The Effects of Ceylon Cinnamon (Cinnamomum Verum) Supplementation on Blood Glucose, Lipid Profile Levels, Body Mass Index, and Pain Intensity Among Adult Individuals With Painful Diabetic Peripheral Neuropathy

Type 2 diabetes mellitus (T2DM) represents a global public health crisis characterized by progressive metabolic dysfunction, chronic hyperglycemia, and systemic vascular and neural complications (World Health Organization [WHO], 2023). Painful diabetic peripheral neuropathy (PDPN) is one of the most disabling microvascular complications of T2DM, arising from complex pathophysiological processes including prolonged exposure to hyperglycemia, insulin resistance (IR), excessive oxidative stress, and chronic neuroinflammation (Atsaves & Ricketts, 2020; Jain & Sahu, 2023; WHO, 2023). Clinically, PDPN presents as persistent burning, shooting, or stabbing pain, severely impairing patient mobility, sleep quality, overall daily functionality, and quality of life (Abu-Shennar & Bayraktar, 2022).

While pharmacological strategies remain the primary modality for managing neuropathic pain in T2DM, many agents carry significant adverse effect profiles or provide incomplete symptomatic relief (Atsaves & Ricketts, 2020). Consequently, there is growing clinical interest in safe, natural nutraceutical adjuncts capable of targeting the underlying metabolic and inflammatory driving factors of nerve injury. Ceylon cinnamon (Cinnamomum verum) has gained considerable attention due to its rich content of bioactive compounds, such as cinnamaldehyde, polyphenols, and type-A procyanidin polymers, which exhibit insulin-mimetic, antioxidant, and anti-inflammatory activities (Akilen et al., 2010; Kermani et al., 2022; Khan et al., 2003; Rani & Sharma, 2021).

Mechanistically, Ceylon cinnamon (Cinnamomum verum) bioactive compounds enhance insulin receptor autophosphorylation, upregulate glucose transporter type 4 (GLUT4) translocation via the phosphatidylinositol 3-kinase (PI3K) pathway, and downregulate glycogen synthase kinase-3β (GSK3β) (Baker et al., 2008; Khan et al., 2003; Zare et al., 2021). Furthermore, Ceylon cinnamon polyphenols mitigate neuroinflammation and nociceptive signaling by dampening pro-inflammatory cytokine secretion (e.g., TNF-α, IL-6) and reducing advanced glycation end-product (AGE) accumulation within peripheral myelin sheaths and Schwann cells (Jain & Sahu, 2023; Rani & Sharma, 2021).

Despite the growing body of global and national literature examining the metabolic effects of cinnamon supplementation in T2DM, significant knowledge gaps remain. On a global scale, prior clinical trials have predominantly focused on short-term glycemic and lipid modulations, largely neglecting the direct therapeutic impact of nutraceuticals on peripheral neuropathic pain severity (Jain & Sahu, 2023; Rani & Sharma, 2021). Locally, while Jordanian clinical and nursing research has comprehensively addressed diabetes self-management, self-efficacy, and pain education among patients with diabetic neuropathy (Abu-Shennar & Bayraktar, 2022; Khattab et al., 2020; Khraisat et al., 2023), no randomized clinical trial has yet evaluated the adjunctive role of bio-standardized phytotherapy in this population.

To our knowledge, this study represents the first double-blind, randomized controlled trial (RCT) both globally and in Jordan to rigorously investigate the therapeutic potential of Ceylon cinnamon (Cinnamomum verum) specifically in patients with PDPN over a prolonged 6-month period, bridging the critical gap between metabolic optimization and neurosensory pain attenuation.

Given the complex interplay between prolonged hyperglycemia, insulin resistance, and neuroinflammatory pathways in the pathogenesis of PDPN, therapeutic modalities that address both metabolic regulation and nociceptive pathways are highly desirable. Ceylon cinnamon offers a dual-action nutraceutical profile; its bioactive constituent, cinnamaldehyde, directly enhances insulin sensitivity through GLUT4 translocation while simultaneously attenuating neurosensory pain transmission by suppressing pro-inflammatory cytokines and lipid peroxidation (Jain & Sahu, 2023; Rani & Sharma, 2021; Sahebkar et al., 2019). Integrating Ceylon cinnamon supplementation as a nutraceutical adjunct may thus provide a synergistic, holistic strategy to mitigate both biochemical dysregulation and peripheral neuropathic pain severity in clinical practice.

