Exploring the Potential Health Benefits of Butyric Acid

Butyric acid is a multifunctional molecule that has long been recognized for its distinct smell, its biting flavor, and—most importantly—its wide range of health benefits. As the body of research highlighting potential health benefits of butyric acid grows, both researchers and health practitioners are starting to recommend bioavailable butyric acid supplements for patients. An increase in the awareness of the benefits of butyric acid has also prompted patients and families to start seeking out butyric acid supplements themselves. Because of the involvement of butyric acid in a wide range of biochemical processes, butyric acid can aid in the prevention, management, and/or treatment of a variety of health conditions, including gastrointestinal problems, colon cancer, diabetes/metabolic disorders, and neurological disorders.

The Basics of Butyric Acid: What It Is, Where It Comes From, How It Works

Butyric acid is a short-chain fatty acid (SCFA): consisting of an acid “head” molecule linked to a chain of carbon and hydrogen atoms. For the human body, there are two sources of butyric acid. First, it can come from diet, either through animal fats, plant oils, or nutritional supplements. In addition, butyric acid is directly synthesized by bacteria in the colon during the fermentation process for non-digestible fiber.

Functionally speaking, butyric acid is a highly versatile molecule, which is why it has such a wide range of benefits. Within the body, butyric acid can act in the following capacities:

  • Epigenetic regulator. Epigenetic regulators are molecules that control where and when certain genes are expressed. Butyric acid is a histone deacetylase (HDAC) inhibitor, which means it is a type of epigenetic regulator that can block the function of proteins that make chemical changes to DNA and DNA storage molecules.
  • Energy substrate. An energy substrate is the starting material for metabolic processes that generate energy in the form of Adenosine triphosphate (ATP): the energy currency of the cell. Butyric acid serves this purpose for both gut bacteria and human colon cells.
  • Transmembrane protein activator. Butyric acid has been shown to activate several different proteins in the G-protein coupled receptor (GCPR) family. This protein family is involved in multiple cell signaling and communication processes, so it is no surprise that the benefits of butyric acid are so wide-ranging.

Alleviating Gastrointestinal Symptoms

Most of the scientific research on the benefits of butyric acid focuses primarily on the GI tract, where it seems to have the most significant effects. That makes sense since butyric acid comes mostly from food and from fermentation in the gut microbiome. Studies have shown that butyric acid can have positive impacts on patients with both functional and inflammatory bowel disorders.

Functional bowel disorders, such as irritable bowel syndrome (IBS): can be characterized by a wide range of symptoms, including constipation, diarrhea, and abdominal pain, among others. Although clinical studies are limited, several have shown that taking butyric acid can lead to statistically significant reductions in abdominal pain and improvements in the normalization of bowel movements in IBS patients. The exact mechanism underpinning these effects is not fully understood. However, the presence of butyric acid in the gut can inhibit the growth of “bad bacteria” that negatively affect function and can cause infection, which may explain reduction of symptoms. Butyric acid may also impact water absorption in the gut, which is relevant for patients who experience diarrhea.

While clinical studies probing the benefits of butyric acid for patients with inflammatory bowel diseases like Crohn’s disease are lacking, there are in vitro studies that support anecdotal evidence. Through its effects on gene expression, butyric acid indirectly impacts the activities of pro-inflammatory mediator proteins in the cell—most notably NF-KB —as well as the differentiation of T-regulatory cells. That means it can have important effects on the inflammatory aspects of the immune response and potentially reduce inflammation. Additionally, researchers have found that exposing human colon cells to butyric acid also increased levels of glutathione (GSH): a powerful antioxidant, and reduced levels of reactive oxygen species, which suggests that butyric acid supplementation may be able to limit the oxidative damage that contributes to inflammation in the gut.

Preventing and Treating Colon Cancer

One of the most intriguing possible benefits of butyric acid is the ability to prevent or even treat colorectal cancer. Currently, the clinical evidence in primarily anecdotal, but when it comes down to the biochemistry, the results are clear: butyric acid can inhibit the growth and proliferation of colon cancer cells. That’s largely because of the well-known “Warburg effect,” which describes the tendency of cancer cells to generate energy almost entirely through anaerobic processes like fermentation—even in the presence of oxygen. Normal cells do not do this because anaerobic metabolism is less energy efficient. Using fermentation as a primary energy generation method leads to the production of unusually high levels of butyric acid. In turn, high levels of butyric acid increase its gene-regulatory activities in the cell, which causes a colon cancer cell to undergo apoptosis—that is, controlled cell death.

