Cinnamon Gymnema Mulberry Complex [Discontinued] by Swanson

POSSIBLY INEFFECTIVE

• Diabetes. Most research shows that oral Ceylon cinnamon does not benefit patients with type 2 diabetes. Details: Clinical research in adults with well-controlled type 2 diabetes shows that taking Ceylon cinnamon 1-9 grams orally daily for 2-3 months does not improve fasting blood glucose when compared with placebo or a control group (99436,99437,99439). However, one small clinical study in adults with poorly controlled type 2 diabetes despite treatment with metformin showed a trend toward improvement in fasting blood glucose. Taking Ceylon cinnamon 3 grams daily for 8 weeks reduced fasting blood glucose by 12 mg/dL, compared with an increase of 9 mg/dL in those taking placebo. Although this difference was not statistically significant, the study might not have been adequately powered to show a difference. Also, the 8-week duration of this study was too short to reliably assess the effect of Ceylon cinnamon on glycated hemoglobin (HbA1c) (99438). Conversely, a large study clinical study in patients with type 2 diabetes conducted in India shows that taking Ceylon cinnamon 1.5 grams daily for 4 months improves fasting blood glucose by 40 mg/dL and HbA1c by 1% when compared with placebo but does not significantly improve either outcome when compared to baseline (112422). However, it is unclear whether modifications to diabetes medications were allowed during the study.
• Obesity. Preliminary clinical research suggests that oral Ceylon cinnamon does not help with weight loss. Details: Preliminary clinical research shows that drinking black tea steeped with 3 grams of Ceylon cinnamon dried powder three times daily for 8 weeks does not affect weight, waist circumference, or blood pressure when compared with baseline or black tea alone in overweight patients with diabetes (95597). Other preliminary research shows that taking Ceylon cinnamon, titrated up from 85 mg to 500 mg, daily for 3 months has no effect on weight or body mass index, but may reduce hip circumference by 1.8 cm, when compared with baseline in healthy, mostly normal weight adults (97250).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Allergic rhinitis (hay fever). A nasal spray containing a Ceylon cinnamon extract might improve symptoms of allergic rhinitis. It is unclear if oral Ceylon cinnamon is beneficial. Details: Using a nasal spray containing a polyphenol-rich standardized extract of Ceylon cinnamon 1 mg/mL, twice daily in each nostril for 7 days, reduces the severity of nasal, eye, and nocturnal symptoms, and improves quality of life and work productivity when compared with placebo in people with seasonal allergic rhinitis who are not using any other medications for the condition (103169). One small clinical study in patients with seasonal allergic rhinitis shows that taking a specific combination product (ClearGuard, Access Business Group LLC) containing Ceylon cinnamon extract, acerola fruit concentrate, and powdered Spanish needles (Bidens pilosa) orally, 450 mg three times daily for 3 days, improves nasal symptoms 8 hours after, but not immediately following, a nasal allergen challenge when compared with placebo (23709).
• Chronic obstructive pulmonary disease (COPD). Ceylon cinnamon has only been studied in combination with other ingredients; its effect when used alone is unclear. Details: A moderate-sized clinical study in adults with COPD shows that taking a combination product containing extracts of Ceylon cinnamon, ginger, alpinia, cardamom, and saffron in honey 3 times daily for 8 weeks improves confidence in leaving home and the ratio of forced exploratory volume per second to forced vital capacity of the lungs (FEV1/FVC) when compared with placebo. However, the combination product does not improve most measures of respiratory function or symptoms such as cough, phlegm, chest tightness, dyspnea, reduced energy levels, sleeping disorders, or activity limitations when compared with placebo (111542). It is unclear if these effects are due to Ceylon cinnamon, other ingredients, or the combination.
• Common cold. Although there has been interest in using oral Ceylon cinnamon for the common cold, there is insufficient reliable information about the clinical effects of Ceylon cinnamon for this purpose.
• Denture stomatitis. It is unclear if topical Ceylon cinnamon is beneficial in patients with denture stomatitis. Details: A small clinical trial in patients with denture stomatitis shows that using 10 mL of a mouthwash, as well as a denture spray, containing Ceylon cinnamon essential oil three times daily for 15 days modestly reduces Candida measurements and improves the severity of stomatitis in the oral mucosa and dentures when compared with baseline (108262). The validity of these findings is limited by the lack of a comparator group.
• Diarrhea. Although there has been interest in using oral Ceylon cinnamon for diarrhea, there is insufficient reliable information about the clinical effects of Ceylon cinnamon for this purpose.
