Thursday, February 28, 2008

Cholesterol (the HDL sort) kills?

This article was picked up by GinnyL, a prolific reader of diabetes news and a poster on Dr Bernstein's site. There are no links to anywhere from the article, so I pubmeded the guy who got a mention by name, Dr Genest, for 2008, and came up with this ref, which I can get at the full text of.

BTW there are some interesting papers of FH he's published, maybe another day.

There's a lot of waffle but you do get the fact he is talking about EPIC-Norfolk and IDEAL. This appears to be a reasonable summary of their findings:

The more HDL particles you have the better, the less cholesterol in the particles the better. ie you want to have a high HDL-C particle count with not too much cholesterol in each particle.

Your lab work merely picks out any HDL it can find, measures the total cholesterol in this fraction and gives you that number. Compare this to the accepted wisdom re LDL-C, typically from Dr Davis:

Your lab work just picks out the LDL, measures the cholesterol and guesses (sorry, calculates) an approximate number. Actually that's completely wrong. The lab measures the TC, subtracts a few numbers, adds VAT, subtracts the first number you thought of and that's the best guess of your LDL-C concentration. Maybe.

Anyway, if your really do measure particle sizes/numbers, the fewer LDL particles you have better, the more cholesterol in each particle the better.

Are you seeing a pattern here? It all comes down to particle numbers, sizes, contents. What controls all of these? Not statin deficiencies, as in IDEAL.

Forget your cholesterol. What marker predicts heart attacks and total mortality without all of the paradoxes?

Follow EPIC and HbA1c (yes, same that same EPIC study as this one) to get some sort of clue. Control what you are doing wrong diet/lifestyle-wise to glycosylate your haemoglobin and your liver will sort out whatever cholesterol particles sizes/numbers it needs for health.

The EPIC/IDEAL paper is quite amusing for the shock horror throughout the discussion that high HDL could be killing people via heart attacks, but you get used this sort of rhetoric from cardiologists. It sort of gets summed up by Dr Genest's comments about torcetrapib:

"The second such compound, torcetrapib, proved toxic despite causing a large increase in HDL-C levels and was withdrawn from clinical use"

No, Dr Genest, think again. Perhaps it's not "despite", perhaps it's "because". Perhaps it is the artificial packing of cholesterol in to HDL particles which was toxic, not the drug per se. Treating a lab number is all torcetrapib did, it's for idiots. Sort out your diet so as to live within the limits of your own personal level of insulin resistance and leave your lipids alone. On Kitava and for the fishing Bantu this can involve 70% of calories from carbohydrate producing an HDL <1.0mmol/l with excellent cardiovascular health. For an insulin resistant Norfolk diabetic it might mean 5% of calories from carbs and the rest from saturated fat giving an HDL of 2.0mmol/l.

It's not the labels on the lipids that do the damage.


PS Also from Dr Genest

"Mutations that impair the function of cholesteryl ester transfer protein (CETP) are associated with marked elevations in HDL-C levels but not necessarily with protection against coronary heart disease (8)"

Ref (8) does not quite say that the mutation (the one which torectrapib mimicked) was neutral, it said it was bad. Naughty mis-citation. He must be a cardiologist. And people are surprised at torcetrapib killing people, using heart attacks? Torcetrapib was a success, it did exactly what it should do! The Zhong et al paper was published in 1996. It was the basis for the development of torcetrapib. You can't say Pfizer didn't know what they were doing. You can't understand why they did it either.


Stephan Guyenet said...

It seems to me that the paradox is resolved if you see high HDL as a marker of cardiovascular health, rather than a cause of it.

Thus, if you manipulate HDL unnaturally by drugs or mutation, you're throwing something out of balance rather than fixing the problem.

Peter, would you agree that high HDL is associated with (but perhaps not necessary for) cardiovascular health? I'm talking about your standard lab measurement here.

That's the impression I have from reading "Good Calories, Bad Calories" and "Protein Power". It sounded like the ratio of HDL:trig was the best lipid predictor of risk we have at this point.

JohnN said...

Does the Genest's paper discuss the trig level? There seems to be a correlation between it and HDL-C's density and LDL-C's fluffiness.
Talking about the drug company's tendency to treat symptoms and ignore the cause: it's easy to predict the availability of compounds to lower your Lp(a) in the near future, probably with disastrous results.

Peter said...

Hi Sasquatch,

In the UK I'd agree. In Kitava, no. The Kitavans have cardiovascular health, but not the HDL-C marker for it. I suspect it all comes down to insulin resistance (whatever that is). And how well within the carb limit imposed by your insulin resistance you are living/eating. Certainly the Kitavans have high trigs, low HDL-C and no heart disease, so these cannot be taken as universal surrogates of cardiovascular health. But the Kitavans have no suggestion of insulin resistance, so can afford to have a high carb diet and high carb lipids...


PS quote from Genest, he's thinking along that same line too, but probably has never heard of Kitava!

"Is HDL-C (simply) a marker of cardiovascular health?

