Glucomannan
Amorphophallus konjac Koch., Amorphophallus rivieri Durieu ex Riviére. Family: Araceae
Konjac , Konjac mannan , glucomannan , konnyaku , gonyak
 
Clinical Overview
Uses
Glucomannan has been investigated for its effects on weight reduction, diabetes, constipation, cholesterol, lung cancer, and atopic diseases, as well as its use as a prebiotic. However, there is a lack of adequately sized quality clinical trials to support these uses.

Dosing
Clinical studies of glucomannan in diabetes, cholesterol control, and obesity have used dosages of 1 to 13 g daily.

Contraindications
Given the risk of esophageal and gastric obstruction, use is not recommended in patients with structural abnormalities of the esophagus or gut.

Pregnancy/Lactation
Information regarding use during pregnancy and lactation is lacking. Until more information is obtained, use is not recommended in pregnant or breast-feeding women.

Interactions
Because of glucomannan's potential ability to lower blood glucose, use caution in patients receiving oral hypoglycemic agents, insulin, or alternative medicines that could potentially lower glucose levels. Additionally, glucomannan may reduce the bioavailability of other oral medications. Thus, it is recommended that other medications be taken 1 hour before or 4 hours after glucomannan administration.

Adverse Reactions
Severe esophageal and GI obstruction have been reported with glucomannan tablets. The hypoglycemic effects are potentially dangerous to patients with diabetes. Glucomannan has been linked in case reports to cholestatic hepatitis and occupational asthma. Minor adverse effects are normally GI related and include diarrhea, flatulence, and bloating.

Toxicology
Glucomannan given at 500 mg/kg/day for 18 months to rats demonstrated no toxicity. Data suggest diarrhea, abdominal pain, and flatulence occur with dosages more than 5 g daily.

 
Source
Konjac mannan is a polysaccharide derived from the tubers or roots of the elephant yam or konjac. 1 It is purified from konjac flour by repeated treatment with cupric hydroxide and subsequent washings with ethanol 2 or by dialysis against water. 3 , 4 The plant is widely grown in southern and southeastern China and Vietnam. It grows well in shady environments in seasonal temperatures of 5° to 43°C (41° to 109°F). 5
 
History
Konjac glucomannan was first used and studied by the Chinese, and its medicinal properties were first described in the Shen Nong Materia Medica during the Western Han Dynasty (ca 206 BC to 08 AD). Konjac flour has been traditionally produced through processing corms, the underground storage organs. After boiling with plant ash, the flour is consumed as cake or gel. 5 Its therapeutic effects are believed to be due to serotonin. Chinese people have used konjac glucomannan for over 2,000 years to treat conditions such as asthma, cough, hernia, breast pain, burns, and hematological and skin diseases. The leaves have also been used as an insect repellent. In the 6th century AD, konjac glucomannan was introduced to Japan as a medicinal product. 5
Glucomannan is commonly used in foods, drinks, and cosmetics for its gelling properties. It has been approved by the Food and Drug Administration (FDA) since 1994 as a food additive and since 1996 as a binder in meat products. China is the largest producer of konjac, and Japan is the second largest. In China, approximately 400 factories manufacture konjac flour. 5
 
Chemistry
Glucomannan is a water-soluble, fermentable dietary fiber composed of mannose and glucose combined by beta-1,4 glucosidic linkages in a molar ratio of 1.6:1. 1 Compared with other dietary fibers, it has the highest viscosity and molecular weight, ranging from 200,000 to 2,000,000 Da, which varies with origin, method of processing, and storage time. 5 Glucomannan possesses hygroscopic properties. The dry formulation swells into a viscous gel in hot or cold water, absorbing up to 50 times its weight when in water. 1 , 5 , 6 A viscous gel forms at pH levels between 4 and 7. 5 , 6 The polysaccharide is easily “denatured” through enzymatic cleavage or treatment with weak alkaline solutions, becoming irreversibly water insoluble. Glucomannan was once believed to be nonbiodegradable; however, certain gut flora bacteria such as Aerobacter mannaolyticus , Clostridium butyricum , and Clostridium beijerinckii contain endo-beta-mannanases that catalyze the degradation of glucomannan into disaccharides and eventually to glucose and mannose. 7 Heat and mechanical agitation enhance the solubility of glucomannan. In Japan, this coagulated product is called “konnyaku” and is commonly used as a foodstuff. In Korea, it is referred to as “gonyak.” 5
Amorphophallus konjac as dormant corms contains various components including the following: 49% to 60% w/w glucomannan, 10% to 30% w/w starch, inorganic elements, 5% to 14% w/w crude protein, 3% to 5% w/w soluble sugars, and 3.4% to 5.3% w/w ash. Fresh corms contain organic compounds, including beta-carotene, choline, niacin, riboflavin, and thiamine. In addition, serotonin and its derivatives have been found in fresh corms. 5
 
