From the Guidelines
Genetic variants in the GC, CYP2R1, and DHCR7 genes are strongly associated with low vitamin D levels, and individuals with these variants may benefit from supplementation with vitamin D3 (cholecalciferol) to maintain optimal levels. Several genes are linked to low vitamin D levels, with the most significant being GC, CYP2R1, and DHCR7, which affect vitamin D binding, metabolism, and synthesis pathways 1. The GC gene encodes vitamin D binding protein, which transports vitamin D in the bloodstream. CYP2R1 is responsible for converting vitamin D to its active form in the liver. DHCR7 influences the availability of 7-dehydrocholesterol, the precursor molecule needed for vitamin D synthesis in the skin. People with certain variants of these genes may have lower vitamin D levels even with adequate sun exposure and dietary intake. Some key points to consider:
- Genetic testing might be informative for individuals with a family history of vitamin D deficiency or those who struggle to maintain normal levels despite supplementation.
- Supplementation with vitamin D3 (cholecalciferol) is typically recommended, with a daily dose of 1,000-2,000 IU for maintenance or higher doses if prescribed for deficiency.
- Regular blood testing to monitor levels is recommended, aiming for a 25-hydroxyvitamin D level between 30-50 ng/mL, as levels below this range have been associated with increased risk of fractures, falls, functional limitations, and other adverse clinical outcomes 1.
From the Research
Genes Linked to Low Vitamin D
- The genetic factors that influence vitamin D levels are not well understood, but studies have shown that circulating vitamin D concentrations are partially determined by genetic factors 2.
- Genetic variants, such as mutations, deletions, amplifications, and inversions, in genes involved in the metabolism, catabolism, transport, or binding of vitamin D to its receptor, may affect vitamin D levels 2.
- Epigenetic modifications, such as DNA methylation, have also been associated with vitamin D levels in several studies 2.
- However, the underlying genetic determinants of plasma 25-hydroxyvitamin D3 [25(OH)D] concentrations remain to be elucidated 2.
- There is a need for further research to understand the genetic and epigenetic factors that influence vitamin D status, as this could help to identify individuals who are at risk of vitamin D deficiency and develop targeted interventions 2.
Vitamin D Deficiency and Health Outcomes
- Vitamin D deficiency has been linked to an increased risk of osteoporosis, cardiovascular disease, and some cancers 3, 4.
- Low vitamin D levels have also been associated with increased risk of falls, fractures, and musculoskeletal decline 3, 4.
- However, the evidence for the association between vitamin D levels and some health outcomes, such as fractures, is inconsistent 4.
Diagnosis and Treatment of Vitamin D Deficiency
- Vitamin D deficiency can be diagnosed by measuring 25-hydroxyvitamin D serum concentrations 5, 3.
- Treatment of vitamin D deficiency typically involves supplementation with vitamin D, either alone or in combination with calcium 3, 4.
- However, the optimal dose and duration of vitamin D supplementation are not well established, and further research is needed to determine the most effective treatment strategies 3, 4.