Around the Web; and Why Is Aspirin Toxic to Cats?

[1] Interesting posts this week: Melissa McEwen assures us: Robb Wolf is not Satan. Kurt Harris’s reader Tara makes the most persuasive case I’ve seen for grass-fed meat through pictures. Emily Deans compares eating disorders to addictions.

[2] Kurt Harris re-re-brands: Paleonu became PaNu became Paleo 2.0 becomes, archevore being a neologism for “one who eats of the essentials.”

Well, it’s more euphonious than “EM2vore,” for “one who eats of the evolutionary metabolic milieu.” A more descriptive name might have been “nontoxivore,” since Kurt’s primary theme is avoidance of “neolithic agents of disease – wheat, excess fructose and excess linoleic acid.”

It will be interesting to see where he’s taking this. Are Archevorean essentials the same as PaNu?

[3] Posts of the week: Chris Masterjohn posts always deserve special notice. On Tuesday he continued his important series investigating whether wheat causes leaky gut, which will trigger a few edits in the next edition of our book. I was asked about this last Saturday and said:

There’s no question that gluten causes problems in non-celiacs – that’s the main result of the Fasano paper Chris cites, and also of papers cited by Andrew Badenoch in a post I linked today. It’s just that leaky gut does not appear to be one of those problems.

It certainly doesn’t mean that wheat is safe to eat.

I may add that pathogens and other food toxins – even perhaps other wheat toxins besides gluten – can cause a leaky gut, providing a way for wheat toxins to enter the body. Moreover, some wheat toxins don’t even need a leaky gut to enter the body. As we discuss in the book (p 134), wheat germ agglutinin can cross barriers via transcytosis, enabling them to enter the body even if the intestinal barrier is intact. Finally, wheat toxins can damage the gut without entering the body at all. So there are many pathways through which wheat toxicity can matter.

Chris had another outstanding post on Friday, about fatty liver disease.

[4] Rosacea is an infection of the skin and vessels: That’s why it can be transmitted through facial skin grafts.

Source: Kanitakis J. Transmission of Rosacea from the Graft in Facial Allotransplantation. Am J Transplant. 2011 Mar 28. [Epub ahead of print]

[5] Special offer: The folks at Emerald Forest Xylitol noticed that we recommend their product and would like to give a special offer to readers. Use the coupon code FIRST to get 10% off all products at

Also, Matt Willer of Emerald Forest Xylitol is looking for recipes that include Xylitol for use in his newsletter. If you have a recipe, send it to

[6] Animal photos: If you saw a grizzly charging straight toward you, would you stop to take this photo?

Photographer Alex Wypyszinski did in Yellowstone. The grizzly was chasing an injured bison, and the pair went right past him:

For the full story, see Grizzly versus Bison: the rest of the story (Drew Trafton, 10/29/10, KRTV, Great Falls, Montana). Hat tip Orrin Judd.

[7] Don’t hate the sun: From Britain comes the sad story of a 21-year-old who “hated the sun” and died of skin cancer at 21.

Dr. John Briffa has a summary of the relevant science.

[8] I couldn’t disagree more: Mike the Mad Biologist and Newt Gingrich are dead wrong in their prescription for research funding. We don’t need more concentrated funding, we need more distributed, decentralized funding that is patient-driven, not top-scientist driven.

Discovering cures can be cheap – if you’re looking in the right place. If you’re looking in the wrong direction, the cost of a cure may be infinite.

[9] I hate when that happens:

(Via Stephen Wangen)

[10] Are choline supplements toxic?: At the very beginning of the book (p 3) we state that “the perfect diet should … deliver … no excess nutrients for pathogens.”

Later in the book we give examples of nutrients that, in excess, primarily benefit pathogens: niacin (the primary vitamin for bacteria), iron (critical for metabolism of most pathogens, and a component of bacterial biofilms), and calcium (a component of bacterial biofilms). These are on our list of micronutrients we recommend not supplementing (beyond a multivitamin).

