Lactose Intolerance (Clinical)

Epidemiology

• In children: low prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency at < 6 years of age → genetically regulated reductions of lactase Lactase An enzyme which catalyzes the hydrolysis of lactose to d-galactose and d-glucose. Defects in the enzyme cause lactose intolerance. Digestion and Absorption of Carbohydrates activity begin after weaning Weaning Techniques for effecting the transition of the respiratory-failure patient from mechanical ventilation to spontaneous ventilation, while meeting the criteria that tidal volume be above a given threshold (greater than 5 ml/kg), respiratory frequency be below a given count (less than 30 breaths/min), and oxygen partial pressure be above a given threshold (pao2 greater than 50mm hg). Weaning studies focus on finding methods to monitor and predict the outcome of mechanical ventilator weaning as well as finding ventilatory support techniques which will facilitate successful weaning. Present methods include intermittent mandatory ventilation, intermittent positive pressure ventilation, and mandatory minute volume ventilation. Invasive Mechanical Ventilation off breast milk^[2,7]
• In adults:^{[1,5,7,11,12]}
  • Prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency varies across racial and ethnic groups:
    • Lowest in European Americans
    • Higher in African Americans, Asian Americans, and Native Americans
  • Worldwide, > 70% of adults have lactase deficiency Lactase deficiency Lactose Intolerance (LD), but many are asymptomatic.

Etiology

Primary LD^[1,7,8,12]

• Also called acquired primary lactase deficiency Lactase deficiency Lactose Intolerance, lactase Lactase An enzyme which catalyzes the hydrolysis of lactose to d-galactose and d-glucose. Defects in the enzyme cause lactose intolerance. Digestion and Absorption of Carbohydrates non-persistence, and primary adult hypolactasia
• Most common type of LD (> 70% adults); a genetically determined epigenetic regulation Epigenetic regulation Epigenetic regulation is regulation of gene expression that does not involve alterations to the DNA sequence or any of its transcribed products. The most common forms of epigenetic regulation are DNA methylation, which suppresses gene expression, and modifications to the histone proteins, which affect the structure of DNA packaging. Epigenetic Regulation of the lactase Lactase An enzyme which catalyzes the hydrolysis of lactose to d-galactose and d-glucose. Defects in the enzyme cause lactose intolerance. Digestion and Absorption of Carbohydrates gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics that decreases lactase Lactase An enzyme which catalyzes the hydrolysis of lactose to d-galactose and d-glucose. Defects in the enzyme cause lactose intolerance. Digestion and Absorption of Carbohydrates activity after weaning Weaning Techniques for effecting the transition of the respiratory-failure patient from mechanical ventilation to spontaneous ventilation, while meeting the criteria that tidal volume be above a given threshold (greater than 5 ml/kg), respiratory frequency be below a given count (less than 30 breaths/min), and oxygen partial pressure be above a given threshold (pao2 greater than 50mm hg). Weaning studies focus on finding methods to monitor and predict the outcome of mechanical ventilator weaning as well as finding ventilatory support techniques which will facilitate successful weaning. Present methods include intermittent mandatory ventilation, intermittent positive pressure ventilation, and mandatory minute volume ventilation. Invasive Mechanical Ventilation, either partially or completely

Secondary LD^[1,10,12]

• Due to LD (and other brush border enzymes Brush border enzymes Digestion and Absorption) as well as abnormalities in transport processes
• Causes include:
  • Acute gastroenteritis Gastroenteritis Gastroenteritis is inflammation of the stomach and intestines, commonly caused by infections from bacteria, viruses, or parasites. Transmission may be foodborne, fecal-oral, or through animal contact. Common clinical features include abdominal pain, diarrhea, vomiting, fever, and dehydration. Gastroenteritis (temporary)
  • Small intestinal bacterial overgrowth Bacterial overgrowth Lactose Intolerance
  • Giardiasis Giardiasis An infection of the small intestine caused by the flagellated protozoan giardia. It is spread via contaminated food and water and by direct person-to-person contact. Giardia/Giardiasis
  • Celiac disease Celiac disease Celiac disease (also known as celiac sprue or gluten enteropathy) is an autoimmune reaction to gliadin, which is a component of gluten. Celiac disease is closely associated with HLA-DQ2 and HLA-DQ8. The immune response is localized to the proximal small intestine and causes the characteristic histologic findings of villous atrophy, crypt hyperplasia, and intraepithelial lymphocytosis. Celiac Disease
  • Crohn disease
  • Radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma enteritis Enteritis Inflammation of any segment of the small intestine. Lactose Intolerance
  • Intestinal surgery
  • Chemotherapy Chemotherapy Osteosarcoma
  • HIV HIV Anti-HIV Drugs enteropathy Enteropathy IPEX Syndrome
  • Cystic Cystic Fibrocystic Change fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans

