Friday, August 6, 2010

IBS, Fructose, Depression, Zinc, and Women

Reader Jad left some terrific references in a comment last week, and having printed the papers up (I'm old-fashioned that way), I finally got a chance to look them over.


But before we get to that, right click on this youtube video for an incredible performance of the finale to Britten's "The Young Person's Guide to the Orchestra." If you have three minutes, take the time to watch. If you only have a minute, skip to 1:50, which is the part that always gives me chills. By "incredible performance," I mean this is literally one of the best orchestral renditions I've ever heard of any song. The Berlin Philharmonic hit it out of the park. And check out how good they look! Most of the musicians are middle aged, but I see scarcely a paunch among them - as near as I can tell, this was recorded around 6 months ago. Maybe it's because they are European. I've heard that concert musicians are less prone to chronic metabolic illness, but I've never seen any scientific proof of that.

Jad's papers (1)(2) also take us to Central Europe, where apparently a huge percentage (30-50%) of the population suffers from certain kinds of carbohydrate malabsorption (3). In the fructose variety, the GLUT5 transporter in the small intestine doesn't take up fructose as it should, so lots of undigested fructose floats down to the colon, feeding the bacteria there and leading to bloating, cramping, and diarrhea - basically the symptoms of irritable bowel. It's diagnosed via testing for excess hydrogen in the exhaled breath after a fructose load of 50mg. A similar test can show if someone has lactose intolerance.

Well, the researchers took a hundred or so "otherwise healthy volunteers" who had complained about gastrointestinal distress at a doctor's visit. None were on medication (except oral contraception) or had any signs of chronic or serious illness. They were given a standard scale test for depression (the Beck Depression Inventory) a fructose malabsorption test, then, a week later, a lactose malabsorption test.

Let's cut to the chase - a positive test for fructose malabsorption corresponded to depressed women, but not men. Lactose malabsorption alone didn't matter in either sex, but the 12% of women in the study who were both fructose and lactose malabsorption positive were by far the most depressed. The normal female controls had an average depression score of 7.5 - the combined malabsorption women had an average score of 14.6. That's a huge difference, and the bars hardly overlap at all.


Well, why would that be?

Turns out that fructose (and lactose) can react chemically with tryptophan, the amino acid precursor for our important happy chemical, serotonin. The sugars can degrade tryptophan so that there isn't as much available to be absorbed into the body. And, indeed, fructose malabsorbers have lower levels of tryptophan in the serum than normal controls (4). And, hey, turns out they have lower serum zinc and folic acid too! (5)(6).

But why would the symptoms of depression be confined to women? The researchers postulated that estrogen made the big difference. Estrogen activates an enzyme called hepatic tryptophan 2,3 dioxygenase that shifts the metabolism of tryptophan from making serotonin (happy) to making kynurenic (not happy). Women already have lower serum levels of tryptophan than men do (which may be part of the reason why we are more vulnerable to depression in the first place), so screwing up whatever available tryptophan in the diet with fructose may lead to even lower levels, and thus depression.

The researchers couldn't figure out why the combination of fructose and lactose malabsorption was worse than fructose alone - they thought maybe the diarrhea from lactose intolerance would interfere with the absorption of zinc and tryptophan, worsening the fructose situation. Since fructose malabsorption was so common in the population they studied, only a few people had isolated lactose intolerance, and they felt the data set wasn't big enough to figure out the lactose component.

It's also important to note that wheat products contain fructans, which can also cause intestinal problems in fructose malabsorbers. Bread with high fructose corn syrup can be especially problematic.

One more snippet - it seems that fructose malabsorption can affect serum zinc in two ways. First, it seems to interfere with the ability of the intestine to take up zinc in the first place. Second, fructose malabsorption is associated with bacterial overgrowth in the large intestine, which is associated with chronic immune stimulation (shown by higher serum neopterin concentrations)(5). As we know, inflammation likely causes us to sequester our zinc.

1/3 of the Western European population has fructose malabsorption. These Michigan researchers found fructose malabsorption in kids of many ethnic groups. Spanish investigators found in a small study that 71% of the depressed adolescents they studied had sugar intolerance, compared to 15% of controls, and that 28% of their known fructose/lactose malabsorbers had depression, which was a higher rate than expected in that population.

Sounds like yet another excuse to get anyone with depression and IBS off fructose and wheat for a while just to see what happens. Actually, one of the papers above suggested that only half of fructose malabsorbers diagnosed by the hydrogen breath test actually have gastrointestinal symptoms. Heck, let's get everyone off wheat and fructose and see what happens :)

Thanks, Jad!

(please see my next post, Dietary Strategies for Fructose Malabsorption for more information on this topic)


  1. Hi Emily. Fascinating post with many aspects that affects a number of the people I work with. I have updated an earlier post of mine on FODMAPS to link to your post here:

    There is also a good list of the fructose content of some foods that those experiencing difficulties might find useful:

  2. wow, very interesting indeed!

  3. interesting! thank you for more reasons to suggest people try a few months without sugar and wheat. most people I meet seem to think their ibs is from milk products, and I've never talked to anyone who thinks that wheat might also be bothering them.
    great recording too.

