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.

Metabolomic Profiling of Obese Patients with Altered Intestinal Permeability Undergoing a Very Low-Calorie Ketogenic Diet

“…While knowledge of the VLCKD effect on the intestinal barrier is still limited and contrasting, our group recently confirmed its positive impact on anthropometric indices [9]. Moreover, our research highlighted that, despite the evident benefits, VLCKD may significantly affect the barrier integrity.…”

Higher-Level Steatosis Is Associated with a Greater Decrease in Metabolic Dysfunction-Associated Steatoic Liver Disease after Eight Weeks of a Very Low-Calorie Ketogenic Diet (VLCKD) in Subjects Affected by Overweight and Obesity

“…Due to the hepato-protective effects of carbohydrate restriction, which are further enhanced by a lower total calorie intake and ketogenesis, we proposed in a previous study that reducing daily carbohydrate intake to less than 50 g, which induces ketosis, could improve MASLD [ 31 ]. Furthermore, it remains plausible that the reduction in steatosis resulting from the use of the VLCKD may be partially attributed to the anti-inflammatory properties of the VLCKD itself [ 34 ]. According to this theory, we recently showed that patients with steatosis have lower WBC and platelet counts, while those without steatosis (CAP ≤ 275 dB/m) did not exhibit a significant decrease in WBC and platelet counts [ 36 ].…”

“…Anthropometric measurements, fasting blood sample data, and results from instrumental testing (BIA and Fibroscan) were gathered at T0 and T1. A discussion of the study’s time scale can be found in earlier publications [ 34 ].…”

“…The VLCKD protocol used in the present study has been published in several previous studies of ours [ 33 , 34 , 36 ], and the first two steps were adopted on the basis of the description in the paper by Bruci et al [ 29 ]. All participants received the VLCKD in accordance with the two-step protocol strategy from New Penta, Cuneo, Italy.…”

“…The rapid mobilization of fat from adipose tissue and the weight loss resulting from a VLCKD offers a very useful option for decreasing liver steatosis and treating MASLD [ 31 , 32 , 33 ]. Remarkably, our earlier research employing VLCKD for eight weeks revealed a drop in circulating TNF-α levels and an increase in IL-10 concentrations, indicating the inhibitory effect of the VLCKD on systemic inflammation, which could potentially be linked to MASLD [ 34 ]. According to Watanabe et al, individuals with insulin resistance benefit more from a VLCKD than those with less IR in terms of improving MASLD, indicating that patients with IR should receive strong recommendations for this dietary intervention [ 35 ].…”