The Effects of a Very-Low-Calorie Ketogenic Diet on the Intestinal Barrier Integrity and Function in Patients with Obesity: A Pilot Study

Abstract

The very-low-calorie ketogenic diet (VLCKD) is effective and safe for obese individuals, but limited information exists on its impact on the intestinal barrier. This study analyzed the effects of 8 weeks of VLCKD on 24 obese patients (11M/13F). Carbohydrate intake was fixed at 20-50 g/day, while protein and lipid intake varied from 1-1.4 g/kg of ideal body weight and 15-30 g per day, respectively. Daily calorie intake was below 800 kcal. The lactulose-mannitol absorption test assessed small intestinal permeability. Multiple markers, such as serum and fecal zonulin, fatty acid-binding protein, diamine oxidase concentrations, urinary dysbiosis markers (indican and skatole), and circulating lipopolysaccharide levels, were analyzed. Inflammation markers (serum interleukin 6, 8, 10, and tumor necrosis factor-α concentrations) were also evaluated. The results showed significant reductions in weight, BMI, and waist circumference post-diet. However, the lactulose-mannitol ratio increased by 76.5%, and a significant increase in dysbiosis markers at the end of the diet occurred. This trend was particularly evident in a subgroup of patients. Despite initial benefits, the VLCKD might negatively affect the intestinal barrier function in obese patients, potentially worsening their compromised intestinal balance.

Keywords: dysbiosis; inflammation; intestinal barrier; intestinal permeability; ketogenic diet; obesity.

Figure 1

The study design.

Figure 2

The flow of the patients through the study.

Figure 3

A sugar absorption test (SAT) evaluated the small intestinal permeability (s-IP) before (pre) and after (post) eight weeks of a very-low-calorie ketogenic diet (VLCKD). Lac% = percentage of ingested lactulose excreted in the urine, (A). Man% = percentage of ingested mannitol excreted in the urine, (B). Lac to Man ratio = lactulose to mannitol ratio, (C). Suc% = percentage of ingested sucrose excreted in the urine, (D). Data are presented as mean ± SEM. Statistical analysis: Wilcoxon matched-pairs signed-rank test with a significant difference set at p < 0.05. The dotted red line indicates the cut-off value for altered small intestinal permeability (Lac to Man ratio ≥ 0.03).

Figure 4

Lactulose to mannitol ratios represented before (pre) and after (post) eight weeks of a very-low-calorie ketogenic diet (VLCKD). Lac to Man ratio = Lactulose to Mannitol ratio. Statistical analysis: Fisher’s exact test with a significant difference set at p < 0.05. The dotted red line indicates the cut-off value for altered small intestinal permeability (Lac to Man ratio ≥ 0.03).

Figure 5

The serum circulating concentrations of interleukin-6 (IL-6, (A)), interleukin-8 (IL-8, (B)), tumor necrosis factor-α (TNF-α, (C)), and interleukin-10 (IL-10, (D)) in obese patients before (pre) and after (post) eight weeks of a very-low-calorie ketogenic diet (VLCKD). Data expressed as means ± SEM. Wilcoxon matched-pairs signed-rank test was used to compare pre-treatment and post-treatment data. Differences were considered significant at p < 0.05.

Figure 6

Urinary indican (A), urinary skatole (B), and serum lipopolysaccharide—LPS (C) levels in patients with obesity before (pre) and after (post) eight weeks of VLCKD. Data expressed as means ± SEM. Wilcoxon matched-pairs signed-rank test was used to compare pre-treatment and post-treatment data. Differences were considered significant at p < 0.05. The dotted line indicates the cut-off level for dysbiosis: indican (20 mg/L) and skatole (20 μg/L).