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Randomized Controlled Trial
. 2024 Oct 9;19(10):e0311501.
doi: 10.1371/journal.pone.0311501. eCollection 2024.

Suppression of the postprandial hyperglycemia in patients with type 2 diabetes by a raw medicinal herb powder is weakened when consumed in ordinary hard gelatin capsules: A randomized crossover clinical trial

Fernanda Duarte Moreira  1   2   3 , Caio Eduardo Gonçalves Reis  4 , Andrea Donatti Gallassi  3 , Daniel Carneiro Moreira  5 , Alexis Fonseca Welker  3
Affiliations
Randomized Controlled Trial

Suppression of the postprandial hyperglycemia in patients with type 2 diabetes by a raw medicinal herb powder is weakened when consumed in ordinary hard gelatin capsules: A randomized crossover clinical trial

Fernanda Duarte Moreira et al. PLoS One. .

Abstract

Introduction: Contradictory claims about the efficacy of several medicinal plants to promote glycemic control in patients with type 2 diabetes mellitus (T2DM) have been explained by divergences in the administration form and by extrapolation of data obtained from healthy individuals. It is not known whether the antidiabetic effects of traditional herbal medicines are influenced by gelatin capsules. This randomized crossover trial aimed to evaluate the acute effect of a single dose of raw cinnamon consumed orally either dissolved in water as a beverage or as ordinary hard gelatin capsules on postprandial hyperglycemia (>140 mg/dL; >7.8 mmol/L) in T2DM patients elicited by a nutritionally-balanced meal providing 50 g of complex carbohydrates.

Methods: Fasting T2DM patients (n = 19) randomly ingested a standardized meal in five experimental sessions, one alone (Control) and the other after prior intake of 3 or 6 g of crude cinnamon in the form of hard gelatin capsules or powder dissolved in water. Blood glucose was measured at fasting and at 0.25, 0.5, 0.75, 1, 1.5 and 2 hours postprandially. After each breakfast, its palatability scores for visual appeal, smell and pleasantness of taste were assessed, as well as the taste intensity sweetness, saltiness, bitterness, sourness and creaminess.

Results: The intake of raw cinnamon dissolved in water, independently of the dose, decreased the meal-induced large glucose spike (peak-rise of +87 mg/dL and Δ1-hour glycemia of +79 mg/dL) and the hyperglycemic blood glucose peak. When cinnamon was taken as capsules, these anti-hyperglycemic effects were lost or significantly diminished. Raw cinnamon intake did not change time-to-peak or the 2-h post-meal glycaemia, but flattened the glycemic curve (lower iAUC) without changing the shape that is typical of T2DM patients.