Less common types of LD^[1]

• Congenital Congenital Chorioretinitis (e.g., rare deficiency of lactase Lactase An enzyme which catalyzes the hydrolysis of lactose to d-galactose and d-glucose. Defects in the enzyme cause lactose intolerance. Digestion and Absorption of Carbohydrates)
• Developmental: in premature infants Premature infants A human infant born before 37 weeks of gestation. Sudden Infant Death Syndrome (SIDS), since lactase Lactase An enzyme which catalyzes the hydrolysis of lactose to d-galactose and d-glucose. Defects in the enzyme cause lactose intolerance. Digestion and Absorption of Carbohydrates activity develops late in gestation

Pathophysiology

General consideration^[5,9,11]

• Adults: Most have primary LD, but the majority do not develop LI.
• Infants: all infants have lactase Lactase An enzyme which catalyzes the hydrolysis of lactose to d-galactose and d-glucose. Defects in the enzyme cause lactose intolerance. Digestion and Absorption of Carbohydrates, which digests lactose → the most abundant carbohydrate in breast milk (accounts for 40% of calories in the milk).
• Carbohydrates Carbohydrates A class of organic compounds composed of carbon, hydrogen, and oxygen in a ratio of cn(H2O)n. The largest class of organic compounds, including starch; glycogen; cellulose; polysaccharides; and simple monosaccharides. Basics of Carbohydrates are only absorbed in the small bowel Small bowel The small intestine is the longest part of the GI tract, extending from the pyloric orifice of the stomach to the ileocecal junction. The small intestine is the major organ responsible for chemical digestion and absorption of nutrients. It is divided into 3 segments: the duodenum, the jejunum, and the ileum. Small Intestine: Anatomy and only as monosaccharides Monosaccharides Single chain carbohydrates that are the most basic units of carbohydrates. They are typically colorless crystalline substances with a sweet taste and have the same general formula CNH2NON. Basics of Carbohydrates.

Lactase Lactase An enzyme which catalyzes the hydrolysis of lactose to d-galactose and d-glucose. Defects in the enzyme cause lactose intolerance. Digestion and Absorption of Carbohydrates^[11,12]

• One of the enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes in the brush border Brush border Tubular System of the small intestine Small intestine The small intestine is the longest part of the GI tract, extending from the pyloric orifice of the stomach to the ileocecal junction. The small intestine is the major organ responsible for chemical digestion and absorption of nutrients. It is divided into 3 segments: the duodenum, the jejunum, and the ileum. Small Intestine: Anatomy
• Hydrolyzes lactose into glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance and galactose Galactose An aldohexose that occurs naturally in the d-form in lactose, cerebrosides, gangliosides, and mucoproteins. Deficiency of galactosyl-1-phosphate uridyltransferase causes an error in galactose metabolism called galactosemia, resulting in elevations of galactose in the blood. Lactose Intolerance, which are actively transported into the enterocytes by the sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia/ glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance ( galactose Galactose An aldohexose that occurs naturally in the d-form in lactose, cerebrosides, gangliosides, and mucoproteins. Deficiency of galactosyl-1-phosphate uridyltransferase causes an error in galactose metabolism called galactosemia, resulting in elevations of galactose in the blood. Lactose Intolerance) co-transporter (SGLT1)
• Primary LD: Lactase Lactase An enzyme which catalyzes the hydrolysis of lactose to d-galactose and d-glucose. Defects in the enzyme cause lactose intolerance. Digestion and Absorption of Carbohydrates activity decreases during weaning Weaning Techniques for effecting the transition of the respiratory-failure patient from mechanical ventilation to spontaneous ventilation, while meeting the criteria that tidal volume be above a given threshold (greater than 5 ml/kg), respiratory frequency be below a given count (less than 30 breaths/min), and oxygen partial pressure be above a given threshold (pao2 greater than 50mm hg). Weaning studies focus on finding methods to monitor and predict the outcome of mechanical ventilator weaning as well as finding ventilatory support techniques which will facilitate successful weaning. Present methods include intermittent mandatory ventilation, intermittent positive pressure ventilation, and mandatory minute volume ventilation. Invasive Mechanical Ventilation and does not persist after age 6.
• Secondary LD: Other enzyme activity levels and transport processes decrease because of small bowel Small bowel The small intestine is the longest part of the GI tract, extending from the pyloric orifice of the stomach to the ileocecal junction. The small intestine is the major organ responsible for chemical digestion and absorption of nutrients. It is divided into 3 segments: the duodenum, the jejunum, and the ileum. Small Intestine: Anatomy infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease or inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation.

