We know that vitamin D controls from anywhere between 0. 5% of the human genome to up to 5%, depending on what review one reads. New genes are being discovered every day that vitamin D either upregulates or down regulates. That is, vitamin D either increases or decreases the protein that gene transcribes.
However, no one has ever done a gene microarray analysis (a way of looking at a large number of genes) of patients before and after vitamin D administration. That is, no one had ever done it until Professor Michael Holick’s lab reported such a study recently in the PLoS One journal.
Hossein-Nezhad A, Spira A, Holick MF. Influence of vitamin D status and vitamin D3 supplementation on genome wide expression of white blood cells: a randomized double-blind clinical trial. PLoS One. 2013;8(3):e58725.
Doctors Arash Hossein-Nezhad, Avrim Spira and Michael Holick conducted a small randomized controlled pilot trial of 8 patients, doing a gene microarray analysis at baseline and again after two months of either 400 or 2,000 IU per day. The 2,000 IU/day group only increased 25(OH)D by 9.8 ng/ml, while 400 IU per day increased 25(OH)D by 5.6 ng/ml, so the two groups were combined for analysis. The study was conducted in the winter.
First, they found 291 genes in white blood cells that vitamin D affected. Vitamin D affects different genes in different tissues so this is only what low dose vitamin D does in white blood cells. Of the 291 genes, 82 genes were downregulated and 209 were upregulated. They found the affected gene pathways controlled immune function, transcription regulation, cell cycle activity, epigenetic modification, DNA regulation, DNA repair, and cellular response to stress.
Forty-seven of the 291 affected genes had never been reported to be affected by vitamin D. That is, they discovered 47 new vitamin D regulated genes. Even the one person who had a relatively high baseline 25(OH)D (level not given) and who obtained a 25(OH)D of above 40 ng/ml after supplementation with 2,000 IU/day for two months had differential expression of 33 genes, suggesting there is a significant genetic difference between 25(OH)D levels of 30 ng/ml and 40 ng/ml.
The authors concluded:
“These results suggest that to maximize vitamin D’s effect on gene expression may require even higher doses than 2,000 IU of vitamin D3 daily.”
Yes, we think that at least 5,000 IU/day is required to obtain natural vitamin D levels. If a genetic expression difference exists between levels of 40 and 80 ng/ml, we will only learn it by further studies, similar to this breakthrough discovery by Michael Holick’s lab.