Butyrate has so many benefits, such as combating autoimmunity, cancer, and psychological disorders. It also changes the epigenetics in our brain. Read on to learn about the benefits of butyrate and possible side effects.

What is Butyrate?

Butyrate occurs naturally in the body and is a molecule that is referred to as a short-chain fatty acid. There are more details on its mechanisms below, but here is a semi-comprehensive list with some benefits of this molecule.

Butyrate:

  • Is a major energy source for colon cells
  • Has anti-cancer effects
  • Increases mitochondrial activity
  • Prevents toxins from crossing the gut barrier
  • Prevents activation of intestinal glucose production
  • Improves insulin sensitivity
  • Increases energy expenditure by improving mitochondrial function, reducing obesity
  • Increases intestinal barrier function with anti-inflammatory potential
  • Protects against diet-induced obesity without necessarily causing a reduction in caloric intake (mediated through gut hormones)
  • Increases the synthesis of leptin (which reduces appetite)

Where Do We Get Butyrate From?

Butyrate is a molecule that is called a short-chain fatty acid [R].

Fatty acids are building blocks of fats and our cells cannot be without them. This particular fatty acid is very small and is usually is made by bacteria living in our gut – mostly from fibers derived from grains, beans, onions, and bananas [R].

Butyrate production is determined by the level of bacteria that produces butyrate, and the pH of the large intestine [R].

Butyrate-producing bacteria seem to thrive in a more acidic environment (lower pH), whereas acetate and propionate bacteria seem to thrive in a more alkaline environment (higher pH) [R].

Butyrate is mainly produced by Firmicutes [R].

Butyrate can also be made by animals’ own cells – for example, it can be found in the form of butyric acid in dairy products (especially butter) [R].

Butter contains about 3 to 4% of butyrate in form of tributyrin and it is actually from butter that butyrate gets its name [R, R].

Plant oils also contain butyrate to some extent [R].

Therefore, people receive butyrate mostly from their diet.

According to research, not all plant-based foods yield butyrate equally; for example, diets rich in fruit or in starch increases butyrate content in rats, but starch-free wheat bran doesn’t [R, R].

Studies have shown that eating more fiber increases butyrate production [R].

There is a positive association between a higher intake of plant foods and increased levels of short-chain fatty acids in stools [R].

Short-chain fatty acids provide about 10% of our daily calorie needs [R].

The following types of fiber produce short-chain fatty acids [R, R]:

  • Inulin: Food sources include artichokes, garlic, leeks, onions, and asparagus
  • Fructooligosaccharides (FOS): Food sources include fruits and vegetables, including bananas, onions, garlic, and asparagus
  • Resistant starch: Food sources include green bananas and rice that has been cooked and then cooled
  • Pectin: Food sources include apples, apricots, carrots, oranges, and others
  • Arabinoxylan
  • Guar gum
  • Arabinogalactan [R]

Health Benefits of Butyrate

1) Butyrate Is Crucial for Gut Health

Butyrate is important for creating tolerance in the gut and promoting an anti-inflammatory environment.

Butyrate is mostly not absorbed because it is primarily used by colon cells, where it serves as a major source of energy [R].

Butyrate-producing bacteria (such as Clostridium butyricum) live in the end part of the gut, in the colon [R].

Colon cells prefer butyrate for sustenance [R].

In the mitochondria of colon cells, 70% to 90% of butyrate is oxidized into acetyl-CoA, which is subsequently processed through the tricarboxylic acid cycle to generate a large quantity of ATP [R].

Butyrate and its “production factories” are imperative for intestinal health [R].

Not enough butyrate-producing bacteria in the gut can lead to serious problems [RR]:

  • Inflammatory bowel diseases (IBD), such as Crohn’s and ulcerative colitis [R, RR]
  • Colorectal cancer [R]
  • Diarrhea – resistant starch has been shown to reduce diarrhea in children [R, R]

Butyrate in combination with several other substances was also shown to be beneficial for the treatment of traveler’s diarrhea – a condition common among tourists, especially those who travel to exotic countries [R].

Human studies show that short-chain fatty acids, especially butyrate, can improve symptoms of ulcerative colitis and Crohn’s disease [R, R, R, R].

Butyrate supplements resulted in improvements in 53% of Crohn’s disease patients [R].

An enema of short-chain fatty acids, twice per day for 6 weeks, helped reduce symptoms of ulcerative colitis by 13% [R].

