For years, low 25 OH Vitamin D has been painted as a simple deficiency issue. The mainstream advice? Just take more Vitamin D and all will be well. But what if that’s missing the bigger picture? What if low 25 OH Vitamin D is actually a clue—a signal that something deeper is going on in the body?
The Vitamin D Puzzle: It's More Than Just a Deficiency
Emerging research suggests that intracellular pathogens, including Bartonella, Borrelia, and Rickettsia, can hijack vitamin D metabolism, throwing off the balance between its different forms. These infections trigger immune cells, particularly macrophages, to crank up the enzyme that converts 25(OH)D into its active form, 1,25(OH)₂D. The result? An apparent “deficiency” of 25 OH Vitamin D while 1,25 OH Vitamin D shoots up.
In real-world clinical cases, patients battling chronic infections often show this pattern—low 25(OH)D but elevated 1,25(OH)₂D. One study even highlighted a patient with a 25(OH)D level of 20.7 ng/mL and a 1,25(OH)₂D level of 67.9 pg/mL, pointing to ongoing intracellular infection (MDPI).
What I See in My Patients
In my practice, about 95% of patients with low 25 OH Vitamin D have normal or even elevated 1,25 OH Vitamin D—the active form that has powerful immune-modulating effects. This tells me that rather than just having a deficiency, their bodies are reacting to chronic inflammation and immune activation.
When 1,25 OH Vitamin D levels get too high, it can actually suppress immune function, making it easier for infections to take hold. The conventional approach—taking high doses of Vitamin D to “fix” the low 25 OH level—can actually backfire, worsening infections and further confusing the immune system.
What the Research Says: Vitamin D Supplementation Doesn't Fix the Problem
Multiple studies have connected low 25 OH Vitamin D with chronic diseases like multiple sclerosis (MS) and sarcoidosis. But when researchers put high-dose Vitamin D supplements to the test, the results were disappointing. Many studies showed little to no benefit in reducing inflammation or improving outcomes. This supports the idea that low 25 OH Vitamin D isn’t the problem itself—it’s a signal of immune dysfunction.
The Takeaway: Test Both Forms Before Supplementing
If you’ve been told you have low Vitamin D, don’t just assume you need to supplement. Before reaching for that high-dose Vitamin D bottle, get both 25 OH and 1,25 OH Vitamin D levels checked.
If your 1,25 OH Vitamin D is high relative to 25 OH, simply pushing up 25 OH levels can suppress immunity and make infections worse. Some people are more prone to this imbalance, and for them, monitoring and treating the root cause—the underlying infections or immune triggers—is the real solution.
The Bigger Picture: Your Vitamin D Levels Are Trying to Tell You Something
So, if your Vitamin D results don’t make sense, take a step back and ask: What is my immune system trying to tell me? Instead of just treating numbers on a lab test, look deeper into potential chronic infections, immune imbalances, and underlying inflammation.
Vitamin D is a powerful tool for the immune system—but only when it’s in balance. The real goal isn’t just to “fix” a lab value. It’s to restore immune health from the inside out.
Sources
- Elevated 1,25(OH)₂D Levels Associated with Chronic Sarcoidosis Treatment Needs: PMC Article
- High 1,25(OH)₂D Levels and Increased Hypertension Risk: AHA Journals
- 1,25-Dihydroxyvitamin D Concentrations in Granulomatous Diseases and Malignancies: Mayo Clinic Laboratories
- Severe 1,25-Dihydroxyvitamin D-Mediated Hypercalcemia in Malignancy: Journal of Clinical Endocrinology & Metabolism
- Hyperparathyroidism Mechanisms: Wikipedia
- Vitamin D Ratio and Intracellular Infections: MDPI