• Dysmenorrhea. It is unclear if oral Ceylon cinnamon is beneficial in patients with dysmenorrhea. Details: One preliminary clinical trial in adults with primary dysmenorrhea shows that taking Ceylon cinnamon orally 1 gram three times daily during the first 72 hours of menstruation over the course of two cycles decreases pain by 1.6 points on a 10-point visual analog scale when compared with placebo (99875). The use of a per-protocol analysis limits the validity of these results.
• Dyspepsia. It is unclear if oral Ceylon cinnamon is beneficial in patients with dyspepsia. Details: A small clinical trial in patients with functional dyspepsia shows that taking one capsule of Ceylon cinnamon oil, providing an unspecified dose, three times daily for 6 weeks does not improve symptoms of dyspepsia when compared with sesame oil as placebo (108263).
• Hypertension. It is unclear if oral Ceylon cinnamon is beneficial in patients with prehypertension. Details: A small clinical trial in patients with prehypertension shows that taking Ceylon cinnamon 500 mg three times daily for 90 days does not affect final blood pressure measurements when compared with placebo. However, there was a modest reduction in mean daytime systolic blood pressure when compared with placebo (108261).
• Impaired glucose tolerance (prediabetes). Although there has been interest in using oral Ceylon cinnamon for impaired glucose tolerance, there is insufficient reliable information about the clinical effects of Ceylon cinnamon for this purpose.
• Influenza. Although there has been interest in using oral Ceylon cinnamon for influenza, there is insufficient reliable information about the clinical effects of Ceylon cinnamon for this purpose.
• Intestinal parasite infection. Although there has been interest in using oral Ceylon cinnamon for intestinal parasite infection, there is insufficient reliable information about the clinical effects of Ceylon cinnamon for this purpose.
• Irritable bowel syndrome (IBS). Oral Ceylon cinnamon has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that taking a combination of powdered Ceylon cinnamon 1.5 grams, dried bilberry fruit 10 grams, slippery elm bark 4.5 grams, and agrimony 3 grams orally twice daily for 3 weeks increases the number of bowel movements and reduces symptoms such as abdominal pain, bloating, flatulence, and straining in patients with diarrhea-predominant IBS (35462).
• Migraine headache. It is unclear if oral Ceylon cinnamon is beneficial in patients with migraine headache. Details: Preliminary clinical research shows that taking Ceylon cinnamon powder orally 600 mg three times daily for 2 months, in addition to regular medications for migraine, decreases the frequency, severity, and duration of migraine attacks when compared with placebo (104520).
• Polycystic ovary syndrome (PCOS). It is unclear if oral Ceylon cinnamon is beneficial in patients with PCOS. Details: Taking Ceylon cinnamon orally 1.5 grams daily for 3 months in adults with PCOS does not appear to improve fasting insulin levels, fasting glucose levels, glycated hemoglobin, testosterone, lipid parameters, body weight, or body mass index when compared with placebo (97248). However, a meta-analysis of 5 low-quality studies shows that taking Ceylon cinnamon 0.5-1.5 grams daily for 8 weeks to 1 year reduces insulin resistance and fasting serum insulin levels (104518). Ceylon cinnamon has also been evaluated in combination with other ingredients. Some preliminary clinical research in overweight adults with PCOS shows that taking three tablets of a combination product containing extracts of Ceylon cinnamon, licorice root, peony root, and St. John's wort, providing the equivalent of 750 mg of dried herb for each ingredient, daily for 3 months, plus tribulus extract for 10 days during the follicular phase, in conjunction with lifestyle modification reduces the time between periods by around 43 days when compared with lifestyle modification alone. The rate of conception was four times higher with this combination when compared with control (97216). Another small clinical study shows that taking a mixture of Ceylon cinnamon, spearmint, ginger, and sweet orange daily for 3 months, in addition to clomiphene citrate for 5 days of each menstrual cycle, improves serum antioxidant levels, fasting blood glucose, and serum insulin levels when compared with clomiphene citrate alone. It is unclear whether these changes are associated with an increase in ovulation and pregnancy rates (103168). In both studies, it is unclear if the effects are related to Ceylon cinnamon, other ingredients, or to the combinations used.
• Premature ejaculation. Topical Ceylon cinnamon has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In patients with premature ejaculation, applying a multi-ingredient cream (SS Cream) containing Panax ginseng root, Angelica root, Cistanches deserticola, Zanthoxyl species, Torlidis seed, clove flower, Asiasari root, Ceylon cinnamon, and toad venom to the glans penis one hour prior to intercourse and washing off immediately before intercourse improves ejaculatory latency when compared with placebo (2537). The effects of Ceylon cinnamon alone are unclear. More evidence is needed to rate Ceylon cinnamon for these uses.

