Chitosan With Glucomannan [Discontinued] by GNC Total Lean

POSSIBLY EFFECTIVE

• Hypertension. Substituting table salt with a chitosan-containing table salt may reduce blood pressure in patients with hypertension. Details: Small clinical studies in patients with prehypertension or moderate hypertension show that taking a specific product (Symbiosal) containing chitosan 3% in table salt for 8 weeks decreases systolic blood pressure compared with table salt alone when used as part of a diet containing a maximum of 3 grams sodium chloride daily (97708,97715). In adults with hypertension, this product increased the number of patients with controlled blood pressure by an additional 39% when compared with table salt alone (97715). In adults with prehypertension, this product increased the number of patients with systolic blood pressure less than 130 mmHg by an additional 67% when compared with table salt alone (97708).
• Obesity. Oral chitosan may lead to slight improvements in body weight when combined with a calorie-restricted diet in patients who are overweight or obese; however, it is unclear if this weight loss is clinically significant. Details: Meta-analyses of clinical research in overweight or obese patients show that taking chitosan 1-3 grams daily for up to one year may slightly-to-modestly reduce body weight when compared with placebo; however, the average weight loss in trials lasting up to one year is only 1 kg more than placebo according to the most recent meta-analysis (41729,92781,100170). These analyses also show that taking chitosan can slightly improve systolic and diastolic blood pressure, as well as low-density lipoprotein (LDL) cholesterol and triglyceride levels, in obese or overweight patients (92781,100170). Chitosan may only be beneficial for weight loss when combined with a calorie-restricted diet. Some of the small clinical studies included in the analyses above show that combining chitosan with a calorie-restricted diet can result in modest weight loss (9610,10022,10023,10024,10025), while taking chitosan without calorie reduction does not seem to cause clinically significant weight loss (3243,3244,9986,14314,41724). It also does not seem to significantly increase fecal fat excretion, which is the suggested mechanism of action for reducing weight (9987,10020,11045,14314).
• Postoperative recovery. Application of chitosan gel dressings after endoscopic sinus surgery may improve recovery by lowering the risk of nasal adhesions. Details: A meta-analysis of three small clinical studies shows that use of chitosan gel dressing following endoscopic sinus surgery reduces the risk of nasal adhesions by 75% when compared with saline or no dressing. The chitosan dressings did not influence swelling, crusting, or infections (97713,97714).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Crohn disease. Oral chitosan has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small, uncontrolled clinical study in adults with Crohn disease shows that taking a combination of chitosan 1.05 grams and ascorbic acid daily for 8 weeks increases fecal excretion of fat, but does not improve disease activity, when compared to baseline (9609). The validity of these findings is limited by a lack of control group.
• Dental caries. While small studies suggest that use of chitosan-containing gum or mouthwash can decrease levels of cavity-causing bacteria, it is unclear if these products reduce the risk of developing dental caries. Details: One small clinical study in healthy adults shows that chewing gum supplemented with chitosan decreases the number of cariogenic bacteria in the mouth when compared with non-supplemented gum (15126). Additionally, a small crossover trial shows that rinsing with chitosan 0.5% mouthwash twice daily for 14 days can also decrease the number of cariogenic bacteria in the mouth when compared with placebo (41697). However, there is no reliable evidence that chitosan gum or mouthwash reduces the risk of developing cavities.
• Dental plaque. Small clinical studies suggest that rinsing with chitosan mouthwash may reduce plaque formation. Details: One small crossover trial shows that rinsing with chitosan 0.5% mouthwash twice daily for 14 days significantly reduces plaque formation when compared with placebo (41697). Another small clinical study in patients with dental plaque and gingivitis shows that rinsing with 10 mL of chitosan 0.5% mouthwash twice daily for 3 months reduces plaque formation when compared to baseline, with similar improvements when compared with chlorhexidine 0.2% mouthwash. However, rinsing with a combination of chitosan and chlorhexidine significantly improves plaque formation when compared with either agent alone (106521).
• Diabetic foot ulcers. It is unclear if topical chitosan is beneficial in patients with diabetic foot ulcers. Details: A small clinical study in adults with diabetic foot ulcers shows that applying a thin smear of chitosan 10% gel to the ulcer is no more effective than placebo gel for ulcer healing. Also, when chitosan 10% gel is used in combination with topical isosorbide dinitrate two sprays daily, it is no more effective than the isosorbide dinitrate spray alone (100171). It is not clear if this study was adequately powered to detect a difference between groups.
• Dry eye. It is unclear if chitosan-containing eye drops are beneficial in patients with dry eye. Details: A small clinical study in patients with dry eye shows that applying a specific eye drop (Lacrimera) containing chitosan-N-acetylcysteine 0.1% once or twice daily to the eyes for 5 days improves general symptoms of dry eye by approximately 60% when compared to baseline (97710). The validity of these findings is limited by a lack of placebo control group.
• Gingivitis. It is unclear if rinsing with chitosan mouthwash is beneficial in patients with gingivitis. Details: A small clinical study in patients with gingivitis and dental plaque shows that rinsing with 10 mL of chitosan 0.5% mouthwash twice daily for 3 months reduces gingivitis scores when compared to baseline, with similar improvements when compared with chlorhexidine 0.2% mouthwash. However, rinsing with a combination of chitosan and chlorhexidine significantly improves gingivitis scores when compared with either agent alone (106521).
