Is the Phenylalanine-Restricted Diet a Risk Factor for Overweight or Obesity in Patients with Phenylketonuria (PKU)? A Systematic Review and Meta-Analysis

Abstract

Although there is a general assumption that a phenylalanine (Phe)-restricted diet promotes overweight in patients with phenylketonuria (PKU), it is unclear if this presumption is supported by scientific evidence. This systematic review aimed to determine if patients with PKU are at a higher risk of overweight compared to healthy individuals. A literature search was carried out on PubMed, Cochrane Library, and Embase databases. Risk of bias of individual studies was assessed using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies, and the quality of the evidence for each outcome was assessed using the NutriGrade scoring system. From 829 articles identified, 15 were included in the systematic review and 12 in the meta-analysis. Body mass index (BMI) was similar between patients with PKU and healthy controls, providing no evidence to support the idea that a Phe-restricted diet is a risk factor for the development of overweight. However, a subgroup of patients with classical PKU had a significantly higher BMI than healthy controls. Given the increasing prevalence of overweight in the general population, patients with PKU require lifelong follow-up, receiving personalised nutritional counselling, with methodical nutritional status monitoring from a multidisciplinary team in inherited metabolic disorders.

Impact of Fruit and Vegetable Protein vs. Milk Protein on Metabolic Control of Children with Phenylketonuria: A Randomized Crossover Controlled Trial

“…Understanding the upper phenylalanine content of fruits and vegetables that can be tolerated without measurement in patients with PKU on dietary treatment only is particularly important. In PKU, the rate of obesity although similar to the general population is high [ 18 ], but fruit and vegetable intake is low [ 19 ]. It is well established that vegetables are good sources of bioactive compounds, including dietary fiber, micronutrients and phytochemicals, and they are associated with a reduced risk of chronic disease; strategies to increase the intake and variety of low-energy-dense vegetables are essential [ 20 ].…”

Dietetic Management of Adults with Phenylketonuria (PKU) in the UK: A Care Consensus Document

“…Since then, several studies have found the female PKU population (both adults and children) to have increased levels of overweight and obesity in comparison to the general population [ 25 , 30 , 31 ]. In a recent systematic review, Rodrigues et al [ 32 ] conducted a meta-analysis and found that the BMI of patients with PKU was similar to their healthy controls; however, a subgroup of patients with classical PKU had a significantly higher BMI. The meta-analysis dataset included both adults and children; the age range was between 0.2 and 52 years.…”

The Impact of the Quality of Nutrition and Lifestyle in the Reproductive Years of Women with PKU on the Long-Term Health of Their Children

“…Obesity : The prevalence of overweight and obesity in all women of childbearing age is high, and approximately 39% of the world’s adult population is overweight, with 13% being obese [ 25 ]. Although a recent systematic review and meta-analysis of women with PKU [ 26 ] found that the body mass index (BMI) of patients with PKU was similar to their healthy controls, a subgroup of patients with classical PKU had a significantly higher BMI. The authors also noted a trend towards a higher BMI in females with PKU in all studies with male and female datasets.…”