Microbiome targeting with nicotinic acid may improve insulin sensitivity in obesity

Last Updated: 2018-01-12

By Lorraine L. Janeczko

NEW YORK (Reuters Health) - Delayed-release nicotinic acid (NA) may boost Bacteroidetes, improve insulin sensitivity, and reduce inflammation in obese people, new research suggests.

"We discovered that it is possible to target the gut in human beings to improve their insulin sensitivity by encapsulating nicotinic acid for ileocolonic release," coauthor Dr. Charles Brenner told Reuters Health by email.

"We found that low niacin status of obese prediabetic people was associated with a particular deficit in Bacteroidetes. . . . We discovered that delivering nicotinic acid for ileocolonic release was safe and that this formulation of nicotinic acid, but not a similar formulation of nicotinamide (NAM), boosted Bacteroidetes, beneficially affected insulin sensitivity, and reduced signs of metabolic inflammation," said Dr. Brenner, who is a professor of biochemistry and internal medicine at the University of Iowa Carver College of Medicine, Iowa City,

Initially, serum and stool samples were collected from 511 adults with various metabolic phenotypes who had participated in the Food Chain Plus cohort. Using these samples, the researchers established that niacin intake in this cohort was associated with adverse gut microbiome changes, prompting them to develop "a microencapsulation procedure to deliver increasing amounts of NA or NAM into the ileocolonic region, where most of the gut bacteria are localized."

They then conducted a bioavailability study of 20 healthy volunteers (10 women) with a median BMI of about 23. They also conducted a proof-of-concept and safety study of 10 healthy volunteers (8 women) without manifest metabolic diseases and with normal glucose and triglyceride profiles; their median BMI was 27.

The effects of different dosages of microencapsulated NA or NAM were examined and then compared with effects after ingestion of a reference dose of free NA (30 mg) or NAM (900 mg).

NAM serum levels in the bioavailability study showed a delayed release 4 hours after oral intake, suggesting that the capsules opened in the ileocolonic region. Given the rapid metabolism of NA into NAM, only minimal fluctuations of NA serum levels were observed in the NA group, but not a consistent and dose-dependent increase. Even at the highest dose of the microencapsulated versions (300-mg NA, 3,000-mg NAM), the serum concentrations were not significantly higher compared with those associated with the reference doses of either NA or NAM.

The researchers write, "This finding clearly indicates that the delayed-release microcapsules deliver high amounts of NA or NAM to the microbiome without significant alterations in serum concentrations. This is important, because high systemic levels of NA are known to be associated with negative side effects such as facial flushing and liver dysfunction."

In the proof-of-concept and safety study, a significant increase in Bacteroidetes abundance was observed in the NA group but not the NAM group. One participant in the NA group showed a mild aspartate aminotransferase elevation at week 5 that returned to normal within 4 days. No other safety issues were reported.

NA also significantly reduced circulating osteopontin levels, suggesting an improvement of metabolic inflammation.

The researchers write, "In the absence of systemic side effects, these favorable microbiome changes induced by microencapsulated delayed-release NA were associated with an improvement of biomarkers for systemic insulin sensitivity and metabolic inflammation."

Dr. Brenner told Reuters Health, "Obese prediabetic individuals are at great risk for developing full-blown type 2 diabetes. Thus, a safe nutritional intervention that can improve their insulin sensitivity and reduce obesity-associated inflammation has tremendous public health potential." He called for larger clinical trials to assess dosing and safety, and to determine who will benefit most.

Dr. Jack Gilbert, faculty director of the Microbiome Center and professor in the Department of Surgery at the University of Chicago, said in an email that this is "a preliminary study."

"(It) could be a valuable tool later on, if we can show that such targeted therapy actually has health benefits," noted Dr. Gilbert, who was not involved in the study. "The association with systemic insulin sensitivity and metabolic inflammation improvements is useful, but it remains to be seen if this association is reproducible."

"If the NA and NAM provision is actually influencing microbial metabolic activity, there is plenty of evidence to suggest that microbial metabolic products can influence insulin sensitivity and inflammatory responses both locally and systemically," he added. "The value of the study comes from the specific nature of the targeted response. . . . If the results hold up to rigor, then it could suggest a potential mechanism for therapeutic treatment of insulin sensitivity."

Dr. Brenner is on the scientific advisory board of ChromaDex. Two authors are employees of CONARIS Research Institute AG, and several authors are inventors on a patent, owned by CONARIS, describing controlled-release formulations for NA and NAM; one author is the supervising board chair. The other authors, and Dr. Gilbert, report no pertinent conflicts of interest.

SOURCE: http://bit.ly/2Fmxbrt

Diabetes Care 2017.