A study involving 150 adults reveals the hypoglycemic effect of Cinnamomum zeylanicum extract, with significant benefits in type 2 diabetes
There is a spice found in every supermarket, sold in dozens of formats and packaging types, often without the botanical species being clearly identified on the label.
Yet that distinction changes everything: it changes the toxicological profile, changes compliance with European regulations, and changes efficacy in clinical trials.
We are talking about cinnamon. More specifically, the difference between Cinnamomum zeylanicum, the Ceylon variety, and Cinnamomum cassia, which makes up most of what is commercially sold and formulated.
A randomized clinical trial published in PLOS ONE in January 2025 compared the two realities. The primary outcome was not what researchers expected: LDL cholesterol did not decrease significantly.
However, fasting blood glucose did. And in patients with type 2 diabetes, the reduction was 78.6 mg/dL compared with 11.2 mg/dL in the placebo group. A finding that changes the way this ingredient is viewed.
Phytochemical Profile of Cinnamomum zeylanicum Extract
The extract used in the trial was standardized to contain a minimum of 30% polyphenols, mainly consisting of type A proanthocyanidins (PAC A), compounds with documented activity in glucose regulation.
The coumarin content was 0.01%. This value is much lower than that of Cinnamomum cassia, historically associated with hepatotoxicity risks during prolonged intake.
The product also contained cinnamaldehyde, eugenol, and cinnamyl acetate as its main compounds, quantified through HPLC analysis.
The precise chemical characterization was one of the protocol’s strengths. It solved the issue of ambiguous cinnamon species nomenclature, which in previous literature had made it difficult to compare results across different studies.
Why Coumarin Content Matters in Nutraceutical Formulation
Coumarin in Cinnamomum cassia is a concrete issue for companies formulating supplements intended for daily use. The EFSA established a tolerable daily intake of 0.1 mg per kg of body weight.
With some commercial cassia preparations, this threshold can easily be reached. With the Ceylon extract used in the trial, containing 0.01% coumarin, the safety margin is considerably wider.
For companies developing formulations intended for long term use, species selection is not a minor detail. It is a variable that directly affects European regulatory compliance and long term product safety.
Effect on Fasting Blood Glucose: Trial Data
The 150 participants had LDL C values between 100 and 190 mg/dL, a mean age of 50.4 years, and 66% were female.
The dosage consisted of 1000 mg/day of extract, administered as two 500 mg capsules before the main meals, for 12 weeks.
The primary endpoint, LDL C reduction, did not reach statistical significance, with an adjusted mean difference of 6.05 mg/dL and a p value of 0.161.
From a glycemic perspective, however, the results were different: there was a significant reduction in fasting blood glucose compared with placebo, with an adjusted mean difference of 8.59 mg/dL and a 95% confidence interval of 0.59 to 16.59 mg/dL with p = 0.036.
No significant changes were observed for HbA1c, HDL C, triglycerides, or anthropometric parameters. The absence of an HbA1c effect is consistent with other trials of similar duration: 12 weeks are generally insufficient to substantially modify glycated hemoglobin, which reflects a longer time frame.
The Type 2 Diabetes Subgroup: The Most Relevant Finding
The study analyzed results separately across three groups: normoglycemic subjects, individuals with prediabetes, and patients with type 2 diabetes mellitus (T2DM).
In participants with T2DM, the extract produced an average fasting glucose reduction of 78.6 mg/dL, compared with 11.2 mg/dL in the placebo group.
The interaction between treatment and glycemic status was statistically robust.
The message is clear: the effect increased alongside the severity of baseline metabolic impairment. In normoglycemic individuals, the response was minimal. In diabetic patients, the signal was strong and clinically relevant.
Mechanisms of Action: From the AMPK Pathway to Proanthocyanidins
Why was the effect selective in patients with T2DM? Preclinical literature points to two main mechanisms.
The first involves the AMPK pathway: C. zeylanicum extract may promote GLUT4 translocation through the LKB1 AMPK pathway, increasing glucose uptake in adipose and muscle tissue.
At the same time, it increases expression of insulin receptors (IR) and insulin receptor substrates (IRS), improving the cellular response to insulin signaling.
The second mechanism involves type A proanthocyanidins. In vitro, they demonstrated anti amyloidogenic activity against human islet amyloid polypeptide (hIAPP), which is implicated in beta cell degeneration in T2DM.
In subjects with already compromised beta cell function, this protective effect could amplify the overall response to the extract. This is likely where the explanation for the selective effect observed in the trial lies.
Safety at 12 Weeks: No Hepatic or Renal Toxicity
After 12 weeks, no significant effects were observed on hepatic function markers such as AST and ALT, nor on renal parameters including eGFR and serum creatinine.
The frequency of adverse events in the treated group, 7.7%, was comparable to placebo at 8.0%. Gastritis was the most common manifestation in both groups, and no adverse event required treatment discontinuation.
These findings are consistent with a previous phase I trial conducted with the same extract in healthy volunteers. The tolerability profile appears suitable for prolonged use at 1000 mg/day.
A direct comparison with Cinnamomum cassia at equivalent dosages remains an open area for future research, but the advantage of Ceylon cinnamon regarding coumarin content is already well documented at the compositional level.
If your company is interested in developing formulations based on Cinnamomum zeylanicum:
Source: Muthukuda D, de Silva CK, Ajanthan S, Wijesinghe N, Dahanayaka A, Pathmeswaran A. Effects of Cinnamomum zeylanicum (Ceylon cinnamon) extract on lipid profile, glucose levels and its safety in adults: A randomized, double blind, controlled trial. PLOS ONE 20(1): e0317904. https://doi.org/10.1371/journal.pone.0317904
