Thursday, May 22, 2008

Gluten links from Bloggeier

My thanks to Bloggeier for these links, especially for the full text of the letter to GUT from the Spanish group.

These are various groups who are interested in innate gluten toxicity (GUT letter), non antibody investigation of food sensitivity and combined reactivity to gluten and casein in some coeliacs.

Quotes from the letter to GUT, which has restricted access:

"Nowadays it is assumed that an innate immunity to gluten plays a key role in the development of coeliac disease (CD). This innate response, mediated by interleukin (IL) 15 and elicited by "toxic peptides", like the 19-mer, through a DQ2-independent mechanism, induces epithelial stress and reprogrammes intraepithelial lymphocytes into natural killer (NK)-like cells leading to enterocyte apoptosis and an increase in epithelium permeability"

Try telling that to a Nottingham gastroenterologist!

"We consider that, to our knowledge, this is the first time that an IL15-mediated innate response to gliadin and gliadin peptides is described in individuals without CD, as well as an IL15-mediated innate response to the "non-toxic" deaminated immunodominant 33-mer peptide"

The 33 amino acid section is supposed to be non toxic itself (which turns out to be incorrect, it is toxic) but provides a focus for antibody production, which leads to severe secondary damage by the antibody. This still happens.

"Moreover, the IL15-mediated response in patients without CD was also triggered by the toxic 19-mer gliadin peptide (three of six) and, especially, by the 33-mer gliadin peptide (five of six). Importantly, none of the basal cultures produced this cytokine and, although not expected, the "non-toxic" immunodominant 33-mer was also able to induce an innate response"

Of their biopsy samples from NON COELIAC DISEASE people, one out of six did NOT respond to the 33-mer with interleukin 15. Five out of six did. I fully accept that there may be things going on with our immune systems to increase the frequency of allergies (grass pollen has always been around, hay fever was first reported just over 100 years ago as a case report in the Lancet...) but gliadin is directly toxic. It looks like allergy comes later, facilitated by toxicity causing intestinal leakage.

So it is just possible that maybe 1 person in six might NOT respond adversely to gluten. Notice that the researchers put "non toxic" in quotation marks, at least twice. These people know what they're talking about. I wonder if any of the group eat digestive biscuits with their coffee at lab meetings?



I'm not sure if I got the full text of the multimodal imaging paper through my athens account or if it's free access, but the interest this group has in getting away from crude antibody tests for food intolerance is impressive. Using some of their techniques would allow you to look at things like salicylate and amine toxicity, which probably have nothing to do with antibody production and very little to do with the immune system at all. The sort of sensitivity that gets you labeled as a malingerer in Nottingham...

Peter

18 comments:

Bruce K said...

"combined reactivity to gluten and casein in some coeliacs."

This study tested "dried cow's milk powder." It is unreasaonable to say that the same would occur with milk or cheese, esp the raw variety. All kinds of studies show that casein's toxic, but where are the studies on milk and cheese that show the same? Most people get reduced fat milk as well, which often has powdered milk added to it. It's reasonable to say that the results might be different if unprocessed foods were tested.

"things like salicylate and amine toxicity, which probably have nothing to do with antibody production and very little to do with the immune system at all."

I'm not so sure. The people having those sensitivities probably spent years damaging their bodies with a variety of drugs (recreational and pharmaceutical), alcohol, tobacco, PUFAs, junk food, stress, etc. Did hunter-gatherers exhibit such food sensitivities? Doubtful. Those are diseases of civilization caused by the modern diet high in toxic fats and sugars. If people had eaten in the proper way, their bodies would be immune to disease and stress.

http://raypeat.com/articles/articles/fats-degeneration.shtml
http://raypeat.com/articles/nutrition/oils-in-context.shtml

Peter said...

Bruce,

I don't buy in to the lack of food intolerances in "non-damaged" people.

Nightshades:

Deadly nightshade is deadly, unless you are a rabbit with an atropinase in your liver. Over half have of them have this enzyme, the rest don’t; it’s genetic.

