Wednesday, April 23, 2008

Lipoprotein(a), a prickly subject

Convergent evolution is a fascinating subject. Lipoprotein(a) has been independently evolved at least twice, not only to produce a remarkably similar (but not identical) molecule each time, but on both occasions it has been by a modification of the same gene, that for plasminogen. The two groups with well characterised Lp(a) are of course old world primates (including man) and the hedgehog. You thought the non primate was the guinea pig? Well, I've not been able to find any replication of Pauling and Rath's work with lipoprotein(a) in guinea pigs and the people who did the work with hedgehogs have looked for the apoprotein(a) gene in guinea pigs, pretty thoroughly... and without success.

What is lipoprotein(a)? It's perhaps best described as a super LDL. Just imagine taking a lethal LDL particle and wrapping it up in a second protein, apo(a), which is not only specifically designed to bind the whole lipid particle to the fibrin present in a blood clot, but which also inhibits clot dissolution. On top of that (could it get worse?) apo(a) is heavily and specifically glycosylated with a sticky sugar coating which will bind to the arterial wall. Hmmmm, if you wanted to clog an artery with lipid, this has got to be your glue!

A quick trip to St Tiggywinkles Hedgehog Hospital would be expected to reveal cages of recuperating hedgehogs, victims of strokes, aortic aneurisms, heart attacks, peripheral vascular disease, all of the problems associated with elevated Lp(a) in humans. In truth my guess is that most of them (the hedgepigs) will actually be victims of road traffic accidents, lung worm infection (a killer in hedgehogs) and late summer birthed toddlers who won't overwinter successfully in the wild.

Perhaps Lp(a) in hedgehogs is different to Lp(a) in humans. It has certain structural differences, but it still acts in as an inhibitor of clot dissolution in models based on human tissue. The fact that it doesn't seem to cause vascular problems in hedgehogs is all the more surprising when you realise that it is THE bulk lipid transport particle in hedgehogs!

The other very strange thing about Lp(a) is that it tends to be rather good for you if you (as a human) make old bones:

"lipoprotein(a) elevation in centenarians, in the absence of other coronary artery disease risk factors, appears as a positive survival factor"

It's worth noting that many of the risk factors for heart disease are turned on their head anyway in the elderly, once you look at all cause mortality. If you are over 65 years old, white or African-American then better think twice about popping that statin! You might end up in that lowest quartile of LDL cholesterol, maybe down at 60mg/dl:

"hispanics had the best overall survival, followed by African-Americans and Whites. Whites and African-Americans in the lowest quartiles of total cholesterol, non-HDL cholesterol and low-density lipoprotein cholesterol (LDL cholesterol) were approximately twice as likely to die as those in the highest quartile"

Just to simplify, low LDL cholesterol=death. That got missed out of the conclusion line! For hispanics, all lipids were irrelevant once you cracked 65 years of age, ie high LDL is not protective in elderly hispanics, nor is it a problem. Of course this is only New York, things may be different in other places. Maybe.

Well, that got me side tracked. Back track with Lp(a) next post.



kris said...

I hope you'll forgive me for not commenting on this particular post, But I happened upon your blog from Seth's board, and after reading quite a lot of your site, I'm compelled to ask you a question for which I could find no realistic answer elsewhere.

As far as my quality of life is concerned, carbs have done much more harm than good. However, every medical professional who would even entertain my thoughts on the subject informed me that I was doing irreparable damage to my kidneys with that amount of protein throughput.

Now, what I want to know is how do you weigh in on the whole low-carb-kidney-damage subject?

Its the one sticking point I have with low-carb living. While I am finding much success with low-carbing I am still concerned with all the kidney-hype and I'm interested in your opinion on the subject. (as well as any research to which you may have access) Thanks!

Chainey said...

Hi Kris

I'll be interested to see what Peter has to say. Just for fun, let me give my perspective and we'll see how it jibes with his.

The first observation I would make is that many low-carbers consider themselves to have converted their bodies to "fat burning" rather than "sugar burning". In other words, it's a high-fat diet rather than a high protein diet.

I'm not sure if I personally eat more protein in absolute terms than I did before. Certainly a mixed diet derives some of its protein from grains, legumes, etc., so that balances the scales a bit.

I buy/eat fatty meats, eat more egg yolks than whites, and so on.

Secondly, as I understand it, some of the research cited about kidney damage from excessive protein was a result of isolated protein powders, not natural sources like meat.

Dr Mike Eades calls the protein-damages-kidneys story a "vampire myth" (i.e. it has been killed but won't lie down).

To see related blogs from his blog, click here.

I think the bottom line is, if you have existing kidney disease, you may need to monitor the protein, otherwise it's unlikely to be a problem.

But keep researching.

Peter said...

Hi Kris,

Have a read here.

In this case report the patient was treated with a LC diet and protein was reported at about 30% of 1800 kcal/d. That's 600kcal or 150g/d of protein. I'm not sure that this is a low protein diet, sounds pretty generous to me (I'm down at 60-80g/d).

Albuminuria reversed completely and creatinine lowered slightly then stabilised despite previous progressive increase.

As far as I can see most people on dialysis are there because of inadequately controlled diabetes. My take home message is that hyperglycaemia=renal failure. Obviously there are other causes, but that's the big one. Protein at 150g/d may not be my personal choice, but I don't see any problem with renal damage at this level. Probably up to 300g/d is fine if you're a Greenland Eskimo on a traditional diet.

In agreement with Chainey, I would specify we eat protein from food.


Dr. B G said...

I've been thinking about this a lot lately too! Your post is as informative as ever. You're AWESOME Peter!!