Proper life-style that includes no smoking, physical activity, and normal body weight are all associated with higher HDL-C levels and stand on their own merits with respect to cardiovascular health."

Peter said...


No, no mention of trigs at all.

The one thing that struck me from the IDEAL study was that these people were on aggressive statin therapy. We know from the J-Litt study that LDL-C below 160mg/dl is associated with increased cardiovascular mortality. Statin inflated HDL-C (can happen in some patients) may actually be a surrogate for very low LDL-C!


Peter said...

The last post, which I've deleted, looks to have been a spam ad for resveratrol. Anyone interested can always wiki the substance!


Anonymous said...

I think when you combine high-carbs with high-PUFAs, you will get heart disease, or some other disease. The carbs are "associated" with disease in cultures eating the Western Diet high in PUFAs and junk food. But we don't seem to find that association when enough animal foods are eaten. We may just be seeing a correlation between malnutrition and disease.

A person's HDL, LDL, triglycerides, and particle size are risk factors. You need a combination of many risk factors to cause disease, IMO. They also might not mean anything if you go outside of the dietary context a given culture tends to provide.

Anonymous said...

Hi Peter,

Sorry to go off topic, but I am still learning about the hyperlipid approach. Have been following it for a few weeks, and have lost a few pounds as well as transitioned into an odd, but welcome, state. I have noticed that I am less hungry during the day, and less apt to eat for entertainment/stimulus' sake. Sometimes I only eat once a day, simply b/c I am not hungry. Very interesting.

Also noticed that when I do eat carb rich food, such as a burrito with rice in it, it tastes better.

Only thing I am struggling with is with is the dearth of hyperlipid recipes. Thus far, subsisting on a lot of cream and egg yolk scrambles.

Anyhow, what I wanted to ask you is would you mind highlighting the differences between your and Eade's approach. I know Eade's is a big promoter of high protein, but I don't know/understand enough to be able to differentiate between the two approaches. Any light you might be able to shed on the matter would be most appreciated. Many thanks in advance.

Peter said...

Hi Varangy,

Protein Power is one of the few LC books I've not read, so it's very thin ice I'd be skating on commenting on an approach I haven't read, bit like Susan Jebb of the MRC in the UK talking garbage about the Atkins diet without reading the book. From reading Eades' blog and from the discussions of Protein Power on Dr Bernstein's site I don't really think there is a huge difference. All really sensible approaches to LC must pan out similarly with protein at around 0.8-1.5g/kg/day. The WHO considers the minimum protein needed to subsist healthily is 40g/d total, for me this would be about 0.6g/kg. The lower the quality the more you need. Basing your diet around eggs (highest possible protein score) and meat (also has a very high quality score) you can comfortably get all the protein you need for maximum health on 1.0g/kg per day. You cannot store protein in an inactive form, if you eat more than you need you just convert it either to glucose or ketone bodies (depending on each amino acid) and that becomes part of your cab/fat intake. So excess protein above muscle building/structural repair etc gets converted to (mostly) glucose and requires a little insulin to manage it.

So, as far as I understand, Protein Power is a misnomer and Eades has commented on his blog that the name was chosen by his publisher, not himself. The other feature of Eades that I like from his blog is the combined lack of fear of saturated fats and of cholesterol. This puts him in to the same group as Lutz, Groves and Kwasniewski. All of these approaches are very similar. In an situation where you are looking to sidestep problems associated with insulin resistance, the formula of low carb, adequate protein and enough animal fat to adjust your weight to where you want it (but not too low) tend to come out pretty much the same.

I wasn't too keen on the Atkins approach, though I started with it, because it included too many non foods such as soy flour and glutens. Also over the years I have essentially eliminated artificial sweeteners too. Atkins progressive increase in carbs with on going weight loss seems a bit silly too. As far as I can tell at the moment I'm pretty well in to this way of eating for the long haul. The biochemistry of what I need is what convinces me. It may be possible that I could increase carbs without problems, but I see no need to go looking to find out.

So I have all these diet books on my shelves, full of LC recipes, and cook from normal cook books! All LC authors give you recipes in their books, where as I seem to cook from memory, Ken Hom, Madhur Jaffrey, a generic Mexican cookbook, Gluten Free Healthy Eating and a generic stir fry book. I used to use a whole load of paperback cook books from Sainsbury's and these, long gone, are the source of most of my high usage memorised recipes. With any recipe, replace any vegetable oil with butter, add extra butter, get rid of any sort of flour, adjust the meat content to give you the protein you need. If in doubt push it through Fitday and away you go.

Is that any help?


PS last night was steak and chips, before that was Donner Kebab, before that was pork Fahita, before that salmon and chips, before that liver and onions (plus a little bacon) and before that bolognaise sauce and chips. Tonight we're eating out and I might do steak again. A 12oz steak gives about 60g of protein. I skipped my eggs today so all set to go...

Stephan Guyenet said...

