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Pectin

Common Name(s): Pectin

Clinical Overview

Use

Pectin has been used in antidiarrheal products and to lower blood lipoprotein levels. Pectin also has been investigated for its effects on cancer, diabetes, and gastroesophageal reflux disease/gastric ulceration. However, quality clinical trials are lacking.

Dosing

Pectin and/or modified pectin have been used in clinical studies in doses of 10 to 20 g daily.

Contraindications

Contraindications have not yet been identified.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

Coadministration of pectin with beta-carotene–containing foods or supplements can reduce blood levels of beta-carotene by more than 50%.

Adverse Reactions

Pectin is generally well tolerated when ingested. Occupational asthma has been associated with the inhalation of pectin dust. A cross-sensitivity to cashew and pistachio nuts may exist.

Toxicology

No major toxicities have been reported with the use of pectin.

History

Pectin is found in the cell walls of all plant tissue, where it acts as an intercellular cement, giving the plant structural rigidity. The compound is found at concentrations of 15% to 30% in the fiber of fruits, vegetables, legumes, and nuts.1 Lemon and orange rinds are among the richest sources of pectin, containing up to 30% of this polysaccharide.2 Pectin is also found in the roots of most plants. 3

French scientists Henri Braconnot and Anselme Payen were the first to discover pectins in 1825.4, 5 Braconnot named it "pectic acid," based on an ancient Greek word meaning "coagulant."4 Pectin has been used in the food industry to add body and texture to jellies, jams, puddings, and other gelatinous products. It has also been added to antidiarrheal products and has been particularly effective when combined with adsorbing clays, such as kaolin.

Chemistry

Pectins are polysaccharides with a molecular weight range from 20,000 to 400,000 daltons, depending on the number of carbohydrate monomers.2 Pectin is a fermentable fiber that results in the production of short-chain fatty acids and methane.6, 7 The simplest type of pectin is a linear polymer of galacturonic acid, a water-soluble viscous fiber8, 9 that is connected with alpha (1→4) bonds.9 More complex pectins are formed by linked D-polygalacturonate and L-rhamnose residues. The neutral sugars D-galactose, L-arabinose, D-xylose, and L-fucose may form side chains on some pectin molecules. Once extracted, pectin occurs as a coarse or fine yellowish powder that is highly water soluble and forms thick colloidal solutions. In the presence of calcium ions, pectin forms a gel that is more resistant to disruption in the gut than alginate gel.3 Additionally, when there is a low degree of esterification, the mucoadhesive capacity of pectin is important along the GI tract.10 The parent compound, protopectin, is insoluble but is readily converted by hydrolysis into pectinic acids (also known generically as pectins).11

Pectin that has been pH-modified into smaller, less complex molecules is called modified citrus pectin. This modification allows better dissolution in water and more complete absorption by the body.12

Uses and Pharmacology

Cancer

The association between pectin's complex structure and its activity against cancer is difficult to assess because of differences in origin and chemical modifications to pectin used in studies are not well described.4 Dietary fiber has been associated with a reduction in the risk of colon cancer4; however, this association has been questioned in a pooled analysis of prospective cohort studies.13 After accounting for other dietary risk factors, no association with a lowered risk of colorectal cancer was found, and analysis of specific food sources also found no association.13

Modified pectin has been evaluated for efficacy in cancer treatment. The mechanisms by which pectins may exert their effect include the ability to bind to cancer cell surface galectins (galactose-binding lectins), causing mitochondrial disruption, enhancing response to chemotherapy, and impeding metastasis.4, 14, 15, 16, 17, 18, 19, 20 Consequent interference with cell-cell or cell-matrix adhesion and induction of apoptosis has been described.15 Pectin-derived galectin-3 receptor binding agents (GBC-590 and GCS-100) have entered phase 2 trials.14, 17

Animal/In vitro data

Modified citrus pectin was studied in a rat model of prostate cancer metastasis. Although primary tumor growth was not affected, metastasis was reduced when compared with control.21 In mice with either human breast cancer cells or human colon cancer cells, modified citrus pectin was found to decrease tumor growth and weight, angiogenesis, and metastasis.20 In vitro experiments have demonstrated the efficacy of modified pectin in inducing apoptosis in human prostate cell lines15 and inhibiting cell proliferation in skin, colon, lung, and melanoma lines.22

Clinical data

A nonrandomized intervention study using modified citrus pectin demonstrated a statistically significant increase in prostate-specific antigen (PSA)–doubling time in 7 of 10 patients with refractory prostate cancer.12, 16 Survival times were not measured in this study, but a slowing of disease progression was postulated based on the increase in PSA-doubling time. Phase 2 trials have evaluated the effect of pectin-derived galectin-3 receptor binding agents in refractory or relapsed colorectal and pancreatic cancer, reporting tumor stabilization and reduction of tumor growth in some patients.14, 17