So why were those hedgehogs all having vascular emboli and dz? Was it their hog chow?


Peter said...

Hee hee, bread and milk might do the trick!


Anna said...

Kris, when I was pregnant 10 years ago I was diagnosed with gestational diabetes. I was also prescribed a LC diet to control the GD, with visits to a dietician to be sure I was getting enough protein, nutrients, etc. It was great in many ways - I ate far healthier than before the diagnosis because I was more aware of every bite, and I gained a healthy weight and kept good BG control with LC, not too much and not too little (28 pounds total - with only 14 to lose after the birth).

My thought is that if LC is healthy enough for a pregnancy (when kidney function is really crucial), it *is* healthy, period.

Stan said...

Another ref for Kris (from Heretical.htm), quote:

#22 Twice as many kidney patients survived after 4 years on a medium protein restricted carb diet, than in a control group of kidney patients on a normally recommended low protein high carb diet.

"A Low-Iron-Available, Polyphenol-Enriched, Carbohydrate-Restricted Diet to Slow Progression of Diabetic Nephropathy "
Francesco S. Facchini1, and Kami L. Saylor, Diabetes 52:1204-1209, 2003

There is also a discussion and a summary of that paper at:


"The composition of the white meat-based diet was 25-30% protein, 30% fat, 35% carbohydrate, and 5-10% alcohol. A control group of kidney-impaired diabetics consumed a low-protein diet comprised of 10% protein, 25% fat, and 65% carbohydrate - a similar macronutrient profile to that recommended to kidney patients - and to the general population by mainstream health authorities."


"After an average follow-up period of 3.9 years, 39% of the control group patients either died or deteriorated to a point necessitating kidney replacement; in the unrestricted white meat-protein group, the corresponding figure was only 20%." [Note: total population N=191]

Dr. B G said...


You heretic! I love that article!!


Douglas Porter said...

I agree with Peter that the protein and kidney problems question has mainly to do with blood sugar. Richard Bernstein whom I consider the authority on how diabetics should take care of themselves has in his appendix A, a discussion on various topics, including protein and if it is a problem (not) for kidney function. This is a good book for everyone to read who wants to understand blood sugar, which should be everyone. If you want to just read the discussion on protein and kidneys, you can go to Amazon and call up his book which has the search inside feature and go to Appendix A and read it on line for free.There is a limit of three pages on a selection but you can jump around until you read it all.

Douglas Porter said...

One more thought, if you are not familiar with Dr. Bernstein, he is a type 1 diabetic, diagnosed in his early teens, of over more than 60 years standing, who when he was a young man in his 20's, had blood markers indicating kidney disfunction, but who now in his 70's has none of the normal long term sequalia of diabetes. He figured out how to control his diabetes on his own, against the advice of the medical establishment, (his personal physician as a child was the president of the American Diabetes Association) and then went to medical school and became a doctor so that people would take him seriously. He has treated thousands of people for diabetes and he states that kidney problems derive from high blood sugar more than anything else and that his own kidney function markers in blood tests normalized once he got his sugars under control. For most people, protein is not a worry for kidney function.


Dr. B G said...

Anna, I have very large obese male patients -- I give them the 'standard' ADA diabetes 'diet' for gestational/pregnant women. I tell them follow this -- (it's low carb per the ADA) -- I say EXACTLY what you were thinking (!!)...

If this is healthy and GOOD for pregnant women (who are even carrying twins or triplets)... then it's good for 'you too'...

Esp if that pregnant lady is spewing out proteins (!!) from her kidneys, even if her BP is high (!!) and even her fetus is endangered (!!). wow... it works??

And the low carb totally works! Why isn't the medical establishment as intuitive?

(btw a lot of women are more pre-eclampsic than ever, delivering preemies, and this is believed to be related to the epidemic of vitamin D deficiency -- which btw of course is reversible)

Sven said...

Liver function going down the drain can be a reason for low LDL-levels. As Dr. K puts it "...this occurs when the body is dying." So low LDL-Levels per se aren´t necessarily a bad thing (if your liver is functioning properly). In my eyes it would be prudent to use the second lowest LDL-group for comparison.
The question is: Are people dying in the low-LDL-group more often (compared to the hig LDL-group) because of low LDL? Or is the high mortality of the low-LDL-Group caused by the fact, that in some people LDL-levels are decreasing while dying?

kris said...

Oh my gosh, but thanks so much to all of you. I'm off to read the links you've given me. (and I already feel so much easier about my diet choices than I did yesterday)

My mom died from heart disease, many years ago at 48, secondary to type 1 diabetes which was diagnosed when she was 8. Her diet consisted of "low GI carbs and very low to no-fat" and I have been questioning the medical establishment's prescribed "heart-healthy diet" ever since.

Thank you again, and I'll absolutely be back.

I am very much enjoying your blog, all low-carbing aside.

Peter said...

Hi Sven,

Yes, association does not mean causation. I really should stop doing that! I would agree that hypocholesterolaemia in hepatopathy is an extraordinary gloomy finding. I also feel that hypocholesterolaemia is normal on a real food diet, especially if you are young. But on a modern diet I would find it very worrying.

These two abstracts suggest that hypocholesterolaemia may be a marker of bad things many years in the future:

Austria study

Honalulu study

For a modern intervention study I posted here on the J-Litt study

You realise that there is never a placebo group in modern cholesterol trials as this is no longer considered ethical, and few are powered to look at all cause mortality...


Peter said...

You're welcome kris


O Primitivo said...

Lipid-lowering treatment to the end? A review of observational studies and RCTs on cholesterol and mortality in 80+-year olds. -