Abstracts

Adult diarrhea

To provide the primary care clinician with a general diagnostic and therapeutic approach to the adult patient with diarrhea.

Basic pathophysiologic mechanisms are described. Important causes and clinical features of each type of diarrhea are highlighted.

A step-by-step diagnostic evaluation is suggested, and an overview of treatment options is presented.

Kroser JA & Metz DC: Evaluation of the adult patient with diarrhea. Prim Care, 23(3):629-47 1996 Sep.

AIDS & diarrhea

AIDS (1)

Diarrhea is a common problem for AIDS patients, and is chronic and debilitating.

A thorough evaluation will reveal a pathogen in the majority of patients, and the organisms most frequently identified in AIDS patients with chronic diarrhea are Cryptosporidium, microsporidia, and Mycobacterium avium complex.

Bacterial pathogens are more common in AIDS patients than in the general population and may present in different ways from infections in immunocompetent hosts. Other pathogens, including Cryptosporidium and microsporidia, are difficult to diagnose and have no effective therapy. Moreover, enteric viruses and HIV itself may contribute to the diarrhea. In addition to microbes, other factors such as medication, immune dysregulation, automatic dysfunction, and nutritional supplementation play a substantial role in diarrhea of AIDS patients.

Framm SR & Soave R: Agents of diarrhea. Med Clin North Am, 81:427-47, 1997 Mar.

AIDS (2)

The spectrum of illness associated with the acquired immunodeficiency syndrome (AIDS) has been increasing since the initial description in 1981. While virtually all organ systems may be affected, the gastrointestinal tract appears to be a major target. Diarrhea is the most common symptom, affecting up to half of all AIDS patients during the course of their disease.

Although diarrhea occurs frequently, its optimal management remains controversial. An extensive evaluation including stool studies and endoscopic biopsies of both the colon and small intestine has been widely recommended to identify all potential pathogenic organisms.

An alternative approach is a more limited evaluation consisting of stool and blood cultures followed by symptomatic treatment with antidiarrheal agents if no specific organisms are identified.

The most common opportunistic pathogens are reviewed, including several recently discovered organisms.

Recommendations for treatment are followed by a brief discussion of management strategies used to care for patients with AIDS-related diarrhea.

Johanson JF Diagnosis and management of AIDS-related diarrhea. Can J Gastroenterol, 10:461-8, 1996 Nov-Dec.

Appendicitis

Appendicitis is an uncommon diagnosis in very young children. It is frequently complicated by delays in diagnosis, perforation, and lengthy hospital stays.

Sixty-three children were identified. Mean age was 2.2 years (range 11 to 35 months). The mean delay from onset of symptoms to presentation was 4.3 days. 57 % were initially misdiagnosed. Diarrhea was reported in 33%.

Perforation and/or gangrene were found in 84%. Perforation and/or gangrene at laparotomy and a history of diarrhea at presentation were independent predictors of a prolonged hospital stay.

Appendicitis in children under 3 years old is characterized by delays in diagnosis and perforation. A history of diarrhea is an important factor that confuses the diagnosis, prolongs the observation period, and delays appropriate therapy.

Horwitz JR et al., Importance of diarrhea as a presenting symptom of appendicitis in very young children. Am J Surg, 173:80-2, 1997 Feb.

Breast-feeding

Breast-feeding

Women may not need to consume extra calcium during breast feeding, according to this randomized, placebo-controlled calcium supplementation conducted over a period of 6 months on breast feeding women. A calcium supplement of 1000 mg/day had no impact on breast milk calcium concentration or on lactation-associated bone mineral changes in the lumbar spine, radius, or total body. Calcium supplementation produced a modest increase in spine bone mineral density in both lactating and nonlactating women, but the potential significance of this effect is unclear.

Stahl, W. Heinrich, U. Jungmann, H. Laar J. von. Schietzel, M. Sies, H. Tronnier, H: Calcium requirements of breast-feeding mothers, Nutr-rev. Washington, D.C.: International Life Sciences Institute--ILSI Press. Apr 1998. v. 56 (4,pt.1) p. 124-127

Celiac disease & diarrhea

The majority of patients with celiac sprue experience diarrhea before diagnosis. There have been no studies of the prevalence or causes of chronic diarrhea in these patients after treatment with a gluten-free diet.

