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Arch Intern Med. 2008 Aug 11;168(15):1629-37.

Melamed ML, Michos ED, Post W, Astor B.

Division of Nephrology, Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Ave, Ullmann 615, Bronx, NY 10461, USA. mmelamed@aecom.yu.edu

BACKGROUND: In patients undergoing dialysis, therapy with calcitriol or paricalcitol or other vitamin D agents is associated with reduced mortality. Observational data suggests that low 25-hydroxyvitamin D levels (25[OH]D) are associated with diabetes mellitus, hypertension, and cancers. However, whether low serum 25(OH)D levels are associated with mortality in the general population is unknown. METHODS: We tested the association of low 25(OH)D levels with all-cause, cancer, and cardiovascular disease (CVD) mortality in 13 331 nationally representative adults 20 years or older from the Third National Health and Nutrition Examination Survey (NHANES III) linked mortality files. Participant vitamin D levels were collected from 1988 through 1994, and individuals were passively followed for mortality through 2000. RESULTS: In cross-sectional multivariate analyses, increasing age, female sex, nonwhite race/ethnicity, diabetes, current smoking, and higher body mass index were all independently associated with higher odds of 25(OH)D deficiency (lowest quartile of 25(OH)D level, <17.8 ng/mL [to convert to nanomoles per liter, multiply by 2.496]), while greater physical activity, vitamin D supplementation, and nonwinter season were inversely associated. During a median 8.7 years of follow-up, there were 1806 deaths, including 777 from CVD. In multivariate models (adjusted for baseline demographics, season, and traditional and novel CVD risk factors), compared with the highest quartile, being in the lowest quartile (25[OH]D levels <17.8 ng/mL) was associated with a 26% increased rate of all-cause mortality (mortality rate ratio, 1.26; 95% CI, 1.08-1.46) and a population attributable risk of 3.1%. The adjusted models of CVD and cancer mortality revealed a higher risk, which was not statistically significant. CONCLUSION: The lowest quartile of 25(OH)D level (<17.8 ng/mL) is independently associated with all-cause mortality in the general population.

Arch Intern Med. 2008 Jun 9;168(11):1174-80.

Giovannucci E, Liu Y, Hollis BW, Rimm EB.

Department of Nutrition, Harvard School of Public Health, 665 Huntington Ave, Boston, MA 02115, USA. egiovann@hsph.harvard.edu

BACKGROUND: Vitamin D deficiency may be involved in the development of atherosclerosis and coronary heart disease in humans. METHODS: We assessed prospectively whether plasma 25-hydroxyvitamin D (25[OH]D) concentrations are associated with risk of coronary heart disease. A nested case-control study was conducted in 18,225 men in the Health Professionals Follow-up Study; the men were aged 40 to 75 years and were free of diagnosed cardiovascular disease at blood collection. The blood samples were returned between April 1, 1993, and November 30, 1999; 99% were received between April 1, 1993, and November 30, 1995. During 10 years of follow-up, 454 men developed nonfatal myocardial infarction or fatal coronary heart disease. Using risk set sampling, controls (n = 900) were selected in a 2:1 ratio and matched for age, date of blood collection, and smoking status. RESULTS: After adjustment for matched variables, men deficient in 25(OH)D (<or=15 ng/mL [to convert to nanomoles per liter, multiply by 2.496]) were at increased risk for MI compared with those considered to be sufficient in 25(OH)D (>or=30 ng/mL) (relative risk [RR], 2.42; 95% confidence interval [CI], 1.53-3.84; P < .001 for trend). After additional adjustment for family history of myocardial infarction, body mass index, alcohol consumption, physical activity, history of diabetes mellitus and hypertension, ethnicity, region, marine omega-3 intake, low- and high-density lipoprotein cholesterol levels, and triglyceride levels, this relationship remained significant (RR, 2.09; 95% CI, 1.24-3.54; P = .02 for trend). Even men with intermediate 25(OH)D levels were at elevated risk relative to those with sufficient 25(OH)D levels (22.6-29.9 ng/mL: RR, 1.60 [95% CI, 1.10-2.32]; and 15.0-22.5 ng/mL: RR, 1.43 [95% CI, 0.96-2.13], respectively). CONCLUSION: Low levels of 25(OH)D are associated with higher risk of myocardial infarction in a graded manner, even after controlling for factors known to be associated with coronary artery disease.

