Vitamin D testing and dosing
Subject: Vitamin D is tested using a 25(OH)D serum measurement. Standard lab values are inadequate for assessing status. We are using the following values to interpret 25(OH)D test results:
Before I start this discussion I must confess I have omitted discussing vitamin D and osteoporosis. Most practitioners consider Vitamin D as an essential ingredient in any treatment plan for osteoporosis to the degree I take it for granted and would like to skip over it. Suffice to say that low vitamin D contributes to low bone density. A meta-analysis of 25 studies looking at calcium and Vitamin D and calcium supplementation on fracture risk. Though many of the studies used inadequate doses of Vitamin D, the analysis concluded that combined supplementation lowered risk of vertebral fractures. [i] It seems clear that supplementation especially among the elderly can reduce fracture rates. [ii]
Current reference ranges for vitamin D levels are wrong. They are still based on average serum levels of what were thought to be healthy individuals with adequate vitamin D. That simply meant they didn't have rickets. We now know that a large proportion of the “healthy American population”, that doesn't have overt signs of rickets, is vitamin D deficient. We can not use these normals, but must look at what normal should be based on research. For most labs the bottom of the reference range is set too low due to the previous under appreciation of the clinical benefits of and physiological requirements for higher Vitamin D levels. The top of the range is set too low due to misinterpretations of the research resulting in a fear of vitamin D toxicity. New reference ranges need to be determined based on the current research.
I hate to get up on a soap box here but setting new standards for non patented vitamins often takes the back seat to changing standards which might increase the use of prescription drugs. There are few financial concerns lobbying for more vitamins in contrast to drug manufacturers and their lobbyists….
Until new standards for vitamin D are set officially, here are the guidelines we are following:
Vitamin D is assessed using a test called a serum 25(OH)D level.
Vitamin D deficiency: Less than 20ng/mL
Vitamin D Insufficiency: Less than 30 ng/mL
Researchers suggest that the way to know when someone has enough vitamin D is that adequate levels will suppress parathyroid hormone (PTH) levels. Elevated PTH increases the risk of the diseases we are trying to prevent through the use of Vitamin D. Various studies have reported levels of vitamin D sufficient to suppress PTH levels. Results vary slightly. Dawson-Hughes says it needs to be above 45 ng/mL [iv] while Need and Horowitz say 40ng/mL [v] . Instead of using PTH as a marker others have simply measured loss of bone mass and calculated at what level elderly people start losing bone. They set the lower level at 37ng/mL [vi]
Again we are being conservative and will say 30 ng/mL.
Vitamin D Optimal Levels: 40-65 ng/mL (100-160 nmol/L)
But isn't too much vitamin D dangerous?
I don't remember much from my first nutrition courses in the 1970's at Cornell but I do remember that D stands for Dangerous. Too much vitamin D is supposed to be very, very dangerous. In fact my textbook from that time, which amazingly I still have in my possession, says vitamin D should never be supplemented at more than 400 iu/day.
What should the upper limit be for 25(OH)D levels in the serum? There is no consistent evidence of vitamin D toxicity at levels below 80-88 ng/mL (200-220) nmol/L). In fact these levels “should be regarded as being within the physiologic ranges for humans.” [ix] Zittermann thinks the levels up to 100 ng/mL are not toxic.
Still let's be conservative and stick with the 65ng/mL as stated before.
Excess Vitamin D: Greater than 80ng/mL (200 nmol/L) with hypercalcemia.
The most important indicator of too much vitamin D is elevated calcium AND high serum 25(OH)D, greater than 90 ng/mL Vitamin D hypervitaminosis is extremely rare and is usually seen with industrial accidents when milk is way over fortified. For infants to become hyper vitamin D typically requires daily doses for 1-4 months of 40,000 IU/day. In adults, toxicity generally requires several months of supplementing 100,000 IU/ day. There are some people who will become hypercalcemic from vitamin D without an elevated 25(OH)D. This is why calcium levels needs to be monitored.
Some authors suggest weekly calcium monitoring of patients receiving High Dose vitamin D treatments. There are several diseases which cause vitamin D hypersensitivity. In these cases vitamin D is more rapidly converted into the active form of the vitamin calcitriol and causes disproportionate increases in calcium.
As humans we have spent thousands of years adapting to a natural environment which included regular and ample sunlight. Full body exposure on clear days near the equator, will generate the equivalent of 4,000-20,000 IU of vitamin D. How much vitamin D people make varies a great deal on their skin pigmentation. In fair skinned people sunburn may produce 50,000 IU. How much oral vitamin D a person should take depends on where they live (the latitude, sun exposure, body weight, skin pigmentation, and dietary sources, efficiency of absorption and medications that may interfere.
Suggested doses for supplementation for people with low Vitamin D levels:
For men 4,000 IU/day is a safe level of supplementation. [xi] I know that's ten times the dose I was taught 25 years ago but this is what the current research says.
There have been studies in which pregnant women were given 100,000 IU/day for extended periods of time without ill effect to mother or child. Data from numerous studies in which pregnant women were supplemented with vitamin D show it results in superior health status for the mother and infant. Based on this data, “the current recommendations of 200-400 IU of vitamin D per day are scientifically unjustifiable and ethically questionable.” [xii] Ideal doses for pregnant women are somewhere between 1,000 and 4,000 IU/day. [xiii] I confess these doses are new to me and I would suggest periodic testing of 25(OH)D and calcium if taking high doses while pregnant. In Finland the suggested daily dose for infants and children was 4-5,000 IU/day, a dose which not only appears safe but protects against Type I diabetes. Doses of 1,000 IU/day are safe for children and infants; higher doses should still probably be monitored.
It would be nice if we could still obtain our vitamin D from sunlight. Here in Denver it's getting hard to conceive of doing this, especially in the colder months. Our current concerns about developing skin cancer may limit our ability to produce vitamin D even in the summer. Typical sunscreens block vitamin D production by 97-100%. Most of us work indoors and even when outdoors keep our clothes on, most of the time. Sunlight is no longer a reliable source for most of us. Food sources provide little vitamin D. Cod liver oil does contain decent amounts of D, but it would still take 3 Tablespoons a day to reach the 4,000 IU dose required to bring up one's status. This doesn't sound like fun and I'm not even going to suggest it to anyone.
