What is lactase

Lactase is an enzyme that breaks down lactose (milk sugar) into two sugars called glucose and galactose, which can be easily absorbed into the bloodstream through the small intestinal lining. In most infants, small intestinal lactase activity is maximal during the perinatal period; however, after 2–12 years of age, two distinct groups emerge, that is, a “lactase non-persistence” group with low lactase activity (hypolactasia) and a “lactase-persistence” group of individuals who retain their neonatal level of lactase activity into adulthood ¹. It is not clear how the lactase gene can be dramatically downregulated with age in most individuals, but remains active in some ². Some researchers believe the answer is a matter of cellular energetics ³. Most mammals (humans notwithstanding) do not consume milk after they have been weaned. Therefore, the energy invested in biosynthesizing lactase is an unnecessary expenditure. This may seem like a very small amount of energy, but remember that everything that occurs in an organism is directed at the cellular level. Cellular energetics are in fact a major evolutionary pressure, and have shaped the evolution of the inner workings of cells since life began.

Reduction in lactase activity causes primary maldigestion of lactose, a condition that is occasionally asymptomatic. When symptoms are present, lactose intolerance is diagnosed. It is important to distinguish between primary hypolactasia and secondary causes of maldigestion of lactose, including celiac disease, infectious enteritis, or Crohn’s disease, which have distinct pathogenic and therapeutic implications. Moreover, primary hypolactasia should be distinguished from congenital lactase deficiency, a rare autosomal recessive disease with unique molecular mechanisms that affects infants from birth ².

Lactase vs Lactose

Lactose is a disaccharide. Lactose is a milk sugar composed of galactose and glucose and has the formula C12H22O11. Lactose makes up around 2–8% of milk (by weight). The name comes from lac (lactis), the Latin word for milk, plus the suffix -ose used to name sugars. The compound is a white, water-soluble, non-hygroscopic solid with a mildly sweet taste. Lactose is used in the food industry.

Where is lactase produced?

Lactase enzyme is produced in your small intestine. It is located in the brush border of the small intestine of humans.

Figure 1. Small intestine and small intestine microvilli

What does lactase do?

Lactase breaks down lactose (milk sugar) into two sugars called glucose and galactose so they can be easily absorbed into the bloodstream. After lactose is broken down into glucose and galactose, the glucose transporters SGLT1 and GLUT2 facilitate the diffusion of glucose and galactose through the enterocyte and into the bloodstream. This process is powered by the diffusion of these molecules down their concentration gradient: there is a higher concentration of glucose and galactose in the lumen of the intestine than in the enterocyte cell body, and there is a higher concentration of glucose and galactose in the enterocyte cell body than in the blood.

Figure 2. Lactase function

In the above diagrams: Lactase is a transmembrane protein on the interior border of the enterocyte. When lactose from the intestine contents comes into contact with the active site of lactase, it is broken down into glucose and galactose. The SGLT1 transmembrane protein (Sodium-Glucose Linked Transporter 1), transports glucose or galactose via facilitated diffusion from the intestine into the enterocyte. Then GLUT2 (Glucose Transporter 2) transports glucose or galactose via diffusion from the enterocyte to the bloodstream.

Lactase deficiency

Lactase enzyme deficiency fails to hydrolyze lactose into absorbable glucose and galactose components.

Normally, lactase turns milk sugar into two simple sugars — glucose and galactose — which are absorbed into the bloodstream through the intestinal lining.

If you’re lactase deficient, lactose in your food moves into the colon (large intestine) instead of being processed and absorbed. In the colon, normal bacteria interact with undigested lactose, causing the signs and symptoms of lactose intolerance.

There are 4 main causes of lactase deficiency ⁴.

Figure 3. Lactase deficiency 

Figure 4. Lactase deficiency -> Lactase intolerance

Primary Lactase Deficiency

This is the most common cause of lactose intolerance, also known as lactose non-persistence. People who develop primary lactase deficiency start life producing plenty of lactase — a necessity for infants, who get all their nutrition from milk. As children replace milk with other foods, their lactase production normally decreases, but remains high enough to digest the amount of dairy in a typical adult diet. There is a gradual decline in lactase enzyme activity with increasing age making milk products difficult to digest by adulthood. Lactase enzyme activity begins to decline in infancy and symptoms manifest in adolescence or early adulthood. Primary lactase deficiency is a hereditary (genetically determined) cause of lactase deficiency ⁴.