Two readers, Leonardo and Patricia (thank you both!), emailed us about a ScienceDaily article suggesting that choline, one of the micronutrients we most frequently recommend, should be added to this list:

When fed to mice, lecithin and choline were converted to a heart disease-forming product by the intestinal microbes, which promoted fatty plaque deposits to form within arteries (atherosclerosis); in humans, higher blood levels of choline and the heart disease forming microorganism products are strongly associated with increased cardiovascular disease risk.

The story didn’t have enough information, so I downloaded the paper. The paper notes that choline is metabolized by gut bacteria to a gas with a fishy odor called TMA, which is then oxidized in the liver to a compound called TMAO:

Briefly, initial catabolism of choline and other trimethylamine-containing species (for example, betaine) by intestinal microbes forms the gas trimethylamine (TMA), which is efficiently absorbed and rapidly metabolized by at least one member of the hepatic flavin monooxygenase (FMO) family of enzymes, FMO3, to form trimethylamine N-oxide (TMAO).

They showed that (a) feeding phosphatidylcholine from egg yolk to mice led to increased blood levels of TMAO and that (b) in a separate study, people with atherosclerosis have elevated blood levels of TMAO, choline, and trimethylglycine.

Supplementing choline at 10 times normal levels to Apoe-knockout mice led to increased TMAO but not choline in blood:

Atherosclerosis-prone mice (C57BL/6J Apoe-/-) at time of weaning were placed on either normal chow diet (contains 0.08–0.09% total choline, wt/wt) or normal chow diet supplemented with intermediate (0.5%) or high amounts of additional choline (1.0%) or TMAO (0.12%)….

Analysis of plasma levels of choline and TMAO in each of the dietary arms showed nominal changes in plasma levels of choline, but significant increases of TMAO in mice receiving either choline or TMAO supplementation (Supplementary Fig. 10).

Serum TMAO levels were correlated with atherosclerotic plaque size and with macrophages turning into foam cells:

[A]ll dietary groups of mice revealed a significant positive correlation between plasma levels of TMAO and atherosclerotic plaque size (Fig. 3e and Supplementary Fig. 9b).

TMA (a gas with a fish odor) has to be converted in the liver to the toxic TMAO in order to produce these bigger atherosclerotic lesions. This conversion happened mainly in mice with low HDL:

Interestingly, a highly significant negative correlation with plasma high-density lipoprotein (HDL) cholesterol levels was noted in both male and female mice (Fig. 4b and Supplementary Fig. 12, middle row).

So if you’re an Apoe(-/-) mouse and eat ten times normal choline, if you have high HDL your arteries are safe but you smell fishy; if you have low HDL you smell fine but your arteries get injured.

What does this tell us about choline supplementation?

For humans with working ApoE alleles, I doubt we can infer anything yet.

For Apoe(-/-) mice fed ten times normal choline, I would suggest shooting for low HDL while dating, then high HDL after marriage.

Reference: Wang Z et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature, 2011; 472 (7341): 57 DOI: 10.1038/nature09922

[11] One-upping the standing desk: Jamie Scott has a walking desk:

[12] Why is aspirin toxic to cats?: In the book we mention that plant foods always contain toxins, but animal foods don’t – because in poisoning us, animals would poison themselves. As we point out in the book, Bruce Ames and Lois Gold estimate that over 99% of the toxins humans ingest come from plant foods – not industrial or environmental toxins.

One of the main functions of the liver is detoxification. A healthy liver enables us to consume plant foods.

But what happens to the livers of animals that never eat plant foods? If they and their descendants avoid plant foods for millions of years, how would their livers evolve?

The answer is in a fascinating piece by Ed Yong at Discover blogs: “Why Is Aspirin Toxic to Cats?”. The puzzle:

[C]ats are extremely sensitive to aspirin, and even a single extra-strength pill can trigger a fatal overdose.

Some scientists have been investigating this puzzle since the early 1990s. It turns out that all 18 of 18 species of cat studied, including housecats, cheetahs, servals, and tigers, have crippling mutations in a gene involved in liver detoxification. The same gene is also lost in other hypercarnivores, including the brown hyena and the northern elephant seal.