• Hypercholesterolemia. Despite conflicting study results in patients with hypercholesterolemia, a meta-analysis of small clinical studies suggests that oral chitosan may slightly improve lipid levels when taken for at least 4 weeks in overweight or obese patients with or without hypercholesterolemia. Details: A meta-analysis of seven small clinical studies of obese or overweight patients with or without hypercholesterolemia shows that taking chitosan 1-4.5 grams daily for 4 weeks or longer can reduce both total cholesterol and low-density lipoprotein (LDL) cholesterol by around 6 mg/dL, increase high-density lipoprotein (HDL) cholesterol by around 1 mg/dL, and reduce triglyceride levels by around 11 mg/dL when compared with placebo (92781). However, individual studies in patients with mild hypercholesterolemia show conflicting results. Some small clinical studies show that taking chitosan 1-3 grams daily for 1-3 months does not decrease total cholesterol or LDL cholesterol (3243,9986,11044), while other studies show that taking chitosan 1.2-1.35 grams daily for 8 weeks modestly reduces total cholesterol by 4% to 10% and LDL cholesterol by about 7% when compared with placebo (11307,41693). Several clinical studies also suggest that chitosan-containing combination products seem to reduce cholesterol levels in obese patients or those with hypercholesterolemia. Combinations studied include chitosan 1.2 grams with glucomannan 1.2 grams daily for 1 month (11046); a fiber supplement containing chitosan, guar meal, ascorbic acid, and other micronutrients (10025); chitosan 240 mg, garcinia 55 mg, and chromium 19 mg once or twice daily for 4 weeks (41720); and a specific product (Tegradoc) containing chitosan 10 mg, berberine 200 mg, red yeast extract providing monacolin K 3 mg, and coenzyme Q10 10 mg daily for 12 weeks (97709). It is unclear if the positive findings associated with these combination products are due to chitosan, other ingredients, or the combination.
• Hyperphosphatemia. It is unclear if chewing chitosan-loaded gum is beneficial in patients with hyperphosphatemia who are undergoing hemodialysis. Details: One very small clinical study in patients undergoing hemodialysis with hyperphosphatemia inadequately controlled with sevelamer shows that chewing 20 mg of chitosan-loaded gum twice daily for 2 weeks reduces serum phosphorous levels by 31% when compared to baseline (92784). The validity of this finding is limited by a lack of control group. Conversely, a slightly larger, placebo-controlled clinical study in patients on hemodialysis with phosphorous levels inadequately controlled on phosphate binders shows that chewing 40 mg of chitosan-loaded gum for 30 minutes three times daily for 3 weeks does not significantly reduce serum phosphorous levels when compared with placebo (92779).
• Iron deficiency anemia. Although there has been interest in using oral chitosan for iron deficiency anemia, there is insufficient reliable information about the clinical effects of chitosan for this purpose.
• Kidney failure. It is unclear if oral chitosan is beneficial in patients with kidney failure who are receiving hemodialysis. Details: One small clinical study in patients with kidney failure receiving chronic hemodialysis shows that taking chitosan 450 mg three times daily for 12 weeks reduces elevated cholesterol levels, improves anemia, and enhances physical strength, appetite, and sleep when compared with no treatment (1942).
• Minor bleeding. Small clinical studies suggest that application of chitosan gel dressings after endoscopic sinus surgery may reduce the risk of minor post-surgical bleeding, while application of chitosan-containing gauze to skin grafts does not appear to reduce bleeding risk. Details: A meta-analysis of two small clinical studies shows that use of chitosan gel dressing following endoscopic sinus surgery increases hemostasis by 70% when compared with saline or no dressing (97714). Over 60% of patients using chitosan gel achieved hemostasis within 2 minutes compared with 17.5% of patients not using chitosan gel (97713). However, one small study in patients with skin grafts shows that using chitosan gauze (AnsCare ChitoClot Gauze, BenQ Materials Corporation) with paraffin dressing for 2 weeks does not reduce the amount of blood loss when compared with paraffin dressing alone (97711). These conflicting results might be related to the form of chitosan used or the type of surgical wound to which it is applied.
• Muscle strength. Although there has been interest in using oral chitosan for increasing muscle strength, there is insufficient reliable information about the clinical effects of chitosan for this purpose.
• Periodontitis. It is unclear if topical chitosan is beneficial in patients undergoing surgery for periodontitis. Details: A very small clinical study in patients with periodontitis undergoing dental surgery shows that applying chitosan ascorbate to the gums improves tooth mobility and pocket depths when compared to baseline (1945). The validity of these findings is limited by a lack of control group.
• Wound healing. Several small clinical studies suggest that application of chitosan-containing dressings to skin grafts improves wound healing, scar formation, and nerve regeneration. Details: One small clinical study shows that applying a chitosan mesh dressing increases healing and regeneration of the skin in the first ten days after skin graft placement and reduces itching by about 50% when compared with paraffin dressing (97707). Another small clinical study in patients receiving skin grafts after surgery, burn wounds, or skin malignancy excision shows that application of a chitosan-containing dressing to the skin graft improves wound re-epithelialization and nerve regeneration, but does not improve the rate of healing, when compared with a conventional dressing (41692). Another small clinical study in patients undergoing plastic surgery shows that applying N-carboxybutyl chitosan topically seems to promote donor site tissue regeneration and reduce scar formation when compared with control donor sites (1944). A small clinical study in adults undergoing extraction of an impacted mandibular third molar shows that applying a topical gel (Bexident Post, ISDIN) containing chitosan, allantoin, dexpanthenol, and chlorhexidine as 10 mL three times daily for ten days increases the rate of good wound healing by an additional 52% and 36% after 7 and 14 days, respectively, when compared with no gel. However, this chitosan-containing gel does not appear to reduce postoperative pain or swelling (97712). It is unclear if these findings are due to chitosan, other ingredients, or the combination. More evidence is needed to rate chitosan for these uses.

