repletion now considered safe.

An evaluation of the vitamin D3 content in fish: Is the vitamin D content adequate to satisfy the dietary requirement for vitamin D? Lu Z, Chen TC, Zhang A, Persons KS, Kohn N, Berkowitz R, Martinello S, Holick MF. J Steroid Biochem Mol Biol. 2007 Mar;103(3-5):642-4. Epub 2007 Jan 30. PMID: 17267210 doi: 10.1016/j.jsbmb.2006.12.010 Surprisingly, farmed salmon had approximately 25% of the vitamin D content as wild salmon had. The vitamin D content in fish varied widely even within species. These data suggest that the tables that list the vitamin D content are out-of-date and need to be re-evaluated. Little is known about the effect of cooking on the vitamin D content in fish. When farm salmon was baked, almost all of the vitamin D content, i.e. 240 IU of vitamin D3 was recovered from 3.5 oz. of salmon. The initial concentration in the uncooked salmon was 245 IU of vitamin D3. However, when the salmon was fried in vegetable oil, approximately 50% (123 IU of vitamin D3 was recovered.) We also evaluated the vitamin D content in mackerel which is traditionally considered to be an excellent source of vitamin D3 because of its oily content. However, in the one sample that we tested, we only observed 24 IU of vitamin D3 in 3.5 oz.

Randomized comparison of the effects of the vitamin D3 adequate intake versus 100 mcg (4000 IU) per day on biochemical responses and the wellbeing of patients. Vieth R, Kimball S, Hu A, Walfish PG. Nutr J. 2004 Jul 19;3:8. PMID: 15260882 doi:10.1186/1475-2891-3-8 CONCLUSION: The highest AI for vitamin D brought summertime 25(OH)D to >40 nmol/L, lowered PTH, and its use was associated with improved wellbeing. The 100 mcg/day dose produced greater responses. Since it was ethically necessary to provide a meaningful dose of vitamin D to these insufficient patients, we cannot rule out a placebo wellbeing response, particularly for those on the lower dose. This work confirms the safety and efficacy of both 15 and 100 mcg/day vitamin D3 in patients who needed additional vitamin D.

An evaluation of the vitamin D3 content in fish: Is the vitamin D content adequate to satisfy the dietary requirement for vitamin D?\nLu Z, Chen TC, Zhang A, Persons KS, Kohn N, Berkowitz R, Martinello S, Holick MF.\nJ Steroid Biochem Mol Biol. 2007 Mar;103(3-5):642-4. Epub 2007 Jan 30.\nPMID: 17267210 \ndoi:10.1016/j.jsbmb.2006.12.010 \n

Lu Z, Chen TC, Zhang A, Persons KS, Kohn N, Berkowitz R, Martinello S, Holick MF. An evaluation of the vitamin D3 content in fish: Is the vitamin D content adequate to satisfy the dietary requirement for vitamin D? J Steroid Biochem Mol Biol. 2007 Mar;

Vieth R, Fraser D. Vitamin D insufficiency: no recommended dietary allowance exists for this nutrient. CMAJ. 2002 Jun 11;166(12):1541-2. PMID: 12074121 In fact, current recommendations for vitamin D are not designed to ensure anything. They are simply based on the old, default strategy for setting a nutritional guideline, which is to recommend an amount of nutrient similar to what healthy people are eating. This approach underlies the circular logic behind a familiar refrain about nutrition: "If you eat a good diet, you won't need supplements." By this logic, the answer to the question, "How much nutrient do you need?" is, "Whatever healthy people happen to be eating." The essential point, lost in the confusing terminology of modern nutrient recommendations, is that a recommended daily allowance (RDA) does not yet exist for vitamin D. Instead, the recommendations for it are referred to as "adequate intake" (AI).12,13 The AI for young adults (5 µg or 200 IU) was chosen to approximate twice the average vitamin D intake reported by 52 young women in a questionnaire-based study reported from Omaha, Neb., in 1997.13,14 Because the available evidence was acknowledged as weak, the Food and Nutrition Board of the US Institute of Medicine called its recommendation an AI.

