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Plantago

Scientific Name(s): Plantago arenaria Waldst. & Kit., Plantago lanceolata L., Plantago major L., Plantago ovata Forsk., Plantago psyllium L.
Common Name(s): Black psyllium, Blond plantago, Flea seed, French psyllium, Indian plantago, Ispaghula, Plantago psyllium, Plantain, Psyllium seed, Spanish psyllium

Clinical Overview

Use

The psyllium in plantago has been used for GI conditions such as irritable bowel syndrome (IBS), diarrhea, constipation, and hemorrhoids. It has also been used to treat hyperlipidemia and for its anticancer effects, and it may be useful for glycemic control in patients with type 2 diabetes. Although some clinical data exist to support use of plantago in constipation, respiratory infections, and hyperlipidemia, clinical information regarding other potential uses is lacking.

Dosing

General Dosing: 3 to 6 g/day of psyllium.

Constipation: 1 teaspoon to 1 tablespoon of powder or granules mixed in 180 to 240 mL of liquid 1 to 3 times/day. Dosage varies according to product; see product labeling. Product is also available as capsules and wafers.

Glycemic Control in Type 2 Diabetic Patients: 6.8 to 13.6 g/day of psyllium for 6 to 12 weeks.

Hyperlipidemia: 10.2 g/day of psyllium in 2 to 3 divided doses.

Respiratory Infections: 3 to 6 g/day as a tea.

Contraindications

Because psyllium acts as a bulk laxative, patients with GI obstruction or fecal impaction should avoid use, as it may worsen these conditions. Additionally, patients with difficulty swallowing should avoid psyllium because there is a risk for choking and esophageal obstruction.

Pregnancy/Lactation

Avoid use. Adverse effects have been documented: uterine activity, laxative.

Interactions

Patients receiving prescription medications should be advised to consult their health care provider before taking psyllium or any other natural products. See Interactions section.

Adverse Reactions

Minor adverse reactions include flatulence, bloating, nausea, vomiting, indigestion, and sternum pain. More serious adverse effects include anaphylaxis, chest congestion, sneezing and watery eyes, and occupational asthma; a case of giant phytobezoar (a trapped mass composed of psyllium seed husks) has also been reported.

Toxicology

The pollen from plantago contains allergenic glycoproteins that react with concanavalin A, as well as components that bind immunoglobulin E (IgE). IgE antibodies have been demonstrated. IgE-mediated sensitization contributes to seasonal allergies.

Botany

Plantago is a perennial weed with almost worldwide distribution. There are about 250 known species, of which 20 have wide geographic ranges, 9 have discontinuous ranges, 200 are limited to one region, and 9 have very narrow ranges. P. lanceolata and P. major are among the most widely distributed.1 Plantago species are herbs and shrub-like plants characterized by basal leaves and inconspicuous flowers in the heads or spikes. P. major can grow up to 15 cm in height.2 These species grow aggressively; plantago is wind-pollinated, which facilitates growth where there are no bees and few other plantago plants. The plant is also very tolerant of viral infections. P. major produces 13,000 to 15,000 seeds per plant, and the seeds are reported to remain viable in soil for up to 60 years. P. lanceolata produces 2,500 to 10,000 seeds per plant and has a somewhat shorter period of seed viability. Plantago seeds can survive passage through the gut of birds and other animals, which further facilitates their distribution.1 Psyllium seeds are small (1.5 to 3.5 mm), oval, boat-shaped, dark reddish-brown, odorless, and nearly tasteless, and are coated with mucilage, which aids in their transportation by enabling them to adhere to various surfaces.1, 3 Plantago herb should not be confused with Musa paradisiaca or the edible plantain. A synonym of P. arenaria is Plantago ramosa Asch.

