NEW YORK (Reuters Health) - Work in mice and humans suggests that the widely-used food preservative propionate (propionic acid) may impair the action of insulin, according to US and Israeli researchers.
The short-chain fatty acid propionate, which has potent anti-mold effects, is generally recognized as being safe and is endogenously produced by gut microbiota, the researchers say.
But as reported online April 24 in Science Translational Medicine, Dr. Amir Tirosh of the Sheba Medical Center, Tel-Hashomer, and colleagues found that the agent stimulates glycogenolysis and hyperglycemia in mice by increasing plasma concentrations of glucagon and fatty acid-binding protein 4 (FABP4). FABP4-deficient mice and mice lacking liver glucagon receptor were protected from its effects.
In addition, compared to control mice, over the course of 20 weeks, mice given drinking water with concentrations of propionate similar to concentrations in preserved foods gained more weight and had higher insulin resistance.
In a double-blind, placebo-controlled crossover study in 14 "lean and healthy" human volunteers, adding a typical preservative amount of propionate to a mixed meal increased glucagon and FABP4 levels and raised insulin resistance.
Furthermore, examination of serum samples from 160 overweight and obese volunteers taking part in a 2-year dietary intervention trial showed that plasma propionate decreased with weight loss. A greater decline in serum propionate (from baseline to 6 months) was associated with a significant improvement in insulin resistance. This was the case regardless of the dietary intervention or initial body weight. It thus served as an independent predictor of improved insulin sensitivity.
These and other data, say the investigators, suggest that "propionate may activate a catecholamine-mediated increase in insulin counter-regulatory signals, leading to insulin resistance and hyperinsulinemia, which, over time, may promote adiposity and metabolic abnormalities."
Dr. Tirosh told Reuters Health by email "The epidemic proportions of obesity and diabetes are attributed, at least in part, to exposure to a yet unidentified environmental and nutritional factors. Therefore, there is an urgent need to extensively assess the potential long-term metabolic effects of many food preservatives and additives that have been incorporated into our diet in the past few decades."
Summarizing the findings, senior author Dr. Gökhan S. Hotamisligi of the Broad Institute of MIT and Harvard, Cambridge, Massachusetts, said by email, "Our study illustrates the great potential of preventive opportunities against common diseases by understanding the molecular components of everyday foods. Propionic acid is one such ingredient and may have important implications for health but, of course, further mechanistic and clinical work is necessary to substantiate the translational value of our findings."
Commenting by email, Dr. Eliana Marino of Monash University, Australia, told Reuters Health, "Confounding results on short-chain fatty acid and their effects in health and disease, might be due to how they are used in processed foods or when they are produced naturally by the gut microbiota from fermentation of good food sources of fiber (i.e. vegetables, grains)."
Dr. Marino. who is Principal Research Fellow and Head of the Immunology and Diabetes Laboratory at the School of Biomedical Science, added, "This study emphasizes the role of high concentrations of propionate that are rapidly absorbed into the circulation. There is a gap on the effect of an excess of propionate on the gut microbiota. This possibly explains why an excess in the circulation counteracts the beneficial effects of propionate when it is produced by the gut microbiota, which is found in very low concentrations in blood."
Sci Transl Med 2019.
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