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It seems too good to be true that one vitamin might slow or prevent the development of cancer, promote healthy newborns, keep our bones healthy, strengthen cardiovascular function, keep the immune system running properly, defend against infections, promote mental health and help keep pain levels in check.
But vitamin D has been associated with all of these benefits and has received much attention in recent years. Clinical laboratorians have become intimately familiar with the importance of vitamin D, as testing for 25-hydroxyvitamin D, or 25(OH)D, has seen a massive uptick in recent years.
The Test
Testing for 25(OH)D is typically performed to determine if a vitamin D deficiency is causing bone weakness or malformation or is affecting metabolism of calcium. This is a long-term measurement looking at the total amount of vitamin D circulating from both sun exposure and diet.
In the U.S., we get most of our vitamin D through exposure to sunlight and dietary supplementation--both sources are then converted by the liver to 25(OH)D. Low levels of 25(OH)D suggest an individual is not getting enough exposure or dietary intake, or there is a problem with the intestine's absorption of vitamin D.
Although 25(OH)D is the major form of vitamin D measured in the blood, 1,25-dihydroxyvitamin D, or 1,25(OH)(2)D, might be ordered if the patient's calcium levels are high or the patient has lymphoma or sarcoidosis. This is the active form of vitamin D, which binds to vitamin D receptors (VDRs) and produces proteins important for cell life cycles.
Low levels of 1,25(OH)(2)D are seen in kidney disease and can alert laboratorians and physicians to early kidney failure. High levels of 1,25(OH)(2)D may be present when there is excess parathyroid hormone or when sarcoidosis or some lymphomas are making 1,25(OH)(2)D outside of the kidneys.1
Associated Illnesses
The most common conditions associated with insufficient vitamin D levels are bone issues-weak or deformed bones, rickets in children, osteomalacia or osteoporosis in adults. But the list of possibly associated diseases and conditions is much longer and includes heart failure, stroke, hypertension, multiple sclerosis, autism, cancer, Type 2 diabetes, systemic lupus erythmatosus and other instances of autoimmunity.2
Cardiovascular problems, particularly hypertension and coronary heart disease, occur at higher rates with increased distance from the equator. Prevalence of vitamin D deficiency also increases the farther away one lives from the equator. Vitamin D affects many tissues and systems critical to cardiovascular health, suggesting its critical role in heart health.
Autoimmune diseases also are more prevalent farther from the equator. Vitamin D has been shown to influence dendritic cell function; it is these cells that either direct the immune system to tolerate or attack a particular cell or protein, which may explain the link between vitamin D deficiency and autoimmune diseases.
Bruce W. Hollis, PhD, professor of Pediatrics and Biochemistry and Molecular Biology and director of Pediatric Nutritional Sciences at the Medical University of South Carolina, Charleston, explained a focus of several recent studies involving vitamin D have looked at nutritional status and the ability to ward off infections.
A randomized, controlled trial out of Japan, for example, supplemented school children with 1,200 IU/d of vitamin D; the results suggested supplementation during the winter may reduce incidence of seasonal influenza.3
Laboratory Uncertainty
The recent attention on vitamin D levels has brought to light challenges in determining both optimum supplementation levels and ideal levels of 25(OH)D in the blood.
Traditionally, levels as low as 8 ng/mL were accepted as the minimum recommended level, but that lower level may be as high as 32 ng/mL, with 50-80 ng/mL considered optimal. Dr. Hollis called 50-70 ng/mL optimal, but said individuals won't get anywhere near that just taking the lowest official recommendation of 200 IU/d.
To reach those optimal levels in the blood, Dr. Hollis said, an infant would need to be receiving around 400-700 IU/d with that number increasing into the several thousands the more body mass a person has.
These levels, he clarified, would allow a person to attain the maximum benefits from vitamin D-musculoskeletal health, cardiovascular benefits, stronger immune system and overall health benefits.
However, when setting the recommended intake, organizations look only at the amount needed to protect against bone health; they are not considered the other benefits of the nutrient.
This is unfortunate, Dr. Hollis noted, because there have been no adverse effects found with increased vitamin D supplementation and the epidemiological and observational data suggest only positive results.
Vitamin D and Fetal Health
Vitamin D has long been considered a critical nutrient for pregnant women due to its importance in proper skeletal formation, but it is now known to play an even more important role in nurturing a healthy fetus.
The current recommended amount is 200 IU/d, but if a pregnant woman receives only that amount, she and the fetus will both be deficient compared to the desired 32 ng/ML circulating 25(OH)D level.4
The correct amount is probably closer to 2,000-4,000 IU/d for a pregnant woman, and even more for a lactating woman (precise amounts vary based on skin color, sunlight exposure, sunscreen use, latitude, etc.).
In fact, three recent studies in which Dr. Hollis was involved showed pregnant women who were supplemented with higher levels of vitamin D had less incidence of bacterial infections, less pre-term labor and less complications of pregnancy (pre-eclampsia, diabetes and hypertension).
"The best outcomes were from the group that took 4,000 IU/d, and we saw not a single adverse event due to vitamin D intake," Dr. Hollis explained.
A Critical Role
Because of the plethora of conditions associated with vitamin D deficiency and the uncertainty over optimal 25(OH)D levels, the clinical lab must be aware of the value of vitamin D testing far beyond its traditional uses in assessing bone health and calcium absorption.
Kelly J. Graham is associate editor at ADVANCE.
References
1. Vitamin D. Lab Tests Online. Accessed at: www.labtestsonline.org. Last accessed July 15, 2010.
2. Blocki F. Vitamin D deficiency. ADVANCE for Administrators of the Laboratory 2009;18(2):36-41.
3. Urashima M, et al. Randomized trial of vitamin D supplementation to prevent seasonal influenza A in schoolchildren. Am J Clin Nutr 2010;91:1255-1260.
4. Hollis BW. Circulating 25(OH)D levels indicative of vitamin D sufficiency: Implications for establishing a new effective dietary intake recommendation for vitamin D. J Nutr 2005;135:317-322.
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