Uses and Pharmacology
GI effects   Polysaccharides, such as glucomannan, guar gum (composed of galactose and mannose; galactomannan), tragacanth, cellulose, methylcellulose, pectin, and wheat bran, have found use as foodstuffs and, more recently, as dietary and therapeutic agents. Their ability to swell by the absorption of water has made them useful as laxatives. Additionally, konjac glucomannan has been investigated for its role as a prebiotic, an agent that stimulates the growth and activity of beneficial gut flora, including Bifidobacterium and Lactobacillus species. 8
Animal data   Konjac mannan has been reported to alleviate moderate constipation in 1 to 2 days and reduces fecal flora by a factor of 1,000 in 10 days. Research on microflora in mice and rats suggests a diet that includes konjac mannan alters microbial metabolism in the intestine. 9 The study noted that in animals bearing human microflora, the differences in microbial composition were only slight despite the metabolic differences observed. A study determined that both unhydrolyzed konjac glucomannan and konjac glucomannan hydrolysate increased cecal anaerobes and bifidobacteria in Balb/c mice at 2 and 4 weeks following dietary consumption. Of note, glucomannan hydrolysate had a 2- to 4-fold larger anaerobe count at 4 weeks compared with unhydrolyzed glucomannan and cellulose treatment groups. Both unhydrolyzed glucomannan and glucomannan hydrolysate decreased cecal Clostridium perfringens , a potentially harmful bacterium, at week 4. Both of these compounds modulated fecal and cecal flora in a dose-dependent fashion. 8 In another similar study, 5% w/v konjac glucomannan hydrolysate fed to Wister mice for 14 weeks stimulated the growth of fecal anaerobes and lactobacilli compared with the control group ( P < 0.001). The compound was also able to decrease counts of fecal Escherichia coli and C. perfringens . 10
Clinical data   Konjac glucomannan's effects on human bowel habits were assessed in a study of healthy adults. Eight adult volunteers (21 to 54 years of age) followed the study design of 3 weeks of placebo and 1 week of adaptation in which konjac glucomannan was titrated from 1.5 to 3 g daily and was maintained at 4.5 g daily during the 3-week treatment period. On days 15 to 21 of the placebo and treatment periods, all stools were collected. Diet was controlled by having the patients adhere to a 7-day cycle menu, consisting of various low-fiber Chinese foods throughout the entire study. The mean frequency of defecation was increased by 27% following supplementation with konjac glucomannan ( P < 0.05). Additionally, the ease of passage of stool also improved with treatment ( P < 0.05).
Supplementation with konjac glucomannan significantly increased fecal lactobacillus concentrations ( P < 0.05), total bacteria concentrations ( P < 0.05), and bifidobacteria output ( P  < 0.05). Supplementation did not cause abdominal cramping, bloating, or flatulence. 11 The same investigators performed a similarly designed study with 7 constipated women. Supplementation with konjac glucomannan led to an increase in defecation each week (4.1 ± 0.6 to 5.3 ± 0.6). The fecal weight wet was not impacted by fiber supplementation, while the fecal dry weight was increased. Supplementation also increased the fecal output of bifidobacteria, lactobacilli, and total bacteria. 12
In a randomized, double-blind, crossover study, the laxative effects of glucomannan were assessed in 31 children (4.5 to 11.7 years of age) with long-term constipation with or without encopresis. Patients were given placebo and glucomannan 100 mg/kg body weight up to 5 g daily with 50 mL of fluid per 500 mg. Each patient received glucomannan or placebo for 4 weeks and then the other treatment for 4 weeks. Treatment with glucomanna was associated with improvements in stool consistency and soiling episodes as well as frequency of bowel movements when compared with the initial evaluation ( P < 0.03). Forty-five percent of participants experienced successful treatment on glucomannan when compared with placebo (13%, P  < 0.02). No side effects were reported by the participants. 13
Antidiabetic effects   By increasing the viscosity of the intestinal contents and slowing gastric emptying time, glucomannan is able to reduce postprandial glucose levels and attenuate insulin surges. This likely improves peripheral insulin sensitivity. 14 , 15