Cardiovascular

Animal/In vitro data

In a study of Zucker rats, fatty rats fed a 10% methoxylated pectin-based diet experienced a reduction in triglyceride levels as well as an increase in high-density lipoprotein (HDL) cholesterol levels.23

Clinical data

Despite many large trials evaluating the effect of dietary fiber on cardiovascular outcomes, few have specifically investigated the role of pectin, and controversy remains regarding its efficacy in affecting the lipid profile.24, 25, 26, 27 Most studies have evaluated pectin in combination with other gums and results have varied, with some showing decreases in total cholesterol level and triglycerides (although HDL cholesterol levels remained unaffected) and others failing to demonstrate lower cholesterol in hypercholesterolemic patients.28, 29, 30, 31, 32 Results have also varied in trials evaluating the effect of pectin alone on serum lipids.25, 33, 34, 35, 36 A meta-analysis of the cholesterol-lowering effects of dietary fiber (comparison of pectin, oat bran, guar gum, and psyllium) showed that increasing soluble fiber may make only a small contribution to lowering cholesterol.27 Results from 1 clinical trial found that pectin source and characteristics such as degree of esterification impacted cholesterol-lowering ability. Citrus and apple pectins with a higher degree of esterification were more effective than pectins from the same source with lower esterification, and citrus and apple pectins lowered cholesterol more effectively than orange pulp fiber pectin.37 Mechanisms of action have been investigated and include an ability to protect against low-density lipoprotein (LDL) peroxidation,38, 39 upregulation of HDL metabolism,26 and a higher water-holding capacity of pectin compared with cereals or bran.26 Systolic blood pressure decreased in adults treated with pectin versus placebo in a double-blind, randomized clinical trial,33 whereas hypertension remained unaltered in another study.40 No significant changes were seen for inflammatory markers of high-sensitivity C-reactive protein or homocysteine in 1 clinical trial.37 Apple pectin was similar to aspirin for reduction in severity and duration, but not incidence, of niacin-induced flushing.41

Chelating effects

Animal/In vitro data

In an in vitro model, calcium pectate exhibited metal-binding properties.42 In a study of rats, lead accumulation in organs such as the kidneys, liver, and heart was reduced with calcium pectate administration. Lead accumulation was also reduced in the femur.42

Clinical data

Modified citrus pectin 15 g/day significantly increased the urinary excretion of arsenic, cadmium, and lead in adults with a normal metal load) after 6 days of administration,43 a chelating effect attributed to the presence of rhamnogalacturonan in pectin.43 In children from Belarus with moderate and high cesium loads, the administration of apple-derived pectin (Vitapect) 10 g/day reduced cesium levels.40, 44 Beneficial effects on the antioxidant level of hematologic systems have also been demonstrated.45

Diabetes

Animal/In vitro data

In a study of Zucker rats, fatty rats fed a highly methoxylated pectin diet experienced a reduction in blood glucose starting at the third study week. By the end of the study, there were no differences between the fatty rats receiving the pectin-based diet and lean rats. Additionally, fatty rats receiving the pectin-based diet had reduced plasma insulin concentrations comparable with those in the lean rats.23

Clinical data

Meals high in soluble fiber have increased satiety and reduced the rise in postprandial blood glucose and insulin concentrations.25, 46 However, the few trials specifically evaluating the effect of pectin on markers of diabetes have been less convincing. No change in fasting plasma glucose levels and no effect on postprandial glucose response were noted in healthy adults or adults with dietary-controlled type 2 diabetes,33, 47 whereas hypoglycemic actions were demonstrated in nondiabetic patients with hyperlipidemia.36

GI

Diarrhea

Animal/In vitro data

In a murine model, rats with short bowel syndrome receiving an enteral diet supplemented with 2% citrus pectin after resection experienced less weight loss, an increase in the solidity of the stool, and increased water absorption in the colon.48

Clinical data

Pectin has been used in the management of diarrhea for many years. It stimulates epithelial growth in the colon, thus reducing diarrhea.49 Pectin supplementation was as effective as green bananas in the management of persistent diarrhea in children. Both pectin and banana reduced the volume of stool, improved stool quality, decreased the amount of oral replacement solutions and intravenous fluids for hydration needed, and shortened the duration of illness.50, 51 In a study of 44 critically ill, tube-fed adults receiving antibiotics, there was a trend toward decreased diarrhea in those receiving fiber and pectin. Pectin stimulates epithelial growth in the colon, thus reducing diarrhea.49 Another suggested mechanism of action in the GI tract is the effect of peptic oligosaccharides on the intestinal microflora.52, 53, 54 A very small study in patients with short bowel syndrome found nonsignificant increases in gastric emptying and orocolonic transit times with pectin ingestion.6

