Butyrate is crucial for gut and brain health, fights autoimmunity and obesity, and may protect against cancer. Read on to learn about the benefits of butyrate, possible side effects, and sources.
Butyrate is a short-chain fatty acid (SCFA). Fatty acids are the building blocks of fats that our cells need to function. Butyrate is made when the bacteria living in our guts ferment otherwise indigestible fibers from grains, beans, onions, bananas, and other foods rich in complex carbs [1, 2, 3].
Butyrate is the preferred energy source for the cells in your colon wall. It is essential for maintaining a healthy barrier between the colon and bloodstream and it prevents inflammation in the gut .
Butyrate production depends largely on the pH of the large intestine. Bacteria that produce butyrate thrive in a more acidic environment (lower pH), whereas bacteria that produce other SCFAs such as acetate and propionate prefer a more alkaline environment (higher pH) .
“I personally take 4 pills of calcium/magnesium butyrate twice a day, with lots of resistant starch, which the gut bacteria feeds off of to produce butyrate.
I like calcium and magnesium butyrate because I don’t consume enough calcium and I prefer to have more magnesium. I already take in enough sodium.
Since I take a total of 8 pills a day, I avoid brands that add excipients.
I also take modified citrus pectin. It has a nootropic and wakefulness-promoting effect for me. It also chelates heavy metals without binding your beneficial minerals. All in all, it’s a great choice.
I find the Hi-Maize stronger than the pills, but it takes about 20 hours for the effects to kick in. GLP-1-related effects can kick in much sooner.
Each source of butyrate is good in different ways. Butyrate gets to the stomach and small intestines, whereas the fibers are obviously better at producing butyrate in the large intestine.
I go into detail about other supplements I take that have had a beneficial impact on my health in various other SelfHacked posts. A condensed and easy-to-navigate list of all the supplements and biohacks that have helped me greatly can be found in my book, SelfHacked Secrets.
Butyrate inhibits histone deacetylase (HDAC), an enzyme that packs up DNA into tight, compact structures and prevents it from being expressed; in other words, butyrate loosens up the DNA structure and increases gene expression [5, 6].
The relationship between butyrate and HDAC helps explain why our gut flora have such a large influence on our mental health. Sure enough, people with major depressive disorder have fewer butyrate-producing bacteria in their intestines .
Butyrate is essential for maintaining a healthy environment in the gut. In the human colon, anaerobic bacteria such as Clostridium butyricum, Roseburia intestinalis, and Faecalibacterium prausnitzii ferment carbohydrates and produce short-chain fatty acids (SCFAs): acetate, propionate, and butyrate [3, 10, 11].
Butyrate nourishes the colon wall, maintains a healthy lining and barrier function of the colon, and prevents intestinal inflammation .
In the mitochondria of colon cells, 70-90% of butyrate is oxidized into acetyl-CoA, which is then used to generate large quantities of ATP, the primary form of cellular energy .
If you don’t have enough butyrate-producing bacteria in your gut, you may be at risk of serious problems such as diarrhea, inflammatory bowel disease (IBD), and even colon cancer [13, 14, 15, 16, 17].
Short-chain fatty acids, especially butyrate, can reduce the symptoms of inflammatory bowel disease (IBD). In one study of 13 people with Crohn’s disease, a type of IBD, butyrate supplements improved 69% of cases, with symptoms completely disappearing in 54% (seven participants) [18, 19, 20, 21].
There are a variety of approaches for using butyrate to manage IBD and colitis. The treatment strategies range from a high-fiber diet to butyrate-producing probiotics, coated butyrate tablets, and rectal enemas [22, 23].
Butyrate can also prevent inflammation and stomach ulcers caused by alcohol. Mice given butyrate before alcohol had less inflammation and damage to the lining of their stomachs .
Sodium butyrate in combination with other SCFAs and silicon dioxide was also shown to benefit traveler’s diarrhea, a condition common among those who travel to exotic countries .
According to overwhelming evidence, butyrate is vital for healthy gut flora, controlling inflammation and maintaining a strong intestinal barrier.
Butyrate suppresses the activity of cells and proteins that drive inflammation .
In one study on human cells, butyrate drastically reduced the activity of interleukin-12 (IL-12), an inflammatory cytokine, while increasing interleukin-10 (IL-10), which is generally anti-inflammatory .
In mice, butyrate-producing dietary fibers counteracted inflammation and illness caused by bacterial toxins. The inflammatory cytokines inhibited by butyrate included interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), and interferon gamma (INF-y) .