Potato fruits (not tubers) are highly toxic, tomato fruits less so. The degree of tolerance to tomatoes varies from person to person, probably so does the tolerance to potato fruits. The failure to cope with potato fruits might result in death rather than the skin rash resulting from failure to cope with tomato toxins.

Anyone with a perfect liver and eating real whole foods is going to have real fun on potato fruits, or deadly nightshade berries. Tomato fruits suit most people, certainly not all.

On another plant:

Eating willow bark is no different from taking aspirin, except it's slightly more toxic as the salicylic acid, a plant toxin, is not had it's toxicity reduced (though far from eliminated) by chemical acetylation to give aspirin.

Why should natural foods be volunteering themselves to get eaten without fighting back in the most toxic manner they can?

Some people have better defences against plant poisons than others. A small percentage of people do very badly on plants. I don’t see why this has to be blamed on their other dietary indiscretions.

We’re talking chemical warfare and plants are damn good at it. We only eat the failures. Otherwise they do their best to kill us. Why should it be any other way?

By comparison meat is pretty helpless once it’s impaled on a spear or has been driven over a cliff.

Peter

gunther gatherer said...

Bruce and Peter,

On the natural toxins subject, have either of you read the studies by Bruce Ames at UC Berkeley? He claims that 99.9% of the toxins humans eat come from natural sources, as opposed to pesticides, pollution, etc.

Assuming we believe this (the study is interesting, so I urge you to look it up), we seem to be in the midst of an "evolutionary arms race", meaning plants evolve to make us carry their seeds and/or to fend off being gobbled by poisoning us, and we in turn evolve to process those very toxins, or at least to somehow neutralize them. This is basic evolutionary biology, I suppose. But where does that leave us?

Peter, you have a good point about the animal (which you have to hunt and kill) vs. vegetable (just sitting there almost "begging" to be eaten)paradox. If a plant has evolved to attract you with its phenotype and get you to ingest it, does it have your best interests in mind? Probably not. So by default, and somewhat counterintuitively, an animal which certainly does NOT want you killing and eating it is better for you? Animals have no use for humans. Plants do. And that says a lot right there about what they do inside us when we eat them.

Just plain Richard Dawkings: If an organism is trying to enter your body from the outside and get any kind of free ride, whether its a virus or a seed, it's not evolved to help you at all. Doesn't mean it will kill you, but definitely not designed with your interests at heart. An animal, though evolved alongside us, is not looking for a "free ride" in any way, and their evolution takes the same "path" as ours and they are most likely our "allies" (as in, they suffer too from plant toxins) in this plant/animal arms race, so I suppose they are better for us to eat in the long run.

And let's talk brains for a second: our brains must be this big for a reason. That reason seems to have to do with needing foresight, devising strategy and making tactical judgements in order to hunt. You don't see strictly vegetarian animals evolving big brains, because it's all too easy to pick a nice shiny red piece of fruit. Too easy, I would say...

Thoughts?

Thanks,
Gunther

Peter said...

Hi Gunther,

I certainly view plants vs animals as a war zone, with an on going evolutionary arms race most certainly. But it's not new, evolution IS an arms race, long term. The biggest mistake would be to think that it has stopped in some way at the present time. If nothing else, there is a huge selection pressure to locate those people genetically able to survive and reproduce well on "a diet of pure crap" (to steal Stephan's phrase re the current diet of the Pima, I just love this phrase).

Of course if you go to Richard Mannings ideas, available from Tracy here, you can regard a plant stratergy of making itself edible as a way of ensuring reproductive success, ie wheat in Canada etc. Obviously this is wheat using the development of agriculture to its own advantage...

Years ago I remember a paper on the evolution and counter-evolution in a war zone between mouse scabies and mice, with front line strung across Europe and moving north and south in waves, tracked by some sort of genetic markers. Each successful development in the mite was countered by one in the mouse and vice versa. This was years ago and I'd never find the paper again, but I remember thinking how interesting it was at the time.