Mr. Yong explains:

Like many other “detoxifying” proteins, UGT1A6 evolved to help animals cope with the thousands of dangerous chemicals in the plants they eat….

But if an animal’s menu consists largely of meat, it has little use for these anti-plant defences. The genes are dispensable…. [T]he ancestral cats gradually built up mutations that disabled their UGT1A6 gene. Evolution is merciless that way – it works on a “use it or lose it” basis.

So – millions of years of hypercarnivory will disable the liver’s ability to metabolize toxins.

Pet owners, be kind to your cats: Don’t feed them plants!

And a new zero-carb danger: After ten thousand generations, your descendants may be unable to take aspirin.

Reference: Shrestha B et al. Evolution of a Major Drug Metabolizing Enzyme Defect in the Domestic Cat and Other Felidae: Phylogenetic Timing and the Role of Hypercarnivory. PLoS One. 2011 Mar 28;6(3):e18046.

[13] Not the weekly video: Best mobile phone commercial I’ve seen:

[14] Weekly video: I grew up near the University of Connecticut campus and have been a fan of their men’s basketball team since the late 1970’s. What Jim Calhoun has done there, building a minor program to national prominence and three championships, is one of the great accomplishment in coaching history. And this year’s team was a minor miracle: with unheralded and under-recruited freshmen playing half the minutes, they won a national championship.

Every year CBS makes a video montage of the tournament. Here it is, One Shining Moment:

Leave a comment ?


  1. Re rosacea, have you seen Art Ayers’ posts at Cooling Inflammation? Good stuff.

  2. Yes, Beth. I don’t agree with him about the etiology, but his posts are always interesting.

  3. The blog was called PaNu from day one – that domain was taken so the url was paleonu. I never called anything by the paleonu moniker.

    The 2.0 is just a descriptive term and essay and never proposed as the name of the blog.

    So the only change is from calling the blog PaNu to calling it Archevore….

  4. Hi Kurt,

    Thanks … we’re looking forward to your book.

    Best, Paul

  5. The reason I secure grass fed meat is worry about nutritionism – all those little parts are in all the right balance in a grass fed animal. I doubt we are smart enough to figure out all the details.

  6. Had a walking desk Paul!! That is where I was standing when our Feb 22nd hit. The desk itself came through very well… the wall with the New York city scape is a bit worse for wear. Luckily, the bike wasn’t in the office that day!

    On standing vs. walking desks; I always found that standing in a fixed position for 2-3 hours at a time is just as hard on the body as sitting. When I did use the desk standing rather than walking, I would tend toward getting very sore knees, and over a period of days, very sore feet.

    As far as back & postural health goes, standing is most certainly preferable to sitting, but there is simply no subsitute for moving through a variety of planes.

    Thanks for your take on the choline study… a bit beyond me that one based on the limited info in the Science Daily report.


  7. Hi Jamie,

    I’ve recently begun using a standing desk. Early returns were stiffness in my legs, butt, and lower back, which I’m now over with; and sore feet, not used to bearing full body weight all day.

    Now I have a cushioned bench that is just the right height for kneeling on, and I alternate kneeling with standing.

    I also try to do some stretching postures — one foot up on the desk, for instance. I sway and shift a lot, and leave my desk more often now.

    I’m still getting used to it, but I think it’s going to be good. For the moment my productivity is a little reduced.

    Still a few mysteries for me in the choline paper — like why atherosclerosis patients, who eat less choline, have higher circulating choline. But Nature seems more interested in the Apoe-/- mice.

    Best, Paul

  8. That is very strange about the atherscerosis patients as, at least in women of childbearing age, serum choline varies inversely with homocysteine.

