GI Modifiers: Hydrocolloids

Summary

Gastrointestinal Modifiers Hydrocolloids

definition: Many medicinal and food herbs contain soluble fiber. Plant soluble fiber is chemically divided into the hydrocolloidal gums and mucilages that absorb water to form soluble gels, and other soluble fiber including pectins, cellulose and hemicelluloses which are not hydrophilic and are hydrolyzed by colonic flora. Soluble fiber is distinguished in turn from the insoluble fiber or lignin, i.e., the woody parts which humans cannot digest.

hydrocolloids - chemistry:
Gums and mucilages cannot be clearly distinguished on chemical grounds, both being hydrophilic polysaccharides; glucuronates which exist as salts, the cations being calcium, magnesium and potassium. Hydrolysis of mucilages and gums yields pentoses and hexoses, the most common being arabinose, galactose, mannose, rhamnose, xylose and glucose. They are distributed widely, especially among the Boraginaceae (Borage), Malvaceae (Mallow), Linaceae (Flax) and Algae (Seaweed) families. The chemistry of the degradation products of gums and mucilages is less important pharmacologically than the physical properties of the intact compounds. These are principally their ability to retain water and form a gel which can physically coat the mucosal surface with a mucilaginous layer (sometimes described as "slime").

Hydrocolloids are used with concurrent water intake as gentle bulk laxatives, or without water to bind excessively fluid bowel contents in diarrhea. They are likely to alter nutrient and drug absorption partly through increasing the viscosity of intestinal contents, and partly by forming a physical coating of mucilage over the mucosa reducing the available surface area and lowering the rate of absorption. They have been used to slow the rate of absorption of oligosaccharides and other sugars in reactive hypoglycemics/glucose intolerant patients, as well as to reduce the absorption of cholesterol in hyperlipidemia. Some gums (e.g. tragacanth gum from Astragalus gummifer) are used in pharmacy as excipients in pill manufacture, or emulsifiers and thickeners.

overview of pharmacokinetic interactions:

• mechanisms: Hydrocolloids may reduce the rate of absorption of many medications by lowering the mucosal surface area available for absorption by forming a semipermeable coating, by binding the intestinal contents into a viscous mass, and by delaying gastric emptying. Several pharmaceuticals are known to be affected by concurrent soluble fiber ingestion, but as a general rule, it would be prudent to assume reduced absorption of any medication if ingested with hydrocolloids. Hydrocolloid ingestion may be dietary or therapeutic, as in the case of bulk laxatives, typically Psyllium seed. In either case, medications should be orally administered at least an hour before hydrocolloid intake.

overview of interactions:

• food/herb positively affecting drug toxicity: Calcium Channel Blockers

• nutritional concern: Colestipol and other Bile Acid Sequestrants

• food/herb affecting drug performance: Digoxin

• food/herb affecting drug performance: Hydralazine

• food/herb affecting drug performance: Insulin

• food/herb affecting drug performance: Lithium

• food/herb affecting drug performance: Lovastatin

• food/herb affecting drug class performance: Sulfonylureas



Herbs

food/herb positively affecting drug toxicity: Calcium Channel Blockers

• mechanism: Individuals taking calcium channel blockers often complain of constipation as an undesirable side effect of taking such drugs. Verapamil is especially known to inhibit colonic motor activity, reduce colonic transit, and increase water absorption.
(Bassotti G, et al. Dis Colon Rectum 1998 Mar;41(3):377-380; Krevsky B, et al. Dig Dis Sci 1992 Jun;37(6):919-924; Threlkeld DS, ed. Nov 1992.)

• nutritional support: Individuals taking calcium channel blockers may be able to reduce drug-induced constipation by increasing daily intake of fiber and fluid, especially water.

nutritional concern: Colestipol and other Bile Acid Sequestrants

• mechanism: Bile acid sequestrants, such as colestipol, often cause adverse effects such as abdominal bloating and may produce or worsen pre-existing constipation. Constipation may aggravate hemorrhoids.