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INSUFFICIENT RELIABLE EVIDENCE to RATE

• Diabetes. It is unclear if oral gymnema is beneficial for diabetes. Details: A meta-analysis of 10 small clinical studies in adults with type 2 diabetes shows that taking gymnema modestly reduces fasting and postprandial blood glucose levels, and also seems to reduce glycated hemoglobin (HbA1c), when compared to baseline. Gymnema may also modestly reduce total cholesterol and triglyceride levels. (110022). Another meta-analysis of 6 small clinical studies, that includes some of the same studies, also shows that taking gymnema modestly reduces fasting blood glucose, total cholesterol, and triglyceride levels when compared with diet or placebo. However, this analysis shows that gymnema does not improve HbA1c, oral glucose tolerance, or low-density lipoprotein cholesterol (112184). The validity of these analyses is limited by the inclusion of mostly low-quality studies that enrolled heterogeneous patient populations and employed varying gymnema dosing regimens of 0.4-10 grams daily, sometimes in conjunction with antidiabetes medications. In addition, many of the included studies were non-randomized and lacked a comparator group.
• Impaired glucose tolerance (prediabetes). It is unclear if oral gymnema is beneficial for impaired glucose tolerance. Details: One small clinical study in overweight or obese patients with impaired glucose tolerance shows that taking gymnema (Swanson Superior Herbs) 300 mg twice daily for 12 weeks does not improve glucose control, lipid profile, anthropometric indices, or blood pressure when compared with placebo (105346). However, this study may have been inadequately powered to detect a difference between groups.
• Metabolic syndrome. It is unclear if oral gymnema is beneficial for metabolic syndrome. Details: One small clinical study shows that taking gymnema leaf (Swanson Premium G. sylvestre leaf, Swanson Health Products) 300 mg twice daily for 12 weeks reduces body weight by 4% and body mass index (BMI) by 2% when compared to baseline in overweight adults with metabolic syndrome. However, it is unclear if these changes are significant when compared with placebo. In addition, gymnema does not appear to improve blood glucose levels, insulin sensitivity, or blood lipid levels when compared with placebo (96235).
• Obesity. It is unclear if oral gymnema improves weight loss in overweight or obese adults. Details: One small clinical study shows that taking gymnema leaf (Swanson Premium G. sylvestre leaf, Swanson Health Products) 300 mg twice daily for 12 weeks modestly reduces body weight and body mass index (BMI) when compared to baseline in overweight adults with metabolic syndrome. However, it is unclear if these changes are significant when compared with placebo (96235). Another small clinical study by the same authors evaluating overweight adults with impaired glucose tolerance shows that taking gymnema (Swanson Superior Herbs) 300 mg twice daily for 12 weeks does not reduce body weight or BMI when compared with placebo (105346). Gymnema has also been studied in combination with other ingredients. One small clinical study shows that taking a combination of gymnema extract 400 mg, hydroxycitric acid 2800 mg, and niacin-bound chromium 4 mg orally daily for 8 weeks decreases BMI and body weight when compared to baseline in overweight and obese adults. This product provided 400 mcg of elemental chromium and 100 mg of gymnemic acids (42604). It is unclear if these effects are due to gymnema, other ingredients, or the combination. More evidence is needed to rate gymnema for these uses.