Butyrate may reduce inflammation by increasing the activity of immune cells called regulatory T cells or Tregs. These specialized cells stop other immune cells – Th1, Th2, and Th17 – in their tracks, before they lose control. In turn, Tregs prevent the lining of the gut from overreacting to harmless food proteins .
Butyrate also strengthens the barrier formed by cells in the colon wall, thus preventing microbes and bacterial toxins from invading the bloodstream .
As we grow older, inflammation increases throughout our bodies. In aging mice, a diet high in fiber that produces butyrate counteracted age-related increases in inflammation, suggesting that butyrate may be especially helpful to the elderly. Human studies will be required to confirm this benefit, however .
Animal and cell studies show that butyrate inhibits inflammatory cytokines and prevents inflammatory bacterial toxins from entering the bloodstream.
As an HDAC inhibitor, butyrate adjusts the immune system in a number of ways.
HDAC inhibitors improve the tumor-targeting abilities of immune cells like T cells and natural killer cells; they are currently under investigation as potential cancer drugs. This class of compounds also reduces many inflammatory signals and increases Tregs, a type of white blood cell that prevents allergies and autoimmunity [34, 35, 36].
Butyrate more specifically protects the gut barrier and prevents pathogens and other harmful agents from crossing into the bloodstream .
Your gut and your microbiome strongly affect your brain. Your gut bacteria talk to your cells by releasing butyrate, which (as an HDAC inhibitor) turns on certain genes .
Butyrate may improve learning and long-term memory. Similar to exercise, sodium butyrate increased brain-derived neurotrophic factor (BDNF) in mice. Simply put, butyrate supplies “brain food” (neuro = brain, trophic = food) to the hippocampus, the brain’s hub for memory and emotions. This gives birth to new neurons, called neurogenesis, a process that can reshape the brain .
There’s a huge overlap between cognitive enhancement and recovery from brain damage. Both rely on neurogenesis, a process that replenishes and reshapes the brain.
In a mouse study, sodium butyrate given after a stroke supported the development of new nerve cells in the damaged areas. It also strengthened the blood-brain barrier in mice with brain trauma, which helped them recover. Butyrate-producing bacteria also strengthened this barrier in mice [40, 41, 42].
Clostridium butyricum, a butyrate-producing species of bacteria, may help manage vascular dementia, a disease whereby blood vessel blockages prevent brain cells from getting enough oxygen. In a mouse study, animals with C. butyricum in the gut experienced less cell death in their brains .
Butyrate may also help manage other types of nerve damage. In guinea pigs, sodium butyrate protected nerve cells in the ear after treatment with antibiotics, thus preventing hearing loss .
Mice with brain damage due to lack of oxygen fared better when they were given the butyrate-producing bacteria Clostridium butyricum before the injury .
Sodium butyrate also prevented the death of nerve cells in the spine of mice with spinal muscular atrophy .
Animal studies show that butyrate is neuroprotective, can improve memory and reduce the impact of brain trauma. Human trials will be needed to confirm this.
Butyrate may impact your social life. Along with other fatty acids produced by your gut bacteria, butyrate is a “social odor.” It may even influence whether people will find you attractive .
Humans can detect even the tiniest amount of butyrate by smell; in fact, our noses are better at picking out butyrate than almost any other chemical on Earth. At high concentrations, it triggers a disgust response because it may indicate that something is rotting or diseased. At low concentrations, however, it can tell us about the immune status of other humans .
A light smell of butyrate in another person’s body odor may indicate that they are healthy, strong, and a good person to socialize with .
Butyrate increases the enzyme that produces dopamine (tyrosine hydroxylase) .
Through its action on dopamine, butyrate may also stabilize your mood; in rodents, it prevents both depression and mania. In mice kept under chronic stress, it acted as an antidepressant; it also stabilized rats with mania. Sodium butyrate also relieved depression and improved cognitive function in mice [48, 49, 50].
Butyrate increases neuronal growth in the hippocampus, a part of the brain that usually shrinks in people with depression. In rats, sodium butyrate increased proteins that help regrow the brain, including brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and glial cell-derived neurotrophic factor (GDNF). This may explain butyrate’s mood-stabilizing benefits .
Sodium phenylbutyrate, a butyrate-containing drug used to treat urea cycle disorders, also lessened anxiety and depression in mice .
Butyrate relieves depression and stabilizes mood in animals. It may be effective for mood disorders, but human trials are needed.
