Lactose Intolerance

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
• In adults:
  • > 70% of adults worldwide have primary 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 deficiency (LD), but less than half of all adults have lactose intolerance (LI).
  • Lowest 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 of LD: Northern Europeans
  • Highest 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 of LD: Africans, African Americans, Asians, Asian Americans, Hispanics, and Native Americans

Etiology

Primary LD

• Also called acquired primary 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 deficiency, 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, either partially or completely, 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 
• More than half of people with primary LD do not have LI.

Secondary LD

• A decrease in 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 and other brush border Brush border Tubular System 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 as well as abnormalities in transport processes
• Due to 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 infection or a primary mucosal disease such as 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

Less common types of LD

• 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 Premature Childbirth before 37 weeks of pregnancy (259 days from the first day of the mother’s last menstrual period, or 245 days after fertilization). Necrotizing Enterocolitis infants, 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

• 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

• 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
• Digests lactose into glucose and galactose, 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 (galactose) co-transporter (SGLT1)
• 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 falls 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 6 years of age in > 70% of people, causing primary LD but not necessarily LI.
• In secondary LD, the activity levels of other 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 and transport processes also fall, secondary to 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 of 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.

Effects of undigested lactose

• 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 (hydrogen, carbon dioxide, and methane):
  • 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.

Clinical Presentation

Children and adolescents

• Uncommon to show signs of LI under 6 years of age
• 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

• Symptoms depend on multiple factors, including lactose load: usually requires ingestion of > 480 mL (2 cups) of milk
• 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

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.

Testing for LD

Note: Tests for LD alone do not confirm LI unless symptoms are also provoked by lactose loading.

• Validated questionnaire
• Lactose hydrogen breath test:
  • Measures lactose malabsorption Malabsorption General term for a group of malnutrition syndromes caused by failure of normal intestinal absorption of nutrients. Malabsorption and Maldigestion
  • Testing method in adults: 
    • Give 50 g of lactose orally and sample breath hydrogen at baseline and every 30 minutes for 3–4 hours. 
    • A rise in hydrogen concentration of 20 parts per million (ppm) over baseline 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.
    • Sensitivity Sensitivity Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Blotting Techniques: 78%; specificity Specificity Specificity is the probability of correctly determining the absence of a condition. Immunoassays: 98%
• 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: 
  • The diagnostic gold standard but rarely performed because it is invasive 
  • Can help distinguish between primary and secondary LD

Secondary causes of LD

Always consider potential secondary causes of LD when making the diagnosis:

• Infectious Infectious Febrile Infant enteritis, 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
• Secondary intestinal bacterial overgrowth

Management

Primary lactose intolerance

• Lactose restriction:
  • Reduce load to ≤ 480 mL (2 cups) of milk or equivalent per day. 
  • 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 consumption of lactose 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 and glucose
• Substitute regular Regular Insulin dairy products with predigested ones, or vegan products.
• 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: do not completely hydrolyze ingested lactose; efficacy 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
• Increase consumption 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 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, with supplements if necessary, if patient avoids all dairy products → monitor blood levels

Secondary lactose intolerance

Treat the primary disorder. It 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.

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 and/or non-IgE-mediated immune response. 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 and/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 Product A molecule created by the enzymatic reaction. Basics of Enzymes, the best way to differentiate between the 2 conditions is via hydrogen breath test 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. The best way to differentiate between the 2 conditions is by a hydrogen breath test or trial of a lactose-free diet.
• Pediatric 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: 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 oligo-, di-, 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 used as artificial sweeteners, and 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 is used as a laxative Laxative Agents that produce a soft formed stool, and relax and loosen the bowels, typically used over a protracted period, to relieve constipation. Hypokalemia. Diagnosis is usually straightforward based on the dietary history or a breath test for fructose.