Sixty-two of the 78 patients (79%) experienced diarrhea before treatment, and 13 (17%) had chronic diarrhea (of lesser severity) after treatment. The causes of diarrhea in 11 patients consenting to this study were microscopic colitis, steatorrhea secondary to exocrine pancreatic insufficiency, dietary lactose or fructose malabsorption, anal sphincter dysfunction causing fecal incontinence, and the irritable bowel syndrome.

Only 1 patient had antigliadin antibodies detected in serum or small intestinal villous atrophy.

After treatment of celiac sprue with a gluten-free diet, chronic diarrhea persists in a substantial percentage of patients. Although ongoing gluten ingestion is one possible cause, other causes may be more frequent. Therefore, diagnostic investigation of diarrhea in celiac sprue after treatment seems warranted.

Fine KD et al., The prevalence and causes of chronic diarrhea in patients with celiac sprue treated with a gluten-free diet [see comments]. Gastroenterology, 112:1830-8, 1997 Jun.

Colitis & diarrhea

Tested the hypothesis that some patients with functional diarrhea could actually suffer from a mild clinical pattern of collagenous or lymphocytic colitis.

Among the 20 patients with diarrhea, the quantitative diagnosis of collagenous colitis was made in 3 patients and the diagnosis of lymphocytic colitis in one.

All the values of fecal weight were below 300 g/d, except in one patient with a past history of truncular vagotomy.

Results suggest that most of the patients with functional diarrhea do not suffer from mild clinical patterns of collagenous or lymphocytic colitis.

Luboinski J et al., [Functional diarrheas are not, in most cases, minor clinical forms of lymphocytic or collagenous colitis]. Gastroenterol Clin Biol, 20:838-43, 1996.

Home therapy

Over 1 billion episodes of acute diarrhea occur yearly in children in the developing world a major cause of childhood mortality. Replacement of fluid and electrolytes at home would reduce the incidence of diarrhea significantly.

Oral rehydration salts (ORS) are frequently recommended by the World Health Organization and UNICEF. Oral rehydration solutions should contain sodium chloride, potassium, trisodium citrate or sodium bicarbonate. The majority of diarrhea cases do not require ORS therapy. Home based sugar and salt solutions are probably more practical and can be made from refined sugar and table salt. They have been shown to reduce mortality in diarrhea associated areas.

Food based oral therapy containing cereals and simple starches increase the effectiveness of salt and water absorption of oral therapy. Most of the food additives have been rice, wheat, potato or other root vegetables. Rice water oral therapy may be used by adding salt to a drained supernatant of boiled rice. The starch must be cooked before use. Rice soups, salt, dahl (lentils) and lemon juice have been utilized as home remedies for diarrhea.

It has not been consistently found that nutritional therapy is well tolerated during diarrhea. In the first few months of life infants have decreased pancreatic enzymes and bile salts and may be less capable of absorbing nutrients. Lactose intolerance is a concern and lactose containing foods may aggravate the problem.

The introduction of rice, wheat and potatoes can provide glucose polymers and short-chain polypeptides which can enhance the absorption of salt in water and reduce diarrhea.

"Review: Home-Based Therapy For Diarrhea", Snyder, John D., et al, Journal of Pediatric Gastroenterology and Nutrition, 1990;11:438-447.

Hospitalizations

Emergency department

Enteric disease represents a significant medical problem on a worldwide basis. The evaluation of patients with diarrhea in the emergency department should follow a stepwise methodology to identify potentially serious disorders.

The evaluation of the stool for fecal leukocytes is an important differentiation point in the evaluation of the moderately to seriously ill diarrhea patient. Oral rehydration alone can treat the vast majority of diarrhea patients. Oral rehydration solution takes advantage of the sodium glucose coupled active absorption mechanism, which is largely unaffected by enteric toxins.

