Tuesday, December 28, 2010

Anacetrapib and phytotoxins

Just starting to find a little time to post. This seems like a worthwhile snippet as a follow on to the anacetrapib post, easier to put up than the cooking epics on insulin and the liver, parts two onwards........

Ok, the usual recap:

First there was cholesterol. It was bad, life was simple.

Then came Good cholesterol, HDL battling the Bad cholesterol, LDL.

Then there was Good LDL, large buoyant battling with Really Bad LDL, small dense LDL, sdLDL.

Not only that but native LDL appears to be harmless, it's only oxidised LDL which is the killer, oxLDL.

So the evil sdLDL is only really evil because it is more easily oxidised than fluffier LDL. Maybe, but in general I tend to have glazed over by now, befuddled by the blur of the moving goal posts.

But just occasionally something does grab my attention, especially if it markedly deepens the hole being dug for itself by the lipid hypothesis, like anacetrapib.

It was thanks to Dr Davis that I grasped the concept of CETP inhibitors as eliminators of sdLDL. That's what they are. If you believe in the lipid hypothesis it must be pretty interesting to have a drug which virtually eliminates sdLDL while increasing the body count for cardiovascular deaths, even if 4 dead out of 808 vs 1 dead out of 804 does not reach statistical significance.

But the real gem from Dr D was the finding that anthocyanins are CETP inhibitors. You no longer need to sign up for the next anacetrapib trial to die of a heart attack in the cause of the lipid hypothesis. You can buy a do-it-yourself CETP inhibitor in the form of a purple plant dye.

EDIT pre posting: It always amazes me that someone as perceptive on blood glucose, and indirectly on blood insulin, as Dr Davis can still believe the lipid hypothesis. Really believe. Fascinating.

There now, we all know plants are all natural, healthy and safe. Perhaps that includes recreational plants like Deadly Nightshade, Nux Vomica and Henbane. As an alternative to anacetrapib you can only hope the anthocyanins don't work!

If they do work at least you might have the consolation that you died with cracking lipids.


PS, taken from here on flavonoids, discussed here:

"However, a similar decrease in protein oxidation [on flavonoid elimination], in 8-oxo-dG excretion and in the increased resistance of plasma lipoproteins to oxidation in the present study points to a more general relief of oxidative stress after depletion of flavonoid- and ascorbate-rich fruits and vegetables from the diet, contrary to common beliefs."

Want oxidative damage? Munch those flavonoids; and the anthocyanin flavonoids come with the added toxicity of CETP inhibition. Mmmmmm, purple fruit!


Nigel Kinbrum said...

Does this mean that I have to step away from the bottle of Blossom Hill Californian Red?

david said...

Peter, you're killing me!
I wish I knew where and what to look for to challenge your theory a bit. It can't be 100% correct. nothing is.

There must be some studies out there, done correctly, which show fat=bad / plant=good to something in our bodies.

any doctors out there?

Paul Jaminet said...

David, there are studies for everything!

I actually rather like the therapeutic potential of anthocyanins. Although they are mildly toxic to humans, they are highly toxic to some gut pathogens, especially fungi and some biofilm-forming bacteria.

Anthocyanins are also relatively more toxic to cancer cells than normal human cells.

There is even an argument that the mild toxicity to humans can provide a beneficial hormesis. Hard to prove this of course ...

john said...
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Somatotropina said...


Do you have any evidence of anthocyanins being beneficial for humans in vivo?

Hormesis is one key aspect on why you should limit your vegetable intake, specially fruit intake to something like once a week or even less....

Emily said...

can someone please explain, in layman's terms what "oxidative stress" or damage really means?

Ned Kock said...

If you want a possible path for hormesis, take a look at this article:


Uric acid is believed to be a powerful antioxidant.

malpaz said...

im way confused... so coconut is bad? as are collard greens and butternut squash??

so, just eat fatty meat...?? doesnt seem right

Paul Jaminet said...

Somatotropina -

Ned's link is a good example of the argument for hormesis as I have seen it made. In the act of cleaning up the plant toxins, the body upregulates activities that also clean up other toxins, damaged proteins, or pathogens. So goes the theory. There is evidence for it but not so far as I am aware anything that would convince a skeptic that these beneficial effects outweigh the toxicity.

But I think the case that eating the berries is health improving for humans is reasonably strong, because of beneficial effects in the gut. In berries, anthocyanins and prebiotic fiber such as inulin modulate the gut flora in a favorable direction. As Ned's link says, only 5% of ingested anthocyanins enter the body; 95% stay in the gut. The dose in the body is too low to be highly toxic. The dose in the gut is toxic - to pathogens.

