DN Forum - May 2024

FORUM

Lactose and the gut Dairy and Sleep from folklore to science

Summary Points

Summary Points

• Lactose is the naturally occurring carbohydrate in milk. The enzyme lactase, is needed for its digestion. Insufficiency of this enzyme results in malabsorption, which may lead to symptoms of gastrointestinal upset. When symptoms are present, the condition is known as lactose intolerance.

• Sleep is a modifiable factor that supports health, contributing to both physiological and psychological functions. Insufficient sleep is a largely unrecognised public health problem globally. The circadian system responds to many signals including the light-dark cycle, food intake, temperature, physical activity, drugs and stress.

disease, coeliac disease, bacterial overgrowth, and inflammation of the gut. Tolerance to lactose can often return in the recovery phase of these conditions.

and melatonin. These hormones play important roles in the regulation of sleep. Small amounts of melatonin also occur naturally in cow’s milk.

Editorial

Editorial

Warm milk before going to bed is a tradition that has been passed down through generations as a practice to facilitate a restful night’s sleep.

The relationship between food and gut health is intricately connected, with gastrointestinal discomfort commonly linked to specific foods. Dairy avoidance is often attributed to being lactose intolerant but selfdiagnosis and misinformation can cause confusion. Many digestive disorders have shared symptoms, which means accurate diagnosis is key to appropriate management.

As with other bedtime routines, it may be the ritual itself that helps to induce the anticipation of sleep. Also, drinking milk before falling asleep could be associated with soothing, early childhood memories that evoke calmness. However, it is also believed that naturally occurring components in milk can support the process of sleep.

In this edition, we explore the latest research on lactose and the gut, with a particular focus on lactose intolerance, potential benefits of lactose and adaptions of the gut.

• The most common form of lactose malabsorption, known as primary lactase deficiency, is genetically driven. This is prevalent in an estimated 68% of the global population but varies from 4% in northern European countries to almost 100% in parts of Asia. However, many of these individuals are non-symptomatic, which means that lactose malabsorption does not always result in intolerance.

Dietary components can act on neurotransmitters which influence sleep, and likewise, sleep deprivation can influence metabolic hormones and appetite. This relationship between food and the internal circadian clock is referred to as chrononutrition.

• Current research indicates that dairy has positive effects on sleep. Cow’s milk protein is rich in tryptophan, which is a precursor for both serotonin

• Secondary Lactase Deficiency is a transient form of lactose intolerance resulting from intestinal damage caused by other conditions. It is secondary to conditions including Crohn’s

• Fermented milk has been shown to significantly improve sleep efficiency. Lactic acid bacteria present in fermented dairy produce gammaaminobutyric acid, a neurotransmitter which is associated with sleep. Calcium inadequacy is associated with poor sleep and therefore, the calcium component of dairy may be another factor which influences sleep.

• The degree to which an individual is lactose intolerant can vary, resulting in a variation in the severity of symptoms and ability to tolerate different levels of dietary lactose. In most cases, milk-based foods do not need to be completely avoided but limited to the person’s individual tolerance. Typically, up to 12g lactose (a glass of milk) can be consumed, with no or minor symptoms.

In this edition of DN Forum, we introduce the science of sleep and explore the research on how food interacts with sleep and the circadian system. We will focus specifically on the scientific evidence which examines the role of milk and dairy products.

On page 4 of this publication, we feature our new research report on dairy intake among Irish teenagers. We hope you enjoy this edition and look forward to any feedback or comments you wish to share: nutrition@ndc.ie

We hope you enjoy this edition of DN Forum and look forward to any feedback or comments you wish to share: nutrition@ndc.ie

• The overall composition of milk also makes it a nutritious bed-time drink. It provides casein-rich protein, which is encouraged as a pre-sleep intervention strategy to increase muscle protein synthesis overnight for both athletes and older people.

• Research suggests that lactose can act as a prebiotic by modulating the gut microbiota and the gut bacteria may play a role in mediating the symptoms of lactose intolerance. Advice on dose and timing of lactose consumption should be given to patients to help them continue to include dairy foods as part of a balanced diet.