Antimicrobial or antidiarrheal agents are rarely indicated in the treatment of diarrhea.

Hogan DE The emergency department approach to diarrhea. Emerg Med Clin North Am, 14:673-94, 1996 Nov.

Hospitalizations

Examined trends in the hospitalizations of children for diarrheal disease in the U.S. and to provide estimates for the burden of disease associated with rotavirus diarrhea.

Data were compiled from the National Hospital Discharge Survey for the years 1979 through 1992. Between 1979 and 1992, 12% of all hospitalizations of U.S. children 1 month through 4 years of age had an International Classification of Diseases code for diarrhea listed in one of the top three positions on the discharge diagnosis.

The annual rate of diarrheal hospitalizations, 97 per 10 000 persons (average, 185,742 per year), did not change substantially during the 14-year study period and accounted annually for 724,394 inpatient days (3.9 days per hospitalization).

For most diarrheal hospitalizations (76%) no causative agent was specified in the National Hospital Discharge Survey records; of the remaining 25%, viruses were most commonly reported (19%), followed by bacteria (5%) and parasites (0.7%).

The proportion of hospitalizations associated with viral diarrheas rose from 13% to 27% during the 14-year study period, whereas the proportion of hospitalizations for noninfectious diarrhea declined from 79% to 60%.

Every year the number of hospitalizations peaked from November through April, the "winter" months, among children ages 4 through 35 months; this peak began in the West during November and December and reached the Northeast by March.

Diarrhea continues to be a common cause of hospitalization among children in the United States and the winter seasonality estimated to be caused in large part by rotavirus would be expected to decrease if rotavirus vaccines currently being developed were introduced.

Jin S et al., Trends in hospitalizations for diarrhea in United States children from 1979 through 1992: estimates of the morbidity associated with rotavirus. Pediatr Infect Dis J, 15:397-404, 1996 May.

Hyperglycemia & diarrhea

To determine the cause of hyperglycemia in childhood diarrhea (Bangladesh).

Prevalence of hyperglycemia among patients aged 2 to 10 years was 9.4%. Compared with the normoglycemic patients, hyperglycemic patients more often had severe dehydration (100% versus 10%), infection with Vibrio cholerae 0 1 or toxigenic Escherichia coli (94% vs 25%), and had similar duration of fasting (16 vs 14 hours).

Concentrations of epinephrine (7.15 vs 2.00 micromol/L), norepinephrine (10.35 vs 3.50 micromol/L), cortisol (1.38 vs 0.82 micromol/L), glucagon (36 vs 14 pmol/L), and C-peptide (1.22 vs 0.35 nmol/L) were all significantly (p < or = 0.014) higher in patients with hyperglycemia than in normoglycemic patients.

The development of hyperglycemia in diarrhea is caused by a stress response to hypovolemia.

Ronan A et al., Hyperglycemia during childhood diarrhea. J Pediatr, 130:45-51, 1997 Jan.

Diabetics

Substance P (SP), vasoactive intestinal polypeptide (VIP), and somatostatin content in rectal mucosa were determined by radioimmunoassay (RIA) in 38 diabetic patients (12 with normal bowel function, 13 with diabetic diarrhea, and 13 with constipation) and in 10 nondiabetic controls with normal bowel function.

SP content (picograms per milligram) in the rectal mucosa of diabetics with normal bowel function was significantly higher than that of nondiabetic controls.

SP content in the rectal mucosa of diabetics with diabetic diarrhea and constipation was significantly lower than in diabetics with normal bowel habits and nondiabetic controls.

No differences were found in the rectal mucosa content of VIP and somatostatin between the different groups of diabetics and controls.

Diabetic diarrhea is a condition with an intermittent nature and frequently alternates with constipation. Findings suggest a possible common role of SP in the pathogenesis of diabetic diarrhea and constipation.

Lysy J et al., Decreased substance P content in the rectal mucosa of diabetics with diarrhea and constipation. Metabolism, 46:730-4, 1997 Jul.

