In the early s Michel-Eugène Chevreul, a French organic chemist, first discovered butyric acid in its impure form while acidifying animal fat soaps. (Source)
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Butyric acid, also known as butanoic acid, is a four-carbon short-chain fatty acid that is found in a number of foods and is also produced in our bodies. Its name comes from the ancient Greek word for butter.
Known as the 'stinky fat,' butyric acid boasts an aromatic odor (to put it kindly) that has been described as both rancid butter and stale cheddar. It's also responsible for the familiar lactic acid flavor that we often associate with fresh, homemade bread, butter, and yogurt.
Although butyric acid is naturally occurring in different types of dairy products, it's found in even greater amounts in the digestive tracts of humans and other mammals. The organic compound is produced when complex sugars are broken down during the process of fermentation. Its main function is to provide energy to cells of the colon, but it also supports the immune system with its powerful anti-inflammatory and antimicrobial properties.
In today's edition, we're exploring butyric acid, AKA the pungent, rancid odor that you might recognize from that time your butter went bad ' and also a powerful healing nutrient in our bodies.
Butyric acid, also known as butanoic acid, is a short-chain, saturated fatty acid (SCFA) that is found in plant oils and animal fats, especially products such as butter, ghee, and raw milk. It's also produced when carbohydrates like fiber are fermented by bacteria in the colon.
Butyric acid is the preferred fuel of your enterocytes, the cells that line the intestines. In other words, it's what your gut cells prefer to burn for energy. Estimates suggest that the compound provides your colon cells with about 70% of their energy needs. (Source)
Note: Although the terms 'butyric acid' and 'butyrate' are commonly used interchangeably even in the literature, scientifically speaking, the two compounds have slightly different structures (butyrate has one less proton than butyric acid). However, research appears to show that they have identical health benefits.
Butyric acid can also help support your immune function and keep your gut barrier healthy. It's known to have anti-inflammatory and anti-carcinogenic properties and to play a role in gut barrier function, immune system regulation, and metabolic regulation. (Source) That's why the compound has gained attention for its potential role in treating inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and colorectal cancer. On the flip side, decreased butyrate concentrations and numbers of butyrate-producing bacteria have been linked with disorders, ranging from dysbiosis to strokes and even metabolic conditions. (Source, Source, Source, Source)
A diet high in fiber has long been considered a cornerstone of gut health, and now science is backing that up. Fiber promotes healthy intestinal flora and helps maintain healthy gut barrier function. It can also help reduce inflammation and insulin resistance, and may help reduce your risk of developing certain diseases, such as diabetes and heart disease.
As dietary fiber is fermented by bacteria in the gut, butyric acid is formed. Research suggests butyric acid in the gut helps kill colon cancer cells, making a high-fiber diet an important cancer prevention tool. (Source) Beyond that, butyrate can affect our brains by acting via the gut'brain axis. Through its ability to cross the blood'brain barrier, butyrate can activate the vagus nerve and hypothalamus, indirectly affecting appetite. (Source)
Thanks to its anti-inflammatory properties, butyrate can help control inflammation and modulate the immune response. In addition, butyric acid helps regulate the production and development of regulatory T cells in the colon, which are responsible for helping your body distinguish between itself and foreign invaders. Without the ability to tell self from nonself, the immune system may begin to attack your own tissues and organs, resulting in an autoimmune condition. (Source)
Related to immune function, butyrate also helps maintain healthy gut barrier function and prevent the incidence of leaky gut. (Source) Emerging evidence suggests there may be a link between butyrate and autoimmunity in humans as well. For example, people with type 1 diabetes ' an autoimmune condition that affects the ability of the pancreas to produce insulin ' have been found to have lower levels of butyrate-producing bacteria in their gut than those without diabetes. (Source)
Studies have revealed that butyric acid has a profound effect on the brain, ranging from memory and cognition issues to neurodegenerative diseases. In rat studies, butyrate stimulated the release of brain-derived neurotrophic factor (BDNF), a molecule that supports the growth and differentiation of healthy neurons in the brain. (Source) And in studies looking at animal models of Huntington's disease and Parkinson's disease, butyric acid has been shown to protect brain neurons from cell death and to extend the lifespan of mice with Huntington's. (Source, Source)
Numerous studies have reported that butyrate metabolism is impaired in patients with IBD. (Source) Butyric acid has been shown to decrease colitis-associated intestinal inflammation and colon cancer in both animal and human models. In a small study looking at the effects of butyrate on Crohn's disease, 69% of patients saw clinical improvements after treatment, with 53% of participants achieving remission. (Source)
Emerging evidence suggests that butyric acid may be a potential treatment option for IBS as well. (Source)
In one double-blind, randomized, placebo-controlled study, 66 adult patients with IBS took either a placebo or 300 milligrams of sodium butyrate (the sodium salt of butyric acid) per day, in addition to receiving standard therapy. Just four weeks into the 3-month study, researchers found that subjects who took the butyric acid had a statistically significant decrease in the frequency of abdominal pain during bowel movements. (Source)
One of the more controversial potential applications of butyric acid is its ability to impact insulin sensitivity and obesity. In many studies, butyrate has been shown to significantly improve insulin sensitivity and reduce insulin resistance in people with metabolic syndrome. (Source) Researchers believe that this may be a result of the compound's ability to increase GLP-1 (glucagon-like peptide-1) and PYY (peptide YY), hormones that help your body to control food intake and increase fat burning (Source, Source, Source).
