Butyrate Side Effects: What Human Trials Report and Who Should Be Careful
Before you take any supplement, it's fair to ask what could go wrong. I asked the same thing about butyrate before we chose one to sell.
We sell a butyrate supplement, which is why we read this research closely.
If butyrate is new to you, start with what butyrate is.
What are the side effects of butyrate supplements?
The side effects of butyrate supplements in human trials have been mild and uncommon, such as short-lived nausea and headache. At the doses those trials used, butyrate has been well tolerated.
Two more things come with some forms: a rancid smell, and extra sodium in sodium butyrate, the most common form. One trial also found a rise in blood pressure.
| Side effect | What trials or labels report | What helps |
|---|---|---|
| Nausea or headache | 2 children in a 54-child trial; mild, first month only | Passed within weeks; both kept taking it |
| Rancid smell | 4 children quit one trial after their first doses | A form with a milder smell |
| Extra sodium | About 313 mg per serving on one well-known label | A form without sodium |
| Higher blood pressure | Rose in a 4-week trial of 23 adults with high blood pressure | Talk to your doctor before you start |
| Gut upset | 1 dropout in a 60-adult trial, on butyrate plus fiber | Stop, and ask your doctor |
What did each human trial report?
Here are 7 human trials, with 492 people in all. Five compared butyrate with a placebo, a look-alike capsule with no butyrate.
| Trial | Who and how long | Side effects reported |
|---|---|---|
| Krokowicz 2014 | 73 adults (52 finished), 12 months | None |
| Coppola 2022 | 54 children, 6 months | 2 had mild, short-lived nausea and headache |
| Mitrović 2025 | 181 adults, 12 weeks | No significant side effects with either form tested |
| Tougaard 2022 | 53 adults, 12 weeks | About even with placebo (18 events against 16) |
| Karłowicz 2025 | 98 adults, 8 weeks | Researchers called it safe |
| La Monica 2025 | 10 men, single doses | None |
| Verhaar 2024 | 23 adults, 4 weeks | Daytime blood pressure rose |
In 6 of the 7, the researchers raised no safety concern. The seventh is the blood pressure trial.
Most of this data is on sodium butyrate, at 300 mg to 4 g a day. Those are trial facts, not advice.
Two limits to keep in mind. The trials were small, and the longest ran 12 months. Most enrolled people with a health condition, so we know less about healthy adults.
Our write-up of butyrate and inflammation covers what several of them measured.
Why does butyrate smell, and does the smell matter?
Butyrate smells because butyric acid, its acid form, has a rancid odor the nose picks up at tiny amounts, and the smell matters mostly for whether you'll keep taking it. That smell is normal, even in a fresh bottle.
Butyric acid is the compound that gives rancid butter its odor. Some people say it smells like vomit.
In a smell test, young adults could detect butyric acid at about 0.26 parts per billion. For the acid in vinegar, they needed about 20 times more (Cometto-Muñiz 2010).
It can decide whether people stick with butyrate. In the 6-month children's trial, 4 children stopped it after their first doses, against 2 on placebo. The researchers pointed to its unpleasant smell and taste (Coppola 2022).
The form is the part you can change. L-lysine butyrate pairs butyrate with an amino acid in place of sodium. It has a milder smell than sodium butyrate, though it isn't odor-free.
Our guide to butyrate smell and taste explains why.
How much sodium is in sodium butyrate?
Sodium butyrate is about 21% sodium by weight. A serving with 1,200 mg of butyric acid carries about 313 mg of sodium, about 14% of your daily sodium.
The FDA sets the daily value for sodium at less than 2,300 mg. That's about 1 teaspoon of table salt, so one serving adds roughly an eighth of a teaspoon.
That matters most if your doctor has you watching sodium, or if you take more than one serving a day.
Check your own label, because the amount varies by product. Three forms carry no sodium: calcium magnesium butyrate, tributyrin (butyrate bound to a fat) and L-lysine butyrate.
Our guide to sodium butyrate has more.
Can butyrate raise blood pressure?
Sodium butyrate raised blood pressure in one human trial of adults who already had high blood pressure. If you have high blood pressure, talk to your doctor before you take butyrate.
The trial followed 23 adults with high blood pressure for 4 weeks. They stopped their blood pressure medicine for the study. One group took sodium butyrate capsules, and the other took a placebo (Verhaar 2024).
Daytime blood pressure rose in the butyrate group. The top number went up about 10 points more than on placebo. The bottom number went up about 5.
Sodium alone doesn't explain it. The placebo capsules held the same amount of sodium.