Reducing the Burden of Disease Through Adequate Intake of Vitamin D3. A presentation at University of California, San Diego, April 9, 2008 by William B. Grant, Ph.D

Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study. Hyppönen E, Läärä E, Reunanen A, Järvelin MR, Virtanen SM. Lancet. 2001 Nov 3;358(9292):1500-3. PMID: 11705562 doi:10.1016/S0140-6736(01)06580-1 INTERPRETATION: Dietary vitamin D supplementation is associated with reduced risk of type 1 diabetes. Ensuring adequate vitamin D supplementation for infants could help to reverse the increasing trend in the incidence of type 1 diabetes.

Dietary recommendations for vitamin D: a critical need for functional end points to establish an estimated average requirement. Whiting SJ, Calvo MS. J Nutr. 2005 Feb;135(2):304-9. Review. PMID: 15671232 In summary, vitamin D has emerged as a critical nutrient for which there is a compelling health need to establish adequate dietary guidelines in North America and worldwide given the increasing evidence of vitamin D deficiency and insufficient links to risk of chronic disease. We strongly argue that now there are enough data to consider setting an estimated average requirement for vitamin D and to recognize the crucial need for more research to determine the role of vitamin D in noncalciotropic functions and prevention of chronic diseases

The Toronto group gave a fixed low dose (2,000 units) of the prehormone, cholecalciferol, a very safe compound that never causes high calcium in the doses used. In fact, the lowest dose of cholecalciferol known to cause high blood calcium is more than 20,000 units. Therefore, the Toronto group got better results with one-tenth the comparable dose of deltanoids! Vieth wanted to use more cholecalciferol but widespread ignorance about the physiology and pharmacology of vitamin D remains and he could not get adequate dosing past the various review committees.

Vitamin D in preventive medicine: are we ignoring the evidence? Zittermann A. Br J Nutr. 2003 May;89(5):552-72. Review. PMID: 12720576 Vitamin D is metabolised by a hepatic 25-hydroxylase into 25-hydroxyvitamin D (25(OH)D) and by a renal 1alpha-hydroxylase into the vitamin D hormone calcitriol. Calcitriol receptors are present in more than thirty different tissues. Apart from the kidney, several tissues also possess the enzyme 1alpha-hydroxylase, which is able to use circulating 25(OH)D as a substrate. Serum levels of 25(OH)D are the best indicator to assess vitamin D deficiency, insufficiency, hypovitaminosis, adequacy, and toxicity. European children and young adults often have circulating 25(OH)D levels in the insufficiency range during wintertime. Elderly subjects have mean 25(OH)D levels in the insufficiency range throughout the year. In institutionalized subjects 25(OH)D levels are often in the deficiency range. There is now general agreement that a low vitamin D status is involved in the pathogenesis of osteoporosis. Moreover, vitamin D insufficiency can lead to a disturbed muscle function. Epidemiological data also indicate a low vitamin D status in tuberculosis, rheumatoid arthritis, multiple sclerosis, inflammatory bowel diseases, hypertension, and specific types of cancer. Some intervention trials have demonstrated that supplementation with vitamin D or its metabolites is able: (i) to reduce blood pressure in hypertensive patients; (ii) to improve blood glucose levels in diabetics; (iii) to improve symptoms of rheumatoid arthritis and multiple sclerosis. The oral dose necessary to achieve adequate serum 25(OH)D levels is probably much higher than the current recommendations of 5-15 microg/d.

Vitamin D A Key Player In Overall Health Of Several Body Organs, Says Biochemist In a paper published in the August issue of the American Journal of Clinical Nutrition, Norman identifies vitamin D's potential for contributions to good health in the adaptive and innate immune systems, the secretion and regulation of insulin by the pancreas, the heart and blood pressure regulation, muscle strength and brain activity. In addition, access to adequate amounts of vitamin D is believed to be beneficial towards reducing the risk of cancer. Norman also lists 36 organ tissues in the body whose cells respond biologically to vitamin D. The list includes bone marrow, breast, colon, intestine, kidney, lung, prostate, retina, skin, stomach and the uterus.