There are a variety of approaches for using butyrate for the treatment of inflammatory bowel disease and colitis. The treatment strategies range from high-fiber diet, butyrate-producing bacteria, coated tablets, and rectal enemas [R, R].

Bacteria that produce butyrate can only live in oxygen-free conditions, so this approach is difficult to apply [R].

Figure-1-Effects-of-butyrate-in-the-gastrointestinal-tract-Acetate-propionate-and

2) Butyrate Increases Gene Activity

Butyrate is able to influence which genes are active.

There are several mechanisms in the cell that control gene activity by changing the composition of the chromosome proteins (or histones).

An addition of a methyl group to a part of the histone (methylation) forces it to cling tightly to the gene nearby, successfully blocking its production.

Another reaction called acetylation (addition of an acetyl group) frees an area of DNA and increases gene production.

Butyrate helps maintain “open” a productive state of genes by blocking a protein that takes off acetyl groups [R].

This activity turns out to be extremely important in many different conditions.

3) Butyrate Fights Inflammation

nutrients-06-04706-ag [R]

Many researchers show that butyrate can influence the activity of the immune system. It was observed rather early that addition of butyrate to the culture of immune cells had a double-edged effect [R].

On one hand, butyrate blocks the development of new immune cells participating in inflammation. On the other hand, it stimulates the production of some inflammatory proteins [R].

Later research also performed on cell cultures showed that butyrate does reduce inflammation. Butyrate suppresses the activity of cells and proteins driving inflammation [R].

In mice, supplementation of their diet with butyrate-producing fibers counterbalanced inflammation caused by bacterial toxins [R].

Butyrate is also good for reversing alcohol damage. Mice given butyrate before being injected with high doses of ethanol had less inflammation and damage to the inner organs compared to controls [R].

These anti-inflammatory properties may be partly connected to the ability of butyrate to support the development of specific immune cells that block inflammation in the lining of the end gut in mice [R].

Butyrate also strengthens barriers between the cells, thus preventing invasion of microbes [R].

4) Butyrate Is Good for the Brain and Nerve Cells

Sodium butyrate, like exercise, places the brain into a state of “readiness for plasticity” and can benefit long-term memory [R].

A stroke model in mice showed that treatment with sodium butyrate after brain injury supported the development of new nerve cells in the damaged areas [R].

Also, treatment with sodium butyrate in mice that had brain trauma strengthened the barrier between brain and blood, which helped recovery [R].

Butyrate is useful in with other types of nerve damage. For example, sodium butyrate was reported to protect nerve cells in the ear after treatment with antibiotics, thus preventing hearing loss [R].

Results are indicative beyond sodium butyrate and are also steadfast for other butyrate-containing preparations. For example, the death of nerve cells obtained from mice with stroke-like injury was prevented by treatment with 3-hydroxy-butyrate (3-OBA) [R].

The same protective effect was indicated for sodium 4-phenylbutyrate (4-PBA), a drug used for a number of genetic disorders [R]

Cultures of butyrate-producing bacteria may also treat nerve damage.

Mice pre-treated with a butyrate-producing bacterial species fared better in a model of brain injury [R].

These bacteria were also beneficial in a more complicated case of brain injury, such as vascular dementia, a disease where nerve cells die progressively due to blood vessel blockages [R].

Butyrate-producing bacteria were also able to improve the quality of the barrier between brain and blood in healthy mice [R].

Sodium butyrate also prevented the death of nerve cells in the spine in the model of spinal muscular atrophy in mice [R].

Sodium phenylbutyrate was beneficial for the treatment of a systemic disease caused by nerve cells death – amyotrophic lateral sclerosis, or ALS. It prevented the death of nerve cells responsible for activating movement [R].

5, 6, & 7) Butyrate for Treating Anxiety, Depression, and Mania

Sodium butyrate and sodium phenylbutyrate are beneficial against depression and other types of mood disorders [R].

In mice kept under chronic stress, sodium butyrate has antidepressant-like effects [R].

It also had an anti-manic and antioxidant effect in rat models of mania [R].

One possible mechanism of such influence may be due to the fact that sodium butyrate influences the processes in the hippocampus, the part of the brain responsible for emotions and emotional memory, as it increases several proteins that support nerve cell development [R].

Sodium butyrate alleviated depression and increased cognition ability in mice [R].

It can also restore memory formation when it is blocked with certain substances [R].

