Dr. Kumar’s Take:
This study is a major step forward in explaining why people with obesity often have low vitamin D levels. The researchers discovered that obesity suppresses the enzyme CYP2R1, which helps convert vitamin D into its usable form. Even more interesting: weight loss from gastric bypass surgery restored this enzyme’s expression in fat tissue. That means vitamin D deficiency in obesity isn’t just about lifestyle or sunlight—it’s rooted in real biological change. If you’re overweight and your vitamin D levels are low, it might not just be about how much sun or supplements you’re getting. Your body may be switching off the machinery that activates vitamin D.
Key Takeaways:
✔ Obesity suppresses CYP2R1, a liver enzyme that activates vitamin D, in both humans and mice
✔ Weight loss from gastric bypass surgery restores CYP2R1 levels in human fat tissue
✔ In mice, CYP2R1 suppression was seen not just in the liver, but also in kidneys, brown fat, and testes
✔ Obesity didn’t affect vitamin D binding protein, suggesting the enzyme repression is the main factor
✔ Vitamin D receptor (VDR) was also repressed in brown fat, potentially disrupting vitamin D action locally
Actionable Tip:
If you’re struggling with vitamin D deficiency and are overweight, talk with your doctor about how weight loss may improve your vitamin D metabolism—not just through supplements, but by helping your body turn on the enzymes needed to use it.
Brief Summary:
This study explored how obesity impacts vitamin D metabolism by focusing on CYP2R1, the enzyme that turns vitamin D into 25-hydroxyvitamin D (25-OH-D), the form typically measured in blood tests. In both humans and mice, obesity was found to suppress this enzyme, which could explain why people with obesity often have low vitamin D levels even with adequate intake or sun exposure. Importantly, weight loss after gastric bypass surgery reversed this effect in human fat tissue, suggesting this enzyme suppression is reversible.
Study Design:
- Human data: Adipose tissue samples were taken from 4 women before and after weight loss from gastric bypass surgery.
- Mouse model: Male and female mice were fed either a high-fat diet or normal chow for 16 weeks. Researchers measured gene expression in the liver and various other organs.
- Molecular analysis: Gene expression was measured using RT-PCR and droplet digital PCR. Protein levels were analyzed by Western blot, and vitamin D levels were measured with EIA kits.
Results:
- In humans, CYP2R1 expression increased 1.5x in subcutaneous fat after weight loss surgery.
- In mice, obesity:
- Decreased plasma 25-OH-D by ~30%
- Repressed CYP2R1 in the liver by up to 90%
- Also repressed CYP2R1 in brown fat, kidney, testis, and colon
- Did not affect expression in white adipose tissue or vitamin D binding protein (VDBP)
- VDR expression was also reduced in brown fat and reproductive organs, potentially compounding the problem.
- Fasting and glucocorticoid stimulation also suppressed CYP2R1, suggesting hormonal involvement.
Why This Matters for Vitamin D and Obesity
This study provides a biologically grounded explanation for why people with obesity often have low 25-OH-D levels. It’s not just because vitamin D gets “trapped” in fat—it’s because obesity shuts down the enzymes that activate it. This also means weight loss may restore proper vitamin D metabolism, even before adding supplements or increasing sun exposure.
Related Studies and Research
Global Prevalence of Vitamin D Deficiency: A Meta-Analysis – Contextualizes obesity-related deficiency against global data.
Obesity-Induced Repression of CYP2R1 and Vitamin D Deficiency Mechanisms – Explores how excess adiposity downregulates 25-hydroxylase activity.
Effect of Two 100 000 IU Vitamin D₃ Bolus Doses on Viral-Induced Asthma in Preschoolers – Assesses high-dose vitamin D’s clinical benefits in pediatric asthma.
Vitamin D Status Modulates Mitochondrial Oxidative Capacity in Skeletal Muscle: Implications for Sarcopenia – Investigates vitamin D’s role in muscle mitochondrial function.
Role of Vitamin D and Calcium in Type 2 Diabetes Prevention: A Systematic Review and Meta-Analysis – Reviews D + Ca supplementation on metabolic outcomes.
Frequently Asked Questions
Why do people with obesity often have low vitamin D levels?
This study suggests that obesity suppresses the enzyme (CYP2R1) that activates vitamin D, which could explain the deficiency seen in so many people with excess body fat.
Can losing weight really fix your vitamin D levels?
Yes—at least partially. In this study, weight loss from surgery increased the vitamin D–activating enzyme in fat tissue. Other studies show that weight loss often boosts circulating vitamin D.
What does CYP2R1 do?
CYP2R1 is the main liver enzyme that converts vitamin D into 25-hydroxyvitamin D, the form doctors check in your blood.
Does this mean vitamin D supplements won’t work in obesity?
Not necessarily—but it suggests you may need higher doses or might benefit more from weight loss or addressing metabolic issues that downregulate vitamin D activation.
Conclusion
Obesity appears to directly interfere with your body’s ability to activate vitamin D—not just by trapping it in fat but by switching off the enzyme CYP2R1 in the liver and other tissues. Encouragingly, weight loss seems to restore this crucial enzyme. For people with obesity and low vitamin D levels, this study suggests a deeper metabolic problem—one that weight loss may help fix.