(Read more about CHITOSAN)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Constipation. Small clinical studies suggest that oral FOS may modestly improve symptoms in patients with constipation when used in combination with probiotics. The benefits of FOS when used alone are unclear. Details: Most clinical research has evaluated the use of FOS for constipation in conjunction with probiotics. Preliminary clinical research in adults with chronic functional constipation shows that taking an unspecified dose of a specific product (Hexbio) consisting of FOS, Lactobacillus acidophilus, Lacticaseibacillus casei, Lactococcus lactis, Bifidobacterium bifidum, Bifidobacterium longum, and Bifidobacterium infantis orally twice daily for 7 days increases defecation frequency by 3-fold when compared with placebo. Taking this product also improved patient reported symptoms of straining, lumpy hard stools, and incomplete evacuation sensations (90266). Other clinical research in adult females with constipation shows that taking a different product (Lactofos, SKL Functional Nutrition Ltda.) containing FOS 6 grams and Lacticaseibacillus paracasei, Lacticaseibacillus rhamnosus, Lactobacillus acidophilus, and Bifidobacterium lactis 0.1-1 billion colony-forming units each, orally twice daily for 30 days, modestly increases the frequency of evacuation and decreases constipation severity when compared with placebo (90300). It is unclear if these effects are due to FOS, other ingredients, or the combination. In children aged 4-8 years with functional constipation, preliminary clinical research shows that taking a mixture of FOS 0.45 grams and polydextrose 4.17 grams orally daily for 45 days improves the weekly frequency of bowel movements, clinical manifestations of constipation, and quality of stool type when compared with baseline (106482). It is unclear if these effects are due to FOS, polydextrose, or the combination. Additionally, the validity of these findings is limited by the lack of a comparator group. Clinical research evaluating the use of FOS alone is limited. Preliminary clinical research in elderly males shows that taking FOS alone 3-10 grams daily for 30 days increases the frequency of defecation by 1.5-fold when compared with baseline (8505). The validity of this study is limited by the lack of a comparator group. In non-breastfeeding infants 6-24 months of age with constipation, preliminary clinical research shows that fortifying formula or milk with FOS daily for 4 weeks increases the frequency of soft stools by 33% and decreases the frequency of straining by 55% when compared with placebo. However, the use of FOS did not increase the percentage of infants who achieved normal bowel pattern. The daily dose of FOS was 6 grams for infants 6-8.9 kg, 9 grams for infants 9-11.9 kg, and 12 grams for infants over 12 kg (98651).
• Diabetes. Oral FOS has only been evaluated in combination with probiotics; its effect when used alone is unclear. Details: Preliminary clinical research in adults with type 2 diabetes shows that taking a combination product containing FOS 500 mg, Bacillus coagulans 100 billion spores, Lacticaseibacillus rhamnosus 10 billion colony-forming units (CFUs), and Lactobacillus acidophilus 1 billion CFUs once daily for 12 weeks reduces fasting blood glucose by 17 mg/dL, compared with an increase of 3 mg/dL with placebo. However, taking this product did not affect body weight, waist circumference, or cholesterol levels. It is unclear if this effect is due to FOS, other ingredients, or the combination (107731).
• Hematopoietic stem cell transplant (HSCT). It is unclear if oral FOS is beneficial in patients undergoing HSCT. Details: Preliminary clinical research in patients undergoing an allogeneic HSCT shows that taking a specific oral FOS supplement, (Fibrulose F97, Cosucra Groupe) 5-15 grams daily for 21 days, beginning 5 days before transplant, does not reduce acute graft-versus-host disease, blood stream infections, or Clostridioides difficile infections or improve overall survival when compared with control (107931). However, this study may have been inadequately powered to detect a difference between groups.
• Hypercholesterolemia. Although there has been interest in using oral FOS for hypercholesterolemia, there is insufficient reliable information about the clinical effects of FOS for this purpose.
• Obesity. Although there has been interest in using oral FOS for obesity, there is insufficient reliable information about the clinical effects of FOS for this purpose.
• Osteoporosis. Oral FOS has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in postmenopausal adults shows that taking a specific FOS product (NutraFlora, Ingredion Inc.) 3.2 grams plus calcium 800 mg daily for 24 months reduces the decline in total-body bone mineral density (BMD) when compared with calcium alone, but not when compared with a maltodextrin control. In a subgroup of patients with osteopenia, this combination reduced the decline in BMD in the lumbar vertebrae when compared with calcium alone or a maltodextrin control (94931).
• Travelers' diarrhea. It is unclear if oral FOS is beneficial for preventing traveler's' diarrhea. Details: Preliminary clinical research shows that taking FOS 10 grams orally daily for 4 weeks, starting 2 weeks before traveling to a medium- to high-risk destination, does not reduce the incidence of travelers' diarrhea when compared with placebo (10373). However, the study may have been inadequately powered to detect a difference between groups. More evidence is needed to rate FOS for these uses.