Clin Endocrinol (Oxf). 2009 Feb 18. [Epub ahead of print]

Pilz S, Dobnig H, Nijpels G, Heine RJ, Stehouwer CD, Snijder MB, van Dam RM, Dekker JM.

Department of Internal Medicine, Division of Endocrinology and Nuclear Medicine, Medical University of Graz, Austria.

SUMMARY Objective: Vitamin D deficiency is common among the elderly and may contribute to cardiovascular disease. The aim of our study was to elucidate whether low serum levels of 25-hydroxyvitamin D [25(OH)D] are associated with an increased risk of all-cause and cardiovascular mortality. Design and patients: The Hoorn Study is a prospective population-based study among older men and women. Measurements: Fasting serum 25(OH)D was determined in 614 study participants at the follow-up visit in 2000-2001, the baseline for the present analysis. To account for sex differences and seasonal variations of 25(OH)D levels we formed sex-specific quartiles, which were calculated from the 25(OH)D values of each season. Results: After a mean follow-up period of 6.2 years, 51 study participants died including 20 deaths due to cardiovascular causes. Unadjusted Cox proportional hazard ratios (with 95% confidence intervals) for all-cause and cardiovascular mortality in the first when compared to the upper three 25(OH)D quartiles were 2.24 (1.28-3.92; p=0.005) and 4.78 (1.95-11.69; p=0.001), respectively. After adjustment for age, sex, diabetes mellitus, smoking status, arterial hypertension, high density lipoprotein cholesterol, glomerular filtration rate and waist to hip ratio, the hazard ratios remained significant for all-cause [1.97 (1.08-3.58; p=0.027)] and for cardiovascular mortality [5.38 (2.02-14.34; p=0.001)]. Conclusions: Low 25(OH)D levels are associated with all-cause mortality and even more pronounced with cardiovascular mortality but it remains unclear whether vitamin D deficiency is a cause or a consequence of a poor health status. Therefore, intervention studies are warranted to evaluate whether vitamin D supplementation reduces mortality and cardiovascular diseases.

Ann Epidemiol. 2009 Feb 18. [Epub ahead of print]

Bertone-Johnson ER.

Division of Biostatistics and Epidemiology, Department of Public Health, University of Massachusetts, Amherst.

Though the relationship between vitamin D and breast cancer remains unclear, a growing body of evidence suggests that vitamin D may modestly reduce risk. A large number of in vitro studies indicate that vitamin D can inhibit cell proliferation and promote apoptosis and cell differentiation in breast tumor tissue. Results from analytic studies of sunlight exposure and dietary intake have been inconsistent but together generally support a modestly protective role of vitamin D, at least in some population subgroups. Studies using blood vitamin D metabolites to assess vitamin D status may be less prone to misclassification than those of diet and sunlight exposure. Overall, the two prospective and four case-control studies of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D tend to support a protective effect in older women. The relationship between common vitamin D receptor polymorphisms and risk remains unclear. Many questions about this relationship clearly remain, including the utility of assessing vitamin D through diet and sunlight exposure, the relationship between plasma metabolites, and the potential modifying effects of age, menopausal status and tumor characteristics. Given that vitamin D status is modifiable, additional prospective studies are necessary to determine if vitamin D may have important potential for breast cancer prevention.

Scand J Immunol. 2008 Sep;68(3):261-9. Epub 2008 May 29. Review.

Szodoray P, Nakken B, Gaal J, Jonsson R, Szegedi A, Zold E, Szegedi G, Brun JG, Gesztelyi R, Zeher M, Bodolay E.

