Almanac A1C

The Coffee Paradox: How Your Morning Cup Powers Metabolic Health and Longevity

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dr. Karunia Valeriani Japar

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Introduction

Coffee is among the most widely consumed beverages worldwide and has attracted significant scientific interest due to its complex chemical composition and multifaceted effects on human health, particularly regarding metabolic outcomes. The global rise in metabolic disorders-including metabolic syndrome, type 2 diabetes, non-alcoholic fatty liver disease and cardiovascular disease- has driven research into dietary patterns and bioactive food components that may modulate disease risk. Coffee, rich in polyphenols, diterpenes, caffeine and other bioactive molecules, has emerged as a promising dietary factor associated with favorable metabolic health profiles [1,2,3].

Epidemiological and interventional studies consistently report that moderate coffee intake (typically 1-5 cups daily) is linked to lower risk of type 2 diabetes; chronic kidney disease, and metabolic syndrome, as well as reduced all-cause and cardiovascular mortality. The underlying biological mechanisms are believed to be multi- dimensional, involving antioxidant, anti-inflammatory, lipid-modulating, insulin-sensitizing, gut microbiome- modulating, and thermogenic effects. Notably, non-caffeine constituents such as chlorogenic acids appear to contribute substantially to coffee’s metabolic actions by improving glucose metabolism, enhancing insulin signaling, and reducing systemic inflammation. Evidence from Mendelian randomization indicates that the associations with type 2 diabetes and chronic kidney disease may reflect causal relationships, whereas effects on other cardiometabolic outcomes remain under investigation [1,2,3,4,5,6].

Given the high prevalence of metabolic disease and the widespread global consumption of coffee, a robust understanding of its health implications is crucial for clinicians, researchers, and public health policymakers. This review aims to comprehensively summarize the current evidence on coffee’s role in metabolic health, elucidate biological mechanisms, and identify practical considerations and future research needs [2,3].

Chemical Composition and Antioxidant Properties

Coffee beans possess a highly complex chemical composition that directly underpins their potent antioxidant properties. The main constituents include carbohydrates (about 60% of raw beans), protein (~13%), fats (~13%), fibers, minerals, and a range of minor compounds such as alkaloids, phenolic acids, diterpenes, and volatile components [7,8,9].

Key Chemical Constituents

  • Caffeine (1,3,7-trimethylxanthine): Principal methylxanthine alkaloid, known for its stimulant and modest antioxidant effect through free radical scavenging and metal chelation [7].
  • Chlorogenic acids (CGAs): The primary antioxidant polyphenols (including caffeolquinic, dicaffeoylquinic, and feruloyquinic acids), present at levels of 200 mg or more per cup. CGAs not only scavenge free radicals but also activate cellular antioxidant pathways, such as Nrf2 [7,11,12,13,14].
  • Other Polyphenols: Flavonoids (catechins, quercetin), hydroxycinnamic acids, tannins, and ferulic acid contribute additional antioxidant function [12,15].
  • Diterpenes (cafestol, kahweol): Lipid-soluble antioxidants, present mainly in unfiltered coffee, also modulate endogenous antioxidant defense [7,15].
  • Trigonelline and Melanoidins: Trigonelline provides antibacterial properties and melanoidins, formed during roasting, make up to 25% of brewed coffee dry matter and are major contributors to antioxidant capacity in roasted coffee [7,13,16].
  • Vitamins and Minerals: Coffee contains magnesium, potassium, niacin, and other micronutrients that support its health benefits. [7,13,16]

Antioxidant Mechanisms

The antioxidant activity of coffee arises through multiple mechanisms:

  • Direct Radical Scavenging: Phenolic acids (especially CGAs) and flavonoids neutralize free radicals, limiting oxidative stress and cellular damage [7,12].
  • Metal Ion Chelation: Polyphenols and melanoidins bind iron and copper ions, reducing their pro-oxidant effect [7,15].
  • Regulation of Antioxidant Genes: CGAs, caffeine, and roasting products can induce endogenous antioxidant enzyme expression (e.g., via Nrf2 activation), enhancing cellular resilience [7,11].
  • Roasting and Antioxidant Formation: While some phenolic content is lost with roasting, melanoidins formed during Mailard reactions compensate by providing substantial antioxidant protection. Light to medium roast generally retain a high antioxidant capacity, while dark roasts rely more on melanoidins [7,13,17].

Quantification of Antioxidant Activity

Antioxidant properties are evaluated by DPPH, ABTS, FRAP, and ORAC assays, demonstrating that both green and roasted coffee extracts have robust antioxidant effects, with substantial contributions from both hydrophilic (e.g., CGAs) and hydrophobic (e.g., diterpenes, melanoidins) components [7,18].

Compound/ClassFunction
Chlorogenic acidsPotent radical scavengers, Nrf2 activators [7,11,13]
MelanoidinsHigh molecular weight radicals scavengers [7,16]
FlavonoidsAntioxidant, anti-inflammatory effects [12,15]
CaffeineMinor antioxidant, metal chelator [7,10]
DiterpenesLipid antioxidant, enzyme modulators [7,15]
Table 1. Main Antioxidant Compounds in Coffee
Compund/ClassMain FunctionsTypical Content (coffee beverage)
CaffeineCNS stimulation, lipolysis, neuroprotection50-380mg/100mL [19,20]
Chlorogenic acidsAntioxidant, glucose control, anti-inflammatory35-500 mg/100mL [19,20]
TrigonellineVitamin B3 precursor, antioxidant, kidney stone prevention10-50mg/100 mL [19,20]
Cafestol, KahweolHepatic detox enzymes, LDL elevation, anticarcinogenic2-7 mg/cup (unfiltered) [19,20]
MelanoidinsAntioxidant, metal chelator, gut microbiome modulationMajor fraction of roasted solids [19,20]
Table 2. Bioactive Compound Profile Summary Table

Synergistic Actions and Health Roles

  • These compounds collectively contribute to coffee’s broad health effects: antioxidative, anti-inflammatory, neuroprotective, metabolic, and gut-protective [19,21].
  • Recent research reveals that coffee bioactive regulate hepatic lipid and glucose metabolism via signaling axes such as FGF21 and AMPK, enhance mitochondrial bioenergetics, and modulate inflammation through Nrf2 and related gene networks [19,22].

