Uric acid is a breakdown product of the purines, adenine and guanine. These compounds are found in relatively high amounts in meat, especially organ meats. Obviously, anyone with gout should avoid dietary sources of purines. Ah, if only life were so simple! It reminds me of the truism that eating fat makes you fat... If that were true your average dietician would have cured the current obesity epidemic easily by now.
No, gout is much more interesting.
Gout is triggered by the presence of crystals of uric acid in your joints. It extremely painful. Many people with gout have high levels of uric acid in their blood stream. Oddly enough some people with gout do not have high levels of uric acid in their blood. Dig deeper.
Fructose is an unusual sugar for humans to eat. We have no system to break down fructose polymers. The only sources of fructose we can use are the simple sugar in fruit or honey and as the molecule combined with glucose as sucrose, ie table sugar. Drenching your metabolism with fructose is a recent innovation for humans. The current preferred sweetener for soft drinks is "high fructose corn syrup", a product of our dearly beloved food industry in the last thirty years or less.
What happens when you drench you metabolism with fructose? It enters the metabolic pathway of carbohydrate below its main control step and is immediately converted to fructose-1-phosphate. Quite why evolution has arranged things this way is a mystery, but my suspicion is that evolution does not like free fructose in human metabolism. So drinking a small bucket of cola will put 100gm of fructose in to your liver. This will require a large input of phosphate to for the fructose-1-phosphate, leaving very little for the generation of adenosine tri phosphate (ATP), the primary energy currency of our cells. A lack of ATP triggers activity of the degradation system for adenine and the production of, guess what, uric acid! Gout, and not a serving of kidneys in sight. Until 100 years ago only the rich could afford enough sugar to get gout, now it is a feature of metabolic syndrome and available to all.
Incidentally the fructose has to be "put" somewhere, and that is in to fat for storage, via elevated triglyceride levels in the blood. It causes insulin resistance too. Even the full metabolic syndrome!
In fact, probably the truth is that fructose causes insulin resistance, which causes gout. The hyper uricaemia and the fact that the joints produce uric acid crystals do not have to be causally related. I'd say they're not.
Incidentally, these bright researchers are looking for ways to minimise the self poisoning caused by fructose. They are actually suggesting looking for a drug to allow you to drink high fructose corn syrup without the rise in uric acid.
A drug for life to enjoy your cola. But of course that won't stop the insulin resistance from fructose, so......
Peter
I am very thankful for you explanation of gout. My neighbor, who doesn't eat red meat told me that her husband who does eat beef has gout. She was interested in buying my grass-fed beef for him and I told her I would investigate wether the "beef" is the problem or is grass-fed beef going to "safe" for his gout problem.
ReplyDeleteThey seem to very intelligent people so I don't know why they would not have investigated this further. I came across your blog as it was posted on PalaoHacks under a completely different topic and I noticed your post on gout.
Hi Wilcox,
ReplyDeleteI think gout is metabolic syndrome of the fingers... In the same way as urate stones are metabolic syndrome of the kidneys. You really have to drop the fructose/alcohol which trigger fatty liver and systemic hyperinsulinaemia.
Peter
Gout is a autoimmune response to depostioin of uric acid crystals. Hyperuricemeia may not casue gout and even low level of hypweruricemican casue gout in sme individuals on accout of difference in the immune reposnse. Hyperuricemeia is asociated with increased risk of cardiovascular disease. Uric acid is also an antiooxidant and theres are trials underway for Parkinson Disease.
ReplyDeleteDear Peter, The reasons for hyperuricemia and gout are vast, it's a multi factorial disease that the major risk factor is hyperuricemia but not an absolute necessity one, like you wrote. What is absolutely needed is inclination to crystallization (No matter how high the uric acid is) and inclination to inflammation.
ReplyDeleteSure the fructose explanation is one of the contributing factors but definitely not the whole story. The main metabolic issue if you ask me is too much mitochondrial coupling which results from too much insulin and leptin (the main effectors ot UCP proteins). There was a interesting study about a mutation in the UCP2 protein that makes hyperuricemia. Many other mutation are known for channels or transporters of uric acid that contribute to hyperuricemia such as GLUT9, ABCG2, OAT family and more.
Another contributing factor is too much iron (uric acid is a chelator of iron) and in the context of too little copper and zinc, and too much molybdenum, you have overproduction and under secretion at the same time.
Also decresing levels of testosterone aids to the hypocopperemia