Dr Marianne Walsh

Dr. Marianne Walsh

Nutrition Manager

Manager

The National Dairy Council (NDC)

The National Dairy Council (NDC)

Lactose and the gut

INTRODUCTION

Lactose is the main source of carbohydrate naturally present in milk. It is a disaccharide, consisting of one molecule of glucose and one molecule of galactose. Unlike free or added sugars, lactose is an intrinsic sugar and is therefore not targeted in sugar reduction policies from health authorities1

Lactose digestion and absorption takes place in the small intestine and relies on the enzyme, lactase2,3. Lactase cleaves lactose into its constituent sugars (glucose and galactose), which are then actively transported into enterocytes for absorption4. Where there is lactose malabsorption, lactose continues to the large intestine, encountering intestinal microbiota. These gut bacteria metabolise lactose by fermentation, which results in the production of hydrogen, methane and carbon dioxide gases as well as short chain fatty acids (SCFA)4. A build-up of gas can cause gastrointestinal upset such as bloating, cramping and flatulence. In the colon, lactose has an osmotic effect, which can cause diarrhoea5 Presentation of such symptoms resulting from the intake of lactose, is known as lactose intolerance6

Lactose intolerance occurs when activity of the lactase enzyme in the small intestine is deficient or insufficient. The degree to which an individual is lactose intolerant can vary, resulting in a variation in the severity of symptoms and ability to tolerate different levels of dietary lactose6. Indeed, some individuals with lactose malabsorption have no symptoms of lactose intolerance after ingesting dairy products5

Recent research has highlighted a beneficial role of lactose on the gut microbiome2 and suggests that the microbiome may play a role in mediating the symptoms of lactose intolerance7. As lactose malabsorption is not always problematic, unnecessary removal of dairy foods from the diet may be a cause for concern in terms of overall human health2. The objective of this DN Forum is to describe the various presentations and management strategies for lactose intolerance, and to explore the potential role of lactose as a prebiotic.

SYMPTOMS OF LACTOSE INTOLERANCE

The symptoms of lactose intolerance are primarily intestinal, usually appearing within 30 minutes to two hours of consumption. They may include abdominal pain and bloating, nausea, diarrhoea, increased or excessive flatulence, and borborygmi5. Lactose intolerance may also cause extra-intestinal symptoms, such as fatigue, loss of concentration and headache, although more research is needed5 Factors impacting symptom development are outlined in Table 1.

TYPES OF LACTOSE INTOLERANCE

There are three main types of lactose intolerance:

1. Congenital lactase deficiency is a rare genetic condition causing severe failure to thrive in infants3. Only a few cases have been

Extrinsic factors

• Dose of lactose3

• Composition of the meal – lactose-containing foods consumed alone or in conjunction with other foods that may affect intestinal transit and the rate of lactose appearing in the colon2,3

Sarah Keogh Founder of Eatwell and Registered Dietitian with the Coeliac Society

described, mainly in Finland6. Symptoms are lifelong, which means that sustained lactose avoidance is necessary in these cases.

2. Primary Lactase Deficiency is the most common form of lactose malabsorption, which may result in lactose intolerance. Most humans can hydrolyse lactose from birth but activity of the lactase enzyme reduces in some populations during childhood6

With the dawning of dairy farming, approximately 10,500 years ago, genetic mutations occurred which enabled the lactase enzyme to persist beyond childhood, in some populations. Positive selection of the lactase gene, facilitated continued lactose digestion into adulthood, providing a source of calories, protein and other nutrients to these individuals8,9. Genetic selection of the lactase gene is among the strongest yet seen for any gene in the genome, suggesting that the mutation was nutritionally advantageous9

Primary lactase deficiency is lowest in northern European countries, at around 4% in Ireland, whereas it approaches 100% in some Asian populations10. Although approximately 68% of the world population carry the genes for primary lactose deficiency, only 55-57% exhibit symptoms on specific testing for lactose intolerance10. Therefore, positive results for genetic markers of lactose malabsorption do not necessarily predict lactose intolerance.