Animal data   In a streptozotocin-induced model of diabetes in pancreatic islets of mice, 3 oligosaccharide fractions from A. konjac were isolated and assessed for their effects on free radical regulation and insulin secretion. Only 1 of the fractions, KOS-A, at concentrations of less than 1.5 mM decreased nitric oxide levels in the islets but did not affect normal nitric oxide release. Additionally, at this concentration, KOS-A did not alter normal insulin secretion. 16
Clinical data   Several small studies have shown that diabetics fed a diet consisting largely of raw vegetables, uncooked seeds, fruits, and goat's milk were able to reduce or discontinue their insulin requirement. 17 Similarly, konjac mannan has been reported to reduce the need for hypoglycemic agents. When 13 diabetic patients received 3.6 or 7.2 g of konjac mannan daily for 90 days, their mean fasting glucose levels fell by 29% and insulin or hypoglycemic agent doses were reduced in most patients. 18 Five healthy men enrolled in the same study underwent a glucose tolerance test with or without a single dose of 2.6 g konjac mannan. The polysaccharide reduced mean blood glucose levels by 7.3% at 30 minutes with a concomitant decrease in serum insulin concentration. Another study of 72 type 2 diabetic patients showed a reduction in fasting blood glucose and postprandial blood glucose after consuming konjac food 30 and 65 days. 19
In 20 patients with type 2 diabetes, glucomannan 1 g given 30 minutes prior to an oral glucose tolerance test reduced prandial ghrelin levels, a hormone that increases appetite and the intake of food. However, this reduction was not statistically significant when compared with a standard glucose load or white rice load. 20
In 2008, a meta-analysis determined that glucomannan significantly affected fasting blood glucose (weighted mean difference, −7.44 mg/dL; 95% confidence interval [CI], −14.16 to −0.72). 21
Weight reduction effects   Upon oral administration, glucomannan passes mostly unchanged into the colon as human salivary and pancreatic amylase enzymes are unable to split the beta-1,4 glucosidic linkages. The polysaccharide is believed to cause weight loss by promoting satiety, delaying gastric emptying time, slowing small-bowel transit time, attenuating postprandial insulin surges, and increasing levels of plasma cholecystokinin. 1
Animal data   Research reveals no animal data regarding the use of glucomannan for weight reduction.
Clinical data   Konjac mannan is often included in “grapefruit diet” tablets. One US patent claims that its use resulted in weight loss without appetite changes; however, no weights were reported. Some research has indicated that patients treated with oral glucomannan have decreased body weight compared with control groups. In 1 study involving an 8-week cardiac rehabilitation program, patients were given 1.5 g of glucomannan twice daily. 22 Body weight among treated patients decreased by 1.5 kg at the end of 4 weeks and by 2.2 kg at the end of 8 weeks. These losses were significant when compared with the placebo group. Another showed that inclusion of resistance (1 hour) and endurance (30 minutes) exercise performed 3 times each week in combination with 3 g of glucomannan for 8 weeks was able to augment a reduction in fat mass (ie, 63% in men, 50% in women) as well as waist circumference; however, it did not affect body mass or body mass index. Cholesterol parameters also improved. 23
Glucomannan's effects on weight reduction have been evaluated in children. Research conducted in 60 children younger than 15 years (mean age, 11.2 years; mean overweight, 46%) found that glucomannan given 1 g twice daily for 2 months to 30 children reduced mean weight from 49.5% to 41% ( P < 0.01). Similarly, 30 children received placebo and the mean weight decreased from 43.9% to 41.7% ( P < 0.01). However, there were no statistically significant differences between the treatment and placebo groups. 24 , 25 Another study found that when compared with a control group, glucomannan given at dosages of 2 to 3 g daily for 4 months reduced excess body weight, total cholesterol, and triglycerides in obese children. 25 , 26