History

Research on pollen shows that plantago was introduced to the Nordic countries during the stone age, parallel to the introduction to the first primitive cultivated fields. Certain plantago species were spread by human colonization, particularly by Europeans. Due to its spread from areas of English settlement, North American Indians and New Zealand Maori refer to plantago as "Englishman's foot" or "white man's footprint."2 P. lanceolata and P. major have been used in herbal remedies and were sometimes brought to colonies intentionally for that purpose. Psyllium seed has been found in malt refuse (formerly used as fertilizer) and in wool imported to England; it has also been commonly used in birdseed.1 Pulverized seeds have been mixed with oil and applied topically to inflamed sites; decoctions have been mixed with honey for sore throats. The seeds and refined colloid are used commonly in commercial bulk laxative preparations.1, 4

Chemistry

Plantago constituents include acids (eg, benzoic, caffeic, chlorogenic, cinnamic, p-coumaric, fumaric, salicylic, ursolic, vanillic, ascorbic), alkaloids (ie, boschniakine), and amino acids (eg, alanine, asparagine, histidine, lysine).5 The seeds are coated with mucilage (20% to 30%; located only in the epidermis of the testa).3 An analysis of 8 of 21 Egyptian species of plantago, including P. major, identified a variety of sugar and polysaccharide components of the seed mucilage, including galactose, glucose, xylose, arabinose, and rhamnose. In addition, galacturonic acid, planteose, plantiobiose, sucrose, and fructose have been identified.6 Other plant carbohydrates such as saccharose, stachyose, sorbitol, and tyrosol have also been reported.5 The seed mucilage of P. ovata had better suspending and emulsifying power than tragacanth and methylcellulose.7 Leaf mucilage has also been reported and includes polysaccharides containing rhamnose, L-arabinose, mannose, galactose, and dextrose.8 Additionally, the seeds contain fixed oil, protein, iridoids, and tannins.3, 4 The gel-forming fraction of the seed was effective in prolonging release rates of tetracycline in vitro.9

Flavonoids found in plantago include apigenin, baicalein, and scutellarein.5 Isolation and identification of flavonoids and saponins from the related species P. tomentosa have been reported.10

Iridoids found in plantago are aucubin, plantarenaloside, and aucuboside.5 The main iridoids aucubin and catalpol have been isolated from P. lanceolata, P. major, and P. media leaves using high-pressure liquid chromatography analysis.11 Iridoid glycosides and phenolic acids have been found in leaf extracts of P. lanceolata and P. media.12

Other components of the plant include choline, fat, resin, steroids, and vitamins.4, 5 Specifically, P. major may be considered a good source of vitamin C and carotenoids.2

Reports on the related species P. asiatica list such constituents as a new phenylethanoid glycoside,13 aucubin,14 plantaginin, and plantamajoside.15

Uses and Pharmacology

GI

Psyllium seed is classified as a bulk laxative. When mixed with water, it produces a mucilaginous mass. The indigestible seeds provide bulk for the treatment of chronic constipation, while the mucilage serves as a mild laxative comparable to agar or mineral oil. The American College of Gastroenterology monograph on the management of IBS and chronic idiopathic constipation (2014) states that soluble fiber, particularly psyllium, increases stool frequency and provides overall symptom relief in IBS with constipation (weak, moderate evidence) and is effective in managing chronic idiopathic constipation (strong, low evidence).16

Animal data

In a study investigating the anti-ulcerogenic effects of P. ovata, rabbits were given acetylsalicylic acid 10 mg/kg orally for either 14 or 28 days with or without P. ovata 100 mg/kg orally. P. ovata attenuated acetylsalicylic acid–induced lesions. Specifically, the rabbits receiving only acetylsalicylic acid had an 18.7% and 23% increase in the percentage of caliciform cells in the duodenal epithelium after 14 and 28 days, respectively, compared with 13.5% in the control group (rabbits receiving only water). In rabbits treated with P. ovata, these values were similar to the control group: 11.8% and 13.15% at 14 and 28 days, respectively. These findings were statistically significant (P < 0.05) compared to treatment with acetylsalicylic acid only.17

Clinical data

In a study of 10 healthy volunteers examining the effects of a 3 g mixture of P. ovata husks (dried psyllium seed husks) given 3 times daily, the mixture decreased intestinal transit time.18 In a postcholecystectomy patient with chronic diarrhea given a 6.5 g dose of a psyllium 50% preparation, symptom resolution occurred in 2 days.19, 20 In a study of 50 adult subjects, psyllium seed powder as a bulk laxative was as effective as a cellulose/pectin mixture.21 The effects of different dietary fibers, including P. ovata seed, on colonic function have been evaluated.22 Gastroprotective action from plantago extract (polyholozidic substances) has also been reported.23

