Top 23 Science-Based Health Benefits Of Butyrate And Its Derivatives

Butyrate has so many benefits, combatting autoimmunity, cancer, and psychological disorders.  It also changes the epigenetics in our brain (R).

Butyrate Executive Summary

Butyrate has so many benefits, combatting autoimmunity, cancer, and psychological disorders.  It also changes the epigenetics in our brain (R).


  • Is a major energy source for colon cells
  • Has anti-cancer effects
  • Increases mitochondrial activity
  • Prevents toxins from crossing gut barrier
  • Prevents activation of intestinal glucose production
  • Improves insulin sensitivity
  • Increases energy expenditure by improving mitochondrial function, reducing obesity
  • Increases intestinal barrier function – an 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 [R2].

Fatty acids are building blocks of fats and our cells can not 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 [R3].

Butyrate production is determined by the level of bacteria that produce 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) [R4].

Butter contains about 3-4% of butyrate in form of tributyrin and it is actually from butter that butyrate gets its name [R5, R6];

Plant oils also contain butyrate to some extent [R4].

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 [R7, R8], but starch free wheat bran doesn’t [R8].

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 of short-chain fatty acids (R, R2):

  • 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 (Hi-Maize): 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 is serves as a major source of energy for them (R).

Butyrate-producing bacteria (such as Clostridium butyricum) live in the end part of the gut, in the colon [R9].

Colon cells prefer butyrate for sustenance [R10].

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 [R15].

Not enough butyrate-producing bacteria in the gut can lead to serious problems [R11R15]:

  • Inflammatory bowel disease (IBD), such as Crohn’s and ulcerative colitis [R11R12R13]
  • Colorectal cancer [R14],
  • Diarrhea – resistant starch has been shown to reduce diarrhea in children [R,R2]. 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 [R60].

Human studies show that short-chain fatty acids, especially butyrate, can improve symptoms of ulcerative colitis and Crohn’s disease [R, R2, R3, R4].

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 is 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 [R58, R59].

Bacteria that produce butyrate can only live in oxygen-free conditions, so this approach is difficult to apply [R59].


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 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” and productive state of genes by blocking a protein that takes off acetyl groups [R16].

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 immune system. It was observed rather early that addition of butyrate to the culture of immune cells has a double-edged effect [R17].

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 [R17].

Later research also performed on cell cultures has proven that butyrate does reduce inflammation. Butyrate suppresses the activity of cells and proteins driving inflammation [R18].

It was also shown in mice that supplementation of their diet with butyrate-producing fibers counterbalances inflammation caused by bacterial toxins [R19].

Butyrate is also good for reversing alcohol damage. It was observed that mice given butyrate before being injected with high doses of ethanol had less inflammation and damage to the inner organs compared to controls [R20].

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 [R21].

Butyrate also strengthens barriers between the cells, thus preventing invasion of microbes [R22].

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].

It was shown on the model of a stroke in mice that treatment of the animals with sodium butyrate after brain injury supports the development of new nerve cells in the damaged areas  [R23].

Also, treatment with sodium butyrate in mice that have brain trauma strengthens the barrier between brain and blood, which helps recovery [R24].

Butyrate is useful in with other types of nerve damage as well: for example, sodium butyrate was reported to protect nerve cells in the ear after treatment with antibiotics thus preventing hearing loss  [R25].

It is not true for sodium butyrate only, but for other butyrate containing preparations, too. For example, the death of nerve cells obtained from mice with stroke-like injury was prevented by treatment with 3-hydroxy-butyrate (3-OBA) [R26].

The same protective effect was shown for sodium 4-phenylbutyrate (4-PBA), a drug used for a number of genetic disorders [R27]

Cultures of butyrate-producing bacteria can also be used to treat nerve damage.

Mice pretreated with a butyrate-producing bacterial species fared better in a model of brain injury [R28].

These bacteria were also beneficial in a more complicated case of brain injury – in vascular dementia, a disease when nerve cells die progressively due to blood vessel blockages [R29]

Butyrate-producing bacteria are able to improve the quality of the barrier between brain and blood in healthy mice as well [R30].

Sodium butyrate can also prevent the death of nerve cells in the spine in the model of spinal muscular atrophy in mice [R31].

Sodium phenylbutyrate was beneficial for the treatment of a systemic disease caused by nerve cells death – amyotrophic lateral sclerosis (ALS). It prevented the death of nerve cells responsible for activating movement [R32].