(Read more about FRUCTO-OLIGOSACCHARIDES (FOS))

POSSIBLY EFFECTIVE

• Constipation. Glucomannan is generally effective for treatment of constipation in adults, but the efficacy in children is less clear. Details: Clinical research in adults shows that taking glucomannan 1-1.5 grams three times daily orally for 3-5 weeks, sometimes followed by 1 gram twice daily for an additional 4 weeks, can relieve constipation. As a nonabsorbable dietary fiber, glucomannan appears to have a bulk laxative effect (11294,57783,57795,57816). Taking glucomannan 1.45 grams with lactulose 4.2 grams twice daily orally for 1-3 months appears to relieve constipation during pregnancy (57818). In children with constipation, glucomannan can increase the frequency of bowel movements but does not seem to improve stool consistency. A meta-analysis of 3 clinical trials including 122 children with functional constipation shows that glucomannan leads to 1.4 more stools per week but does not improve stool consistency when compared with placebo or a maltodextrin control (97935). Two studies included in this analysis show that taking a specific glucomannan supplement (Dicoplus, Dicofarm) 100 mg/kg once or twice daily (maximum daily dose 5 grams) along with fluids for up to 12 weeks relieves constipation in children (11295,57775). However, the other clinical study included in the analysis shows that taking a different glucomannan supplement (Dicoman Junior, Vitis Pharma) 1.26 grams twice daily for 4 weeks does not improve constipation in children (92005).
• Diabetes. Limited clinical research suggests that glucomannan may improve glycemic control and lipid profiles in patients with type 2 diabetes. Details: Taking glucomannan orally seems to reduce serum cholesterol and blood glucose levels in patients with type 2 diabetes (183,11357,11359,57791,57797,57798,112702). Most clinical research shows that a glucomannan dose of 3-15 grams daily for 4-12 weeks may reduce fasting blood glucose (183,11357,57791,57797,111225). Eating cookies containing glucomannan 0.5-0.7 grams per 100 kcal for 3 weeks has also been used (11358,11359,57797). Accordingly, a meta-analysis of 5 mostly small, low-quality clinical studies in adults with type 2 diabetes, that includes several of these studies, shows that taking glucomannan 1.2-15 grams daily for 4-16 weeks modestly improves fasting blood glucose when compared with placebo or wheat bran. This analysis also shows that taking glucomannan modestly improves 2-hour post-prandial glucose, total cholesterol, and low-density lipoprotein (LDL) levels but not triglycerides (112702). In healthy people, adding a specific glucomannan supplement (PolyGlycopleX, InovoBiologic Inc.) as granules, 2.5-7.5 grams before meals, or as capsules 3-6 grams with meals, can reduce the glycemic index of starchy foods (92003,92007). Also, taking this glucomannan product reduces postprandial glucose in a dose-dependent fashion in healthy people (92002,92007). However, the interpretation of this evidence is limited by low-quality research and variations in dosages and formulations.
• Hyperlipidemia. Most clinical research shows that glucomannan can reduce cholesterol levels in healthy people and those with hyperlipidemia. Details: Although some conflicting evidence exists (57794), most research shows that taking glucomannan orally can improve lipid levels in healthy adults, children and adults with hyperlipidemia, and adults with diabetes (178,11357,11358,11359,57779,57781,57784,57791,57799,97936)(112702). Meta-analyses of clinical research show that taking glucomannan 2.5-15.1 grams daily for up to 12 weeks can reduce total cholesterol by 19 mg/dL, low-density lipoprotein (LDL) cholesterol by 13-16 mg/dL, non-high-density lipoprotein cholesterol by 12 mg/dL, and triglycerides by 11 mg/dL when compared with a control (57797,97936). Clinical research has not demonstrated a dose-response relationship, and the most common glucomannan doses are 5-10 grams daily for up to 6 weeks for adults and 2-3 grams daily in divided doses for up to 8 weeks for children (11358,11359,57797,97936).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Dumping syndrome. It is unclear if oral glucomannan is beneficial in patients with dumping syndrome. Details: Preliminary clinical research shows that taking glucomannan (Propol, Pharmacia) 2.6 or 5.2 grams as a single dose reduces the incidence of reactive hypoglycemia following an oral glucose load in adult patients with previous gastric surgery (57805). Other preliminary clinical research shows that taking glucomannan improves glucose tolerance, but not glucose absorption, in children experiencing gastric dumping syndrome after gastric surgery (57804).
• Hypertension. It is unclear if oral glucomannan is beneficial in patients with hypertension. Details: Preliminary clinical research in patients with hypertension shows that eating cookies containing 0.7 grams of glucomannan per 100 kcal, for a total dose of up to 13 grams of glucomannan daily for 3 weeks, can lower systolic blood pressure by about 7% when compared with placebo (11359).
• Hyperthyroidism. It is unclear if oral glucomannan is beneficial in patients with hyperthyroidism. Details: Preliminary clinical research in patients with hyperthyroidism shows that taking glucomannan 1.3 grams twice daily orally, plus methimazole and propranolol for 2 months, reduces serum triiodothyronine (T3) and thyroxine (T4) levels during the first few weeks of therapy, when compared with methimazole and propranolol alone. However, these effects seem to diminish after 6 weeks of therapy (57793).
• Metabolic syndrome. It is unclear if oral glucomannan is beneficial for metabolic syndrome. Details: A small crossover study in adults with metabolic syndrome, defined as impaired glucose tolerance, reduced high-density lipoprotein (HDL) cholesterol, elevated serum triglycerides, and moderate hypertension, shows that consuming biscuits containing glucomannan 0.5 grams per 100 kcal (equivalent to approximately 8-13 grams/day) daily for 3 weeks may modestly improve fasting glucose, but does not improve blood pressure or levels of triglycerides or HDL cholesterol when compared with wheat bran biscuits (11358). However, the 2-week washout period between interventions may be too short to detect differences in some outcomes.
• Obesity. Although some low-quality research shows that oral glucomannan is beneficial for achieving slight improvements in body weight, other research does not support this. Details: Meta-analyses of clinical research on the use of glucomannan for improving body weight and body composition in adults and children with overweight or obesity show mixed results, with one analysis suggesting that taking glucomannan reduces body weight by around 0.8 kg when compared with placebo (57797), and another showing no improvement in body weight (92014). Reasons for these discrepant findings are not clear, but the discrepancies may relate to differences in the study populations and dosing and duration of glucomannan treatment, as well as the low methodological quality of many studies conducted to date. Similar to the pooled analyses described above, individual clinical study results are also mixed. Several small clinical studies show that taking glucomannan can improve body weight, body mass index (BMI), fat mass, and other measures of body composition in children and adults with overweight or obesity, usually when used in combination with a calorie-restricted diet (180,181,182,183,54240,92008,92010,92011,111224,112701). However, conflicting evidence exists (179,57784,57790,57796,92009,112430). Doses that have been used with positive outcomes in adults are 3-4 grams daily, taken in divided doses, for up to 3 months (181,182,183,92008,112701). In children, doses were 2-3 grams daily for 4 months (180). Specific products evaluated include Propylene TM (Natural Alternatives International), PolyGlycopleX (InovoBiologic, Inc.) 3-5 grams 2-3 times daily for 15 weeks, and. Chrombalance 338 mg before each meal and 226 mg in the afternoon daily for 5 weeks (54240,92010,92011). More evidence is needed to rate glucomannan for these uses.

