Digestive Enzymes and MTHFR

Digestive enzymes are special chemicals naturally produced by the body to break down fats, proteins, and carbohydrates in the food we eat. Protease enzymes break down general proteins such as casein and gluten, while specific enzymes including prolyl endopeptidases and other specific proteases target gluten peptides.¹

Digestive enzymes are produced in the salivary glands, stomach, pancreas, and small intestine, and also help with the absorption of nutrients.²

Digestive enzymes can also be taken as supplements. These can be helpful if your body isn’t producing enough enzymes on its own.  The secretion of pepsin and pancreatic enzymes declines with age, and can also be affected by medications and certain health conditions.³

There are three main types of digestive enzymes: carbohydrases, proteases and lipases.

• Carbohydrases (amylase, maltase, cellulase, xylanase, pectinase, and lactase)
  Carbohydrases break down starch molecules to simple sugars, such as glucose
  - Amylase: breaks down starch into maltose
  - Maltase: breaks down maltose into glucose
• Proteases (pepsin, trypsin)
  Proteases break down proteins into smaller polypeptide chains (amino acids).
  - Pepsin: breaks down proteins from meats and legumes into smaller peptides in the acidic environment of the stomach.
  - Trypsin: continues the breakdown of the partially digested proteins into smaller peptides and amino acids that the body can absorb and use.
• Lipases (pancreatic lipase)Lipases break down lipids (fats) into fatty acids and glycerol. Primarily pancreatic lipase.

Lactose intolerance is a common condition in which the body doesn’t produce enough lactase, the enzyme required to break down lactose (the sugar in milk). This can lead to symptoms such as gas, bloating, and diarrhea after eating or drinking dairy products.

Lactose intolerance is usually genetic but it can result from other health conditions.

Exocrine pancreatic insufficiency is a condition in which the body doesn’t produce enough pancreatic enzymes to break down and absorb nutrients in food.⁴ This can lead to undigested food fermenting in the gut, which causes symptoms such as gas, bloating cramping, abdominal pain, and other digestive discomfort; diarrhea; loose and greasy stools; and sometimes weight loss.

EPI may result from other health conditions such as pancreatitis, cystic fibrosis, pancreatic cancer, or surgeries that affect the pancreas. Chronic pancreatitis (inflammation of the pancreas) can lead to scarring and fibrosis, causing permanent damage that impairs the secretion of digestive enzymes.⁵

Cystic fibrosis (CF) is a genetic disease that affects the respiratory tract, but also the pancreas, gut, and hepatobiliary tract. It causes thickened secretions to block pancreatic ducts, reducing delivery of digestive enzymes to the intestines and impairing digestion of key nutrients.⁶

Pancreatic cancer occurs when carcinomas develop in pancreatic duct cells. This can significantly impair digestive enzyme production.

Congenital sucrase-isomaltase deficiency is a rare genetic disorder that causes deficiency of the sucrase-isomaltase (SI) enzyme, the final step of carbohydrate digestion. This can lead to carbohydrate malabsorption, with symptoms such as watery diarrhea, abdominal pain, bloating, flatulence, and/or cramps.⁷

The MTHFR genetic mutation does not directly affect digestive enzyme production or functionality. However, people with MTHFR may be at higher risk of developing digestive issues such as leaky gut syndrome, especially if their homocysteine is elevated. High homocysteine is common in those with MTHFR due to low folate levels, and can increase inflammation in the body. This inflammation can damage the intestinal barrier, causing intestinal permeability (leaky gut) and impairing nutrient absorption.⁸ Intestinal permeability can lead to further inflammation when food particles and toxins pass through the gut lining into the bloodstream, where they trigger an immune response.

• Supplementing with digestive enzymes can help with nutrient absorption when the body’s own production of enzymes is impaired. Enzymes also act as a barrier to pathogens that enter the body from food.⁹ In the case of leaky gut, supplementing with digestive enzymes could help to reduce the risk of further inflammation. Proteases not only assist digestion but may also help maintain gut barrier function and modulate immune responses in the gut.¹⁰
  Enzyme replacement therapy using digestive enzymes has also been shown to improve symptoms of non-celiac gluten sensitivity (NCGS).
• Gut microflora is also important when digestive function is weak or impaired. Probiotic bacteria such as Lactobacillus and Bifidobacterium help to metabolize proteins and carbohydrates, synthesize vitamins, and help with nutrient absorption. They also produce short-chain fatty acids that support the integrity of the gut lining.¹¹

People with MTHFR variants may be affected by digestive issues due to impaired methylation, which can affect the repair and maintenance of the gut lining as well as enzyme production. Gluten contains proline and glutamine sequences that human proteases may not efficiently break down, especially in people with poor enzyme production.

Digestive supplementation with a multi-enzyme blend containing proteases and papain is shown to significantly reduce gastrointestinal symptoms caused by gluten.¹² This may be helpful for those with MTHFR who are experiencing digestive symptoms.