Sodium butyrate protects from stress in general. Some doctors prescribe sodium butyrate together with anti-seizure drugs because they are less effective if an afflicted person is under stressful conditions [R]

Another butyrate-containing drug form, sodium phenylbutyrate, also improved anxiety and depression in mice [R].

8) Butyrate Is Both a Cure and an Enemy in Case of Addictions

Butyrate-containing drugs are a double-edged sword when treating addiction. In alcohol-addicted rats, supplementation of their diet with sodium butyrate lessened the quantity of alcohol the animals consumed [R].

Phenylbutyrate also reduced the desire for cocaine in a rat model of cocaine addiction [R].

On the other hand, there is increasing evidence that butyrate can act in concert with such drugs of abuse as cocaine, helping to establish certain behaviors caused by the addiction [R].

9) Butyrate Has Anti-Cancer Properties

The possibility of using butyrate for the treatment of cancer was entertained as early as the 1980s. In a clinical trial of sodium butyrate for leukemia treatment, it was established that the drug is too easily eliminated from the body to be really effective [R].

Experimentally, butyrate was able to destroy cancer cells in cancer cell cultures, which may result in:

  • Cancer cell death [R, R]
  • The partial self-destruction of the cancerous cells [R]
  • Prevention of nourishment for the tumors [R]

However, butyrate is not effective enough on its own in a whole organism, as mentioned [R].

So, there are several strategies and new drugs employed for fighting cancer.

First of all, there is tributyrin, a novel prodrug that is found in dairy products. This prodrug was tested in patients with advanced solid tumors and was evaluated as effective [R].

There are at least 2 more butyrate-containing preparations with anti-cancer activity that are being potentially tested at present:

  • Pivanex, which prevented metastases and blood vessel growth in tumors [R]
  • Butyroyloxyalkyl, a substance that transforms into formaldehyde in the cell (formaldehyde is highly poisonous for living cells and can kill cancer cells effectively) [R]

There is another promising strategy – using sodium butyrate together with other substances. For example, administration of sodium butyrate with nicotinamide and calcium glucarate prevented the formation of skin tumors in mice [R].

In leukemia cancer cells, a combination of sodium butyrate and artemisinin, a plant-derived anticancer compound, was very effective in killing cancerous cells at low doses [R].

Some proposed to combine IL-2, a cytokine that activates killer cells, with butyrate [R].

The suggestion is based on the trials performed on rats that show butyrate making tumor cells into better targets for killer immune cells stimulated by IL-2 [R].

The last untested approach is to inject butyrate-producing bacteria into the tumors in order to destruct them from within [R].

Colon Cancer

Lab studies show that butyrate prevented the growth of tumor cells and encouraged cancer cell destruction in the colon [R, R, R, R].

Several observational studies show a link between high-fiber diets and a reduced risk of colon cancer [R, R].

Mice on a high-fiber diet who had butyrate-producing bacteria got 75% fewer tumors than the mice who did not have the bacteria [R].

The high-fiber diet without the bacteria to make butyrate did not have protective effects against colon cancer [R].

10) Butyrate Can Help with Weight Loss

It is well established that supplementing resistant starch and dietary fibers in diet offer metabolic benefits in humans [R].

Supplementing the diet of animals with sodium butyrate can prevent obesity [R].

In animal studies, butyrate caused obese mice to lose 10.2% of their original body weight, and body fat was reduced by 10% [R].

In rodent models of genetic or diet-induced obesity, supplementation of butyrate in the diet suppressed weight gain in part by inhibiting caloric intake, and by increasing energy expenditure [RR].

Activation of AMPK and increased mitochondrial function were observed in these models, but only after chronic short-chain fatty acid treatment [R].

11 & 12) Butyrate May Be Good for Balancing Blood Sugar

Butyrate also improved various aspects of diabetes.

People with diabetes have an imbalance of gut flora. A review of the evidence reported that butyrate had positive effects in both animals and humans with type 2 diabetes [R].

Human studies have also reported associations between fermentable fiber and improved blood sugar control, in addition to insulin sensitivity [R, R].

In mice, butyrate makes pancreatic cells sensitive to insulin [R].

In young diabetic rats, sodium butyrate protected and supported insulin-producing cells, and prevented the release of sugar into blood [R].

In mice, butyrate increased insulin sensitivity [R].

13) Butyrate Can Help Treat Allergies

Sodium butyrate decreased several parameters characteristic for allergy in mice with allergic rhinitis [R].