(Read more about GLUCOMANNAN)

POSSIBLY EFFECTIVE

• Constipation. Most clinical research shows that oral inulin modestly improves stool frequency, but may not improve discomfort, in adults and children with constipation. Details: A meta-analysis of clinical research in adults with constipation shows that consuming inulin improves stool frequency by approximately 0.7 stools per week. It also seems to improve stool transit time, consistency, and hardness, but does not reduce pain or bloating (93718). Additional clinical research shows that taking a specific type of inulin (OraftiGR, BENEO GmbH) 12 grams daily in three divided doses for 4 weeks increases stool frequency by approximately one stool per week when compared with a maltodextrin control. Taking inulin also reduces the number of patients experiencing hard and lumpy stools by 13%, but does not improve symptoms of bloating, distension, physical discomfort, or gas (96850). In children aged 2-5 years, one small clinical study shows that taking a specific combination of two inulin products (Orafti P95 oligofructose and Orafti GR inulin, BENEO GmbH), 2 grams twice daily in a dairy liquid for 6 weeks, improves the softness of stools, but not pain with stooling or stool frequency, when compared with a maltodextrin control (96848). Research in older adults is conflicting. One small study shows that taking inulin 20-40 grams daily for 19 days increases the number of stools from 1-2 per week to 8-9 per week (10415). However, other preliminary clinical research in this population shows that taking a specific inulin supplement (Fibruline Instant, Cosucra Groupe Warcoing) 15 grams daily in yogurt or stewed fruit for 4 weeks does not improve bowel symptoms, stool frequency, or stool consistency (93724).
• Diabetes. Short-term use of oral inulin along with antidiabetes drugs may improve glycemic control in some patients with type 2 diabetes; however, the benefits of long-term use are unclear. Details: Two meta-analyses of clinical research in normal weight and obese patients with type 2 diabetes show that taking inulin 0.8-10 grams orally daily for 6-12 weeks reduces glycated hemoglobin (HbA1c) by 0.65% and fasting plasma glucose by 16 mg/dL when compared with control. Taking inulin also improved HOMA-IR, a measure of insulin resistance, when compared with control. Researchers did not evaluate the most effective dose of inulin; however, most studies used 8.4-10 grams daily (103198,105533). In females treated with metformin and glyburide, taking inulin 10 grams daily for 8 weeks reduces fasting blood glucose by 15 mg/dL and HbA1c by 1% when compared with placebo (93719). Population research in adults has also found that high dietary intake of inulin over 8 years of follow up is associated with a 6% lower risk of type 2 diabetes when compared with low dietary intake (110515). Inulin has also been studied in combination with other supplements. Preliminary clinical research in elderly patients with diabetes shows that drinking a milk powder product supplemented with inulin and resistant dextrin 30 grams before breakfast and 15 grams before dinner for 12 weeks decreases fasting plasma glucose by 17 mg/dL, HbA1c by 0.38%, postprandial glucose by 27 mg/dL, body weight by 0.8 kg, and systolic and diastolic blood pressure by 5 mmHg when compared with placebo (99843). Other clinical research in adults with type 2 diabetes shows that taking a specific combination product (Orafti Synergy1, BENEO GmbH), containing 50% inulin and 50% fructo-oligosaccharides, 8 grams orally twice daily for 6 weeks does not reduce body weight or caloric intake or increase satiety scores when compared with placebo (107934).
• Obesity. Oral inulin might modestly improve short-term weight loss. Additional research is needed to determine the long-term effects of inulin on weight loss and weight maintenance in overweight or obese individuals. Details: Some clinical research in overweight and obese females with diabetes shows that taking inulin 10 grams daily for 8 weeks results in weight loss of 2.6 kg, compared with no weight loss in those taking placebo (93719). Preliminary clinical research in overweight or obese patients with prediabetes shows that taking a specific brand of inulin (Orafti Synergy 1, BENEO GmbH) 30 grams orally daily for 6 weeks reduces body weight by 0.4 kg, compared with a 0.4 kg increase in those in the control group (93721). Preliminary clinical research in adults with obesity shows that taking inulin 16 grams orally daily for 3 months moderately reduces body weight and body mass index (BMI) when compared with placebo. However, these effects were most prominent in subjects that also increased physical activity (110514). Additional preliminary clinical research in adults with overweight shows that adding 18 grams of inulin powder to green tea daily increases weight loss when compared with green tea alone. Over six weeks, individuals taking inulin lost 2 kg, compared with no weight loss in those taking green tea. Weight loss was maintained for at least 2 weeks (93726). Clinical trials in children show conflicting results. In children aged 7-12 years, a small clinical study shows that taking a specific oligofructose-enriched inulin product (Orafti Synergy1, BENEO GmbH) 8 grams orally in water before one meal daily for 16 weeks decreases weight gain by 2.4-fold and attenuates an increase in BMI when compared with placebo (96847). However, other preliminary clinical research in children with obesity aged 7-15 years shows that taking inulin extract 13 grams orally daily for 6 months does not reduce body weight or BMI when compared with placebo (110598). However, other clinical research shows that taking inulin orally in combination with other ingredients might not improve weight loss. Combining inulin, chromium picolinate, capsicum, L-phenylalanine, and other nutrients with caloric reduction and exercise doesn't seem to reduce weight in moderately obese patients when compared to caloric reduction and exercise alone (7607). Another preliminary clinical trial shows that taking inulin 10 grams with maltodextrin 10 grams daily for 12 weeks does not reduce body weight or improve body composition when compared with placebo in adults with overweight or obesity following a calorie-restricted diet (103202). Preliminary clinical research in adults with obesity also shows that consuming a seafood-based dietary product fortified with inulin 1.7 grams, fish oil 370 mg (containing eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and bifidobacterium animalis daily for 12 weeks does not lower body weight, waist circumference, abdominal fat, serum cholesterol levels, or blood pressure when compared with placebo. However, consuming the product modestly improved some markers of insulin resistance (110600).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Alcohol use disorder. It is unclear if oral inulin is beneficial in patients with alcohol use disorder. Details: Preliminary clinical research in adults with alcohol use disorder who were recently admitted to the hospital shows that taking a specific inulin product (Fibruline, Cosucra) 4-16 grams orally daily for 17 days does not improve liver function tests when compared with placebo. Some liver function tests were also worse in those treated with inulin (110601).
• Antibiotic-associated diarrhea. Oral inulin has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in children aged 6 months to 14 years receiving antibiotics for common infections shows that taking a combination of inulin and fructo-oligosaccharides, up to 5 grams daily depending on age, does not reduce the rate of antibiotic-associated diarrhea (93720).