  4. No worries! Ive been waiting for someone in the paleoblogosphere to comment on fructmal for a while now. Thanks for the summary :-)
    Fructose malabsorption is big in my home city (Melbourne) as one of the leading researchers in the area is based here. I work in a health food store and have people coming in daily being recently diagnosed with it. I find it all very interesting when viewed through the perspective of human dietary evolution.
    Thanks for the great blog by the way!

  5. Thank you for writing about fructose malabsorption. I have it, was probably born with it, wasn't diagnosed until I was in my early thirties and the American food supply had gotten filled with HFCS, and soy and wheat fillers (sources of fructans). I'm still anxiously waiting for some of that research being done in Australia to finally make its way to the USA - but I'm not expecting that to happen soon, since our entire economy is so closely tied to the production of corn and soy, and the marketing of drugs to diminish their negative effects.

  6. Hi Emily and your readers,
    I live in Melbourne, Australia and have been diagnosed with Lactose Intolerance and Fructose Malabsorption about 3 months ago. I suspected the LI but the FM was a surprise. 12 months ago I suffered a "mild depressive" episode, which shocked me in it's intensity and bemused me as to it's real cause. It could have been due to a stressful , un resolved event 3 years previously. However, I do wonder if the FM exacerbated the effects due to a lack of Tryptophan etc.? Your article also makes me wonder that the unprecedented high intake of anti-depressant drugs being prescribed is due to increased FM in the population?

  7. Hi Liz - Fructose malabsorption may end up being the biggest psychiatry story in history this side of the B vitamins - the potential from the numbers from those little studies I linked are staggering. Something is causing the increase in depression, and as I speculate in other posts, I don't believe it is an increase in stress. However, as yet there is NO solid proof for the fructmal-depression link - these were all observational studies and some speculation. What we need, really, is a dietary trial with some depression metrics. In other words a randomized controlled trial.

  8. Hi Emily! I want to thank you and the people who have posted here for the information on FM. My daughter(also named Emily!) was recently diagnosed with FM here in Germany, and she suffers from Asperger syndrome as well. We have just started the elimination diet. I am frustrated with the amount of contradictions about foods with glucose out there, however. In Germany they say papaya is as safe as bananas and not to eat maple syrup. How can I find out the true balance of foods?
    All the best!

  9. hi Mary - I have a paper linked in the next blog post (dietary strategies for fructose malabsorption) that may have more links to more information. It may be worth getting the paper. Also, there's no reason to think there aren't variations in the fructose tolerance of individuals with the disorder - for some a papaya would be fine, for others it would be too much fructose. All these individuals in the dietary study had GI symptoms - it might not be a specific enough test but maybe remove all the questionable items and add maple syrup one day, or papaya another and see if there are any changes? I'm certainly not a GI doctor though, and apparently fructmal is becoming a big deal, and a specialist should be on the forefront of that sort of info.

  10. Also, if memory serves the Australian team of researchers has a webpage - might be worth a google.

  11. Thanks, Emily!You are very kind to respond so quickly and give so much good info! All the best!


  12. Hey everyone im here with review, and I finally know this helped my IBS. Im a healthy woman in her mid-40s, just slightly overweight, but not too much. I have been taking fiber supplements for a few months now, but the brand really matters. My nutritionist recommended the Lady Soma brand after trying some supplements that did not work. Specifically, it was the Lady Some Fiber Cleanse which is made just for women.

    I can tell you what a difference it has made for me. Not only just going to the bathroom but for general well being. i felt a very constipated before. I would recommend this to anyone looking to try a fiber supplement for the first time. even though you only get 30 days or less with this its still a GREAT price for a fiber supplement.

  13. Hi Emily, I was recently "diagnosed" as bi-polar after having my first baby. I think it is a misdiagnosis.
    Ever since I heard of FM (about 2 weeks ago) I am convinced this is the cause of two decades of severe stomach pain, bloating, gas and food restrictions...(severe Lactose intolerance, onions, kale, cabbage, beans, apples, pears, berries, most grains, FOS, and allergies to nuts seeds and soy.... etc) and the struggle with 10+years of depression. (I also think my diagnosis of IBS is a misdiagnosis)
    The depression seems to be linked with severe stomach pain and gas.They seems to go hand in hand. I have tried to explain this both to psychiatirsts and general MD's along with Gastro MDs but everyone ignores it.
    I want to get a Hydrogen breath test but my insurance wont cover it. Is it considered not a legitimate test? Are its results questionable? CAn the breath test not show FM and one could still have it? (false neg?)
    ANy advice would be greatly welcomed....I feel I am at the end of a 20 year search for this pain! So excited! Thanks for your blog!!!!

    1. Hi Olivia, I was wondering if you had gotten any answers. My symptoms/situation seem to have many similarities to yours. Depression symptoms started 10 months postpartum, bloating/gas, IBS, many of the same "trigger foods." I've been wheat-free a few days and feeling amazing. All of a sudden tonight after dinner (used some maple syrup with banana almond pancakes) and feel terrible. Starting to wonder if it's fructose not just wheat. Thanks.

  14. I haven't read your entire blog so you may have covered this, but check out MTHFR mutation, this could be a huge variable that is being overlooked when dealing with these same sorts of issues. It requires supplementation with Methyl folate and cobalamine, TMG and other ones to help support your genotype.


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