Effects of undigested lactose^[8,11–13]

• Undigested lactose causes an osmotic load that pulls water and electrolytes Electrolytes Electrolytes are mineral salts that dissolve in water and dissociate into charged particles called ions, which can be either be positively (cations) or negatively (anions) charged. Electrolytes are distributed in the extracellular and intracellular compartments in different concentrations. Electrolytes are essential for various basic life-sustaining functions. Electrolytes into the bowel → watery diarrhea Watery diarrhea Rotavirus
• Gas is produced by bacterial fermentation of lactose in the colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy → bloating Bloating Constipation, flatulence, and abdominal pain Abdominal Pain Acute Abdomen
  • Results in excessive bloating Bloating Constipation, flatulence, and abdominal pain Abdominal Pain Acute Abdomen
  • Colonic adaptation or “enhanced colonic lactose processing”: a reduction of intolerance symptoms, likely related to a change in microbiome Microbiome Commensal organisms living in and on the body Innate Immunity: Barriers, Complement, and Cytokines → reduction of symptoms
• The likelihood of developing symptoms after lactose ingestion depends on a number of factors:
  • Local factors
  • GI hypersensitivity
  • Amount of lactose ingested

Clinical Presentation

Children and adolescents^[7,8,11,13]

• Uncommon to show signs of LI under 6 years of age
• Usually requires ingestion of > 8‒12 oz of milk (12‒18 g of lactose)
• Symptoms:
  • Diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea, with bulky, frothy, and watery stools
  • Inability to gain weight
  • Abdominal pain Abdominal Pain Acute Abdomen
  • Bloating Bloating Constipation
  • Flatulence
  • Nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics
  • Vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia

Adults^[10–12]

• Depends on multiple factors (e.g., lactose load, local GI factors, GI hypersensitivity) 
• Usually requires ingestion of > 8‒12 oz of milk
• Symptoms:
  • Abdominal pain Abdominal Pain Acute Abdomen 
  • Bloating Bloating Constipation
  • Flatulence
  • Nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics
  • Vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia
  • Diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea is rare in adults.

Diagnosis

There are no clear consensus guidelines for the diagnosis of LI. The following information is based on the US, UK, and European medical literature.

Initial testing^[5,10,12]

Consider a diagnosis of LI if typical symptoms occur within a few hours after ingestion of a lactose-containing meal and resolve after 5–7 days. The following items can be a starting point in the diagnostic workup.

• Trial of dietary lactose elimination Elimination The initial damage and destruction of tumor cells by innate and adaptive immunity. Completion of the phase means no cancer growth. Cancer Immunotherapy:^[8,13,14]
  • Can be diagnostic
  • May be done over a 2-week period
  • Ideally, symptoms will resolve.
  • If lactose is reintroduced → recurrence of symptoms
• Standardized symptom questionnaires are under investigation.^[4]
• Always consider potential secondary causes of LD when making the diagnosis:^[10,12]
  • Infectious enteritis Enteritis Inflammation of any segment of the small intestine. Lactose Intolerance, including giardiasis Giardiasis An infection of the small intestine caused by the flagellated protozoan giardia. It is spread via contaminated food and water and by direct person-to-person contact. Giardia/Giardiasis
  • Celiac disease Celiac disease Celiac disease (also known as celiac sprue or gluten enteropathy) is an autoimmune reaction to gliadin, which is a component of gluten. Celiac disease is closely associated with HLA-DQ2 and HLA-DQ8. The immune response is localized to the proximal small intestine and causes the characteristic histologic findings of villous atrophy, crypt hyperplasia, and intraepithelial lymphocytosis. Celiac Disease
  • Inflammatory bowel disease (especially Crohn‘s disease)
  • Drug- or radiation-induced enteritis Enteritis Inflammation of any segment of the small intestine. Lactose Intolerance
  • Secondary intestinal bacterial overgrowth Bacterial overgrowth Lactose Intolerance

Other tests to consider

The following testing may be considered if symptoms persist despite lactose restriction. Consider gastroenterology consultation when the diagnosis is not clear.

