REVIEWVitamin D Insufficiency
Section snippets
VITAMIN D METABOLISM
The terminology related to the biochemistry of vitamin D can be confusing. Vitamin D has 2 forms and several metabolites. The 2 forms are vitamin D2 and vitamin D3, also called ergocalciferol and cholecalciferol, respectively. Vitamin D3 is produced in the skin in response to ultraviolet B radiation from sunlight or can be obtained from the diet (ie, animal sources such as deep sea fatty fish, egg yolks, or liver) or from supplements. Few foods naturally have substantial vitamin D content, and
ASSESSING VITAMIN D STATUS
Determination of vitamin D status is not based on measurement of serum 1,25(OH)2D concentrations. Vitamin D status is assessed by measuring the prohormone 25(OH) D, which is an indicator of supply rather than function. The most stable and plentiful metabolite of vitamin D in human serum, 25(OH)D has a half-life of about 3 weeks, making it the most suitable indicator of vitamin D status. In the past, vitamin D deficiency was identified by the presence of bone disease, either rickets or
SOURCES OF VARIATION IN VITAMIN D STATUS
Factors known to influence 25(OH)D levels include race, vitamin D intake, sun exposure, adiposity, age, and physical activity. Even when all the factors known to influence 25(OH)D concentrations are taken into account, most of the individual variation of 25(OH)D values is difficult to explain. Consequently, it is difficult to assess the risk of clinical or biochemical consequences of vitamin D insufficiency in a patient on the basis of concentrations of 25(OH) D alone. The duration of vitamin D
MEASUREMENT OF 25(OH)D LEVELS
Some controversy exists regarding the best method for measuring 25(OH)D levels. Radioimmunoassay has been the most common method reported in the literature and was the method used in some of the large-scale population studies of vitamin D, such as the National Health and Nutrition Examination Survey (NHANES) and the Women's Health Initiative (WHI).
The accuracy of measurement varies widely between individual laboratories and between different assay methods. In one study, identical serum samples
Nutritional Rickets
The classical manifestation of vitamin D deficiency is nutritional rickets, which results from inadequate mineralization of growing bone. Consequently, rickets is a disease of children. Far from being eradicated, nutritional rickets continues to occur throughout the world, with reports from at least 60 countries in the past 20 years.29 In a review of published cases of rickets in the United States, most occurred in children younger than 30 months.30 The vast majority of cases in the United
POTENTIAL BENEFITS OF VITAMIN D
Apart from the deficiency diseases of rickets and osteomalacia, recent evidence suggests other skeletal and nonskeletal benefits of vitamin D. In evaluating the evidence, it is important to recognize the limitations inherent in the study design and methodology. Important issues that apply to vitamin D research include the following:
- (1)
Was the study design observational, which can only demonstrate associations and is subject to confounding, or was it an RCT that generally balances unmeasured
INDICATIONS FOR VITAMIN D TESTING
Measurement of serum 25(OH)D levels is indicated in select circumstances. If clinical symptoms of rickets in children or osteomalacia in adults are present, measurement of 25(OH)D levels will confirm vitamin D deficiency. Such testing would be appropriate in adults or children with bone pain, elevated serum alkaline phosphatase or PTH levels, and low serum calcium or phosphorus levels. Persons of advanced age, those with osteoporosis, or those at increased risk of falls or fractures may also
CONCLUSION
Critically evaluating the evidence regarding the purported benefit of vitamin D on a multitude of health outcomes is difficult. The bulk of current data is based on observational, epidemiological studies, which are useful for generating hypotheses but not for proving causality. It is particularly difficult to tease out the effects of confounding variables that relate both to health outcomes and to vitamin D status, such as physical activity, milk intake, and adiposity. Few of the observational
REFERENCES (93)
- et al.
Evidence that vitamin D3 increases serum 25-hydroxyvitamin D more efficiently than does vitamin D2
Am J Clin Nutr
(1998) - et al.
Vitamin D across the lifecycle: physiology and biomarkers
Am J Clin Nutr
(2008) - et al.
Early response to vitamin D2 in children with calcium deficiency rickets
J Pediatr
(2006) Functional indices of vitamin D status and ramifications of vitamin D deficiency
Am J Clin Nutr
(2004)- et al.
Serum vitamin D metabolites and intestinal calcium absorption efficiency in women
Am J Clin Nutr
(2010) - et al.