Diet therapies

Contents:

Diet (Infants)
Diet therapy
Milk diets
Porridge
Psyllium
Soy fiber

Diet (Infants)

A diet based on rice powder, soya-bean oil, glucose, egg-white and salts was given to patients of different nutritional status aged 4-18 months with persistent diarrhoea and controls without diarrhoea.

Clinical response was monitored during 1 week of dietary treatment and absorption of macronutrients was estimated during a 72 h balance study. Twenty-one patients (81%) recovered from diarrhoea within 7 d.

Results indicate that a rice-based diet is highly effective in the management of persistent diarrhoea.

Malnutrition and the initial severity of diarrhoea are significant determinants of clinical prognosis and nutrient absorption in persistent diarrhoea.

Persistent diarrhoea: efficacy of a rice-based diet and role of nutritional status in recovery and nutrient absorption. Roy-SK et al., Br-J-Nutr. 1994 Jan; 71(1): 123-34.
Milk diets

Previous studies have shown increased stool output when children with persistent diarrhea (PD) received milk as the predominant source of nutrition.

Evaluated the efficacy of milk given in modest amounts as a part of a mixed diet in children with PD.

The two diets were isocaloric (86.9 calories/100 g for < or = 9 months; 95.6 cal/100 g for > 9 months) consisting of puffed rice cereal, sugar, and oil differing in only their source of protein, which was either milk or egg white, respectively. An average of 30% of the calories were constituted by milk in the milk-cereal diet. Both diets were offered at the rate of 150 kcal/kg per day. Children receiving milk-cereal consumed an average of 1.9 g/kg lactose per day.

The baseline characteristics in the two groups were similar. Comparable amounts of diet were consumed in both groups. The milk-cereal group did not have higher median (range) stool output (g/kg/h) compared with the milk-free group during a 0- to 48-hour (milk-cereal, 1.7 ?0.2 to 8.7?; milk-free, 1.5 ?0.1 to 6.6?) or 0- to 120-hour (milk-cereal, 1.6 ?0.4 to 7.2?; milk-free, 1.3 ?0.1 to 7.6?) period. The percentage of weight gain was similar in the two groups, and there were no significant differences in the duration of diarrhea. Overall, 23 children had treatment failures, 10 (17%) in the milk-cereal and 13 (23.6%) in the milk-free groups.

Modest intakes of milk are well tolerated as a part of mixed diet during PD.

Bhatnagar S et al., Efficacy of milk-based diets in persistent diarrhea: a randomized, controlled trial. Pediatrics, 1996 Dec, 98:6 Pt 1, 1122-6.

Diet therapy

A dietary algorithm for management of persistent diarrhea in developing countries, using locally available foods, is yet to be standardized.

Identified factors related to poor outcome among 75 malnourished hospitalized male patients aged 3-48 months with persistent diarrhea (> or = 14 days) treated on soy and cereal-based diet (Diet I).

The significant association of diarrhea treatment failures with carbohydrate malabsorption suggests that in the initial diet itself, part of polysaccharide be substituted with sucrose or glucose to obtain the right balance between osmolarity and energy density.

Data suggest that prompt identification and treatment of systemic infection is critical, as its eradication achieved recovery in more than half of the treatment failures without a dietary change.

Bhatnagar S et al., Prognostic factors in hospitalized children with persistent diarrhea: implications for diet therapy. J Pediatr Gastroenterol Nutr, 23:151-8, 1996 Aug.

Porridge

Addition of a small amount of amylase rich flour (ARF) to a thick porridge instantly liquefies the porridge and increase the energy intake even by sick children.

Examined the absorption of macronutrients and calories from an energy dense diet liquefied with ARF in children aged 6-11 months with acute watery diarrhea.

After adequate hydration with oral rehydration fluid over a period of 24 hours, children were randomly assigned to receive either an ARF treated liquefied porridge (test diet) or a porridge diluted with water (control diet).

The energy dense diet liquefied with ARF was well absorbed in children with acute diarrhea and there was a positive nitrogen balance that may have a positive impact in preventing weight loss during acute illness.

