Understanding the Health Effect of a Bioactive Peptide From Egg: A Pilot Study

Bioactive peptides derived from food proteins show vast potential for improving human health, in addition to providing nutritional value. One of such promising peptides is a short tripeptide IRW (made of three amino acids, isoleucine-arginine-tryptophan), the first discovered peptide that can activate ACE2 (angiotensin converting enzyme 2) preclinically. ACE2 is best known as the entry receptor of some coronaviruses, including the pandemic's SARS-CoV-2, while the primary role of ACE2 is to provide protection on the cardiometabolic system. Therefore, activation of ACE2 is a novel strategy to mitigate cardiometabolic diseases. A decade-long collaborative research on IRW has established a large body of knowledge about IRW's health effects on hypertension, type-2 diabetes (T2D)/insulin resistance (IR), oxidation, and inflammation. To translate the knowledge for human applications, it is essential to investigate the bioavailability and efficacy of bioactive peptide IRW in egg white hydrolysate.

IRW is derived from ovotransferrin, which accounts for ~12% of total egg white protein. Egg white powder without a process of hydrolyzation will not liberate the IRW, therefore, this will be used as a negative control. However, it is too costly to prepare IRW from pure ovotransferrin for functional food applications. To reduce the cost of production, whole egg white could be used as the starting material. IRW can only be released by a combination of thermolysin and pepsin. If only thermolysin is applied, a pentapeptide IRWCT is formed; as pepsin is naturally secreted in the stomach, egg white hydrolysate will be prepared using thermolysin. It is expected that IRW will be released in vivo by the gastrically secreted pepsin.

This study is the first to translate a peptide ACE2 activator as a functional food for human applications against metabolic syndrome (MetS, hypertension, T2D/Insulin Resistance). A functional food containing IRW provides a dietary strategy for the mitigation of metabolic syndrome and presents a value-added opportunity for the Canadian egg industry.

Inclusion criteria

Healthy control group:

• Men and women aged between 18 and 70 years living in Edmonton (or Edmonton area/driving distance).
• Normal weight (BMI below 25 kg/m2 or Asian population below 23 kg/m2 )
• Waist circumference below the following ethnic specific cut offs: Canada / USA: <102 cm men and <88 cm women; Europids, Middle-Eastern, Sub-Saharan African, and Mediterranean: <94 cm men and <80 cm women; Asians, Japanese, South and Central Americans: <90 cm men and <80 cm women
• Fasting glucose <5.6 mmol/L
• HbA1c <5.6 %
• Blood pressure <130/85 mmHg
• Triglycerides <1.7 mmol/L
• HDL-Cholesterol >1.03 mmol/L men and >1.29 mmol/L women
• Body weight stable (within 3% fluctuation) for at least 6 months prior to the study
• Individuals who have never smoke, have smoke less than 100 cigarettes in their life or who are long term quitter (quit smoking a year or more ago)

Individuals at risk of diabetes/having type 2 diabetes:

• Men and women aged between 18 and 70 years living in Edmonton (or Edmonton area/driving distance).
• Overweight or obesity (BMI above 25 kg/m2 or Asian population above 23 kg/m2)
• Waist circumference at or above the following ethnic specific cut offs: Canada / USA: ≥ 102 cm men and ≥ 88 cm women; Europids, Middle-Eastern, Sub-Saharan African, and Mediterranean: ≥ 94 cm men and ≥ 80 cm women; Asians, Japanese, South and Central Americans: ≥ 90 cm men and ≥ 80 cm women
• Fasting glucose ≥ 6.0 mmol/L
• HbA1c ≥ 6.0 %
• Body weight stable (within 3% fluctuation) for at least 6 months prior to the study
• Individuals who have never smoke, have smoke less than 100 cigarettes in their life or who are long term quitter (quit smoking a year or more ago)

Exclusion criteria

• Individuals with a previous history of CVD, renal disorder, monogenic dyslipidemia, with endocrine disorders other than T2D
• Individuals taking chronic anti-inflammatory drugs (including aspirin, antihistamines, and omega-3 supplements)
• Pregnant/lactating women
• Individuals aged above 70 years
• Smokers (current smokers: daily/occasional and those who have smoked more than 100 cigarettes in their life)
• Individuals with specific nutritional restrictions (e.g. vegetarianism excluding eggs from their diet, vegan or with egg allergy) will be excluded
• Individuals with poorly controlled (HbA1c >12.0%) diabetes or taking exogenous insulin will be excluded. Other anti-diabetic and lipid-lowering medications will be documented.