Lactose hydrogen breath test Hydrogen breath test Lactose Intolerance (LHBT):^{[1,5,8,10‒14]}

• Performed with simultaneous symptom assessment
• Indicated if dietary elimination Elimination The initial damage and destruction of tumor cells by innate and adaptive immunity. Completion of the phase means no cancer growth. Cancer Immunotherapy is inconclusive
• Benefits:
  • Noninvasive
  • Easy to perform
  • High sensitivity and specificity Sensitivity and Specificity Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Specificity is the probability of correctly determining the absence of a condition. Epidemiological Values of Diagnostic Tests (78 % and 98 %, respectively)
• Notes:
  • False positive False positive An FP test result indicates that a person has the disease when they do not. Epidemiological Values of Diagnostic Tests result possible with:
    • Recent smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases (< 1 week)
    • Small bowel Small bowel The small intestine is the longest part of the GI tract, extending from the pyloric orifice of the stomach to the ileocecal junction. The small intestine is the major organ responsible for chemical digestion and absorption of nutrients. It is divided into 3 segments: the duodenum, the jejunum, and the ileum. Small Intestine: Anatomy bacterial overgrowth Bacterial overgrowth Lactose Intolerance
  • False negative False negative An FN test result indicates a person does not have the disease when, in fact, they do. Epidemiological Values of Diagnostic Tests result possible with:
    • Recent antibiotic use (< 1 month)
    • Presence of methane-producing bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology
• Procedure:
  • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship should fast for 12 hours.
  • Give oral lactose load:
    • Adults: 25‒50 g 
    • Children: 2 g/kg (maximum: 25 g)
  • Sample breath hydrogen at baseline and every 30 minutes for 3–4 hours. 
  • Breath hydrogen > 20 parts per million (ppm) after lactose load is diagnostic of lactose malabsorption Malabsorption General term for a group of malnutrition syndromes caused by failure of normal intestinal absorption of nutrients. Malabsorption and Maldigestion.

Lactose tolerance Tolerance Pharmacokinetics and Pharmacodynamics test:^[5,10,12,13]

• Rarely performed owing to high rate of false positive False positive An FP test result indicates that a person has the disease when they do not. Epidemiological Values of Diagnostic Tests and false negative False negative An FN test result indicates a person does not have the disease when, in fact, they do. Epidemiological Values of Diagnostic Tests results
• Essentially replaced with LHBT
• Procedure:
  • An oral lactose load of 50 g is given.
  • Serial blood glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance levels are measured (at 0, 30, 60, and 120 minutes after ingestion).
  • Rise in blood glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance of ≥ 20 mg/dL from baseline indicates adequate lactose digestion Digestion Digestion refers to the process of the mechanical and chemical breakdown of food into smaller particles, which can then be absorbed and utilized by the body. Digestion and Absorption and absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption.

Fecal pH pH The quantitative measurement of the acidity or basicity of a solution. Acid-Base Balance:^[8,13]

• Used in infants: pH pH The quantitative measurement of the acidity or basicity of a solution. Acid-Base Balance reduced with malabsorption Malabsorption General term for a group of malnutrition syndromes caused by failure of normal intestinal absorption of nutrients. Malabsorption and Maldigestion
• Does not differentiate lactose from other carbohydrates Carbohydrates A class of organic compounds composed of carbon, hydrogen, and oxygen in a ratio of cn(H2O)n. The largest class of organic compounds, including starch; glycogen; cellulose; polysaccharides; and simple monosaccharides. Basics of Carbohydrates (e.g., fructose)
• Lower sensitivity and specificity Sensitivity and Specificity Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Specificity is the probability of correctly determining the absence of a condition. Epidemiological Values of Diagnostic Tests than LHBT

Gaxilose test:^[5] 