Vitamin D deficiency and insufficiency is fast becoming epidemic in the developed world and attempts at supplementation have been at inadequate levels to prevent long term health consequences. For example, 57% of 290 inpatients in Massachusetts , many of whom were getting “adequate dietary intake” were Vitamin D deficient. [xiv] In Minnesota 93% of patients with chronic musculoskeletal pain were deficient. [xv] Or 48% of patients with multiple sclerosis, 50% of patients with fibromyalgia and systemic lupus, 42% of healthy adolescents [xvi] , and 42% African American Women [xvii] and more than 62% of obese patients. [xviii] These percentages are consistent with numbers from Europe , Australia , Israel , Turkey and Saudi Arabia . In Saudi Arabia , 83% of patients with chronic back pain were deficient. [xix] The research provides us with no end of examples tying low vitamin D with illness: 73% of Austrian patients with ankylosing spondylitis, [xx] 58% of Japanese women with Grave's disease, [xxi] and so on.
Something between 23,000 and 47,000 cancer deaths might be prevented in the United States each year if we used simple interventions, either sunlight or supplementation, to raise vitamin D to adequate levels. [xxii]
Scientists knew for years that folic acid would prevent neural tube defects and deaths from heart disease. The years it took from when this information was known by researchers until it was applied by the medical community resulted in untold numbers of lives lost. Given the weight of evidence in support of using vitamin D, let us not repeat the same mistake of waiting too long.
Nutr J. 2004 Jul 19;3(1):8.
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.
Department of Laboratory Medicine and Pathology, University of Toronto , Canada . firstname.lastname@example.org
BACKGROUND: For adults, vitamin D intake of 100 mcg (4000 IU)/day is physiologic and safe. The adequate intake (AI) for older adults is 15 mcg (600 IU)/day, but there has been no report focusing on use of this dose. METHODS: We compared effects of these doses on biochemical responses and sense of wellbeing in a blinded, randomized trial. In Study 1, 64 outpatients (recruited if summer 2001 25(OH)D <61 nmol/L) were given 15 or 100 mcg/day vitamin D in December 2001. Biochemical responses were followed at subsequent visits that were part of clinical care; 37 patients completed a wellbeing questionnaire in December 2001 and February 2002. Subjects for Study 2 were recruited if their 25(OH)D was <51 nmol/L in summer 2001. 66 outpatients were given vitamin D; 51 completed a wellbeing questionnaire in both December 2002 and February 2003. RESULTS: In Study 1, basal summer 25-hydroxyvitamin D [25(OH)D] averaged 48 +/- 9 (SD) nmol/L. Supplementation for more than 6 months produced mean 25(OH)D levels of 79 +/- 30 nmol/L for the 15 mcg/day group, and 112 +/- 41 nmol/L for the 100 mcg/day group. Both doses lowered plasma parathyroid hormone with no effect on plasma calcium. Between December and February, wellbeing score improved more for the 100-mcg/day group than for the lower-dosed group (1-tail Mann-Whitney p = 0.036). In Study 2, 25(OH)D averaged 39 +/- 9 nmol/L, and winter wellbeing scores improved with both doses of vitamin D (two-tail p < 0.001). 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.
PMID: 15260882 [PubMed - as supplied by publisher]
[i] Endocr Rev. 2002 Aug;23(4):560-9.
Meta-analyses of therapies for postmenopausal osteoporosis. VIII: Meta-analysis of the efficacy of vitamin D treatment in preventing osteoporosis in postmenopausal women.
Papadimitropoulos E, Wells G, Shea B, Gillespie W, Weaver B, Zytaruk N, Cranney A, Adachi J, Tugwell P, Josse R, Greenwood C, Guyatt G; Osteoporosis Methodology Group and The Osteoporosis Research Advisory Group.
OBJECTIVE: To review the effect of vitamin D on bone density and fractures in postmenopausal women. DATA SOURCE: We searched MEDLINE and EMBASE from 1966 to 1999 and examined citations of relevant articles and proceedings of international meetings. We contacted osteoporosis investigators and primary authors to identify additional studies and to obtain unpublished data. STUDY SELECTION: We included 25 trials that randomized women to standard or hydroxylated vitamin D with or without calcium supplementation or a control and measured bone density or fracture incidence for at least 1 yr. DATA EXTRACTION: For each trial, three independent reviewers assessed the methodological quality and abstracted data. DATA SYNTHESIS: Vitamin D reduced the incidence of vertebral fractures [relative risk (RR) 0.63, 95% confidence interval (CI) 0.45-0.88, P < 0.01) and showed a trend toward reduced incidence of nonvertebral fractures (RR 0.77, 95% CI 0.57-1.04, P = 0.09). Most patients in the trials that evaluated vertebral fractures received hydroxylated vitamin D, and most patients in the trials that evaluated nonvertebral fractures received standard vitamin D. Hydroxylated vitamin D had a consistently larger impact on bone density than did standard vitamin D. For instance, total body differences in percentage change between hydroxylated vitamin D and control were 2.06 (0.72, 3.40) and 0.40 (-0.25, 1.06) for standard vitamin D. At the lumbar spine and forearm sites, hydroxylated vitamin D doses above 50 microg yield larger effects than lower doses. Vitamin D resulted in an increased risk of discontinuing medication in comparison to control as a result of either symptomatic adverse effects or abnormal laboratory results (RR 1.37, 95% CI 1.01-1.88), an effect that was similar in trials of standard and hydroxylated vitamin D. CONCLUSIONS: Vitamin D decreases vertebral fractures and may decrease nonvertebral fractures. The available data are uninformative regarding the relative effects of standard and hydroxylated vitamin D.
PMID: 12202471 [PubMed - indexed for MEDLINE]
[ii] J Am Med Dir Assoc. 2004 Mar-Apr;5(2):98-100.
Underutilization of calcium and vitamin D supplements in an academic long-term care facility.