Similarly, there is evidence suggesting that butyric acid can promote the expression of a GCPR that induces cancer cell apoptosis. Normally, the GCPR is not active in colon cancer cells, but evidence indicates that when butyric acid is introduced, it can cause the GCPR to activate, which can cause the cancer cell to undergo apoptosis. This cell communication pathway is entirely separate from the HDAC-mediated pathway, which makes butyric acid an even more exciting treatment possibility for researchers to explore in the future, since it may combat colorectal cancer through multiple pathways—which would make the treatment more effective by coming at the cancer from multiple directions.

Aiding in Weight Loss and Diabetes Management

Although the research on the potential for butyric acid to contribute to weight loss efforts is still in the early stages, animal studies suggest that there may be benefits of butyric acid for patients with diabetes, metabolic syndrome, and obesity. For instance, in one study, a supplement of butyric acid significantly reduced obesity and insulin resistance in mice that were fed a high-fat diet. There is also some evidence suggesting that butyric acid may promote the release of hormones that suppress appetite. While it is clear that human studies will be needed before any strong conclusions can be drawn, butyric acid supplementation presents an exciting avenue for researchers and clinicians who are looking for innovative ways to help patients confront issues related to energy intake and metabolism.

The Potential Benefits of Butyric Acid for Neurological Health

So far, most of the evidence-based benefits of butyric acid are tied to the gut microbiome and/or the GI tract, but the growing understanding of the gut-brain axis within the medical community has prompted researchers to consider a possible role for butyric acid for brain health. As a group of researchers from Weill College of Cornell University pointed out in a 2016 review, butyric acid may be an ideal candidate for treating complex neurological disorders, since it has such wide-ranging functionality.

A variety of studies provide preliminary evidence for this hypothesis. For instance, several studies suggest that the sodium salt form of butyric acid can protect neurons from cell death in animal models of Huntington’s disease and Parkinson’s disease. Many neurological disorders are also associated with a reduction in the availability of glucose in the brain, which may be directly impacted by the effects that butyric acid has on the expression of energy metabolism-related genes, as well as the compound’s interaction with GPCRs that are involved in energy balance and metabolism. Interestingly, the Cornell researchers propose that butyric acid could also serve as an energy substrate for brain cells, the way it does for colon cells, which could potentially help restore energy homeostasis in patients with neurological disorders.

Future Explorations of the Benefits of Butyric Acid

Future explorations of the benefits of butyric acid will likely proceed in many different directions, but the early laboratory and clinical evidence clearly indicates that butyric acid can have positive impacts on patients with a wide range of conditions. Given the strong biochemical support for the potential efficacy of butyric acid for preventing and treating gastrointestinal, neurological, and metabolic disorders, researchers and clinicians alike are looking ahead to larger-scale clinical studies that support the growing body of anecdotal evidence on the real-world benefits of butyric acid supplementation for patients. Some are already recommending it to their patients, and many well-informed patients are discovering it for themselves as well.

Foundational Medicine Review is dedicated to exploring innovative treatment options for addressing gastrointestinal, neurological, and metabolic disorders. Join our mailing list for monthly updates on the latest news and research.

Works Cited

Bourassa MW, Alim I, Bultman SJ, Ratan RR, et al. 2016. Butyrate, neuroepigenetics, and the gut microbiome: can a high fiber diet improve brain health? Neuroscience Letter., 625:56-63.

Den Besten G, van Enen K, Groen AK, Venema K, Reijnoud D, et al. 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.

Gao Z, Yin J, Zhang J, Ward RE, Martin RJ, et al. 2009. Butyrate improves insulin sensitivity and increases energy expenditure in mice. Diabetes. 58(7):1509-17.

Hammer HM, Jonkers DM, Bast A, Vanvoutvin SALW, Fischer MAJG, et al. 2009. Butyrate modulates oxidative stress in the colonic mucosa of healthy humans. Clinical Nutrition. 28(1):88-93.

Kimura, I., Inoue, D., Maeda T, Hara T, Ichimura A, et al. 2011. Short-chain fatty acids and ketones directly regulate sympathetic nervous system via G protein-coupled receptor 41 Proceedings of the National Academy of Sciences of the United States of America. 108(19):8030-5.

Ogawa H, Rafiee P, Fisher PJ, Johnson NA, Otterson MF, et al. 2011. Butyrate modulates gene and protein expression in human intestinal endothelial cells. Biochemical and Biophysical Research Communications. 309(3):512-9.

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.

Segain JP, Bletiere R, Boureille A, Leray V, Gervois V, et al. 2000. Butyrate inhibits inflammatory responses through NFkappaB inhibition: implications for Crohn’s disease. Gut. 47(3):397-403.

Smith JG, Yokoyama WH, German, JB. 1998. Butyric acid from the diet: actions at the level of gene expression. Critical Review of Food Science and Nutrition, 38(4):259-97.

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): 350-53.

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