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> Yet there are many studies that show healthy individuals with serum levels < 10 ng/mL, and they do not seem to suffer the bone abnormalities expected. The pr

> Yet there are many studies that show healthy individuals with serum levels < 10 ng/mL, and they do not seem to suffer the bone abnormalities expected. The problem is that any apparently healthy individual may still develop a chronic disease decades down the line. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5440113/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5440113/ > There's been a great deal of debate on safe Vit D levels, and the consensus (such as it is) is that a serum level of 30 ng/mL is likely optimal. If you look at dark-skinned hunter-gatherer tribes which are living in a way closer to our common ancestors, the "natural" Vitamin-D levels in their relatively sunny environment is more like 40 to 50. The body seems regulate Vitamin-D production up that level, so that's probably closer to optimal than 30.

valarauko 6y ago
>The problem is that any apparently healthy individual may still develop a chronic disease decades down the line. Sure. My impression is that sub 10 ng/mL levels warrant supplementation. However, I have also seen studies that included wrist X-rays of subjects to determine bone loss, and most subjects were sub-20 ng/mL with acceptable bone densities. This was a study in Indians, and another study in rural healthy Indians showed most were in the sub-20 ng/mL range, coupled with low dietary calcium intake, and no ill effect. While it's true that they may develop problems decades down the line, a longitudinal study like this demonstrates that Vit D related deficiency diseases are actually quite rare, and at levels far lower than would be expected from the serum levels alone. There's clearly more going on. https://pubmed.ncbi.nlm.nih.gov/17413106/ https://pubmed.ncbi.nlm.nih.gov/17413106/ On the Hunter-Gatherer levels, I'm guessing you're referring to the Masaai and Hadzabe study. However, is this the optimal vitamin D level? https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6180659/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6180659/ This study from healthy black blood donors in Nairobi found much lower levels (95% CI 12.73–22.07), and these people had significant sun exposure as well. Rather importantly, they note that while parathyroid hormone levels are inversely proportional to Vit D serum levels, they start to go up with high levels of Vit D. Individuals with 50 ng/mL vit D had PTH levels similar to people with a Vit D serum level of 15 ng/mL. PTH causes calcium levels in the blood to go up, drawing them out from skeletal reserves. The health implications of high Vitamin D supplementation are linked to the inappropriate deposition of calcium. Keeping PTH levels low is likely beneficial. The Nairobi study found PTH levels were lowest in people with vit D levels around 30 ng/mL.
- gridlockd 6y ago
  > Rather importantly, they note that while parathyroid hormone levels are inversely proportional to Vit D serum levels, they start to go up with high levels of Vit D. ...in that particular polynomial fit. > Keeping PTH levels low is likely beneficial. The Nairobi study found PTH levels were lowest in people with vit D levels around 30 ng/mL. The minimum of the polynomial fit is around 35. If you look at the scatter plot, there are only six samples near 50 ng/ml and they're all over the place. You can not draw your conclusion from that. There's no significant deviation between 40-50 ng/ml. My question is, why would the body stop producing Vitamin D around 40-50 ng/ml if 30 was optimal? Why not stop earlier? > Keeping PTH levels low is likely beneficial. Not sure where you get that.
  - valarauko 6y ago
    To me, I am less convinced that the elevated levels in the Masaai represent an ideal. Do all hunter gatherers have such high levels? Unclear. Perhaps the Masaai have such high levels as a quirk of their genetics, and their particular lifestyle. Does that necessarily translate into an ideal level for all humans? Possible, but there just isn't enough data. On the other hand, there are many studies across populations that find levels plateauing around 20 ng/mL for healthy rural cohorts, with no negative outcomes. Why does the body stop producing Vitamin D around 50 ng/mL, if it wasn't the ideal? Vitamin D toxicity only kicks in at extremely high levels, several orders of magnitude higher than are naturally produced. So why would nature even bother to set an upper limit at 50 ng/mL? It doesn't, though. Vitamin D3 is produced by a reversible photosynthetic reaction, and is constantly being degraded as well under sun exposure. 50 ng/mL possibly represents the upper limit at the speed with which D3 can be transported away from the dermis, and the limits of natural exposure levels. My feeling is that rather than an evolutionarily fine tuned level, this is a "good enough" local maxima as an upper limit for D3 production under natural conditions. If the Masaai were somehow exposed to 20 hours of full sun, their levels might very well be much higher. As a thought experiment, if humans were exposed to 20 hours of sunlight, would we evolve fewer keratinocytes to keep vitamin D levels at the 50 ng/mL level? Or perhaps evolve less efficient enzymes to produce lower levels of the precursor? My impression is that there isn't a strong enough disadvantage to higher levels of Vitamin D for evolution to push in that direction. So rather than an ideal level, 50 ng/mL might simply represent the upper limit of what humans can produce under natural conditions.