Division of Clinical Immunology, 3rd Department of Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary. szodoray@gmail.com

Vitamin D, besides having well-known control functions of calcium and phosphorus metabolism, bone formation and mineralization, also has a role in the maintenance of immune-homeostasis. The immune-regulatory role of vitamin D affects both the innate and adaptive immune system contributing to the immune-tolerance of self-structures. Impaired vitamin D supply/regulation, amongst other factors, leads to the development of autoimmune processes in animal models of various autoimmune diseases. The administration of vitamin D in these animals leads to improvement of immune-mediated symptoms. Moreover, in human autoimmune diseases, such as multiple sclerosis, or rheumatoid arthritis the pathogenic role of vitamin D has been described. The review aims at describing the complex immune-regulatory role of vitamin D from the cellular level through autoimmune animal models and depicting the known contribution of vitamin D in the pathogenesis of human autoimmune diseases.

Nutr Rev. 2008 Oct;66(10 Suppl 2):S135-8. Review

Cantorna MT.

The Center for Immunology and Infectious Disease, Department of Veterinary and Biomedical Science, The Pennsylvania State University, University Park, Pennsylvania 16802, USA. mxc69@psu.edu

Observational studies document a positive relationship between vitamin D from the environment (sunlight or diet), circulating vitamin D status, and improved symptoms or prevention of multiple sclerosis (MS). Experimental animal models of MS reproduce the beneficial effects of vitamin D and 1,25(OH)(2)D(3). The geographical distribution of MS can be explained by both the hygiene hypothesis and the vitamin D hypothesis. It therefore seems more likely that both hypotheses may be correct and that there are interactions between multiple environmental factors like vitamin D and the rate of infection that might explain the etiology of MS. The effects of vitamin D on the immune system and in the CNS have begun to be described and there is some information on the mechanisms underlying the effects of vitamin D in MS. A need exists for better understanding of the interactions of the environmental factors on MS, communication with the physicians treating MS patients as to the benefits of vitamin D, and clinical interventions with both vitamin D and analogs of 1,25(OH)(2)D(3).

Arch Intern Med. 2009;169(4):384-390.

Adit A. Ginde, MD, MPH; Jonathan M. Mansbach, MD; Carlos A. Camargo Jr, MD, DrPH

Author Affiliations: Department of Emergency Medicine, University of Colorado Denver School of Medicine, Aurora (Dr Ginde); and Department of Medicine, Children's Hospital Boston (Dr Mansbach), and Department of Emergency Medicine, Massachusetts General Hospital (Dr Camargo), Harvard Medical School, Boston.

Background Recent studies suggest a role for vitamin D in innate immunity, including the prevention of respiratory tract infections (RTIs). We hypothesize that serum 25-hydroxyvitamin D (25[OH]D) levels are inversely associated with self-reported recent upper RTI (URTI).

Methods We performed a secondary analysis of the Third National Health and Nutrition Examination Survey, a probability survey of the US population conducted between 1988 and 1994. We examined the association between 25(OH)D level and recent URTI in 18 883 participants 12 years and older. The analysis adjusted for demographics and clinical factors (season, body mass index, smoking history, asthma, and chronic obstructive pulmonary disease).

Results The median serum 25(OH)D level was 29 ng/mL (to convert to nanomoles per liter, multiply by 2.496) (interquartile range, 21-37 ng/mL), and 19% (95% confidence interval [CI], 18%-20%) of participants reported a recent URTI. Recent URTI was reported by 24% of participants with 25(OH)D levels less than 10 ng/mL, by 20% with levels of 10 to less than 30 ng/mL, and by 17% with levels of 30 ng/mL or more (P < .001). Even after adjusting for demographic and clinical characteristics, lower 25(OH)D levels were independently associated with recent URTI (compared with 25[OH]D levels of 30 ng/mL: odds ratio [OR], 1.36; 95% CI, 1.01-1.84 for <10 ng/mL and 1.24; 1.07-1.43 for 10 to <30 ng/mL). The association between 25(OH)D level and URTI seemed to be stronger in individuals with asthma and chronic obstructive pulmonary disease (OR, 5.67 and 2.26, respectively).

