Thursday, December 13, 2012

Cholesterol and Sunlight

If you do not like serious fitness-health geekiness, then won't you please look away now, madame or sir.

Humans make Vitamin D in our bodies when UV radiation (sunlight) strikes 7-dehydrocholesterol (7DHC) molecules in the skin. These same molecules are used as precursors in cholesterol synthesis. One day while running in sunny San Diego I thought about this and wondered what the relationship was between cholesterol and vitamin D. And of course the whole reason we care about cholesterol is because high cholesterol causes heart attacks. (It's rare in biomedicine to be able to make such an unequivocal statement as that, but it's very well-supported.) So how might this work?

Possibility 1: if you have a lot of cholesterol does this mean you have a lot of precursor available and therefore will also have a lot of vitamin D? And does this mean that by taking a statin, you'll lower your vitamin D production? My excuse for geeking out about this is my own high cholesterol. Half of your blogger's LDL receptors have a glutamine instead of an arginine at the 3500th amino acid residue. (Thanks Mom!) Hence without pharmacologic intervention, my LDL runs about 160. So did I save myself from premature coronary syndrome more by moving to California and getting lots of sun during my runs, than by taking that statin?

Possibility 2: Can a blockade of one or the other pathway result in diversion of more precursor to the other pathway?  By that argument, (a.) people congenitally unable to synthesize cholesterol would have loads of vitamin D from all the piled-up 7DHC, assuming they get enough sun and that the reaction does have some kind of ceiling.
OR (b) the opposite - do people who don't get much sunlight have loads of cholesterol from all the piled-up 7DHC not getting turned into vitamin D?

For Possibility 2a above, it turns out there are people missing the enzyme to make cholesterol (7DCHR); the disease is called Smith-Lemli-Opitz Syndrome (SLOS), and people born with it have significant deformities and health problems. Most interesting for our purposes is that although they DO have piles of 7DHC sitting around (because they can't make cholesterol out of it), they do NOT have more vitamin D or D precursors than other people. The research team even matched patients for season of collection (to make sure we didn't get all winter samples from SLOS patients, and sunny summer samples from healthy controls.) We don't yet understand how they can avoid poisoning themselves with vitamin D, but somehow they're compensating.

Which brings us to Possibility 2b. In 1996 a British group looked at the relationship between sunlight exposure and cardiovascular disease. These plots show what they found.  (Click on them if they're hard to see, especially the first one with the countries, which is kind of cool.)

Note that they included a cholesterol plot but a) this paper doesn't investigate the direct relationship between vitamin D and cholesterol and b) consequently they can't show vitamin D to be in the causal pathway, despite the interesting figures. The relationship with sunlight exposure they show is definitely interesting but we already know that physical activity, diet, and genetic differences all definitely play an enormous, hence confouding role. It's tough to compare Japanese with Swedes and say that sunlight is a causative factor in cardiovascular differences, rather than diet, which as you might recognize all differ substantially!

Furthermore, the SLOS patients are able to "rebalance their accounts" with respect to precursor utilization, so it's not unreasonable to expect that a similar mechanism could be operating the other way in health, erasing any benefits that cholesterol-precursor-eating sun may have. (For a different opinion, you can read That Paleo Guy's take on this, which is where I originally found this paper. I do not endorse most of his opinions, so if you want a hint on how to weight our conflicting arguments, consider that I'm the one in medical school. Just sayin.)

My conclusion is that this is interesting and I'll certainly be reading any articles that come out on this, but for now we just don't have evidence that sun exposure lowers cholesterol and therefore coronary syndrome risk. And if your output in thinking about sun exposure is all-cause mortality, then even with a putative cardiovascular benefit, we're going to be looking at a U-shaped curve because there are other considerations, chiefly among them skin cancer of course. So if you're concerned about your cholesterol, exercise regularly and take a statin if recommended by your physician.  In the meantime, I'll be running in the sun because it makes me happy.

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