Conclusions: This cinnamon's antihyperglycemic action confirms its acarbose-like property to inhibit the activities of the carbohydrate-digesting enzymes α-amylases/α-glucosidases, which is in accordance with its exceptionally high content of raw insoluble fiber. The efficacy of using raw cinnamon as a diabetes treatment strategy seems to require its intake at a specific time before/concomitantly the main hyperglycemic daily meals. Trial registration: Registro Brasileiro de Ensaios Clínicos (ReBEC), number RBR-98tx28b.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Study flowchart diagram of the participants (following CONSORT).
T2DM men after eating a standardized meal alone (Control) or after prior ingestion of 3 g of raw cinnamon in capsules (3gCaps), 6 g of raw cinnamon in capsules (6gCaps), 3 g of raw cinnamon powder dissolved in water (3gPowder), or 6 g of raw cinnamon powder (6gPowder).
Fig 2
Fig 2. Post-meal blood glucose peak rise and Δ1hour of T2DM patients without or with raw cinnamon.
(A) Post-meal mean blood glucose peak rise (mg/dL) and (B) mean difference between 1-hour post-meal blood glucose and fasting blood glucose (Δ1hour) of T2DM men after eating a standardized meal alone (Control) or after prior ingestion of 3 g of raw cinnamon in capsules (3gCaps), 6 g of raw cinnamon in capsules (6gCaps), 3 g of raw cinnamon powder dissolved in water (3gPowder), or 6 g of raw cinnamon powder (6gPowder). The line at the value of +63 mg/dL (+3.5 mmol/L) indicates the maximum mean blood glucose rise achieved by healthy individuals after ingesting 50 g of carbohydrate from 27 tested foods [194]. *p ≤ 0.013 in relation to control.
Fig 3
Fig 3. Post-meal blood glucose peak and 1-h post-meal of T2DM patients without or with raw cinnamon.
(A) Post-meal mean blood glucose peak (mg/dL) and (B) mean 1-hour post-meal blood glucose (mg/dL) of T2DM men after eating a standardized meal alone (Control) or after prior ingestion of 3 g of raw cinnamon in capsules (3gCaps), 6 g of raw cinnamon in capsules (6gCaps), 3 g of raw cinnamon powder dissolved in water (3gPowder), or 6 g of raw cinnamon powder (6gPowder). The line at the value of 180 mg/dL (10 mmol/L) indicates the level up to which renal glucose reabsorption is preserved at physiological rates [–202] and insulin therapy is not yet necessary [203, 204]. The line at the value of 200 mg/dL (11.1 mmol/L) indicates the 1-h post-meal threshold used to diagnose T2DM [205] and strongly associated with metabolic disturbances [206]. *p ≤ 0.017 in relation to control.
Fig 4
Fig 4. Post-meal time to blood glucose peak and 2-h post-meal of T2DM patients without or with raw cinnamon.
(A) Post-meal mean time (min) to reach blood glucose peak and (B) mean 2-hour post-meal blood glucose (mg/dL) of T2DM men after eating a standardized meal alone (Control) or after prior ingestion of 3 g of raw cinnamon in capsules (3gCaps), 6 g of raw cinnamon in capsules (6gCaps), 3 g of raw cinnamon powder dissolved in water (3gPowder), or 6 g of raw cinnamon powder (6gPowder).
Fig 5
Fig 5. Post-meal glycemic curve of T2DM patients without or with raw cinnamon.
(A) Mean blood glucose (mg/dL) and (B) mean Δ blood glucose (difference between post-meal blood glucose and fasting blood glucose) of T2DM men throughout 120 minutes after eating a standardized meal alone (Control) or after prior ingestion of 3 g of raw cinnamon in capsules (3gCaps), 6 g of raw cinnamon in capsules (6gCaps), 3 g of raw cinnamon powder dissolved in water (3gPowder), or 6 g of raw cinnamon powder (6gPowder). The line at the value of 180 mg/dL (10 mmol/L) indicates the level up to which renal glucose reabsorption is preserved at physiological rates [–202] and insulin therapy is not yet necessary [203, 204]. The line at the value of 200 mg/dL (11.1 mmol/L) indicates the 1-h post-meal threshold used to diagnose T2DM [205] and strongly associated with metabolic disturbances [206]. The line at the value of 63 mg/dL (3.5 mmol/L) indicates the maximum mean blood glucose rise achieved by healthy individuals after ingesting 50 g of carbohydrate from 27 tested foods [194]. The post-meal blood glucose levels along the glycemic curve were significantly decreased by raw cinnamon ingested in the form of powder (p ≤ 0.042), independently of the dose (p > 0.05), but not in the form of capsule (p ≥ 0.159) (two-way ANOVA with repeated measures). The levels of post-meal Δ blood glucose along the curve were significantly decreased by raw cinnamon ingested in the form of powder (p ≤ 0.013) and in the form of capsule (p ≤ 0.020), independently of the dose (p > 0.05), and the decreases caused by the form of powder were significantly stronger than by the form of capsule (p ≤ 0.003).
Fig 6
Fig 6. Post-meal incremental area under the glycemic response curve (iAUC) of T2DM patients without or with raw cinnamon.
Post-meal incremental area under the glycemic response curve (iAUC) of T2DM men after eating a standardized meal alone (Control) or after prior ingestion of 3 g of raw cinnamon in capsules (3gCaps), 6 g of raw cinnamon in capsules (6gCaps), 3 g of raw cinnamon powder dissolved in water (3gPowder), or 6 g of raw cinnamon powder (6gPowder). *p ≤ 0.012 in relation to control.
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This study was partially supported by the Núcleo de Apoio à Pesquisa (NAP) of the Instituto Laboratório Sabin – Medicina Diagnóstica (https://www.sabin.com.br/envie-seu-projeto/; Award Number: 957963981-72; Recipient: F.D.M.). Sabin measured baseline levels of fasting blood glucose, insulin, HbA1c, HOMA-IR and HOMA-β of patients before experimental sessions, but did not have any additional role in other data collection and analysis, study design, decision to publish, or preparation of the manuscript. This study was also partially supported by Fundação de Apoio à Pesquisa do Distrito Federal (FAPDF; https://www.fap.df.gov.br/; Award Number: 244/2022; Recipient: F.D.M.) by providing publication fee, but had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.