Oral Multienzyme Supplementation Alters Postprandial Plasma Nutrient Concentrations after a Mixed Meal in Healthy Middle-Aged and Older Adults: A Randomized, Double-Blind, Placebo-Controlled, Crossover Trial.

Max T Deutz, Andrew T Askow, Sean M Garvey, David A Alvarado, Takeshi M Barnes, Žan Zupančič, Alexander V Ulanov, Jared W Willard, Hannah D Holscher, Brett R Loman, Nicholas A Burd

Journal: The Journal of nutrition 2026;156(4):101400

PMID: 41662956

Plain Language Summary

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Ageing is associated with changes in the digestive system including reduced secretion of digestive enzymes. In tandem, ageing is associated with reduced nutrient intake leaving some individuals at risk of malnutrition. This study investigated the effects of an oral multi-enzyme supplement on nutrient levels in the blood after eating a mixed meal in healthy middle-aged and older adults. The researchers aimed to see if these enzymes could enhance the digestion and absorption of nutrients, which can decline with age, potentially leading to malnutrition.

The results showed that taking the multi-enzyme supplement significantly accelerated the presence of protein-derived nutrients and increased the levels of glucose and fatty acids in the blood. The presence of protein-derived nutrients was more pronounced in adults with a lower body mass index and higher lean mass.

It was concluded that multi-enzyme supplementation was associated with improved protein, carbohydrate and fat digestion in middle-aged and older adults, especially those who had a lower body mass index and higher lean mass. This study could be used by healthcare professionals to understand how oral multi-enzyme supplementation can enhance nutrient absorption after meals in older adults.

Abstract

BACKGROUND

Age-related decline in digestive function increases malnutrition risk. Supplementing meals with digestive enzymes may improve macronutrient digestion and bioavailability in adults reaching older ages.

OBJECTIVES

To assess postprandial plasma nutrient concentrations after co-ingestion of a mixed meal and a mixture of 6 enzyme preparations (ENZ), including proteases, lipase, amylase, and glucoamylase.

METHODS

Thirty middle-aged and older adults (56 ± 11 y; 18 females, 12 males) ingested chicken, peas, potatoes, and butter (435 kcal; 34 g protein, 51 g carbohydrate, 11 g fat) with either ENZ or placebo (PLA) in a randomized crossover fashion. Blood samples were collected at baseline and throughout a 0-5 h postprandial period for measurement of plasma amino acid, insulin, glucose, and nonesterified fatty acid (NEFA) concentrations. Clustering of postprandial amino acid responses was conducted in MFuzz, and logistic regression for response groups was conducted in JMP 18.2.0 (JMP Statistical Discovery LLC).

RESULTS

Plasma amino acid concentrations were not statistically different between treatments (PLA compared with ENZ) over the postprandial period (all P > 0.05). Leucine time to maximum concentration was significantly faster (P = 0.047) with ENZ (121.2 ± 55.9 min) compared with PLA (141.0 ± 49.2 min). Postprandial plasma glucose concentrations (P = 0.04) and total NEFA (P = 0.001) were higher with ENZ compared with PLA. Three distinct response patterns (clusters) were detected within and across all postprandial amino acid categories. Differences in habitual macronutrient intake and interactions between sex, lean mass, and BMI distinguished participants with an earlier time to maximum postprandial leucine concentration when consuming ENZ compared with PLA from those with stable responses.

CONCLUSIONS

Multienzyme supplementation improved macronutrient digestion of a mixed meal in middle-aged and older adults. For plasma amino acids, this benefit was most pronounced in adults with lower BMI and higher lean mass, and the effect was sex-dependent. This study was registered at clinicaltrials.gov as NCT05211440.

Copyright © 2026 The Author(s). Published by Elsevier Inc. All rights reserved.

Address: Division of Nutritional Sciences, University of Illinois Urbana-Champaign, Urbana, IL.; Department of Health and Kinesiology, University of Illinois Urbana-Champaign, Urbana, IL.; Department of Research and Development, BIO-CAT, Inc., Troy, VA; SAPIOME LLC, Jericho, VT.; Roy J. Carver Biotechnology Center, University of Illinois Urbana-Champaign, Urbana, IL.; Christie Clinic, Orthopedics & Sports Medicine, Champaign, IL.; Division of Nutritional Sciences, University of Illinois Urbana-Champaign, Urbana, IL; Department of Food Science and Human Nutrition, University of Illinois Urbana-Champaign, Urbana, IL.; Division of Nutritional Sciences, University of Illinois Urbana-Champaign, Urbana, IL; Department of Food Science and Human Nutrition, University of Illinois Urbana-Champaign, Urbana, IL; Department of Animal Sciences, University of Illinois Urbana-Champaign, Urbana, IL.; Division of Nutritional Sciences, University of Illinois Urbana-Champaign, Urbana, IL; Department of Health and Kinesiology, University of Illinois Urbana-Champaign, Urbana, IL. Electronic address: [email protected].

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