• Test availability is limited.
• Measures lactase Lactase An enzyme which catalyzes the hydrolysis of lactose to d-galactose and d-glucose. Defects in the enzyme cause lactose intolerance. Digestion and Absorption of Carbohydrates activity
• Gaxilose (4-galactosyl xylose (a lactase Lactase An enzyme which catalyzes the hydrolysis of lactose to d-galactose and d-glucose. Defects in the enzyme cause lactose intolerance. Digestion and Absorption of Carbohydrates substrate Substrate A substance upon which the enzyme acts. Basics of Enzymes)) is ingested.
• Lactase Lactase An enzyme which catalyzes the hydrolysis of lactose to d-galactose and d-glucose. Defects in the enzyme cause lactose intolerance. Digestion and Absorption of Carbohydrates normally cleaves gaxilose to galactose Galactose An aldohexose that occurs naturally in the d-form in lactose, cerebrosides, gangliosides, and mucoproteins. Deficiency of galactosyl-1-phosphate uridyltransferase causes an error in galactose metabolism called galactosemia, resulting in elevations of galactose in the blood. Lactose Intolerance and D-xylose.
• Urine and/or blood are tested for D-xylose levels.

Small bowel Small bowel The small intestine is the longest part of the GI tract, extending from the pyloric orifice of the stomach to the ileocecal junction. The small intestine is the major organ responsible for chemical digestion and absorption of nutrients. It is divided into 3 segments: the duodenum, the jejunum, and the ileum. Small Intestine: Anatomy biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma:^[5,8,11] 

• Invasive and rarely performed unless another indication for endoscopy Endoscopy Procedures of applying endoscopes for disease diagnosis and treatment. Endoscopy involves passing an optical instrument through a small incision in the skin i.e., percutaneous; or through a natural orifice and along natural body pathways such as the digestive tract; and/or through an incision in the wall of a tubular structure or organ, i.e. Transluminal, to examine or perform surgery on the interior parts of the body. Gastroesophageal Reflux Disease (GERD) is present
• Can be used to measure lactase Lactase An enzyme which catalyzes the hydrolysis of lactose to d-galactose and d-glucose. Defects in the enzyme cause lactose intolerance. Digestion and Absorption of Carbohydrates activity → can help distinguish between primary and secondary LD
• Indicated in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with persistent symptoms plus:
  • Positive celiac serology Serology The study of serum, especially of antigen-antibody reactions in vitro. Yellow Fever Virus
  • Likely exposure to Giardia Giardia A genus of flagellate intestinal eukaryotes parasitic in various vertebrates, including humans. Characteristics include the presence of four pairs of flagella arising from a complicated system of axonemes and cysts that are ellipsoidal to ovoidal in shape. Nitroimidazoles
  • Bacterial overgrowth Bacterial overgrowth Lactose Intolerance due to prior surgery
  • If LHBT is unavailable

Other tests:^[5,11‒13]

• Genotype Genotype The genetic constitution of the individual, comprising the alleles present at each genetic locus. Basic Terms of Genetics testing: used in some European countries but not widely available elsewhere
• ¹³C-labeled lactose breath test: under investigation for future use

Management

The goal of management is to eliminate symptoms of LI while maintaining a sufficient calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes and vitamin D Vitamin D A vitamin that includes both cholecalciferols and ergocalciferols, which have the common effect of preventing or curing rickets in animals. It can also be viewed as a hormone since it can be formed in skin by action of ultraviolet rays upon the precursors, 7-dehydrocholesterol and ergosterol, and acts on vitamin D receptors to regulate calcium in opposition to parathyroid hormone. Fat-soluble Vitamins and their Deficiencies intake.^[5] The following information is based on the US, European, and UK medical literature.

Diet changes^[5,10‒14]