Conclusions Serum 25(OH)D levels are inversely associated with recent URTI. This association may be stronger in those with respiratory tract diseases. Randomized controlled trials are warranted to explore the effects of vitamin D supplementation on RTI.

Altern Med Rev. 2008 Mar;13(1):6-20. Review.

Cannell JJ, Hollis BW.

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 adjuvant treatment in patients with serious illnesses and never replace standard treatment. Theoretically, pharmacological doses of vitamin D (2,000 IU per kg per day for three days) may produce enough of the naturally occurring antibiotic cathelicidin to cure common viral respiratory infections, such as influenza and the common cold, but such a theory awaits further science.

British Journal of Cancer (2009) 100, 450–454. doi:10.1038/sj.bjc.6604865

S Tretli¹,2, E Hernes¹,3, J P Berg⁴,5, U E Hestvik¹ and T E Robsahm1

1The Cancer Registry of Norway, Institute of Population-based Cancer Research, Oslo, Norway ²Department of Community Medicine and General Practice, NTNU, Trondheim, Norway ³The Norwegian Radium Hospital, Montebello, Norway ⁴Hormone Laboratory, Aker University Hospital, Oslo, Norway ⁵Faculty Division Ullevål University Hospital, University of Oslo, Oslo, Norway

Based on observations that for certain cancers, mortality varies according to sun exposure, vitamin D has been proposed to influence on disease progression. This study aims to investigate whether serum levels of 25(OH)D are associated with prognosis in patients with prostate cancer. In total, 160 patients with a serum sample in the JANUS serum bank were included. For 123 patients a pre-treatment serum sample was taken, whereas 37 of the patients had received hormone therapy prior to the blood collection. The serum level of 25(OH)D was classified as low (< 50 nmol l^-1), medium (50–80 nmol l^-1) or high (>80 nmol l^-1). A Cox proportional hazard regression model was used to assess the association between serum 25(OH)D and cancer mortality. During follow-up, 61 deaths occurred, of whom 52 died of prostate cancer. The median time of follow-up was 44.0 months (range, 1.2–154.6). Serum 25(OH)D at medium or high levels were significantly related to better prognosis (RR 0.33; 95% CI 0.14–0.77, RR 0.16; 95% CI 0.05–0.43) compared with the low level. Analysis restricted to patients receiving hormone therapy gave a stronger association. The serum level of 25(OH)D may be involved in disease progression and is a potential marker of prognosis in patients with prostate cancer.

PLoS Med. 2007 Mar;4(3):e103.

Li H, Stampfer MJ, Hollis JB, Mucci LA, Gaziano JM, Hunter D, Giovannucci EL, Ma J.

Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America. haojie.li@channing.havard.edu