Primary lactase deficiency occurs in a large proportion of people with African, Asian or Hispanic ancestry. Primary lactase deficiency is also common among those of Mediterranean or Southern European descent.

Secondary Lactase Deficiency

Injury to intestinal mucosa due to several infectious, inflammatory or other diseases can cause secondary lactase deficiency. Common causes include:

• Gastroenteritis
• Celiac disease
• Crohn disease
• Ulcerative colitis
• Chemotherapy
• Antibiotics

Treatment of the underlying disorder may restore lactase levels and improve signs and symptoms, though it can take time.

Congenital Lactase Deficiency

There is a decrease or absence of lactase enzyme activity since birth due to autosomal recessive inheritance, meaning that both the mother and the father must pass on the same gene variant for a child to be affected. Congenital lactase deficiency manifests in the newborn after ingestion of milk. It is a rare cause of the lactase deficiency.

Developmental Lactase Deficiency

It is seen in premature infants born at 28 to 37 weeks of gestation ⁵. The intestine of the infant is underdeveloped resulting in an inability to hydrolyze lactose. This condition improves with increasing age due to the maturation of intestine, which results in adequate lactase activity.

Risk factors for lactase deficiency

Factors that can make you or your child more prone to lactose intolerance include:

• Increasing age. Lactose intolerance usually appears in adulthood. The condition is uncommon in babies and young children.
• Ethnicity. Lactose intolerance is most common in people of African, Asian, Hispanic and American Indian descent.
• Premature birth. Infants born prematurely may have reduced levels of lactase because the small intestine doesn’t develop lactase-producing cells until late in the third trimester.
• Diseases affecting the small intestine. Small intestine problems that can cause lactose intolerance include bacterial overgrowth, celiac disease and Crohn’s disease.
• Certain cancer treatments. If you have received radiation therapy for cancer in your abdomen or have intestinal complications from chemotherapy, you have an increased risk of lactose intolerance.

Lactase deficiency signs and symptoms

Lactase deficiency is usually responsible for lactose intolerance. Many people have low levels of lactase but are able to digest milk products without problems. If you’re actually lactose intolerant, though, your lactase deficiency leads to symptoms after you eat dairy foods.

Most people with lactose intolerance can manage the condition without having to give up all dairy foods. Lactose intolerance has an excellent prognosis. Most patients have a considerable improvement in signs and symptoms with dietary modification alone.

Lactose intolerance is defined as a syndrome that manifests with characteristic signs and symptoms upon the consumption of food substances containing lactose, a disaccharide. Normally upon consumption lactose is digested into glucose and galactose by lactase enzyme, which is found in the intestinal brush border. Deficiency of lactase due to primary or secondary causes results in the disease. Disease severity varies among individuals. Lactose is present in dairy, milk products, and mammalian milk ⁶. Lactose intolerance is also sometimes referred to as lactose malabsorption.

Symptoms of lactose intolerance usually develop within 30 minutes to two hours of consuming food or drink that contains lactose. They may include:

• flatulence (wind)
• diarrhea
• bloated stomach
• stomach cramps and pains
• stomach rumbling
• feeling sick

The severity of your symptoms and when they appear depends on the amount of lactose you’ve consumed.

Some people may still be able to drink a small glass of milk without triggering any symptoms, while others may not even be able to have milk in their tea or coffee.

The symptoms of lactose intolerance can be similar to several other conditions, so it’s important to see your doctor for a diagnosis before removing milk and dairy products from your diet.

For example, the symptoms above can also be caused by:

• irritable bowel syndrome (IBS) – a long-term disorder that affects the digestive system
• milk protein intolerance – an adverse reaction to the protein in milk from cows (not the same as a milk allergy)

If your doctor thinks you have lactose intolerance, they may suggest avoiding foods and drinks containing lactose for two weeks to see if your symptoms improve.

Lactase deficiency diagnosis

It’s important to visit your doctor if you think you or your child may have lactose intolerance, as the symptoms can be similar to other conditions.

Before seeing your doctor, keep a diary of what you eat and drink, and what symptoms you experience. Tell your doctor if you notice any patterns, or if there are any foods you seem particularly sensitive to.

Your doctor may suggest trying to remove lactose from your diet for two weeks to see if it helps to relieve your symptoms. This will provide further evidence of whether you’re lactose intolerant.

