We use essential cookies (authentication, your saved goals/stack) by default. With your permission we’ll also enable privacy-respecting analytics (Vercel Web Analytics, anonymous load-time metrics) and error-replay diagnostics (Sentry — DOM snapshots only when an error fires) so we can fix bugs faster. Learn more about cookies
Dge6.0
Digestive Enzymes Research
Likely helps
20 peer-reviewed studies
What the evidence says
Likely helps
Digestive Enzymes appears to help in 5 of 5 studies with measurable effects — the evidence leans clearly favourable.
Most evidence is from high-quality meta-analyses and randomised trials published 2006–2026 with a typical study size of 39 participants.
Based on 20 studies · 1 meta-analysis · 9 RCTs · 962 total participants
Confidence
Moderate confidence
What the studies found
5helped· 15 more without graded effect data
By outcome
Pancreatic insufficiency & GI symptomsReduced bloating and improved food tolerance within 1-2 weeks · 1-2 weeks
Likely helps17 studies
Therapeutic & clinical
Mostly mechanism / observational5 studies
Safety profile
Mostly mechanism / observational3 studies
Glucose & metabolic
Too few graded studies2 studies
By the numbers
Pulled from 13 studies with measurable effects
Likely real effects
100%
across studies
People studied
962
typical study: 39 people
Strongest designs
10
1 pooled, 9 randomised
Showed benefit
100%
5/5 studies
How long studies ran
3+ months
2
Populations Studied
Patients with exocrine pancreatic insufficiency due to chronic pancreatitis or pancreatic surgery2
Chronic pancreatitis patients1
Children with ASD1
Functional dyspepsia patients1
Active research area
10 studies in the last 5 years · Latest meta-analysis: 2017
200620162026
1Coefficient of fat absorptionMeta-AnalysisCited 140×n=511 · large study2017
PERT is indicated to correct EPI and malnutrition in CP and may be improved by higher doses, enteric coating, administration during food and acid suppression.
de la Iglesia-García D et al. · Gut (2017)
Noticeable benefit
← WorseNo effectBetter →
Likely real
PERT improved CFA compared with baseline (83.7±6.0 vs 63.1±15.0, p<0.00001; I2=89%) and placebo (83.2±5.5 vs 67.4±7.0, p=0.0001; I2=86%).
PERT is indicated to correct EPI and malnutrition in CP and may be improved by higher doses, enteric coating, administration during food and acid suppression.
Further studies are required to determine optimal regimens, the impact of health inequalities and long-term effects on nutrition.
The results also found that the main interventions used were dietary interventions and nutraceuticals, including targeted supplements, vitamins and minerals, omega 3 s and prebiotics, probiotics and digestive enzymes.
Doherty M et al. · Journal of autism and developmental disorders (2025)
The results of this systematic review identified that for autistic people, vitamin and mineral supplements may only be of benefit if there is a deficiency.
The results also found that the main interventions used were dietary interventions and nutraceuticals, including targeted supplements, vitamins and minerals, omega 3 s and prebiotics, probiotics and digestive enzymes.
Therapeutic intervention, which may consist of supplementation of pancreatic enzymes and/or vitamins in aged individuals with proven exocrine pancreas insufficiency, could contribute to healthy ageing.
Löhr JM et al. · Journal of internal medicine (2018)
Five per cent of people older than 70 years and ten per cent older than 80 years have pancreatic exocrine insufficiency (PEI) with a faecal elastase-1 below 200 μg g-1 stool, and 5% have severe PEI with faecal elastase-1 below 100 μg g-1 stool.
Malnutrition consists of deficits of fat-soluble vitamins and is affecting both patients with PEI and the elderly.
Secondary consequences may include decreased bone mineral density and results from impaired absorption of fat-soluble vitamin D due to impaired pancreatic exocrine function.
The results showed an improvement in NDI-SF1, NDI-SF2-5, VAS, and PSQI scores in subjects treated with the multi-enzyme blend, indicating an improvement in quality of life and of sleep, and a decre...
Ullah H et al. · Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (2023)
The results showed an improvement in NDI-SF1, NDI-SF2-5, VAS, and PSQI scores in subjects treated with the multi-enzyme blend, indicating an improvement in quality of life and of sleep, and a decreased severity of pain, following the supplementation with digestive enzymes, without side effects.
In conclusion, treatment with digestive enzymes was found to be effective in the reduction of functional dyspepsia symptoms and in the improvement of sleep quality, and is well-tolerated.