valarauko 6y ago

>The problem is that any apparently healthy individual may still develop a chronic disease decades down the line. Sure. My impression is that sub 10 ng/mL levels warrant supplementation. However, I have also seen studies that included wrist X-rays of subjects to determine bone loss, and most subjects were sub-20 ng/mL with acceptable bone densities. This was a study in Indians, and another study in rural healthy Indians showed most were in the sub-20 ng/mL range, coupled with low dietary calcium intake, and no ill effect. While it's true that they may develop problems decades down the line, a longitudinal study like this demonstrates that Vit D related deficiency diseases are actually quite rare, and at levels far lower than would be expected from the serum levels alone. There's clearly more going on. https://pubmed.ncbi.nlm.nih.gov/17413106/ https://pubmed.ncbi.nlm.nih.gov/17413106/ On the Hunter-Gatherer levels, I'm guessing you're referring to the Masaai and Hadzabe study. However, is this the optimal vitamin D level? https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6180659/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6180659/ This study from healthy black blood donors in Nairobi found much lower levels (95% CI 12.73–22.07), and these people had significant sun exposure as well. Rather importantly, they note that while parathyroid hormone levels are inversely proportional to Vit D serum levels, they start to go up with high levels of Vit D. Individuals with 50 ng/mL vit D had PTH levels similar to people with a Vit D serum level of 15 ng/mL. PTH causes calcium levels in the blood to go up, drawing them out from skeletal reserves. The health implications of high Vitamin D supplementation are linked to the inappropriate deposition of calcium. Keeping PTH levels low is likely beneficial. The Nairobi study found PTH levels were lowest in people with vit D levels around 30 ng/mL.

gridlockd 6y ago
> Rather importantly, they note that while parathyroid hormone levels are inversely proportional to Vit D serum levels, they start to go up with high levels of Vit D. ...in that particular polynomial fit. > Keeping PTH levels low is likely beneficial. The Nairobi study found PTH levels were lowest in people with vit D levels around 30 ng/mL. The minimum of the polynomial fit is around 35. If you look at the scatter plot, there are only six samples near 50 ng/ml and they're all over the place. You can not draw your conclusion from that. There's no significant deviation between 40-50 ng/ml. My question is, why would the body stop producing Vitamin D around 40-50 ng/ml if 30 was optimal? Why not stop earlier? > Keeping PTH levels low is likely beneficial. Not sure where you get that.
- valarauko 6y ago
  To me, I am less convinced that the elevated levels in the Masaai represent an ideal. Do all hunter gatherers have such high levels? Unclear. Perhaps the Masaai have such high levels as a quirk of their genetics, and their particular lifestyle. Does that necessarily translate into an ideal level for all humans? Possible, but there just isn't enough data. On the other hand, there are many studies across populations that find levels plateauing around 20 ng/mL for healthy rural cohorts, with no negative outcomes. Why does the body stop producing Vitamin D around 50 ng/mL, if it wasn't the ideal? Vitamin D toxicity only kicks in at extremely high levels, several orders of magnitude higher than are naturally produced. So why would nature even bother to set an upper limit at 50 ng/mL? It doesn't, though. Vitamin D3 is produced by a reversible photosynthetic reaction, and is constantly being degraded as well under sun exposure. 50 ng/mL possibly represents the upper limit at the speed with which D3 can be transported away from the dermis, and the limits of natural exposure levels. My feeling is that rather than an evolutionarily fine tuned level, this is a "good enough" local maxima as an upper limit for D3 production under natural conditions. If the Masaai were somehow exposed to 20 hours of full sun, their levels might very well be much higher. As a thought experiment, if humans were exposed to 20 hours of sunlight, would we evolve fewer keratinocytes to keep vitamin D levels at the 50 ng/mL level? Or perhaps evolve less efficient enzymes to produce lower levels of the precursor? My impression is that there isn't a strong enough disadvantage to higher levels of Vitamin D for evolution to push in that direction. So rather than an ideal level, 50 ng/mL might simply represent the upper limit of what humans can produce under natural conditions.