Monday 8 August 2016

Vitamin D kills

. . . bacteria.
As an institutionalised person, I like a regular schedule. Sundays with Pat the Salt my aged father-in-law; Summer Thursdays up to Dublin for the Comparative Immunology Lab Meeting in TCD. When I went up last week, I found that a) the Lab Meeting was cancelled; so I was mildly pissed off but b) there were two talks from visiting speakers which I was delight to catch.  If I'd known the lab meeting was cancelled, I would have missed the talks.

The second talk was given by Gill Diamond [hard G in the Gill, he's a bloke] long-time from Rutgers NJ and more recently at U Florida, Gainesville. He was talking about the importance of vitamin D in maintaining oral hygiene. WFT? Isn't vitamin D the one that stops you getting rickets? What they add to milk and Oatly and margarine? Which you don't need if you get enough sunshine? Its fancy name is calciferol to indicate its primary role in calcium metabolism. Now here's a funny thing: in New England and Northern Europe you have to worry about rickets and vitamin D deficiency during the long dark blizzardy Winter. In Florida it can be a problem in the high Summer when only mad dogs go out in the midday sun. Sensible people dash from the air-con homes to their air-con cars to drive to the air-con mall or air-con office; by avoiding the sun to stave off the melanoma they can fail to make enough vitD.

What's vitamin D doing controlling bad bacteria in your mouth? That question can best be answered with another: What is vitamin D? It's complicated! Vitamin D3 cholecalciferol is typically made from cholesterol in the skin by the action of UVB radiation from direct sunlight. If you eat salmon and a few other foods, you can get enough D3 in the diet but the incidence of rickets shows that it is not that easy to get enough from what you eat. Hence the active supplementation of certain food mandated by many governments. D3 is marvellously stable: it has a sell-by date of two+ years on the shelves in your pharmacy. But stable = inactive and it must first be converted into calcidiol in the liver and then further modified by enzymes in the kidney to calcitriol the active form. That's what the text-books say aNNyway. It is a super example of homeostatic checks and balances that no matter how much you crank up the dietary vitamin D [or lie about in the sun], the amount of circulating calcitriol barely fluctuates. That's what human physiology and 100 million years of evolution can achieve - balance. Medical interventions to tilt the balance when it is out of kilter are galumphingly crude, as we saw with meds for hemophilia and diabetes. The thing with vitamin D [and vitamin C!] is that you want enough but over-egging the pudding is just a waste. You can't really over-dose on it either because the liver & kidney enzymes only process a little and the inert rest just circulates until you pee it out.

Another important aspect to keep in mind is that the bendy bones of rickets reflects the structural function of calcium as the bony matrix of calcium phosphate. But calcium balance is also vital for the activity of muscles and nerves and the bones serve as a reservoir of calcium which is eked out into the circulation under the competing demands of two other homeostatic hormones. These functions are privileged over mere engineering, so calcium gets sucked out of the bones if it is in short supply.

That's the bible story on vitamin D: cholesterol - skin - UVB - liver - kidney - bone calcium.

In one of those stories that shows the science lives in the world of Serendip, it came to Prof Diamond's attention that, in the DNA sequence upstream from one of the genes than make anti-microbial peptides AMP, there was a signal that looked like a VDRE - vitamin D response element. That was really peculiar because nobody had suggested this AMP had a role in calcium metabolism. His team speculated that the gene might be under the control of vitamin D. Some delicate biochemical tricking around indicated that the enzymes that process stolid D3 into its working-but-transitory form were present in the gum epithelium. That turned what everyone knew to be true [calcitriol=kidney] on its head.

So we produce AMPs, in particular one called LL-37 aka cathelicidin, in the epithelium surrounding our teeth and these help manage the soup of bacteria that bathe the gingival crevice [see R marked 3]. LL-37 kills some [(presumably the bad guys) but not all microbes. As I get older (it's all ahead of you, young readers), my gums are receding from the frontier between the enamelled cap of my teeth and the root. This exposes the unprotected root [R the grey area marked as 2+3] and allows bad bacteria to adhere and start to eat. Getting old is a series of breakdowns in the dozens and hundreds of homeostatic mechanisms that maintain things in healthy equilibrium. The over-the-counter 'medical' intervention for oral hygiene is to swill out your gob with Listerine to 'kill them bacteria' and make everything fresh for snogging. Not that old people get a whole lot of snogging - YMMV. This is about as sensible as "Caedite eos. Novit enim Dominus qui sunt eius" killing ALL the citizens of a sacked medieval town, so that there was nobody to make bread or bury the bodies the next morning. Let's work on the hypothesis that the AMP cathelicidin is polished by evolution to kill some bacteria (the baddies) in the crevice to help out the benign commensals. Maybe tooth loss in the elderly is caused by a falling off of the production of cathelicidin as yet another homeostatic system gets wobbly. Maybe we can boost it by upping the stimulation of the VDRE with topical vitD? It's so damned elegant as an idea, it should l be easy to pull down some venture capital to monetise it. The thing about working in Florida is that its where rich old white folks go in retirement. They all have receding gums and horrendous dental bills, crowdfunding a few retirement villages on the coast should quickly raise the necessary millions.

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