There is age, as well as population, differences in the onset of primary lactose intolerance. African, Asian or Hispanic children may experience symptoms at 2-3 years whereas European children, may see symptoms appear at 5-14 years11. In addition, research suggests that lactose metabolism by gut bacteria may play a role in reducing symptoms in populations with lower lactase enzyme activity, accounting for some symptom variations12

3. Secondary Lactase Deficiency is a transient form of lactose intolerance, resulting from intestinal damage caused by other conditions. It is secondary to conditions including Crohn’s disease, coeliac disease, food allergy, bacterial overgrowth, and enteritis resulting from chemotherapy or radiotherapy. It may also occur during or after gut infections2

Lactose Intolerance in Crohn’s Disease: There is a 60% higher risk of lactose intolerance in patients with Crohn’s disease (ranging from no increased risk to 257% increased risk)13. However, risk of lactose intolerance was more closely linked to ethnic makeup of the population studied, indicating the presence of primary lactose intolerance as the driving factor in lactose-related symptoms experienced in this group13

Lactose Intolerance in Coeliac Disease: Lactose intolerance is more common in people with coeliac disease. Ojetti et al.14 found that 24% of patients with lactose intolerance were subsequently diagnosed with coeliac disease. After 1 year on a gluten-free diet, 64% of patients recovered tolerance to lactose15

Intrinsic factors

• Variation in expression of lactase enzyme by enterocytes2

• History of gut disorders and/or abdominal surgery, chemotherapy, radiation3

• Variation in fermentation by gut bacteria: Small intestinal bacterial overgrowth increases the likelihood of diarrhoea8

Other factors

• Anxiety disorders, increased stress and functional gut disorders are associated with increased risk of lactose intolerance2

• Sensitivity of the gut to mechanical stimulation (e.g. bloating in IBS)3

Table 1 - Factors impacting symptom development in Lactose Intolerance

Lactose Intolerance and Irritable Bowel Syndrome (IBS): Up to 70% of patients with IBS report symptoms related to intake of fermentable carbohydrates including lactose16. Risk of lactose intolerance and severity of symptoms increases in people with IBS. They are also more likely to experience symptoms of lactose intolerance at low to moderate doses of lactose17. People with functional GI disorders may experience higher rates of visceral hypersensitivity to physical and dietary stimuli which may partially explain increased symptoms18 Symptoms reflect high levels of gas production on consumption of lactose and biopsies of gut mucosa are more likely to show increased numbers of mast cells, increased intraepithelial lymphocytes and higher release of inflammatory cytokines in people with IBS who report lactose intolerance6

Premature birth: Another transient form of lactose intolerance can occur in premature babies, where gut immaturity results in lower or absent expression of the lactase enzyme3. However, it is thought that this becomes resolved shortly after birth, as the gut matures.

DIAGNOSIS OF LACTOSE INTOLERANCE

Hydrogen Breath Test

The lactose hydrogen breath test measures excretion of hydrogen in expiratory air after an oral challenge with a standard dose of lactose. As hydrogen is not produced by mammalian enzymes, its presence indicates lactose malabsorption. False negative or false positive results can be due to recent use of antibiotics, a lack of hydrogen producing bacteria, ingestion of high fibre before the test, bacterial overgrowth in the intestine, or motility disorders3,4

Genetic Testing

Patients can be tested for primary lactose intolerance with genetic tests. In Caucasians, development of primary lactose intolerance is usually mediated by changes in one specific gene. Patients with African or Asian heritage have a more complex genetic pattern making genetic tests less valuable in these populations. A positive genetic test for lactose malabsorption does not necessarily predict lactose intolerance13

Testing Lactase Enzymes on Intestinal Biopsies

Tests for lactase enzymatic activities on intestinal biopsies will detect primary and secondary lactose malabsorption. This test can be performed if endoscopy is indicated for other reasons. For adequate lactose digestion, the presence of 50% of lactase activity is sufficient5

Lactose Elimination Diet

Elimination of lactose from the diet followed by resolution of symptoms can indicate lactose intolerance. Many patients have already self-diagnosed lactose intolerance on this basis19. Best practice is to confirm diagnosis of lactose intolerance with a hydrogen breath test as patients may be reacting to other foods or other components of the food. It is also important that secondary causes of lactose intolerance, such as coeliac disease, are investigated13

MANAGEMENT OF LACTOSE INTOLERANCE

Dairy foods provide a range of important nutrients including calcium, protein, vitamin B12 and riboflavin20. Any reduction in these foods may impact overall nutrition for patients. For example, when dairy foods are decreased or fully avoided, it may lead to reduced bone density and increased risk of fractures for these individuals6. It is not necessary for patients to remove all dairy foods from the diet, although this is not understood by many patients and must form part of patient education.

