Calcium and Vitamin D 3 Combinations Improve Fatty Liver Disease Through AMPK-independent Mechanisms

Eur J Nutr. 2018 Mar;57(2):731-740. doi: 10.1007/s00394-016-1360-4. Epub 2016 Dec 17.


Purpose: Some research findings suggest that calcium plus vitamin D (VitD) might have a preventive effect on nonalcoholic fatty liver disease development. Moreover, contradictory evidence also exists regarding calcium and VitD deficient diets. This study aimed to evaluate the effect of four different dietary calcium and VitD3 (cholecalciferol) levels on the development of high-fat, high-fructose (HFHFr) diet-induced nonalcoholic fatty liver disease and AMP-activated protein kinase (AMPK) phosphorylation.

Methods: Thirty male Wistar rats were fed with normal or HFHFr diet containing low calcium (0.2%) and VitD3 (250 IU/kg) (LCD), normal calcium (0.5%) and VtD3 (1000 IU/kg) (CN), high calcium (1.2%) and VitD3 (4000 IU/kg) (HCD) or very high amount of calcium (2.4%) and VitD3 (10,000 IU/kg) (VHCD). After 60 days, anthropometric, metabolic and hepatic parameters were evaluated. The effect of the experimental diets on liver AMPK phosphorylation was also investigated.

Results: Rats fed on high calcium plus VitD3 diets, especially VHCD, demonstrated lower adiposity, serum liver enzymes, hepatic lipid accumulation and steatosis. The LCD diet also decreased hepatic lipid content and fatty changes. No evidence indicating the involvement of AMPK in the observed associations was found (P value = 0.51).

Conclusions: The results showed high calcium plus VitD3 intakes considerably prevent biochemical and hepatic changes induced by HFHFr diet, probably via an insulin and AMPK-independent pathway. A low intake of these two nutrients was also linked with a significant decrease in HFHFr diet-induced hepatic steatosis.

Keywords: AMP-activated protein kinase; Calcium; Nonalcoholic fatty liver disease; Vitamin D3.

Publication types

  • Comparative Study

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Adiposity*
  • Animals
  • Biomarkers / blood
  • Biomarkers / metabolism
  • Blood Glucose / analysis
  • Calcium, Dietary / administration & dosage
  • Calcium, Dietary / therapeutic use*
  • Cholecalciferol / administration & dosage
  • Cholecalciferol / therapeutic use*
  • Diet, Western / adverse effects
  • Dietary Supplements*
  • Insulin / blood
  • Lipid Metabolism*
  • Lipid Peroxidation
  • Liver / metabolism*
  • Liver / pathology
  • Liver / physiopathology
  • Male
  • Non-alcoholic Fatty Liver Disease / metabolism
  • Non-alcoholic Fatty Liver Disease / pathology
  • Non-alcoholic Fatty Liver Disease / physiopathology
  • Non-alcoholic Fatty Liver Disease / prevention & control*
  • Organ Size
  • Phosphorylation
  • Protein Processing, Post-Translational
  • Random Allocation
  • Rats, Wistar


  • Biomarkers
  • Blood Glucose
  • Calcium, Dietary
  • Insulin
  • Cholecalciferol
  • AMP-Activated Protein Kinases