  9. Yeah, they didn’t present the data, just a spline-fit curve to the data that showed CVD risk rising with serum choline levels. Normal was about 7 microM serum choline, double risk at 11 microM, quadruple risk at about 20 microM. 95% confidence intervals were surprisingly narrow. It’s a very surprising result but the paper has very little discussion of it, except to say that individuals in their cohort who had high TMA levels often became vegetarians to reduce the fishy odor from choline metabolism!

    I find it all a little too pat (i.e. anti-fat, anti-animal food) to be true. But, it makes me curious whether there are other studies of serum choline levels.

  10. It’s quite terrifying what happened to that young girl. For five years straight, since I was sixteen, I became obsessed with slathering on sunscreen to protect myself from the sun. I took advice from various forums to apply sunscreen even indoors to protect myself. I’m glad I have stopped that nasty habit, but hopefully my sunscreen use hasn’t damaged me in any way, those things are loaded with unnatural chemicals.

  11. Emily,

    This paper may shed some light on the choline issue:

    Phosphorylcholine is a phospholipid on some bacteria and on oxLDL. Natural antibodies against this clear this form of choline from the blood and also fight the bacteria. In the process they protect against atherosclerosis and CVD. Immunization with anti-phosphorylcholine antibodies is protective against atherosclerosis and CVD.

    So it may be that people with impaired immune defenses have higher phophorylcholine and this is what they are detecting.

  12. Ghee, why didn’t anybody tell those poor animals that you shouldn’t run barefoot on asphalt? Where is PETA when you need them?

    SCNR… 🙂

  13. Great collection (as always!)! I love the mobile phone video, I was slack-jawed by it!

  14. Hey Paul,

    I just finished listening to your interview with Jimmy Moore,
    I was wondering if your Rosacea did actually cleared up after changing your diet? if so, how long did it take?

    Thanks :).

  15. The girl with skin cancer sounds eerily similar to me. I am exceptionally pale and up till last year I used spf 100 religiously. I am going to try to build up a tan this year, but with tennis being 6 or so hours outside every day, I’ll probably still have to use some type of sunscreen.

  16. Paul, how long before the benefits of Choline kick in?

    I’ve been following the PHD cum supplements (stopped Iodoral and Vit. K for four weeks while I took Coumadin following knee replacement surgery) scrupulously for six months and 500 mg of Choline for a month and still have quite a bit of joint pain and pain the area around the incision.

    Three days ago, I added a tablespoon of CMT and aside from a couple of gastric eruptions the first day, I’ve tolerated it well I think. BTW – although it is very greasy/oily, it is absolutely taste and odor free — big plus for me.

    I also loved the wooden cell phone video and look forward to your Saturday posts to see what’s caught your interest in the previous week!

  17. Hi Danny,

    I’m preparing an upcoming series on rosacea and acne.

    My rosacea gradually improved over about 2 years on the diet, and wasn’t obviously visible this winter. Then I experimented with lithium supplements at the beginning of March and it came back dramatically, in just a few days. I took advantage of the opportunity to experiment with various home treatments, some of which made it worse, some better. I’ve got to say, the remedies publicized on the Internet are mostly awful.

    But the experience allowed me to test and refine a protocol I had in mind, which has worked extremely well at clearing my rosacea – about 3 weeks to clear the whole face. When I do the series I’ll put some pictures up.

    I don’t think all rosacea cases are exactly the same, but I expect what is working for me will also work for many others.

  18. Paul,

    just listened to an interview with Art De Vany ( where he suggests that it is actually bacteria that misuse the gut damaging effects of gluten to get inside the body.

    This would explain the many differences people have when exposed to grains + the difficulty proving this in vivo/vitro.

    Also have you read the excellent website :

    They claim that much of the IBS ailments can be attributed to gut parasites.

    Personally, I can attest to the fact that my tummy ‘blows up’ 10 minutes after eating bread/pasta/rice/beans … not so much with sugar.
    It returns to normal after 30-45 minutes.

  19. Hi Abby,

    Tanning is mainly a reflection of vitamin D status. When D is low you won’t tan. When D is high you start tanning. If you supplement D you’ll find you tan very quickly with sun exposure. Of course, with your sun exposure I wouldn’t supplement D at all. Just skip the sunscreen for your first 30 minutes – use it only enough to stop burning.

