Digestive enzymes are critical for breaking down food into nutrients that the body can absorb and utilize, transforming the saying "You are what you eat" into the more accurate "You are what you can absorb and digest." These enzymes, produced naturally by the body or supplemented as needed, are essential for healthy digestion. In gut health protocols, digestive enzymes are often first picks in the Replace phase of the 5R framework (Remove, Replace, Replenish, Revive, and Rebalance).

When digestive enzymes are insufficient, digestion becomes impaired, affecting the absorption of vitamins, minerals, fats, protein, and carbohydrates. These deficiencies can disrupt systems throughout the body, from immune function and energy production to mood regulation, reproductive health, and musculoskeletal integrity.

Digestive enzymes specialize in breaking down specific macronutrients:

• Amylase: Breaks down carbohydrates (like starch) into simple sugars. Found in saliva and pancreatic juices.
• Protease: Breaks down proteins into amino acids. Found in the stomach and small intestine. 
• Lipase: Breaks down fats (triglycerides) into fatty acids and glycerol. Works with bile in the small intestine. 

Digestive enzyme supplements may support individuals with the following:

• Common digestive complaints, such as occasional bloating, gas, constipation, or feeling of fullness after eating small amounts of food. 
• Suboptimal enzyme production, pancreatic insufficiency, gastrointestinal conditions, and even diabetes. For example, digestive enzymes may support individuals with insufficient production of lactase enzymes, which are needed to digest lactose sugar in dairy products. This is called lactose intolerance and is estimated to affect 68% of the global population.
• Individuals following a primarily plant-based diet, corresponding to a higher intake of anti-nutritional factors that may impair digestion (e.g., trypsin inhibitors, tannins, phytic acid, lectins, saponins, and protease inhibitors).
• Food sensitivities. Research suggests that impaired gastric digestion, including suboptimal levels of digestive enzymes of proteases and amylases, may be associated with food allergies. Furthermore, healthy digestion has been shown to significantly reduce immunoglobulin E (IgE) binding and histamine release while digestive enzymes may readily degrade potentially allergenic components of foods.

Digestive enzyme supplements come from three primary sources: 

• Animal-derived: Contains a blend of pancreatic enzymes derived from porcine or bovine sources. 
• Plant-based: Examples include papain (papayas) and bromelain (pineapples), suitable for vegans and vegetarians. 
• Microbial-derived: Sourced from fungi or bacteria, offering stability across pH levels, suitable for vegans or vegetarians.

Pancreatic enzyme insufficiency (PEI) 

PEI can be caused by conditions such as chronic pancreatitis (CP), cystic fibrosis, duct obstruction, pancreatic or gastric resection, short bowel syndrome, or celiac disease. Chronic pancreatitis is one of the most common causes of PEI in adults. 

Although more robust clinical trials are needed to fully elucidate their supportive effect in these conditions, researchers suggest that pancreatic enzyme replacement therapy (PERT) may be one of the most supportive protocols in the setting of maldigestion and malabsorption for patients with CP. Multiple randomized controlled trials demonstrate that treatment groups who received PERT experienced reduced steatorrhea, fecal fat, and stool frequency, demonstrating that it enables the normal absorption of dietary fats and promotes weight gain in those with malabsorption and/or malnutrition. In a meta‑analysis, individuals with CP who were given PERT experienced improved fat and protein absorption and stool consistency, and reduced abdominal pain and flatulence compared to controls. In another systematic review, PERT was also shown to have a positive effect on quality of life, weight maintenance, and malnutrition in those with PEI.

Can digestive enzymes be paired with betaine hydrochloric acid (HCl)? 

Betaine HCl supplementation may help promote healthy gastric pH or stomach acid (HCl) status. Thus, the decision to pair digestive enzymes with HCl depends on the individual’s specific needs.

There is a large variance in the reported prevalence of low stomach acid in the general population. It is believed that stomach acid secretion may gradually decline with natural aging. Low stomach acid may be secondary to an underlying medical condition, such as pernicious anemia, gastric bypass, hypothyroidism, and Helicobacter pylori (H. pylori) infection. H. pylori is estimated to occur in approximately half of the world’s population. It is well understood that long-term use of protein-pump inhibitors is associated with low stomach acid. 

Having low stomach acid is problematic for overall health. Stomach acid is required for proper protein digestion, as gastric protein-digesting enzymes function optimally at a low pH. When protein is poorly digested, it may result in inadequate mineral absorption and is potentially associated with food allergenicity. Too little stomach acid may be linked to reduced absorption of key micronutrients, such as calcium, iron, folate, vitamin B6, and vitamin B12. Moreover, having low stomach acid is associated with potentially harmful microbial environments that may be seen in individuals with dysbiosis, small-intestinal bacterial overgrowth, or organisms such as Clostridium difficile, Campylobacter, or Salmonella. 

The adverse consequences of low stomach acid may amount to various undesirable gastrointestinal complaints. For instance, this may be associated with occasional nausea, bloating, diarrhea, abdominal pain, postprandial fullness, vomiting, or constipation. Symptoms such as occasional heartburn or acid regurgitation may also be associated with low stomach acid, even though these symptoms may be mistakenly assumed to result from excess stomach acid. 

Can digestive enzymes be paired with ox bile? 

Ox bile supplementation is designed to support digestion by helping maintain healthy bile status. Like betaine HCl, ox bile supplementation is dependent on individual needs. 

Bile is a complex fluid produced in the liver and stored in the gallbladder, composed primarily of water, bile salts, bilirubin, phospholipids, cholesterol, amino acids, and various other components. It plays a critical role in emulsifying and absorbing dietary fats. Disruptions in bile production or flow, due to liver or gallbladder complications or an imbalanced gut microbiome, can impair fat digestion and absorption. Research suggests that bile salt supplementation can help maintain healthy bile acid metabolism, which supports digestion in cases of bile production or flow issues.

Is enteric coating important for digestive enzyme supplementation? 

For individuals who use digestive enzyme supplements, enteric coating has been shown to be important for maintaining their effectiveness. Enteric-coated enzymes are more protected than non-enteric-coated enzymes from being degraded by gastric acid and pepsin in the stomach, ensuring they reach the duodenum (small intestine), where they are most active. A systematic review and meta-analysis of 17 studies involving 511 patients with CP found that enteric-coated enzymes were more effective than non-coated formulations. Similarly, a Cochrane review showed that enteric-coated microspheres performed better than non-coated tablets in improving stool frequency in individuals with cystic fibrosis.

Conclusion 

Digestive enzymes supplementation can play a supportive role in maintaining optimal digestion and nutrient absorption, particularly when digestive function is compromised. They can fit seamlessly into the replace phase of the 5R gut health framework (alone or with betaine HCl or ox bile, when warranted) to help restore proper digestive function and promote overall gut health.

Learn more about digestive enzymes and histamine intolerance: 

Histamine Intolerance and Diamine Oxidase Deficiency

The Relationship Between Histamine Intolerance and Gastrointestinal Health

Histamine Intolerance and Inflammatory Bowel Disease: Any Connection?

By Danielle C. Male, MS, CNS, LDN