Very-Low-Calorie Ketogenic Diets With Whey, Vegetable, or Animal Protein in Patients With Obesity: A Randomized Pilot Study

J Clin Endocrinol Metab. 2020 Sep 1;105(9):dgaa336. doi: 10.1210/clinem/dgaa336.


Context: We compared the efficacy, safety, and effect of 45-day isocaloric very-low-calorie ketogenic diets (VLCKDs) incorporating whey, vegetable, or animal protein on the microbiota in patients with obesity and insulin resistance to test the hypothesis that protein source may modulate the response to VLCKD interventions.

Subjects and methods: Forty-eight patients with obesity (19 males and 29 females, homeostatic model assessment (HOMA) index ≥ 2.5, aged 56.2 ± 6.1 years, body mass index [BMI] 35.9 ± 4.1 kg/m2) were randomly assigned to three 45-day isocaloric VLCKD regimens (≤800 kcal/day) containing whey, plant, or animal protein. Anthropometric indexes; blood and urine chemistry, including parameters of kidney, liver, glucose, and lipid metabolism; body composition; muscle strength; and taxonomic composition of the gut microbiome were assessed. Adverse events were also recorded.

Results: Body weight, BMI, blood pressure, waist circumference, HOMA index, insulin, and total and low-density lipoprotein cholesterol decreased in all patients. Patients who consumed whey protein had a more pronounced improvement in muscle strength. The markers of renal function worsened slightly in the animal protein group. A decrease in the relative abundance of Firmicutes and an increase in Bacteroidetes were observed after the consumption of VLCKDs. This pattern was less pronounced in patients consuming animal protein.

Conclusions: VLCKDs led to significant weight loss and a striking improvement in metabolic parameters over a 45-day period. VLCKDs based on whey or vegetable protein have a safer profile and result in a healthier microbiota composition than those containing animal proteins. VLCKDs incorporating whey protein are more effective in maintaining muscle performance.

Trial registration: NCT04019431.

Keywords: VLCKD; animal proteins; intestinal microbiota; obesity; therapy; vegetable proteins; very low calorie ketogenic diet; whey proteins.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Caloric Restriction* / methods
  • Diet, Ketogenic* / methods
  • Diet, Reducing / methods*
  • Female
  • Gastrointestinal Microbiome
  • Hand Strength / physiology
  • Humans
  • Insulin Resistance / physiology
  • Male
  • Meat Proteins / administration & dosage
  • Middle Aged
  • Obesity / diet therapy*
  • Obesity / microbiology
  • Obesity / physiopathology
  • Obesity / urine
  • Pilot Projects
  • Vegetables / physiology
  • Weight Loss / physiology
  • Whey Proteins / administration & dosage


  • Meat Proteins
  • Whey Proteins

Associated data