• Celiac disease. Small clinical studies suggest that patients with celiac disease who take oral inulin may have a lower risk of vitamin and mineral deficiency. Details: Preliminary clinical research in a small number of children and adolescents with vitamin and mineral malabsorption due to celiac disease shows that taking a specific oligofructose-enriched inulin product (Orafti Synergy 1, BENEO GmbH) 10 grams daily for 3 months improves the absorption of vitamin D, vitamin E, and iron, but not vitamin A (99841,99842). Levels of 25-hydroxy vitamin D and vitamin E increased by 42% and 19%, respectively, compared with no significant improvements in those taking placebo (99842). Although taking inulin did not improve serum ferritin levels, it did decrease serum hepcidin concentrations by 61% when compared with baseline, while no significant improvement was reported with placebo. Hepcidin is a regulator of iron homeostasis, and increased levels are associated with iron-deficiency anemia (99841).
• Child growth. Oral inulin has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in healthy, exclusively formula-fed, infants less than 4 months of age shows that supplementing formula with 0.8 grams/dL of a specific combination product (Orafti Synergy1, Beneo-Orafti) containing 50% inulin and 50% fructo-oligosaccharide until 12 months of age does not improve markers of child growth, including body weight, length, and head circumference, when compared with placebo. The combination product was associated with a reduced duration of fever during infectious episodes, but not with a reduction in the number of infections. It is unclear if any potential effects are due to inulin, fructo-oligosaccharide, or the combination (107937).
• Chronic kidney disease (CKD). It is unclear if oral inulin is beneficial in patients with CKD. Details: In adults with CKD, adding inulin 19 grams daily for 6 months to a low-protein diet reduces serum insulin, fasting plasma glucose, total serum cholesterol, triglycerides, and markers of systemic inflammation, while increasing serum high density lipoprotein (HDL) cholesterol, when compared with baseline (105534). However, it is unclear if similar changes occur with a low-protein diet alone, or if the rate of progression of CKD is reduced. Population research in adults has found that high dietary intake of inulin over 8 years of follow up is not associated with a lower risk of CKD when compared with low dietary intake (110515).
• Hypercholesterolemia. It is unclear if oral inulin reduces cholesterol levels in patients with hypercholesterolemia. Details: Research in patients with hypercholesterolemia has shown mixed results, with some studies showing a small decrease and others showing no improvement in serum cholesterol levels (7604,8450,10412,10413,96849). A typical dose of inulin used is 6 grams orally three times daily for up to 6 weeks (10412). A meta-analysis of healthy, dyslipidemic, overweight or diabetic patients shows that inulin reduces levels of low-density lipoprotein (LDL) cholesterol by approximately 5% (96849). Another meta-analysis of randomized clinical trials in the same population shows that taking inulin 1.5-30 grams daily for 2-12 weeks reduces LDL cholesterol levels by 7 mg/dL and increases high-density lipoprotein cholesterol levels by 2 mg/mL when compared with control. However, this meta-analysis also included data from patients treated with fructo-oligosaccharides instead of inulin (107940).
• Hypertension. It is unclear if oral inulin is beneficial in patients with hypertension. Details: Population research in adults has found that high dietary intake of inulin over 8 years of follow up is associated with a 21% lower risk of hypertension when compared with low dietary intake (110515).
• Hypertriglyceridemia. It is unclear if oral inulin is beneficial in patients with hypertriglyceridemia. Details: A meta-analysis of clinical trials in normal and moderately hyperlipidemic patients suggests that taking inulin-type fructans at an approximate average dose of 14 grams daily reduces triglyceride levels by about 15 mg/dL when compared with control (93737). However, other research, including a meta-analysis of healthy, dyslipidemic, overweight or diabetic patients shows that taking inulin 1.5-30 grams daily for 2-12 weeks does not reduce triglyceride levels when compared with control. However, these negative studies are limited by small sample sizes and inclusion of data from patients treated with fructo-oligosaccharides instead of inulin (7604,107940).
• Impaired glucose tolerance (prediabetes). Several small clinical studies suggest that oral inulin is not beneficial in patients with prediabetes. Details: Preliminary clinical research in adults with prediabetes shows that taking inulin 15 grams orally daily for 24 weeks does not improve fasting blood glucose, glycated hemoglobin (HbA1c), or lipid levels when compared with placebo. However, taking inulin modestly improved markers of insulin resistance (107938). Two other, small, clinical trials show that taking specific inulin products (Orafti Synergy 1, BENEO GmbH or Frutafit IQ, Sensus American) 10-30 grams daily for 6 weeks does not improve blood glucose, insulin resistance, glucose homeostasis, or insulin sensitivity when compared with placebo (93721,107936). However, these studies may have been inadequately powered to detect a difference between groups.
• Iron deficiency anemia. Oral inulin has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in young adult females with iron deficiency anemia shows that taking inulin 963 mg/kg and iron supplementation orally daily for 3 months modestly improves serum hemoglobin, hematocrit, and iron levels when compared with a control group consuming iron-fortified flour (110599).
• Menopausal symptoms. It is unclear if oral inulin is beneficial in patients with hypertriglyceridemia. Details: Preliminary clinical research in adults experiencing menopause shows that consuming yogurt enriched with a specific inulin (Frutafit TEX, Sensus Company) 1.5% daily for 6 weeks moderately improves menopausal symptom scores, including depression, anxiety, and vasomotor symptoms, when compared with yogurt alone (107659).
• Nonalcoholic fatty liver disease (NAFLD). Taking oral inulin alone does not seem to improve liver transaminase levels in patients with NAFLD. Details: Preliminary clinical research in patients with NAFLD shows that taking metronidazole 400 mg twice daily for one week plus inulin 4 grams twice daily for 12 weeks reduces levels of alanine aminotransferase and aspartate aminotransferase when compared with placebo. However, when inulin is taken without metronidazole, these measures are not improved (103200).
• Polycystic ovary syndrome (PCOS). It is unclear if oral inulin is beneficial in patients with PCOS. Details: Preliminary clinical research in overweight or obese females with PCOS shows that taking specific products containing inulin (FrutaFit TEX, Sensus American) or inulin and fructo-oligosaccharides (FrutaFit IQ, Sensus American) 10 grams orally once daily for 12 weeks does not reduce systolic or diastolic blood pressure when compared with placebo. However, the validity of this study is limited by the inclusion of subjects with and without hypertension at baseline (107941). More evidence is needed to rate inulin for these uses.