In a triple-blind, crossover study of 17 female patients, a P. ovata seed preparation was investigated for its effects on appetite. The preparation was deemed useful in weight control diets in which a feeling of fullness was desired. Total fat intake was also decreased, which suggests that the product might be a beneficial weight control diet supplement.24

In a trial of 393 patients with anal fissures, a psyllium preparation as part of a conservative therapy approach was effective. Patients were followed for approximately 5 years. Of the trial participants, 44% were cured without surgery within 4 to 8 weeks. Complications (ie, abscesses and fistulas requiring surgery) occurred in 8% of patients. The recurrence rate following healing was 27%, but about one-third of these cases were fistulas that responded to further conservative management.25

A double-blind study of 51 patients with symptomatic hemorrhoids showed Vi-Siblin, a psyllium-containing preparation, to be effective in reducing bleeding and pain during defecation: 84% of patients receiving the preparation reported improvement or elimination of symptoms, compared with 52% taking placebo.26

Hyperlipidemia

According to many reports, psyllium can be helpful in treating various types of hyperlipidemia.27, 28 Issues of cereal companies including plantago seed in their products and claiming cholesterol reduction have been addressed.29 A polyphenolic compound from P. major leaves exhibited hypocholesterolemic activity,30 but the mechanism by which psyllium reduces cholesterol may also include enhancement of cholesterol elimination as fecal bile acids.31

Animal data

In animal studies, psyllium lowered total plasma lipids, cholesterol, and triglycerides in arteriosclerotic rabbits.5 However, other animals may be less sensitive to psyllium's hypocholesterolemic actions.32

Clinical data

In one study, 28 patients received 3 doses (3.4 g/dose) per day of psyllium hydrophilic mucilloid (Metamucil, Procter & Gamble) for 8 weeks. After 4 weeks, psyllium-treated patients showed decreases in total serum cholesterol levels compared with the placebo group. Decreases were also observed in low-density lipoprotein (LDL) cholesterol and in the LDL/high-density lipoprotein (HDL) ratio. At the end of 8 weeks, values for total cholesterol, LDL cholesterol, and the LDL/HDL ratio were 14%, 20%, and 15%, respectively, below baseline (P < 0.01 for all). This study suggests that high cholesterol levels can be managed by a diet that includes psyllium preparations.33

Similar cholesterol reductions have been reported in other studies. In a study that evaluated the effects of long-term treatment with hydrophilic colloid on serum lipids, psyllium colloid administration for 2 to 29 months reduced cholesterol levels by 16.9% and triglycerides by 52%.34 In a trial of 75 hypercholesterolemic patients, psyllium as an adjunct to a low-cholesterol diet was effective in the management of mild to moderate hypercholesterolemia.35 A 16-week, double-blind trial of patients with primary hypercholesterolemia receiving psyllium seed while on either a high- or low-fat diet demonstrated improvements in both total and LDL cholesterol.36 In a study of 105 hyperlipidemic patients, psyllium seed in combination with colestipol was better tolerated and as effective as monotherapy with either agent.37 Another study of P. ovata husk demonstrated reductions of −6% in LDL cholesterol, −6% in total cholesterol, −21.6% in triglycerides, and −6.7% in apolipoprotein B-100, as well as reductions in oxidized LDL, insulin resistance, and systolic blood pressure.38

Psyllium seed was more effective than P. ovata husk in reducing serum cholesterol in healthy and ileostomy subjects.39 However, in a study of 20 hypercholesterolemic pediatric patients receiving low-fat diets, psyllium seed was ineffective in lowering total cholesterol or LDL cholesterol levels.40

Anticancer

The proposed mechanism of anticancer effects associated with P. ovata has been attributed to the production of butyric acid in the colonic fermentation of dietary fiber, which induces apoptosis and is involved in the regulation of some cancer genes. Production of butyric acid has been noted to be increased following the ingestion of P. ovata.41

Animal data

The antitumor effects of plantago have been studied in animals. The alpha-mannosidase inhibitor plantagoside isolated from seeds of the related species P. asiatica suppressed immune response in mouse tissue.42 P. major has also inhibited carcinogen synthesis in induced toxic liver damage and has decreased tumor incidence in rats.43 In mice given subcutaneous injections of P. major, mammary cancer tumor formation frequency was 18%, compared to 93% with placebo, which suggests benefit of P. major as prophylactic therapy for cancer of this type.44 Immunotropic activity of P. lanceolata extract on murine and human lymphatic cells in vivo and in vitro has also been demonstrated.45

