Absorption, Pharmacokinetics, and Urinary Excretion of Pyridines After Consumption of Coffee and Cocoa‐Based Products Containing Coffee in a Repeated Dose, Crossover Human Intervention Study

Abstract

Scope The present study assesses the absorption, pharmacokinetics, and urinary excretion of coffee pyridines and their metabolites after daily regular exposure to specific dosages of coffee or cocoa‐based products containing coffee (CBPCC), considering different patterns of consumption. Methods and results In a three‐arm, crossover, randomized trial, 21 volunteers are requested to randomly consume for 1 month: one cup of espresso coffee per day, three cups of espresso coffee per day, or one cup of espresso coffee plus two CBPCC twice per day. The last day of the one‐month treatment, blood and urine samples are collected for 24 h. Trigonelline, N‐methylpyridinium, N‐methylnicotinamide, and N‐methyl‐4‐pyridone‐5‐carboxamide are quantified. Trigonelline and N‐methylpyridinium absorption curves and 24‐h urinary excretion reflect the daily consumption of different servings of coffee or CBPCC, showing also significant differences in main pharmacokinetic parameters. Moreover, inter‐subject variability due to sex and smoking is assessed, showing sex‐related differences in the metabolism of trigonelline and smoking‐related ones for N‐methylpyridinium. Conclusion The daily exposure to coffee pyridines after consumption of different coffee dosages in a real‐life setting is established. This data will be useful for future studies aiming at evaluating the bioactivity of coffee‐derived circulating metabolites in cell experiments, mimicking more realistic experimental conditions.

Coffee Bioactive N-Methylpyridinium Attenuates Tumor Necrosis Factor (TNF)-α-Mediated Insulin Resistance and Inflammation in Human Adipocytes

“…Here, we report that, at concentrations equivalent to those attainable in vivo [25,26] after the ingestion of 350 mL of freshly prepared dark coffee brew [25] or 1 to 3 espresso coffees [26], NMP exerts anti-inflammatory effects and prevents insulin resistance in human adipocytes made dysfunctional by prolonged exposure to the pro-inflammatory adipokine TNF-α. TNF-α has been proposed as one of the primary humoral links between obesity and insulin resistance [47,48].…”

“…The conversion of the water-soluble yellow dye MTT to insoluble purple formazan crystals by the action of mitochondrial reductases (MTT assay) was used to evaluate whether concentrations of NMP or TRIGO (Figure 1A,B), equivalent to those attainable in vivo [25,26], might cause cell damage or toxicity [27]. To this end, fully differentiated SGBS adipocytes were incubated with increasing concentrations of NMP or TRIGO for 5 h before being challenged, or not, with TNF-α for a further 18 h. As shown in Figure 1C,D…”

Effect of Coffee and Cocoa-Based Confectionery Containing Coffee on Markers of DNA Damage and Lipid Peroxidation Products: Results from a Human Intervention Study

“…As already reported [ 25 , 26 , 27 ], coffee capsules were chosen based on the results of a previous paper [ 2 ], while the amount of cocoa-based confectionery containing coffee was decided in order to provide approximately half of the caffeine content than the coffee.…”

“…In light of these controversial observations, there is a clear need to perform dietary intervention studies devoted to elucidating the impact of coffee consumption on human health. Within this context, the Pocket-4-life project [ 24 ] was developed with the specific purpose of investigating the bioavailability of the bioactive compounds of espresso coffee and cocoa-based confectionery containing coffee [ 25 , 26 ], as well as to study the potential beneficial effect of these products on cardiometabolic and oxidative stress markers [ 24 , 27 ]. Specifically, within the Pocket-4-Life project, we investigated the effect of one-month consumption of different doses of coffee or of cocoa-based products containing coffee on markers of oxidative stress, such as DNA damage and lipid peroxidation.…”

Impact of Caffeine on Alzheimer’s Disease Pathogenesis—Protective or Risk Factor?

“…The causes for this increased demand and consumption pleasure result from the pharmacokinetic and pharmacodynamics properties of caffeine. After ingestion, caffeine is rapidly absorbed in the gastrointestinal tract, more precisely in the small intestine, reaching a high concentration in the blood after 30–60 min, with individual variations up to 120 min in cases with delayed gastric emptying [ 5 ]. A particularity of caffeine compared to other nutritive principles is the negligible pre-systemic metabolism which occurs in the liver, resulting in high absorption rates [ 6 ].…”