Friday, July 01, 2016
Prediabetes, type 2 diabetes (T2D), and diabetes that is complicated by nerve damage (neuropathy) are increasingly common conditions worldwide. These conditions are the result of progressive problems in metabolism. Prediabetes and T2D are characterized by increasing levels of blood sugar and circulating fats (lipids) in conjunction with insulin resistance. Many prediabetics and half of T2D patients develop progressive damage to their nerves that can be painful or lead to a loss of sensation. Diabetic neuropathy can lead to loss of limbs and is severely debilitating. We know that weight management and keeping active are among the most important components for preventing these conditions and arresting their progression. However, scientists are always on the lookout for healthy ingredients that can help people control their weight, improve their blood glucose control, and help their nerves stay healthy. Recent research at the University of Iowa, supported by the Fraternal Order of Eagles Diabetes Research Center (FOEDRC), suggests that an over-the-counter vitamin supplement called nicotinamide riboside (NR) may do just that.
Initial studies were conducted in obese and diabetic mice. An overweight person might weigh more than 100 kilograms or 220 pounds while an overweight mouse weighs just 50 grams. But scientists frequently use mice to model human diseases such as obesity and diabetes. Just as human overweight conditions can be brought on by our sedentary lifestyles, mice that don’t have to forage for food can be made overweight by providing them with a high fat diet in their cages. The FOEDRC research groups of Dr. Charles Brenner, the Roy J. Carver Chair of Biochemistry, teamed up with Dr. Mark Yorek, associate chief of staff at the Iowa City Veterans Administration, to test the hypothesis that NR might help mice cope with obesity, diabetes and nerve damage. Brenner’s group had discovered NR as a vitamin 12 years ago (1) and had evidence that it would improve function of a metabolically stressed liver. Work from Washington University suggested that NR can help damaged nerves. Dr. Yorek’s group made 40 mice fat with a lard-filled diet and made half of those mice diabetic by damaging their insulin-producing cells. While the researchers continued to supply the fatty diet to all of these mice, half were given a diet supplemented with NR. To the investigator’s astonishment, NR helped prediabetic and diabetic mice control their blood sugar, reduced fatty liver and protected against nerve damage (2).
Like most vitamins, NR is a building block for other molecules. Using a technique called targeted metabolomics, the Brenner group determined that obesity and diabetes depressed levels of a key molecule called NADPH in the liver of mice and that NR helped keep NADPH in a normal range. This experiment suggests that NR may have aided the whole body metabolism and nerve health of mice by helping them control damage from reactive oxygen species. While more experiments are needed to fully understand the beneficial effects of NR in these prediabetic and diabetic models, the researchers are excited by the potential of an over-the-counter dietary supplement to improve metabolism. They aim to conduct clinical trials of NR for obesity, diabetes and complications in coming months.
These studies, which were published in the Journal Scientific Reports, were supported by the FOEDRC, the NIH, the Veteran’s Administration, and the Roy J. Carver Trust. Dr. Brenner has commercial interests in NR with its manufacturer, ChromaDex, Inc., and Healthspan Research, LLC, an NR supplier.