5-7) Butyrate Is Used for Treating Anxiety, Depression, and Mania


Sodium butyrate and sodium phenylbutyrate are beneficial against depression and other types of mood disorders [R33].

In mice kept under chronic stress, sodium butyrate has antidepressant-like effects [R34].

It also had an anti-manic and anti-oxidant effect in rat models of mania [R35].

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 (it increases several proteins that support nerve cell development) [R36].

Sodium butyrate alleviates depression and increases cognition ability in mice [R37].

It can also restore memory formation when it is blocked with certain substances [R38].

Sodium butyrate protects from stress in general.  It is proposed to prescribe sodium butyrate together with anti-seizure drugs because they are less effective if an afflicted person is under stressful conditions [R39]

Another butyrate-containing drug form, sodium phenylbutyrate, was also shown to be good for improving anxiety and depression in mice [R40].

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 has lessened the quantity of alcohol the animals consumed [R41].

It was also shown that phenylbutyrate can reduce the desire for cocaine in a rat model of cocaine addiction [R42].

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 [R43].

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 [R46].

It was also shown experimentally that butyrate is able to destroy cancer cells in cancer cell cultures which may result in:

  • cancer cell death [R47, R48];
  • the partial self-destruction of the cancerous cells [R49];
  • prevention of  nourishment for the tumors [R50].

But butyrate is not effective enough on its own, in a whole organism, as mentioned [R46].

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

First of all, there is tributyrin, a novel prodrug that can be found in dairy products. This prodrug was tested in patients with advanced solid tumors and was evaluated as effective [R51].

There are at least two more butyrates – containing preparations with anti-cancer activity that are being potentially tested at present:

  • pivanex that was shown to prevent metastases and blood vessel growth in tumors [R52];
  • butyroyloxyalkyl, a substance that transforms into formaldehyde in the cell. Formaldehyde is highly poisonous for living cells and can kill cancer cells effectively [R53]

There is another promising strategy – using sodium butyrate together with other substances. For example, administration of sodium butyrate with nicotinamide and calcium glucarate can prevent the formation of skin tumors in mice [R54].

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 [R55].

Some authors proposed to combine IL-2 – a cytokine that activates killer cells – with butyrate [R56].

The suggestion is based on the trials performed on rats that have shown butyrate to be able to make tumor cells into better targets for killer immune cells stimulated by IL-2 [R56].

The last untested approach is to inject butyrate – producing bacteria into the tumors in order to destruct them from within [R57].

Colon Cancer

Lab studies show that butyrate prevents the growth of tumor cells and encourages cancer cell destruction in the colon [R, R2, R3, R4].

Several observational studies show a link between high-fiber diets and a reduced risk of colon cancer [R, R2].

Mice on a high-fiber diet and 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, confer metabolic benefits in humans [R65].

Supplementing the diet of animals with sodium butyrate can prevent obesity [R65].

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 was shown to suppress weight gain in part by inhibiting caloric intake [R65] and by increasing energy expenditure [R].

Activation of AMPK and increased mitochondrial function were observed in these models, but only after chronic Short Chain Fatty Acid treatment [R65].

11-12) Butyrate May Be Good For Balancing Blood Sugar


Butyrate was also shown to improve various aspects of diabetes.

People with diabetes have an imbalance of gut flora. A review of the evidence reported that butyrate can have 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 and insulin sensitivity [R, R2].

In mice, butyrate makes pancreatic cells sensitive to insulin [R63].

It was shown in young diabetic rats that sodium butyrate protects and supports insulin-producing cells and prevents the release of sugar into blood [R64].

In mice, butyrate increases insulin sensitivity [R].

13) Butyrate Can Help Treat Allergies

It was shown that sodium butyrate has decreased several parameters characteristic for allergy in mice with allergic rhinitis [R67].

14) Butyrate May Help Autism

There are at least two studies on mice demonstrating that treatment with sodium butyrate is good for autism [R71R72].

It was shown in mice that addition of sodium butyrate improves autistic behavior [R71].

Another study has shown that sodium butyrate helped autistic mice to recognize objects better  [R72].

But it is also known that propionic acid, a chemical relative of butyrate (also found in the gut), can be used for creating autism-like behavior in mice and rats [R73].