Again, this is a judgment call. But I think it would be rash to give up plant foods because they have toxins.

john said...
This comment has been removed by the author.
John said...


About the green tea/flavonoid-free paper: what data makes you conclude that the drop in oxidative damage was caused by a reduction in fruit consumption? Perhaps I missed something, but I cannot find any details in the paper about the participants' habitual diet. I can only derive that it contained some source of vitamin C (from Fig. 3).

In other words, we have a comparison of an unknown habitual diet (with some source of vitamin C) to 10 weeks on a well-specified diet (which was devoid of fruit and flavonoids). The well-specified diet caused a decrease in oxidative damage.
Without details about the habitual diet, I think it's quite impossible to pinpoint the cause for the decrease in oxidative damage. Which is very unfortunate.

Like the investigators, we can speculate. Maybe the participants ate a lot of fruit prior to the intervention, and the fructose in the fruit was the cause of oxidative damage. But perhaps they just drank a lot of soft drinks, providing ample fructose for oxidative damage. Maybe they ate a lot of food fried in PUFA rich oils. Or some combination.

So, could you please expand on the reasons for your conclusion?


Chris Masterjohn said...

This discussion is pretty funny. There is so little evidence for hormesis, but the evidence is compelling enough that we have a developed dose-response where we know we should eat one serving of fruit or vegetables per week? Hmm, we can't have our anthocyanins and eat them too!

Actually there is some solid evidence of hormesis in animal models and it will be pouring in over the next year or two I think. I'll post about this a bit after New Years's. Have a happy holiday everyone!


Somatotropina said...

@Paul Jaminet:

Agree, but remember that the hormetic curve has an inverted J-shape. Fruits arent essential for an optimal health. Its use is more flavor-wise. Nevertheless, a bowl of berries is healthier than a bowl of cheerios.

Happy New Year to everbody.

Kytriya said...

ROFL This study sounds like another dogmatic attempt to prove that most Vegans will die of Heart Attack. The truth? Fruit and Veggies are no more harmful then sleeping at night or feeding Men Soy. (See 2nd Truth below, for explanation.)

The Truth: More non-Vegans die from Heart Attacks each year eating their flavanoid free animal then Vegans do in 20 years on a Vegan diet.

The Truth: If Soy really caused men to be impotent, then why is the Japanese and the Chinese population so high? Or, do the researchers really think that Asian's with their high Soy content is immune?

Yep, you can bias your research and your results to prove anything you want. And, if you use critical thinking, you can even find the truth and reason out the erroneous conclusions those biased researchers make.

Bottom line: In my opinion, most researchers are biased and can't be trusted. Usually, they are paid to prove something true, that might not be true. Thankfully, we have the PCMA that proved how a Vegan diet didn't harm Kidneys, the ADA diet (all animal meats) did harm Kidneys, and the control diet (fish and chicken) only had some damage to kidneys. Bias? It wasn't biased. If it would have been biased, they would have found more kidney damage in the Control group in order to prove the Vegan diet. And, at least one of the Doctors involved grew up on Bacon fat in North Dakota.

Martin Levac said...

Kobe beef is fed soy because soy is fattening. We feed our cattle corn because corn is fattening. We also feed our cattle wheat and soy because wheat and soy are fattening.

Gee, I wonder why we feed ourselves soy, wheat and corn. Maybe we want to fatten ourselves? Considering the current obesity epidemic, it sure looks that way.

Oh, you meant the soy-sterility thing? That's a moot point now.

Martin Levac said...


Considering the subject of this latest blog post, it would be more appropriate to say:

A bowl of berries is less toxic than a bowl of cheerios.

john said...


Yes, the last time I was in northern China, I remember drinking soy milk and eating tofurkey, not lard and duck fat.

The sad thing is that they now think their traditional diet is unhealthy because they don't have enough fruits and vegetables.

blogblog said...


The Chinese and Japanese eat very little soy - about 10g per day - less than many westerners. Soy products are used primarily as flavour enhancers in Asian cooking not as bulk protein.

The soy in Asian foods is nearly always fermented which denatures most of the toxic and allergenic proteins and renders the hormones inert.

Rates of cancers and strokes have plummeted in Japan as they have adopted high-fat western diets.

The supposed "longevity" of the Japanese is actually due to systematic welfare fraud and poor record keeping. More than 230,000 Japanese centenarians cannot be located by the authorities.

blogblog said...
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blogblog said...