Geriatrics and Extended Care, St. Joseph's Mercy Health Center, Hot Springs, AR, USA. email@example.com
BACKGROUND : Good scientific evidence indicates that calcium and vitamin D supplementation decrease the incidence of osteoporosis-related fractures among institutionalized elderly . OBJECTIVE: The objective was to study the frequency of prescribing calcium and vitamin D supplements in elderly institutionalized individuals in a large community teaching nursing home. METHODS: A cross-sectional chart review study of 177 consecutively located elderly residents from an 899-bed academic long-term care facility. RESULTS: Calcium and vitamin D supplements were prescribed in only 12% and 9% of subjects, respectively. Among subjects with the diagnosis of osteoporosis (n = 12), 66% were prescribed calcium and 58% were prescribed vitamin D supplements. Among subjects with hip fractures (n = 8), only 25% were prescribed calcium with a similar percentage prescribed vitamin D supplements. Female residents were more likely than male residents to receive calcium (P <0.05) and vitamin D supplements (P = 0.08). CONCLUSION : There is a major need to increase the utilization of calcium and vitamin D supplementation among institutionalized elderly to decrease the risk of osteoporotic fractures, including hip fractures.
PMID: 14984620 [PubMed - indexed for MEDLINE]
[iii] Am J Clin Nutr. 2003 Nov;78(5):912-9.
Long-latency deficiency disease: insights from calcium and vitamin D.
Creighton University , Omaha , NE 68131 , USA . firstname.lastname@example.org
Nutrient intake recommendations and national nutritional policies have focused primarily on prevention of short-latency deficiency diseases. Most nutrient intake recommendations today are based on prevention of the index disease only. However, inadequate intakes of many nutrients are now recognized as contributing to several of the major chronic diseases that affect the populations of the industrialized nations. Often taking many years to manifest themselves, these disease outcomes should be thought of as long-latency deficiency diseases. Sometimes they come about by the same pathophysiologic mechanism that produces the index disease, but sometimes the mechanisms are completely different. Well-documented examples of both short- and long-latency deficiency states involving calcium and vitamin D are described briefly. Then, the insights derived from these nutrients are tentatively applied to folic acid. Discerning the full role of nutrition in long-latency, multifactorial disorders is probably the principal challenge facing nutritional science today. The first component of this challenge is to recognize that inadequate intakes of specific nutrients may produce more than one disease, may produce diseases by more than one mechanism, and may require several years for the consequent morbidity to be sufficiently evident to be clinically recognizable as "disease." Because the intakes required to prevent many of the long-latency disorders are higher than those required to prevent the respective index diseases, recommendations based solely on preventing the index diseases are no longer biologically defensible.
PMID: 14594776 [PubMed - indexed for MEDLINE]
Link to Full text of review article:
[iv] Am J Clin Nutr. 1997 Jan;65(1):67-71.
Plasma calcidiol, season, and serum parathyroid hormone concentrations in healthy elderly men and women.
Dawson-Hughes B, Harris SS, Dallal GE.
Jean Mayer US Department Agriculture Human Nutrition Research Center on Aging, Tufts University , Boston 02111 , USA . email@example.com
Wintertime declines in vitamin D lead to increased concentrations of parathyroid hormone (PTH) and accelerated bone loss in postmenopausal women. We conducted this study to compare calcidiol (25-hydroxyvitamin D) concentrations of men and women, to examine the influence of season, travel, vitamin D intake, and other variables on these concentrations, and to compare associations between calcidiol and PTH concentrations in elderly men and women. In this cross-sectional study of 182 men and 209 women aged > 65 y, mean calcidiol concentrations were higher in men than in women overall (mean +/- SD: 82.4 +/- 35.8 compared with 68.9 +/- 32.1 nmol/L, P < 0.001). In the subset measured in winter (February-May), plasma calcidiol concentrations were lower and not significantly different in men (59.4 +/- 21.8, n = 52) and women (57.7 +/- 23.4 nmol/L, n = 83). In a multiple-regression model, calcidiol concentrations were positively influenced by wintertime travel (P = 0.012), vitamin D intake (P = 0.002), and time spent outdoors (P = 0.096) and negatively influenced by weight (P < 0.001) and age (P = 0.039). Plasma calcidiol and serum PTH concentrations were inversely related, with PTH rising slowly as calcidiol concentrations declined below 110 nmol/L (95 CI: 60, 168 nmol/L). More than 90% of the men and women had calcidiol concentrations below this value in the wintertime. The high prevalence of lower wintertime calcidiol values may increase risk of bone loss in elderly men and women.
PMID: 8988915 [PubMed - indexed for MEDLINE]
[v] Am J Clin Nutr. 2000 Jun;71(6):1577-81.
Vitamin D status: effects on parathyroid hormone and 1, 25-dihydroxyvitamin D in postmenopausal women.
Need AG, Horowitz M, Morris HA, Nordin BC .
Division of Clinical Biochemistry, Institute of Medical and Veterinary Science, and the Department of Medicine, Royal Adelaide Hospital , Adelaide , Australia . firstname.lastname@example.org
BACKGROUND: Low serum 25-hydroxyvitamin D inverted question mark25(OH)D concentrations are commonly found in the elderly and are associated with hip fracture. Treatment with vitamin D and calcium can reduce the risk of fracture. The relation between the rise in parathyroid hormone (PTH) with age and the decrease in 25(OH)D is not clear. Neither is there any consensus on the serum concentration of 25(OH)D required for bone health. OBJECTIVE: Our objective was to study the relations between serum PTH, serum vitamin D metabolites, and other calcium-related variables in postmenopausal women. DESIGN: This was a cross-sectional study of 496 postmenopausal women without vertebral fractures attending our menopausal osteoporosis clinics. RESULTS: PTH was significantly positively related to age and serum 1, 25-dihydroxyvitamin D inverted question mark1,25(OH)(2)D and inversely related to 25(OH)D and plasma ionized calcium. There was a step-like increase in PTH as serum 25(OH)D fell below 40 nmol/L. In women with 25(OH)D concentrations >40 nmol/L, 1,25(OH)(2)D was positively related to 25(OH)D; in women with 25(OH)D concentrations </=40 nmol/L, the relation was the inverse. In women with 25(OH)D concentrations </=40 nmol/L, 1,25(OH)(2)D was most closely related to PTH; in women with 25(OH)D concentrations >40 nmol/L, 1,25(OH)(2)D was most closely (inversely) related to plasma creatinine. Therefore, with serum 25(OH)D concentrations increasingly <40 nmol/L, serum 1,25(OH)(2)D becomes critically dependent on rising concentrations of PTH. CONCLUSION : The data suggest that aging women should maintain 25(OH)D concentrations >40 nmol/L (which is the lower limit of our normal range for healthy young subjects) for optimal bone health.