Such contradicting results indicate that this issue should be researched more extensively.

15-16) Butyrate Can Be Useful In Alzheimer’s and Huntington’s

Butyrate can be beneficial in protecting nerve cells [R28,R31].

Sodium butyrate and phenylbutyrate are effective in Alzheimer’s [R75, R76 ].

Those drugs improve  memory in afflicted mice by increasing gene activity in relevant brain areas [R75].

Phenylbutyrate also prevents protein accumulation in the brain [R76].

Sodium butyrate was also demonstrated to beneficial in a mouse model of Huntington’s disease [R69].

Huntington’s disease is a condition caused by damage in nerve cells that slowly begin to die out. It was shown that therapy with phenylbutyrate in mice with this condition has improved their movements, body weight, ability to recognize objects and gene production [R69].

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 [R70].

17) Butyrate is Good For The Mitochondria


It was proposed to use butyrate with lipoic acid for prevention and treatment of radiation injury [R77].

Butyrate can protect cells against radiation because it is good for cells’ “energy factories” – mitochondria, which are often destroyed by radiation [R77].

18-20) Butyrate Protects the Liver, Pancreas, and Heart

Butyrate helped to improve liver disease in animals [R61].

Sodium butyrate was also reported to protect the pancreas from damage [R62].

Sodium butyrate can prevent atherosclerosis [R66].

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 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 [R68].

22) Butyrate Can Kill Certain Bacteria Directly

It was recently found that n-butyric acid  can directly kill Salmonella (a bacteria that causes salmonellosis and severe diarrhea) and Clostridia perfringes (causes gangrene) [R78].

Moreover, butyrate can directly influence gene activity in Salmonella, making the bacteria less dangerous and vulnerable to killing [R80].

At present butyrate is used mostly for treating salmonellosis in poultry [R81].

Recently, the researchers discovered that butyrate can destroy the cell wall in Helicobacter pylori  – a bacteria causing gastritis [R82].

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 [R83].

The trial was successful, but it mostly reports the favorable reaction to butyrate intake and health improvement but does not register direct antibacterial effect [R83].

Butyrate can also kill bacteria indirectly by increasing the production of specific antimicrobial proteins that help the organism to destroy bacteria [R84].

This fact is also true for phenylbutyrate [R85].

23) Butyrate May Increase Dopamine

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

Increasing Butyrate Levels 

I personally take 4 pills of calcium/magnesium Butyrate 2X a day and 50g of Hi-Maize daily.  The Hi-maize turns into resistant starch, which the gut bacteria feed off of and produce 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.

Buying Butyrate

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.


  • Calcium, Magnesium Butyrate by Body Bio
  • Hi-Maize (Honeyville, available in 5-pound bag) [R] – the best option



  • Fiber (bran, etc.) [R]
  • Dairy (butter, milk, etc.) [R]

Gamma-hydroxybutyric acid or GHB is a prescription and recreational drug that contains butyrate [R44].

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”

Butyrate And The Immune System (Technical)

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


HDAC inhibitor (class)



Tumor cells


Depsipeptide (Class I)

Valproic Acid (panHDAC)

Trichostatin A (panHDAC)

LAQ824 (panHDAC)

Panobinostat (panHDAC)


Co-stimulatory molecules

Recognition by T cells


Valproic Acid (panHDAC)

Trichostatin A (panHDAC)

Expression NKG2D ligands/

Recognition by NK cells


Vorinostat (panHDAC)

Immunogenic cell death

[60, 61, 63]

Effector lymphocytes

CD4 T cells

Trichostatin A (panHDAC)


Scriptaid (panHDAC)

Vorinostat (panHDAC)

Romidepsin (Class I)



Pro-inflammatory cytokines

[39, 9193,98,99,126]

Vorinostat (panHDAC)




CD4 T cells

Vorinostat (panHDAC)




CD8 T cells

Panobinostat (panHDAC)

Trichostatin A (panHDAC)

Pro-inflammatory cytokines


Memory function

[39, 100,101, 126]

NK cells

Valproic Acid (panHDAC)




Entinostat (Class I)




NK cells

Vorinostat (panHDAC)

Cytotoxicity =


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


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


Tumor cells

Vorinostat (panHDAC)

Trichostatin A (panHDAC)

Valproic Acid (panHDAC)

Tumorigenic sol. factors / cytokines

[86, 87]

