Tuesday, December 25, 2012

Beyond Celiac: Study Sheds New Light on Obesogenic Effects of Gluten - Are PPARs & Bacteria Both Involved?

Cornflakes peanut butter cookies - guaranteed not gluten free ;-)
With Christmas Eve being over, and grandma's cookies, Christmas stollen, and all sorts of other stuff from the bakery in front of you (literally), Christmas Day may actually prove to be a way more "dangerous" than Christmas Eve - not just because of the total amount of calories, but also because of the low satiety effect of these sweet treats.

A recent paper by scientists from the Universidade Federal de Minas Gerais in Belo Horizonte in Brazil does now point to another reason you better give those bakery products a wide berth - not just, but especially with the energy overshoot on Christmas day: Gluten!

Study confirms for the first time what scientists and laymen alike have been speculating about

In what the scientists claim is the first well-controlled study of the effects of gluten intake on metabolic health in a non-celiac, but Western-style diet scenario, Fabíola Lacerda Pires Soares and her colleagues put two groups of C57BL/6 mice on identical, iso-caloric high fat (hypercaloric) diets that differed only in terms of the amount of gluten that was added to the chow (0% gluten vs. 4.5% gluten).

Interestingly, the gluten diet did not influence any of the usual suspects, like food intake, total fat-free mass, fecal lipids excretion, blood lipid profile, blood total protein and ectopic (liver and muscle) lipid concentration (if you look closely you will realize that the gluten-free group actually had higher TRIGs, although the difference did not reach statistical significance).
Figure 1: Usual suspects and closer look at the effects 8 weeks gluten supplemented vs. gluten-free diets had on serum markers of metabolic syndrome and visceral fat parameters (Soares. 2012)
The data in figure 1 (right) does yet also show that the gluten content of the diet did nevertheless have a significant impact on the total body mass, visceral fat mass, lipid content and most importantly the adipocyte size.
Figure 2: Absolute adipokine levels (left) and fasting glucose and insulin levels, as well as Homa-IR (Soares. 2012)
Add to that the blunted expression of the anti-inflammatory and anti-diabetic fat hormone adiponectin and the increased the >5x higher expression of leptin (figure 2). And mix that with the reduced expression of PPAR-alpha and gamma of which Soares et al. argue that they may well be the key factor in the detrimental modulatory effect the addition of gluten had on the visceral fat structure and the lowered expression of the fat liberating enzymes LPL and and HSL, as well as reduced levels of the fat burning proteins ACC and CPT-1 (figure 3).
Figure 3: PPAR-alpha, -gamma, LPL, HSL, ACC and CPT-1 expression compared to rodents on regular chow (left); crown like structures in stained slices from visceral fat, inflammatory markers TNF-alpha and IL-6 (Soares. 2012)
So, even if the initially mentioned blood markers (aka the usual suspects) would suggest that both the gluten-consuming and gluten-free rodents were similarly bad off, the profound difference in inflammatory markers within the adipose tissue and the presence of comparatively many necrotic and inflammatory adipocytes in the crown like structures stand in line with increases in HOMA-IR, fasting glucose and insulin and an already compromised glucose clearance which are well-known harbingers of the metabolic syndrome.

These observations do not simply shed a whole new light on a hitherto largely ignored contributer to the etiology of the metabolic syndrome, they do also show that one of the reasons it has not been identified before is an over-reliance on BMI, total fat mass and serum lipids in the early stages of diabesity.

Reardless of whether the gut microbiome is part of the mechanism by which gluten predisposes the development of metabolic syndrome. Eating more inulin- and beta-glucan rich foods like Jerusalem artichokes, agave, bananas, onion, steel cut oats, wild yams, yacon, etc. certainly won't hurt your efforts to get lean, stay lean and leave the role of the obese diabetic to the other (read more)
Bottom line: The study at hand provides a good reason to limit your intake of "healthy whole grains" and other gluten containing foods, regardless of whether you suffer from celiac or not. Whether the established detrimental effects of gluten on the integrity of the intestinal wall and the increased leakage of bacterially produced endotoxins from the highly unfavorably changes in the gut microbiome in response to the high fat diets (Hildebrandt. 2009) are part of, or even the primary cause of these observations still has to be elucidated. The same goes for strategies to counter the translocation of the endotoxins across the gut lining (cf. "Shedding some light on the leaky gut") and the dose response relationship between the total amount of gluten in your diet and its effects on your metabolism. With 7% of pure gluten, it goes without saying that you would basically have to live of wheat in order to get to anywhere similar amounts of gluten in the diet... that said: Is it possible that the effects occur only in the presence of the high fat diet? After all, this alone has been shown to favor a pro-inflammatory gut microbiome.

You see there are enough questions to be answered in 2013 and the SuppVersity is going to be the place you will read the respective answers first ;-)

  • Hildebrandt MA, Hoffmann C, Sherrill-Mix SA, Keilbaugh SA, Hamady M, Chen YY, Knight R, Ahima RS, Bushman F, Wu GD. High-fat diet determines the composition of the murine gut microbiome independently of obesity. Gastroenterology. 2009 Nov;137(5):1716-24.e1-2.
  • Soares FL, de Oliveira Matoso R, Teixeira LG, Menezes Z, Pereira SS, Alves AC, Batista NV, de Faria AM, Cara DC, Ferreira AV, Alvarez-Leite JI. Gluten-free diet reduces adiposity, inflammation and insulin resistance associated with the induction of PPAR-alpha and PPAR-gamma expression. J Nutr Biochem. 2012 Dec 17.


