The effect of chromium picolinate supplementation on insulin resistance, liver enzymes, steatosis and fibrosis in individuals with normal weight and metabolic dysfunction-associated steatotic liver disease: A parallel double-blind randomized controlled clinical trial

To determine the effect of chromium picolinate supplementation on insulin resistance, liver enzymes, steatosis and fibrosis in individuals with normal weight and metabolic dysfunction–associated steatotic liver disease

A parallel randomized, double-blinded, controlled trial on 80 MASLD patients (40 in each group). Stratified block-randomization based on BMI is used.

This study will be conducted on 80 MASLD patients referred to gastroenterology clinic in Tehran, Iran. Patients will be randomly divided into 2 equal groups and will receive chromium picolinate and placebo for 12 weeks. To blind all researchers and participants, supplement and placebo are similar in appearance and color and a third person outside the study knows their content.

Inclusion criteria: 18-65 y adults of both genders; BMI of 18.5 to 25; diagnosis to have MASLD based on fibroscan by a gastroenterologist. Exclusion criteria: alcohol consumption; pregnant/lactating females; having other liver diseases (hepatitis B and C), biliary diseases, autoimmune diseases, cancer, kidney diseases, thyroid diseases, and diabetes; use blood sugar-lowering drugs and insulin; use of medications that affect liver fat, corticosteroids, antibiotics, hepatotoxic medications, and levothyroxine; weight loss in the last 3 months; withdrawal to continue the study; weight loss more than 10% during the study; pregnancy during the study; any severe gastrointestinal complications related to the intervention.

Two groups (n=40 in each): intervention group (1 tablet containing 500 mcg chromium picolinate per day) and placebo group (1 tablet per day of corn starch).

Primary outcome: changes in liver steatosis; Secondary outcome: FBS, serum insulin, HOMA-IR, QUICKI, ALT, AST, GGT, fibrosis, weight, waist circumference, adverse events

At the beginning of the study and before the intervention, random assignment of individuals to intervention groups will be done using the Stratified Block Randomization method. First, individuals will be grouped based on BMI (18.5 to 20.5, 20.5 to 22.5, and 22.5 to 25), and in each of these blocks, individuals who are matched in terms of BMI will be placed. Then, in each block, individuals will be randomly divided into two supplement and placebo groups. Randomization will be done using the Random Allocation Software (RAS). In this method, each group will be assigned one of the letters A and B, and randomization will be done in blocks of 4. Within each stratum, individuals will be randomly placed in one of the two study groups in a 1:1 ratio.

The present study will be conducted in a double-blind manner, meaning that the participants, the principal investigator, and the evaluators will not identify individuals receiving the chromium picolinate supplement or the placebo. The appearance, color, taste, and odor of the chromium supplement and the placebo will be similar. As a result, the study participants will not know which supplement/placebo they were taking. Also, the supplements/placebos will be coded, and a person outside the study will know the codes and the type of supplement/placebo. The evaluators will deliver the supplements/placebos to the participants based on the code labeled on them and will not know the content of each supplement.

The study protocol will be written and published in the form of an article. The clinical report of the study will be published in the form of an article.

8 months after the end of the study

The data will only be available for people working in academic institutions.

To use the findings in the clinic or to write other articles, including review articles. In the case of original articles, researchers will be allowed to do so.

Data and documents related to the present study will be available via email from the study researchers, Dr. Ahmad Esmaillzadeh (a.esmaillzadeh@gmail.com) and Keyhan Lotfi (keyhanlotfi75@gmail.com).

After receiving the request from the person in charge of updating, the study will be provided to the researcher in consultation with the scientific officer.