Nutritional Deficiencies - Health Concerns

Vitamin D - updated: 01 December 2008

Vitamin D in health and disease

Clin J Am Soc Nephrol. 2008 Sep;3(5):1535-41. Epub 2008 Jun 4

Heaney RP.

Vitamin D functions in the body through both an endocrine mechanism (regulation of calcium absorption) and an autocrine mechanism (facilitation of gene expression). The former acts through circulating calcitriol, whereas the latter, which accounts for more than 80% of the metabolic utilization of the vitamin each day, produces, uses, and degrades calcitriol exclusively intracellularly. In patients with end-stage kidney disease, the endocrine mechanism is effectively disabled; however, the autocrine mechanism is able to function normally so long as the patient has adequate serum levels of 25(OH)D, on which its function is absolutely dependent. For this reason, calcitriol and its analogs do not constitute adequate replacement in managing vitamin D needs of such patients. Optimal serum 25(OH)D levels are greater than 32 ng/mL (80 nmol/L). The consequences of low 25(OH)D status include increased risk of various chronic diseases, ranging from hypertension to diabetes to cancer. The safest and most economical way to ensure adequate vitamin D status is to use oral dosing of native vitamin D. (Both daily and intermittent regimens work well.) Serum 25(OH)D can be expected to rise by about 1 ng/mL (2.5 nmol/L) for every 100 IU of additional vitamin D each day. Recent data indicate that cholecalciferol (vitamin D(3)) is substantially more potent than ergocalciferol (vitamin D(2)) and that the safe upper intake level for vitamin D(3) is 10,000 IU/d.

Publication Types:

• Review

Vitamin D in preventive medicine: are we ignoring the evidence?

Br J Nutr. 2003 May;89(5):552-72

Zittermann A.

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.

Publication Types:

• Review

Vitamin D in systemic lupus erythematosus

Curr Opin Rheumatol. 2008 Sep;20(5):532-7

Kamen D, Aranow C.

PURPOSE OF REVIEW: There is growing interest in the contribution of vitamin D deficiency to autoimmunity. It is therefore timely to review the immunologic actions of vitamin D and the evidence linking vitamin D deficiency to autoimmune disease in animal models and to systemic lupus erythematosus in epidemiologic studies. RECENT FINDINGS: A number of recent studies have highlighted the association between systemic lupus erythematosus and vitamin D deficiency. Vitamin D deficiency skews the immunologic response towards loss of tolerance. Adding vitamin D in vitro reverses immunologic abnormalities characteristic of systemic lupus erythematosus. SUMMARY: Multiple systemic lupus erythematosus cohorts have low vitamin D levels. The physiologic and clinical consequences of vitamin D deficiency in systemic lupus erythematosus are not entirely known. Prospective studies of vitamin D in systemic lupus erythematosus are limited, but most cross-sectional studies show an inverse relationship between levels of vitamin D and disease activity. This suggests that repletion of vitamin D may have benefits beyond bone health for patients with systemic lupus erythematosus.

Publication Types:

• Review

Review: vitamin D, immunity and lupus

Lupus. 2008;17(1):6-10.

Cutolo M, Otsa K.

The identification of vitamin D receptor in cells involved in the immune response and the discovery that activated dendritic cells produce vitamin D hormone suggested that vitamin D could exert immunoregulatory effects. Patients with autoimmune diseases such as multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus (SLE) show low 25-OH vitamin D serum levels. In particular, SLE patients have multiple risk factors for vitamin D deficiency and disease severity seems correlated with lower 25-OH vitamin D serum levels. Treatment of vitamin D deficiency could be particularly important in SLE patients due to concomitant insults on their tissues such as bone, and in view of the possible immunomodulatory effects exerted by vitamin D.

Publication Types:

• Review

Vitamin D: important for prevention of osteoporosis, cardiovascular heart disease, type 1 diabetes, autoimmune diseases, and some cancers.

South Med J. 2005 Oct;98(10):1024-7

Holick MF.

Vitamin D is very important for overall health and wellbeing. A major source of vitamin D comes from exposure to sunlight. Measurement of 25-hydroxyvitamin D in the blood and not 1,25-dihydroxyvitamin D is used to determine vitamin D status. A blood level of 25-hydroxyvitamin D of at least 20 ng/mL is considered to be vitamin D sufficient. Vitamin D deficiency increases the risk of many common cancers, multiple sclerosis, rheumatoid arthritis, hypertension, cardiovascular heart disease, and type I diabetes.

Publication Types:

• Review

Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease

Am J Clin Nutr. 2004 Dec;80(6 Suppl):1678S-88S

Holick MF.

