July 6, 2023

Alpha Lipoic Acid, Myo-Inositol, Propolis, and Weight Loss for Nonalcoholic Fatty Liver Disease

Which is most effective?
While supplements may help, a calorie-restriction diet may offer the best results.


Tutunchi H, Arefhosseini S, Ebrahimi-Mameghani M. Clinical effectiveness of α-lipoic acid, myo-inositol and **propolis supplementation on metabolic profiles and liver function in obese patients with NAFLD: a randomized controlled clinical trial. Clin Nutr ESPEN. 2023;54:412-420. 

Study Objective

To compare the effects of dietary recommendations along with alpha lipoic acid (ALA), myo-inositol (MI), or propolis supplementation on metabolic parameters and liver function in obese patients with nonalcoholic fatty liver disease (NAFLD)

Key Takeaway

A calorie-restriction diet that results in weight loss among obese patients appears to be the most effective approach to NAFLD management and metabolic parameters, followed by myo-inositol and then alpha lipoic acid for improving hepatic steatosis.


Double-blind, placebo-controlled, randomized clinical trial


The study was conducted in Iran on 100 male and female obese patients (aged 18–50 years) with low or moderate physical activity level and body mass index (BMI) greater than or equal to 30 kg/m2 with NAFLD confirmed by ultrasonography in a fasting state. Steatosis was classified as mild (grade 1), moderate (grade 2), and severe (grade 3). Researchers excluded patients who were pregnant; lactating; postmenopausal; smokers; drinkers of alcohol; following weight-loss diets; taking dietary supplements, antidiabetic drugs, lipid-lowering agents, contraceptives, or medications affecting liver function and enzymes; or who had chronic or acute liver or metabolic diseases. 


Researchers randomly allocated the participants with NAFLD into 1 of 4 groups:

  1. alpha lipoic acid (n=21), receiving 1,200 mg ALA + placebo,
  2. myo-inositol (n=23), receiving 4 g MI powder + placebo,
  3. propolis group (n=24), receiving 1,500 mg Iranian propolis + placebo, and
  4. control group, receiving placebo.

All groups received dietary recommendations for a calorie-restricted diet designed by a dietitian. Researchers assessed each participant’s individual energy requirements, and the prescribed low-calorie diet was considered as a 500 Kcal deficit. Macronutrient distributions were as follows: fat 25% to 30% of total energy expenditure; protein 10% to 15%; and carbohydrates 55% to 60% of total energy expenditure. Meal plans were prepared based on these calculations, according to the food-based dietary guidelines for Iranians. The duration of the intervention was 8 weeks.

Study Parameters Assessed

Fasting body weight (in kilograms) and height were measured, as well as waist circumference and hip circumference. BMI, waist-to-hip ratio, and waist-to-height ratio were assessed. In addition, fasting blood samples were taken at baseline and at the end of the study, which consisted of glucose, total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), serum insulin, and homeostasis model assessment of insulin resistance (HOMA-IR), which was calculated as fasting insulin x fasting glucose/405. Liver enzymes, including alanine aminotransferase (ALT) and aspartate transaminase (AST) were included.

Primary Outcome

To compare the effects of ALA, MI, and propolis supplementation, as well as caloric deficit, on metabolic parameters and liver function in obese patients with NAFLD.

Key Findings

After 8 weeks, all anthropometric measures decreased significantly in all groups except waist-to-hip. While the largest improvement in glycemic index was seen in the MI group (P<0.05), the difference between the groups was not significant. The control group showed the largest reduction in serum triglycerides (P=0.026), but the MI group demonstrated the greatest improvements in serum total cholesterol, HDL-C, and LDL-C levels (P=0.043, P=0.019, and P=0.041, respectively). All groups showed significant reductions in ALT levels, particularly in the propolis group (P=0.012). AST levels were reduced to the greatest extent in the control group; however, the difference among the groups was “statistically marginal” (P=0.058). 

The estimated Number Needed to Treat (NNT) for 1-grade reduction in liver steatosis for the MI, ALA, and propolis supplementation groups compared with the control group were 1.5, 2.2, and 3, respectively.


The study was funded by the Research Vice-Chancellor of Tabriz University of Medical Sciences, Tabriz, Iran. The authors declare that they have no competing financial interests or personal relationships that could have influenced the work reported in this article.

Practice Implications & Limitations

Nonalcoholic fatty liver disease is the most common liver disease worldwide and the leading cause of liver-related morbidity and mortality.1

The incidence of NAFLD is increasing at an alarming rate, and the prevalence worldwide is estimated to be 32.4%.1 It has been projected that by 2030, the incidence of NAFLD globally will increase by up to 56%.2

NAFLD has metabolic, genetic, epigenetic, and environmental risk factors.3 Metabolic risk factors for NAFLD include being overweight or obese, insulin resistance or type 2 diabetes, high levels of triglycerides, high total cholesterol, high LDL and/or low HDL, or metabolic syndrome.4

In recent years, NAFLD has become a biological biomarker of social affluence and a sedentary lifestyle.3 Diets high in fructose5 and increased consumption of carbohydrates, animal proteins, and refined sugars, as well as smoking, air pollution, and low levels of physical activity,3 all contribute. The complex interactions among environmental factors, metabolism, genetic variants, and gut microbiota are all thought to be involved in the pathogenesis of NALFD.6

Nonalcoholic fatty liver disease is the most common liver disease worldwide and the leading cause of liver-related morbidity and mortality.