PMID: 10837301 [PubMed - indexed for MEDLINE]
[vi] Osteoporos Int. 2000;11(9):739-44.
Low vitamin D levels in outpatient postmenopausal women from a rheumatology clinic in Madrid , Spain : their relationship with bone mineral density.
Aguado P, del Campo MT, Garces MV, Gonzalez-Casaus ML, Bernad M, Gijon-Banos J, Martin Mola E, Torrijos A, Martinez ME.
Rheumatology and Clinical Biochemistry Divisions, H.U. La Paz , Madrid , Spain . email@example.com
To evaluate a possible relationship between vitamin D levels and bone mineral density (BMD) and the prevalence of hypovitaminosis in a population of postmenopausal women from a rheumatologic outpatient clinic in Madrid, Spain, 171 postmenopausal women (aged 47-66 years) divided into two groups (osteoporotic and nonosteoporotic, according to WHO criteria) were studied between November and June. Liver and kidney function were normal in all subjects. Serum parathyroid hormone (PTH) and calcidiol levels were determined and bone densitometry carried out at the lumbar spine and hip level. PTH and calcidiol serum levels did not show any correlation. Serum PTH was inversely related to BMD at both hip and lumbar spine in the total group, and at the hip with calcidiol levels lower than 37 nmol/l. Calcidiol was directly related to hip BMD only when levels were lower than 37 nmol/l. Results of a stepwise multiple regression analysis showed that the single factor which affected BMD at the hip was calcidiol in the subgroup with serum calcidiol levels below 37 nmol/l, while in the subgroup with serum calcidiol levels above 37 nmol/l, the main factor affecting hip BMD was serum PTH. The prevalence of vitamin D deficiency at a cutoff of 37 nmol/l was 64%. In summary, calcidiol serum levels below 37 nmol/l seem to affect bone mass, regardless of the effect of PTH. Vitamin D deficiency is a frequent finding in the postmenopausal women who attend a rheumatology outpatient clinic in Madrid . Vitamin D supplementation should therefore be considered in this population during the winter season.
PMID: 11148801 [PubMed - indexed for MEDLINE]
[vii] Br J Nutr. 2003 May;89(5):552-72.
Vitamin D in preventive medicine: are we ignoring the evidence?
Department of Nutrition Science, University of Bonn , Endenicher Allee 11-13, 53115 Bonn , Germany . firstname.lastname@example.org
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.
PMID: 12720576 [PubMed - indexed for MEDLINE]
[viii] J Neuroimmunol. 2003 Jan;134(1-2):128-32.
Cytokine profile in patients with multiple sclerosis following vitamin D supplementation.
Mahon BD, Gordon SA, Cruz J, Cosman F, Cantorna MT.
Graduate Program in Nutrition, Pennsylvania State University , University Park , PA 16802 , USA .
Multiple sclerosis (MS) patients were randomized, in a double blind design, and placed into either a vitamin D supplemented group or a placebo control group. As expected, serum 25-hydroxyvitamin D levels increased significantly following 6 month vitamin D supplementation (17+/-6 ng/ml at baseline to 28+/-8 ng/ml at 6 months). Vitamin D supplementation also significantly increased serum transforming growth factor (TGF)-beta 1 levels from 230+/-21 pg/ml at baseline to 295+/-40 pg/ml 6 months later. Placebo treatment had no effect on serum TGF-beta 1 levels. Tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, and interleukin (IL)-13 were not different following vitamin D supplementation. IL-2 mRNA levels decreased following vitamin D supplementation but the differences did not reach significance. Vitamin D supplementation of MS patients for 6 months was associated with increased vitamin D status and serum TGF-beta 1.
Randomized Controlled Trial
PMID: 12507780 [PubMed - indexed for MEDLINE]
[ix] Am J Clin Nutr. 1999 May;69(5):842-56.
Am J Clin Nutr. 1999 May;69(5):825-6.
Am J Clin Nutr. 2001 Dec;74(6):862-4.
Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety.
Department of Laboratory Medicine and Pathobiology, University of Toronto , Mount Sinai Hospital , Ontario , Canada . email@example.com
For adults, the 5-microg (200 IU) vitamin D recommended dietary allowance may prevent osteomalacia in the absence of sunlight, but more is needed to help prevent osteoporosis and secondary hyperparathyroidism. Other benefits of vitamin D supplementation are implicated epidemiologically: prevention of some cancers, osteoarthritis progression, multiple sclerosis, and hypertension . Total-body sun exposure easily provides the equivalent of 250 microg (10000 IU) vitamin D/d, suggesting that this is a physiologic limit. Sailors in US submarines are deprived of environmentally acquired vitamin D equivalent to 20-50 microg (800-2000 IU)/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. To ensure that serum 25(OH)D concentrations exceed 100 nmol/L, a total vitamin D supply of 100 microg (4000 IU)/d is required. 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.
PMID: 10232622 [PubMed - indexed for MEDLINE]
[link to FREE full text:
[x] Clin Lab Med. 2000 Sep;20(3):569-90.
Calcium and vitamin D. Diagnostics and therapeutics.
Department of Medicine, Boston University School of Medicine , Massachusetts , USA .
Vitamin D is neither a vitamin nor a nutrient if adequate exposure to sunlight is available to produce adequate quantities of vitamin D3 in the skin. It is well known that an adequate supply of vitamin D, either from the diet or from the skin, is important for maximum bone health throughout life. The new revelation that 25(OH)D can be metabolized to 1,25(OH)2D in the colon, prostate, and skin opens a new chapter in the vitamin D story. It is quite possible that there are two levels of vitamin D sufficiency. One level requires that the serum 25(OH)D levels be at least 20 ng/mL to satisfy the body's requirement for the renal production of 1,25(OH)2D that regulates calcium absorption, and bone calcium mobilization and bone mineralization. The second level may need higher circulating levels of 25(OH)D for maximum cellular health because of the conversion of 25(OH)D to 1,25(OH)2D in extrarenal tissues, such as the prostate, colon, and skin.