Hi Peter,

I'm reading Protein Power right now. I'm about halfway through. I really like it. Don't let the cheesy title fool you. Dr. Eades is well-read and well-reasoned. I agree with all his major points.

He starts out talking about how we lived for the majority of our time as a species. Then he gets into how our diets have changed and how it's hurt us. Insulin is central to the book.

The only big thing on which we differ is supplementation. He supports the judicious use of supplements for people who are recovering from metabolic syndrome/high blood pressure/CVD etc. He may have a point, but I can't imagine supplementation could improve a healthy diet for a healthy person.

I'm learning a few things from it, so I'm glad I bought it. He doesn't reference many of his statements though, which is very annoying.

Stephan Guyenet said...


A lot of cultures eat stews or stir-frys that they put on some kind of bulk starch-- potatoes, rice, pasta etc.

These dishes are easily adapted to LC; you just eat them without the carb.

French stews, Indian "curries", and Chinese stir-fries come to mind.

Peter said...

Hi Sasquatch,

It's come up in distant comments that I've a lot of time for Dr Eades. Have you got to the protein calculation aspects? What's his formula? Did you read on his blog that the title was chose by his publisher, against his wishes? I gather he is in favour of moderate protein, low carb and so high fat comes by default. He doesn't worry about saturated fat either. Sound very sensible to me, I read his blog.


Stephan Guyenet said...

Hi Peter,

I haven't finished the book yet but flipping through, it doesn't look like he gives any specific recommendations for protein beyond minimum requirements.

He seems to deliberately avoid giving specific guidelines for macronutrients. I like his approach actually; he seems to be against obsessively counting and dissecting your diet.

As far as fat, he's concerned with quality but not quantity. He says eat as much as it takes to feel full. He's against polyunsaturated and hydrogenated oils.

He's also against grains and concentrated carb in general, which of course means you'd have to eat protein or fat to make up for it. I haven't seen anything in the book that promotes one over the other so far.

JohnN said...

If you read Dr Eades' blog, the post-Christmas ham sandwich is not moderate in protein by any standard and I don't mean to disparage that at all. Even if one subscribes to a certain proporion of the 3 macronutrients (CHO:protein:fat), it should be done dynamically - over a time period rather than statically (e.g., fixed ratio at every meal). Pareto distribution in any complex system is a sign of robustness.

Regarding sasquatch's comment:
"...but I can't imagine supplementation could improve a healthy diet for a healthy person."

I believe some supplements are warranted. You may not synthesize enough vitamin D wrapped in clothes and earning your wage in an office; your diet may not contain enough EPA & DHA or its presursor (ALA). And my favorite example is ascorbic acid. What if my vegetables and meats are cooked at high heat which denatures vitamin C and I'm not willing to consume a lot of fresh fruits which have been selected for high fructose? What if CHD is a silent, low-grade form of scurvy?

. said...

The Hyperlipid Approach? I'm waiting with bated (not baited) breath for the Hyperlipid Life Plan (incl. recipes).

Peter said...

Hee hee, just took some pics of the remains of the breast of mutton we had for Sunday supper and the cheesecake we managed to find room for by 9pm. If Squiggs sleeps this afternoon I was going to stick them up as a post! Cheesecake for breakfast and lunch today and it will be stir fried mutton in orange butter sauce for supper tonight. And cheesecake too, if there is any left. Now if only I could live on raw brussel sprouts. Sigh.


Anonymous said...

Varangy: one way to boost fat is to eat raw meat, eggs/yolks, and dairy (like raw cheese or butter). I have done this in the past, but now I am eating a mix of raw and cooked. You shouldn't rely on recipes, IMO. The simpler you make it, the more easy. This was a point that The Bear made often. It is easier to fix meals if you eat raw, amd easier to clean up afterwards. But I don't think it is wise for most folks to eat all raw. Throw in some boiled potatoes, some cooked meat/eggs, etc.

I think many fail because they just don't eat enough fat. It's not easy to get in as much fat as Peter, and Jan Kwasniewski. Grass-fed meat can be very lean, unless you eat kidney suet or butter with it. Fatty meats and cheeses and egg yolks have like 50% more fat than protein. They are the place to start. Unless you keep the focus on foods like that or add a lot of fat to your food, you will not get near 75-85% fat, IMO. It is not easy to stay high-fat.

Ed Terry said...

Over the last six years, I've tried numerous methods of raising my HDL while ignoring my LDL. I started taking niacin because of its effect on lipid parameters. It raised my HDL from 32 to 42.

However, the biggest change came when I transitioned to a high fat eating style. 67% of my calories come from fat; most of that is saturated. I also keep carbs low (<70g/day).

Today my HDL is 76 and I have a low LDL particle count. Will this help prevent heart disease? I don't know but I'm sticking with my approach because my cardiologist's approach will probably kill me a lot sooner.

Olga said...

Hi Peter,

Did you ever post a follow up to this comment:

"Should all homozygous FH people be on a pharmaceutical statin? Another post there." Thanks.