I also see a distinct need for a Normal distribution of attributes. This is essential for surviving in a changing environment. But what happens at the extremes? To hark back to Emma's ideas, the genes for intelligence probably, if taken to the extremes available in the worst case scenario of those people with the least effective mono amine oxidase enzyme compatible with life, may well result in higher dopamine levels and a more focused/perceptive person than someone with a run of the mill MAO (That's an awful sentence, sorry!). Give that extreme person chocolate/cheese/sugar and they drop in to autism. Skip the chocolate etc and perhaps they will just be very very very intelligent.

This may be useful.

Peter

gunther gatherer said...

Peter,

We both agree on the evolutionary duel that takes place between all organisms. But I'm still confused about fruit and vegetables, because let's face it: the mammal who eats the fruit will eventually move its bowels at some point anyway, just like any other animal. What's the use of a plant evolving fruit to contain toxins that force mammals to place the free-riding seeds faster? And if the animal is useful to the plant in that it propagates the seeds for it, why would the plant who relies on the animal need to harm it at all? Is the harmful nature of toxins, fructose, PUFAs, etc. in plants just a by-product of the plant's greater reproductive needs that happens to cause us damage? I understand Nature's never been nice, and she sure doesn't care if organisms get hurt if it means better reproduction (ie. katydids who bite their mate's head off during sex, etc.), but it seems like a lot of time and energy for the plant to develop the toxins just to hurt an animal that helps it. I'm trying to think of the interests of the plant, and STRICTLY for the case of fruit, which "wants" to be eaten, I still don't see the logic. (Natural pesticides and poisons to ward off animals are something else.)

And now, a practical question framed for the 21st century with this in mind: You said somewhere that you dump the fruits and all fructose in favor of glucose (dextrose) as your means of staying just above ketosis. I've read your posts about fructose and its harm, but don't both glucose and fructose have to report to the liver for processing? This isn't really in line with JK's diet if you're hoping to reduce liver stress as much as possible.

Thanks for your help. The evolutionary context for optimal eating seems much more complex than I thought...

Gunther

Peter said...

Hi Gunther,

The prime gut toxin approach is wheat with it's gliadin, though many other herbs are simply purgative... I can see two reasons for this, seed transport with a rapid transit to minimise seed destruction. The other is straightforward toxicity to ward off consumption.

I can see very little use for fructose other than as a lure for seed consumption and it's greater sweetness would aid in this. But then you can argue that fruitivores find fructose attractive because it's good for them too... After all it does convert to fat easily. Just 10g/d is not the same as 300g/d. I don't have a ref but Eades claims that low dose fructose increases insulin sensitivity. So I still eat some sucrose in my chocolate and some fructose/sucrose in sweet potatoes, raspberries etc and a minute amount from potatoes. My total dextrose intake is probably under 5g/d, just in cocoa.

It's also very likely that substances such as salicylate, while fairly toxic to mammals, may in fact be aimed at fungal or bacterial infections, not mammals deliberately. We may well be getting caught in the crossfire while trying to do some looting in a war zone!

An interesting aside from the nightshade comments, there is a less toxic berry in the UK (probably world wide) called Woody Nightshade. Consuming the berries when green will result in profound CNS changes in humans, presumably other mammals too. As the berries ripen the alkaloid content drops and there is no tripping on the purple berries! Is the plant protecting the seeds until ready to let them go?????? Henbane, another nightshade, has small wind dispersible seeds and is simply toxic throughout plant and seeds at all stages of development. The plant is simply toxic for self defense and has no use for mammals.

Fructose is always directed to the liver and should never be present in significant concentrations in the systemic circulation. Not so glucose, it gets shared around from absorption onwards, some to liver, some to muscles, brain etc. I think Kwasniewski might want the 40-60g/d of carbs to stop the rise in fasting blood glucose which can happen in very LC eating. Some hepatic glycogen has its uses, undoubtedly.

