Butyrate, a.k.a. butyric acid, is a short-chain fatty acid that occurs naturally in dairy fat, including human breast milk. Butter is the richest known source of butyrate (about 3-4% of its total fat)—in fact, the word butyrate is derived from the Greek word for butter. Apart from being consumed in the diet, butyrate is synthesized in the human body as a byproduct of colonic microbes fermenting prebiotic fibers that reach the colon intact. (Resistant starch is known to be especially butyrogenic.) Other short-chain fatty acids (SCFAs), such as propionate and acetate, are also synthesized via bacterial fermentation of prebiotic fiber, but 4-carbon butyrate is the most widely studied and has the most evidence supporting beneficial effects on gut health, gut-associated immune function, and neurological function. Here we’ll take a closer look at the anti-inflammatory effects of supplemental butyrate. 

Butyrate may be responsible for many of the positive effects associated with consumption of dietary fiber. And while most North Americans could likely benefit from increased fiber intake, various circumstances may make it undesirable to increase fiber consumption. (For example, in a seemingly paradoxical outcome, rather than increased dietary fiber ameliorating idiopathic constipation, eliminating fiber completely resolved all signs and symptoms, as documented in a provocative study in the World Journal of Gastroenterology.) In such cases, and for individuals who may benefit from higher levels of butyrate in the body, supplementing directly with this unique fatty acid may have positive effects. 

Butyrate appears to be a major player in influencing the gut-brain axis, in part by promoting assembly of tight junctions to support the crucial barrier function of the intestine, as well as by stimulating intestinal mucus production. Butyrate also directly nourishes colonocytes, serving as their primary fuel source and also stimulating their growth and differentiation. By promoting intestinal integrity, butyrate may influence a number of physical and psychological health concerns. 

Crosstalk between the gut and the brain is well known and gut dysfunction and/or altered gut flora may contribute to pathologies in the brain and central nervous system (CNS). In particular, neurological and neurodegenerative disorders, such as Parkinson’s disease, as well as select psychiatric disorders, may have their origins in gut disturbances. Targeting butyrate production is being investigated as a potential therapeutic intervention for various neurodegenerative conditions and mood disturbances such as Parkinson’s disease, depression, Alzheimer’s, Huntington’s, and even autism. Some of these conditions may have their roots in neuroinflammation, so to the extent that butyrate supports gut function and a healthy microbiota, as well as serving as a histone deacetylase inhibitor, it may play a role in lessening immune responses that may be triggering neuroinflammation. 

Beyond effects in the gut that may affect the brain, butyrate may have direct functions in the brain and CNS. Butyrate crosses the blood-brain barrier via transmembrane proteins in the epithelial layer, and neurons, astrocytes, microglia and oligodendrocytes all express monocarboxylate transporters that may be used to import SCFAs. 

In terms of having an impact on various intractable neurological and neurodegenerative conditions, it may be necessary to supplement with butyrate at supraphysiological doses—concentrations much higher than would be produced by consuming a diet high in fiber and/or dairy fat. According to researchers, “Supraphysiological doses of butyrate exert potent neuropharmacological effects,” and “We find fundamental differences in natural butyrate at physiological concentrations and its use as a neuropharmacological agent at rather high, supraphysiological doses in brain research.”

Moving south from the brain and looking at the gut, numerous studies have shown that among patients with irritable bowel syndrome (IBS), supplemental sodium butyrate results in reductions in frequency of abdominal pain during defecation, postprandial abdominal pain, and urge after defecation, with increased quality of life and no observed adverse side-effects. The beneficial effect of butyrate on IBS may be due in part to butyrate’s suppression of inflammation in the gut, an effect substantiated in mice. Rodent research also indicates that butyrate increases the proportion of cholinergic enteric neurons and helps to regulate colonic motility, leading researchers to speculate that butyrate “might be used, along with nutritional approaches, to treat various gastrointestinal motility disorders associated with inhibition of colonic transit.”

For inflammatory bowel conditions in general, “IBD patients have dysbiosis with reduced numbers of SCFAs-producing bacteria and reduced BT [butyrate] concentration that is linked to a marked increase in the number of proinflammatory immune cells in the gut mucosa of these patients. Thus, microbial dysbiosis and reduced BT concentration may be a factor in the emergence and severity of IBD.”

Butyrate may also be beneficial for individuals with diverticulosis. In a randomized clinical trial of such patients, compared to placebo, 300mg of sodium butyrate taken daily over 12 months resulted in a significant reduction in the sensation of lower abdominal pain and no adverse events were reported. Compared to placebo, the treatment group also had fewer diagnoses and hospitalizations for diverticulitis, but the overall numbers were very small and did not reach significance. The authors concluded that administration of sodium butyrate in asymptomatic patients with diverticulosis can lead to a significant decrease in clinical diverticulitis incidence and the need for imaging studies related to diverticulitis.

High-fiber diets have long been recognized for their numerous beneficial effects on health. Some of these effects may be mediated through butyrate production, and intriguing research continues to elucidate mechanisms by which supplementing directly with butyrate may produce favorable changes not achievable through diet alone.