PMID: 10986622 [PubMed - indexed for MEDLINE]
[xi] Am J Clin Nutr. 2001 Feb;73(2):288-94.
Am J Clin Nutr. 2001 Dec;74(6):862-4.
Am J Clin Nutr. 2001 Dec;74(6):864-5; author reply 866-7.
Am J Clin Nutr. 2001 Dec;74(6):865-7.
Efficacy and safety of vitamin D3 intake exceeding the lowest observed adverse effect level.
Vieth R, Chan PC, MacFarlane GD.
Mount Sinai Hospital , Toronto , Ontario , Canada . firstname.lastname@example.org
BACKGROUND: The Food and Nutrition Board of the National Academy of Sciences states that 95 microg vitamin D/d is the lowest observed adverse effect level (LOAEL). OBJECTIVE: Our objective was to assess the efficacy and safety of prolonged vitamin D3 intakes of 25 and 100 microg (1000 and 4000 IU)/d. Efficacy was based on the lowest serum 25-hydroxyvitamin D [25(OH)D] concentration achieved by subjects taking vitamin D3; potential toxicity was monitored by measuring serum calcium concentrations and by calculating urinary calcium-creatinine ratios. DESIGN: Healthy men and women (n = 61) aged 41 +/- 9 y (mean +/- SD) were randomly assigned to receive either 25 or 100 microg vitamin D3/d for 2-5 mo, starting between January and February. Serum 25(OH)D was measured by radioimmunoassay. RESULTS: Baseline serum 25(OH)D was 40.7 +/- 15.4 nmol/L (mean +/- SD). From 3 mo on, serum 25(OH)D plateaued at 68.7 +/- 16.9 nmol/L in the 25-microg/d group and at 96.4 +/- 14.6 nmol/L in the 100-microg/d group. Summertime serum 25(OH)D concentrations in 25 comparable subjects not taking vitamin D3 were 46.7 +/- 17.8 nmol/L. The minimum and maximum plateau serum 25(OH)D concentrations in subjects taking 25 and 100 microg vitamin D3/d were 40 and 100 nmol/L and 69 and 125 nmol/L, respectively. Serum calcium and urinary calcium excretion did not change significantly at either dosage during the study. CONCLUSIONS: The 100-microg/d dosage of vitamin D3 effectively increased 25(OH)D to high-normal concentrations in practically all adults and serum 25(OH)D remained within the physiologic range; therefore, we consider 100 microg vitamin D3/d to be a safe intake .
Randomized Controlled Trial
PMID: 11157326 [PubMed - indexed for MEDLINE]
[xii] Integrative Medicine vol 3 no 5 october/November 2004 pg 51
[xiii] Am J Clin Nutr. 2004 May;79(5):717-26.
Assessment of dietary vitamin D requirements during pregnancy and lactation.
Hollis BW, Wagner CL.
Division of Neonatology, Department of Pediatrics, Medical University of South Carolina, 114 Doughty Street, PO Box 205770, Charleston, SC 29403, USA. email@example.com
Concerns about vitamin D have resurfaced in medical and scientific literature because the prevalence of vitamin D deficiency in the United States , particularly among darkly pigmented persons, has increased. The primary goals of this review were to discuss past and current literature and to reassess the dietary reference intake for vitamin D in adults, with particular focus on women during pregnancy and lactation. The appropriate dose of vitamin D during pregnancy and lactation is unknown, although it appears to be greater than the current dietary reference intake of 200-400 IU/d (5-10 microg/d). Doses of < or =10 000 IU vitamin D/d (250 microg/d) for up to 5 mo do not elevate circulating 25-hydroxyvitamin D to concentrations > 90 ng/mL, whereas doses < 1000 IU/d appear, in many cases, to be inadequate for maintaining normal circulating 25-hydroxyvitamin D concentrations of between 15 and 80 ng/mL. Vitamin D plays no etiologic role in cardiac valvular disease, such as that observed in Williams syndrome, and, as such, animal models involving vitamin D intoxication that show an effect on cardiac disease are flawed and offer no insight into normal human physiology. Higher doses of vitamin D are necessary for a large segment of Americans to achieve concentrations equivalent to those in persons who live and work in sun-rich environments. Further studies are necessary to determine optimal vitamin D intakes for pregnant and lactating women as a function of latitude and race.
PMID: 15113709 [PubMed - indexed for MEDLINE]
[xiv] N Engl J Med. 1998 Mar 19;338(12):777-83.
N Engl J Med. 1998 Jul 30;339(5):344-5; author reply 345-6.
N Engl J Med. 1998 Jul 30;339(5):345-6.
N Engl J Med. 1998 Mar 19;338(12):828-9.
Hypovitaminosis D in medical inpatients.
Thomas MK, Lloyd-Jones DM, Thadhani RI, Shaw AC, Deraska DJ, Kitch BT, Vamvakas EC, Dick IM, Prince RL, Finkelstein JS.
Endocrine Unit, Massachusetts General Hospital and Harvard Medical School , Boston 02114 , USA .