However, although a large body of evidence has suggested that butyrate may attenuate obesity and insulin resistance, a few studies have shown the opposite effect. Therefore, more research is needed to understand the effects of butyrate on obesity.
-23: first observed in impure form by Michel Eugène Chevreul (Chevreul ) | : first synthesized by Lieben and Rossi (Goldberg )
Butyric acid is a four-carbon straight short chain fatty acid (SCFA) found in the esters of animal fats and plant oils. Its name comes from the Ancient Greek for butter, which is where it was first identified. Butyric acid is responsible for the foul smell found in rancid butter, parmesan cheese, vomit and body odor (Huang et al. ). Interestingly, as for isovaleric acid, some esters of butyric acid have a more appealing scent, and are often used in perfumes.
Butyric acid is one of three common SCFAs in the human gut, alongside acetic acid and propionic acid, which together make up 90-95% of the SCFAs in the colon (Ríos-Cavián et al. ). It is a major source of energy for the colon and is used in treatments for colorectal cancer, hemoglobinopathies and gastrointestinal diseases (Huang et al. ).
In industry, butyric acid has applications in food, textile production, animal feed, and biofuels, often chemically synthesized through the oxidation of propylene-derived butyraldehyde, or through syngas fermentation (Huang et al. ).
Most SCFAs in the gut come from dietary fibers: because humans lack the enzymes to digest these, they pass through the intestinal tract and are fermented by host bacteria. Butyric acid is a conjugate of butyrate, which is produced through the fermentation of hydrolysis-resistant starches and dietary fiber by anaerobic bacteria in the colon (Wong et al. ). Some butyrate is also produced as proteins and peptides are digested in the bowel (Macfarlane et al. ).
Diet, composition of the microbiome, and intestinal transit time all influence butyric acid formation, as with the other SCFAs (Morrison et al. ). Most of the dietary fiber from which butyric acid is produced comes from plant sources, such as resistant starch, cruciferous vegetables, and foods with a high sulphur content (Rivière et al. ). Dietary butyric acid is found in dairy products, red meat, and fermented foods such as sauerkraut. Around 5% of the saturated fat in dairy products comes from butyric acid (Månsson ). Butyric acid can also be taken in supplement form.
SCFAs are a popular research topic in medical biochemistry because of their potential role in gut function, glucose homeostasis, metabolic regulation, and appetite (Blakeney et al. ; Vijay et al. ). They are also known to influence inflammation and immune response.
In the colon, butyrate is a source of energy for endothelial cells, promotes cell differentiation and apoptosis, and can inhibit colonic acidification (Wong et al. ). Some studies suggest that butyrate can suppress colorectal cancer, though results are inconclusive (Silva et al. ). Butyric acid has been shown to influence pathogenesis of gastrointestinal disease and gut dysbiosis, and animal studies show that higher concentrations of butyric acid in the colon reduce the severity of inflammation.
SCFAs are known to act as signaling molecules between gut microbiota and host, with receptors in many different cell and tissue types (Morrison et al. ). Butyric acid is an endogenous agonist of one of these receptors, hydroxycarboxylic acid receptor 2 (HCA2). HCA2 is a protein receptor that can inhibit the breakdown of fats, giving butyric acid a key role in lipid metabolism. Butyric acid is also an agonist of the peroxisome proliferator-activated receptor (PPAR), a nutrient sensor which helps to stabilize lipid metabolism and inhibit cancer cell proliferation in the colon (Hong et al. ).