Research Questions

• What are the effects of Ceylon cinnamon (Cinnamomum verum) supplementation on fasting plasma glucose (FPG), Glycated Hemoglobin (HbA1c), Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), lipid profile parameters, BMI in adult patients with PDPN compared to placebo?
• Does Ceylon cinnamon (Cinnamomum verum) supplementation reduce the severity and intensity of neuropathic pain, as measured by the Numeric Rating Scale (NRS), in adult patients with PDPN?
• Is there a statistically significant relationship between socio-demographic characteristics, clinical/biochemical parameters, and neuropathic pain intensity (NRS scores) in the intervention group at 6 months post-intervention? Methods and Study Design Study Design A prospective, double-blind, randomized controlled trial (RCT) design was implemented in this study. This design compares pre- and post-intervention outcomes across Ministry of Health (MOH) outpatient clinics in Jordan. Participants were randomly assigned in a 1:1 ratio to either the intervention group or the placebo control group.

Population, Eligibility Criteria, and Sample Size The study population comprised adult patients (age ≥ 18years) diagnosed with PDPN according to established MOH criteria, with documented T2DM.

Patients were excluded if they had coexisting chronic conditions, including chronic kidney disease (CKD), hypertension, cardiovascular disease (CVD), or cognitive/sensory impairments (e.g., reading or hearing difficulties). Furthermore, individuals receiving medications that could confound blood glucose control or pain perception (such as systemic glucocorticoids, weight-loss agents, or iron and vitamin B12 supplements) were excluded to isolate the effects of the study intervention. Two participants were subsequently excluded due to non-compliance.

The sample size was calculated using G*Power software to detect a minimum improvement of 1 point in primary outcomes. Assuming an estimated effect size of 0.70 (Abu-Shennar & Bayraktar, 2022), a statistical power of 80%, and a 95% confidence level (α = 0.05), a minimum sample size of 68 participants was required. To account for potential dropouts and non-compliance, 124 eligible adults (N = 124) were enrolled and randomized into two equal groups (n = 62 per group).

Intervention and Blinding Protocol

Participants were randomly allocated in a 1:1 ratio to receive one of the following protocols for a total duration of 6 months alongside standard diabetic care:

• Intervention Group (n = 62): Received 500 mg of pure Ceylon cinnamon (Cinnamomum verum) extract capsules twice daily with meals (total daily dose: 1,000 mg) and structured dietary guidance.
• Control Group (n = 62): Received 500 mg of inert, identical-looking placebo capsules (containing microcrystalline cellulose) twice daily with meals and received routine diabetic care provided to adult patients with PDPN.

Adherence was monitored through monthly capsule counts and biweekly structured telephone check-ins. A strict double-blind protocol was implemented; neither the participants nor the attending clinical research team were aware of treatment assignments until trial completion and final statistical analysis. A total of 124 participants completed the six-month study and were included in the final analysis.

Data Collection Tools

Data were gathered using standardized instruments at baseline, 3 months, and 6 months post-intervention:

• Part 1 (Sociodemographics): Personal patient data, including age, duration of diabetes, gender, smoking status, education level, marital status, and job status.
• Part 2 (Clinical & Biochemical Profile): Weight, height, waist circumference (WC), FBG, serum insulin, HOMA-IR, HbA1c, total cholesterol (TC), LDL-C, HDL-C, and triglycerides (TG) retrieved from official clinic records.
• Part 3 (Pain Intensity): Pain was assessed using the Numeric Rating Scale (NRS), a validated tool measuring pain intensity from 0 to 10 (0 = "None", 1-3 = "Mild", 4-7 = "Moderate", 8-10 = "Severe"). The Cronbach's alpha of the revised scale was = 0.90 [19, 20]. Participants rated their average pain intensity over the preceding 7 days.

Implementation and Evaluation Strategy The intervention was conducted between March and August 2022 in compliance with the Declaration of Helsinki and Good Clinical Practice (GCP) guidelines. Clinical parameters, biochemical markers, and NRS pain scores were systematically evaluated at baseline, 3 months, and 6 months post-intervention to assess overall effectiveness.

Data Synthesis and Statistical Analysis Data were analyzed using IBM SPSS Statistics for Windows, Version 25.0 (IBM Corp., Armonk, NY, USA). Continuous variables were expressed as mean ± standard deviation (±SD), while categorical variables were presented as frequencies (n) and percentages (%). To evaluate within-group longitudinal changes across the three measurement time points (baseline, 3 months, and 6 months), repeated measures ANOVA (F) was conducted. Bivariate associations between biochemical markers and NRS scores were analyzed using Pearson's correlation coefficient (r). All statistical tests were two-tailed, and a p-value of less than 0.05 (p < 0.05) was deemed statistically significant.

Inclusion criteria

• Age ≥ 18years diagnosed with PDPN
• With documented T2DM

Exclusion criteria

• If they had coexisting chronic conditions, including chronic kidney disease (CKD), hypertension, cardiovascular disease (CVD), or cognitive/sensory impairments (e.g., reading or hearing difficulties).
• individuals receiving medications that could confound blood glucose control or pain perception (such as systemic glucocorticoids, weight-loss agents, or iron and vitamin B12 supplements)