Protein Pre-Hydrolysis as a Nutritional Strategy to Support Glycaemic Control and Blood Pressure Regulation

The modulation of glucose metabolism through dietary interventions has become an area of growing scientific interest, particularly with the rising prevalence of type 2 diabetes mellitus (T2DM) and related metabolic disorders. While plant proteins are increasingly promoted as sustainable alternatives to animal proteins, relatively little is known about how protein hydrolysis influences their physiological effects in humans. In particular, evidence comparing pre-hydrolysed and non-hydrolysed plant proteins using both mechanistic and clinical approaches remains limited. Furthermore, few studies have combined mechanistic in vitro approaches with human intervention trials to evaluate the translational potential of plant protein hydrolysates.
To address these gaps, this thesis employed a combined systematic review, in vitro, and human intervention approach to investigate whether pre-hydrolysed pea protein could improve postprandial metabolic responses compared with non-hydrolysed pea protein. First, a systematic review and meta-analysis was conducted to summarise and quantify the evidence on the acute and long-term effects of protein hydrolysates on glycaemic outcomes in humans. Across acute and long-term interventions, protein hydrolysates significantly reduced postprandial glucose concentrations (–1.05 mmol/L in healthy adults and –1.72 mmol/L in individuals with T2DM), while also improving fasting glucose (–0.38 mmol/L) and glycated haemoglobin (–0.19%) in clinical populations. However, the majority of included studies focused on animal-derived proteins, highlighting a critical gap in evidence for plant proteins.
To address this limitation, pea protein was selected as a sustainable plant-based protein source and used as a model system to investigate the effects of protein hydrolysis. A randomised controlled crossover trial demonstrated that co-ingestion of pre-hydrolysed pea protein with a carbohydrate-rich meal attenuated postprandial glucose excursions, reduced blood pressure, and enhanced satiety compared with non-hydrolysed pea protein and carbohydrate control. Complementary pepsin hydrolysis and static starch digestion studies demonstrated that pre-hydrolysed pea protein exhibited enhanced inhibition of α-amylase, α-glucosidase, DPP-IV, and ACE activities, and substantially reduced in vitro starch digestibility compared with intact pea protein. To further explore strategies for optimising the metabolic effects of pea protein, a second randomised crossover trial investigated the impact of protein timing by administering pea protein as a preload before carbohydrate ingestion. Preload consumption significantly reduced peak postprandial glucose excursions, improved subjective satiety, and lowered diastolic blood pressure compared with the carbohydrate control condition. Overall, this thesis demonstrates that protein hydrolysis can enhance the physiological functionality of pea protein and improve multiple postprandial metabolic outcomes, including glycaemic control, hormone secretion, satiety, and blood pressure regulation.