Dr K doesn't talk in evolutionary terms at all really. He works more from straight biochemistry and logic, but never gives you all of the little nooks and crannies of metabolism that made him choose what he did. If I had continued to consume gluten, at say half a gram a day, would my changes in lipids have altered my immune system function to increase tolerance? Then I could drink beer. No way of telling now I'm so far clear of gluten that exposure produces a marked reaction every time. Interestingly Lutz, who did a huge amount of work with inflammatory bowel disease, doesn't eliminate grains. He is looking for improvement over several years, not weeks. Lutz certainly takes an evolutionary stance, so I find it a little odd that he doesn't go grain free with his IBD patients. Maybe the quick fix of gluten elimination stops the development of long term tolerance. With the effects of gluten whole body I'm not willing to be the one to try on-going low grade exposure to see if tolerance develops!

Yes, it's complex!

Peter

gunther gatherer said...

Hi Peter,

Thanks again for these interesting insights. They are definitely orienting me towards a more complete understanding of our modern-day predicament in terms of optimal lifespan and health.

So assuming we're able to avoid as many toxins, PUFAs and inflammatory agents as possible, keep our insulin as low as possible by keeping protein adecuate and dietary sugar low (or intermittent fasting), and avoid buildup of AGEs and oxidative waste products, etc., I'd be interested in knowing about the activity factor, something which you don't address in the blog.

Using the evolutionary model and context for optimal eating, isn't all eating, for all animals and throughout our evolution, associated with activity of some kind? Not exercise by our definition or running, biking or lifting weights, but traditionally ALL eating meant activity. The two are inseparably linked if you've going to kill and eat another animal.

I´ve seen conflicting studies on exercise. Cardio seems to cause chronic inflammation which affects immune function and creates lots of oxidation products and you see distance bikers and marathon runners getting cancer and heart disease. Alberto Salazar, Greta Waitz, Lance Armstrong, etc.

On the other hand, there is reliable research showing that weight training and briefer, more intense exercise raises insulin sensitivity. But it creates lactic acid, which I'm not sure we need running around our blood stream any more than necessary. However, this is much more in line with our evolution. I doubt we ran marathons every day in the Kalahari, and I'll bet we only even became active when we absolutely had to (ie. hunger!).

I'd love to see a blog on whether exercise has ANY health merit at all. I notice you gave up exercising. Was this a health choice or just out of convenience?

I have to admit, I've never seen anyone lose weight with exercise, or improve their health much at all... In fact, my appearance and vitality didn't really change over the years I spent at the gym, that is until I practically gave up the gym and concentrated on changing my diet... Makes me wonder if we're healthier without it...

Thanks,
Gunther

Peter said...

Hee hee, I break concrete, lay paving slabs, gut bathrooms, carry an 11.5kg weight large chunks of the time (my son) and am about one third of the way through digging the first plot of my 3 plot allotment. I think Chris talks about functional exercise... This is pretty functional and leaves no time for the gym! I've had to stop the pushbike hill climbs as they had to be mid morning, again dictated by my son, and there is a major pipe laying project going on at the top of the hill. This involves a large number of HUGE earth shifting lorries. The first one that overtook me during the climb forced me on to the bank, after several horn blares. Got a fantastic view of its undercarriage and back wheels, from far too close! So digging is in at the moment.

Do you read Chris' blog? No need for re inventing the wheel!

BTW Barry Groves is VERY anti exercise. I enjoy it. Just might get surfing next weekend...

Peter

scott said...

I was just spending a pleasant evening re-reading some of your posts. Sorry for asking this off-topic, but question arises regarding dextrose powder, used by you for sweetening cocoa and ice cream. Does the source of the dextrose matter? Seems that most easily available stuff comes from grain like corn. But dextrose is dextrose once it has been processed, right? No grain baggage left in it?

Thanks and I really enjoy your work, check for updates every day.

Scott

Peter said...