BACKGROUND: Vitamin D deficiency is a major risk factor for bone loss and fracture. Although hypovitaminosis D has been detected frequently in elderly and housebound people, the prevalence of vitamin D deficiency among patients hospitalized on a general medical service is unknown. METHODS: We assessed vitamin D intake, ultraviolet-light exposure, and risk factors for hypovitaminosis D and measured serum 25-hydroxyvitamin D, parathyroid hormone, and ionized calcium in 290 consecutive patients on a general medical ward. RESULTS: A total of 164 patients (57 percent) were considered vitamin D-deficient (serum concentration of 25-hydroxyvitamin D, < or = 15 ng per milliliter), of whom 65 (22 percent) were considered severely vitamin D-deficient (serum concentration of 25-hydroxyvitamin D, <8 ng per milliliter). Serum 25-hydroxyvitamin D concentrations were related inversely to parathyroid hormone concentrations. Lower vitamin D intake, less exposure to ultraviolet light, anticonvulsant-drug therapy, renal dialysis, nephrotic syndrome, hypertension, diabetes mellitus, winter season, higher serum concentrations of parathyroid hormone and alkaline phosphatase, and lower serum concentrations of ionized calcium and albumin were significant univariate predictors of hypovitaminosis D. Sixty-nine percent of the patients who consumed less than the recommended daily allowance of vitamin D and 43 percent of the patients with vitamin D intakes above the recommended daily allowance were vitamin D-deficient. Inadequate vitamin D intake, winter season, and housebound status were independent predictors of hypovitaminosis D in a multivariate model. In a subgroup of 77 patients less than 65 years of age without known risk factors for hypovitaminosis D, the prevalence of vitamin D deficiency was 42 percent. CONCLUSIONS: Hypovitaminosis D is common in general medical inpatients, including those with vitamin D intakes exceeding the recommended daily allowance and those without apparent risk factors for vitamin D deficiency.
PMID: 9504937 [PubMed - indexed for MEDLINE]
[xv] Mayo Clin Proc. 2003 Dec;78(12):1463-70.
Mayo Clin Proc. 2003 Dec;78(12):1457-9.
Mayo Clin Proc. 2004 May;79(5):694; author reply 694-5.
Mayo Clin Proc. 2004 May;79(5):695; author reply 695-6.
Mayo Clin Proc. 2004 May;79(5):696, 699; author reply 699.
Prevalence of severe hypovitaminosis D in patients with persistent, nonspecific musculoskeletal pain.
Plotnikoff GA , Quigley JM.
Department of Internal Medicine, University of Minnesota Medical School , Minneapolis , Minn , USA . firstname.lastname@example.org
OBJECTIVE: To determine the prevalence of hypovitaminosis D in primary care outpatients with persistent, nonspecific musculoskeletal pain syndromes refractory to standard therapies. PATIENTS AND METHODS: In this cross-sectional study, 150 patients presented consecutively between February 2000 and June 2002 with persistent, nonspecific musculoskeletal pain to the Community University Health Care Center, a university-affiliated inner city primary care clinic in Minneapolis , Minn (45 degrees north). Immigrant (n = 83) and nonimmigrant (n = 67) persons of both sexes, aged 10 to 65 years, from 6 broad ethnic groups were screened for vitamin D status. Serum 25-hydroxyvitamin D levels were determined by radioimmunoassay. RESULTS: Of the African American, East African, Hispanic, and American Indian patients, 100% had deficient levels of vitamin D (< or = 20 ng/mL). Of all patients, 93% (140/ 150) had deficient levels of vitamin D (mean, 12.08 ng/mL; 95% confidence interval, 11.18-12.99 ng/mL). Nonimmigrants had vitamin D levels as deficient as immigrants (P = .48). Levels of vitamin D in men were as deficient as in women (P = .42). Of all patients, 28% (42/150) had severely deficient vitamin D levels (< or = 8 ng/mL), including 55% of whom were younger than 30 years. Five patients, 4 of whom were aged 35 years or younger, had vitamin D serum levels below the level of detection. The severity of deficiency was disproportionate by age for young women (P < .001), by sex for East African patients (P < .001), and by race for African American patients (P = .006). Season was not a significant factor in determining vitamin D serum levels (P = .06). CONCLUSION: All patients with persistent, nonspecific musculoskeletal pain are at high risk for the consequences of unrecognized and untreated severe hypovitaminosis D. This risk extends to those considered at low risk for vitamin D deficiency: nonelderly, nonhousebound, or nonimmigrant persons of either sex. Nonimmigrant women of childbearing age with such pain appear to be at greatest risk for misdiagnosis or delayed diagnosis. Because osteomalacia is a known cause of persistent, nonspecific musculoskeletal pain, screening all outpatients with such pain for hypovitaminosis D should be standard practice in clinical care.
PMID: 14661675 [PubMed - indexed for MEDLINE]
[xvi] Arch Pediatr Adolesc Med. 2004 Jun;158(6):531-7.
Prevalence of vitamin D deficiency among healthy adolescents.
Gordon CM, DePeter KC, Feldman HA, Grace E, Emans SJ.
Division of Adolescent/Young Adult Medicine, Children's Hospital Boston and Harvard Medical School , Boston , Mass 02115, USA . email@example.com
BACKGROUND: Although vitamin D deficiency has been documented as a frequent problem in studies of young adults, elderly persons, and children in other countries, there are limited data on the prevalence of this nutritional deficiency among healthy US teenagers. OBJECTIVE: To determine the prevalence of vitamin D deficiency in healthy adolescents presenting for primary care. DESIGN: A cross-sectional clinic-based sample. SETTING: An urban hospital in Boston . PARTICIPANTS: Three hundred seven adolescents recruited at an annual physical examination to undergo a blood test and nutritional and activity assessments. MAIN OUTCOME MEASURES: Serum levels of 25-hydroxyvitamin D (25OHD) and parathyroid hormone, anthropometric data, nutritional intake, and weekly physical activity and lifestyle variables that were potential risk factors for hypovitaminosis D. RESULTS: Seventy-four patients (24.1%) were vitamin D deficient (serum 25OHD level, </=15 ng/mL [</=37.5 nmol/L]), of whom 14 (4.6%) were severely vitamin D deficient (25OHD level, </=8 ng/mL [</=20 nmol/L]). By using a broader definition (25OHD level, </=20 ng/mL [</=50 nmol/L]), 129 patients (42.0%) were vitamin D insufficient. Serum 25OHD levels were inversely correlated with parathyroid hormone levels (r = -0.29), and were 24% lower during winter compared with summer. In a final multivariate model, season, ethnicity, milk and juice consumption, body mass index, and physical activity were significant independent predictors of hypovitaminosis D. CONCLUSIONS: Vitamin D deficiency was present in many US adolescents in this urban clinic-based sample. The prevalence was highest in African American teenagers and during winter, although the problem seems to be common across sex, season, and ethnicity.
