Yesterday, somebody asked me “What is the protein and uric acid connection?”
I can sum it up in two words.
Very complex.
But you want more than that, don’t you?

The simplest explanation is that purines from cell metabolism and some foods get broken down to uric acid in the human body. Most other animals produce other enzymes (uricase) that continue to breakdown uric acid further, so that it is easier to excrete. Humans do not have that enzyme because we want to keep some of the uric acid. It neutralizes free oxygen radicals in our body that would otherwise cause extensive cell damage. That is why normal human lifespan is greater than many animals.

From that, we can see that the protein and uric acid connection is a simple one:

[2017 Correction]
There is no really simple explanation. But, if you want to understand more, start with the difference between protein and purine for gout sufferers.

The trouble with simple explanations is they lead to simple gout solutions. “Stop eating high purine foods and your gout will be cured,” is one of them.

In real life, eating a low purine diet has been shown to have a minimal effect on uric acid levels and on gout. A study(1) of 60 gout patients showed a 1 mg/dL reduction after 7 days, though they note that no significant reduction occurred after 5 days. What we don’t know from this study is just how the diet changed. What replaced the purine foods? Could this account for the reduction?

Even that study was just a preliminary to determine the number of days of diet change required to have a significant effect on uric acid. The main part of the study, and several other similar studies show that changes to the purine content of diet has a much bigger effect on the amount of uric acid excreted in urine than it does on uric acid in the blood.

Not only that, but there are several different types of purines. Nearly all published information about the purine content of food, including my own purines in food table, relates to total purines. Each of these follows a different pathway in our bodies. The presence of different enzymes controls if and how these purines breakdown to uric acid. Some become reabsorbed at different stages. Finally, the kidneys reabsorb or excrete uric acid according to mechanisms in our bodies that are not fully understood.

Several studies have taken place, and no doubt more will continue, to try to understand the protein and uric acid connection. Many of these studies show, that by introducing artificial diets (necessary to achieve scientific control points), then adding different oral purine compounds (2), there is a direct connection between protein and uric acid.

The problem with this, is that it does not help us gout sufferers in the real world. The interaction between food and body chemistry is too complicated for simple “No Purine” rules. What about naturally occurring antioxidants in foods in our diets? Do these have a neutralizing effect that might help prevent the formation of excess uric acid? What about compounds in food that restrict the activity of enzymes that cause the breakdown of purine proteins to uric acid – a kind of natural allopurinol?

Many questions reveal themselves as the protein and uric acid connection gets more complicated. I don’t have answers for all of them, but I’ll be revealing some significant aids to understanding over the next few weeks.

Best make sure that you are subscribed to my newsletter, this gout blog, and your gout forum to make sure that you don’t miss anything.

(1) URIC ACID PRODUCTION IN GOUT By J. E. SEEGMILLER, ARTHUR I. GRAYZEL, LEONARD LASTER AND LOIS LIDDLE. (From the National Institute of Arthritis and Metabolic Diseases, Bethesda, Md.)

(2) Effect of Oral Purines on Serum and Urinary Uric Acid of Normal, Hyperuricemic and Gouty Humans
Department of Nutrition and Food Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139


  • Brian

    Not all purines are created equal. You probably know about the study done by Dr. HK Choi and associates based on a twelve-year study tracking 50,000 men from the medical professions. The men were asked to periodically fill out questionaires on food consumption. All of the men were gout-free at first but 730 developed gout. The basic outcome was that: (1) the men consuming the seafood and meats were more likely to get gout, (2) consuming high-purine vegetable foods did not increase the risk of gettin gout, (3) men consuming dairy products were less likely to get gout, and (4) men consuming low-fat dairy were the least likely of all to get gout. (Purine-Rich Foods, Dairy and Protein Intake, and the Risk of Gout in Men.)

    The purines in meat, seafood, and vegetables are all the same. Why the difference? If the real villains of the piece are the meat and seafood, then the answer might be in the minerals they contain. The liver, clams, oysters, etc. that we have been warned so often are storehouses of minerals including iron. As far as food is concerned, there are two types of iron. The first is heme which is found in animal foods. The other is non-heme which is found in plant foods. The problem with the non-heme is that the body has a hard time extracting it. Without help, the body usually gets only two percent. However, if you eat the vegetable with meat, the body can extract the non-heme with the heme. Similarly, if you eat the vegetable with a food high in vitamin C, the body can get some of the non-heme iron. I believe this is why the study concluded that the vegetables that were high in purines weren’t the villains of the piece.