Your doctor may suspect lactase deficiency based on your symptoms and your response to reducing the amount of dairy foods in your diet. Your doctor can confirm the diagnosis by conducting one or more of the following tests:

• Lactose tolerance test. The lactose tolerance test gauges your body’s reaction to a liquid that contains high levels of lactose. Two hours after drinking the liquid, you’ll undergo blood tests to measure the amount of glucose in your bloodstream. If your glucose level doesn’t rise, it means your body isn’t properly digesting and absorbing the lactose-filled drink.
• Milk tolerance test. In a milk tolerance test, you’ll be given a glass of milk (about 500ml) and your blood sugar levels will be tested. If your blood sugar levels don’t rise after drinking the milk, you may be lactase deficient.
• Hydrogen breath test. A hydrogen breath test is a simple way of determining if you may be lactase deficient. You’ll be asked to avoid eating or drinking during the night before the test. When you arrive for the test, you’ll be asked to blow up a balloon-like bag. This sample of your breath will be tested to find out how much hydrogen is present, measured in parts per million (ppm). You’ll then be given a drink of lactose solution and your breath will be tested every 15 minutes over the next few hours to see if the level of hydrogen changes. If your breath contains a large amount of hydrogen (more than 20ppm above your baseline) after consuming the lactose solution, it’s likely that you’re lactase deficient. Larger than normal amounts of exhaled hydrogen measured during a breath test indicate that you aren’t fully digesting and absorbing lactose. This is because lactase deficiency can cause the bacteria in the colon (large intestine) to produce more hydrogen than normal.
• Stool acidity test. For infants and children who can’t undergo other tests, a stool acidity test may be used. The fermenting of undigested lactose creates lactic acid and other acids that can be detected in a stool sample.

Small bowel biopsy

A small bowel biopsy is rarely used to diagnose lactose intolerance. However, it may be carried out to see if your symptoms are being caused by another condition, such as celiac disease.

In a small bowel biopsy, a sample of your small intestinal lining is taken using an endoscope (a thin, flexible tube with a light and a tiny cutting tool at the end) that’s passed down your throat. This will be carried out under local anaesthetic, so it won’t hurt.

The sample of intestinal lining will be tested to see how much lactase it contains. If it only contains a small amount of lactase, it’s likely you’re lactose intolerant. The sample can also be examined to look for signs of possible underlying conditions such as celiac disease.

Lactase deficiency treatment

There’s currently no way to boost your body’s production of lactase, but you can usually avoid the discomfort of lactose intolerance by:

• Avoiding large servings of milk and other dairy products
• Including small servings of dairy products in your regular meals
• Eating and drinking lactose-reduced ice cream and milk
• Drinking regular milk after you add a liquid or powder to it to break down the lactose

Management of lactose intolerance consists of dietary modification, lactase supplements and the treatment of an underlying condition in people with secondary lactase deficiency.

Dietary Modification

Lactase containing milk products and calcium supplements are recommended. Limiting dietary intake of lactose by avoiding intake of lactose-containing products improves the symptoms of the disease. Following products contain lactose and therefore must be avoided:

• Soft and processed cheese
• Buttermilk
• Cream
• Milk
• Ice cream
• Sour cream
• Whey
• Yogurt
• Pancakes and waffles
• Mashed potatoes
• Butter
• Margarine
• Custard and pudding

Sources of lactose

Some of the main sources of lactose you may need to cut down on or avoid if you’re lactose intolerant are described below.

Milk

A major source of lactose is milk, including cow’s milk, goat’s milk and sheep’s milk. Depending on how mild or severe your lactose intolerance is, you may need to change the amount of milk in your diet.

For example:

• you may be able to have milk in your tea or coffee, but not on your cereal
• some products containing milk, such as milk chocolate, may still be acceptable in small quantities
• you may find that drinking milk as part of a meal, rather than on its own, improves how the lactose is absorbed

If even a small amount of milk triggers your symptoms, there are some alternatives you can try, such as soya or rice milk (see below).

Dairy products

Other dairy products made from milk – such as cream, cheese, yogurt, ice cream and butter – also contain lactose and may need to be avoided if you’re lactose intolerant.

But the level of lactose in these products varies and is sometimes quite low, so you may still be able to have some of them without experiencing any problems.

It’s worth experimenting with different foods to find out if there are any dairy products you can eat because they’re a good source of essential nutrients such as calcium.

Other foods and drinks

As well as milk and dairy products, there are other foods and drinks that can sometimes contain lactose.

