Cinnamon Supplementation in Patients with Type 2 Diabetes Mellitus
Diabetes mellitus is the sixth leading cause of death in the United States, and most patients with the disease have type 2 diabetes. The effectiveness of cinnamon supplementation in patients with type 2 diabetes has received a great deal of media attention after a study was published in 2003. Although the efficacy of cinnamon in patients with diabetes has not been established, many patients seek other therapies and supplement their prescribed pharmacologic therapy with cinnamon. We conducted a literature search, limited to English-language human studies, using MEDLINE (1966-August 2006), EMBASE (1980-August 2006), International Pharmaceutical Abstracts (1970-August 2006), and Iowa Drug Information Service (1966-August 2006). References from articles and clinical trials were reviewed for additional sources; no abstracts were reviewed. We found two prospective, randomized, double-blind, placebo-controlled, peer-reviewed clinical trials and one prospective, placebo-controlled, peer-reviewed clinical trial that evaluated the efficacy of cinnamon supplementation in patients with type 2 diabetes; a total of 164 patients were involved in these trials. Two of the studies reported modest improvements in lowering blood glucose levels with cinnamon supplementation in small patient samples. One trial showed no significant difference between cinnamon and placebo in lowering blood glucose levels. Overall, cinnamon was well tolerated. These data suggest that cinnamon has a possible modest effect in lowering plasma glucose levels in patients with poorly controlled type 2 diabetes. However, clinicians are strongly urged to refrain from recommending cinnamon supplementation in place of the proven standard of care, which includes lifestyle modifications, oral antidiabetic agents, and insulin therapy.
[Show abstract] [Hide abstract] ABSTRACT: Human exposure to trans-cinnamic aldehyde (t-CA; cinnamaldehyde; cinnamal; (E)-3-phenylprop-2-enal) is common through diet, use of cinnamon powder for diabetes, and to provide flavor and scent in commercial products. We evaluated the likelihood of t-CA to influence metabolism by inhibition of cytochrome P450 enzymes. IC50 values from recombinant enzymes indicated that an interaction is most probable for CYP2A6 (IC50 = 6.1 μM. t-CA was 10.5-fold more selective for human CYP2A6 than CYP2E1; IC50 values for CYPs 1A2, 2B6, 2C9, 2C19, 2D6, and 3A4 were 15.8-fold or more. t-CA is a type I ligand for CYP2A6 (KS = 14.9 μM). Inhibition of CYP2A6 by t-CA was metabolism-dependent; inhibition required NADPH and increased with time. Glutathione lessened the extent of inhibition modestly and statistically significantly. The carbon monoxide binding spectrum was dramatically diminished after exposure to NADPH and t-CA, suggesting degradation of the heme or CYP2A6 apoprotein. Using a static model and mechanism-based inhibition parameters (KI = 18.0 μM; kinact = 0.056 min-1), changes in the area under the concentration curve (AUC) for nicotine and letrozole were predicted in the presence of t-CA (0.1 and 1 μM). The AUC fold-change ranged from 1.1 to 3.6. In summary, t-CA is a potential source of pharmacokinetic variability for CYP2A6 substrates due to metabolism-dependent inhibition, especially in scenarios when exposure to t-CA is elevated due to high dietary exposure or when cinnamon is used as a treatment for specific disease states (e.g., diabetes).0Comments 0Citations
- "The concentration of t-CA in commercial cinnamon powder ranges from 8.2 to 27.5 mg per gram (Friedman et al., 2000). Doses from 1 to 10 g of encapsulated cinnamon powder are used for diabetes mellitus to lower blood sugar (Pham et al., 2007; Crawford, 2009; Akilen et al., 2010), corresponding, therefore, to exposure of 8 to 275 mg of t-CA (Friedman et al., 2000; Kirkham et al., 2009). There are also reports of cinnamon exhibiting antimicrobial, anti-inflammatory, lipid-lowering, anticancer, and amyloid plaque-reducing effects (George et al., 2013; Long et al., 2015). "
[Show abstract] [Hide abstract] ABSTRACT: We previously demonstrated that cinnamon extract (CE) ameliorates type 1 diabetes induced by streptozotocin in rats through the up-regulation of glucose transporter 4 (GLUT4) translocation in both muscle and adipose tissues. This present study was aimed at clarifying the detailed mechanism(s) with which CE increases the glucose uptake in vivo and in cell culture systems using 3T3-L1 adipocytes and C2C12 myotubes in vitro. Specific inhibitors of key enzymes in insulin signaling and AMP-activated protein kinase (AMPK) signaling pathways, as well as small interference RNA, were used to examine the role of these kinases in the CE-induced glucose uptake. The results showed that CE stimulated the phosphorylation of AMPK and acetyl-CoA carboxylase. An AMPK inhibitor and LKB1 siRNA blocked the CE-induced glucose uptake. We also found for the first time that insulin suppressed AMPK activation in the adipocyte. To investigate the effect of CE on type 2 diabetes in vivo, we further performed oral glucose tolerance tests and insulin tolerance tests in type 2 diabetes model rats administered with CE. The CE improved glucose tolerance in oral glucose tolerance tests, but not insulin sensitivity in insulin tolerance test. In summary, these results indicate that CE ameliorates type 2 diabetes by inducing GLUT4 translocation via the AMPK signaling pathway. We also found insulin antagonistically regulates the activation of AMPK.0Comments 22Citations
- "Preparations made from the bark of trees of the genus Cinnamomum have been prescribed for more than 2000 years in China, and the first record for their use as Chinese medicine appeared in Shen- Nong's Herbal . There have been a number of in vitro and in vivo studies showing that cinnamon improves both insulin resistance and glucose metabolism1112131415161718192021222324252627. However, the detailed mechanism of this anti-diabetic activity has not yet been clarified and is still controversial. "
[Show abstract] [Hide abstract] ABSTRACT: Eighteen type II diabetics (9 women and 9 men) participated in a 12-week trial that consisted of 2 parts, a 3-week control phase followed by a 9-week experimental phase where half of the subjects received 1000 mg of Cinnamomum cassia while the other half received 1000 mg of a placebo pill. All of the subjects that were in the cinnamon group had a statistically significant decrease in their blood sugar levels with a P-value of 3.915 × 10(-10). The subjects in the cinnamon group had an average overall decrease in their blood sugar levels of about 30 mg/dL, which is comparable to oral medications available for diabetes. All subjects were educated on appropriate diabetic diets and maintained that diet for the entire 12 week study. Greater decreases in blood glucose values were observed in patients using the cinnamon compared to those using the dietary changes alone.0Comments 2Citations
- "Cinnamon has been shown to significantly help patients with type II diabetes manage their condition. It appears to help control and normalize the glucose levels of diabetics who have an inability to respond to insulin.8–12 The compound in cinnamon responsible for its insulin-like behavior is still up for debate. "