Calcium absorption in Nigerian children with rickets
Am J Clin Nutr
(2004) - et al.
Circulating vitamin D3 and 25-hydroxyvitamin D in humans: an important tool to define adequate nutritional vitamin D status
J Steroid Biochem Mol Biol
(2007) - et al.
Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol
Am J Clin Nutr
(2003) - et al.
Vitamin D intake to attain a desired serum 25-hydroxyvitamin D concentration
Am J Clin Nutr
(2008) - et al.
25-OH-vitamin D assay variation and subject management in clinical practice
Clin Biochem
(2010)
Nutritional rickets among children in the United States: review of cases reported between 1986 and 2003
Am J Clin Nutr
Noninvasive testing in the diagnosis of osteomalacia
Am J Med
Those confounded vitamins: what can we learn from the differences between observational versus randomised trial evidence?
Lancet
Vitamin D and pancreatic cancer
Ann Epidemiol
The role of vitamin D in cancer prevention and treatment
Endocrinol Metab Clin North Am
Vitamin D and multiple sclerosis
Lancet Neurol
Maternal intake of vitamin D during pregnancy and risk of recurrent wheeze in children at 3 y of age
Am J Clin Nutr
Maternal vitamin D intake during pregnancy and early childhood wheezing
Am J Clin Nutr
Vitamin D supplementation during the first year of life and risk of schizophrenia: a Finnish birth cohort study
Schizophr Res
Prevalence of severe hypovitaminosis D in patients with persistent, nonspecific musculoskeletal pain
Mayo Clin Proc
Correlation of symptoms with vitamin D deficiency and symptom response to cholecalciferol treatment: a randomized controlled trial
Endocr Pract
A new system for grading recommendations in evidence based guidelines
BMJ
Vitamin D2 is much less effective than vitamin D3 in humans
J Clin Endocrinol Metab
Vitamin D2 is as effective as vitamin D3 in maintaining circulating concentrations of 25-hydroxyvitamin D
J Clin Endocrinol Metab
The effect of vitamin D2 and vitamin D3 on intestinal calcium absorption in Nigerian children with rickets
J Clin Endocrinol Metab
The functional metabolism and molecular biology of vitamin D action
Vitamin D deficiency
N Engl J Med
Vitamin D deficiency in adults: when to test and how to treat
Mayo Clin Proc
Prevalence of vitamin D insufficiency in an adult normal population
Osteoporos Int
Relationships among vitamin D levels, parathyroid hormone, and calcium absorption in young adolescents
J Clin Endocrinol Metab
Preliminary findings: 25(OH)D levels and PTH are indicators of rapid bone accrual in pubertal children
J Am Coll Nutr
Vitamin D deficiency, insufficiency, sufficiency and intoxication: What do they mean?
Seasonal deficiency of vitamin D in children: a potential target for osteoporosis-preventing strategies?
J Bone Miner Res
Relationship between serum parathyroid hormone levels, vitamin D sufficiency, and calcium intake
JAMA
Comparison of metabolism of vitamins D(2) and D(3) in children with nutritional rickets
J Bone Miner Res
Vitamin D metabolites and calcium absorption in severe vitamin D deficiency
J Bone Miner Res
Genome-wide association study of circulating vitamin D levels
Hum Mol Genet
Assay variation confounds the diagnosis of hypovitaminosis D: a call for standardization
J Clin Endocrinol Metab
Quantitation of 25-OH-vitamin D (25OHD) using liquid tandem mass spectrometry (LC-MS-MS)
Methods Mol Biol
Nutritional rickets around the world: causes and future directions
Ann Trop Paediatr
Radiographic scoring method for the assessment of the severity of nutritional rickets
J Trop Pediatr
Nutritional rickets without vitamin D deficiency in Bangladesh
J Trop Pediatr
A comparison of calcium, vitamin D, or both for nutritional rickets in Nigerian children
N Engl J Med
Nutritional rickets with normal circulating 25-hydroxyvitamin D: a call for reexamining the role of dietary calcium intake in North American infants
J Clin Endocrinol Metab
Bone mineralization defects and vitamin D deficiency: histomorphometric analysis of iliac crest bone biopsies and circulating 25-hydroxyvitamin D in 675 patients
J Bone Miner Res
Prevention of rickets and vitamin D deficiency in infants, children, and adolescents
Pediatrics
Cited by (0)
This article is freely available on publication, because the authors have chosen the immediate access option.