Lipoprotein(a) and ascorbate

OK, ascorbate and Lp(a).

There are some posts which are quite hard to write. I really like the "Lp(a) is a surrogate for ascorbate" hypothesis. It's neat and elegant, so the more information I read which undermines it, the more depressing I find it.

We humans are members of the sub order haplorrini of the order primates. Haplorrhini, that is humans and apes, Old World Monkeys and New World monkeys, have all lost function of that gene for the last enzyme in the formation of ascorbate from glucose.

Of course the crucial species are the tarsiers.

Tarsiers are quite interesting as they have been batted back and forth from the haplorrhini, ie us lot, to the prosimians, ie the rest of the primates. It's a very very close call genetically as to whether tarsiers are haplorrini or not.

There is one isolated report that tarsiers cannot make vitamin C. This should put them firmly in to the haplorrini but geneticists still argue the exact grouping.

It matters because the loss of ascorbate synthesis appears to have occurred in haplorrhini very soon after the split between our sub order and the rest of the primates.

Now, there is this concept that humans lost the ability to synthesise ascobate because a common ancestor to all of us haplorrini sat around all day eating melons and nectarines. Of course it's quite hard to say exactly what the ancestor of the tarsiers actually ate, but it's quite simple to say what current tarsiers eat. They eat insects, lizards and small snakes. I've seen at least one textbook entry which suggest that tarsiers are about as close to anything resembling the common ancestor of we haplorrhini as anything alive today.


Perhaps tarsiers use Lp(a) as an ascorbate replacement? No one has checked this, but what they have checked is whether the New World monkeys make Lp(a). They don't. Or, if they do, it is unrecognisable using human Lp(a) sensing antibodies. If tarsiers can make an Lp(a) like substance it puts them firmly down with the Old World monkeys and apes. They're certainly not an Old World monkey or an ape.

To summarise: Only Old World monkeys and apes make recognisable Lp(a). All haplorrhini have lost ascorbate. The haplorrhini are probably derived from an ascorbate-less near carnivore. New World monkeys are doing fine without Lp(a) or ascorbate. Modern tarsiers are doing fine as pure carnivores without ascorbate....

Of course the guinea pig is a fascinating little beast too. As far as I am aware, it does not make Lp(a) (Pauling and Rath appear to have made a mistake here), it doesn't make ascorbate and it doesn't eat much fruit either. OK, guinea pigs never ever, ever eat fruit in the wild. They live in the high Andes where the year round fruit availability is probably as good as it is in Antarctica.

They eat grass. And guinea pig pooh. That puts ascorbate intake down at very low, but not zero, levels. Like rabbits, they actually live primarily on volatiile fatty acids produced by hind gut fermentaion of cellulose. The minute you feed them cr@pinabag they will immediately become either hyperglycaemic, hyperinsulinaemic or both compared to living on short chain saturated fats. That's not exactly how they are designed to run and their ascorbate requirement rockets. BTW they become obese too. Feed them rabbit cr@pinabag and they die. It's a bit like feeding sailors or tarsiers on dried salt beef and ships biscuits, but probably doesn't taste as good. Doesn't have the weevils either.

Then there is that fruit bat which has also lost its ability to synthesise ascorbate because, well, it eats fruit. This sounds quite convincing as a reason for losing ascorbate until you realise that it seems as if all bats have lost their ability to synthesise ascorbate. Most ascorbate-less bats are pure carnivores. Insects are where it's at. Insects don't synthesise or supply much ascorbate. Fruitbats are the oddballs among bats and it's probably not why they don't make ascorbate. That's just a bat-thing.

Now, I hate to mention hedgehogs again but, here I go, we all know that they not only do make ascorbate, but they also make an Lp(a)-like substance too. As an aside to pointing out that this doesn't go along with Lp(a) as a surrogate for ascorbate, I'd just like to mention kringles III and IV to clear up a minor point:

Humans repeat kringle IV from plasminogen in their Lp(a). Hedgehogs repeat kringle III. How convergent is that? Not very. But in hedgehogs it is kringle III of plasminogen which binds to fibrin, in humans it is kringle IV. So hedgehog Lp(a) seems to be markedly convergent with human Lp(a). This makes me happy as it suggests Lp(a) is not some idiotic mistake only made by humans and their kin. It's worth evolving by non related species. That just leaves the big unknown of whether hedgehogs are also using Lp(a) to deliver oxidised lipids to where they are most needed (guess yes!).... And what we are both doing with those lipids. And their kringles in addition to binding to fibrin.

Anyway, the simple concept that humans and guinea pigs make Lp(a) as an ascorbate substitute seems to be so full of holes that I can't see it. Sigh.

Mega dosing on C in the attempt to put the clock back 40 million years and so reduce Lp(a) and heart disease does not hold water. Whether there is a pharmacological benefit of mega dosing ascorbate, along the lines of using niacin to mimic beta hydroxyburytate, seems possible. But if this is the case it's an accidental benefit derived from faulty logic...

Oh, a last comment on bats. None of them make ascorbate. Some, but not all, are VERY long lifespan species. Not in the league of Naked Mole rats of course, but some certainly live far longer than the same sized mouse.

Never mind mega dosing on ascorbate, that's without making any ascorbate and living on insects.

Peter