  1. typo: (if you look closely you will realize that gluten group actually had higher TRIGs, although the difference did not reach statistical significance) <-- should be the gluten free group

    Great stuff! My girlfriend will probably just become more zealous over not eating gluten after seeing this.

    It'd be nice to see this done in humans but that goes for most studies.

    1. thanks for the hint on the typo. And yeah, you are right human studies would be better, but since this is actually the first study even bothering to dig somewhat deeper into that matter, I won't complain ;-)

  2. Excellent post as always Adel! Just another reason why I am gluten-free. With regard to the bottom line, what is your opinion on FODMAPS and the over-consumption of inulin- and beta-glucan rich foods? Aside from excessive gas and potential bloating, is their a downside?

    1. hmm... I thought I had replied to this already!? Whatever, ... I guess there may be a problem with too much FODMAPS when you already have some issues with your gut microbiota. On the other hand meat & co of which most of you probably eat some everyday appear to modulate the gut microbiome in an opposite direction. I guess it's once more about the spectrum of foods you ingest and not so much about one or the other being only good or bad.

  3. No one here eating gluten anyway, so I wanna talk about SHR.
    Yesterday I caught up with the latest episode of Suppversity Sniff Test (btw, who came up with that name...) and it was delight to listen sound and content wise quality, except Carl again putting emphasis on obese (female) individuals, who I doubt ever will listen such radio show. Skype plus new mic really pays off.

    Also first hour with NAC salesman was real crap. "Don't buy bulk powders." FU.

    1. hmmm. I don't know about the NAC salesman. I must was just back home in time to accept Carl's Skype call. On a related note. The facebook followers show that (to my own surprise) there are more not exactly size 0 women listening to the show, which I believe won't hurt any of them ;-)

      I also felt that the interaction via skype works much better. There is no real delay on my side when we did the show on phone, but after the last show, I realized that it does obviously take time, until Carl realizes, when I take a pause ... could also be due to the fact that with the messy line you can hardly say, when the other person actually stopped, though *lol*

    2. Oy, that's rather unfair. I'm sure I'm not the only woman with a 25+ BMI listening and reading. Nutrition and health are extremely important subjects, and while yes, probably most things will help obese women, having good information doesn't hurt. Some will over think things, but others just want to stay updated on what's out there, what works, what doesn't, what the *science* says.

      Not everything is about personal weight loss, either.

    3. I hope you did not misunderstand my comment, because I actually wanted to say basically what you just said. It is in fact about getting good information and that's also why I feel Super Human Radio is so awesome. Alright, there are the sales pitches, but those are easily to identify and as of late Carl has a hell lot of "real" scientists on the show. Also presenting opposing positions on different matters. That's really a "Dr. Oz Alternative". Regardless of whether you have still 10kg or just 1kg of body fat to shed.

      What's more, in the end you will become leaner and fitter and all of a sudden you will realize that what may have worked before doesn't work anylonger, so you can nicely progress with what you have learned about nutritional for people who actually don't have weight issues.

      This is totally unrelated, but here in Germany they tread anorexia and adiposity with an almost identical whole food approach to eating + psychotherapy. With actually flies in the face of the "just don't eat so much and you would not be so fat" you hear explicitly or implicitly so often.

    4. I was replying to Maxim, rather than you, Prof Andro. The idea that you shouldn't speak of or for obese women as well irks me, as it seems to club us obese women as dumb. I'm not sure if that's cause we're obese or women or both, but I will disagree with Maxim anyway. Saying that obese women (or obese men, or any category really) get "confused" or "overwhelmed" and then "over-think" is quite offensive to me.

      I'm in my third year for a Bachelor's degree in meal science and nutrition, and while I may spend more time downing sports drinks to finish my degree than I do at the gym, I'm hardly confused, overwhelmed or over-thinking things. Nor would I assume that the majority of obese women listening to the show are.

    5. Then I am wrong and have to apologise. I will try to justify how I came to this conclusion.

      All obese-overweight women I know (my colleagues, friends and even close relatives) aren't really care to break vicious circle. Immediate meal satisfaction is more important for them than health, longevity and looking good naked. Being fat isn't something you blush about anymore.
      Also local health blogosphere isn't strong in these parts and most people don't know any foreign languages, so they only have access to utter stupidity like monodiets (aka carrot\apple only), dukan, tenday fasts, homeopathy, fat blocker supplements etc.
      Media and word of mouth are prevalent sources of information and noone gives scientists more creditability than say weather forecasts. Don't see how the rest of the world is different.