Rahman MM et al., Absorption of nutrients from an energy-dense diet liquefied with amylase from germinated wheat in infants with acute diarrhea. J Pediatr Gastroenterol Nutr, 24:119-23, 1997 Feb.

Psyllium

Investigated the efficacy of psyllium hydrophilic mucilloid (PHM) for prevention of diarrhea and to compare methods of PHM delivery.

OUTCOME MEASURES: Diarrhea, stool frequency and consistency, and feeding tube obstruction.

Receipt of PHM (7 gm, twice-daily) added to continuous feeding or given as a bolus with intermittent feeding, or receipt of No PHM for 7 days after initiation of enteral feeding.

Fifteen subjects (25%) developed diarrhea (defined as 3 or more liquid stools per day, or 2 or more liquid stools on successive days). There were no significant differences in incidence of diarrhea or percentage of days of diarrhea between subjects who did and did not receive PHM. However, subjects who received PHM in their continuous feedings had a significantly higher number of gelatinous stools, and the combined PHM groups had a significantly lower number of liquid stools and a higher number of normal stools than did subjects who did not receive PHM.

Further study with a larger sample is necessary to evaluate trends found in this pilot study and to determine PHM efficacy for prevention of diarrhea. PHM administration may result in small-bore feeding tube obstruction, and thus requires adequate dilution and close monitoring.

Belknap D et al., The effects of psyllium hydrophilic mucilloid on diarrhea in enterally fed patients. Heart Lung, 26:229-37, 1997 May-Jun.

Soy fiber

Soy fiber has been shown to reduce the duration of watery stools during acute diarrhea caused by bacterial and viral pathogens in underdeveloped countries.

A randomized blinded clinical trial was conducted with middle-class American children to assess the efficacy of soy fiber-supplemented infant formula. Stool characteristics, intake, and weight were recorded.

Infants > 6 months of age (n = 44) fed soy fiber-supplemented formula (Isomil DF) had a significantly shorter estimated median duration of diarrhea (9.7 hours vs. 23.1 hours) than those fed soy formula (Isomil).

The use of fiber-supplemented soy formula may reduce the duration of diarrheal symptoms in U.S. infants more than 6 months of age with acute diarrhea.

Vanderhoof JA et al., Use of soy fiber in acute diarrhea in infants and toddlers. Clin Pediatr (Phila), 36:135-9, 1997 Mar.

Iron supplementation

Evaluated the effect of long-term oral iron supplementation on morbidity due to diarrhea, dysentery and respiratory infections in 349 children, aged 2-48 mo, living in a poor community of Bangladesh.

The treatment group received 125 mg of ferrous gluconate (15 mg elemental iron) plus multivitamins and the controls received only multivitamins, daily for 15 mo. House-to-house visits were made on alternate days by trained community health workers for recording symptoms and duration of illnesses and for monitoring medicine intake.

The attack rates for diarrhea, dysentery and acute respiratory tract infections (ARI) were 3, 3 and 5 episodes per child per year, respectively. Each episode of diarrhea lasted a mean of 3 d, and those of dysentery and ARI, 5 d. The two treatment groups did not differ in the number of episodes, mean duration of each episode, or total days of illnesses due to diarrhea, dysentery and ARI.

However, a 49% greater number of episodes of dysentery was observed with iron supplementation in a subset of the study children who were less than 12 mo old.

Long-term oral iron supplementation is not harmful for older children in a poor community. Further studies are needed to demonstrate the safety and efficacy of iron administration in young infants.

Mitra AK et al., Long-term oral supplementation with iron is not harmful for young children in a poor community of Bangladesh. J Nutr, 127:1451-5, 1997 Aug.

Linoleic acid

Linoleic Acid Inhibition of E-Coli

Escherichia coli is responsible many times for outbreaks of infantile enteritis in developing countries. The ability of E-coli to to mucosal cells is related to its virulence

Linoleic acid inhibits the adhesion of the bacteria. Linoleic acid inhibited nineteen different strains of E-coli. Linoleic acid deficiency is definitely present in malnourished children in developing countries and this could be a predisposing factor to E-coli dependent diarrhea. Supplementation of common foodstuff with vegetable oils which are high in linoleic acid may help prevent the colonization of e. coli on the intestinal mucosa and decrease the incidence of infantile diarrhea.