• research: Research by Spence et al suggests that adding psyllium to half the usual dose of bile acid sequestrant resins maintains the efficacy and improves the tolerability of these resins.
(Spence JD, et al. Ann Intern Med 1995 Oct 1;123(7):493-499.)

• nutritional support: Individuals taking colestipol would most likely benefit from increased fluid and fiber intake alleviate the constipation. Psyllium seed husk could be particularly beneficial, but only with proportionately increased water intake.

food/herb affecting drug performance: Digoxin

• mechanism: Hydrophilic fiber slows absorption of oral drugs and specifically reduces absorption of digoxin; most studies thus far have indicated that the clinical implications of this reduced absorption may be negligent.
(Huupponen R, et al. Eur J Clin Pharmacol 1984;26(2):279-281; Johnson BF, et al. J Clin Pharmacol 1987 Jul;27(7):487-490.)

food/herb affecting drug performance: Hydralazine

• mechanism: Hydralazine absorption and/or disposition kinetics may be altered by food, especially foods such as fiber that would slow the rate of nutrient absorption.
(Semple HA, et al. Ther Drug Monit 1991 Jul;13(4):304-308.)

food/herb affecting drug performance: Insulin

• mechanism: Diets containing large quantities of some hydrocolloidal fiber sources can delay gastric emptying and reduce the rate of absorption of dietary carbohydrates.

• nutritional concerns: Insulin requirements for diabetics using such fiber sources need to be closely monitored and dosages may need to be modified due to changes in glucose absorption.

food/herb affecting drug performance: Lithium

• mechanism: Hydrophilic fiber such as Psyllium can reduce absorption of lithium taken orally.

• reports: There have been reports of individuals taking lithium who experienced decreased lithium levels after they started consuming psyllium husk, in one case two times per day; lithium levels increased to therapeutic levels after stopping the psyllium.
(Toutoungi M, et al. Therapie1990 Jul-Aug;45(4):358-60; Perlman BB. Lancet 1990 Feb 17;335(8686):416.)

• nutritional concerns: Adverse effects from this interaction can usually be avoided by taking the lithium at least one hour before the psyllium or other dietary fiber.

food/herb affecting drug performance: Lovastatin

• mechanism: Research indicates that dietary fiber, from foods such as oatmeal or fruit, can reduce gastrointestinal absorption, and thereby effectiveness, of lovastatin by binding the drug. The resulting reduction in effectiveness could increase LDL cholesterol levels.
(Pronsky ZM. 1995, 121.)

• report: Richter et al have reported that fruit pectin and oat bran have a particular tendency to interact with lovastatin.
(Richter W, et al. Lancet 1991;Sep 14;338(8768):706.)

• dietary concerns: While the consumption of oat bran and whole fruit might in themselves contribute to lowering cholesterol, individuals taking lovastatin should separate taking the drug from the consumption of foods high in soluble fiber by at least two hours. Foods high in soluble fiber include fruit, oats and beans; oat bran, pectin and glucomannan are highly concentrated fiber sources.

food/herb affecting drug class performance: Sulfonylureas

• nutritional synergy: The co-administration of guar gum significantly enhances the insulinogenic and blood glucose lowering effect of glyburide, and possibly other sulfonylurea drugs. If taken at the same time as the medication, guar gum may reduce the dosage of the drug needed or, if unsupervised, could potentially cause blood glucose levels to drop excessively.
(Huupponen R. Res Commun Chem Pathol Pharmacol 1986 Oct;54(1):137-140; Neugebauer G, et al. Beitr Infusionther Klin Ernahr 1983;12:40-47; Uusitupa M, et al. Int J Clin Pharmacol Ther Toxicol 1990 Apr;28(4):153-157.)