14) Butyrate May Help Autism

There are at least 2 studies on mice demonstrating that treatment with sodium butyrate is good for autism [R, R].

It was shown in mice that the addition of sodium butyrate improved autistic behavior [R].

Another study showed sodium butyrate helped autistic mice to recognize objects better [R].

However, propionic acid, a chemical relative of butyrate that is also found in the gut, is used for creating autism-like behavior in mice and rats [R].

Such contradicting results indicate that this issue requires more research.

15 & 16) Butyrate for Alzheimer’s and Huntington’s

Butyrate is beneficial for protecting nerve cells [R, R].

Sodium butyrate and phenylbutyrate are effective for Alzheimer’s treatment [R, R].

Those drugs improve memory in afflicted mice by increasing gene activity in relevant brain areas [R].

Phenylbutyrate also prevents protein accumulation in the brain [R].

Sodium butyrate was also beneficial in a mouse model of Huntington’s disease [R].

Huntington’s disease is a condition caused by damage in nerve cells that slowly begin to die out. Therapy with phenylbutyrate in mice with this condition improved their movements, body weight, ability to recognize objects, and gene production [R].

The same beneficial effect was shown on the cell culture that carried the faulty gene causing Huntington’s disease in humans, where the addition of sodium butyrate to the culture allowed the cells to live longer [R].

17) Butyrate Is Good for Mitochondria

It was proposed to use butyrate with lipoic acid for the prevention and treatment of radiation injury [R].

Butyrate can protect cells against radiation because it is good for cells’ “energy factories” – the mitochondria, which are often destroyed by radiation [R].

18, 19, & 20) Butyrate Protects the Liver, Pancreas, and Heart

Butyrate helped improve liver disease in animals [R].

Sodium butyrate was also reported to protect the pancreas from damage [R].

Sodium butyrate can prevent atherosclerosis [R].

Butyrate is thought to interact with key genes that make cholesterol, possibly reducing cholesterol production [R].

21) Butyrate May Increase Red Blood Cells

Due to butyrate’s gene-influencing activity, it can switch on the hemoglobin gene that works during the development of the child in the womb, thus ensuring the appearance of properly working red blood cells [R].

22) Butyrate Can Kill Certain Bacteria Directly

Studies show n-butyric acid can directly kill Salmonella (a bacteria that causes salmonellosis and severe diarrhea) and Clostridium perfringens (which causes gangrene) [R].

Moreover, butyrate can directly influence gene activity in Salmonella, making the bacteria less dangerous and vulnerable to killing [R].

At present, butyrate is used mostly for treating salmonellosis in poultry [R].

Recently, researchers discovered butyrate can destroy the cell wall in H. pylori – a bacteria that causes gastritis [R].

There are no reports found about direct applications of butyrate against human bacterial infections, except a trial of butyrate treatment against shigellosis carried out on rabbits [R].

The trial was successful, but it mostly reports the favorable reaction to butyrate intake and health improvement. It does not register a direct antibacterial effect [R].

Butyrate can also kill bacteria indirectly by increasing the production of specific antimicrobial proteins that help the organism to destroy bacteria.

This is also true for phenylbutyrate [R].

23) Butyrate May Increase Dopamine

Butyrate increases the enzyme that produces dopamine (tyrosine hydroxylase) [R].

Cautions and Side Effects of Butyrate

Butyrate may drive cancerous cell growth in the gut in antibiotic-treated mice [R].

Butyrate may prevent stem cells in the gut from growing and repairing the gut after an injury or autoimmune diseases like inflammatory bowel disease (IBD) [R].

Butyrate inhibits the growth of these cells by increasing the Foxo3 gene, which is associated with IBD [R].

Gut crypt and butyrate

Gut crypt and butyrate [R]

The gut crypts are structured such that the stem cells at the top are protected from butyrate in the gut. However, in conditions where the villi are sufficiently damaged, the stem cell in the gut may not be protected [R].

Increasing Butyrate Levels 

I personally take 4 pills of calcium/magnesium butyrate twice a day, with lots of resistant starch, which the gut bacteria feeds off of and produces butyrate.

I like the 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’d rather not have a brand that has excipients.

I also take modified citrus pectin. I actually find that it has a nootropic and wakeful promoting effect for me. It also chelated heavy metals, while leaving your beneficial minerals. So, this is a great choice.