BACKGROUND: Vitamin D insufficiency is a common public health problem nationwide. Circulating 25-hydroxyvitamin D3 (25[OH]D), the most commonly used index of vitamin D status, is converted to the active hormone 1,25 dihydroxyvitamin D3 (1,25[OH]2D), which, operating through the vitamin D receptor (VDR), inhibits in vitro cell proliferation, induces differentiation and apoptosis, and may protect against prostate cancer. Despite intriguing results from laboratory studies, previous epidemiological studies showed inconsistent associations of circulating levels of 25(OH)D, 1,25(OH)2D, and several VDR polymorphisms with prostate cancer risk. Few studies have explored the joint association of circulating vitamin D levels with VDR polymorphisms. METHODS AND FINDINGS: During 18 y of follow-up of 14,916 men initially free of diagnosed cancer, we identified 1,066 men with incident prostate cancer (including 496 with aggressive disease, defined as stage C or D, Gleason 7-10, metastatic, and fatal prostate cancer) and 1,618 cancer-free, age- and smoking-matched control participants in the Physicians' Health Study. We examined the associations of prediagnostic plasma levels of 25(OH)D and 1,25(OH)2D, individually and jointly, with total and aggressive disease, and explored whether relations between vitamin D metabolites and prostate cancer were modified by the functional VDR FokI polymorphism, using conditional logistic regression. Among these US physicians, the median plasma 25(OH)D levels were 25 ng/ml in the blood samples collected during the winter or spring and 32 ng/ml in samples collected during the summer or fall. Nearly 13% (summer/fall) to 36% (winter/spring) of the control participants were deficient in 25(OH)D (<20 ng/ml) and 51% (summer/fall) and 77% (winter/spring) had insufficient plasma 25(OH)D levels (<32 ng/ml). Plasma levels of 1,25(OH)2D did not vary by season. Men whose levels for both 25(OH)D and 1,25(OH)2D were below (versus above) the median had a significantly increased risk of aggressive prostate cancer (odds ratio [OR] = 2.1, 95% confidence interval [CI] 1.2-3.4), although the interaction between the two vitamin D metabolites was not statistically significant (pinteraction = 0.23). We observed a significant interaction between circulating 25(OH)D levels and the VDR FokI genotype (pinteraction < 0.05). Compared with those with plasma 25(OH)D levels above the median and with the FokI FF or Ff genotype, men who had low 25(OH)D levels and the less functional FokI ff genotype had increased risks of total (OR = 1.9, 95% CI 1.1-3.3) and aggressive prostate cancer (OR = 2.5, 95% CI 1.1-5.8). Among men with plasma 25(OH)D levels above the median, the ff genotype was no longer associated with risk. Conversely, among men with the ff genotype, high plasma 25(OH)D level (above versus below the median) was related to significant 60% approximately 70% lower risks of total and aggressive prostate cancer. CONCLUSIONS: Our data suggest that a large proportion of the US men had suboptimal vitamin D status (especially during the winter/spring season), and both 25(OH)D and 1,25(OH)2D may play an important role in preventing prostate cancer progression. Moreover, vitamin D status, measured by 25(OH)D in plasma, interacts with the VDR FokI polymorphism and modifies prostate cancer risk. Men with the less functional FokI ff genotype (14% in the European-descent population of this cohort) are more susceptible to this cancer in the presence of low 25(OH)D status.

Autoimmun Rev. 2007 Nov;7(1):59-64. Epub 2007 Aug 14.

Cutolo M, Otsa K, Uprus M, Paolino S, Seriolo B.

Research Laboratory and Academic Clinical Unit of Rheumatology, Department of Internal Medicine, University of Genova, Viale Benedetto XV, 6 - 16132 Genova, Italy. mcutolo@unige.it

The discovery of the vitamin D receptor (VDR) in the cells of the immune system and the fact that activated dendritic cells produce the vitamin D hormone suggested that vitamin D could have immunoregulatory properties. VDR, a member of the nuclear hormone receptor superfamily, was identified in mononuclear cells, dendritic cells, antigen-presenting cells, and activated T-B lymphocytes. In synthesis, the most evident effects of the D-hormone on the immune system seem to be in the downregulation of the Th1-driven autoimmunity. Low serum levels of vitamin D3 might be partially related, among other factors, to prolonged daily darkness (reduced activation of the pre vitamin D by the ultra violet B sunlight), different genetic background (i.e. vitamin D receptor polymorphism) and nutritional factors, and explain to the latitute-related prevalence of autoimmune diseases such as rheumatoid arthritis (RA), by considering the potential immunosuppressive roles of vitamin D. 25(OH)D3 plasma levels have been found inversely correlated at least with the RA disease activity showing a circannual rhythm (more severe in winter). Recently, greater intake of vitamin D was associated with a lower risk of RA, as well as a significant clinical improvement was strongly correlated with the immunomodulating potential in vitamin D-treated RA patients.

Curr Opin Clin Nutr Metab Care. 2008 Nov;11(6):752-7. Review.

Zittermann A, Koerfer R.