Because of its action as a histone deacetylase (HDAC) inhibitor, butyrate might prevent or even help reverse drug addiction. Sodium butyrate reduced the quantity of alcohol addicted rats chose to drink .
Phenylbutyrate also reduced the desire for cocaine in rats with cocaine addiction .
However, there is evidence that very high doses of butyrate can act in concert with drugs of abuse and help to promote addiction, while lower doses of butyrate prevent dependence .
One review study found that butyrate’s effect on addiction also depends on timing: small doses of butyrate given at the same time as cocaine most effectively prevented drug-seeking behavior and accelerated recovery time .
The evidence for treating drug addiction with butyrate is somewhat conflicting. Further studies will clarify the circumstances in which butyrate fights or promotes addiction.
However, butyrate is not effective enough on its own because it is eliminated too quickly. For this reason, a prodrug of butyrate – that is, another chemical which the body metabolizes into butyrate – is often used instead .
At least two more butyrate-containing preparations with anti-cancer activity have been or are currently being tested:
Another possible approach is to inject butyrate-producing bacteria into the tumors to destroy them from within. This strategy has not yet been tested .
In leukemia cells, a combination of sodium butyrate and artemisinin, a plant-derived compound, was very effective at killing cancer cells, even at low doses .
Some have proposed to combine interleukin-2 (IL-2), a cytokine that activates killer cells, with butyrate. According to rat trials, this combination helps the immune system target the cancer cells .
Mice on a high-fiber diet who had butyrate-producing bacteria in their guts got 75% fewer colon tumors than mice without the bacteria. Mice were only protected from colon cancer if they had the appropriate bacteria; the high-fiber diet alone was not protective .
High fiber diets that promote butyrate production may help prevent colon cancer. On its own, butyrate is not effective as an oral cancer treatment, but prodrugs of butyrate could be.
Firmicutes and Bacteroidetes are two major groups of microbes that live in the human gut. A higher ratio of Firmicutes to Bacteroidetes has been associated with weight gain and obesity. Interestingly, supplementation of SCFAs (including butyrate) has been shown to promote Bacteroidetes, leading to weight loss in mice [78, 79].
In a trial of 118 overweight people, butyrate-producing fiber supplements also led to reduced body weight and BMI .
In a trial of 12 men, SCFAs delivered directly into the colon increased the amount of fat being burned and energy being spent .
In another mouse study, butyrate caused obese mice to lose 10% of their body weight, while their body fat was reduced by 10%. In combination with calorie restriction and exercise, butyrate may promote weight loss in obesity .
SCFAs may prevent weight gain and obesity through several mechanisms, including :
Butyrate – and fibers that ferment into butyrate – can promote weight loss by reducing food intake and increasing fat burning and energy use.
People with diabetes often have gut flora imbalances; less butyrate tends to be produced in their guts. A review study found that butyrate helped control blood sugar in both animals and humans with type 2 diabetes .
Additionally, in diabetic mice, butyrate decreased blood hemoglobin A1c (HbA1c, a measure of long-term blood sugar), inflammatory cytokines, and lipopolysaccharides (LPS). It also strengthened the gut barrier .
Butyrate may help manage diabetes by balancing gut flora, inhibiting inflammation and increasing insulin sensitivity. Human trials are needed to confirm this.
Sodium butyrate improved symptoms and biological markers of allergy in mice with allergic rhinitis (hay fever) .
In human cells and mice, SCFAs including butyrate inhibited the increase in white blood cells called eosinophils in response to allergens. During an allergic reaction, eosinophils are highly activated and produce harmful inflammation; butyrate helps deactivate these cells and resolve the inflammatory response .
Notably, propionic acid, another SCFA, is used to simulate autism-like behavior in mice and rats. The contrasting effects of propionate and butyrate demonstrate just how important it is to fine-tune the gut flora and their products; not all SCFAs are created equal .
According to animal studies, butyrate may protect nerves and brain cells from degenerative disease. In mice, butyrate promoted the survival of nerve cells in mice with amyotrophic lateral sclerosis (ALS), a disease which makes the nerves responsible for movement die off .
In a mouse model of Alzheimer’s disease, the most common neurodegenerative condition, sodium butyrate improved memory function through inhibition of histone deacetylase (HDAC). In mice, phenylbutyrate also prevented the accumulation of beta-amyloid proteins in the brain. When these proteins build up into plaques, the cognitive symptoms of Alzheimer’s progress [95, 96].