"Linoleic Acid Inhibition of Adhesion of Enteropathogenic Escheria Coli to HEp-2 Cells", Chart, Henrik, et al, The Lancet, July 13, 1991;338:126-127.

Normal mucosa

Determined the practice of routine rectal biopsy in the United Kingdom, and assess the diagnostic yield and complications of rectal biopsy in patients presenting with diarrhea.

Ninety five (35%) consultants "nearly always" biopsy normal looking mucosa, with a further 56 (20%) taking a biopsy in more than fifty percent of cases. Fifty five (20%) almost never biopsy if the mucosa looks normal, with 68 (20%) taking a biopsy less than fifty percent of the time.

Biopsies were taken from 50 patients referred with diarrhea whose rectal mucosa looked normal. Abnormal histology was reported in 11 (22%) cases. The rectal biopsy led to a positive diagnosis and change in management in 4 (8%) cases. The remaining biopsies showed minor inflammatory changes that were not considered clinically important. One significant complication occurred due to rectal biopsy.

Clinicians disagree on the value of routine rectal biopsy in the investigation of diarrhea. In patients presenting with diarrhea, the diagnostic yield from biopsy of normal looking rectal mucosa is low. Life threatening complications can occur and in unselected patients routine biopsy should not be performed.

Robinson RJ et al., Normal rectal mucosa. Should we biopsy? Hepatogastroenterology, 44:703-5, 1997 May-Jun.

Optimal nutrition

Nutritional support of the seriously ill patient has evolved with time and reflects new developments in the field of critical care. Current information suggests that optimal nutritional support can be provided by supplying at least 80% of energy requirements with at least 70% of the energy given as carbohydrate and the remaining 30% or less administered as fat (with > or = 3% of energy requirements as essential fatty acids).

The caloric load may be reduced to 50% of requirements if growth factors (e.g., growth hormone) are utilized and the patient has adequate fat stores.

Protein should be given as 1.5 g/kg/day; more catabolic patients, such as patients with burn injury, should receive 2 g/kg/day.

All protein or amino acid feeding should include glutamine. There is an increased need for vitamins (especially A, C, and E) and minerals (zinc, selenium, and magnesium).

The preferred route of feeding should be enteral, followed by enteral plus supplemental parenteral nutrition. If the gastrointestinal tract cannot be used, parenteral nutrition should be given. Nutrients should be administered early in the catabolic course, especially glucose, sodium, potassium, vitamins, and minerals.

Over time (approximately 7 days) amino acids should be added and approximately 50% of caloric support should be provided. Finally, full nutritional support should be provided (by 7 to 10 days) if the catabolic course is expected to continue.

DeBiasse MA & Wilmore DW: What is optimal nutritional support? New Horiz, 2:122-30, 1994 May.

Risk factors & diarrhea

Data collected in a case-control study of risk factors for dehydrating diarrhea in infants have been used to present a hierarchized approach to the assessment of risk factors.

The final model resulted in a gamma of 0.74. The children's ages did not improve the prediction of cases and controls, but they have been kept in the model as they affect some exposures such as breastfeeding.

Fuchs SC et al., [Hierarchical model: a proposal for a model to be applied in the investigation of risk factors for severe diarrhea]. Rev Saude Publica, 30:168-78, 1996 Apr.

Traveler's diarrhea

Traveler's diarrhea (1)

Traveler's diarrhea occurs with considerable frequency in individuals traveling to underdeveloped countries. It is acquired through the ingestion of fecally contaminated food and water. Traveler's diarrhea is caused by a variety of bacterial, protozoal, viral, and parasitic organisms.

Typically self-limiting, traveler's diarrhea is more of an inconvenience than a life-threatening process.