Department of Thoracic and Cardiovascular Surgery, Heart and Diabetes Center North-Rhine Westfalia, Ruhr University Bochum, Bad Oeynhausen, Germany. azittermann@hdz-nrw.de

PURPOSE OF REVIEW: The pathogenesis of coronary heart disease is of multifactorial origin. Probably, not all risk factors are satisfactorily understood. This article outlines beneficial vitamin D effects on cardiac function and the vasculature. In addition, human data associating serum vitamin D metabolite levels or oral vitamin D dosages or both with coronary heart disease outcome parameters are reviewed. RECENT FINDINGS: There is accumulating evidence that the vitamin D hormone calcitriol exerts important physiological effects in cardiomyocytes, vascular smooth muscle cells, and the vascular endothelium. Low levels of the calcitriol precursor 25-hydoxyvitamin D are associated with myocardial infarction, congestive heart failure, and calcific aortic stenosis. Deficient calcitriol concentrations probably contribute to the massive vascular calcification seen in chronic kidney disease. In patients with end-stage renal disease and end-stage heart failure, very low-circulating calcitriol levels or nonuse of active vitamin D or both are independently associated with high mortality rates. SUMMARY: Despite these exciting data, it is still too early to recommend exact dosages for the prevention or therapy of coronary heart disease. Prospective, randomized controlled trials with different amounts of vitamin D and probably with its active form calcitriol are needed to determine whether vitamin D can prevent coronary heart disease events and mortality.

Mol Aspects Med. 2008 Dec;29(6):361-8. Epub 2008 Sep 2. Review.

Holick MF.

Department of Medicine, Section of Endocrinology, Nutrition, and Diabetes, Vitamin D, Skin and Bone Research Laboratory, Boston University Medical Center, Boston, MA, USA. mfholick@bu.edu

Vitamin D, the sunshine vitamin, is important for childhood bone health. Over the past two decades, it is now recognized that vitamin D not only is important for calcium metabolism and maintenance of bone health throughout life, but also plays an important role in reducing risk of many chronic diseases including type I diabetes, multiple sclerosis, rheumatoid arthritis, deadly cancers, heart disease and infectious diseases. How vitamin D is able to play such an important role in health is based on observation that all tissues and cells in the body have a vitamin D receptor, and, thus, respond to its active form 1,25-dihydroxyvitamin D. However, this did not explain how living at higher latitudes and being at risk of vitamin D deficiency increased risk of these deadly diseases since it was also known that the 1,25-dihydroxyvitamin D levels are normal or even elevated when a person is vitamin D insufficient. Moreover, increased intake of vitamin D or exposure to more sunlight will not induce the kidneys to produce more 1,25-dihydroxyvitamin D. The revelation that the colon, breast, prostate, macrophages and skin among other organs have the enzymatic machinery to produce 1,25-dihydroxyvitamin D provides further insight as to how vitamin D plays such an essential role for overall health and well being. This review will put into perspective many of the new biologic actions of vitamin D and on how 1,25-dihydroxyvitamin D is able to regulate directly or indirectly more than 200 different genes that are responsible for a wide variety of biologic processes.

Breastfeed Med. 2008 Dec;3(4):239-50.

Wagner CL, Taylor SN, Hollis BW.

Department of Pediatrics, Pediatric Nutritional Research Center, Darby Children's Research Institute, Medical University of South Carolina, Charleston, South Carolina 29425, USA. wagnercl@musc.edu

Abstract Vitamin D has emerged from obscurity, and its effects on various organ systems throughout the body down to the cellular level are being discovered. What was once thought to be a simple hormone affecting only bone and calcium metabolism has shifted. We no longer see vitamin D as a "vitamin" important only in childhood, but as a complex hormone that is involved not only in calcium homeostasis but also in the integrity of the innate immune system. Vitamin D deficiency is linked to inflammatory and long-latency diseases such as multiple sclerosis, rheumatoid arthritis, tuberculosis, diabetes, and various cancers, to name a few. In this review, we trace how we came to view vitamin D and how that view led to one of the largest epidemics of nutrient deficiency beginning in the late 20(th) century. We then discuss the needs of vitamin D in the context of the breastfeeding mother and her infant and child, why breastfed infants are particularly at risk, and what to do about it.