Common food/medicinal plants with high hydrocolloid content:
• Acacia senegal (Gum Arabic)
• Aloe spp. (Aloe gel)
• Althaea officinalis (Marshmallow)
• Astragalus gummifera (Tragacanth gum)
• Avena sativa (Oat seed, Oat Bran)
• Ceratonia siliqua (Locust [carob] seed gum)
• Cetraria islandica (Iceland Moss lichen)
• Chondrus crispus (Carageen)
• Cyamopsis tetragonolobus (Guar gum)
• Gelidium spp., Gracilaria spp. and others (Agar agar [red algae] )
• Laminaria spp., Macrocystis spp. (Alginic acid [brown algae])
• Linum utissitatum (Flax seed )
• Malus spp. (Pectin powder)
• Plantago ovata (Psyllium seed)
• Prosopis spp. (Mesquite gum)
• Prunus spp. (Cherry gum)
• Sterculia urens (Sterculia gum)
• Symphytum officinale (Comfrey)
• Ulmus fulva (Slippery Elm)

Please read the disclaimer concerning the intent and limitations of the information provided here.
Do not rely solely on the information in this article.

References

Bassotti G, Calcara C, Annese V, Fiorella S, Roselli P, Morelli A. Nifedipine and verapamil inhibit the sigmoid colon myoelectric response to eating in healthy volunteers. Dis Colon Rectum 1998 Mar;41(3):377-380.
Abstract: BACKGROUND: Constipation is not an infrequent side effect complained of by patients taking calcium channel blockers. This effect may reduce patients' compliance and yield potentially serious consequences. However, the underlying mechanisms for constipation caused by such compounds are not known. AIMS: The purpose of the present study was to assess the effects of nifedipine and verapamil on the sigmoid myoelectric response to eating, a physiologic test of colonic motor function. SUBJECTS AND METHODS: Nine healthy male volunteers with no previous abdominal surgery were recruited for the study and underwent three paired studies at two-week intervals. Myoelectric sigmoid activity was recorded by means of two clip electrodes introduced within the viscus without preparation for 30 minutes basally and 90 minutes postprandially. Each study was preceded by placebo, nifedipine (20 mg), or verapamil (120 mg). RESULTS: Analysis of the tracings revealed that nifedipine strongly inhibited the sigmoid myoelectric response to the meal. This response was also significantly reduced in those taking verapamil compared with the placebo group, although to a much lesser extent than in those taking nifedipine. CONCLUSIONS: We conclude that constipation as a result of some calcium channel blockers may be caused by inhibition of colonic motor activity by nifedipine and, to a lesser extent, by verapamil. The latter compound probably displays other mechanisms (reduced colonic transit, increased water absorption) also responsible for this side effect.

Huupponen R, Seppala P, Iisalo E. Effect of guar gum, a fibre preparation, on digoxin and penicillin absorption in man. Eur J Clin Pharmacol 1984;26(2):279-281.
Abstract: The effect of guar gum on the absorption of digoxin and phenoxymethyl penicillin was studied in a double blind study in 10 healthy volunteers. Guar gum reduced serum digoxin concentration during the early absorption period, but a similar amount of digoxin was found in 24 h urine whether given with or without guar gum. Both the peak penicillin concentration and the area under the serum curve were significantly reduced by the gum.

Johnson BF, Rodin SM, Hoch K, Shekar V. The effect of dietary fiber on the bioavailability of digoxin in capsules. J Clin Pharmacol 1987 Jul;27(7):487-490.
Abstract: Sixteen healthy volunteers were regularly given 0.4 mg of digoxin daily as two capsules with breakfast. After ten days during which breakfast was supplemented with 11 g of bran fiber, steady-state predose mean serum digoxin was lower (0.89 +/- 0.19 versus 0.84 +/- 0.18 ng/mL, P less than .05) and mean 24-hour area under curve determination was lower (30.5 +/- 6.1 versus 28.4 +/- 6.0 ng X hr/mL, P less than .05) than during the control period without bran. Height and time of peak serum digoxin, and 24-hour urinary digoxin were not significantly different. The 6 to 7% reduction in digoxin absorption from capsules is less than that reported from tablets and is probably clinically unimportant.