Patient education is an important element in the management of traveler's diarrhea; the well-informed traveler can manage most cases empirically without sophisticated medical technology. The presence of fever, bloody stool, abdominal pain, or profound dehydration indicates a more severe infection requiring medical attention.

Larson SC: Traveler's diarrhea. Emerg Med Clin North Am, 15:179-89, 1997 Feb.

Traveler's diarrhea (2)

Most patients with traveler's diarrhea can be efficiently treated with available pharmacological agents.

A more difficult problem is the persistent diarrhea (lasting > or = 14 days) that occurs in approximately 3% of travelers who have acute diarrhea. In the initial evaluation of these patients, ideally three stool samples should be obtained for examination for pathogens. If an agent is not identified or the patient has not responded to specific therapy, he or she may be empirically treated with an antimicrobial drug directed toward common bacterial enteropathogens, if such treatment has not already been administered.

For those patients whose conditions do not respond, antiprotozoal therapy may be employed empirically. If diarrhea continues, then an endoscopic evaluation is indicated, and specific treatment can be given if an agent or condition is identified. A proportion of patients will continue to have diarrhea following empirical therapy and a gastroenterologic workup. These individuals are best given symptomatic treatment and reassured that the prognosis is good.

DuPont HL & Capsuto EG: Persistent diarrhea in travelers. Clin Infect Dis, 22:124-8, 1996 Jan.

Zinc supplementation

Zinc supplementation (1) INDIA

Determined whether daily zinc supplementation reduces the incidence and prevalence of acute diarrhea, especially in those with zinc deficiency.

Children 6-35 mo of age were randomly assigned to zinc (n = 286) and control (n = 293) groups and received a supplement daily for 6 mo. Zinc gluconate (10 mg elemental Zn) was given, with both zinc and control groups also receiving multivitamins.

The primary outcome measures determined by home visits every fifth day and physician examinations were the number of acute diarrheal episodes (incidence) and total diarrheal days (prevalence). Zinc supplementation had no effect in children 6-11 mo old.

In children aged > 11 mo there was significantly less diarrhea in the zinc group. In boys > 11 mo old, supplementation resulted in a 26% lower diarrheal incidence and a 35% lower prevalence. In zinc-supplemented girls > 11 mo of age, the incidence was 17% lower and the prevalence was 19% lower.

Overall, zinc supplementation resulted in a 17% lower diarrheal incidence in children with plasma zinc concentrations < 9.18 mumol/L at enrollment and a 33% lower incidence in children with concentrations < 50 mumol/L.

Zinc supplementation had a significant effect on acute diarrheal morbidity in children > 11 mo old and in children with low plasma zinc concentrations.

Sazawal S et al., Efficacy of zinc supplementation in reducing the incidence and prevalence of acute diarrhea--a community-based, double-blind, controlled trial. Am J Clin Nutr, 66:413-8, 1997 Aug.

Zinc supplementation (2) (Guatemala)

Measure the impact of zinc supplementation on young Guatemalan children's morbidity from diarrhea and respiratory infections.

High rates of diarrhea and respiratory infections were reported. Children from the placebo group had a 20% episodic prevalence of diarrhea, with 8 episodes/100 d, and a 7% episodic prevalence of respiratory infections, with 3 episodes/100 d.

The median incidence of diarrhea among children who received zinc supplementation was reduced by 22% (Wilcoxon rank test), with larger reductions among boys and among children with weight-for-length at baseline lower than the median of the sample (39% reductions in both subgroups).

Zinc supplementation also produced a 67% reduction in the percentage of children who had one or more episodes of persistent diarrhea.

No significant effects were found on the episodic prevalence of diarrhea, the number of days per episode, or the episodic prevalence or incidence of respiratory infections.

The large impact of zinc supplementation on diarrhea incidence suggests that young, rural Guatemalan children may be zinc deficient and that zinc supplementation may be an effective intervention to improve their health and growth.

Ruel MT et al., Impact of zinc supplementation on morbidity from diarrhea and respiratory infections among rural Guatemalan children. Pediatrics, 99:808-13, 1997 Jun.

