Effects of a Paleolithic diet compared to a diabetes diet on leptin binding inhibition in secondary analysis of a randomised cross-over study.

Background: Beneficial effects from practising a Paleolithic diet as compared to a diabetes diet on weight, waist circumference, satiety, leptin, HbA1c and glucose control in randomised controlled trial participants with type 2 diabetes could be due to lower leptin resistance. Support for this hypothesis comes from an in vitro experiment that showed that digested wheat gluten, which is excluded from a Paleolithic diet, inhibits leptin from binding to its receptor, thus indicating a possible dietary cause of leptin resistance. However, the clinical relevance of the latter finding is unclear since removal of enzyme activity from the gluten digest by heat treatment also abolished leptin binding inhibition. Assessment of leptin binding inhibition in vivo is possible by comparison of total leptin levels with those of 'biologically active' leptin bound to its receptor (bioLep).

Objectives: To assess the effects of a Paleolithic diet compared to a diabetes diet on leptin binding inhibition and to replicate our in vitro study.

Methods: BioLep and total leptin levels were measured in secondary analysis of fasting plasma samples from our open label random order three plus three-month long cross-over trial performed in 2005-2007, that compared a Paleolithic diet with a diabetes diet in participants with type 2 diabetes without insulin treatment (per protocol). BioLep was also measured in vitro for known recombinant leptin concentrations incubated with a series of concentrations of 10 kDa spin-filtered digested wheat gluten, with or without prior heat treatment, at 100ºC for 30 min and centrifugation.

Results: There was no difference between diets when comparing differences between bioLep and total leptin levels and their ratio in the 13 participants, three women and 10 men, aged 52-74 years with a mean BMI of 30 kg/m² and a mean diabetes duration of eight years. We found no carry-over or period effect for bioLep and total leptin. In vitro, wheat gluten digest inhibited leptin binding in a dose-dependent manner but not after heat treatment.

Conclusions: We found no leptin binding inhibition after the Paleolithic or diabetes diet, possibly due to its abolishment from cooking-related heat treatment of wheat gluten.

Trial registration: Registered on 14/02/2007 at ClinicalTrials.gov Identifier: NCT00435240.