One of the major differences between our industrial diets of today compared to even the recent agricultural past is the massive increase in the consumption of sugar.  Tom Naughton's blog has some graphs with data that Americans consume on average 216 liters of soda annually.  A liter of soda has 108 grams of sugar.  

What does that have to do with depression? Well, sugar's most common form is sucrose, which is 1/2 glucose and 1/2 fructose.  High fructose corn syrup, the sweetener in American non-diet soft drinks, is typically 55% fructose. Why would this matter?  Well, depends on your genes and possibly your gender.

Turns out that in Central Europe, a large percentage (30-50%) of the population suffers from certain types of carbohydrate malabsorption (1)(2).  I asked a friend of mine, an academic gastroenterologist who just left Johns Hopkins, what she thought the percentage of Americans was, and she felt it was 15-20%.  In fructose malabsorption, the GLUT5 transporter in the small intestine doesn't take up fructose as efficiently as it could.  That means 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 syndrome. It is 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 in Central Europe 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 data between the unaffected individuals and the carbohydrate malabsorbers 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 (3). And, hey, turns out they have lower serum zinc and folic acid too (4)(5) - both of these findings are associated with depression.

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. 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.

Well.  All of that is observational data, and correlation does not equal causation.  All we have to hang our hats on is a small study from Austria in 2000.  In this study, folks with known fructose malabsorption were put on a low-fructose diet, which reduced their depression scores by 65% after 4 weeks.  The findings were more pronounced in women than in men.

Assuming these findings hold up, let's do the numbers.  300 million people in America, half of them women.  Assuming 20% have some sort of fructose malabsorption, we are talking about 30 million women.  Depression afflicts about 10% of the population in any year, primarily women.  How many have both depression and fructose malabsoprtion?  How many could be much improved by simply limiting soda and other high fructose items (such as fruit juice or watermelon)?

We don't know.  More research must be done.  I hope it is done with all expediency. 

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Copyright Emily Deans, M.D.

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