A Randomized, Double-blind, Placebo-Controlled, Crossover Study to Investigate the Effects of Microbial Enzyme Supplementation on Postprandial Nutrient Levels and Gastrointestinal Symptoms in Healthy Middle-Aged and Older Adults

Digestive enzymes of the human stomach, pancreas, and small intestine, are proteins that help facilitate the breakdown of dietary macronutrients for adequate nutrient supply across tissues and organs. Protease enzymes hydrolyze dietary proteins and release the amino acid building blocks of human proteins. Lipase enzymes hydrolyze dietary fats and release monoglycerides and fatty acids which can be absorbed by enterocytes and distributed across tissues and organs for energy, immune support, and structural support. Some carbohydrase enzymes, such as a combination of amylase and glucoamylase, hydrolyze carbohydrates and release monosaccharides that fuel the grand majority of metabolism within cells of most individuals on a diet that includes carbohydrates.

Digestive function and digestive enzyme output have been shown to decline in several clinical observational studies of younger and older adults, suggesting the potential value of oral, supplemental enzymes in older adults. Supplemental enzyme preparations manufactured by fermentation of non-genetically engineered, microbial source organisms, e.g., Aspergillus spp., have been on the market for decades to support digestive health and gastrointestinal tolerance. However, clinical data in older adult subjects is lacking.

BIO-CAT's proprietary mixture of 6 microbial enzymes ("BC-006") has previously been shown in in vitro gastrointestinal simulations to promote dietary protein, fat, and carbohydrate break down better than control conditions with endogenous enzymes alone (unpublished data). BC-006 comprises a mixture of proteases, lipase, amylase, and glucoamylase. The primary objective of this clinical study is to investigate the effect of BC-006 supplementation on postprandial nutrient levels in healthy, middle-aged to older adults during a mixed meal tolerance test. Abdominal bloating, flatulence, bowel function, and sleep quality will also be measured across 3 weeks of twice daily supplementation.

This study will be a randomized, placebo-controlled, crossover design trial consisting of a preliminary virtual screen and 4 study visits (Visits 1-4). During the preliminary virtual screening, subjects will provide voluntary informed consent, subjects will undergo medical history, prior and current medication/supplement use assessments, as well as inclusion and exclusion criteria assessments. At Visit 1, subjects will arrive at the clinic in a fasting state. Height, body weight, and vital signs will be measured and BMI will be calculated from a dual-energy X-ray absorptiometry (DEXA) scan. A blood sample will be collected for rapid fasting blood glucose analysis. Upon assessment of all eligibility criteria, subjects may be enrolled and randomized to BC-006 or placebo arms. Subjects will be dispensed their assigned study product and will be instructed to consume it twice daily (2 capsules/day) with their largest meals for 21 days. Subjects will be dispensed a paper Bowel Function and Gastrointestinal Tolerance Factors Questionnaire (BF-GITFQ) to be completed daily. The BF-GITFQ contains a series of questions regarding bowel function and the presence and severity of GI symptoms occurring during the past 24 hours. Subjects will also be dispensed a paper Gastrointestinal Tolerance Questionnaire (GITQ) which contains a series of questions regarding GI symptoms occurring during the past 7 days. To assess sleep quality, subjects will be dispensed a paper Single-Item Sleep Quality Scale (SI-SQS) to be completed weekly, leading up to Visit 2.

At Visit 2, subjects will arrive at the clinic fasted and undergo clinic visit procedures (concomitant medication/supplement use, assess inclusion/exclusion criteria, body weight and vital signs measurements), and adverse event (AE) assessment. Subjects will undergo a mixed meal tolerance test (MMTT). The MMTT includes antecubital vein placement, baseline blood sample collection, provision of a standardized test meal with BC-006 or placebo, and blood sampling thereafter for 5 hours. Blood samples will be collected for analysis of free amino acids, free fatty acids, glucose, iron, and insulin. An electronic Appetite Questionnaire will also be conducted hourly during the MMTT.