Humans and our ancestors have been eating fruit for at least 55-65 million years. The probability that moderate consumption (<50g/day) of wild fruits is harmful to humans is therefore close to zero.

All traditional human societies actively seek out fruit as do most carnivores.

It is possible that anthocyanins are used primarily as pigments by plants. The antioxidant effects may simply be coincidental.

Most plants use sugars as energy reserves - not to attract animals. The plants with the highest sugar content - beets and sugar cane - do not produce edible fruits. These plants go to a lot of effort to protect their sugar stores from animals - buried tubers or tough stems.

Sugars are also used as effective anti-freezes by plants such as as potatoes and daffodils that must survive cold winters.

Antioxidants are unlikely to be intended to protect the plant against sugars. The vascular systems of plants are made of cellulose and lignin which do not react with carbohydrates.

There is typically an inverse relationship between sugar content and antioxidant content in plants.

Studies on isolated nutrients are absolutely worthless because they simply don't behave the same way as complete foods.

Matthew said...

Regarding the green tea study:

Some of the authors carried out a follow up antioxident depletion study with better contols in place. Full text is free.


Owen said...

Peter, I have a question I'm hoping you can give me your opinion on: how serious do you think oxidized cholesterol in food is? I seem to remember you saying you cook your egg yolks whole, rather than scrambled to avoid this issue.

This study found 12.3% of sterols were oxidized in a sample of ghee: http://www.ncbi.nlm.nih.gov/pubmed/2887943?dopt=Abstract

Of course I wonder how browned some Indians like their ghee, compared to something like French clarified butter, which isn't usually as toasted.

I worry because I've been eating about 8 tablespoons of ghee a day in place of butter, trying to avoid casein. Maybe I will try using Kerrygold Irish butter which is grassfed and may have more A2 casein than American dairy and be less problematic... I wonder what the common breeds of cow are in Ireland?

Peter said...

No time for more but to Owen, I don't worry about oxidised sterols at all. We wouldn't accummulate them in Lp(a) unless they are useful. I have a stack of links from Leib's work on THINCS showing oxidised sterols are great solubulisers of crystaline cholesterol (which appears to be bad). He makes an interesting case...


John said...

Peter, sorry if this is a weird question, but do you find you are still regular (IE having at least a bowel movement daily) on this type of diet? Did it take a while to adjust to, or do you think that most of the bacteria die off so you dont produce as much waste (since it is mainly water and bacteria that make up our feces).

Do you have to continually eat your fermented foods to maintain your bacterial population in your gut since you eat so low fiber?

nigel said...

Great Post! The anthocyanin flavonoids come with the added toxicity of CETP inhibition.

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Galina L. said...

What about fermented veggies? I almost always have homemade sourcraut in my fridge and it is what I usually have with my stake.It is not so sour and salty as the one in the store and could be eaten in place of a salad. My mother going even further and regularly consume fermented eggplants, tomatoes and cucumbers

Susan said...

Peter, Is your "what I eat" post still current. It seems you eat a lot of chocolate which is brimming with flavanols and procyanidins. Have you updated your diet?

karl said...

Did you see :

Owen said...

Thanks for the reference to Leib's views on oxysterols. I find it convincing too, and it's interesting that he notes that glucose promotes the crystallization of cholesterol. Also interesting were his comments about oxysterols being progressively eliminated from the human diet as refrigeration technology improved. I hadn't considered the amount of oxysterols that might form in eggs, butter or yogurt at even room temperature, so with this in mind, it's easy to imagine we've been adapted to this for some time.

Also, it was really cool to hear Gary Taubes mention Hyperlipid in both parts of his new interview with Jimmy Moore. Did you have a chance to listen to it yet?

braeside_golfer said...

Peter: I have been reading your posts starting at the beginning and I have a question from an old post about your use of dextrose powder as a sweetener. Does the dextrose cause less of an insulin spike than say sucrose and/or fructose? Thanks for great work. Ron

Galina L. said...

My husband has a theory that prehistoric people started to eat plans because people and plants have similar enemies - parasites in human case. As a prove he claims that people in a hot climate like India and Malaysia consume o lot of spices and consider it to be healthy.
His theory looks convincing. Primates like chimpanzees seek particular plants in order to get reed of internal parasites. Prehistoric people had to do the same. Why else we eat garlic, hot peppers, onion, mustard?
Peter, did you ever witness such behavior in animals?