The evidence is convergent. Multiple independent sources reach the same conclusion, the underlying mechanism is well-characterized, and even the field's most cautious voices treat it as worth doing.
So these Mendelian randomization studies have found that people that can't convert into the precursor, the 25-hydroxy vitamin D, which is usually what's measured. It's the most stable form of vitamin D in the body. They have a higher all-cause mortality, if they can't do it. So people that don't have it have a lower all-cause mortality. They have a higher respiratory-related mortality. They have a higher cancer-related mortality.
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So, you're not looking at vitamin D levels at all. You're looking at just the snips and you know if they have it they have low vitamin D. People randomly have these genes and it's not like there's no health status. So um these these mandelium randomization studies have found that people that can't convert um into the the precursor the 25 hydroxy vitamin D which is usually what's measured. It's the most stable form of vitamin D in the body. Um they have a higher all-c cause mortality if they can't do it. So people with you know that don't have it have a lower all-c cause mortality. They have a higher respiratory related mortality. They have a higher cancer related mortality. They also are more likely to get multiple scerosis. This has all been done with mandelian randomization.
This was a Mendelian Randomization study - which helps establish causation because people with genetic SNPs that result in low vitamin D had a higher risk of premature death.
Other studies have also found that low vitamin D from serum and genes is linked to higher death rates from respiratory diseases.
This is THE biggest argument against reverse causation being the cause of vitamin D deficiency associations with mortality from respiratory infections.
Mendelian randomization studies have found that genetically low vitamin D levels are associated with higher mortality from respiratory infections.
And these people have a much higher mortality from respiratory tract infections. They have a higher all-cause mortality, they have a higher cancer mortality. Cardiovascular-related mortalities is unchanged. But respiratory tract infections are much higher.
So these Mendelian randomization studies have found that people with genetically low vitamin D levels, you know, have a higher all cause mortality. They're like, you know, 25, they've got like a 25% higher mortality from respiratory disease.
and so melan randomization takes these genes this these single nucleotide polymorphisms in these genes and says okay we're going to randomize them people that have these genes that we know make them basically have lower levels of 25 hydroxy vitamin D and see what they're you know correlate that to health outcomes like all cause mortality so it's kind of in a way a way of randomizing people and people that have genetically low vitamin D levels independent of what their lifestyle is they have a much higher all cause mortality they have a higher cancer related mortality and they have a higher respiratory disease mortality um with very little or no effect on cardiovascular mortality
So in this case we have genes that convert vitamin D3 into the active steroid hormone. And so we can look at people there are people that actually have single nucleotide polymorphisms in in those genes where they're not working as effectively. And therefore people are actually they have lower levels of either the stable circulating form of vitamin D which is 25 hydroxy vitamin D or the active steroid hormone which is 125 hydroxy vitamin D. And we know that people with those genes, they're they have genetically low levels of vitamin D. They have a higher all-c cause mortality than people that don't have those genes. They they also have a higher respiratory related mortality and they have a higher cancer related mortality.