MTHFR and Gout

Gout is a painful form of arthritis and a condition that is steadily increasing worldwide. It is now the most common type of inflammatory joint condition in adults, affecting around 8.3 million adults in the U.S. alone. 

Cases of hyperuricemia have also increased dramatically over the last 50 years, with an estimated 43.3 million Americans now affected. 

Gout causes severe joint pain and swelling, especially in the toes, knees, elbows, wrists, and fingers. If left untreated, it can cause severe damage to joints, kidneys, and overall quality of life. It has also been described as one of the most understood and manageable arthritic diseases.

While gout is often associated with poor diet and obesity, recent research has suggested that the risk of gout may be linked to the MTHFR polymorphism. This common genetic mutation affects some 30-40 percent of the American population.

There is also evidence that elevated homocysteine may be linked to uric acid levels.

This article will explain gout and its etiology. We will also discuss the link between MTHFR and gout and how the risk of developing gout can be minimized with the right nutrients. 

Gout is one of the most common causes of chronic inflammatory arthritis in the United States. This painful condition is characterized by the deposition of uric acid crystals (monosodium urate monohydrate) in the tissues.

The leading cause of gout is hyperuricemia, a metabolic disorder resulting from excess uric acid levels in the blood. 

The exact cause of hyperuricemia is often linked to dietary factors. Uric acid is a waste product formed in the body following the breakdown of purines (adenine, guanine, and xanthine), which are naturally present within the body's cells and in certain foods.

Consumption of foods and beverages high in purines will increase uric acid levels. Purine compounds are either produced in the body or accumulate from eating high-purine foods. If the body is unable to break down these purines, uric acid levels will increase. 

The excess uric acid can then produce uric acid crystals, which build up in soft tissues and joints, causing the painful symptoms of gout. 

High-purine sources include: 

Other causes of gout include hereditary disorders that affect uric acid excretion and purine metabolism.

In males, the risk of developing hyperuricemia has also been linked to low intake of folate and B12. 

The common MTHFR mutation C677T has been shown to lead to elevated homocysteine levels, contributing to higher uric acid levels. Researchers have noted that an MTHFR mutation is a risk factor for hyperuricemia in older men.

A 2018 study published in the Journal of Clinical Medicine investigated the role of folate, B6, and B12 on hyperuricemia. Men with hyperuricemia were found to have lower intakes of folate, folic acid and vitamin B12. Women with higher intakes of total folate high a lower risk of hyperuricemia; not there was no relationship associated with vitamin B6 or vitamin B12. Folate appears to be particularly crucial as it helps to inactivate xanthine oxidoreductase (XOR), the enzyme responsible for the oxidation of hypoxanthine to xanthine and xanthine to uric acid.

Hyperuricemia and hyperhomocysteinemia are both believed to be risk factors for cardiovascular disease. However, the exact relationship has not yet been determined. Some studies have reported a direct correlation between uric acid and homocysteine, while others have claimed no significant correlations between homocysteine levels in patients with gout and control groups. 

One study found that homocysteine levels were elevated in male patients with gout. Hyperhomocysteinemia was not correlated with uric acid levels, but it appeared to be higher in patients who had impaired renal function.

In a large cohort study, hyperuricemia was found in 24.9% and 14.6% of subjects with elevated and normal homocysteine serum levels, suggesting a significant association between hyperhomocysteinemia and hyperuricemia. The researchers concluded that accelerated atherosclerosis might be a consequence of the combined effect of these two factors.

A 2011 study found that elevated homocysteine levels and uric acid were associated with albuminuria (a sign of kidney disease) independently of one another and of renal function.

Strong associations have been noted between homocysteine levels and MTHFR polymorphisms due to the way MTHFR deficiency disrupts homocysteine metabolism. Previous research has demonstrated that the C677T polymorphism increases homocysteine concentration and decreases folate.

People with hyperhomocysteinemia were also found to have lower levels of folic acid and vitamin B12 and higher uric acid levels than those with normal homocysteine levels. Uric acid was positively associated with higher homocysteine.

Folate, vitamin B6, and vitamin B12 all play major roles in lowering homocysteine by converting it to methionine.  However, a lack of these nutrients can impair the conversion process, resulting in higher accumulating homocysteine levels.

People with gout should be aware that their condition may not be preventable through lifestyle changes alone, especially if they have an MTHFR mutation. In the case of an MTHFR mutation, mediation and/or supplements may help to get their condition under control. 

Uric acid is a significant factor in gout, and many epidemiological studies have shown the relationship between uric acid and obesity, metabolic syndrome, hypertension, and coronary artery disease. These disorders are also linked to elevated homocysteine. 

Several studies have shown a link between uric acid concentrations and homocysteine levels. However, this exact relationship is uncertain. 

It is vital to note that deficiencies in folic acid, vitamin B12, and vitamin B6 levels have also been linked to both elevated homocysteine and uric acid levels. 

Folate, vitamin B6, and vitamin B12 all play crucial roles in lowering homocysteine. Folate also helps to inactivate xanthine oxidoreductase (XOR), the enzyme responsible for the oxidation of hypoxanthine to xanthine and xanthine to uric acid. 

However, both of these processes require the active form of folate, methylfolate. An MTHFR mutation impairs the conversion of dietary folate and synthetic folic acid into L-Methylfolate. 

The most effective way to overcome this impairment and optimize folate levels is to take a bioactive form of folate. L-Methylfolate is the only form of folate that crosses the blood-brain barrier and can be used instantly in the body. 

Studies have shown that methylated folate can help to reduce both homocysteine and uric acid levels. Supplementation with folate and vitamin B12 could help to prevent excess uric acid levels in both men and women and ultimately prevent the incidence and recurrence of gout.

Some of the best methylfolate supplements for those with MTHFR mutations or cardiovascular risks include Methyl-Life® products (B-Methylated II, Methylated Multivitamin, Methylfolate 7.5+ or Methylfolate 15+.) This product range has been created by a team of natural health experts and used successfully by those with cardiovascular conditions or nutritional deficiencies.  The form of L-Methylfolate used in Methyl-Life® products is the purest, most stable, and most potent of the world’s four industry-leading patented L-Methylfolates.