A meta-analysis from 2008 determined that glucomannan administration had a statistically significant impact on weight reduction (weighted mean difference, −0.79 kg; 95% CI, −1.53 to −0.05). 21 A novel polysaccharide, PolyGlycopleX or PGX , has been developed by reacting glucomannan with various polysaccharides. This new compound possesses the highest viscosity and water-holding properties compared with other fibers. In a study of 29 overweight or obese adults, PGX supplemented 2 to 3 times daily before meals for 14 weeks significantly reduced weight (−5.79 ± 3.55 kg), waist circumference (−12.07 ± 5.56 cm), and percentage of body fat (−2.43 ± 2.39%) when compared with baseline values ( P < 0.05). Specifically, women experienced an average weight loss of 5.14 ± 3.49 kg and men 8.30 ± 2.79 kg. Total cholesterol, low-density lipoprotein (LDL) cholesterol, and fasting blood glucose levels were also reduced. 27
Effects on lipids   The activity of konjac mannan cannot be explained by a simple interaction with bile acids because it shows no in vitro or in vivo bile acid–binding activity. Rather, it appears to inhibit the active transport of cholesterol in the jejunum and the absorption of bile acids in the ileum, yielding improvements in plasma LDL and apolipoprotein B levels 15 , 28 It has also been suggested that glucomannan increases the activity of 7-alpha-hydroxylase, an enzyme required for cholesterol conversion to bile acids. 29
Animal data   Konjac mannan reduced plasma cholesterol levels in rats 30 ; however, only water-soluble konjac mannan had this effect. The hypocholesteremic effect is completely eliminated when the mannan is coagulated to a water-insoluble form. Rats fed high cholesterol diets containing 3% crude konjac mannan for 7 days exhibited plasma cholesterol levels 16% lower than controls. Rats fed highly-purified konjac mannan had plasma cholesterol levels 23% lower than controls. Rats treated with konjac mannan that had been coagulated with cellulase had mean cholesterol levels greater than the controls. The implication is that the foodstuff konnyaku (coagulated water-insoluble product) most likely has no cholesterol-reducing activity. A study on bile output in rats fed a diet of 5% konjac mannan showed an increase in the volume of bile juice secreted and the release of bile acids, protease and amylase compared with animals fed a control diet without fiber. 31 This effect was only observed after prolonged feeding of the experimental diet with konjac mannan and could not be produced with a single dose.
Clinical data   In a study of 10 overweight patients, the daily administration of 100 mL of 1% solution of konjac mannan for 11 weeks resulted in a mean decrease in serum cholesterol levels of approximately 18%. 3 In a separate double-blind crossover trial involving 63 men, total cholesterol was reduced by 10% among subjects given a daily dose of 3.9 g of konjac glucomannan for a 4-week period. 32 No change in high-density lipoprotein (HDL) cholesterol was observed as a result of the treatment. The diabetic patients treated in another study 18 showed a reduction in mean serum cholesterol levels of 11% after 20 days of konjac mannan treatment. Several other studies confirm the effects of konjac mannan on lipid metabolism. 33 , 34 , 35
In a double-blind, placebo-controlled, parallel study, 30 overweight and obese men received glucomannan 3 g daily (n = 15) or placebo (n = 15) for 12 weeks. From baseline to 12 weeks, a reduction in total cholesterol (−10%, −6.3%), plasma triacylglycerol (−35.%, −42.5%), and increase in HDL cholesterol (−12.3%, −6%) levels occurred in the glucomannan and placebo groups, respectively. No differences were noted between groups. LDL cholesterol levels declined from baseline to 6 weeks in the glucomannan group but not in the placebo group; however, at 12 weeks, both groups experienced a reduction compared with baseline (−14.1% for glucomannan compared with −6% for placebo). Additionally, this study also determined that glucomannan reduced body weight, percent body fat, systolic blood pressure, waist circumference, and glucose levels. 36
A meta-analysis published in 2008 evaluated 14 studies with a total of 531 patients and suggested that glucomannan reduced total cholesterol levels (weighted mean difference [WMD], −19.28 mg/dL; 95% CI, −24.30 to −14.26), LDL cholesterol (WMD, -15.99 mg/dL; 95% CI, −21.31 to −10.67), and triglycerides (WMD, −11.08 mg/dL; 95% CI, −22.07 to 0.09). However, HDL and blood pressure were not affected by glucomannan therapy. 21
Glucomannan's cholesterol-lowering effects have been evaluated in children. In a clinical study of 40 children with hypercholesterolemia, patients underwent a 1-week diet run-in phase followed by randomization to either glucomannan 1 to 1.5 g twice daily plus diet or diet alone for 8 weeks. Treatment with glucomannan was associated with a significant reduction in total cholesterol and LDL cholesterol values from baseline compared with the control group. Specifically, significant reductions were noted in favor of women compared with men (total cholesterol: 24% vs 9%, P = 0.004; LDL: 30% vs 9%, P = 0.046). 37