The dose was large. The trial's public record lists it as 4 g a day, split across 26 capsules.
It was one small trial, and it didn't test people with normal blood pressure. I haven't found the same test run with a sodium-free form.
So I'd apply this caution to every form of butyrate, ours included.
Can butyrate cause bloating, gas, constipation or diarrhea?
Butyrate supplements did not cause more bloating, gas or diarrhea than placebo in three human trials that tracked gut symptoms. In a fourth trial, 1 person taking butyrate with a prebiotic fiber dropped out with a severe gut symptom.
In one trial, 53 adults with type 1 diabetes took sodium butyrate or a placebo for 12 weeks. Gut symptoms were no different between the two groups (Tougaard 2022).
In another, 52 adults with type 2 diabetes and irritable bowel symptoms did the same. In the butyrate group, belly pain, diarrhea and bloating went down. The placebo group saw no change (Panufnik 2026).
In 66 adults with irritable bowel syndrome, urgency and bowel habits improved over 12 weeks on a coated sodium butyrate. The change in gas was too small to be sure (Banasiewicz 2013).
The fourth trial split 60 adults with type 2 diabetes into four groups for 45 days. The 1 dropout was taking sodium butyrate together with 10 g of a prebiotic fiber. No one on butyrate alone dropped out (Roshanravan 2017).
I haven't found a trial that reports constipation at the doses on supplement labels. If gut symptoms are why you're here, see our guide to butyrate for IBS and bloating.
Who should talk to a doctor before taking butyrate?
Talk to your doctor before taking butyrate if you have high blood pressure or heart disease, or are pregnant or nursing. The same goes if you have kidney or liver disease, or take prescription medication.
Most of this is ordinary caution for any supplement.
High blood pressure or heart disease. One trial saw blood pressure rise.
Pregnant or nursing. I couldn't find a human trial of butyrate supplements in pregnancy or nursing. With no data, ask first.
Kidney or liver disease. Ask first, and count the sodium if you're on a low-sodium diet. Our guide to butyrate and liver health covers what has been studied.
Prescription medication. Your doctor or pharmacist can check butyrate against what you take.
Children. The children's trial was run at a university clinic, with the dose set by body weight. Ask their pediatrician first.
Butyrate supplements are not a treatment for high blood pressure, diabetes, colitis, IBS or any other condition named here. If you have one, work with your doctor.
How do you take butyrate supplements to keep side effects low?
To use a butyrate supplement safely, take the serving on its label, with a meal if the label says so. Check the label for sodium, and stop and call your doctor if something feels wrong.
Follow the label. There is no official daily amount for butyrate. Very large doses are another matter. In a 1998 dose-finding study of tributyrin, the worst side effects were nausea, vomiting and muscle pain. Milder ones included diarrhea and constipation (Conley 1998).
Take it with a meal if your label says so. Most labels we've read tie the serving to a meal. I've seen no trial that compares taking butyrate with food and without.
Which butyrate supplement do we suggest?
If you want to try butyrate, a supplement gives it to you directly. It adds to what your gut bacteria make from fiber, and here is how to increase butyrate naturally.
Our pick is L-lysine butyrate, for three reasons: a milder smell, no sodium and no added oils. Some softgels and capsules add a carrier oil such as MCT oil.
No trial has compared side effects between forms yet. The closest gave 181 adults sodium or calcium butyrate for 12 weeks. The two groups rated how well they tolerated it at 8.4 and 8.7 out of 10, too close to tell apart (Mitrović 2025).
L-lysine butyrate is the newest form, with one human study so far.
In that study, 10 men took single doses of three forms, and none reported a side effect. L-lysine butyrate reached the blood in about 20 minutes, about even with sodium butyrate (La Monica 2025).
We sell it as BIOMEnd Butyrate: 4 capsules once a day with water. The same butyrate, at 500 mg a serving, is in our Natural GLP-1 Supplement capsules and our Crave Crusher drink. If you take more than one, the amounts add up, so ask your doctor.
To compare, see the best form of butyrate and our best butyrate supplement guide. The butyrate research hub has the rest, including butyrate and GLP-1.
The form we chose
Ozzi BIOMEnd Butyrate
1,000 mg of BIOMEnd L-lysine butyrate per daily serving of 4 capsules. No sodium carrier and no added oils. 112 capsules, 28 servings per bottle. It is a dietary supplement.
See the butyrate supplement →Frequently asked questions
Are butyrate supplements safe?
In human trials so far, butyrate supplements have been well tolerated. At the doses those trials used, side effects were mild and uncommon, such as short-lived nausea and headache. In one trial, blood pressure rose in adults with high blood pressure, so they should ask a doctor first.