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POSSIBLY SAFE. ..when used orally, short-term. Chitosan has been used with apparent safety in clinical studies at a dose of up to 1.35 grams daily for up to 3 months (1942,9609,9610,10022,10023,10024,10025,11307,13171,14314)(15126,92781,97708). ...when used topically, short-term (1944,1945,4269,4270,97712,106521).

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

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POSSIBLY SAFE ...when used orally and appropriately, alone or in combination with probiotics, in doses up to 30 grams daily for up to 4 weeks (741,745,8505,90266,107729,107931). ...when a specific FOS product (NutraFlora, Ingredion Inc.) is used orally in combination with calcium at doses up to 3.2 grams daily for up to 24 months (94931).

CHILDREN: POSSIBLY SAFE
when short-chain FOS are included in approved infant formulas for healthy term infants at a level of up to 4 grams/L or 1 gram/kg daily (94929,94930,98651).

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

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LIKELY SAFE ...when used orally as food (11358,11359). Glucomannan powder or flour is often used to enrich noodles in traditional Japanese foods.

POSSIBLY SAFE ...when used orally with at least 250 mL (8 ounces) of water or other fluid. Glucomannan has been safely used in studies lasting up to 4 months (178,179,181,182,11046,11294,11357,11294,54240,57775)(57781,57783,57784,92004,92008,92009,92010,92011,106410). In the European Union, the maximum permitted level in foods is 10 grams/kg (106411).

POSSIBLY UNSAFE ...when used orally without any liquid, especially when in tablet form. There have been reports of choking and esophageal or gastrointestinal obstruction when glucomannan products are taken dry. A safety alert for this has been issued by Health Canada (11293,57785,106410).

CHILDREN: POSSIBLY SAFE
when used orally and appropriately with at least 250 mL (8 ounces) of water or other fluid. Glucomannan has been safely used in children for up to 4 months (179,180,11295,57775,57779,92005,92006,97935).

CHILDREN: LIKELY UNSAFE
when used orally without any liquid, especially when in tablet form. There have been reports of esophageal and gastrointestinal obstruction when glucomannan products are taken dry (11293,57785,106410).

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

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LIKELY SAFE ...when used orally in amounts commonly found in foods. Inulin has Generally Recognized As Safe status (GRAS) in the US (93728).

POSSIBLY SAFE ...when used orally and appropriately in supplemental doses, short-term. Doses of 8-18 grams daily have been used safely for up to 24 weeks (7604,7605,7606,7607,8451,93716,93719,93726,103200,107936,107935,107938). Also, 20 grams daily has been used with apparent safety for up to 3 weeks (96836,96850). There is insufficient reliable information available about the safety of inulin when used long-term.

CHILDREN: LIKELY SAFE
when used orally in amounts commonly found in foods. Inulin has Generally Recognized As Safe status (GRAS) in the US (93728).

CHILDREN: POSSIBLY SAFE
when used orally and appropriately in supplemental doses, short-term. Clinical studies have used doses of 3-6 grams daily for 10 days in children 3-6 years of age and 5-13 grams daily for up to 6 months in children 7-15 years of age with apparent safety (96847,110598,110602). ...when used in infant formula. A formula containing chicory fructans (Orafti Synergy1, BENEO GmbH), approximately 50% of which were inulin, has been used with apparent safety in infants for 8-12 months (93717,107937).

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in amounts commonly found in foods (93728). There is insufficient reliable information available about using inulin in medicinal amounts during pregnancy or lactation; avoid use.

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ACYCLOVIR (Zovirax) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Chitosan can reduce the absorption of acyclovir, potentially increasing the risk for treatment failure.  Details Clinical research in humans shows that taking chitosan along with acyclovir 200 mg reduces acyclovir absorption. Concomitant administration of chitosan 400 mg or 1000 mg reduced the acyclovir area under the curve (AUC) and peak plasma concentration by about 30% and 40%, respectively, compared with control. Concomitant administration with chitosan 1000 mg also increased time to peak concentration from 1 hour to 2 hours (92780). In vitro research suggests that the mechanism for reduced absorption is due to acyclovir entrapment in chitosan-mucus complexes, which reduces intestinal absorption (112352).