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LIKELY SAFE ...when consumed in amounts commonly found in foods. Ceylon cinnamon has Generally Recognized As Safe (GRAS) status in the US for use as a spice or flavoring agent (4912).

POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts. Ceylon cinnamon 0.5-3 grams daily has been safely used in studies lasting up to 6 months (4,12,97248,97250,99874). ...when used as a mouth rinse for up to 15 days (92071). There is insufficient reliable information available about the safety of Ceylon cinnamon when used orally in greater amounts or for longer periods. Ceylon cinnamon contains trace amounts of coumarin (108260). In very high doses, coumarin can cause hepatotoxicity (15302). However, since the amount of coumarin in Ceylon cinnamon is negligible, it is unlikely to cause toxic effects (89652,92072,92073).

PREGNANCY: LIKELY SAFE
when consumed in amounts commonly found in foods (4912).

PREGNANCY: LIKELY UNSAFE
when used orally in amounts greater than those found in foods. Fetal abnormalities have been reported in animals (4,12).

LACTATION: LIKELY SAFE
when consumed in amounts commonly found in foods (4912). There is insufficient reliable information available about the safety of Ceylon cinnamon in amounts greater than those found in foods.

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POSSIBLY SAFE ...when used orally and appropriately. Gymnema leaf extract has been used safely in doses of 200 mg twice daily for up to 20 months or 300 mg twice daily for 12 weeks (45,46,42604,105346).

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

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ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, Ceylon cinnamon may have additive effects with antidiabetes drugs.  Details Ceylon cinnamon may lower blood glucose levels (11247,11248,11973). Dose adjustments might be necessary.

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, Ceylon cinnamon might have additive effects with antihypertensive drugs and increase the risk of hypotension.  Details Animal research shows that Ceylon cinnamon extract has vasorelaxant properties and reduces blood pressure in rat models of hypertension, possibly via inhibition of calcium influx through L-type voltage-sensitive channels (92085,92086).

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ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Theoretically, taking gymnema with antidiabetes drugs might increase the risk of hypoglycemia.  Details Gymnema reduces blood glucose levels in some human and animal research. In human studies, it has been shown to enhance the blood glucose lowering effects of hypoglycemic drugs (45,46,92119,92121,92123). However, other research in adults with prediabetes or metabolic syndrome suggests that gymnema does not reduce fasting levels of blood glucose (96235,105346). Until more is known, monitor blood glucose levels closely.

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, gymnema might increase levels of drugs metabolized by CYP1A2.  Details Animal and in vitro research shows that gymnema can inhibit the CYP1A2 enzyme (96236,96237,96238). In one animal study, oral administration of gymnema for 7 days increased the plasma concentrations of phenacetin, a CYP1A2 substrate, by about 1.4-fold and reduced the clearance of phenacetin by about 29% (96237).

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, gymnema might increase or decrease levels of drugs metabolized by CYP2C9.  Details Animal research shows that gymnema can induce the CYP2C9 enzyme. In one animal study, gymnema caused a 2.4-fold increase in the clearance of tolbutamide, a CYP2C9 substrate, in rats (96237). In vitro research also shows that gymnema can inhibit CYP2C9 (96236,96238).

