Updated on January 3, 2023
Butyrate, also known as butyric acid, is an emerging alternative nutritional support therapy for a wide range of health conditions, particularly gastrointestinal disorders and GI-associated neurological conditions like autism spectrum disorder (ASD). Because many of the traditional therapies for these conditions have significant side effects that can interfere with the user’s quality of life, patients, families, and providers are naturally wary of the possible side effects of innovative new supplements that are gaining traction within the research and clinical communities. However, butyrate differs from pharmacological therapies in part because it is natural-based: not only do you eat it every day, but it is directly produced in the body, making it uniquely compatible with human physiology. Understanding how this compound works offers valuable insight into why butyrate supplement side effects are limited, and why this option is widely considered to be safe.
Butyrate is one of the most common short-chain fatty acids found in the gut. Together, butyrate, acetate, and propionate comprise 95 percent of the short-chain fatty acids in the body. The butyrate in the gastrointestinal tract comes from two sources. First, it enters the GI tract when fat-containing animal or plant products are eaten. The other source of butyrate in the body comes from the fermentation of non-digestible fiber by bacteria in the gut. These bacteria ferment insoluble fiber for energy, and butyrate is generated as a byproduct.
Of course, just because butyrate is synthesized by the body does not mean that a butyrate supplement will be free of side effects. However, the way butyrate works in the body suggests that the risk of side effects is minimal. Under normal conditions, the cells of the colon rapidly absorb short-chain fatty acids when they are synthesized by bacteria or introduced with food. In total, about 95 percent of short-chain fatty acids are quickly taken up by colon cells, and any excess butyrate the body doesn’t need is harmlessly excreted in feces—about 5 percent of the butyrate that is synthesized under normal conditions.
Although there are relatively few clinical studies on the safety and effectiveness of butyrate supplements for patients with gastrointestinal and neurological disorders, early studies indicate that side effects are unlikely to occur. In one double-blind, randomized, controlled study that explored the potential for the use of sodium butyrate to address IBS symptoms, none of the 66 trial participants reported adverse side effects. In another preliminary report on the possibility of using sodium butyrate for IBS, the result was the same—none of the participants experienced side effects.
For patients and providers who are concerned about potential butyrate supplement side effects, it can also be helpful to consider the FDA’s insight. The FDA relies on a wide range of data to determine the safety status of different compounds, and the FDA’s status of butyrate is that it is categorized as Generally Recognized As Safe (GRAS).
The safety profile of butyrate makes sense when you consider the way it works in the body. Once butyrate enters a cell, it can play a wide range of essential roles, which suggests that insufficient butyrate is much more likely to produce adverse effects than butyrate supplementation. Patients with autism and/or gastrointestinal disorders are at heightened risk for insufficient butyrate levels due to compromised gut microbiome health, which diminishes the efficiency of butyrate generation. This can have a broad range of detrimental effects, because butyrate plays a range of essential roles, including:
Butyrate supplements make sense for nutritionally supporting patients with gastrointestinal and neurological disorders in part because biochemical evidence suggests that the healthy functioning of the colon is directly linked to some of these activities. For instance, as a gene regulator, butyrate ensures the appropriate expression of the proteins needed to form “tight junctions,” which determine the permeability of the gut. Improper functioning of tight junctions can cause “Leaky Gut” syndrome, which can produce adverse gastrointestinal symptoms and might exacerbate the behavioral symptoms of autism by enabling harmful metabolites to enter the blood and circulate to the brain.
Based on an evaluation of the existing biochemical and clinical literature, the evidence is clear that the risks of having too little butyrate outweigh the risks of butyrate supplementation side effects. So far, reports of side effects in clinical trials are non-existent, and the normal processing of butyrate in the body indicates that extra butyrate not used for essential cell processes is simply excreted. Overall, its appealing safety and functionality profile is one of the main reasons why butyrate is considered to be one of the most promising emerging supplements on the market for providing nutritional support for gastrointestinal and neurological disorders.
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