Krevsky B, Maurer AH, Niewiarowski T, Cohen S. Effect of verapamil on human intestinal transit. Dig Dis Sci 1992 Jun;37(6):919-924.
Abstract: Although constipation is a well-known side effect of calcium channel blockers such as verapamil, this side effect has not been evaluated in a quantitative manner. In a double-blind, randomized, crossover trial, the effect of verapamil (240 mg/day) was compared to placebo in 15 normal male volunteers. Subjects recorded their bowel movements and any side effects. Scintigraphy was used to quantitate gastric emptying, small intestinal transit, and colonic transit. In the study period of four days, verapamil did not change the frequency, consistency, or passage of bowel movements. A significantly increased number of side effects was noted during verapamil treatment--notably abdominal pain and dry mouth. The slope of gastric emptying was not significantly different for verapamil (0.012 +/- 0.02) than for placebo (0.013 +/- 0.001). Distal ileum filling was also not different for verapamil (0.41 +/- 0.13%/min) than placebo (0.33 +/- 0.05%/min). Progression of the colonic geometric center was significantly delayed at 48 hr by verapamil (5.2 +/- 0.4 vs 6.2 +/- 0.23; P less than 0.01). This study suggests that the constipating effect of verapamil is due to a delay of colonic transit and not due to an effect on upper gastrointestinal transit.

Perlman BB. Interaction between lithium salts and ispaghula husk. Lancet 1990 Feb 17;335(8686):416. (Letter)

Neugebauer G, Akpan W, Abshagen U. [Interaction of guar with glibenclamide and bezafibrate]. Beitr Infusionther Klin Ernahr 1983;12:40-47. [Article in German]

Pronsky Z. Powers and Moore's Food-Medications Interactions. Ninth Edition. Pottstown, PA. Food-Medication Interactions, 1991.

Richter W, Jacob B, Schwandt P. Interaction between fibre and lovastatin. Lancet 1991;Sep 14;338(8768):706. (Letter)

Semple HA, Koo W, Tam YK, Ngo LY, Coutts RT. Interactions between hydralazine and oral nutrients in humans. Ther Drug Monit 1991Jul;13(4):304-308.
Abstract: To help clarify whether food or enteral nutrients decrease hydralazine relative bioavailability, eight subjects were given oral hydralazine under four nutritional conditions: fasted (F), with a standard breakfast (SB), with a bolus of enteral nutrients (EB), and with a slow infusion of enteral nutrients administered by nasogastric tube (EI). The area under the curve and maximum concentration values were much higher under the fasted and enteral infusion conditions than under the standard breakfast or enteral bolus conditions, indicating that the absorption and/or disposition kinetics of hydralazine may be altered by food. The median (range) values for these parameters were 2,641 (385-4,747) and 87 (4.5-224) for F; 1,189 (202-1,737) and 15 (3.5-33.9) for SB; 999 (227-3,576) and 11 (2.5-50) for EB; and 3,068 (313-4,917) ng/ml/min and 113 (3.6-235) ng/ml for EI. Furthermore, the rate of nutrient administration, but not necessarily the physical form, of the nutrients appears to be a significant factor in determining the magnitude of the food effect. The nutrient interaction should be accounted for in patients receiving hydralazine and enteral nutrition concomitantly.