PMID: 15184215 [PubMed - indexed for MEDLINE]
[xvii] Am J Clin Nutr. 2002 Jul;76(1):187-92.
Am J Clin Nutr. 2002 Jul;76(1):3-4.
Hypovitaminosis D prevalence and determinants among African American and white women of reproductive age: third National Health and Nutrition Examination Survey, 1988-1994.
Nesby-O'Dell S, Scanlon KS, Cogswell ME, Gillespie C, Hollis BW, Looker AC, Allen C, Doughertly C, Gunter EW, Bowman BA.
Division of Nutrition and Physical Activity, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta 30341-3717 , USA .
BACKGROUND: Recent reports of rickets among African American children drew attention to the vitamin D status of these infants and their mothers. African American women are at higher risk of vitamin D deficiency than are white women, but few studies have examined determinants of hypovitaminosis D in this population. OBJECTIVE: We examined the prevalence and determinants of hypovitaminosis D among African American and white women of reproductive age. DESIGN: We examined 1546 African American women and 1426 white women aged 15-49 y who were not pregnant and who participated in the third National Health and Nutrition Examination Survey (1988-1994). Hypovitaminosis D was defined as a serum 25-hydroxyvitamin D concentration < or =37.5 nmol/L. Multiple logistic regression was used to examine the independent association of dietary, demographic, and behavioral determinants of hypovitaminosis D. RESULTS: The prevalence of hypovitaminosis D was 42.4 +/- 3.1% ( +/- SE) among African Americans and 4.2 +/- 0.7% among whites. Among African Americans, hypovitaminosis D was independently associated with consumption of milk or breakfast cereal <3 times/wk, no use of vitamin D supplements, season, urban residence, low body mass index, and no use of oral contraceptives. Even among 243 African Americans who consumed the adequate intake of vitamin D from supplements (200 IU/d), 28.2 +/- 2.7% had hypovitaminosis D. CONCLUSIONS: The high prevalence of hypovitaminosis D among African American women warrants further examination of vitamin D recommendations for these women. The determinants of hypovitaminosis D among women should be considered when these women are advised on dietary intake and supplement use.
PMID: 12081833 [PubMed - indexed for MEDLINE]
LINK TO FREE FULL ARTICLE TEXT:
[xviii] Obes Surg. 1993 Nov;3(4):421-424.
Vitamin D Deficiency in the Morbidly Obese.
Buffington C, Walker B, Cowan GS Jr, Scruggs D.
Department of Surgery, University of Tennessee , Memphis , TN 38163 USA .
Although vitamin D deficiency has been well-documented following gastric bypass surgery, there are few studies of vitamin D status in the non-operative morbidly obese patient. We examined 25-hydroxyvitamin D (25-OHD) levels in 60 morbidly obese pre-operative females ; 62% of them had 25-OHD levels below normal range (16-74 ng/ml) which were not associated with reductions in serum calcium or phosphorus, liver or kidney dysfunction, and were not significantly correlated to patients' age. However, 25-OHD levels were significantly (p < 0.0001) and negatively correlated to body mass (r = -0.49). These data suggest that low vitamin D may be associated with obesity per se . Hypovitaminosis D, when it is found in post-bariatric surgery patients, may not be caused by the surgery since it may have been present to some degree pre-operatively.
PMID: 10757956 [PubMed - as supplied by publisher]
[xix] Spine. 2003 Jan 15;28(2):177-9.
Vitamin D deficiency and chronic low back pain in Saudi Arabia .
Al Faraj S, Al Mutairi K.
Department of Medicine, Riyadh Armed Forces Hospital , Riyadh , Saudi Arabia . firstname.lastname@example.org
STUDY DESIGN: Initial assessment involved 360 patients (90% women and 10% men) attending spinal and internal medicine clinics over a 6-year period who had experienced low back pain that had no obvious cause for more than 6 months. The patients ranged in age from 15 to 52 years. OBJECTIVES: To investigate the contribution of vitamin D deficiency as a cause for idiopathic chronic low back pain, to find a simple and sensitive test for screening patients with low back pain for vitamin D deficiency, and to determine the correlation between the vitamin deficiency and pain. METHODS: A biochemical assay of serum calcium, phosphate, alkaline phosphatase, and 25-hydroxy vitamin D level was performed before and after treatment with vitamin D supplements. RESULTS: Findings showed that 83% of the study patients (n = 299) had an abnormally low level of vitamin D before treatment with vitamin D supplements. After treatment, clinical improvement in symptoms was seen in all the groups that had a low level of vitamin D, and in 95% of all the patients (n = 341). CONCLUSIONS: Vitamin D deficiency is a major contributor to chronic low back pain in areas where vitamin D deficiency is endemic. Screening for vitamin D deficiency and treatment with supplements should be mandatory in this setting. Measurement of serum 25-OH cholecalciferol is sensitive and specific for detection of vitamin D deficiency, and hence for presumed osteomalacia in patients with chronic low back pain.
PMID: 12544936 [PubMed - indexed for MEDLINE]
[xx] Wien Klin Wochenschr. 2001 Apr 30;113(9):328-32.
Serum 25-hydroxyvitamin D and parathyroid hormone in patients with ankylosing spondylitis before and after a three-week rehabilitation treatment at high altitude during winter and spring.
Falkenbach A, Tripathi R, Sedlmeyer A, Staudinger M, Herold M.
Research Institute Gastein, Bad Gastein.
Does a sojourn at high altitude during the winter and spring improve vitamin D status (and possibly suppress parathyroid hormone [PTH]) in patients with ankylosing spondylitis (AS)? In 73 patients with AS, serum concentrations of 25-hydroxy-vitamin D [25(OH)D] and PTH were determined before and after a three-week rehabilitation treatment at Bad Gastein (1000 m above sea level). At the first examination, serum 25(OH)D was median (25th, 75th percentile) 15.5 ng mL-1 (10.0 ng mL-1, 20.6 ng mL-1). Thirteen patients (18%) had a 25(OH)D concentration below 8 ng mL-1. In 53 patients (73%) the level was below 20 ng mL-1. After the sojourn, 25(OH)D significantly (p = 0.02) increased to 19.7 (11.3, 24.6) ng mL-1. PTH did not change significantly, being 32 (22.4, 43.9) pg mL-1 before and 30.3 (24.1, 39.9) pg mL-1 after the sojourn. Analysing different periods of sojourn, a significant (p < 0.001) increase in 25(OH)D was found in April but not in the other months. Patients with ankylosing spondylitis may have extremely low levels of 25(OH)D. The results of the present study suggest that a sojourn at high altitude in early spring is liable to reduce vitamin D deficiency.