These include:

• salad cream, salad dressing and mayonnaise
• biscuits
• chocolate
• boiled sweets
• cakes
• some types of bread and other baked goods
• some breakfast cereals
• packets of mixes to make pancakes and biscuits
• packets of instant potatoes and instant soup
• some processed meats, such as sliced ham

Check the ingredients of all food and drink products carefully, because milk or lactose are often hidden ingredients.

The lactose found in some foods won’t necessarily be listed separately on the food label, so you need to check the ingredients list for milk, whey, curds and milk products such as cheese, butter and cream.

Some ingredients may sound like they contain lactose when they don’t, such as lactic acid, sodium lactate and cocoa butter. These ingredients don’t need to be avoided if you’re lactose intolerant.

Medication

Some prescription medicines, over-the-counter medicines and complementary medicines may contain a small amount of lactose. While this isn’t usually enough to trigger the symptoms of lactose intolerance in most people, it may cause problems if your intolerance is severe or you’re taking several different medicines.

If you need to start taking a new medication, check with your doctor or pharmacist in case it contains lactose.

Maintain good nutrition

Reducing the dairy products doesn’t mean you can’t get enough calcium. Calcium is found in many other foods, such as:

• Broccoli
• Calcium-fortified products, such as breads and juices
• Canned salmon
• Milk substitutes, such as soy milk and rice milk
• Oranges
• Pinto beans
• Rhubarb
• Spinach

Also make sure you get enough vitamin D, which is typically supplied in fortified milk. Eggs, liver and yogurt also contain vitamin D, and your body makes vitamin D when you spend time in the sun. Even without restricting dairy foods, though, many adults don’t get enough vitamin D. Talk to your doctor about taking vitamin D and calcium supplements to be sure.

Lactase Supplements

Lactase enzyme supplements contain lactase which breaks down lactose in milk and milk containing products. They are available as lactase enzyme tablets or drops (Dairy Ease, Lactaid, others).

Use lactase tablets/drops as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Take lactase tablets/drops with the first bite or drink of a dairy product.
• If you are still eating or drinking dairy products after 30 to 45 minutes, you may need to take another dose. Follow what your doctor has told you to do.

Adult Dose for Lactose Intolerance

• Original Strength: Swallow three caplets with first bite of dairy foods to help prevent symptoms.
• Extra Strength: Swallow two caplets with first bite of dairy foods to help prevent symptoms.
• Ultra Caplets: Take one caplet with first bite of dairy foods to help prevent symptoms.
  • Maximum Dose: Two caplets at a time.
• Ultra Chewables: Chew one chewable tablet with first bite of dairy foods to help prevent symptoms.
  • Maximum Dose: Two chewable tablets at a time.

Pediatric Dose for Lactose Intolerance

• Original Strength: Swallow three caplets with first bite of dairy foods to help prevent symptoms.
• Extra Strength: Swallow two caplets with first bite of dairy foods to help prevent symptoms.
• Ultra Caplets: Take one caplet with first bite of dairy foods to help prevent symptoms.
  • Maximum Dose: Two caplets at a time.
• Ultra Chewables: Chew one chewable tablet with first bite of dairy foods to help prevent symptoms.
  • Maximum Dose: Two chewable tablets at a time.

Renal Dose Adjustments

• Data not available

Liver Dose Adjustments

• Data not available

Dialysis

• Data not available

What do I do if I miss a dose?

• Take a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.

References

1. Mattar R, de Campos Mazo DF, Carrilho FJ. Lactose intolerance: diagnosis, genetic, and clinical factors. Clin Exp Gastroenterol. 2012;5:113-21. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3401057/
2. Labrie V, Buske OJ, Oh E, et al. Lactase nonpersistence is directed by DNA-variation-dependent epigenetic aging. Nat Struct Mol Biol. 2016;23(6):566-73. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4899171/
3. https://lbc.msu.edu/evo-ed/pages/Lactase/cellbio.html
4. Malik TF, Whitten R. Lactose Intolerance. [Updated 2018 Oct 15]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2018 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK532285
5. Mobassaleh M, Montgomery RK, Biller JA, Grand RJ. Development of carbohydrate absorption in the fetus and neonate. Pediatrics. 1985 Jan;75(1 Pt 2):160-6.
6. Mattar R, de Campos Mazo DF, Carrilho FJ. Lactose intolerance: diagnosis, genetic, and clinical factors. Clin Exp Gastroenterol. 2012;5:113-21.