Reviewed: Beejmohun V, Peytavy-Izard M, Mignon C, et al. Acute effect of Ceylon cinnamon extract on postprandial glycemia: alpha-amylase inhibition, starch tolerance test in rats, and randomized crossover clinical trial in healthy volunteers. BMC Complement Altern Med. 2014;14(1):351. doi: 10.1186/1472-6882-14-351.
Hyperglycemia, or high blood sugar, is central to the etiology of type 2 diabetes. Controlling postprandial (after-meal) hyperglycemia is important to maintaining overall health and reducing the risk of both type 2 diabetes and cardiovascular diseases. “Ceylon” or “true” cinnamon (Cinnamomum verum syn. C. zeylanicum, Lauraceae) has been used traditionally for gastrointestinal problems and continues to be used for respiratory infections. Although clinical trials have addressed the potential hypoglycemic activity of various types and preparations of cinnamon, studies conflict as to its efficacy. This in vitro, in vivo, and randomized, placebo-controlled, crossover human clinical trial investigated the starch tolerance of rats and healthy humans supplemented with Ceylon cinnamon bark extract.
Ceylon cinnamon bark extract (CCE; MealShape™; Dialpha; Montferrier sur Lez, France) is a 10:1 concentrate extracted with water and ethanol (50:50), which is then filtered and dried. [Note: Four of the seven study authors are Dialpha employees.] The resultant powder is standardized to contain at least 40% polyphenols, primarily oligomeric procyanidins composed of catechin and epicatechin. As a comparison for using the alcoholic solvent, an aqueous extract also was made. An enzymatic plate assay was used to gauge the inhibition of α-amylase (an enzyme that breaks down starches into sugars) activity, with acarbose (an anti-diabetic drug sold as Precose® in North America; Bayer; Whippany, New Jersey) as a positive control.
The authors used male Wistar rats for the in vivo experiments. Various groups comprising eight to 20 animals were tested to determine effects of CCE on glucose and insulin at 50 mg/kg body weight; dose-effects of CCE on glucose response at 6.25, 12.5, 25, 50, or 100 mg/kg body weight; and comparative responses between CCE and aqueous extracts at 50 mg/kg body weight. Fasted rats underwent a starch tolerance test (STT) and were fed wheat (Triticum aestivum, Poaceae) starch alone at 1.5 g/kg body weight as a control, or wheat starch with cinnamon extract at 20 mL/kg body weight. Blood glucose levels were measured at baseline, 15, 30, 60, 90, and 120 minutes.
During the STT, rats administered CCE and starch at 50 mg/kg body weight experienced a significant 20.4% decrease in glucose area under the curve (AUC; a calculation used to estimate a compound’s bioavailability and clearance from the body) from 0-120 minutes, as compared to the control group (P<0.05). At the same dose, insulin AUC was significantly less after 60 minutes compared to control (P<0.05), with an insulin peak reduction of 40.6%. Glucose AUC from 0-120 minutes also was significantly less in rats given CCE at 12.5, 25, 50, and 100 mg/kg body weight (P<0.05 for all). Compared to the aqueous cinnamon extract, CCE consumption in rats resulted in a significantly greater reduction in glucose AUC from 0-15 (P<0.05), 0-30 (P<0.01), and 0-60 minutes (P<0.05).
In vitro analysis
In the pancreatic α-amylase activity assay, CCE had an inhibitory concentration of 50% (IC50; a measure of how much a substance inhibits a biological process) of 25 µg/mL, while the acarbose control had an IC50 of 18 µg/mL. When comparing the aqueous and alcoholic cinnamon extracts, the CCE had an IC50 of 30 µg/mL while the water extract had an IC50 of 40 µg/mL.
The clinical trial took place at the Clinic Nutrition Center at Hôpital Saint Vincent de Paul in Lille, France, and was administered by Naturalpha, a contract research company based in Lille, France. The study’s primary endpoint was glucose AUC from 0-120 minutes following consumption of a standard white bread meal. Secondary endpoints included glucose AUC from 0-60 minutes, insulin AUC from 0-60 and 0-120 minutes, maximum concentrations of glucose and insulin, and concentrations of both at each time point. Adverse side effects (ASEs) were recorded and classified as mild, moderate, or severe.
Included subjects (aged 18 to 45 years) had a body mass index between 18.5 and 25 kg/m2 and less than a 5% variation in body weight for the three months prior to the study. Those with fasting glucose concentrations greater than 110 mg/dL, a history of diabetes, a smoking habit, or who took any supplements or pharmaceuticals that could impact glucose or insulin were excluded. Subjects who had two-hour postprandial capillary blood glucose concentrations greater than 140 mg/dl were excluded as well.
Subjects were instructed to maintain their current lifestyle and were randomly assigned to receive either CCE followed by placebo or placebo followed by CCE. Treatment consisted of two capsules of CCE (500 mg each) or placebo (500 mg; containing 20% microcrystalline cellulose and 80% dicalcium phosphate). After an overnight fast, participants had blood drawn 35 minutes prior to the test and were given CCE or placebo five minutes later with 125 mL water. At baseline, a standardized meal was consumed with 250 mL water within eight minutes (103 g of white bread containing 52.2% carbohydrates [3.6% of which were sugars], 7.4% protein, 0.1% lipids, and 3.3% fiber). Fasting glucose concentrations were calculated as an average of measurements taken five and 10 minutes before the meal; fasting insulin was determined five minutes before the meal; and glucose and insulin were measured at 15, 30, 45, 60, 90, and 120 minutes following the meal.
Of the 22 subjects initially screened, 18 were randomly assigned to CCE (n=9) or placebo (n=9). Two subjects were not included in the per-protocol analysis due to protocol deviations, leaving 16 subjects in the final analysis. Upon supplementation with CCE, there was a significantly lower glucose AUC from 0-60 minutes compared to placebo (P<0.05). No other significant effects were noted, and no ASEs were observed.
In summary, CCE consumption in rats decreased both glucose and insulin concentrations during a starch tolerance test, and doses of 12.5 mg/kg body weight and above resulted in decreased glucose concentrations. Comparable IC50 levels for CCE and acarbose in the α-amylase activity assay suggest that enzyme inhibition is a likely mechanism of action for the alcoholic cinnamon extract. Although CCE significantly lowered glucose concentrations in healthy subjects, no effects were seen on insulin concentrations, which points to mechanisms independent of increased insulin in humans.
The authors mention that Ceylon cinnamon contains much less coumarin (a potentially toxic compound) than cassia (Cinnamomum aromaticum syn. C. cassia), although alcohol extraction can increase an extract’s coumarin content due to its solubility. The CCE used in the study exposed participants to less than 0.2 mg coumarin per day (per one gram dose), well below the European Food Safety Authority’s tolerable daily intake guideline of seven mg/day for a 70-kg (154-lb) person. This study reports more robust bioactivity with the alcoholic extract than the aqueous extract, which deserves further investigation. Future clinical trials of hyperglycemic individuals should continue to examine the use of Ceylon cinnamon extract in managing this condition.
—Amy C. Keller, PhD