Effects on lung cancer
Animal data   A study from China has investigated the ability of konjac powder to inhibit lung cancers in mice. 38 Mice fed a diet of 8% konjaku powder, mixed in with a common diet, showed a reduction in cancer rate from 70.87% in the positive control group to 19.38% in the group fed with konjac powder. Lung tumors were induced with N -methyl- N ′-nitro- N -nitrosoguanidine (MNNG). The study reported no adverse reactions to the konjaku powder. 38
Clinical data   Research reveals no clinical data regarding the use of glucomannan for lung cancer.
Atopic disease effects
Animal data   In a model of atopic dermatitis, NC/Nga mice were supplemented with pulverized konjac glucomannan for 8 or 9 weeks. Scratching behaviors and skin severity scores were reduced in those mice fed glucomannan in a dose-dependent fashion. The mice receiving placebo experienced an increase in this behavior. The mice that continued to receive glucomannan experienced an inhibition of eosinophilia and hyperkeratosis. 39 Only pulverized konjac glucomannan, not konjac glucomannan, high-viscous konjac glucomannan, or regranulated fine konjac glucomannan, were effective in this model, suggesting that particle size is important. Another study demonstrated that NC/Nga mice fed pulverized konjac glucomannan did not exhibit cervical lymphadenopathy, splenomegaly, or increases in anti–double-stranded DNA, rheumatoid factor immunoglobulin G autoantibodies, or B lymphocyte-activating factor levels. 40
Clinical data   Research reveals no clinical data regarding the use of glucomannan for atopic diseases.
Other uses   In a prospective, randomized, placebo-controlled study, 48 newly diagnosed hyperthyroid patients were randomized to receive treatment with methimazole and propranolol plus glucomannan 1.3 g twice daily or placebo for 2 months. At the end of the second, fourth, and sixth weeks, patients receiving glucomannan had significantly lower thyroid hormone levels (ie, T3, T4, FT3, and FT4) compared with those receiving placebo ( P < 0.05), with the exception that T3 was not lower with glucomannan treatment compared with placebo at 2 weeks. Hormone levels more rapidly declined in patients receiving glucomannan. Thyroid stimulating hormone levels were suppressed in both groups at weeks 2, 4, and 6; however, it normalized after 8 weeks of treatment in patients receiving glucomannan. At the end of 8 weeks of treatment, these levels were not different between groups. Thus, glucomannan may have a role in the initial treatment of patients with hyperthyroidism to rapidly lower thyroid hormone levels. It is hypothesized that glucomannan's effect on hyperthyroidism may be explained by alterations in enterhepatic circulation, which reduces thyroid hormone levels. 41
Dietary administration of konjac glucomannan prevented allergic rhinitis symptoms in mice following immunization and nasal sensitization. Specifically, sneezing was reduced in mice receiving glucomannan compared with controls. Additionally, supplementation with konjac glucomannan reduced total immunoglobulin E concentrations. 42
Carboxylated konjac glucomannan has been investigated for its application as a plasma substitute or expander during periods of critical blood and fluid loss. In a rabbit model, the colloid osmostic pressure of a solution containing 1% carboxylated konjac glucomannan was higher than a 6% solution of hydroxyethyl starch and 5% solution of human serum albumin. This allows for a lower dosage of the konjac glucomannan solution to be infused. 43
In an in vitro study, the presence of konjac glycomannan hydrosylates was able to inhibit the growth of Propionibacterium acnes . 44
Given that konjac glucomannan is degraded in the colon by beta-mannases produced from natural flora and is not degraded in the small intestines, it has gained attention as an excipient for colonic drug delivery. 45 Additionally, glucomannan possesses unique biodegradable, solubility, and gelling properties that make it attractive for use as an excipient in tablets, films, beads, micro- and nanoparticles, and hydrogels. Also, glucomannan has been combined with other polysaccharides including carrageenan, xanthan, acetan, gellam gum, alginate, and chitosan to improve gelling properties as part of drug delivery applications. 7
 