7Fat and protein absorptionRCTCited 19×n=36 · small study2016
Pancrelipase improved fat and protein absorption in patients with EPI due to chronic pancreatitis or pancreatectomy, with or without DM, and matched the safety profile previously reported.
Whitcomb DC et al. · Pancreas (2016)
Huge benefit
← WorseNo effectBetter →
Likely real
Mean changes in nutrient absorption were greater with pancrelipase versus placebo in patients with DM (CFA, 36.0% vs 7.5%, P < 0.0001; CNA, 33.4% vs 3.7%, P = 0.0002) and without DM (CFA, 25.2% vs 12.3%, P = 0.0326; CNA, 39.1% vs 17.6%, P = 0.1187).
Diabetes mellitus was not significantly associated with outcomes for CFA (P = 0.0802) and CNA (P = 0.2934).
Pancrelipase improved fat and protein absorption in patients with EPI due to chronic pancreatitis or pancreatectomy, with or without DM, and matched the safety profile previously reported.
8Weight gain and stool frequencyRCTCited 84×n=51 · small study2011
Pancrelipase was well tolerated over 6 months and resulted in statistically significant weight gain and reduced stool frequency in patients with EPI due to CP or PS previously managed with standard PERT.
Gubergrits N et al. · Alimentary pharmacology & therapeutics (2011)
The mean age was 50.9 years, 70.6% of patients were male, 76.5% had CP and 23.5% had undergone PS.
TEAEs were reported by 22 patients (43.1%) overall.
Only four patients (7.8%) had TEAEs that were considered treatment related.
9Nonverbal intellectual ability improvementRCTCited 131×n=67 · small study2018
Parents reported that the vitamin/mineral supplements, essential fatty acids, and HGCSF diet were the most beneficial.
Adams JB et al. · Nutrients (2018)
Noticeable benefit
← WorseNo effectBetter →
Likely real
There was a significant improvement in nonverbal intellectual ability in the treatment group compared to the non-treatment group (+6.7 ± 11 IQ points vs. -0.6 ± 11 IQ points, p = 0.009) based on a blinded clinical assessment.
Based on semi-blinded assessment, the treatment group, compared to the non-treatment group, had significantly greater improvement in autism symptoms and developmental age.
The treatment group had significantly greater increases in EPA, DHA, carnitine, and vitamins A, B2, B5, B6, B12, folic acid, and Coenzyme Q10.
Berry N et al. · Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology (2026)
Fat maldigestion occurs when lipase secretion falls to below 10% of normal.
This threshold is defined as severe PEI and is a definite indication for pancreatic enzyme replacement therapy (PERT).
In this review, we shall discuss about conditions, other than pancreatitis, which cause PEI, and understand the possible mechanisms by which they cause PEI.
11nutritional status and pancreatic functionReview2026
de Pretis N et al. · European journal of gastroenterology & hepatology (2026)
Not only pancreatic secretions but also the interaction between exocrine and endocrine pancreatic function have relevance on nutritional status, and there is increasing evidence that nutritional status impacts the prognosis of both inflammatory and pancreatic neoplastic diseases of the pancreas.
Signs of malnutrition need to be investigated and identified in patients with pancreatic diseases to optimize the medical management and, potentially, to improve the clinical outcome.
This narrative review summarizes the diagnosis and treatment of EPI along with a focused review of the pathophysiology, clinical consequences, diagnostic approaches, and treatment principles of EPI for a variety of conditions.
Williams V, Funk S. · Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition (2026)
Exocrine pancreatic insufficiency (EPI) is a clinically significant disorder characterized by inadequate secretion or activity of pancreatic digestive enzymes, leading to maldigestion, malabsorption, and adverse nutritional and metabolic consequences.
The causes of EPI can be divided into loss of pancreatic parenchyma, inhibition or inactivation of pancreatic secretion, and postcibal pancreatic asynchrony.
This narrative review summarizes the diagnosis and treatment of EPI along with a focused review of the pathophysiology, clinical consequences, diagnostic approaches, and treatment principles of EPI for a variety of conditions.
This is the first review to provide insights into the potential roles of exogenous digestive enzymes as prebiotics.