Antibiotics

Antibiotics

A recent Harvard study notes that Vitamin C inhibits bacterial resistance to antibiotic therapy and might reduce the dose of antibiotics necessary to effectively suppress bacterial growth

"Vitamin C Enhances Antibiotic Therapy", The Nutrition Report, April, 1992;10(4):3 1/"Decreased Resistance to Antibiotics and Plasmid Loss in Plasmid-Carrying Strains of Staphylococcus Aureus Treated With Ascorbic Acid", Mutation Research, 199 1;264:119-125.

In a study evaluating the relationship between vitamin C intake and mortality in 11,3 84
noninstitutionalized adults aged 25 to 74 years who were nutritionally examined, with follow up, found
there was an inverse relationship between vitamin C intake and the standard mortality ration which was
strong for males and weak for females. The findings were generally consistent with earlier cohort studies
showing a reduced overall mortality associated with increased dietary vitamin C intake. Even if
increased vitamin C per se only has a small beneficial effect, the total population impact would be quite
substantial because of the large variations in vitamin C intake and widespread use of vitamin C
supplements.         1

"Vitamin C Intake and Mortality Among a Sample of the United States Population", Enstrom, James E., Epidemiology, May 1992;3(3):195-202.

500 mg of ascorbic acid given with every 250 mg of tetracycline increased tetracycline blood levels at 2 hours 3 to 15 fold compared to tetracycline administration alone. Vitamin C therapy in conjunction with tetracycline medications may reduce the duration of their use and allow for lower doses of this family of antibiotics to be used thereby reducing potential side effects.

"Adjunctive Ascorbic Acid Administration and Antibiotic Therapy", Freinberg, N. and Lyte, T., Journal of Dental Research, 1957;36: 260-262. "Vitamin C Potentiates Antibiotic Therapy", Gaby, A, Townsend Letter for Doctors, August/September 1990;523

In this study of 9 volunteers, after 2 weeks at a dose of 2g/day blood histamine levels fell by 40 per cent. It is noted that at the 500mg dose, the level of vitamin C achievable by a conscientious diet, there was not a histamine reducing effect.

"Antihistamine Effects and Complications of Supplemental Vitamin C", Johnston, CS et al, J of the American Dietetic Association, August 1992;92(8):988-989.

Psyllium

Psyllium

This study demonstrated that psyllium reduces the acceleration of colon transit time, possibly by delaying the production of gaseous fermentation products. Small bowel transit time was unaltered. Progression through the colon was delayed with an increase in the percentage of the dose at 24 hours in the ascending and transverse colon with correspondingly less in the descending colon. Psyllium significantly delayed the rise in breath-hydrogen concentrations.

Washington, Neena, et al: Moderation of Lactulose- Induced Diarrhea by Psyllium: Effects on Motility and Fermentation, American Journal of Clinical Nutrition, 1998;67:317-321.

Zinc and Vitamin A Supplementation

Zinc and vitamin A supplementation

A combination of zinc and vitamin A supplements may reduce persistent diarrhea and dysentery in children, according to this randomized, double-blind placebo controlled study conducted on 800 children in Bangladesh. For two weeks, the children (aged 12-35 months) were given either 20 mg zinc once a day, a single dose of 200,000 IU vitamin A on day 14, a combination of zinc and vitamin A, or placebo. Weekly follow ups, in which the incidence and prevalence of diarrhea and the occurrence of acute lower respiratory infection were recorded, were performed over a period of six months. The group of children who received the combination of zinc and vitamin A had less prevalence of diarrhea than those in the control group. The group who received only zinc had an increased occurrence of acute lower respiratory infection, while the group who received the combination of zinc and vitamin A did not. This suggests that the interaction between zinc and vitamin A hinders zinc's ability to increase susceptibility to respiratory infection.

Rahman MM, Vermund SH, Wahed MA, Fuchs GJ, Baqui AH, Alvarez JO: Simultaneous zinc and vitamin A supplementation in Bangladeshi children: randomized double blind controlled trial, BMJ 2001 Aug 11;323(7308):314-8