A group of 54 very obese children, 5 to 17 year of age, were placed on a standard weight loss diet plus either a butyrate supplement or a placebo for six months (JAMA Netw Open, Dec 5, 2022;5(12):e2244912). The butyrate group took sodium butyrate capsules, 20 mg/kg body weight per day, up to a maximum of 800 mg per day for six months. Those given butyrate lost significantly more weight than those in the placebo group. They also had:
• greater reduction in their waist circumference (risk factor for diabetes and heart disease)
• lower blood sugar levels (risk factor for diabetes)
• lower blood insulin levels (risk factor for certain cancers)
• lower insulin resistance (as measured by HOMA-IR test, risk factor for diabetes)
• lower blood total cholesterol and bad LDL cholesterol levels
• lower ghrelin (a hormone that makes you feel hungry)
• lower microRNA221 relative expression (gene regulatory RNA that increases cancer risk)
• lower IL-6 level (measure of inflammation that can cause cancer, heart attacks and premature death)

Adverse side effects included transient mild nausea and headache in two patients during the first month of taking butyrate. Symptoms disappeared during the following four weeks, and both patients were able to continue their assigned treatment.

Several studies show that butyrate pills help animals to lose weight and control blood sugar levels, but the few studies showing weight loss in obese humans have been done on very small sample sizes (Obesity Reviews, Oct 2022;23(10):e13498). So far the studies in humans have been short and not controlled with placebos. A few earlier studies on humans have found increased insulin sensitivity only in lean, healthy people but not in those who have diabetes (Clin Transl Gastroenterol, 2018; 9(5):e155).

What is Butyrate?
Butyrate is a by-product of the breakdown of soluble fiber by bacteria in your colon (Molecules, 2021;26(3):682). All plants contain soluble fiber that cannot be absorbed until it reaches your colon, where the good bacteria metabolize it to produce short chain fatty acids (SCFAs) that are absorbed into your bloodstream. SCFAs help to lower high blood pressure and high blood levels of cholesterol, sugar, and insulin. This study showed a dramatic lowering of insulin resistance, body fat, waist circumference, a hormone that makes you hungry, and DNA susceptibility to forming cancer cells. There are several different SCFAs and each is defined by its number of carbon atoms. Butyrate is a SCFA with four carbon atoms.

Obesity is Common and Hard to Treat
Fifty-seven percent of obese children will still be obese at age 35 and therefore will be at very high risk for the diseases and premature death it causes (N Engl J Med, Nov 2017; 377:2145-2153). Bacteria in your colon have been shown to affect the absorption and storage of food that you eat (Science, 2018;362:776–780), and obesity is strongly associated with a low intake of plant foods that are rich sources of soluble fiber (Prz Gastroenterol, 2020;15(2):119-125). Some foods, such as those with added sugars, promote the growth of harmful bacteria that try to invade your colon cells, which can cause inflammation that increases risk for metabolic disease and fat deposition (Science, 2018;362:776–780). In the future, we may be able to prevent obesity by altering the balance of healthful and harmful bacteria in the colon, and increasing butyrate from the breakdown of soluble fiber by the healthful bacteria (Molecules, 2021;26(3):682).

My Recommendations
I will watch for further studies on butyrate supplements for weight loss and control of diabetes. Meanwhile, you can get the possible benefits of butyrate supplements by eating more plants, since soluble fiber from any source will be metabolized to SCFAs including butyrate.

If you can pinch more than two inches of fat underneath the skin next to your belly button, you are at significant risk for diabetes and a heart attack because that usually means that your liver is full of fat. A fatty liver is the major cause of insulin resistance and diabetes that cause heart attacks and premature death. Part of your program to get rid of the excess fat is to eat a diet rich in soluble fiber in plants and avoid high rises in blood sugar caused by foods with added sugar, drinks with any sugar and all refined carbohydrates. Not eating enough vegetables is a significant risk factor for obesity, diabetes and heart attacks.