Hi Scott,

I'd expect the refinement process to be pretty effective in producing pure dextrose from corn. But before we went to tapioca flour my wife occasionally used corn flour in pretty small amounts and neither of us had any obvious reaction to this, sooooo...

Just checked the packet, no mention of gluten free, but then not quite everything tells you!

Peter

ItsTheWooo said...

Peter,
I totally agree with your point of view regarding the toxic nature of many "natural" food stuffs. I find it very difficult to tolerate the mentality that "natural is good" that seems to spread on dieting and health forums. It is totally irrational, and I'm pretty sure it stems from an intuitive religious perspective (that humans are the center of the universe and everything else natural around is just there for us to use, all self sacrificing-like).

However I don't necessarily agree that meat is comparatively harmless. In the natural world, meat is a very dangerous as well as nutritious food, it's loaded with bacteria because frankly it is dead and decaying. The female hormones promote nausea, and in the first trimester of pregnancy they can be so high that morning sickness results. Morning sickness, and estrogen nausea, invariably produce an aversion not to plant food but to meat, coffee, and other strong smells/flavors that are vaguely bitter and/or meat like.
Scientists hypothesize morning sickness was evolutionarily adaptive; the fetus is most vulnerable to damage in the first trimester. Anything that tastes/smells bitter or strongly meaty is probably toxic to a vulnerable <3 month old fetus, therefore, the mother cannot consume these potentially dangerous foods.

One of the reasons sudden low blood sugar with high fat burning tends to produce nausea is because this condition is associated with pregnancy, or rapid growth, a time of particular vulnerability to toxins. People think ketones cause nausea. No, ketones aren't nauseating; low blood sugar with high fat burning is nauseating. This is another major cause of first trimester morning sickness.

Fruit is probably one of the least toxic foods, and while no means nutritionally complete, it is the easiest to tolerate while nauseated and metabolically vulnerable. I agree with Gunther, I don't think plants need to poison us to make us spread their seeds. They just have to make a non-essential seed carrying part of themselves sweet, colorful, and not pungent or bitter or toxic like the plant itself. We'll gobble the fruit and leave the seed with a pile of fertilizer somewhere.

But the plant part itself is probably toxic, as well as bitter and gross, to dissuade animals from eating it.

ItsTheWooo said...

This is sort of an off topic comment but I was wondering what was your opinion of dry vs moist cat food? I've always opted for canned cat food, particularly those with very little corn or carbohydrate in it (diabetes is a huge problem for cats). My vet told me that dry food is better for cats because it doesn't muck up their teeth and prevents kidney stones.

Knowing that human doctors know screw all about human nutrition, I am obviously wary about what a cat doctor thinks about cat nutrition. The food he recommended I buy my cat had rice and corn in it, and he clearly had no idea why cats get diabetes (he just gave that vibe like he didn't understand it was from the carbohydrate being fed to a carnivore). So, I especially doubt he is correct.

Since you are both a vet and understand proper diet, if you had to feed a pet commercial food, is it better to go moist or dry? Assuming, of course, the moist food is the pure meat kind (which, ironically enough, is usually the store brand or the plain non-fancy cat food).

I also thought it was interesting that they said my cat looks like he's 8 or 9 (he's 14). They couldn't believe how old he was. My cat has always had a low appetite so calorie restriction may have something to do with it... but I'm sure that making sure not to feed him carby cat food might have had something to do with it too.

ItsTheWooo said...

Oh and one more thing (this time related)... I always found it interesting that a discrepancy between positioning and balance would produce nausea. Superficially it seems pointless, but given that so many toxins affect the CNS first, it must have been evolutionary adaptive in the past for our hunter gatherer ancestors to upchuck their guts the moment position and space stopped making sense.

