Saturday, January 24, 2009

The Tokelau Island Migrant Study: Gout

Gout is a disorder in which uric acid crystals form in the joints, causing intense pain. The body forms uric acid as a by-product of purine metabolism. Purines are a building block of DNA, among other things. Uric acid is normally excreted into the urine, hence the name.

On Tokelau between 1971 and 1982, gout prevalence fell slightly. In migrants to New Zealand, gout prevalence began at the same level as on Tokelau but increased rapidly over the same time period. Here are the prevalence data for men, from Migration and Health in a Small Society: the Case of Tokelau (I don't have data for women):

This paper found that the age-standardized risk of developing gout was 9 times higher in New Zealand than on Tokelau for men, and 2.7 times higher for women.

Gout is usually treated by taking drugs and avoiding purine-rich foods. According to Wikipedia's entry on purines, these include:
sweetbreads [calf thymus or pancreas], anchovies, sardines, liver, beef kidneys, brains, meat extracts (e.g Oxo, Bovril), herring, mackerel, scallops, game meats, and gravy. A moderate amount of purine is also contained in beef, pork, poultry, fish and seafood, asparagus, cauliflower, spinach, mushrooms, green peas, lentils, dried peas, beans, oatmeal, wheat bran and wheat germ.
Those include some of the most nutritious foods available! The idea that the human body would not have evolved to tolerate most of the foods listed above is beyond comprehension, given our species' carnivorous tendencies. As a matter of fact, the only controlled trial I found suggests that a diet high in purines from animal protein has no effect on the uric acid concentration in the blood, because the body simply excretes any excess. In any case, like cholesterol, the majority of purines in the body are synthesized on-site, rather than coming from the diet. The only thing I found in support of the purine-gout hypothesis was a prospective study from 2004 that found an association between dietary purines and gout. I think we need to consider other possibilities.

Is there anything else that elevates uric acid in humans? Ah, sugar, one of my favorite punching bags. You never let me down, old friend. Refined sugar (sucrose) increases serum uric acid under controlled conditions, as does fructose when compared to starch. This has never been demonstrated for purine-rich foods that I could find.

Another clue comes from a disorder called "hereditary fructose intolerance". These patients are missing an enzyme required for metabolizing fructose, and must avoid it or risk becoming very ill. Some of the relatives of these patients are "heterozygous" for the mutation, meaning they have one mutated copy of the gene and one normal copy. They can metabolize fructose, but at a slower rate than someone with two functional copies. And they also have a very high incidence of gout.

Tokelauan migrants to New Zealand consumed significantly more sugar than Tokelauans on Tokelau during this study period (13 vs. 8 percent of calories in 1982). This explanation makes much more sense to me than the idea that gout is caused by the very foods that have sustained us as long as our species has existed.

There is one piece that doesn't fit, however. If sugar is causing gout, then why didn't gout incidence increase on Tokelau as their sugar consumption increased? I don't know. Perhaps there is another factor involved as well. Any thoughts?

The Tokelau Island Migrant Study: Background and Overview
The Tokelau Island Migrant Study: Dental Health
The Tokelau Island Migrant Study: Cholesterol and Cardiovascular Health
The Tokelau Island Migrant Study: Weight Gain
The Tokelau Island Migrant Study: Diabetes
The Tokelau Island Migrant Study: Asthma

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