Lowering Dietary Glycemic Index Reduces Plasma Uric Acid

Janis C. Kelly

January 13, 2016

A low–glycemic index (GI) diet including foods such as legumes, dairy products, and some fruits might help prevent the development of gout or the occurrence of gout flares, according to a new analysis of diet and plasma uric acid. Stephen P. Juraschek, MD, PhD, a fellow in the Division of General Internal Medicine, Johns Hopkins Hospital, Baltimore, Maryland, and colleagues report the results of the study in an article published online December 4 in Arthritis & Rheumatology.

"Most of the dietary recommendations for the treatment of gout are based on observational studies or clinical anecdotes. Clinical trials on uric acid reduction in patients with hyperuricemia and gout are lacking," Dr Juraschek told Medscape Medical News.

"While our study was not conducted in a population with hyperuricemia or gout, we show that a low-GI, high-carbohydrate diet can modestly reduce uric acid levels. While similar studies are needed in patients with hyperuricemia or gout, it is reasonable for clinicians to recommend GI reduction as one aspect of a lifestyle-based strategy to reduce uric acid levels," he said.

The effects of GI on uric acid were unexpected. "The primary OmniCarb paper on the effects of GI on cardiovascular disease risk factors showed little impact of GI on lipids, insulin sensitivity, and blood pressure. However, the current manuscript demonstrates that it does play a role in intracellular metabolism, as uric acid is a product of the pentose phosphate shunt pathway. It is possible that these changes in intracellular metabolism contribute to alterations in gene expression and cell function that could contribute to the development of the metabolic syndrome downstream. Further research is needed to substantiate these hypotheses, however," Dr Juraschek said.

The OmniCarb Trial

The researchers analyzed the effect of changing carbohydrate intake on plasma uric acid levels as an ancillary study, using data from the Effect of Amount and Type of Dietary Carbohydrates on Risk for Cardiovascular Heart Disease and Diabetes Study (OmniCarb) trial. OmniCarb was a randomized, crossover clinical feeding study that compared the effect of different diets on cardiovascular risk factors in 163 overweight or obese adults who did not have cardiovascular disease, about half of whom were women and half of whom were non-Hispanic blacks. Mean plasma uric acid was 4.7 mg/dL. Only 5% of the participants met criteria for hyperuricemia, but 56% were obese, and 26% were hypertensive but not receiving antihypertensive treatment.

Body weight was maintained at constant levels while participants were fed each of the study diets for 5 weeks, separated by 2-week washout periods. The study diets were: high GI (GI ≥ 65) with a high percentage of carbohydrates (58% kcal), low GI (GI ≤ 45) with a low percentage of carbohydrates (40% kcal), low GI with high percentage of carbohydrates, and high GI with low percentage of carbohydrates. The low-percentage-of-carbohydrates diet was also a high-protein diet. Plasma uric acid was measured at baseline and after each feeding period.

The authors write, "We hypothesized that decreasing glycemic index would increase uric acid concentration, as higher insulin levels are known to lower renal uric acid excretion. Furthermore, since decreasing carbohydrate amount was achieved by increasing the amount of dietary protein, we expected that decreasing carbohydrate amount would increase uric acid concentration as well."

They were therefore surprised to find that reducing dietary GI actually decreased uric acid concentrations, whereas reducing the proportion of dietary carbohydrate increased uric acid concentrations, and that the greatest effect on uric acid was when the GI was reduced at the same time the amount of carbohydrates was increased.

Changing the GI seemed to be more important than changing the proportion of carbohydrate with regard to effect on uric acid concentration, Dr Juraschek explained.

Reducing GI lowered uric acid by 0.24 mg/dL when the percentage of carbohydrates was low and by 0.17 mg/dL when the percentage of carbohydrates was high (both P < .001). Conversely, reducing the percentage of carbohydrates increased uric acid by 0.10 mg/dL when GI was high (P = .05) and had no significant effect when GI was low. The largest effect was seen with reducing the GI while increasing the percentage of carbohydrates, which reduced uric acid by 0.27 mg/dL (P < .001), an effect maintained even after adjustment for changes in kidney function, insulin sensitivity, and products of glycolysis.

"We were surprised that GI was more important than carbohydrate quantity," Dr Juraschek said. "It has long been thought that dietary protein is a major determinant of uric acid levels. Recent observational data suggest that animal-based protein, not vegetable-based protein, is important for uric acid levels. Our findings confirm these observations, as changes in vegetable-based protein in OmniCarb had less of an impact on uric acid levels. It should be noted, however, that these changes in protein were coupled with simultaneous increases/decreases in fat, which could confound these observations."

Tom Osborn, MD, a rheumatologist at Mayo Clinic in Rochester, Minnesota, who was not involved in the study, told Medscape Medical News, "The data appear valid. Clinically this would not seem likely to be of significant benefit since the change in uric acid was only about 5% less, −2.4 to −4.7 mg/dL."

The study also raised new questions about alcohol consumption, diet, and uric acid levels.

"Alcohol consumption among all participants in the OmniCarb trial was minimal; however, we found that the effects of GI on uric acid were greater in participants consuming less than 1.045 g per week (or about 1 drink every 14 days) in the context of a high-carb diet or when [percentage of carbohydrates] was also reduced," said Dr Juraschek.

"It should be noted that this difference in effect was not observed when GI was reduced in the context of a low-carbohydrate diet or when GI was reduced as [percentage of carbohydrates] was increased. As a result, we have a mixed message from the data. We know alcohol plays an important role in uric acid concentrations and gout; however, mild alcohol consumption did not negate the effects of GI all the time. This represents an area of interest for future research," he added.

The study was funded by the National Institutes of Health. Study food was donated by the Almond Board, International Tree Nut Council, Olivio Premium Products Inc, and tThe Peanut Institute. The authors have disclosed no relevant financial relationships.

Arthritis Rheum. Published online December 4, 2015. Abstract

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