I bet we can learn a lot about what is or is not dangerous to eat in a natural world by studying the conditions and quality of nausea in modern people. Meat and bitter pungent aromas (like coffee) produce profound nausea when estrogen increases, presumably to protect an early pregnancy. Car sickness tricks our brain into thinking we were poisoned, so we vomit. And, few things are as emetogenic as seeing your friend vomit. The profound reflex to vomit by seeing or smelling vomit is probably also adaptive (if yer friend ate the green berries, you probably ate them too; at worst you lose a few hundred cals of nutrition, at best you save your life).

Peter said...

Quickie on cat food: Meat, animal derivatives, vits/mins, permitted colourants is about the best commercial cat food you'll find. Will probably contain MSG and other excitotoxins in the animal derivatives, which may not be completely without pancreatic effects and cats are absolutely capable of alzheimers, but it's far better than the cr*p-in-a-bag we vets love. The CIAB doesn't clean their teeth much either! At least one old style canned food claims that cats self regulate their appetitie on tinned food. Pouches (contain high fructose corn syrup!) and the micro tins (dunno what they do to these, but terminal moribund cats will occasionally eat them as their last act in life, scary!) are very different.

Peter

Peter said...

Hi ItsTheWoo,

Too slow getting back on this one,but yes, I can see what you mean re nausea and the advantages of group vomiting! Do you have any info on blood glucose levels and hyperemesis of pregnancy? My wife had this very badly. I followed it through HCG, hyperthyroidism and possibly phase two hepatic enzyme inactivity but never got to the bottom of it.

I've seen one paper suggesting high fat diet is a trigger and another that low fat veganism (Peter vomits quietly in the corner) is protective, but both, though in medical journals (I think), were single case reports. I'm now wondering whether a higher carb in take, of paleo carbs, might be the route for the next time around... Need more data and I'd not gone the glucose route. Ketosis is a big result, never thought it might be a cause.......

Peter

Ed said...

Hi Peter,

Looks like the whole letter is public now,

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1954879/

Ed said...

According to wikipedia (it's unreferenced, so ... ), quote:

"In humans with history of acute infectious mononucleosis (the syndrome associated with primary Epstein-Barr virus infection), IL-15R expressing lymphocytes are not detected--even 14 years after infection."

Suggesting that getting the Epstein-Barr virus will mean you can't get full blown celiac disease... now that's an odd thought.

Recent work by Arranz and his group, if I'm reading it right, notes that the primary difference between celiac and non-celiac is the interleukin 15 receptor expression.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2561095/

quote

Figure 1 shows that the expression of IL15Rα mRNA is higher in CD patients, with independence of gluten ingestion (CD patients on GFD, median 4·320 U; CD patients on a gluten-containing diet, median 7·921 U), when compared with non-CD controls (median 0·795 U, P = 0·0334 and P = 0·0062, respectively).

chart:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2561095/figure/fig01/

Ed said...

Sorry for the flurry of posts, but this was interesting in that most recent paper.

"However, this model does not seem to reflect the in vivo situation, where the gliadin-induced IL-15 should be expected to have some biological effects in non-CD individuals (thought not enough for triggering the adaptive response), as suggested by the finding of IL-15 not only in the whole protein biopsy explants but even in culture supernatants after gliadin challenge, which excludes an intracellular storage of the cytokine. Therefore, after a normal gluten-containing meal, some IL-15-driven effects should be expected in all individuals (i.e. dendritic cell activation, intraepithelial lymphocyte NK-like reprogramming, increased tight-junction-mediated permeability, or enterocyte apoptosis through NKG2D-MICA interaction). Nevertheless, gliadin seems to be well tolerated by the majority of the general population and the features mentioned above are specific for CD patients."

It's that last part, "gliadin seems to be well tolerated by the majority of the general population." Really?

Anyway, this paper suggests that the difference between a celiac and a non-celiac is a matter of degree: if you produce "more" interleukin 15 receptors, you are more likely to be celiac. This might go a way towards explaining both why we still have celiacs even after 10 thousand-ish years of gluten challenge, and why the incidence seems to be rising in recent decades. We may all be latent celiacs, just waiting for the conditions at which we produce more IL-15 receptors. *shrug*