Journal of Bone Mineral Research https://doi.org/10.1002/jbmr.3686
Jeffrey D Roizen Caela Long Alex Casella Lauren O'Lear Ilana Caplan Meizan Lai Issac Sasson Ravinder Singh Andrew J Makowski … See all authors
- Vitamin D insufficiency was 3.7 X more likely if CYP2R1 gene variation– June 2014
- Search VitaminDWiki for CYP2R1 895 items in VitaminDWiki as of June 2019
- CYP2R1 (vitamin D 25-hydroxylase ) semiactivates vitamin D in many places in the body
- Note: More Vitamin D activation appears to take place in skin than liver
Genetics category listing contains the following
355 articles in Vitamin D Receptor 135 articles in Vitamin D Binding Protein = GC 28 articles in CYP27B1
Vitamin D blood test misses a lot
- Snapshot of the literature by VitaminDWiki as of early 2019
- Vitamin D from coming from tissues (vs blood) was speculated to be 50% in 2014, and by 2017 was speculated to be 90%
- Note: Good results from a blood test (> 40 ng) does not mean that a good amount of Vitamin D actually gets to cells
- A Vitamin D test in cells rather than blood was feasible (2017 personal communication)
- Commercially available 2019
However test results would vary in each tissue due to multiple genes
- Good clues that Vitamin D is being restricted from getting to the cells
1) A vitamin D-related health problem runs in the family
especially if it is one of 51+ diseases related to Vitamin D Receptor
2) Slightly increasing Vitamin D show benefits (even if conventional Vitamin D test shows an increase)
3) Vitamin D Receptor test (<$30) scores are difficult to understand in 2016
easier to understand the VDR 23andMe test results analyzed by FoundMyFitness in 2018
4) Back Pain
probably want at least 2 clues before taking adding vitamin D, Omega-3, Magnesium, Resveratrol, etc
The founder of VitaminDWiki took action with clues #3&4
Overview Obesity and Vitamin D contains the following summary
- FACT: People who are obese have less vitamin D in their blood
- FACT: Obese need a higher dose of vitamin D to get to the same level of vit D
- FACT: When obese people lose weight the vitamin D level in their blood increases
- FACT: Adding Calcium, perhaps in the form of fortified milk, often reduces weight
- FACT: 140 trials for vitamin D intervention of obesity as of Sept 2019
- FACT: Less weight gain by senior women with > 30 ng of vitamin D
- FACT: Dieters lost additional 5 lbs if vitamin D supplementation got them above 32 ng - RCT
- FACT: Obese lost 3X more weight by adding $10 of Vitamin D
- FACT: Those with darker skins were more likely to be obese Sept 2014
- SUGGESTION: Probably need more than 4,000 IU to lose weight if very low on vitamin D due to
risk factors such as overweight, age, dark skin, live far from equator,shut-in, etc.
- Obesity category has
- Normal weight Obese (50 ng = 125 nanomole)
/How does a high-fat diet influence vitamin D metabolism?
"Obesity reduces the ability of the liver to convert vitamin D into calcidiol"
Normal vitamin D homeostasis is critical for optimal health; nevertheless, vitamin D deficiency is a worldwide public health problem. Vitamin D insufficiency is most commonly due to inadequate cutaneous synthesis of cholecalciferol and/or insufficient intake of vitamin D, but can also arise as a consequence of pathological states such as obesity. Serum concentrations of 25(OH)D (calcidiol) are low in obesity, and fail to increase appropriately after vitamin D supplementation.
Although sequestration of vitamin D in adipose tissues or dilution of ingested or cutaneously synthesized vitamin D in the large fat mass of obese patients has been proposed to explain these findings, here we investigate the alternative mechanism that reduced capacity to convert parent vitamin D to 25(OH)D due to decreased expression of CYP2R1, the principal hepatic vitamin D 25‐hydroxylase.
To test this hypothesis, we isolated livers from female mice of 6 to 24 weeks of age, weaned onto either a normal chow diet or a high‐fat diet, and determined the abundance of Cyp2r1 mRNA using digital droplet‐quantitative PCR. We observed a significant (p < 0.001) decrease in Cyp2r1 mRNA in the liver of high‐fat diet–fed mice relative to lean‐chow–fed female mice. Moreover, there was a significant (p < 0.01) relationship between levels of Cyp2r1 mRNA and serum 25(OH)D concentrations as well as between Cyp2R1 mRNA and the ratio of circulating 25(OH)D3 to cholecalciferol (p < 0.0001).
Using linear regression we determined a curve with 25(OH)D3/cholecalciferol versus normalized Cyp2R1 mRNA abundance with an R2 value of 0.85. Finally, we performed ex vivo activity assays of isolated livers and found that obese mice generated significantly less 25(OH)D3 than lean mice (p < 0.05). Our findings indicate that expression of CYP2R1 is reduced in obesity and accounts in part for the decreased circulating 25(OH)D.