Autism Gastrointestinal

What You Need to Know About Butyrate Supplement Side Effects

butyrate supplement side effects

Butyrate, also known as butyric acid, is an emerging treatment option for a wide range of health conditions, particularly gastrointestinal disorders and GI-associated neurological conditions like autism spectrum disorder (ASD). Many of the traditional treatment options for these conditions have significant side effects that can interfere with the user’s quality of life, so patients, families, and providers are naturally wary of possible side effects of new supplements that are gaining traction within the research and clinical communities. However, butyrate differs from pharmacological therapies in part because it is all-natural: not only do you eat it every day, but it is directly produced in your body, making it uniquely compatible with our physiology. Understanding how this compound works offers valuable insight into why butyrate supplement side effects are limited and why this treatment option is widely considered to be safe.

Evaluating the Risk of Butyrate Supplement Side Effects

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 you eat fat-containing animal or plant products. The other source of butyrate in the body the fermentation of non-digestible fiber by the 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 your body does not necessarily mean that a supplement will be free of side effects. However, the way it 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 the bacteria or introduced with food. In total, about 95% of short chain fatty acids are quickly taken up by these cells, and any excess that the body doesn’t need is harmlessly excreted in feces—about 5% 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 exploring the potential for the use of sodium butyrate to treat patients with IBS, not one of the 66 participants in the trial reported adverse side effects. In another preliminary report on the possibility of using sodium butyrate for IBS, the result was the same—not a single participant said they experienced side effects.

For patients and providers who are concerned about potential butyrate supplement side effects, it can also be helpful to consider the insight of the FDA. The FDA relies on a wide range of data to determine the safety status of different compounds, and the status of butyrate is Generally Recognized As Safe (GRAS).

How Butyrate Works in the Body

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, diminishing the efficiency of butyrate generation. This can have a broad range of detrimental effects, as butyrate plays a range of essential roles, including:

  • Gene regulation. In vitro evidence indicates that butyrate regulates epigenetic to DNA and the surrounding molecules, which determines when and where certain genes are expressed. Not only does this ensure that colon cells are producing the proteins they need for normal functioning—such as those that form tight junctions—but the role of butyrate as a gene regulator also has implications for colon cancer: the activities initiated by butyrate help prevent unchecked cell growth and proliferation.
  • Transmembrane protein activation. Studies show that butyrate can activate several types of G-protein-coupled receptors (GPCRs). The proteins in this family play a role in a wide range of cell signaling and communication activities.
  • Energy substrate for metabolic processes. Butyrate serves as the substrate for metabolic processes in both human colon cells and gut bacteria. This keeps them functioning at optimal levels.

Butyrate supplements make sense for 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 that are 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 gastrointestinal symptoms and may exacerbate behavioral symptoms of autism by enabling harmful metabolites to enter the blood and circulate to the brain.

Butyrate also offers protective effects against cancer due to its role in preventing the unchecked growth and proliferation of colon cancer cells. Butyrate promotes the expression of a GPCR that initiates apoptosis, and some studies also show that when butyrate levels are high—leading to increased gene regulatory activities—cancer cells respond by initiating apoptosis.

The Benefits Outweigh the Risks

Based on an evaluation of the existing biochemical and clinical literature, evidence is clear that the risks of having too little butyrate outweigh the risks of butyrate supplement side effects. So far, reports of side effects in clinical trials are nonexistent, and the normal processing of butyrate in the body indicates that any extra butyrate that is not used for essential cell processes would simply be excreted. Overall, the 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 the treatment of gastrointestinal and neurological disorders.

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Works Cited

CFR – Code of Federal Regulations Title 21. 2017. FDA.

Den Besten G, Van Eunen K, Groen AK, Venema K, Reijngoud DJ, Bakker BM. 2013. The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism. Journal of Lipid Research. 54(9): 2325-2340.

Fellows R, Denizot J, Varga-Weisz P. 2018. Microbiota derived short chain fatty acids promote histone crotonylation in the colon through histone deacetylases. Nature Communications. 105(2018).

MacFabe, DF. 2012. Short-chain fatty acid fermentation products of the gut microbiome: Implications in autism spectrum disorders. Microbial Ecology in Health and Disease. 23.

Michielan A, D’Inca R. 2015. Intestinal permeability in inflammatory bowel disease: Pathogenesis, clinical evaluation, and therapy of leaky gut. Mediators of Inflammation.

Reckhemmer G, Ronnau K, von Engelhardt W. 1988. Fermentation of polysaccharides and absorption of short chain fatty acids in the mammalian hindgut. Comparative Biochemistry and Physiology A. 90(4): 563-8.

Rios-Covian D, Ruas Madiedo P,  Margolles A. 2016. Intestinal short chain fatty acid and their link with diet and human health. Frontiers in Microbiology. 7:185.

Thangaraju M, Cresci G, Liu, K, Ananth S, Gnanprakasam JP, et al. 2008. GPR109A is a G-protein-coupled receptor for the bacterial fermentation product butyrate and functions as a tumor suppressor in colon. Cancer Research. 69(7):2826-32.

Zaleski A, Banaszkiewicz A, Walkowiak J. 2013. Butyric acid in irritable bowel syndrome. Przeglad Gastroenterologiczny. 8(6): 350-3.

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