Administration & Dosage
Clinical studies of glucomannan in diabetes, cholesterol control, and obesity have used doses of 1 to 13 g daily. 1 , 46 , 47 , 48 , 49 Specifically, 1 to 3 daily has been suggested for weight loss and 3.6 to 13 g daily for type 2 diabetes, insulin-resistance syndrome, and dyslipidemia. 1
 
Pregnancy/Lactation
Information regarding use during pregnancy and lactation is lacking. Until more information is known, use is not recommended in pregnant or breast-feeding women.
 
Interactions
Given the possibility of reducing blood glucose levels, caution should be used in patients receiving oral hypoglycemic agents, insulin, or alternative medicines that lower glucose levels. Additionally, glucomannan may reduce the bioavailability of other oral medications. Thus, it is recommended to take other medications 1 hour before or 4 hours after glucomannan administration. 1
 
Adverse Reactions
Several cases of severe esophageal obstruction due to glucomannan diet tablets have been reported. 50 , 51 Seven cases were noted during 1984 and 1985 by the Australian Adverse Drug Reactions Advisory Committee. Four of these obstructions occurred in the proximal one-third of the esophagus. One patient developed mediastinitis due to perforation of the esophagus. 52 Thus, patients with conditions of the esophagus or who experience difficulty swallowing in general may be at increased risk of esophageal obstruction associated with glucomannan. Glucomannan-containing tablets have been banned in Australia since May 1985 because these also carry the potential for inducing lower GI obstruction. Encapsulated and powder forms remain available.
Glucomannan use is associated with a reduction in the need for hypoglycemic agents, and the product may result in a loss of glycemic control in patients with diabetes. Therefore, glucomannan should be used with caution by these patients.
A case report described a 31-year-old man who had taken glucomannan capsules for weight loss and subsequently developed short-term cholestatic hepatitis. The patient took 1 to 2 capsules daily 45 days prior to the onset of symptoms. Glucomannan was considered the likely causative agent given the temporal relationship. This suggests a potential hepatotoxic effect may be due to the presence of serotonin. 53
“Konjac asthma” is a type of occupational asthma occurring in factories that manufacture konjac flour documented in a 1952 survey. During the production process, “konjac dancing powder” is produced. Inhalation of this powder has lead to the development of asthma among workers and nearby residents. 54
Minor adverse effects include GI effects such as diarrhea, flatulence, and bloating. 1
 
Toxicology
Glucomannan given to rats at dosages of 500 mg/kg/day for 18 months revealed no toxicity. 7 , 55 Data suggests minor GI effects (eg, diarrhea, abdominal pain, flatulence) occur with dosages higher than 5 g daily. 7
 
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