Clinical data

In an ecological study conducted in Spain between 1995 and 2000, an inverse correlation between the consumption of P. ovata and mortality from colorectal cancer was observed.41

In a parallel-designed clinical study, 665 patients with colorectal adenomas were randomly assigned to receive calcium gluconolactate and carbonate (2 g of elemental calcium daily), P. ovata husk (3.5 g/day), or placebo, with a follow-up colonoscopy after 3 years. After 3 years, 552 patients underwent a colonoscopy, and at least 1 adenoma occurred in 28 patients (15.9%) receiving calcium, in 58 patients (29.3%) receiving P. ovata husk, and in 36 patients (20.2%) receiving placebo. The odds ratio of recurrence of adenoma in the P. ovata husk group was 1.63 (95% confidence interval [CI], 1.01 to 2.64), suggesting an increased risk of recurrent adenoma in patients receiving P. ovata husk.46

Glycemic control

Animal data

In a study of diabetic rabbits, supplementation of feed with P. ovata husk at a dosage of 3.5 mg/kg/day was associated with lower glucose concentrations than those observed in rabbits receiving standard feed.47 In rats with type 1 and type 2 diabetes, P. ovata 0.5 g/kg improved glucose tolerance. This was attributed to inhibition of the intestinal absorption of glucose; it was not associated with stimulation of insulin secretion.48

Clinical data

While one report found that psyllium administration had no effect on postprandial plasma glucose,49 a meta-analysis of data from 35 randomized clinical trials including euglycemic, at-risk, and treated diabetic patients showed improvements in fasting blood glucose (FBG) (−37 mg/dL) and hemoglobin A1C (−10.6 mmol/mol) with long-term psyllium supplementation (6.8 to 13.6 g/day for 6 to 12 weeks) in patients being treated for type 2 diabetes mellitus. Overall, glycemic effects were proportional to baseline FBG, with no, modest, and greatest improvements being observed in euglycemic, prediabetic, and diabetic patients, respectively.50

Respiratory infections

Animal data

An aqueous extract of plantago may have bronchodilatory activity in guinea pigs; however, this effect is less active and of shorter duration than that of salbutamol or atropine.5

Clinical data

In human studies, plantago has reportedly been effective for treating chronic bronchitis,4, 51 asthma, cough, and cold.4

Other uses

One report described the topical use of crushed plantago leaves to treat poison ivy in 10 people. The treatment eliminated itching and prevented the spread of dermatitis in all cases, with 1 to 4 applications being required; however, the trial was not conducted scientifically.52 Fresh leaves of the plant have been poulticed onto herpes sores, ulcers, boils, and infections. Plantago has been used to treat insect bites and gout.4 Leaf extracts reportedly have wound healing activity in rabbits; this activity is associated with the chlorogenic and neochlorogenic acid content of the extracts.46 An aqueous extract of P. lanceolata improved wound healing in rats, with increased myofibroblasts at wound sites.53

Plantago oils have exhibited therapeutic action on chemical burns in rabbit eyes.54

Aqueous extracts of plantago leaves demonstrate antimicrobial activity caused by aglycone and aucubigenin.3

In folk medicine, aerial parts of Plantago have been used as an anti-inflammatory and as a diuretic.55 P. lanceolata's phenylethanoids, acteoside and plantamajoside, have been evaluated for inhibitory effects on arachidonic acid–induced mouse ear edema.56 Anti-inflammatory effects were observed for various aqueous and alcoholic extracts from P. major.57 Plantago extract has decreased arterial blood pressure by 20 to 40 mm Hg in normotensive dogs.5

Dosing

General dosing

3 to 6 g/day of psyllium.58

Constipation

1 teaspoon to 1 tablespoon of powder or granules mixed in 180 to 240 mL of liquid 1 to 3 times/day. Dosage varies according to product; see product labeling. Product is also available as capsules and wafers.

