Gout and Folate

Folate, a B vitamin, plays a critical role in many biological processes. It participates in the crucial biological process known as methylation and plays an important role in cell division: without sufficient amounts of folate, cells cannot divide properly.

Folate has been recommended as a preventive treatment for gout for at least 20 years. Some clinicians report that it can be highly effective.

Read more details about Folate.

However, what little scientific evidence we have on the method is contradictory.^1,2,3 It has been suggested that a contaminant found in folate, pterin-6-aldehyde, may actually be responsible for the positive effects observed by some clinicians.

Very high dosages of folate may be helpful for gout,⁷⁴ although some authorities suggest that it was actually a contaminant of folate that caused the benefit seen in some studies.⁷⁵ Furthermore, other studies have found no benefit at all.^76,77

Folate requirements rise with age. The official US and Canadian recommendations for daily intake are as follows:

• Infants o 0-6 months: 65 mcg o 7-12 months: 80 mcg
• Children o 1-3 years: 150 mcg o 4-8 years: 200 mcg
• Males o 9-13 years: 300 mcg o 14 years and older: 400 mcg
• Females o 9-13 years: 300 mcg o 14 years and older: 400 mcg
• Pregnant women: 600 mcg
• Nursing women: 500 mcg

Safety Issues

Folate at nutritional doses is extremely safe. The only serious potential problem is that folate supplementation can mask the early symptoms of vitamin B 12 deficiency (a special type of anemia), potentially allowing more irreversible symptoms of nerve damage to develop. For this reason, when taking more than 400 mcg daily, it is important to get your B 12 level checked. See the article on Vitamin B 12 for more information.

Very high dosages of folate, greater than 5 mg (5,000 mcg) daily, can cause digestive upset. The maximum recommended dosage of folate for pregnant or nursing women is 1,000 mcg daily (800 mcg if under 19 years old). ¹ Media reports that use of folate by pregnant women may increase their risk of breast cancer are based on a single study of highly questionable validity. ² At present, this is not considered a significant concern, but further research will follow.

As mentioned previously, the antiseizure drug phenytoin may interfere with folate absorption. However, folate may reduce the effectiveness of phenytoin. ^{3 4 5 6 7} If you are taking phenytoin, you should consult with a physician about the proper dosage of folate for you.

Also, as noted above, individuals who are taking the drug methotrexate for rheumatoid arthritis, juvenile rheumatoid arthritis, or psoriasis can safely take folate supplements at the same time. However, if you are taking methotrexate for any other purpose, do not take folate except on the advice of a physician.

Interactions You Should Know About

If you are taking

• Aspirin and other anti-inflammatory medications , drugs that reduce stomach acid (such as antacids , H 2 blockers , and proton pump inhibitors ), bile acid sequestrants (such as cholestyramine and colestipol ), carbamazepine , estrogen-replacement therapy , nitrous oxide , oral contraceptives , oral hypoglycemic drugs , phenobarbital , primidone , sulfa antibiotics , triamterene , valproic acid or the antibiotic trimethoprim-sulfamethoxazole : You may need to take extra folate.

• Phenytoin : You may need more folate. However, too much folate can interfere with this medication and cause seizures! Physician supervision is essential.

• Drugs in the nitroglycerin family: Folate may help them remain effective

• Pancreatin (a proteolytic enzyme ): It may be advisable to separate your dose of pancreatin from your dose of folate by at least 2 hours in order to avoid absorption problems.

• Methotrexate for rheumatoid arthritis, juvenile rheumatoid arthritis, or psoriasis: Evidence suggests that folate supplements may reduce side-effects of the drug without decreasing its benefits. Nonetheless, physician supervision is highly recommended. Note: If you are taking methotrexate for other conditions, folate might decrease the drug's effectiveness.

• Green tea and black tea may decrease the absorption of folic acid into the blood stream. ⁸

1. Dietary reference intakes for thiamin, riboflavin, niacin, vitamin B 6 , folate, vitamin B 12 , pantothenic acid, biotin, and choline. Available at: http://www.nap.edu. Accessed October 4, 2001.
2. Charles D, Andy R Ness AR , Campbell D, et al. Taking folate in pregnancy and risk of maternal breast cancer BMJ. 2004;329:1375-1376.
3. Butterworth CE Jr, Tamura T. Folic acid safety and toxicity: a brief review. Am J Clin Nutr. 50(2):353-8.
4. Lewis DP, Van Dyke DC, Willhite LA, Stumbo PJ, Berg MJ. Phenytoin-folic acid interaction. Ann Pharmacother. 29(7-8):726-35.
5. Berg MJ, Stumbo PJ, Chenard CA, Fincham RW, Schneider PJ, Schottelius DD. Folic acid improves phenytoin pharmacokinetics. J Am Diet Assoc. 95(3):352-6.
6. Ono H, Sakamoto A, Eguchi T, Fujita N, Nomura S, Ueda H, Sakura N, Ueda K. Plasma total homocysteine concentrations in epileptic patients taking anticonvulsants. Metabolism. 46(8):959-62.
7. Kishi T, Fujita N, Eguchi T, Ueda K. Mechanism for reduction of serum folate by antiepileptic drugs during prolonged therapy. J Neurol Sci. 145(1):109-12.
8. Alemdaroglu NC, Dietz U, Wolffram S, Spahn-Langguth H, Langguth P. Influence of green and black tea on folic acid pharmacokinetics in healthy volunteers: potential risk of diminished folic acid bioavailability. Biopharm Drug Dispos. 29(6):335-48.

1. Lewis AS, Murphy L, McCalla C, et al. Inhibition of mammalian xanthine oxidase by folate compounds and amethopterin. J Biol Chem. 1984;259:12-15.

2. Flouvier B, Duvulder B. Folic acid, xanthine oxidase, and uric acid [letter]. Ann Intern Med. 1978;88:269.

3. Boss GR, Ragsdale RA, Zettner A, et al. Failure of folic acid (pteroylglutamic acid) to affect hyperuricemia. J Lab Clin Med. 1980;96:783-789.

74. Oster KA. Evaluation of serum cholesterol reduction and xanthine oxidase inhibition in the treatment of atherosclerosis. Recent Adv Stud Cardiac Struct Metab. 1973;3:73-80.

75. Boss GR, Ragsdale RA, Zettner A, et al. Failure of folic acid (pteroylglutamic acid) to affect hyperuricemia . J Lab Clin Med . 1980;96:783-789.

76. Flouvier B, Devulder B. Folic acid, xanthine oxidase, and uric acid [letter]. Ann Intern Med. 1978;88:269.

77. Boss GR, Ragsdale RA, Zettner A, et al. Failure of folic acid (pteroylglutamic acid) to affect hyperuricemia . J Lab Clin Med . 1980;96:783-789.