Most humans depend on sun exposure to satisfy their requirements for vitamin D. Solar ultraviolet B photons are absorbed by 7-dehydrocholesterol in the skin, leading to its transformation to previtamin D3, which is rapidly converted to vitamin D3. Season, latitude, time of day, skin pigmentation, aging, sunscreen use, and glass all influence the cutaneous production of vitamin D3. Once formed, vitamin D3 is metabolized in the liver to 25-hydroxyvitamin D3 and then in the kidney to its biologically active form, 1,25-dihydroxyvitamin D3. Vitamin D deficiency is an unrecognized epidemic among both children and adults in the United States. Vitamin D deficiency not only causes rickets among children but also precipitates and exacerbates osteoporosis among adults and causes the painful bone disease osteomalacia. Vitamin D deficiency has been associated with increased risks of deadly cancers, cardiovascular disease, multiple sclerosis, rheumatoid arthritis, and type 1 diabetes mellitus. Maintaining blood concentrations of 25-hydroxyvitamin D above 80 nmol/L (approximately 30 ng/mL) not only is important for maximizing intestinal calcium absorption but also may be important for providing the extrarenal 1alpha-hydroxylase that is present in most tissues to produce 1,25-dihydroxyvitamin D3. Although chronic excessive exposure to sunlight increases the risk of nonmelanoma skin cancer, the avoidance of all direct sun exposure increases the risk of vitamin D deficiency, which can have serious consequences. Monitoring serum 25-hydroxyvitamin D concentrations yearly should help reveal vitamin D deficiencies. Sensible sun exposure (usually 5-10 min of exposure of the arms and legs or the hands, arms, and face, 2 or 3 times per week) and increased dietary and supplemental vitamin D intakes are reasonable approaches to guarantee vitamin D sufficiency.

Publication Types:

• Review

Vitamin D deficiency: a worldwide problem with health consequences.

Am J Clin Nutr. 2008 Apr;87(4):1080S-6S

Holick MF, Chen TC.

Vitamin D deficiency is now recognized as a pandemic. The major cause of vitamin D deficiency is the lack of appreciation that sun exposure in moderation is the major source of vitamin D for most humans. Very few foods naturally contain vitamin D, and foods that are fortified with vitamin D are often inadequate to satisfy either a child's or an adult's vitamin D requirement. Vitamin D deficiency causes rickets in children and will precipitate and exacerbate osteopenia, osteoporosis, and fractures in adults. Vitamin D deficiency has been associated with increased risk of common cancers, autoimmune diseases, hypertension, and infectious diseases. A circulating level of 25-hydroxyvitamin D of >75 nmol/L, or 30 ng/mL, is required to maximize vitamin D's beneficial effects for health. In the absence of adequate sun exposure, at least 800-1000 IU vitamin D3/d may be needed to achieve this in children and adults. Vitamin D2 may be equally effective for maintaining circulating concentrations of 25-hydroxyvitamin D when given in physiologic concentrations.

Publication Types:

• Review

Vitamin D as an immune modulator in multiple sclerosis, a review

J Neuroimmunol. 2008 Feb;194(1-2):7-17.

Smolders J, Damoiseaux J, Menheere P, Hupperts R.

The role of vitamin D in calcium homeostasis is well known. More recently vitamin D has become a topic of interest in immune regulation and multiple sclerosis. The main reason for this is the observed geographical distribution of multiple sclerosis. Areas with high sunlight exposure, the principal inducer of vitamin D synthesis, have a relatively low prevalence of multiple sclerosis and vice versa. Furthermore, low levels of the principal vitamin D metabolite (25-hydroxy vitamin D) in the circulation are associated with a high incidence of multiple sclerosis. Other epidemiological evidence also supports the view that vitamin D metabolites have an immune and disease modulating effect in multiple sclerosis. Experimental research in vitro and in animal models has further clarified the interaction of vitamin D metabolites with the immune system. The evidence obtained from these studies strongly supports a model in which vitamin D mediates a shift to a more anti-inflammatory immune response, and in particular to enhanced regulatory T cell functionality. In the current review we link the basic knowledge on vitamin D and immune regulation with the vitamin D related observations in multiple sclerosis. We conclude that there is a sound basis on which to initiate double-blind placebo-controlled trials that not only address the effect of vitamin D on the clinical outcome of multiple sclerosis, but also on the regulatory T cell compartment.

Publication Types:

• Review

Multiple sclerosis and vitamin D: an update

Eur J Clin Nutr. 2004 Aug;58(8):1095-109

VanAmerongen BM, Dijkstra CD, Lips P, Polman CH.

MS is a chronic, immune-mediated inflammatory and neurodegenerative disease of the central nervous system (CNS), with an etiology that is not yet fully understood. The prevalence of MS is highest where environmental supplies of vitamin D are lowest. It is well recognized that the active hormonal form of vitamin D, 1,25-dihydroxyvitamin D (1,25-(OH)(2)D), is a natural immunoregulator with anti-inflammatory action. The mechanism by which vitamin D nutrition is thought to influence MS involves paracrine or autocrine metabolism of 25OHD by cells expressing the enzyme 1 alpha-OHase in peripheral tissues involved in immune and neural function. Administration of the active metabolite 1,25-(OH)(2)D in mice and rats with experimental allergic encephalomyelitis (EAE, an animal model of MS) not only prevented, but also reduced disease activity. 1,25-(OH)(2)D alters dendritic cell and T-cell function and regulates macrophages in EAE. Interestingly, 1,25-(OH)(2)D is thought to be operating on CNS constituent cells as well. Vitamin D deficiency is caused by insufficient sunlight exposure or low dietary vitamin D(3) intake. Subtle defects in vitamin D metabolism, including genetic polymorphisms related to vitamin D, might possibly be involved as well. Optimal 25OHD serum concentrations, throughout the year, may be beneficial for patients with MS, both to obtain immune-mediated suppression of disease activity, and also to decrease disease-related complications, including increased bone resorption, fractures, and muscle weakness.

Publication Types:

• Review

Publication Types:

• Review