02 September 2009

The Causes of Gout

In a previous post, I mentioned that a bout of gout had been my wakeup call for getting my diet right. That wakeup call led to a much deeper understanding of metabolism and the biochemistry of the body.

I recently had a minor recurrence of gout and it followed a similar pattern to what happened in 2007, so I did more research on it.

The Pattern

I noticed in mid-2007, that the day after a really hard workout, usually a leg workout, my feet hurt--not badly though. It almost felt as if I had a bone a little out of joint or something. I attributed it to something about the way I was doing my calf raises. When I had bad gout in November of 2007, it was after a leg workout, and as it got worse, I thought it was related to an infection on my foot. Finally, it just went away on its own and my podiatrist told me it was probably gout.

I have had a few very minor cases since then, each time it went away after a day or two, So last week, after a leg workout, my foot hurt. It was just a little bit, and I thought that it was related to a splinter or something I had in the ball of my foot (my feet are a mess). But then it got worse, and I realized that it was the onset of gout. Again, it was following exercise.

First, it is generally accepted that gout is caused by the formation of crystals of uric acid in the joints. It usually expresses itself in the foot. The crystals form often when the blood concentration of uric acid reaches a high level.

For a long time, the standard cure was to lay off organ meats and red wine, because those contain purines (of which uric acid is a by-product). The problem is that I was not eating organ meat, and I wasn't drinking that much red wine. So the standard advice was useless for me.

I have found a number of interesting things about the accumulation of uric acid in the blood.

Under normal conditions, uric acid is pulled out of the blood and excreted in urine. However, there are some situations that can cause an imbalance and lead to higher levels of uric acid. According to Cordain, the problem in 90% of gout cases is that people underexcrete uric acid, not overgenerate it.

1. +Uric acid production - fructose and alcohol both increase uric acid production in the liver.

1. - Lactic acid, as can be generated by strenuous exercise, fructose (e.g. from high fructose corn syrup (HFCS)), or alcohol consumption, reduces the excretion of uric acid.
2. - Insulin in the bloodstream, as from high glycemic foods
3. - Dehydration/lack of proper hydration can inhibit excretion of uric acid
4. - Fasting or a starvation diet inhibits uric acid excretion
5. - The initial stages of ketosis can inhibit excretion of uric acid from competition in the kidneys with the ketones. Once the body is adapted to using ketones for fuel (6-12 weeks), this is no longer a problem for most.

Neutral Effect
1. +/-High purine foods (organ meat, seafood, protein) increase uric acid production and stimulate excretion. The net effect is very low. (references below)

1. The standard medical recommendations--stop eating purine-containing foods and drinking red wine--are not well supported by research. Purine foods have only a minor impact on uric acid and red wine is part of the larger alcohol problem.
2. Sucrose and HFCS have a triple whammy effect on uric acid levels. They increase production and inhibit excretion through both lactic acid and insulin pathways.
3. Alcohol is a double whammy (increase production and lactic acid).
4. Strenuous exercise can inhibit excretion of uric acid via the lactic acid pathway.
5. Lack of sufficient water and nutrients can inhibit excretion of uric acid.

E4E Recommendations
If you find yourself with excruciating pain in your feet, see a doctor. He can make the gout diagnosis. He will likely give you a list of foods to avoid and a prescription for painkillers and/or allopurinol for treatment of chronic gout. Gout is really painful and this will help get you through any acute crisis.

Once allopurinol was instituted as a cure for gout, little research was done on prevention through other means. Allopurinol works well for many people. However, in my view, behavioral interventions are always better than chemical (if they work of course).

So longer term, reduce consumption of fructose, especially in the forms of sucrose (table sugar) and HFCS, and reduce alcohol consumption. If you feel gout symptoms coming on, reduce exercise intensity, make sure you are well-hydrated, and eat at maintenance calories.

Some References
Loren Cordain Paleo Diet Newsletter (The Insider) Vol 2 No 4 I have a pdf of the full article
Chris Kresser on Gout
Petro Dobromylskyj from Hyperlipid had two posts on gout here (1) and here (2). He puts the blame on excess fructose.
Very interesting article by Ed Yong (Not Exactly Rocket Science) on the evolutionary aspect of gout and the enzyme that breaks down uric acid in many animals.
Exercise and Gout from Journal of Biological Chemistry JBC
Taubes on Gout
Mark Sisson of Mark's Daily Apple totally agrees with me
Dr. Lustig from UCSF video about fructose
BBC article on Gout and sweet drinks
Gout website with some folk or popular remedies
Nice Google Answers site on gout.
Ketosis and Gout post from August 2018 by Amy Berger "... 10% of cases of hyperuricemia are caused by overproduction of uric acid; the other 90% result from impaired excretion."
Addendum: March 2, 2010
A paper with the purine content of many foods. Biological and Pharmaceutical Bulletin
A paper came out called Lack of association between dietary fructose and hyperuricemia risk in adults.  

It used a large database called NHANES to search for an association between dietary fructose and hyperuricemia. It found that there is no statistical association between even high "normal" fructose intake and hyperuricemia. Alcohol was positively correlated; fiber was negatively correlated with hyperuricemia. This does not mean you get a free ride on fructose--large amounts do cause hyperuricemia--just that you should not overdo it. Alcohol and fructose are metabolized similarly, but there was no mention in the article about whether the effects may compound.

References regarding Neutral Effect of Dietary Purines and Protein from
Cordain Paleo Newsletter, Vol 2, No. 4
"Further, the recommendation to reduce high purine foods such as fish, shellfish, meats, poultry and organ meats may be of dubious therapeutic value (11) because clinical trials of low purine diets only marginally reduce (1-2 mg/ dl) blood uric acid concentrations (15-17). Although high protein, meat based diets contain high amounts of purines and would be expected to promote gout symptoms, protein ingestion actually decreases blood uric acid levels by increasing uric acid excretion (18). This seemingly paradoxical effect occurs because the kidney increases its excretion of uric acid when faced with elevated dietary purines (19).
"So, let’s put 2 and 2 together. If high protein, meat-based diets actually increase uric acid excretion, and 90 % of all gout patients have the disease because they are underexcretors, it makes little sense to implicate meat and high protein diets as a fundamental cause of gout. What we really need to look for are dietary factors which can simultaneously increase uric acid synthesis in the liver and suppress its secretion by the kidneys – Bingo!"
18. Matzkies F, Berg G, Madl H. The uricosuric action of protein in man. Adv Exp Med Biol 1980;122A:227-31.
19. Loffler W. Grobner W, Medina R, Zollner N. Influence of dietary purines on pool size, turnover, and excretion of uric acid during balance conditions. Isotope studies using 15N-uric acid. Res Exp Med (Berl). 1982(2):113-123.