Spence JD, Huff MW, Heidenheim P, Viswanatha A, Munoz C, Lindsay R, Wolfe B, Mills D. Combination therapy with colestipol and psyllium mucilloid in patients with hyperlipidemia. Ann Intern Med 1995 Oct 1;123(7):493-499.
Abstract: OBJECTIVE: To test whether combining psyllium mucilloid with half the usual dose of colestipol reduces the adverse effects associated with colestipol and maintains or increases its efficacy in the treatment of hyperlipidemia. This strategy might make bile acid sequestrants, which are seldom used because they cause adverse effects such as bloating and constipation, more tolerable and less expensive. DESIGN: A randomized, parallel-group, double-blind, controlled trial. SETTING: An outpatient clinic in a tertiary care hospital. PATIENTS: 121 patients who had moderate primary hypercholesterolemia (total cholesterol level > 6 mmol/L and < 8 mmol/L; triglyceride level < 3 mmol/L) after following a low-fat diet for 1 year (National Cholesterol Education Program Step Two diet). INTERVENTION: 5 g of cellulose placebo; 5 g of colestipol; 2.5 g of colestipol plus 2.5 g of psyllium; or 5 g of psyllium three times daily before meals for 10 weeks. MAIN OUTCOME MEASURES: At baseline and at weeks 4 and 10, fasting blood lipid levels and apoprotein concentrations were measured and a quality-of-life instrument was completed. RESULTS: A combination of 2.5 g of psyllium and 2.5 g of colestipol was better tolerated than and as effective as either 5 g of colestipol alone or 5 g of psyllium alone. The combination therapy and colestipol alone did not differ significantly with respect to changes in individual lipid values. The ratio of total cholesterol to high-density lipoprotein cholesterol (HDL) was reduced by 18.2% (95% CI, 12.3% to 24%) with the combination therapy; by 10.6% (CI, 2.0% to 15.4%) with colestipol alone; by 6.1% (CI, 1.5% to 10.6%) with psyllium alone; and by 0.1% (CI, -4.8% to 7%) with placebo (P = 0.0002). Combination therapy reduced the ratio of total cholesterol to HDL significantly more than did colestipol alone or psyllium alone (P < 0.05). CONCLUSIONS: These findings suggest that adding psyllium to half the usual dose of bile acid sequestrant resins maintains the efficacy and improves the tolerability of these resins.

Toutoungi M, Schulz P, Widmer J, Tissot R. [Probable interaction of psyllium and lithium]. Therapie 1990 Jul-Aug;45(4):358-360. [Article in French] (Letter)

Threlkeld DS, ed. Diuretics and Cardiovasculars, Calcium Channel Blocking Agents. In: Facts and Comparisons Drug Information. St. Louis, MO: Facts and Comparisons, Nov 1992.

Uusitupa M, Sodervik H, Silvasti M, Karttunen P. Effects of a gel forming dietary fiber, guar gum, on the absorption of glibenclamide and metabolic control and serum lipids in patients with non-insulin-dependent (type 2) diabetes. Int J Clin Pharmacol Ther Toxicol 1990 Apr;28(4):153-157.
Abstract: Nine patients with non-insulin-dependent diabetes (NIDDM) treated with glibenclamide (3.5 mg b.i.d.) participated in this randomized double-blind placebo controlled crossover study to evaluate the effects of granulated guar gum (5 g t.i.d. with meals) on the absorption of glibenclamide and metabolic control and serum lipids. Each treatment period lasted for 4 weeks, and there was a wash-out period of one week between the treatments. The fasting blood glucose (10.5 +/- 3.4 mmol/l on guar gum vs 11.3 +/- 3.7 mmol/l on placebo, p less than 0.05) and serum total cholesterol (5.9 +/- 1.4 mmol/l on guar gum vs 6.6 +/- 1.6 mmol/l on placebo; p less than 0.05) levels were lower after the treatment with guar gum than placebo. No significant differences were observed in serum triglycerides or HDL cholesterol between guar gum and placebo treatments. The administration of guar gum together with glibenclamide did not change significantly the maximum concentration (223 +/- 196 ng/ml on guar gum vs 184 +/- 138 ng/ml on placebo; n = 7, NS) or area under the curve (AUC0-6) [729 +/- 813 (ng/ml) X h on guar gum vs 560 +/- 513 (ng/ml) X h on placebo; NS] of glibenclamide. The fasting serum glibenclamide concentrations were similar at the end of the 4-week treatment period with guar gum and placebo. In conclusion, guar gum improved the metabolic control and decreased serum lipids of patients with NIDDM. In addition, guar gum ingested with glibenclamide did not interfere with the absorption of glibenclamide.