The varying levels of lactose in dairy foods means that many can be incorporated into a healthy diet21 (see Figure 1). A strict lactose-free diet is rarely required as most patients can tolerate up to 12g of lactose, spread over the day22. This is equivalent to one glass of milk.

There is a greater tolerance for lactose if it is consumed in mixed meals7. Continuing to include small amounts of lactose in the diet may help to maintain some tolerance to lactose and provide some prebiotic benefits of lactose in the colon23. Table 2 provides a guide to choosing foods on a low lactose diet. Evidence also shows that lactose is important for the development of the gut microbiome in infants and so lactose-reduced formulas should be used with caution and under professional supervision2. Some medicines do contain lactose

If you have lactose intolerance, you should remove all dairy from your diet

FACT

Lactose intolerance can occur in individuals who have low levels of the enzyme lactase, which is needed to digest the naturally occurring milk sugar (lactose). Tolerance levels vary, with some individuals having no symptoms or only having digestive discomfort following the consumption of large amounts of lactose-containing foods.

as an excipient, but the levels are low enough that most patients can tolerate them24

Lactase enzyme supplementation improves lactose digestion and symptoms in people with lactose intolerance25. There is growing research on the potential effects of probiotic supplements that produce lactase in the gut, although more research is needed5

In most cases, milk-based foods do not need to be completely avoided, but need to be limited to the person’s individual tolerance. Most people can consume some lactose and this can promote tolerance. Typically, up to 12g at a time can be consumed with no, or minor, symptoms. Some dairy foods have negligible amounts of lactose (see graphic below).

Persistence of symptoms in patient with lactose intolerance

Reducing or removing lactose from the diet does not consistently result in symptom resolution, particularly in patients with functional bowel disorders who may be sensitive to other foods in addition to lactose2. Lactose intolerance can be part of a wider intolerance of fermentable carbohydrates and patients with irritable bowel syndrome may require a low-FODMAP diet to improve symptoms4,26

Worldwide, it is estimated that about 65% of people do not express the lactase enzyme but it varies largely across populations, ranging from 4% to over 80% across different parts of the world. Due to genetic evolution, Ireland has a lower prevalence, with 4-5% affected.

Most individuals with lactose maldigestion can tolerate up to 12g of lactose as a single dose with no, or minor, symptoms

The European Food Safety Authority (EFSA)

Whole/low-fat Milk 200ml 9-10g lactose

Cheese 25g 0.03g lactose

Whole Milk Yogurt 125g 6g lactose

Table 2 - Choosing foods on a low-lactose diet

200ml 0g lactose

Milk

Dairy foods with very low levels of lactose (well-tolerated)

Figure 1 8

Lactose-free milk

Hard cheeses and mature cheeses, e.g. Cheddar

Butter

Cream

Low to moderate levels of lactose (tolerated in smaller amounts & in mixed meals):

Yogurt

Fresh soft cheeses, e.g. Cottage cheese

Milk chocolate

Foods that may contain lactose (many patients tolerate small amounts of these foods)

Biscuits and cakes (if milk or milk solids are added)

Processed breakfast cereals

Cheese sauce

Custard

Pancakes

Some breads and spreads (containing milk)

Foods containing milk solids, non-fat milk solids whey, milk sugar

High lactose levels (to be limited)

Milk - most people can tolerate up to 240ml of milk over the day. Milk may also be tolerated in small amounts e.g. in tea or coffee

Foods made with milk including milk puddings, hot chocolate, milk-based coffees, ice-cream

LACTOSE AS A PREBIOTIC - ADAPTIONS OF THE GUT

A recent study by Luo et al. suggests that lactose can act as a prebiotic by modulating the gut microbiota (increased Bifidobacterium and reduced Prevotella)27. These adaptions were linked to a protective association between milk intake and reduced risk of type 2 diabetes, in individuals with lactase non-persistence.

Cheddar

Lactose-free