Yang Y, Kumrungsee T, Okazaki Y, Watanabe T, Inoue J, Iguchi T, Fukuda S, Kuroda M, Nishio K, Yamaguchi S, Kato N. · Nutrients (2025)
Consistent with the hypothesis, all 13 studies in this review reported significant improvements in animal gut microbiota composition with the dietary supplementation of proteases and lipases.
Additionally, the possible mechanisms of the prebiotic-like effects of the enzymes through increased nutrient digestion were discussed.
This review explores how exogenous proteases and lipases influence gut microbiota composition and overall health.
This review describes the role of these non-pancreatic digestive enzymes in supporting nutritional health.
Borowitz D. · Biomolecules (2025)
The major post-pancreatic intestinal carbohydrate-digesting enzymes are sucrase-isomaltase, maltase-glucoamylase and lactase-phlorizin hydrolase.
There are no post-pancreatic mucosal enzymes that act on dietary triglycerides; however, the complete digestion of phospholipids depends on several brush border phospholipases.
Intestinal processing is an important contributor to digestion of proteins, although mucosal proteases may serve as signaling proteins rather than as primary adjuncts to dietary protein digestion and absorption.
16Fat and nitrogen maldigestionRCTCited 149×n=25 · very small study2010
Pancrelipase delayed-release 12,000-lipase unit capsules were effective in treating fat and nitrogen maldigestion with a TEAE rate similar to that of placebo in patients with EPI due to CP or PS.
Whitcomb DC et al. · The American journal of gastroenterology (2010)
Huge benefit
← WorseNo effectBetter →
Likely real
In total, 25 patients (median age of 54 years, 76% male) received pancrelipase and 29 patients (median age of 50 years, 69% male) received placebo.
Th e mean ± s.d. change from baseline in CFA was significantly greater with pancrelipase vs. placebo: 31.9 ± 18.6 vs. 8.7 ± 12.4 % ( P < 0.0001) [corrected].
Treatment-emergent adverse events (TEAEs) were reported in five patients (20.0%) in the pancrelipase group and in six (20.7%) in the placebo group; the most common were gastrointestinal (GI) events and metabolism/nutrition disorders.
17Gas production reductionRCTn=8 · very small study2007
The administration of 1200 GalU of alpha-galactosidase induced a significant reduction of both breath hydrogen excretion and severity of flatulence.
Di Stefano M et al. · Digestive Diseases and Sciences (2007)
Alpha-galactosidase reduced gas production following a meal rich in fermentable carbohydrates and may be helpful in patients with gas-related symptoms.
A reduction in severity was apparent for all considered symptoms, but both 300 and 1200 GalU induced a significant reduction in the total symptom score.
Randomized double-blind placebo-controlled crossover in healthy volunteers given a bean-rich test meal
18Fat excretionRCTCited 33×n=18 · very small study2006
EC-high-buffered pancrelipase decreased fat excretion, symbolizing improved fat absorption, when compared with EC-nonbuffered pancreatic enzymes given at equivalent, reduced (approximately 50% of usual) lipase doses in nourished subjects with cystic fibrosis and mild pulmonary disease.
Brady MS et al. · Journal of the American Dietetic Association (2006)
Large benefit
← WorseNo effectBetter →
Likely real
Mean fat excretion decreased significantly in each subject during periods when given EC-high-buffered pancrelipase compared with periods when given EC-nonbuffered enzymes (fat excretion 18.2% vs 24.9% or fat absorption 81.8% vs 75.1%, respectively; P=0.01).
Thirteen of 18 subjects (72%) excreted less fat when receiving EC-high-buffered pancrelipase whereas 10 (56%) decreased fat excretion by more than 5%, and five subjects did not respond.
EC-high-buffered pancrelipase decreased fat excretion, symbolizing improved fat absorption, when compared with EC-nonbuffered pancreatic enzymes given at equivalent, reduced (approximately 50% of usual) lipase doses in nourished subjects with cystic fibrosis and mild pulmonary disease.
Digestive enzymes are able to break down proteins and carbohydrates and lipids, and their supplementation may play a role in the management of digestive disorders, from lactose intolerance to cystic fibrosis.
Ianiro G et al. · Current Drug Metabolism (2016)
Animal-derived enzymes represent an established standard of care, however the growing study of plant-based and microbe-derived enzymes offers great promise in the advancement of digestive enzyme therapy.
New frontiers of enzyme replacement are being evaluated also in the treatment of diseases not specifically related to enzyme deficiency.
Reviews use of pancreatic enzymes, lactase (β-galactosidase) and conjugated bile acids