What are the side effects of sodium butyrate?
In human trials, sodium butyrate has caused few side effects, and they were mild, such as short-lived nausea and headache. It adds about 313 mg of sodium per serving of 1,200 mg butyric acid and has a rancid smell. In one 4-week trial, it raised blood pressure in adults who already had high blood pressure.
Does calcium magnesium butyrate have side effects?
I haven't found a published human trial of calcium magnesium butyrate, so its side effects haven't been measured. The closest data is on calcium butyrate. In a 12-week trial, 60 adults took it and reported no significant side effects.
Can butyrate cause constipation?
Butyrate has not been shown to cause constipation at the doses used in supplement trials. Constipation was listed as a mild side effect in one study of very large tributyrin doses. If your bowel habits change after you start butyrate, stop and ask your doctor.
Can butyrate cause diarrhea?
In the trials we've read that tracked gut symptoms, butyrate did not cause more diarrhea than placebo. In one 12-week trial of 52 adults, diarrhea went down in the group taking sodium butyrate. Diarrhea was reported in a study of very large tributyrin doses.
When should you take butyrate?
I've seen no trial that tested the best time of day to take butyrate. Most labels we've read say to take it with a meal or just before one, so follow yours.
How much butyrate should I take per day?
There is no official daily amount for butyrate, so follow the serving on your product's label. Human trials have used from 300 mg to 4 g a day. That is a fact about the research, not advice.
Is butyrate safe during pregnancy?
I couldn't find a human trial of butyrate supplements in pregnancy or nursing. With no data either way, talk to your doctor before you take one.
This article is for educational purposes and isn't medical advice. It describes published research on butyrate, not the effects of any Ozzi product. Ozzi products are dietary supplements and are not intended to diagnose, treat, cure, or prevent any disease. Talk to your healthcare provider before starting any supplement, especially if you have a medical condition or take medication.
References
- Krokowicz L, et al. Microencapsulated sodium butyrate administered to patients with diverticulosis decreases incidence of diverticulitis: a prospective randomized study. Int J Colorectal Dis. 2014. PubMed 24343275
- Coppola S, et al. Therapeutic effects of butyrate on pediatric obesity: a randomized clinical trial. JAMA Netw Open. 2022. PubMed 36469320
- Mitrović M, et al. Exploring the potential of oral butyrate supplementation in metabolic dysfunction-associated steatotic liver disease: subgroup insights from an interventional study. Int J Mol Sci. 2025. PubMed 40565024
- Tougaard NH, et al. Effects of butyrate supplementation on inflammation and kidney parameters in type 1 diabetes: a randomized, double-blind, placebo-controlled trial. J Clin Med. 2022. PubMed 35806857
- Karłowicz K, et al. Efficacy of microencapsulated sodium butyrate as add-on therapy in inducing remission in patients with mild-to-moderate ulcerative colitis: results from a multi-center, double-blind, randomized, placebo-controlled study. Med Sci Monit. 2025. PubMed 41422374
- La Monica MB, et al. A pharmacokinetic comparison of three butyrate products. Journal of Exercise and Nutrition. 2025;8(1):4. Journal page
- Verhaar BJH, et al. Effects of oral butyrate on blood pressure in patients with hypertension: a randomized, placebo-controlled trial. Hypertension. 2024. PubMed 39034917
- Cometto-Muñiz JE, Abraham MH. Structure-activity relationships on the odor detectability of homologous carboxylic acids by humans. Exp Brain Res. 2010. PubMed 20931179
- U.S. Food and Drug Administration. Sodium in your diet. 2024. FDA page
- Panufnik P, et al. Effect of microencapsulated sodium butyrate on abdominal symptoms and carbohydrate metabolism in patients with type 2 diabetes: a randomized placebo-controlled trial. Sci Rep. 2026. PubMed 41974937
- Banasiewicz T, et al. Microencapsulated sodium butyrate reduces the frequency of abdominal pain in patients with irritable bowel syndrome. Colorectal Dis. 2013. PubMed 22738315
- Roshanravan N, et al. The effects of sodium butyrate and inulin supplementation on angiotensin signaling pathway via promotion of Akkermansia muciniphila abundance in type 2 diabetes; a randomized, double-blind, placebo-controlled trial. J Cardiovasc Thorac Res. 2017. PubMed 29391930
- Conley BA, et al. Phase I study of the orally administered butyrate prodrug, tributyrin, in patients with solid tumors. Clin Cancer Res. 1998. PubMed 9533530