Regulatory Immune Cells


Trichostatin A (panHDAC)

Vorinostat (panHDAC)

Valproic Acid (panHDAC)

Tubacin (Class II)

Entinostat (Class I)

Cell numbersFoxP3 expression

Immune suppressive capacity


Entinostat (Class I)

Numbers =/ FoxP3 expression

Immune suppressive capacity

[39, 118]

Bone marrow cells

Trichostatin A (panHDAC)

Vorinostat (panHDAC)





Valproic Acid (panHDAC)





Trichostatin A (panHDAC)

Valproic Acid (panHDAC)

MHCII expression

[123, 124]


  1. Andy

    does HMB/calcium-hydroxymethylbutyrate (the supplement used by athletes/bodybuilders) offer the same benefits as butyrate?

  2. Sam

    Great research as always, thank you, Joe. But… here is some food for thought…

    “Treatment with either antibiotics or a low-carbohydrate diet reduced cell proliferation as well as the number of tumors in the small intestines and colons of these mice. These two treatments also reduced levels of certain gut microbes that metabolize carbohydrates to produce a fatty acid called butyrate. When the researchers increased butyrate levels in the antibiotic-treated mice, cell proliferation and the number of tumors increased in the small intestines. Taken together, the findings suggest that carbohydrate-derived metabolites produced by gut microbes drive abnormal cell proliferation and tumor development in mice genetically predisposed to colorectal cancer.”

    New research at Washington University School of Medicine in St. Louis indicates stem cells are located in “pockets” in the intestine to avoid contact with a prominent metabolite produced by beneficial microbes living in the gut. That metabolite — butyrate — restricts the proliferation of stem cells, potentially hampering the intestine from repairing itself after an injury or damage resulting from inflammatory bowel disease (IBD), such as Crohn’s and colitis.”

    “When there’s damage to the lining of the intestine — whether from acute injury or disease — stem cells have to divide to repair that damage,” Stappenbeck said. “Inhibiting stem cell proliferation could be an unfortunate side effect of butyrate treatment.”

    • “Butyrate suppresses proliferation by acting as a histone deacetylase (HDAC) inhibitor therefore allowing for increased promoter activity of the negative cell-cycle regulator Foxo3 during injury. Butyrate utilization by enterocytes limits the access of butyrate to the intestinal crypts, thereby protecting stem cells from the anti-proliferative effect during homeostasis [14] . This study suggests that SCFAs contribute to the maintenance of the epithelial barrier.”

  3. Richard Price

    Really excellent site , have just discovered nice blend of cutting edge science well presented articles and info , the human body-biochemistry is all most infinitely complex and a multi level phenomena . info must be useful ll and not too shocking in my opinion so great keep it up!

  4. I’ve come across pheylbutyric acid in more than one stress or sleep formula – how does it relate to the forms of butyrate you mention, and how might it be beneficial, or not? Thanks!

  5. anna burns

    what about arabinogalactan…is that considered a resistant starch? If so what do you think of it?

    • Joseph M. Cohen

      Just with water or with a shake or with stevia. Or you can use it in baking. You can be creative.

  6. anna burns

    Hello, Thanks for all the informative articles that you have been sharing. So interesting and helpful. Regarding h maize…will any type of resistant starch be affective, such as banana or
    potato flour, or does it need to be h maize? Also, I assume that it is made from corn. Just
    wondering about the GMO issue and the corn. Does that concern you at all?

  7. Lara

    Brilliant article, just a bit concerned about the choice of supplement Nutricology, ButyrAid as reading the reviews on the Iherb and Amazon site, apparently it contains lead. Not recommended for people with heavy metal issues.

    • Liduina Wildenburg

      It doesn’t specify it contains lead in the supplement contents details, but apparently it’s on the label.

  8. daniel

    How many pills do you take?

    I got me the butyrate supplement along with others (berberine etc) And I took it for a few weeks now. Doesn’t do much to me regarding feeling, immunity (at least to my skin), gut…

    So far a powerful IR lamp, minerals/electroliytes/sodium dicarbonate, choline+dha+ broccoli+ still waiting for UMP), ICES on head are making the biggest differences, protein, coffee, green tea.

    I could feel how Berberine/R ALA tinker with my blood suger.

    Primal Defense Ultra was the only Probiotic supplement that made a huge difference in my gut…

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