Dissecting high from low responders in a vitamin D3 intervention study
The Journal of Steroid Biochemistry and Molecular Biology, online 13 November 2014 https://doi.org/10.1016/j.jsbmb.2014.11.012
Noora Saksaa, 1, Antonio Nemea, 1, Jussi Ryynänena, Matti Uusitupab, Vanessa D.F. de Mellob, Sari Voutilainenb, Tarja Nurmib, Jyrki K. Virtanenb, Tomi-Pekka Tuomainenb, Carsten Carlberga,
- The genes ASAP2, CAMP, CD14, CD97, DUSP10, G0S2, IL8, LRRC8A, NINJ1, NRIP1, SLC37A2 and THBD are primary VDR targets.
- On the level of the expression of primary VDR target genes only 55–62% of the study participants were vitamin D3 responders.
- Only 12 biochemical and clinical parameters show a highly significant correlation with serum 25(OH)D3 levels.
- All 24 parameters together define a network with parathyroid hormone in the center.
- Transcriptomic and serum biomarkers allow a dissection of study subjects into high and low vitamin D3 responders.
Vitamin D3 is a pleiotropic signaling molecule that has via activation of the transcription factor vitamin D receptor (VDR) a direct effect on the expression of more than 100 genes. The aim of this study was to find transcriptomic and clinical biomarkers that are most suited to identify vitamin D3 responders within 71 pre-diabetic subjects during a 5-month intervention study (VitDmet). In hematopoietic cells, the genes ASAP2, CAMP, CD14, CD97, DUSP10, G0S2, IL8, LRRC8A, NINJ1, NRIP1, SLC37A2 and THBD are known as primary vitamin D targets. We demonstrate that each of these 12 genes carries a conserved VDR binding site within its genomic region and is expressed in human peripheral blood mononuclear cells (PBMCs).
The changes in the expression of these genes in human PBMCs at the start and the end of the vitamin D-intervention were systematically correlated with the alteration in the circulating form of vitamin D3, 25-hydroxyvitamin D3 (25(OH)D3).
Only 39–44 (55–62%) of the study subjects showed a highly significant response to vitamin D3, i.e., we considered them as “responders”.
In comparison, we found for 37–53 (52–75%) of the participants that only 12 biochemical and clinical parameters, such as concentrations of parathyroid hormone (PTH) and insulin, or computed values, such as homeostatic model assessment and insulin sensitivity index, show a correlation with serum 25(OH)D3 levels that is as high as that of the selected VDR target genes.
All 24 parameters together described the pleiotropic vitamin D response of the VitDmet study subjects. Interestingly, they demonstrated a number of additional correlations that define a network, in which PTH plays the central role.
In conclusion, vitamin D3-induced changes in human PBMCs can be described by transcriptomic and serum biomarkers and allow a segregation into high and low responders.
This article is part of a Special Issue entitled ‘17th Vitamin D Workshop’ (June 2014)
Download the PDF from SciHub via VitaminDWiki
For the same vitamin D dose, the blood level response can be >2X average or < 50% of average
- Apparently people with < average response are called “low responders”
- This study explores the genetic reasons for “low response”
- Virtually everyone (not government recommendations, however) agrees that the response is a function of weight
- About half of vitamin D researchers believe that the obese have a 2-3X lower response.
- Note: This study appears to ignore cases where the blood level was raised,
but the active form of vitamin D was not
- due to low magnesium, poor kidney, lack of Omega-3, other genes, etc.
Click on charts for details
See also VitaminDWiki
- Reasons for low response by vitamin D level in the blood 27 reasons as of Dec 2014
- How you might double your response to vitamin D - in addition to just taking more vitamin D
- Overview Vitamin D Dose-Response which has the following
Half of seniors did not get ANY response to 1600 IU of vitamin D daily for a year
RED square = reduction in serum level