    6. You make a good point about not blushing any more. I don't think overweight/obese people should be ridiculed, but the health risks are completely glossed over by the "big is beautiful" crowd. Smokers and drinkers are demonised, so why aren't sugar-bingers fair game for criticism? A culture in which complete acceptance of overweight is promoted is far more damaging for health than any amount of food industry advertising and laughable government dietary advice, although the latter play a big role in keeping people fat when they decide to do something about it.

    7. I agree, the solution is certainly not to bully overweight and obese people, but the way so many of them say "I have just always been like this, so what the fuck" is self-destructive and plain lazy.

      On the other hand you got those, you hop from one diet bandwagon to the next and all that happens is that they get fatter and sicker.

      Only few will take the time to learn enough about nutrition and exercise to follow and constantly tweak THEIR diet and not the 10 points program from GURU X...

  4. Problem with salesmen that they are too bold for their own good and making sound product they promoting like panacea (improving physical/mental performance, digestion, curing AIDS etc). Also it is never gets old to take some common cheap stuff, invent new delivery or processing method and sell it trifold. Microcoldexpelled reverse osmosis isotope processed argentinian grass-fed whey anyone?

    Don't these ladies scared by often mentioned androgens and HRT? Also, looking at studies - EVERYTHING works for obese women as long as there is exercise and\or caloric deficit. So any supplementation advice and overthinking over details only hurts them.

    1. I guess, you underestimate the rate many of these women do already "overthink" details. That said it is easier to lose weight when you are obese, 'cause the body doesn't like this state, but doing any type of exercise and just eating 800kcal per day is not a long-term solution and has stopped working for many women (AND MEN) after the 10th diet anyway.

  5. Assuming gluten was shown to have the same effect in humans in realistic doses, how many decades do you think it'd take for the wholegrain foundation of the "healthy" food pyramid to be demolished?

    I associate wheat/gluten with junk food, low-quality ingredients and carb-overload, so I minimise it anyway, and it's one of the only foods that gives me acid reflux. A long gluten-free period did nothing for my health, and the "paleo", WAPF etc shill dogma puts me off being more strict about it though.

    1. >"healthy" food pyramid to be demolished
      As soon as cigarettes banned.

      Btw Prof, even enormous Suppversity archive is lacking information on buckwheat. You often poke around oats, potatoes and rice, but entirely skipped this kind of "grain" as gluten-free alternative. I am russian, so it is very close to my heart and stomach.

    2. *lol* I believe the corn industry has more lobbyists than the cig business, so it will take at least 2x as long - in the US I am pretty sure it will never happen.

      In that note, Javeaux is probably right. If you avoid all the processed junk, and exercise regularly, you don't really have to care about eating only gluten free items (of which studies have shown that many still contain gluten anyway; I remember one on gluten-free beer, where a normal beer had less gluten than most of the gluten free ones and one of the "gluten free" ones had more gluten than the average beer)

      Another thing that makes me point to the convenience highly processed food in particular, is the hypothetical possibility that it's not the gluten load alone, but just like with glucose the onslaught of processed gluten containing items, which have all the gluten readily available in nastily small molecules, so that it actually gets into the blood or at least the enterocytes of the gut without being predigested.

      @Maxim: I will have to look for buckwheat. Did not appear on my radar as of now.

  6. Any thoughts on other gluten containing grains - such as rye? -fermented/not?

    1. Rye has gluten buddy. not as much as wheat, but its still there.

    2. there is some evidence that fermentation can reduce the gluten content to what would be negligible for some, yet still way too much for people with problems. In general sourdough rye may thus be the better choice - as far as industrially produced bread goes, I would yet exert caution, especially if the bread is still fresh and not dry and crumbly after 1 week, you can safely assume that the number of E-Numbers is way higher than that of natural ingredients.

  7. Replies
    1. that's not really different. Probably even less than your average "rye bread", but since there is gluten in rye there is gluten (residues maybe) in pumpernickel. That said, have you thought of the fact I mention that we don't know if it makes a difference for lean physical culturists? I mean you should by now have read on the suppversity that PPAR alleviates metabolic syndrome in obesity partly by allowing the expansion of the adipose tissue by the means of new fat cells (PPAR-GAMMA antagonists like CLA impede this)

  8. Prof. Dr. Andro. I'm a big fan of your blog. Thanks for your generosity in sharing knowledge.

    Interesting exchange here re. heavier women. And loads of (unfair) generalisations! From knowing (science) to doing (experiencing) there is a big gap. I love helping women bring these 2 together -I am both a scientist and a Personal Trainer. But in order to change, you need a first be step: willingness.

    Alexandra Road

  9. Prof. Dr Andro, do you believe that gluten/grains have an opioid type of effect on humans ? Just out of curiosity I’ve been experimenting with a grain-free diet for 4 days and I feel like a drug addict in rehab (would almost kill for cereal or bread). I have not cut down on calories and my diet is the same as before except for grains. Instead of grains I have gotten my carbs from fruit, potatoes and carrots but I am still craving for grains like mad. This is obviously not a carb craving but purely a grain craving. I’ve always eaten only whole grains such as whole wheat (All-Bran), whole rye bread and oat porridge so it is not a question of withdrawal from pastries or other junk carbs. Gosh, I am about to believe that grains do have an effect on dopamine and serotonin receptors.

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