• Complete elimination Elimination The initial damage and destruction of tumor cells by innate and adaptive immunity. Completion of the phase means no cancer growth. Cancer Immunotherapy of dietary lactose is not required.
• Lactose restriction:
  • Reduce load to ≤ 240–375 mL (8–12 oz) of milk or equivalent per day (thresholds vary among individuals).
  • Dairy products should be consumed with other food to delay gastric emptying Gastric emptying The evacuation of food from the stomach into the duodenum. Gastrointestinal Motility.
  • Routine daily lactose consumption is better than intermittent intake due to colonic adaptation. 
  • Milk and ice cream deliver the highest lactose loads → high fat content can mitigate symptoms as it decreases gastric emptying Gastric emptying The evacuation of food from the stomach into the duodenum. Gastrointestinal Motility rate.
  • Cheeses → usually contain lower amounts of lactose
  • Live-culture yogurt contains endogenous lactase Lactase An enzyme which catalyzes the hydrolysis of lactose to d-galactose and d-glucose. Defects in the enzyme cause lactose intolerance. Digestion and Absorption of Carbohydrates → breaks down lactose into galactose Galactose An aldohexose that occurs naturally in the d-form in lactose, cerebrosides, gangliosides, and mucoproteins. Deficiency of galactosyl-1-phosphate uridyltransferase causes an error in galactose metabolism called galactosemia, resulting in elevations of galactose in the blood. Lactose Intolerance and glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance
  • Consider “hidden” sources of lactose in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with unresponsive symptoms:
    • Bread/baked goods
    • Salad dressings
    • Breakfast drinks
    • Soups
    • Margarine
• Additional considerations:
  • Substitute reduced-lactose, lactase-treated, or vegan nondairy products.
  • Ensure adequate intake (particularly in children and adolescents) of:
    • Calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes (700–1200 mg/day for adults)
    • Vitamin D Vitamin D A vitamin that includes both cholecalciferols and ergocalciferols, which have the common effect of preventing or curing rickets in animals. It can also be viewed as a hormone since it can be formed in skin by action of ultraviolet rays upon the precursors, 7-dehydrocholesterol and ergosterol, and acts on vitamin D receptors to regulate calcium in opposition to parathyroid hormone. Fat-soluble Vitamins and their Deficiencies
    • Protein

Oral lactase Lactase An enzyme which catalyzes the hydrolysis of lactose to d-galactose and d-glucose. Defects in the enzyme cause lactose intolerance. Digestion and Absorption of Carbohydrates enzyme preparations^[5,8,14]

• Can be taken when the individual is planning to eat lactose-containing foods
• Commercially available
• Do not completely hydrolyze ingested lactose
• Efficacy is highly variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables.

Supplements and probiotics

• Calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes supplementation may be considered for patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with limited dietary intake.^[6,10,11,13]
• Probiotics:^[3,5]
  • Some evidence supports effectiveness.
  • Limited by inconsistent results among strains

Secondary LI management^[10,13,14]

• Treat the primary disorder.
• May take months for normal lactase Lactase An enzyme which catalyzes the hydrolysis of lactose to d-galactose and d-glucose. Defects in the enzyme cause lactose intolerance. Digestion and Absorption of Carbohydrates activity to return to normal (usually 3–4 weeks)^[14]