In the 2006 DIALOG II study, a placebo-controlled, double-blind study in children evaluating the efficacy of an apple pectin–chamomile extract, in the treatment of acute diarrhea, 241 children between 6 months and 6 years of age received the extract (dosed according to the child’s age) or placebo for 5 days at the onset diarrhea. The frequency of stools was reduced in patients receiving treatment compared with those receiving placebo on days 3 and 5.55

Gastroesophageal reflux/gastric ulceration

Animal data/In vitro data

In a study of horses, a commercial feed supplement containing pectin and lecithin, among other components (Egusin), was found to reduce the severity of gastric ulceration in feed-deprived, stall-confined horses after 35 days of administration.56

Clinical data

A pectin-based, raft-forming, antireflux agent available in Europe has been studied for use in patients with heartburn. This product reduces the amount of food and acid concentration that reaches the esophagus, reducing heartburn.57, 58, 59 The pectin-based agent also delayed the recurrence of moderate or severe heartburn and erosive esophagitis when used as maintenance treatment.60 However, in a study of patients with an ileal pouch–anal anastomosis, neither pectin nor fiber had any effect on stool frequency.61 Gastric emptying rate increased with coadministration of pectin in an experiment in healthy adults.62 Additionally, pectin combined with liquid nutrients was found to be effective prophylaxis against gastroesophageal reflux in elderly patients receiving feedings via percutaneous endoscopic gastrostomy.63

In a 2012 clinical study of 18 children with cerebral palsy and gastroesophageal reflux symptoms (chronic cough, vomiting, laryngitis, and pH levels less than 4), a high-pectin diet was found to decrease the medium percentage time for the pH to fall below 4, the number of reflux episodes per day, the duration of longest reflux, the number of vomiting episodes, and the median cough score.64

Other uses

Drug delivery systems

An alginate-pectin-polylysine combination has shown promise as a vehicle for controlled-release medications. The presence of a rigid pectin gel inside the particulates imparts a stronger and more stable vehicle in acidic and alkaline solutions, which could prolong drug release. This particulate system may have potential use as a carrier for drugs that are poorly absorbed after oral administration.3, 65

Immunomodulation

Plants such as Comarum palustre, Glinus oppositifolus, Vernonia kotschyana, and Bergenia crassifola and pectic polysaccharides, including arabinogalactin, rhamnogalacturonan, and comaruman, originating in various plants used in traditional medicine have been evaluated for their effect on the immune system.66, 67, 68, 69, 70, 71 Various actions have been described from in vitro experiments, including interference with neutrophil adhesion, complement-fixing actions, and upregulation of cytokine secretion. The immunomodulatory effects of pectin depend on the structure of the backbone and branched regions of the polysaccharide.5

Allergy

Galacto-oligosaccharides have been evaluated for their preventive effect on food sensitization in infants. Insufficient data exist to support or refute a use for prebiotic supplementation to prevent food allergy.72 Although pectin may have a physical influence on the digestion of food proteins as allergens,73 an allergy to pectin itself has been reported.74

Dosing

Pectin and/or modified pectin have been used in clinical studies of cholesterol reduction at doses of 10 to 20 g daily.29, 35, 37, 40, 43

Pregnancy / Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

Coadministration of pectin with beta-carotene–containing foods or supplements can reduce beta-carotene blood levels by more than 50%.75 There is some evidence that concomitant ingestion of pectin with high-energy diets may reduce the nutritional benefits of these diets, as demonstrated in a controlled trial of undernourished children; urea production was also lower in children who ingested pectin with a caloric supplement.76

In 3 patients with hypercholesterolemia, concomitant use of pectin 15 g and lovastatin 80 mg daily produced an increase in LDL cholesterol compared with taking lovastatin alone.77 When pectin was discontinued, LDL cholesterol decreased. Pectin may decrease GI absorption of lovastatin. Based on pharmacologic and pharmacokinetic considerations, a similar interaction may be expected to occur with concurrent use of pectin and other HMG-CoA reductase inhibitors (eg, atorvastatin).

Adverse Reactions

Occupational asthma associated with the inhalation of pectin dust is a well-recognized hazard.78, 79, 80, 81 Positive skin test results for pectin suggest an immunoglobulin E–mediated hypersensitivity reaction.81 Case reports of allergy (anaphylaxis) to pectin and cross-reactivity to cashews and pistachios exist.74, 82

Doses of pectin 50 to 100 mg/kg in rats increased the number of gastric mucosal lesions produced by ethanol or aspirin, no increase was produced by application of pectin 25 mg/kg.83 Whether these pectin-induced physicochemical changes are reproducible in humans has yet to be studied.

Toxicology

No major toxicities have been reported with the use of pectin.

References

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