Vitamin D paradox
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Vitamin D paradox
Taking HD vitamin D3 but still low blood measures!
This paradox is due to a drawback, a defensive mechanism, not to malabsorption issues, interference from medications, insufficient sun exposure, or the liver and kidneys' inability to convert vitamin D to its active form. At least, most of the time.
Highlights
Taking HD vitamin D3 can be counterproductive if on a usual way
The vitamin D receptor is then downregulated
Calcitriol plays a role in plasma calcium regulation in concert with PTH
Metabolites of excess vitamin D3 enhance protective reactions. Too much of a good thing is bad.
This downregulation prevents excessive and prolonged activation of the VDR pathway.
I'm taking 5,000 IU of vitamin D3, but I'm hitting a plateau. Why?
Vitamin D and thermoregulation
Preamble
We’re not talking here about a punctual HD supplement when suffering from a viral or bacterial attack. Not even when results of your last blood test is under 30 ng/mL D3.
But you could have been taking HD vitamin D3 (5 000 UI) on several months, without reaching your target. I target 45 ng/mL.
You don't understand why you're stuck in a rut. Yet you think you're doing pretty much what you could to supply: magnesium and vitamin D3 supplements. Fruits and vegetables in good proportions, although a little tight (10 portions and 30g of fiber targeted). 20 to 30 minutes of exercise or walking 4x/week. A relaxation technique. In short, you're wondering why you're lacking energy and drive a little too often!
How can I be low in vitamin D3 when I take high doses?
This is actually a relatively common scenario – where a person is taking a lot of vitamin D3 but without getting the expected benefits read in most studies, but suffering from either weak thermoregulation, hair loss or poor energy metabolism. Of course, it’s not due to a one-side problem (additional contributors: combination of various factors, which add up).
Part of the explication: Vit D leaves metabolites
How does HD vitamin D3 leave metabolites?
The vitamin D receptor is downregulated by the high exogenous vitamin D. So, in short, too much of a good thing is bad. The VDR receptor is downregulated. What does it imply?
Research suggests that 25% of people are low responders to vitamin D supplementation, which occurs independently of vitamin D levels in serum. Low VDR function means serum vitamin D can remain high while vitamin D function is actually low.
When does calcitriol leave excess metabolites?
Why do metabolites from excess D3 induce a downregulation of The VDR receptors?
Excess vitamin D metabolites lead to VDR downregulation as a negative feedback mechanism to prevent excessive VDR activation and potential toxicity, including the downregulation of genes involved in vitamin D metabolism. (*) This could be seen as a reno-protective property of the vitamin D-VDR signaling. Why this is Important?
Preventing Toxicity & Maintaining Homeostasis
This downregulation prevents excessive and prolonged activation of the VDR pathway, which could lead to vitamin D counter-effects (excessive).
This feedback mechanism ensures that vitamin D signaling remains within a balanced range, preventing harmful effects and maintaining overall physiological homeostasis. At least it should be act on this way, if you do not overburden the metabolism with a continuous extra take (supplementing with HD Vit D3).
Warning
Don’t question ChatGPT or you’ll get an inappropriate answer. Temperature influences conversion rate, not detection. This is a chemical property rather than a physiological "heat sensor" mechanism. If you still want to search, use the words: ‘the metabolites’ of vitamin D and VDR. Good luck anyway
Sources and References
0. Initial post:
https://mirzoune-ciboulette.forumactif.org/t2131-english-corner-vitamin-d-paradox#30341- 3 forms of D3 (simplified approach)
- Figure 1: Pathway of vitamin D formation
- Figure 2: Steps in vitamin D metabolism involving CYP450 enzymes
- Low VDR function or overburden nuclear receptors (RXR). VDR and Transcriptional Regulation.
- Excess vitamin D metabolites lead to VDR downregulation as a negative protective feedback
- How to manage.
*) Excess vitamin D metabolites lead to VDR downregulation as a negative feedback mechanism to prevent excessive VDR activation and potential toxicity, including the downregulation of genes involved in vitamin D metabolism, such as the enzyme that produces calcitriol (the active form of vitamin D) and the induction of the enzyme that breaks it down. High levels of calcitriol bind to the VDR, leading to changes in VDR gene and protein expression, which ultimately reduces the number of receptors available to bind to the active form of vitamin D.
https://doi.org/10.1210/jc.2016-1516 JCEM
*) Here Travis discussed how vitamin D lowers heat production, lowers uncoupling protein (maybe as it’s a signal you are getting heavy sun exposure)
https://raypeatforum.com/community/threads/is-vitamin-d-supplementation-even-neccessary.23844/post-341522
*) Vitamin D and thermoregulation
Induction of uncoupling protein (UCP) & link with vitamin D3.
Energy Metabolism and uncoupling proteins (UCPs)
*) Importance of magnesium ratio to enhance vitamin D absorption
Magnesium status and supplementation influence vitamin D status and metabolism: results from a randomized trial
=> When baseline storage D3 are >30 ng/mL, vitamin D–deactivating enzyme CYP3A4 starts to elevate and the activity is further enhanced by magnesium supplementation. Not under this threshold. -
@LucH What vitamin d do you take Luc?
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@heyman said in Vitamin D paradox:
What vitamin d do you take Luc?
I take Now Foods softgels.
I was taking 5 000 IU during 6 months (latitude 50° N). Not from mi-April till mid- October, when the sun is high in the sky.
The sun's wavelength is good when your shadow does not exceed your height (+/ 1m65 - 1.85 m for most people) (+/ 6 feet).
Mine comes from iherb.com. 2 kinds of softgels. I always take 1 drop K2 MK4 (1 000 mcg) at breakfast. But you need 15 - 25 - 33 g fat to optimize the assimilation of K2.
Once a week I took 10 000 IU retinyl palmitate. But I should have take 2 x 5000 UI. Best bioavailability .
Now, I'm going to take Vit D differently, since I read Travis' post.1° virus: special period: 5 000 UI vit D. 10 000 UI the first 2 days.
2° winter time: 2 000 UI vit D if > 35 ng/ML. More if under the target. Mind magnesium (420 mg) with HD Vit d.
3° summer time: No need if I go out 20-30', otherwise 1 000 every 2 days.
NB: I'm 72 years old. So the assimilation is rather bad.
I take Now Foods.Edit: My info sources come from RP, CM and Travis. Otherwise you make a nervous breakdown if you try to compare different sources. Do not use ChatGPT (errors); or only if you want to summarize a doc.
Note I still need to cross the information and to adapt it to my feeling. I don't always match with the read sources. In a interview, it not the ideal place to inform ... Just a way to search deeper if you have time and energy) -
Useful info on magnesium:
High-Dose Vitamin D Depletes Magnesium – Carolyn DEAN, MD ND.
https://mirzoune-ciboulette.forumactif.org/t2130-dynamique-entre-vitamine-d-magnesium-et-calcium#30339Excerpt 1:
Magnesium expert Andrea Rosanoff, Ph.D., is one of the few people who understands the dynamic between vitamin D, magnesium, and calcium. She makes it the subject of her 2016 article, “Essential Nutrient Interactions: Does Low or Suboptimal Magnesium Status Interact with Vitamin D and/or Calcium Status?”Excerpt 2:
Magnesium is required for many steps in vitamin D metabolism, including its conversion from its storage form (which is also the supplement form) to its active form. This means that taking extremely high doses of vitamin D can lead to magnesium deficiency without anyone realizing it.