International guidelines for the treatment of NAFLD commonly include weight loss and exercise, which have already been shown to improve serum liver enzymes, hepatic inflammation, and fibrosis.7 A Mediterranean-style hypocaloric diet has demonstrated improvements in intrahepatic lipid content, as well as reduction in transaminases.8

This study evaluated a caloric deficit in all groups and then compared a control group to interventions with alpha lipoic acid, myo-inositol, and propolis on metabolic parameters related to NAFLD. Rationale for including the selected supplements is as follows:

  • ALA is a cofactor for mitochondrial enzymes and has been shown to improve insulin resistance,9 as well as reduce BMI.10 ALA regulates the secretion of adipokines associated with the development of NAFLD.11
  • MI is a 6-carbon sugar alcohol that is endogenously produced as well as being present in vegetables, fruits, legumes, nuts, and milk. MI deficiency is associated with increased fatty liver in animals.12 A human study showed that 2 grams of inositol per day improved blood glucose, insulin, total and HDL cholesterol, BMI, and waist circumference after 12 months in 80 postmenopausal women with metabolic syndrome.13
  • Propolis, a resinous substance collected by honeybees, has been shown to have protective effects on hepatic steatosis and fibrosis in patients with NAFLD.14

The study results under review here are relevant to clinicians since patients frequently hope to take a supplement for conditions such as NAFLD. However, caloric restriction resulting in weight loss has the most significant impact on NAFLD management and metabolic parameters over an 8-week timeframe vs supplement interventions. It may also make sense to consider MI for improving hepatic steatosis, followed by ALA. 

Limitations include a relatively short study interval of 8 weeks, which may not have been long enough to see the full impact of the interventions, as well as a diet still relatively high in carbohydrates at 55% to 60%. A lower-carbohydrate diet may have yielded additional benefits. 

Categorized Under


  1. Riazi K, Azhari H, Charette JH, et al. The prevalence and incidence of NAFLD worldwide: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2022;7(9):851-861.
  2. Huang DQ, El-Serag HB, Loomba R. Global epidemiology of NAFLD-related HCC: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol. 2021;18:223-238.
  3. Juanola O, Martínez-López S, Francés R, Gómez-Hurtado I. Non-alcoholic fatty liver disease: metabolic, genetic, epigenetic and environmental risk factors. Int J Environ Res Public Health. 2021;18(10):5227.
  4. NIH National Institute of Diabetes and Digestive and Kidney Diseases. Symptoms & causes of NAFLD & NASH. NIDDK website. https://www.niddk.nih.gov/health-information/liver-disease/nafld-nash/symptoms-causes. Accessed June 3, 2023.
  5. Jegatheesan P, De Bandt JP. Fructose and NAFLD: the multifaceted aspects of fructose metabolism. Nutrients. 2017;9(3):230.
  6. Caviglia GP, Rosso C, Fagoonee S, Saracco GM, Pellicano R. Liver fibrosis: the 2017 state of art. Panminerva Med. 2017;59(4):320-331.
  7. European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD), European Association for the Study of Obesity (EASO); EASL-EASD-EASO Clinical Practice Guidelines for the Management of Non-Alcoholic Fatty Liver Disease. Obes Facts. 2016;9(2):65-90.
  8. Houttu V, Csader S, Nieuwdorp M, Holleboom AG, Schwab U. Dietary interventions in patients with non-alcoholic fatty liver disease: a systematic review and meta-analysis. Front Nutr. 2021;8:716783.
  9. Mahmoudi-Nezhad M, Vajdi M, Farhangi MA. An updated systematic review and dose-response meta-analysis of the effects of α-lipoic acid supplementation on glycemic markers in adults. Nutrition. 2021;82:111041.
  10. Vajdi M, Abbasalizad Farhangi M. Alpha-lipoic acid supplementation significantly reduces the risk of obesity in an updated systematic review and dose response meta-analysis of randomised placebo-controlled clinical trials. Int J Clin Pract. 2020;74(6):e13493.
  11. Namazi N, Larijani B, Azadbakht L. Alpha-lipoic acid supplement in obesity treatment: a systematic review and meta-analysis of clinical trials. Clin Nutr. 2018;37(2):419e28.
  12. Pani A, Giossi R, Menichelli D, Fittipaldo VA, Agnelli F, Inglese E, et al. Inositol and non-alcoholic fatty liver disease: a systematic review on deficiencies and supplementation. Nutrients. 2020;12(11):3379.
  13. Santamaria A, Giordano D, Corrado F, et al. One-year effects of myo-inositol supplementation in postmenopausal women with metabolic syndrome. Climacteric. 2012;15(5):490-495.
  14. Soleimani D, Rezaie M, Rajabzadeh F, et al. Protective effects of propolis on hepatic steatosis and fibrosis among patients with nonalcoholic fatty liver disease (NAFLD) evaluated by real-time two-dimensional shear wave elastography: a randomized clinical trial. Phytother Res. 2021;35(3):1669-1679.