Huntington’s disease is a condition in which brain cells die out, causing muscle problems and disordered movement. In mice with this condition, phenylbutyrate improved movement, body weight, and ability to recognize objects .
The same beneficial effect was demonstrated in human cell cultures. In neurons with a buildup of the mutated protein huntingtin, the marker of Huntington’s disease, sodium butyrate allowed the cells to live longer .
In animal studies, butyrate is neuroprotective and may protect against neurodegenerative diseases such as ALS, Alzheimer’s and Huntington’s disease. However, human trials have not yet been conducted.
One cell study suggests butyrate may protect mitochondria – the energy factories inside cellS – against radiation. Butyrate may also protect the mitochondria from other forms of oxidative stress, but its potential against radiation poisoning is especially encouraging .
Sodium butyrate prevented mice from developing non-alcoholic steatohepatitis (NASH), an inflammatory disease caused by fat building up in the liver .
Sodium butyrate also blocked inflammation and protected the pancreas from inflammation in mice .
In a combined mouse and cell study, sodium butyrate prevented hardening of the arteries (atherosclerosis) by inhibiting inflammation .
What’s more, a cell study revealed that butyrate can decrease the expression of genes that make cholesterol, possibly reducing cholesterol production .
If these results can be reproduced in humans, butyrate may decrease the risk of cardiovascular disease.
Butyrate can switch on a hemoglobin gene that generates red blood cells. Thus, butyrate may prevent or manage some forms of anemia, especially during pregnancy .
Butyrate is toxic to certain harmful species of bacteria. Cell studies revealed that butyric acid can directly kill or inhibit the common foodborne pathogen Salmonella and Clostridium perfringens, which causes gangrene .
Moreover, butyrate can influence gene activity in Salmonella, reducing the bacteria’s ability to invade tissues and possibly cause disease .
Recently, researchers discovered butyrate can destroy the cell wall in H. pylori, a bacterium that causes gastritis and ulcers .
A trial of butyrate against shigellosis in rabbits demonstrated that it is anti-inflammatory during infection. As many symptoms of infection stem from inflammation, this result suggests that butyrate may lessen the severity of bacterial disease .
In cell and animal studies, butyrate is antibacterial and may lessen the inflammation associated with infection. Human trials have not yet confirmed this benefit.
Butyrate is considered safe and beneficial in quantities normally produced by a healthy gut flora. Eating dietary fiber instead of supplements to increase butyrate likely prevents any risk of overdose.
In a rat study, supplementation of butyrate during pregnancy and breastfeeding led to insulin resistance and fat accumulation in the offspring. If you are pregnant or nursing, it is best to avoid butyrate supplements until we know more .
High fiber diets that promote butyrate production are likely safe for most people. If you are pregnant or nursing or have been diagnosed with colon cancer, avoid butyrate supplements.
Butyrate supplements come in a few different forms, the most common among them being sodium butyrate and “cal mag” butyrate. These supplements, as their names suggest, deliver butyrate bound to either sodium or calcium and magnesium.
You may also be able to find coated butyrate tablets, in which butyrate “beads” are protected by a layer of fatty acids. In theory, the fatty coating should prevent the release of butyrate before it reaches the intestine.
Unfortunately, we didn’t find any studies comparing and contrasting the different forms of butyrate supplements. However, there may be a simple reason to choose cal mag butyrate over sodium butyrate: most Americans get too much sodium and not enough magnesium in their diets already [112, 113]!
You get can butyrate from food. For example, butyric acid abounds dairy products, especially butter. Butter, which actually gave butyrate its name, contains about 3 to 4% of butyrate in the form of tributyrin. Plant oils also contain butyrate to some extent [114, 115, 116].
Eating more fiber increases butyrate production. There is a generally an association between a higher intake of plant foods and increased levels of short-chain fatty acids (SCFAs), including butyrate, in stools. However, not all plant-based foods yield butyrate; for example, diets rich in fruit or starch increase butyrate content, but starch-free wheat bran doesn’t [117, 118, 119, 120].
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Among the short chain fatty acids, butyrate may be the most crucial for health. Butyrate, produced by healthy gut bacteria, reduces inflammation, protects the brain and may help prevent obesity and cancer.
While supplementation with butyrate directly is possible, it is likely safer and more efficient to use dietary fiber to boost butyrate production by the gut flora. The best fibers for this purpose include inulin (as in artichokes and garlic), resistant starches (rice, potatoes, and green bananas), pectin (many fruits), and oat bran.
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