One notable way in which butyric acid regulates the inflammatory process is by stimulating the production of eicosanoids, which are lipid mediators derived from arachidonic acid (Vinolo et al. ). These are also known to regulate other immune processes involved in cancer, asthmas, and arthritis (Harizi et al. ).
As noted, butyric acid exerts several effects in the human gut which affect immune processes (Kovarik et al. ). Butyric acid is thought to increase acetylation of histone H3, in turn influencing the behavior of regulatory T cells, which can inhibit the immune response (Borycka-Kiciak et al. ). Through this mechanism, SCFAs link crosstalk between the human microbiome and immune system, though it is not clear whether this is by increasing tolerance in the microbiome, or by reducing the inflammatory response (Morrison et al. ).
Recent research has highlighted the significance of butyric acid in the gut microbiome, particularly its role in maintaining immune function and metabolic balance. For instance, a study investigating age-associated gut dysbiosis in older individuals living with HIV found a notable decrease in butyrogenic potential, correlating with alterations in plasma tryptophan metabolites (Brivio et al. )
A few clinical studies have observed an anti-inflammatory effect from the therapeutic use of SCFAs in cases of inflammatory bowel disease, radiation proctitis, and diabetes. Growing evidence suggests SCFAs support the immune system and metabolism through gut-liver inflammatory pathways (Morrison et al. ).
In addition to its role in the gastrointestinal tract, butyric acid may also contribute to links between gut dysbiosis and neurological conditions, such as depression, Alzheimer's disease, Parkinson's disease, and autism spectrum disorder (Silva et al. ).
Studies looking at the use of probiotics to increase butyrate-producing bacteria in the gut suggest butyrates could help reduce anxiety and lower stress (Bourassa et al. ). A review by Bourassa et al. proposed possible mechanisms for butyric acid's neuroprotective effects, including mitochondrial activity, G-protein coupled receptors, histone acetylation, and microbiome homeostasis. A clear line was drawn between the consumption of a high fiber diet, butyrate production, and protection against multiple neurological conditions through these pathways (Bourassa et al. ).
The role of SCFAs in lipid and energy metabolism links them to certain metabolic conditions. Butyrate has been shown to protect against diet-induced obesity and insulin resistance, which suggests it may offer potential therapeutic role in obesity-related diseases and diabetes (Lin et al. ). Animal studies confirm that butyric acid supplementation can improve insulin sensitivity: in one study, butyric acid caused fat loss and improved insulin tolerance in mice (Heimann et al. , Gao et al. ). More research is needed to confirm the effect in humans.
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Gut microbiota have a well-established link to coronary artery disease and atherosclerosis. One animal study has shown that butyrate supplementation could reduce atherosclerotic lesions, while another suggested that butyric acid seems to mediate gut microbiota and the circulatory system (Onyszkiewicz et al. ). Some studies have suggested that butyric acid affects arterial blood pressure, with one showing a significant hypotensive effect when butyric acid concentration in the colon was increased (Onyszkiewicz et al. ). The precise mechanism is unknown: it may result from bacterial metabolites having a stimulating enterosyne effect on the enteric nervous system, or from metabolite-derived molecules entering the circulatory system and influencing arterial blood pressure through various organs (Onyszkiewicz et al. ).
As noted, butyric acid has been shown in several studies to inhibit the proliferation of cancer cells in the colon, by inducing apoptosis, inhibiting cancer gene expression, inhibiting cancer cell proliferation, and promoting anti-inflammatory processes (Williams et al. ). However, other studies challenge the notion of a chemopreventive effect from butyrate, and there is a lack of agreement particularly when comparing in vitro and in vivo studies, referred to as the butyrate paradox (Lupton ). It seems likely that butyrate's chemopreventive effect depends on the amount of butyrate, time of exposure during the tumorigenic process, and type of dietary fat. Our understanding of the underlying molecular mechanisms is likely to grow with the advance of genomic and metabolomic technologies. Because butyric acid is a by-product of fiber fermentation, this could explain why high fiber diets help to protect against colorectal cancer, as well as obesity, stroke, type 2 diabetes and other conditions.
Learn more about the roles of butyric acid and other SCFAs in complex chronic diseases such as cancer, Alzheimer's disease, depression, inflammatory bowel disease, multiple sclerosis and diabetes in our whitepaper 'Complex chronic diseases have a common origin'.
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