Hormonal and metabolic effects of carbohydrate restriction in children with Prader‐Willi syndrome

Abstract

Objective: Macronutrient regulation of hyperphagia and adiposity in Prader-Willi syndrome (PWS) is poorly understood. We compared fasting and postprandial concentrations of hormones and metabolites in eight PWS children (age 9-18 years) fed, in random order, low carbohydrate, high-fat (LC, 15% carb; 65% fat; 20% protein) and low-fat, high carbohydrate (LF, 65% carb, 15% fat, 20% protein) diets matched for calories and protein.Methods: Participants were randomized to consume either the LC or LF diet during a first hospital admission and the second diet during a subsequent admission. Blood samples were obtained after overnight fasting and 1 hour after a mixed meal.Results: Relative to subjects consuming the LF diet, subjects consuming the LC diet had: lower postprandial insulin concentrations (P = 0.02); higher fasting GLP-1 AND GIP concentrations and increased postprandial GLP-1 (P < 0.02); reduced ratio of fasting ghrelin to GLP-1 (P = 0.0078); increased FFA and fatty acid oxidation, as assessed by concentrations of even-chain acylcarnitines (P < 0.001); lower fasting TG and TG/HDL ratio (P < 0.01); and higher concentrations of branch chain amino acids (P < 0.01). There were no changes in glucose, PYY, or adiponectin. CRP, AST and ALT were all higher (P < 0.01) on the LC diet.Conclusions: Increases in GLP-1 with low carbohydrate feeding and reductions in the ratio of ghrelin to GLP-1 might limit food intake and improve glycaemic control in PWS. Other potential benefits of carbohydrate restriction may include fat mobilization and oxidation and reductions in the TG/HDL ratio, a marker of insulin resistance.However, increases in CRP, AST and ALT necessitate longer-term studies of low carbohydrate efficacy and safety. K E Y W O R D Sbranch chain amino acids, ghrelin, GLP-1, GIP, insulin, low carbohydrate diet, Prader-Willi syndrome, PYY

Dietary macronutrient regulation of acyl and desacyl ghrelin concentrations in children with Prader‐Willi syndrome (PWS)

“…Meals high in carbohydrates (≥65% of total energy intake) are generally more potent than meals high in fat in suppressing ghrelin concentrations. [11][12][13][14] In a recent study, 15 we compared the effects of low-fat, high-carbohydrate (LF-HC) and low carbohydrate, high-fat (LC-HF) intake in children with PWS, and we found that the LC-HF diet lowered post-prandial insulin concentration, increased fasting and post-prandial glucagon-like peptide 1 (GLP-1) concentrations and increased fatty acid oxidation relative to the LF-HC diet. However, the effect of dietary protein on AG and DAG has not yet been examined.…”

Current and emerging therapies for managing hyperphagia and obesity in Prader‐Willi syndrome: A narrative review

“…Due to lower fat oxidation, extra dietary carbohydrates can potentially lead to excess fat deposition in patients with PWS. Individuals with PWS were also found to have a preference for simple carbohydrates . Although limited, evidence suggests excessive carbohydrate intake, particularly simple carbohydrates, may contribute to weight gain before the onset of hyperphagia in children with PWS …”

“…Very recently, Irizarry et al examined the impact of carbohydrate restriction on hyperphagia and adiposity in children with PWS . Children with PWS (n = 8, age 9‐18 years) were randomly assigned to either the low carbohydrate, high‐fat (LC, 15% carb; 65% fat; 20% protein) diet or the low‐fat, high carbohydrate (LF, 65% carb, 15% fat, 20% protein) diet during a first hospital admission and the second diet during a subsequent admission.…”

<p>Dietary Management for Adolescents with Prader–Willi Syndrome</p>

“…22 Because of these issues, some groups have studied the effects of a carbohydrate-restricted diet for weight control in adolescents with PWS (15% carbohydrates, 65% fat, and 20% protein). 23 This diet, while effective, at least in the short term, for improved glycemic and weight control, is associated with deficiencies in vitamin D, calcium, and fiber. Elevations in C-reactive protein, as well as liver function tests (ALT, AST), have been shown in individuals with PWS following a low-carbohydrate diet.…”

“…Elevations in C-reactive protein, as well as liver function tests (ALT, AST), have been shown in individuals with PWS following a low-carbohydrate diet. 23 Additionally, a low-carbohydrate diet can affect the gut microbiome, including bacteria taxa, richness and diversity. 24 Although a few studies have shown potential beneficial effects of a low-carbohydrate diet on the gut microbiome, most studies have reported that a lowcarbohydrate diet has more significant negative effects on the gut microbiome, including lowered species diversity and increased pro-inflammatory bacteria.…”