Researchers in Brazil investigated how participants with relatively higher versus lower BMI exhibit different sRAGE responses to caffeinated and decaffeinated coffee.
“Results suggest that caffeine may improve metabolic parameters of lipid and glycemic pathways,” they wrote in the journal Nutrients.
Coffee may benefit heart and metabolic health beyond caffeine content
Coffee contains numerous bioactive compounds that influence metabolic and cardiovascular health beyond the effects of caffeine. These compounds regulate key biological pathways involved in inflammation, oxidative stress, glucose and lipid metabolism, and advanced glycation.
Sirt-1 plays a central role in maintaining metabolic homeostasis by regulating glucose and lipid metabolism, improving insulin sensitivity, supporting mitochondrial function and suppressing inflammation. Coffee-derived polyphenols have been suggested to enhance Sirt-1 activity, promoting beneficial metabolic effects.
In contrast, activation of the AGE–RAGE signaling pathway triggers oxidative stress and inflammatory responses while promoting Sirt-1 degradation, which may impair metabolic regulation. Soluble RAGE (sRAGE) counteracts this process by acting as a circulating decoy receptor that binds advanced glycation end-products (AGEs) before they can activate membrane-bound RAGE.
By reducing AGE–RAGE signaling, sRAGE helps limit inflammation and vascular damage and has been associated with a lower risk of cardiovascular disease and other adverse metabolic outcomes.
Because higher BMI is linked to chronic low-grade inflammation, insulin resistance, oxidative stress, and alterations in the AGE–RAGE axis, the researchers suggested that BMI may influence the biological response to coffee consumption.
Coffee affects metabolic pathways differently based on BMI
The researchers recruited 30 adults with coronary artery disease (CAD) aged 40–80 years to participate in the randomized, double-blind, crossover study.
Following a 22-day washout period, the investigators randomly assigned participants to consume either caffeinated or decaffeinated coffee for 28 days, followed by the alternate coffee type for an additional 28 days without an intermediate washout.
At baseline and after each intervention period, the investigators measured body weight, calculated BMI, and collected fasting blood samples to assess glucose, lipid profile, HbA1c, homocysteine, apolipoproteins, lipoprotein(a), Sirt-1, small dense LDL (sdLDL), and sRAGE.
The investigators compared participants with relatively higher (Group A) and lower (Group B) mean BMI, although both groups had similar baseline biochemical characteristics. Most biochemical markers remained stable throughout the intervention. Neither caffeinated nor decaffeinated coffee changed body weight, BMI, or blood pressure during the study, however there was an increase in Sirt-1 levels after caffeinated coffee consumption in Group B.
The authors hypothesized that participants with a higher average BMI did not show the same increase in Sirt-1 due to obesity-related chronic inflammation and activation of the AGE–RAGE pathway impair Sirt-1 activity.
They also examined factors associated with sRAGE levels. In Group A, sRAGE was associated with glucose and lipoprotein(a) only at baseline, and these associations disappeared after coffee consumption. In Group B, the factors associated with sRAGE changed during the intervention. After decaffeinated coffee, sRAGE was associated with glycated hemoglobin, small dense LDL, and Sirt-1, whereas after caffeinated coffee, sRAGE became positively associated with Sirt-1 and glucose and inversely associated with lipoprotein(a).
The researchers suggested that decaffeinated and caffeinated coffee may affect different metabolic pathways, with caffeine potentially enhancing energy-sensing pathways and Sirt-1 activation.
“Exploratory findings suggest that the sRAGE-Sirtuin-1 axis may exhibit distinct association patterns across BMI phenotypes following coffee consumption,” the researchers concluded. “Specifically, homocysteine emerges as an upstream determinant of RAGE signaling only in leaner individuals after consuming either caffeinated or decaffeinated coffee.”
They noted that future cellular studies, animal experiments and larger cohort studies are required to validate the findings.
Source: Nutrients; doi: 10.3390/nu18142305; “BMI-Dependent Modulation of the Soluble RAGE-Sirtuin-1 Axis by Coffee Type in Coronary Artery Disease.” Authors: Roggerio, A. et al.