Arabinogalactan is good if you want to boost your immune system, but not if you’re Th1 dominant or have an overactive immune system.

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.

I discuss more of what other supplements I take that have had a beneficial impact on my health all across the site. A condensed and easy-to-find list of all the supplements and biohacks that have helped me greatly can be found in my book, SelfHacked Secrets.

Butyrate and the Immune System (Technical)

Butyrate is an HDAC inhibitor, which results in a variety of immune modulating effects.

 

HDAC inhibitor (class)

Observations

References

Tumor cells

 

Depsipeptide (Class I)

Valproic Acid (panHDAC)

Trichostatin A (panHDAC)

LAQ824 (panHDAC)

Panobinostat (panHDAC)

TAA MHCIMHCII

Co-stimulatory molecules

Recognition by T cells

[4143,4548,126]

Valproic Acid (panHDAC)

Trichostatin A (panHDAC)

Expression NKG2D ligands/

Recognition by NK cells

[5156]

Vorinostat (panHDAC)

Immunogenic cell death

[60, 61, 63]

Effector lymphocytes

CD4 T cells

Trichostatin A (panHDAC)

N-butyrate(panHDAC)

Scriptaid (panHDAC)

Vorinostat (panHDAC)

Romidepsin (Class I)

Viability

Proliferation

Pro-inflammatory cytokines

[39, 9193,98,99,126]

Vorinostat (panHDAC)

Viability=

[94]

Activated

CD4 T cells

Vorinostat (panHDAC)

Viability=

Cytotoxicity=

[99]

CD8 T cells

Panobinostat (panHDAC)

Trichostatin A (panHDAC)

Pro-inflammatory cytokines

Cytotoxicity

Memory function

[39, 100,101, 126]

NK cells

Valproic Acid (panHDAC)

Proliferation

Cytotoxicity

[104]

Entinostat (Class I)

Cytotoxicity

[105]

Activated

NK cells

Vorinostat (panHDAC)

Cytotoxicity =

[99]

APC / Cytokine production

Macrophages /DC

Trichostatin A (panHDAC)

Vorinostat (panHDAC)

LAQ824 (panHDAC)

Panobinostat (panHDAC)

Valproic Acid (panHDAC)

Entinostat (Class I)

Co-stimulatory molecules

Pro-inflammatory cytokines

APC function

[68, 69, 76,7883,85]

Cytokines / inflammation

Vorinostat (panHDAC)

Givinostat (panHDAC)

Pro-inflammatory cytokine production

Inflammation

[34, 35, 74,76, 77,84]

Macrophages

Tumor cells

Vorinostat (panHDAC)

Trichostatin A (panHDAC)

Valproic Acid (panHDAC)

Tumorigenic sol. factors / cytokines

[86, 87]

Regulatory Immune Cells

Treg

Trichostatin A (panHDAC)

Vorinostat (panHDAC)

Valproic Acid (panHDAC)

Tubacin (Class II)

Entinostat (Class I)

Cell numbersFoxP3 expression

Immune suppressive capacity

[107113,116,117]

Entinostat (Class I)

Numbers =/ FoxP3 expression

Immune suppressive capacity

[39, 118]

Bone marrow cells

Trichostatin A (panHDAC)

Vorinostat (panHDAC)

DifferentiationMDSC

Macrophages/DC

[120]

MDSC

Valproic Acid (panHDAC)

DifferentiationMDSC

Macrophages/DC

[121]

TAM

Trichostatin A (panHDAC)

Valproic Acid (panHDAC)

MHCII expression

[123, 124]

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4196144

Buy Butyrate Supplement

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.

Gamma-hydroxybutyric acid or GHB is a prescription and recreational drug that contains butyrate [R].

Note: The brand that I take has minute traces of lead, as do many supplements and foods that you eat. If you have a heavy metal sensitivity then take sodium butyrate or the butyrate by Ecological Formulas.

I hear the same answer from many companies: “The United States Pharmacopeia mandates no more than 10 µg/lead per day from any product, and all of our products are far below that level. California Proposition 65, however, sets the lead standard 20 times lower, at 0.5 µg/day.”

FDA Compliance

The information on this website has not been evaluated by the Food & Drug Administration or any other medical body. We do not aim to diagnose, treat, cure or prevent any illness or disease. Information is shared for educational purposes only. You must consult your doctor before acting on any content on this website, especially if you are pregnant, nursing, taking medication, or have a medical condition.

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