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, gymnema might increase levels of drugs metabolized by CYP3A4.  Details One in vitro study using rat liver microsomes shows that gymnema can modestly inhibit the CYP3A4 enzyme (96238). However, other in vitro research using human liver microsomes shows that gymnema does not affect CYP3A4 activity (96236). Animal research also shows that gymnema does not alter the function of CYP3A4. In one study in rats, oral administration of gymnema for 7 days did not alter the clearance of amlodipine, a CYP3A4 substrate (96237).

PHENACETIN Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking gymnema with phenacetin might increase the levels of phenacetin.  Details Animal research shows that gymnema, administered orally for 7 days, decreases the clearance of phenacetin in a dose-dependent manner by about 21% to 29% and increases plasma levels about 1.3- to 1.4-fold when compared to control (96237,96238).

TOLBUTAMIDE (Orinase) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking gymnema with tolbutamide might the decrease levels of tolbutamide.  Details Animal research shows that gymnema, administered orally for 7 days, increases the clearance of tolbutamide by 2.4-fold when compared to control (96237).

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General ...Orally, Ceylon cinnamon is generally well tolerated, and adverse reactions are uncommon.
Most Common Adverse Effects:
Orally: Bloating, dyspepsia, nausea.
Topically: Allergic dermatitis, irritation of mucous membranes and skin.

Dermatologic ...Orally, a case of systemic contact dermatitis has been reported in a patient who consumed cinnamon (type not specified) after being previously sensitized to cinnamyl alcohol via cutaneous exposure (95599). In a small study of oral Ceylon cinnamon, two patients reported itching (104520). In another small study, two patients reported rashes (108263).
Topically, cinnamon oil can cause skin irritation and allergic dermatitis, probably due to cinnamaldehyde which makes up 60% to 80% of cinnamon oil (2537,12635,92071,95596,95599). In one case report, a 16-year-old female experienced worsening dermatitis after using a homemade facial scrub containing cinnamon powder (type not specified). Symptoms improved after discontinuation of the scrub (95596). Several cases of intraoral allergic contact dermatitis have been reported in patients consuming cinnamon (type not specified) or using products containing constituents of cinnamon (95598).

Gastrointestinal ...Orally, gastrointestinal side effects such as heartburn, nausea, bloating, and dyspepsia have been reported (97250).

Hematologic ...Orally, a case of postoperative hemorrhage is reported in a 49-year-old patient after taking Ceylon cinnamon 1 tablespoon daily for 10 months. One day post-colectomy, the patient had an INR of 1.59 and intraabdominal bleeding that required exploratory laparotomies, blood transfusion, and fresh frozen plasma. Ultimately, the patient was discharged (112421).

Hepatic ...While there is concern about the coumarin content in cassia cinnamon increasing the risk for hepatic adverse effects and bleeding, the amount of coumarin in Ceylon cinnamon is negligible and unlikely to cause toxic effects (89652,92072,92073). In one case report, a 73-year-old female taking rosuvastatin for several months developed elevated liver function tests (LFTs), abdominal pain, nausea, and vomiting after taking cinnamon (unknown dose and type) for 7 days. The acute hepatitis and elevated LFTs resolved after stopping both cinnamon and rosuvastatin. The patient was later able to resume rosuvastatin without recurrence (97249).

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General ...Orally, gymnema seems to be well tolerated.

Hepatic ...A case of drug-induced hepatitis characterized by weakness, fatigue, jaundice, and elevated liver enzymes, has been reported for a patient who consumed gymnema tea three times daily for 10 days. The patient was administered prednisone 60 mg once daily and was eventually tapered off prednisone and discharged. Laboratory values normalized after 6 months (95005). A case of hepatitis-associated aplastic anemia characterized by jaundice, elevated liver function tests, and pancytopenia has been reported for a patient who consumed gymnema 2 grams twice daily for at least a month. Treatment with ursodeoxycholic acid for 8 weeks led to resolution of cholestatic hepatitis; however, the pancytopenia was not responsive to treatment with immunosuppressive drugs and the patient died 5 months after presentation (110021). The exact reason for these adverse effects is not clear; they may have been idiosyncratic.

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