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, chitosan might increase the risk of bleeding when taken with warfarin.  Details In a case report, a patient taking warfarin had a significantly increased international normalized ratio (INR) after starting chitosan 1200 mg daily. The INR normalized after chitosan was discontinued and vitamin K was administered. The patient once again started taking chitosan and again had a significant increase in INR. The INR stabilized again once chitosan was discontinued (15909). Researchers theorize that this interaction might occur because chitosan decreases absorption of fat-soluble vitamins, including vitamin K, which could increase the anticoagulant effect of warfarin.

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ORAL DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Theoretically, glucomannan may decrease absorption of drugs taken orally.  Details Due to its viscosity and bulking effects, there is concern that glucomannan can decrease the absorption of oral drugs. A small clinical study in healthy volunteers shows that taking glyburide 2.5 mg plus glucomannan 3.9 grams with breakfast reduces plasma levels of glyburide when compared with breakfast and glyburide alone (11360). In addition, animal research demonstrates this effect on amoxicillin, but shows increased absorption of metronidazole. This mouse model also demonstrates that metronidazole elimination is prolonged, but amoxicillin elimination is enhanced by 38%; glucomannan may also affect the distribution of some drugs (112703). To avoid changes in absorption, take glucomannan 30-60 minutes after taking oral drugs.

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ANTIDIABETES DRUGS Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, inulin might increase the risk of hypoglycemia with antidiabetes drugs.  Details Some clinical research shows that inulin improves glycemic control in patients with diabetes; however, it is unclear if it has hypoglycemic effects (93719,99843,103198).

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General ...Orally and topically, chitosan seems to be well tolerated, short-term.
Most Common Adverse Effects:
Orally: Constipation, diarrhea, flatulence, epigastric discomfort, and nausea.

Dermatologic ...In one clinical trial, a subject with kidney failure reported itching during 12 weeks of oral chitosan treatment (1942). It is not clear if this was related to the underlying renal failure or the use of oral chitosan.

Gastrointestinal ...Orally, chitosan has been reported to cause epigastric discomfort, constipation, flatulence, diarrhea, nausea, and dryness of the throat (1942,3243,9986,11307,14314,41688,92781,100170). Excessive discharge of fat in the feces, also known as steatorrhea, has been reported with chitosan therapy (41724,41726). Theoretically, chitosan may alter the normal intestinal flora via antimicrobial activity, which could interfere with lipid digestibility and bile acid metabolism, leading to the growth of resistant pathogens (41687,41709,41725).

Musculoskeletal ...Orally, chitosan has been reported to cause swollen heels and wrists in two patients (41688).

Neurologic/CNS ...Headaches have been reported in patients taking oral chitosan (41688).

Ocular/Otic ...Topically, an eye drop containing chitosan-N-acetylcysteine has been reported to cause itching and irritation of the eyes (97710).

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General ...Orally, FOS are generally well tolerated.
Most Common Adverse Effects:
Orally: Abdominal pain, bloating, flatulence.

Gastrointestinal ...Orally, FOS may cause flatulence, belching, abdominal pain, intestinal sounds, constipation, and bloating. These symptoms can occur commonly in some patients, but are generally mild at doses under 10 grams per day (745,750,8509,98651,107931). However, a meta-analysis of 8 small clinical studies shows that taking FOS at doses ranging from 2.5 grams to 15 grams daily for up to 8 weeks does not increase the rate of abdominal pain, bloating, flatulence, or intestinal sounds when compared with control groups (110710).

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General ...Orally, glucomannan is generally well tolerated when taken with plenty of water or other liquid.
Most Common Adverse Effects:
Orally: Abdominal pain, bloating, constipation, diarrhea, flatulence, nausea, and vomiting.
Serious Adverse Effects (Rare):
Orally: Choking and esophageal or gastrointestinal obstruction, especially when taken as a dry powder or in tablet form.

Gastrointestinal ...Orally, glucomannan can cause gastrointestinal disturbances, including abdominal pain, bloating, constipation, diarrhea, flatulence, nausea, and vomiting, especially when taken in doses of more than 3 grams daily (57781,57784,92004,92010,92011,97935,106411). Esophageal and gastrointestinal obstructions have been reported when dry glucomannan-containing products are taken with insufficient fluid (11293,57785,106410).

Hepatic ...Acute cholestatic hepatitis occurred in a 31-year-old male after taking glucomannan orally for 45 days (57777). He was also taking other supplements, including garlic and chitosan, so it is unclear whether the hepatitis was due to glucomannan, other supplements, or the combination.

Pulmonary/Respiratory ...Cases of occupational respiratory disorders, including respiratory sensitization and bronchial asthma, have been reported in workers exposed to glucomannan (57789,57810).

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General ...Orally, inulin is well tolerated.
Most Common Adverse Effects:
Orally: Bloating, constipation, diarrhea, flatulence, and gastrointestinal cramps.
Serious Adverse Effects (Rare):
Orally: Anaphylaxis has occurred following consumption of foods high in inulin.

Gastrointestinal ...Orally, inulin may cause flatulence, bloating, diarrhea, constipation, and gastrointestinal cramps, especially at doses over 30 grams (7604,8450,8509,93716,93721,93724,96836,96850,96851,99843)(107936,107940,107941,110602).

Immunologic ...Severe allergic reactions to inulin-containing foods have been reported. There is one report of anaphylaxis following consumption of foods with a high concentration of inulin including salsify, artichoke leaves, and margarine (7608).

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