Low-Glycemic Diet May Stop Age-Related Eye Disease

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Age-related macular degeneration is the leading cause of vision loss in adults over the age of 50. Now researchers at Tufts University have published a new paper that suggests that development of age-related macular degeneration (AMD) can be arrested by switching from a diet high in starches (high-glycemic) to a low-glycemic diet that slows the release of sugars into the blood stream.

The researchers also believe that these findings, published in PNAS, point to potential biomarkers that can be used to predict when a person is at risk for AMD.

In early stages, AMD results in blurred vision. In advanced stages, AMD can make life very challenging. The National Eye Institute estimates that the number of people with AMD will double by 2050, from 2.07 million to 5.44 million. In the United States, white Americans are most likely to develop AMD and, in 2010, 2.5 percent of white adults aged 50 and older had AMD.

AMD is typically diagnosed only when vision loss has already begun, and unfortunately, there is no cure.

Using an aged mouse model, the researchers randomized 59 mice into two groups: 19 low-glycemic fed mice and 40 high-glycemic fed mice. The diets differed only in carbohydrate source. Carbohydrates comprised 45 percent of the diet in both cases. The carbohydrate source varied in the ratio of amylose and amylopectin, the two starches used for this work. The high-glycemic starch was 100 percent amylopectin while low-glycemic starch was 70 percent amylose and 30 percent amylopectin.

After six months, the high-glycemic group of mice either remained on the high-glycemic diet or were switched to the low-glycemic diet.

The researchers observed that a high-glycemic diet resulted in the development of many AMD features, including loss of function of cells at the back of the eye called retinal pigmented epithelial atrophy (RPE) and of the cells that capture light, called photoreceptors – precursors to dry AMD – whereas a low-glycemic diet did not. Importantly, switching from a high-glycemic diet to a low-glycemic diet arrested damage to the retina.

“We were genuinely surprised that the retinas from mice whose diets were switched from high- to low-glycemic index diets midway through the study were indistinguishable from those fed low-glycemic index diet throughout the study. We hadn’t anticipated that dietary change might repair the accumulated damage in the RPE so effectively. Our experimental results suggest that switching from a high-glycemic diet to a low-glycemic one is beneficial to eye health in people that are heading towards developing AMD,” said lead author Sheldon Rowan, Ph.D., scientist in the Laboratory for Nutrition and Vision Research at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University.

Potential Biomarkers

The researchers also identified potential biomarkers of AMD features. Such biomarkers can be used to predict who will get the disease. The biomarkers included advanced glycation end products (AGEs) that are formed when sugar metabolites react with proteins. They also included oxidized fats, C3-carnitine and serotonin levels. The low-glycemic diet limited the accumulation of AGEs and the oxidation of long-chain polyunsaturated fats. AGEs can be a factor in aging and the development of many degenerative diseases, in addition to AMD. Fat oxidation results in the degradation of fats in cell membranes, which can lead to cell damage.

The researchers also found that higher levels of C3-carnitine and serotonin in the blood were related to consuming the low-glycemic index diet and less AMD features. C3-carnitine, also known as propionylcarnitine, plays a role in fatty acid metabolism in cells and is found in many low-glycemic foods, such as whole wheat and legumes. Serotonin is made in the intestine, in response to signals that are produced by microbes in the gut. The researchers showed that the composition of gut microbes, collectively called the gut microbiome, changes in response to the diet. Higher serotonin levels are associated with retinal health and reduced frequency of AMD features. The researchers identified several other metabolites that were associated with protection from AMD and with the composition of the gut microbiome, which together led the authors to speculate on a potential gut-retina axis that may communicate diet to eye health.

Altogether, the findings suggest that changes in metabolism associated with the different glycemia diets, AGEs accumulation, production and oxidation of fats, and C3-carnitine and serotonin levels are related to development of AMD features.

Clinical tests are already available to test for some of these potential biomarkers. A screening of C3-carnitine levels is a standard part of the newborn screening profile, so it would not be challenging to adapt the existing screening to evaluate levels in AMD. There are also efficient clinical measures for serotonin. AGEs, however, are still emerging biomarkers, and have not been used on large-scale human studies yet. Even so, AGEs are among the most exciting potential AMD biomarkers, since we understand their damaging molecular effects very clearly.

Source: Sheldon Rowan, Shuhong Jiang, Tal Korem, Jedrzej Szymanski, Min-Lee Chang, Jason Szelog, et.al. Involvement of a gut–retina axis in protection against dietary glycemia-induced age-related macular degenerationProceedings of the National Academy of Sciences, 2017; 201702302 DOI: 10.1073/pnas.1702302114