Gout is a type of inflammatory arthritis that typically attacks the big toe and ankle. Gout primarily occurs when there is an accumulation of uric acid crystals in the joints, leading to inflammation and intense pain. Uric acid is a normal waste product that forms when the body breaks down purines, substances found in certain foods and also produced by the body. Normally, uric acid dissolves in the blood and passes through the kidneys into the urine. However, if too much uric acid is produced or if the kidneys do not eliminate enough of it, uric acid can build up, leading to gout.

It tends to attack the feet and toes because of temperature and gravity. The peripheral parts of the body are cooler than the core which allows uric acid to crystalize. It’s classically called a “disease of kings” because of the association of rich diets and alcohol. How accurate is this? Like most conditions of the body, there is more nuance to this. Research has confirmed that purine rich foods can contribute to the development of gout, but many of these foods are animal products such as red meat, turkey, organ meat etcetera, that are nutrient dense. Do we need to give these foods? This is a classic case of correlation does not equal causation. 

Some studies have found that ingesting high levels of purines is not enough to provoke a gout attack (Zhang, 2021). Other studies found that consumption of purines and proteins increases the excretion of uric acid and is associated with increased inflammatory markers such as CRP and IL-6 (Urano et al., 2002). So what is going on here?

This is a bit of an innocent bystander effect and is similar to the sugar and salt debate as it pertains to high blood pressure. Salt does increase blood volume but normally the kidneys are able to regulate salt levels. However, in the context of a high sugar diet and insulin resistance, the kidneys lose this regulating ability and retain too much salt. So salt takes the blame, when insulin resistance is the real problem. This is more or less the same situation, and it appears, possibly the same culprit; insulin resistance. Hyperinsulinemia causes a decrease in urinary excretion of uric acid (Galvan, 1995). So it appears that high levels of purines result in elevated uric acid which the kidneys will normally excrete. In an insulin resistant state, we do not excrete adequate levels of uric acid leading to a “back up” effect.

There are some other players that may be contributors to gout flare ups. Fructose (as in high fructose corn syrup) appears to have a role. It can increase serum uric acid levels by enhancing the production of purines and reducing uric acid excretion. Iron is another marker that tends to be elevated which is no surprise given the correlation between increased iron and diabetes.

So what can we do about this? Lowering sugar levels and alcohol intake will certainly help. Vitamin C increases the excretion of uric acid and this is part of why cherry juice is recommended for gout. Blood donation reduces iron levels, so it would stand to reason it would reduce gout. In 2003, a study by Facchini found that phlebotomy to a near iron deficient state affected gout ranging from a complete remission to a marked reduction of incidence and severity of gouty attacks.

So if you do get a gout attack, it’s probably a good idea to get a blood panel. Besides uric acid, I’d be looking out for blood sugar markers, as this may be a sign of insulin resistance. I’d look at inflammatory markers, and iron/ferritin levels. 

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References:

Facchini FS. Near-iron deficiency-induced remission of gouty arthritis. Rheumatology (Oxford). 2003 Dec;42(12):1550-5. doi: 10.1093/rheumatology/keg402. Epub 2003 Jun 27. PMID: 12832712.

Quiñones Galvan A, Natali A, Baldi S, Frascerra S, Sanna G, Ciociaro D, Ferrannini E. Effect of insulin on uric acid excretion in humans. Am J Physiol. 1995 Jan;268(1 Pt 1):E1-5. doi: 10.1152/ajpendo.1995.268.1.E1. PMID: 7840165.

Wako Urano, Hisashi Yamanaka, Hiroshi Tsutani, Hiroshi Nakajima, Yuko Matsuda, Atsuo Taniguchi, Masako Hara, Naoyuki Kamatani

The Journal of Rheumatology Sep 2002, 29 (9) 1950-1953;

Zhang WZ. Why Does Hyperuricemia Not Necessarily Induce Gout? Biomolecules. 2021 Feb 14;11(2):280. doi: 10.3390/biom11020280. PMID: 33672821; PMCID: PMC7918342.