PMID: 11388078 [PubMed - indexed for MEDLINE]
J Rheumatol. 2001 Nov;28(11):2535-9.
Vitamin D levels in women with systemic lupus erythematosus and fibromyalgia.
Huisman AM, White KP, Algra A, Harth M, Vieth R, Jacobs JW, Bijlsma JW, Bell DA.
Department of Medicine, University of Western Ontario , London , Canada . Margriet.Huisman@planet.nl
OBJECTIVE: Many patients with systemic lupus erythematosus (SLE) and fibromyalgia (FM) may spend less time exposed to the sun than healthy individuals and thus might have low vitamin D levels. It is known that hydroxychloroquine (HCQ) inhibits conversion of 25(OH)- to 1,25(OH)2-vitamin D both in vitro and in patients with sarcoidosis. We assessed winter serum 25(OH)- and 1,25(OH)2-vitamin D levels in patients with SLE and FM. METHODS: We recruited 25 consecutive female SLE and 25 female FM patients in London , Ontario , between January and March 2000. Subjects completed a brief questionnaire. Serum levels of 25(OH)-, 1,25(OH)2-vitamin D, and parathyroid hormone (PTH) were measured. RESULTS: In SLE patients mean 25(OH)-vitamin D was 46.5 nmol/l and mean 1,25(OH)2-vitamin D was 74.4 pmol/l. In FM patients these means were 51.5 nmol/l and 90.1 pmol/l, respectively. Serum 25(OH)-vitamin D levels did not significantly differ between SLE and FM patients, nor after adjusting for age and vitamin D, milk consumption, and sun block use. In 14 of the SLE patients and 12 of the FM patients 25(OH)-vitamin D levels < 50 nmol/l were found. SLE patients not using vitamin D supplements had lower 25(OH)-vitamin D levels than those who did. 1,25(OH)2-vitamin D tended to be lower in the SLE compared to the FM patients. This difference could be attributed to HCQ use: HCQ users (n = 17) had lower 1,25(OH)2-vitamin D levels than nonusers (n = 33); the mean adjusted difference was 24.4 pmol/l (95% CI 2.8-49.9). CONCLUSION: Half the SLE and FM patients had 25(OH)-vitamin D levels < 50 nmol/l, a level at which PTH stimulation occurs. Our data suggest that in SLE patients HCQ might inhibit conversion of 25(OH)-vitamin D to 1,25(OH)2-vitamin D.
PMID: 11708429 [PubMed - indexed for MEDLINE]
[xxi] Endocr J. 2001 Feb;48(1):63-9.
Endocr J. 2001 Aug;48(4):515-6.
High prevalence of vitamin D deficiency in Japanese female patients with Graves' disease.
Yamashita H, Noguchi S, Takatsu K, Koike E, Murakami T, Watanabe S, Uchino S, Yamashita H, Kawamoto H.
Noguchi Thyroid Clinic and Hospital Foundation, Beppu, Oita , Japan .
We reported previously that vitamin D deficiency is a causal mechanism of postoperative tetany in patients with Graves' disease. The aim of the present study was to determine the prevalence of vitamin D deficiency by reviewing serum 25(OH)D levels in 208 patients with Graves' disease (146 women, 62 men) during a 1 year period. Serum 25(OH)D levels were significantly lower (p < 0.001) in female Graves ' patients (31.8 +/- 13.3 nmol/l) than in male patients (41.3 +/- 15.0 nmol/l). Vitamin D deficiency (defined as a serum 25(OH)D value below 25 nmol/l) was found in 40% of female patients and in 18% of male patients (p < 0.005). There was a significant seasonal variation in the 25(OH)D concentrations in female patients [amplitude 6.38 (95% CI, 5.42-7.56)], with values below 25 nmol/l found in 58% of female patients during the winter months. There were significant (p < 0.001) differences in serum 25(OH)D levels between age groups in the female patients. The concentrations were lowest in patients in their twenties (25.1 +/- 8.2 nmol/l) and highest in patients in their fifties and sixties (43.2 +/- 13.7 nmol/l). Serum 25(OH)D concentrations might be monitored in patients with Graves' disease during antithyroid drug therapy, and vitamin D and/or calcium supplements are recommended for patients with vitamin D deficiency.
PMID: 11403104 [PubMed - indexed for MEDLINE]
[xxii] Recent Results Cancer Res. 2003;164:371-7.
Ecologic studies of solar UV-B radiation and cancer mortality rates.
Solar ultraviolet B (UV-B) radiation (280-320 nm) has been associated with reduced risk of cancer of the breast, colon, ovary, and prostate, as well as non-Hodgkin's lymphoma (NHL) through the production of vitamin D in papers extending back to 1980. Using data on the geographic distribution of cancer mortality rates in the US, another ten cancers have been added to the list for which UV-B/vitamin D is a risk reduction factor (Grant 2002b; submitted). These associations persist even after additional cancer risk and risk reduction factors such as smoking, urban or rural residence, Hispanic heritage, poverty, dietary factors, and use of nonsteroidal anti-inflammatory drugs are added to the analysis. As a further test of the protective role of UV-B radiation, an ecologic study of cancer mortality rates in Europe with UV-B radiation and dietary factors was conducted. Inverse correlations are found for UV-B radiation for a number of cancers, with those for bladder, breast, endometrial, ovarian, prostate, and renal cancer, and multiple myeloma and NHL having the strongest correlations in this and ongoing multicountry ecologic studies. These studies add further support for the role of UV-B radiation and vitamin D in reducing the risk of a large number of cancers.
PMID: 12899536 [PubMed - indexed for MEDLINE]