    The traditional picture of one of us eating a feast of high purine foods and alcohol, then going to bed only to wake up with a gout attack after some hours of sleep is correct. The conclusion that the purines and alcohol were the only things responsible is incorrect. I believe the heme iron contained in the foods were a necessary part of it. The answer with the enzyme, xanthine oxidase, which converts purines to uric acid. This enzyme contains the minerals molybdenum, iron, and sulphur. The meats and seafood would supply all of these in relative abundance. In addition, the increase iron in the blood would serve to make the existing xanthine oxidase more active. It is the combination of high purines and heme iron that make the meat and seafood so dangerous for us. Can I prove this? No.

    Take a look at the conclusions about dairy foods and low-fat dairy. Certain minerals impede the absorption of iron across the lining of the intestines. Also certain foods have substances in them that do the same. These work to keep iron stores in the body down. In dairy, it is the mineral calcium. Milk is a collection of substances, some of which assist the uptake of iron and some of which impede it. In addition to calcium, there is casein which is an iron uptake inhibitor. If consumed with other foods, these substances would help to block not only the uptake of the iron in the milk but the iron in the other foods as well. The low-fat dairy is like regular dairy but with some substances removed which might help to explain why it seemed to protect against gout better than dairy.

    There are other foods having substances that inhibit iron uptake. Coffee is one such food. In a separate study by Dr. Choi and his associates, they concluded that coffee was effective in fighting gout. They didn’t find the same true for tea. They also found that caffeine wasn’t the cause because decaffeinated coffee worked as well. Coffee contains a number of chemical compounds and there are other possible explanations to why it might be effective. However, coffee is a very potent iron uptake inhibitor.

    Another point is that pre-menepausal women, as a rule, don’t suffer gout attacks. Part of this is due to the fact that they secrete more uric acid than men do because of estrogen’s effect on the kidneys. However, if iron is a factor, the monthly periods would also help protect them because their iron stores are generally lower.

    The point is that iron might play a key role. There have been studies done but they are not strong enough to prove it. However, I have started including six cups of decaffeinated coffee and two servings of low-fat dairy in my daily diet. I have stopped taking a vitamin c pill(contributes to iron absorption) and have switched to a multivitamin without iron. Frankly, I don’t think I need a supplement with iron in it anyway. This is what I believe to be reasonable steps based on what I have read. However, before making any changes to your supplement, you might want to talk to your physician. Again, this is only what I suspect and it is not really proven

  • Great comments, Brian. Thank you.

    I am aware of the Choi study, though readers need to be aware that this is only a statistical study. All it can really conclude is that different diets infer different risks of gout. It is dangerous to attribute reasons for this, as not all factors are known, and no randomized trialling takes place.

    In real life, we all eat a different combination of foods, and that combination is more important than individual foods within it. My own experience is that meat and seafood balanced with sufficient vegetables is fine, but large portions of meat or fish alone spell trouble. Even that is not a given, as other factors like time of eating, amount of exercise and volume of fluids play a big part.

    Of course, unless we are treating food and drink as pain relief, the only true test of whether a certain food combination is any good is to test uric acid. As uric acid in the blood fluctuates widely, it is difficult to get an accurate measure, but I would think a test immediately before and one hour after would show if level had risen or fallen. To be meaningful, this ought to be repeatable.

  • Brian

    The study by Choi and associates is a population study. That’s true but it does point to the possibility of heme iron being a central player in the inflammation process. I’ve posted since to this forum about research work that was done by Drs Hugh McGrath, Jr and PG Rigby. The results of Choi’s work make a lot of sense when you read the other work that has been done on the role of iron in inflammation.

    If only we could get blood tests just prior to the attack and afterward. If we could only know the serum uric acid levels and ph levels of both the blood in general and the synovial fluids in particular. The problem is that the attacks are unpredicatable and happen in the home. The tests run by the physician on the patient are way too late. It is like trying to figure out what happened at the site of a fatal automobile crash after the cars have been towed away.

    Also, it would help if we could track the ph levels and uric acid levels of people who have sleep apnea and suffer gout attacks. I have been reading about how sleep apnea works and can see how it could trigger the attacks.

  • donal777

    hi gouties. just to let ye know,been on allopurinol 300mg for ua is 2-3mg.very good for last two months -just afew twinges.last week upped my dose to 400mg to clear crystals a bit quicker.bang within 4 days i had a bad attack which lasted a few days .back on 300mg allopurinol, no more messing with doses for me. dont know now the attack was coming or from raising my dose great site GP

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