Differential Diagnosis

• Cow’s milk allergy Allergy An abnormal adaptive immune response that may or may not involve antigen-specific IgE Type I Hypersensitivity Reaction: the most common food allergy Allergy An abnormal adaptive immune response that may or may not involve antigen-specific IgE Type I Hypersensitivity Reaction in young children but uncommon in adults. Cow’s milk proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis can provoke IgE-mediated or non–IgE-mediated immune responses. Diagnosis is made by testing for specific IgE antibodies IgE antibodies An immunoglobulin associated with mast cells. Overexpression has been associated with allergic hypersensitivity. Type I Hypersensitivity Reaction or by elimination Elimination The initial damage and destruction of tumor cells by innate and adaptive immunity. Completion of the phase means no cancer growth. Cancer Immunotherapy diet.
• Food protein intolerance: can present with similar symptoms as LI due to unabsorbed substrate Substrate A substance upon which the enzyme acts. Basics of Enzymes in the intestine. Although the temporal association of the symptoms with the type of food ingested can point toward the responsible food product, the best way to differentiate between these2 conditions is via a hydrogen breath test Hydrogen breath test Lactose Intolerance or trial of a lactose-free diet.
• Irritable bowel syndrome Irritable bowel syndrome Irritable bowel syndrome (IBS) is a functional bowel disease characterized by chronic abdominal pain and altered bowel habits without an identifiable organic cause. The etiology and pathophysiology of this disease are not well understood, and there are many factors that may contribute. Irritable Bowel Syndrome: can present with similar symptoms ( abdominal pain Abdominal Pain Acute Abdomen, bloating Bloating Constipation, and diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea) and may worsen coexisting LI, but the temporal association of the symptoms only with the ingestion of lactose products points toward lactose intolerance Lactose intolerance Lactose intolerance (LI) describes a constellation of symptoms due to lactase deficiency (LD), the enzyme located in the brush border of the absorptive cells in the small intestine. Lactose is the disaccharide present in milk and requires hydrolysis by lactase to break it down into its 2 absorbable constituents, glucose and galactose. Lactose intolerance typically presents with bloating, abdominal cramping, diarrhea, and flatulence. Lactose Intolerance. Diagnosis includes lab testing and possible endoscopy Endoscopy Procedures of applying endoscopes for disease diagnosis and treatment. Endoscopy involves passing an optical instrument through a small incision in the skin i.e., percutaneous; or through a natural orifice and along natural body pathways such as the digestive tract; and/or through an incision in the wall of a tubular structure or organ, i.e. Transluminal, to examine or perform surgery on the interior parts of the body. Gastroesophageal Reflux Disease (GERD) in adults over 45 to exclude an alternative diagnosis. Treatment includes lifestyle and dietary modification plus fiber supplementation for individuals with constipation Constipation Constipation is common and may be due to a variety of causes. Constipation is generally defined as bowel movement frequency < 3 times per week. Patients who are constipated often strain to pass hard stools. The condition is classified as primary (also known as idiopathic or functional constipation) or secondary, and as acute or chronic. Constipation as the predominant symptom. Antispasmodics and antidepressants are occasionally needed.
• Pediatric diarrhea Pediatric diarrhea Diarrhea is described as passage of large amounts stools that are often loose, liquid, or watery, resulting in excess loss of fluids and electrolytes. Diarrhea is one of the most common illnesses in children, representing the largest percentages of morbidity and mortality worldwide in the pediatric age group. Pediatric Diarrhea: has many potential causes, including secretory and osmotic diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea, motility Motility The motor activity of the gastrointestinal tract. Gastrointestinal Motility disorders, and diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea due to decreased surface area. Multiple diagnostic tools are available.
• Incomplete absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption of orally ingested simple carbohydrates Carbohydrates A class of organic compounds composed of carbon, hydrogen, and oxygen in a ratio of cn(H2O)n. The largest class of organic compounds, including starch; glycogen; cellulose; polysaccharides; and simple monosaccharides. Basics of Carbohydrates: these carbohydrates Carbohydrates A class of organic compounds composed of carbon, hydrogen, and oxygen in a ratio of cn(H2O)n. The largest class of organic compounds, including starch; glycogen; cellulose; polysaccharides; and simple monosaccharides. Basics of Carbohydrates include sorbitol Sorbitol A polyhydric alcohol with about half the sweetness of sucrose. Sorbitol occurs naturally and is also produced synthetically from glucose. It was formerly used as a diuretic and may still be used as a laxative and in irrigating solutions for some surgical procedures. It is also used in many manufacturing processes, as a pharmaceutical aid, and in several research applications. Laxatives, mannitol Mannitol A diuretic and renal diagnostic aid related to sorbitol. It has little significant energy value as it is largely eliminated from the body before any metabolism can take place. It can be used to treat oliguria associated with kidney failure or other manifestations of inadequate renal function and has been used for determination of glomerular filtration rate. Mannitol is also commonly used as a research tool in cell biological studies, usually to control osmolarity. Osmotic Diuretics, xylitol, fructose, and FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols). Sorbitol Sorbitol A polyhydric alcohol with about half the sweetness of sucrose. Sorbitol occurs naturally and is also produced synthetically from glucose. It was formerly used as a diuretic and may still be used as a laxative and in irrigating solutions for some surgical procedures. It is also used in many manufacturing processes, as a pharmaceutical aid, and in several research applications. Laxatives, mannitol Mannitol A diuretic and renal diagnostic aid related to sorbitol. It has little significant energy value as it is largely eliminated from the body before any metabolism can take place. It can be used to treat oliguria associated with kidney failure or other manifestations of inadequate renal function and has been used for determination of glomerular filtration rate. Mannitol is also commonly used as a research tool in cell biological studies, usually to control osmolarity. Osmotic Diuretics, and xylitol are sugar alcohols used as artificial sweeteners. Diagnosis is based on the dietary history, and sometimes a fructose breath test is helpful. Treatment is an elimination Elimination The initial damage and destruction of tumor cells by innate and adaptive immunity. Completion of the phase means no cancer growth. Cancer Immunotherapy diet.