Glycemic control in type 2 diabetic patients

6.8 to 13.6 g/day of psyllium for 6 to 12 weeks.50

Hyperlipidemia

10.2 g/day of psyllium in 2 to 3 divided doses.33, 34, 35

Respiratory infections

3 to 6 g/day of P. lanceolata as a tea.3

Pregnancy / Lactation

Avoid use. Adverse effects have been documented: uterine activity, laxative.5

Interactions

Lithium: Coadministration of psyllium with lithium may decrease the GI absorption of lithium, thereby reducing lithium plasma concentrations and thus its pharmacologic effect. Decreased lithium plasma levels were observed in a 47-year-old woman receiving lithium and plantago seed (P. ovata husk; psyllium hydrophilic mucilloid).60 Four days after starting lithium treatment and 2 days after starting liquid P. ovata husk, the woman's lithium plasma level was 0.53 mmol/L. Subsequently, the dose of lithium was increased; however, lithium levels continued to decrease. Within 4 days of stopping P. ovata husk, lithium levels increased.

Carbamazepine: Coadministration of psyllium with carbamazepine may decrease the oral bioavailability and absorption of carbamazepine, thereby reducing carbamazepine plasma concentrations and its pharmacologic effect.61

Carbidopa/Levodopa: In patients 60 to 80 years of age with Parkinson disease who were maintained on levodopa/carbidopa oral medication 3 times daily for at least 3 months, coadministration of P. ovata husk (3.5 g dispersed in 200 mL water) with levodopa 100 mg/carbidopa 25 mg resulted in significantly fewer peaks in levodopa concentrations compared with placebo and no statistically significant differences in absorption (time to maximum concentration), area under the curve, or peak plasma concentration.62

Antidiabetes Agents: In patients with diabetes taking oral agents or insulin to achieve glycemic control, blood glucose levels should be monitored more closely when initiating or adjusting doses of psyllium; psyllium can lower blood glucose levels and impair carbohydrate absorption.

Adverse Reactions

Minor adverse reactions include flatulence, bloating, nausea, vomiting, indigestion, and sternum pain.63

Anaphylactoid/Allergic Reactions

There are many reported incidences of varying degrees of psyllium allergy. Nurses who dispensed psyllium in powder form experienced symptoms such as anaphylactoid reaction, chest congestion, sneezing, and watery eyes (some of these reactions took several years to occur).64, 65 A case report described severe anaphylactic shock following psyllium laxative ingestion by a pharmaceutical worker dispensing the product, suggesting its role as an occupational respiratory allergen in pharmaceutical workers exposed to the substance.66 Consumption of plantago seed in cereal was responsible for anaphylaxis in a 60-year-old woman (IgE-mediated sensitization was documented, and the patient was successfully treated with oral diphenhydramine).67 A report evaluating sensitization to psyllium in workers in a psyllium processing plant also revealed prevalences of occupational asthma and IgE sensitization to psyllium of at least 3.6% and 27.9%, respectively.68

GI/Esophageal Obstruction and Choking

A case of giant phytobezoar composed of psyllium seed husks has been reported. The bezoar, located in the right colon, resulted in complete blockage of gastric emptying.69 In addition, there is concern that inadequate ingestion of water with psyllium intake could cause choking and/or esophageal blockage. All psyllium preparations must be taken with adequate volumes of fluid. The Food and Drug Administration (FDA) has issued a warning on the labeling of products with psyllium that states the following: "Taking this product without adequate fluid may cause it to swell and block your throat or esophagus and may cause choking. Taking this product without enough liquid can cause choking. If you experience chest pain, vomiting, or difficulty in swallowing or breathing after taking this product, seek immediate medical attention."70

Other

Ingestion of unsoaked psyllium seeds releases a pigment that may be harmful to the kidneys,14, 71 but the pigment has been removed from commercial preparations.72

Toxicology

Plantago pollen contains at least 16 antigens, of which 6 are potentially allergenic. The pollen contains allergenic glycoproteins that react with concanavalin A, as well as components that bind IgE.73 Antigenic and allergenic analysis of psyllium seed showed that all 3 fractions (husk, endosperm, and embryo) contain similar antigens.74 The formation of IgE antibodies to psyllium laxative has been demonstrated.75 In addition, IgE-mediated sensitization to plantago pollen has been performed; plantago pollen sensitivity should be considered during diagnosis of seasonal allergy.76

References

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