Sunday, March 07, 2010

Lipoprotein(a) and the Fairies at the bottom of my garden

Just a brief giggle. You recall that a reduced fat diet, packed with plant antioxidants raises Lp(a). Without the plant toxins it works even better to raise Lp(a). This paradox is explained by the immense power of the low fat diet to physically tear Lp(a) out of atheromatous plaque and place it in to the circulation in antigenically recognisable form. It's healing. Snigger.

This is powerful medicine. I don't know how many covalent bonds the lysines and glutamines in apo(a) have made to the lysines and glutamines in fibronectin. Let's say quite a few. But the low fat diet appears to be able to tear several hundred of these covalent bonds apart and then it reassembles the apo(a) molecule in to its original shape in the plasma. Gasp in awe. Well that's incredible.

So incredible that anyone who believes it does not realise what incredible means.

Incredible means unbelievable. Better not to believe unbelievable things. These are the believers who published (just a little name and shame here):

Silaste ML, Rantala M, Alfthan G, Aro A, Witztum JL, Kesäniemi YA, Hörkkö S.

and the believers who editorialised:

Mohamad Navab; Srinivasa T. Reddy; Brian J. Van Lenten; Alan M. Fogelman

Even the Fairies at the bottom of my garden tell me not to believe stuff this stupid!



Pål Jåbekk said...

By making up creative ad hoc hypotheses, even the most wonderfully strange paradoxes can live on and prosper.

I like it Peter!

Brad Reid said...


Nothing at all to do with your most recent post, but I thought I'd drop this here for you and everyone to review and comment on, an absolutely fascinating history of scurvy:

Cheers! Brad Reid

donny said...
Lipoproteins can bind lipopolysaccharide (LPS) and decrease LPS-stimulated cytokine production. Lipoprotein(a) [Lp(a)] was as potent as low-density lipoproteins (LDL) in inhibiting LPS-stimulated tumor necrosis factor synthesis by human mononuclear cells. The kinetics of LPS inhibition by Lp(a) was similar to that of LDL. This suggests that circulating Lp(a) may be an important factor determining the amplitude of the response to LPS in humans.

So maybe the lp(a) bandaid is anti-infection? ApoB count going down might reduce ability to fight endotoxin effects?

Stuff that's effective against endotoxins (less fructose, more glycine, taurine, vitamin D) also have an effect on ldl size, etc.

Peter said...

Hi Pål, the Fairies are generally pretty gullible, certainly compared to the Voices in my head, but there are limits!

Brad, nice link, thanks. Quite what people will make of the Lipid Hypothesis in 100 years time...

Donny, I've just been sent a paper which goes in to great detail of how the oxidised phospholipids are specifically anti endotoxin. Lots to read before I can post on it. You NEED those oxPLs. Apo(a) is there for a reason.


karl said...

I think it is prudent with our limited knowledge to try to keep Lp(a) low -- but..

What if a high SatFat diet reduces Lp(a) by depositing it into our artery walls? ( I'm not saying it is so - I don't know ) What if SatFats use up PON-1 from HDL and reduces it's effectiveness?

Lowering Lp(a) sounds like a good idea, but there is little evidence that it does anything other than the association ( is it the horse or the cart?). ( Niacin therapy is associated with lowering Lp(a) - but it also does other things.) Lp(a) seems like it might have more affinity for oxLipids than regular LDL - is it elevated due to oxlipids? Is it's purpose to clean out oxLipids?

We need to figure out what is the smoke and what is the fire... I'm playing devils advocate here - hope it inspires..

Florida Butterfly said...

High fat diet?
That raises LDL, we want it low. Lp(a) attaches to the LDL. Promotes blockages.
I just found out two months ago that I have elevated lp(a). I was told low carb, low fat diet. And I'm on 100mg Niacin already. I'm young, but they just wanted me on it to see if it will get lowered, since some Niacin doesn't work for all cases.

Peter said...

Hi Karl,

Yes, we need to keep thinking. It was Krauss' group who showed that Lp(a) accepts oxidised phospholipids from LDL, hence the post that Lp(a) is oxLDL. The oxPL, shepherded by Lp(a), are undoubtedly anti endotoxin (post coming). So too is native LDL (another post there), but I suspect Lp(a) does a far better job than LDL.

The big problem most people have is with the concept that oxidised lipids have specific uses. In fact one of the best arguments AGAINST saturated fat is that Lp(a) is a useful carrier of oxPL and reducing it is a potential catastrophe.... Because CVD only worsens associated with low Lp(a) at the very lowest levels of Lp(a), my preferred hypothesis is still that the liver makes as much as it thinks the body needs on the basis of markers it looks for of tissue damage. Unless it has genes which make it hard for it to make any. There are people with null alleles. Lowering Lp(a) by excess arterial wall consumption should be catastrophic, like the fall in LDL in major trauma. Bad news.

Lowering it pharmacologically will be a catastrophe. Niacin is a ketosis mimic and so we get away with it as it probably throws all sorts of beneficial switches, but there's not a lot published on that.

But as you say, you have to keep thinking.

Hi Florida Butterfly,

I'm afraid you will be very confused here. As far as I am ware LDL has nothing to do with arteriosclerosis (I certainly have no wish to lower my LDL), Lp(a) is a highly functional molecule and niacin mimics ketosis (but ketosis is probably better).

It's a bit difficult to set this out in a paragraph in a believable form. If it was, I wouldn't have this blog.

Good luck


AlphaMale said...

Hi Peter,

Could you say more on the link between niacin and ketosis? I was under the impression that niacin is pretty much a ketosis inhibitor. In fact I have heard of people using it to deplete their glycogen stores faster (and hence enter ketosis after).

When I take a high dose of niacin (say 1g), after the flush I often feel cold. Also, twice recently I've had angina and I'm too young for this. It could be many other things, but I was under the impression the niacin therapy at the same time as a high fat diet could be the cause. The first time was after taking MCT oil for the first time (90g).

I wanted to try the niacin therapy for hyperlipidemia and also for other health claims, but now I'm torn because I dont want to stop my new diet (that is quite high in SFA, low in PUFA, sugars, etc)