    Hi erp,

    Choline is not for wound recovery or pain reduction, it should help with weight loss however.

    For wound recovery high-dose vitamin C (up to 10 g/day) is most important. Some are helped by niacinamide (maybe 300 mg/day). If you have any negative reactions to niacinamide stop immediately, it promotes bacterial infections. In general the B-complex vitamins, the A/D/K2 complex, and our recommended minerals are important.

  20. Hi Ahrand,

    I agree that IBS is caused by pathogens, and with Art that wheat and pathogens together are a bad mix. In biology problems usually compound each other, and wheat toxins + pathogens may be 10 times worse than either individually.

    It is hard to prove though! There aren’t good in vitro models for the intestine, and it’s hard to see the details in vivo.

    Your experience may also speak to location of the pathogens — sugars are absorbed earlier in the small intestine than complex plant foods, so the grains and legumes penetrate farther down the bowel and thus can feed pathogens in those locations much better than sugars.

  21. Hi Paul, I recently ordered your book and can’t wait to read it and learn a ton more. I am looking forward to your posts on acne and rosacea. I think many people will benefit from them.
    I was also wondering why you recommend synthetic vitamins (Centrum) instead of whole food based ones?
    Also do you consider plantains a safe starch? I remember really enjoying them when I was traveling in Costa Rica a couple of years ago along with some gallo pinto(Beans and rice). I know the beans are not on the PHD, but it did make for a delicious meal :-).

    All the best

  22. Hi Hans,

    Whole food vitamins are better, we just recommend Centrum out of consideration for those living on a budget.

    Yes, plantains are a safe starch, and recommended.

    I had some Brazilian friends who frequently ate their version of gallo pinto. As you say, beans are not PHD, but any meat can be substituted. We much prefer Cambridge Fried Rice:

    Best, Paul

  23. Paul, which B vitamins to you recommend?

    I just googled vit. C to find out where I can get large dosages in one pill and the PHD came up twice on the first page.

    Way to go bro!

  24. Hi erp,

    We recommend all of them except niacin and folic acid. Niacin can be taken temporarily for wound healing in those who don’t have bacterial infections.

    B-50 complexes are an easy way to get all of them … I wouldn’t do this every day (too much folic acid and niacin), but temporarily.

    I think we probably came up at the bottom of the page under “Results for people in your social circle – BETA.” Our page rank isn’t high enough to get us near the top of a popular search. I wish it were so!

    Best, Paul

  25. I had sun damaged skin from sunbathing way too much – ie lots of burns as a teen. In my 40’s I started getting a lot small round rough patches (typical sun damaged skin). I figured out I was probably highly D deficient after 20 years of sun avoidance and sunblock. When I took D supplements the rough spots just went away.

  26. Hey Paul !

    Any update on the Acne & Rosacea ETA ?

    Thank you for sharing your knowledge. You’ve helped so many 🙂

  27. Hi Davor,

    I’m trying to finish some non-blog business obligations before I do research-intensive posts.

    In the meantime, there’s going to be a hypothyroidism series guest-posted by Mario and I might go back and finish the LDL series before getting to rosacea/acne/infections which is quite a big topic.

    Sorry for the delay. I know people are waiting.

    Best, Paul

  28. About the standing desk…the very best desk ‘chair’ I have found is one of those really big exercise balls. You can move side to side, front to back, around in a circle (hoola hoop-like), you can also bounce and it promotes very good posture. I also have one that is in a holder of sorts, but I prefer the plain ball.

    This blog is endlessly interesting, I wish I could take more time to explore it.

  29. Hi Paul.

    As a follower of PHD, I have been trying to eat liver once a week in addition to 2 -3 eggs daily because of choline.

    One of my friends forwarded the below article about the choline and prostate cancer relation and I was scared. Is this something we should be worried about choline?

    Thank you very much for all the useful information.

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