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Objectives: Anorexia nervosa (AN) is an eating disorder accompanied by a low body mass index and (self-) restricted food intake. Nutritional limitations can cause complaints of the digestive system, because of a disturbed absorption of food components. The absorption of carbohydrates may be seriously affected and reduced to a minimum. On this basis, a possible connection between AN, and the prevalence of gastrointestinal symptoms due to malabsorption was examined. Methods: For the systematic literature research with the aim of a better understanding of the topic the databases PubMed, Web of Science, Cochrane Library, Livivo and Google Scholar were used. Results: After the manual selection process of 2215 retrieved studies, 89 full texts were read and according to the predetermined eligibility criteria, finally 2 studies on the monosaccharide fructose and disaccharide lactose were included in this review. Conclusion: Malabsorption is often observed in patients with AN. It may contribute to the gastrointestinal complaints reported by patients and hamper body weight regain. Among others, mucosal atrophy and duodenal transporter dysfunction are discussed as main reasons. In the future more studies on carbohydrate malabsorption related to low body weight as observed in AN are warranted and may be conducted rather in an outpatient setting. Plain English summary: People with anorexia nervosa (AN) may experience a preference for foods containing fewer calories but more carbohydrates, e.g. fruits and vegetables. The consequences of this food restriction and selection may include malabsorption of sugars such as fructose and lactose, the mechanism of which is incompletely understood. This may contribute to symptoms similar to those seen in people with lactose intolerance, e.g. bloating, and make it harder for people to eat recommended foods. This paper presents a comprehensive literature search for research on this topic. However, only two studies were identified which highlights that further investigation is needed to explore this clinically relevant field. [ABSTRACT FROM AUTHOR]

During preclinical development of canagliflozin, an SGLT2 inhibitor, treatment-related pheochromocytomas, renal tubular tumors (RTT), and testicular Leydig cell tumors were reported in the 2-year rat toxicology study. In a previous 6-month rat mechanistic study, feeding a glucose free diet prevented canagliflozin effects on carbohydrate malabsorption as well as the increase in cell proliferation in adrenal medulla and kidneys, implicating carbohydrate malabsorption as the mechanism for tumor formation. In this chronic study male Sprague-Dawley rats were dosed orally with canagliflozin at high dose-levels (65 or 100 mg/kg/day) for 15 months and received either a standard diet or a glucose-free diet. Canagliflozin-dosed rats on standard diet showed presence of basophilic renal tubular tumors (6/90) and an increased incidence of adrenal medullary hyperplasia (35/90), which was fully prevented by feeding a glucose-free diet (no RTT's; adrenal medullary hyperplasia in ≤5/90). These data further confirm that kidney and adrenal medullary tumors in the 2-year rat study were secondary to carbohydrate (glucose) malabsorption and were not due to a direct effect of canagliflozin on these target tissues. [ABSTRACT FROM AUTHOR]

Canagliflozin is an SGLT2 inhibitor used for the treatment of type 2 diabetes mellitus. Studies were conducted to investigate the mechanism responsible for renal tubular tumors and pheochromocytomas observed at the high dose in a 2-year carcinogenicity study in rats. At the high dose (100 mg/kg) in rats, canagliflozin caused carbohydrate malabsorption evidenced by inhibition of intestinal glucose uptake, decreased intestinal pH and increased urinary calcium excretion. In a 6-month mechanistic study utilization of a glucose-free diet prevented carbohydrate malabsorption and its sequelae, including increased calcium absorption and urinary calcium excretion, and hyperostosis. Cell proliferation in the kidney and adrenal medulla was increased in rats maintained on standard diet and administered canagliflozin (100 mg/kg), and in addition an increase in the renal injury biomarker KIM-1 was observed. Increased cell proliferation is considered as a proximal event in carcinogenesis. Effects on cell proliferation, KIM-1 and calcium excretion were inhibited in rats maintained on the glucose-free diet, indicating they are secondary to carbohydrate malabsorption and are not direct effects of canagliflozin. [ABSTRACT FROM AUTHOR]