Antioxidant Capacity Assessment

The antioxidant capacity of coffee is assessed through a variety of analytical methods, each illuminating different facets of coffee’s redox potential. The main techniques include [7,23]:

  1. Chemical Assay Methods
    • DPPH (2,2-diphenyl-1-picrylhydrazyl) Radical Scavenging Assay:
      • Measures the ability of coffee antioxidants to donate protons to the stable DPPH radical, resulting in a color change detectable by spectrophotometry [23,24].
      • Fast, cost-effective, and commonly used, though coffee’s color can interfere with readings. DPPH is not the most physiologically relevant radical [24].
    • ABTS(2,2’-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid)) Assay:
      • Evaluates the capacity of antioxidants to quench ABTS-+ radicals, generating a color change measured spectrophotometrically [23,25].
      • Suitable for both hydrophilic and lipophilic antioxidants, but sensitivity may vary by sample type [25].
    • FRAP (Ferric Reducing Antioxidant Power) Assay:
      • Quantifies the reduction of ferric (Fe3+) to ferrous (Fe2+) ions by coffee antioxidants, correlated with electron-donating capacity [18,23,26].
      • Often closely matches total phenolic content results and is sensitive for roasting effects.
    • ORAC (Oxygen Radical Absorbance Capacity):
      • Measures the ability of coffee antioxidants to protect a fluorescent marker (e.g., fluorescein) from peroxyl radical-induced oxidation [7,25].
      • Suitable for both hydrophilic and hydrophobic compounds, reflecting kinetic differences in antioxidant action [7].
    • Non-conventional Biosensors:
      • Advanced methods like DNA-based biosensors detect radical damage to DNA and the protective effects conferred by coffee antioxidants [27].
  2. Effects of Roasting
    • Roasting alters coffee’s antioxidant profile by decreasing polyphenol content but increasing melanoidin formation [18,28].
    • Light and medium roast retain more phenolic compounds and thus typically have higher antioxidant capacity than dark roasts [29].
    • Melanoidins formed via Mailard reactions in roasting contribute substantial antioxidant potential, compensating for some loss of polyphenols [7,29].
  3. Influence of Coffee Type and Quality
    • Antioxidant activity varies with coffee species (Arabica vs. Robusta), bean quality, and origin. Arabica often shows higher phenolic content and overall antioxidant activity compared to Robusta [30,31].
    • Extraction and brewing methods also impact measured antioxidant capacity [32].
  4. Example Results and Interpretation
    • Typical values for antioxidant capacity in coffee are reported as Trolox Equivalents (TE) using DPPH and FRAP assays, e.g., light roast extract showed the highest DPPH activity (~23,000 μmol TE/g) [25].
    • Total phenolic content, as assessed by Folin-Ciocalteu, is strongly correlated with antioxidant capacity across methods [33].
    • Despite roasting-related decline in phenolics, all coffee brews maintain high antioxidant activity at typical consumption levels [18,28].
Assay/MethodPrincipleSensitivity to Roasting
DPPHRadical scavenging (colorimetric)Moderate [23,24]
ABTSRadical scavenging (colorimetric)Moderate [23,25]
FRAPElectron donation (colorimetric)High [18,23]
ORACFluorescence protectionSensitive [7,25]
BiosensorDNA/radical damage protectionHigh [27]
Table 3. Coffee Antioxidant Capacity Assessment

Metabolic Health Benefits of Coffee

Coffee consumption is robustly associated with metabolic health benefits, particularly a reduced risk of type 2 diabetes and improved glycemic control in long-term epidemiological studies, though mechanistic and short-term intervention studies reveal nuanced effects on glucose and insulin sensitivity [34,35,36].

Glucose and Insulin Sensitivity

  • Epidemiological Evidence: Habitual coffee intake (3-4 cups/day) correlates with a ~25% lower risk of developing type 2 diabetes compared to no consumption. These benefits are seen for both caffeinated and decaffeinated coffee, implicating non-caffeine phytochemicals [34,37].
  • Intervention and Mechanistic Studies: Acute consumption of caffeinated coffee can transiently reduce insulin sensitivity and increase blood glucose due to caffeine’s antagonism of adenosine receptors, stimulation of catecholamine release, and increases in free fatty acid mobilization [4,36,38,39]. However, these acute effects typically do not persist with long term coffee use, where adaptive (tolerance) responses and the influence of other coffee components become dominant.
  • Clinical Trials: Meta-analyses of randomized controlled trials (RCTs) show minimal or nonsignificant effects of long-term coffee consumption on HOMA-IR (insulin resistance index) and Matsuda index (insulin sensitivity). Large studies in women also suggest black coffee may improve insulin sensitivity and glucose control [36,40,41].

Mechanism of Glycemic Control

Coffee’s positive effects on glycemic control are strongly linked to its rich polyphenol content, especially chlorogenic acids (CGAs):

  • Inhibition of Carbohydrate Digestion: CGAs inhibit a-amylase and a-glucosidase, reducing intestinal absorption of glucose from starch and other carbohydrates [37].
  • Reduced Glucose Absorption: CGAs may directly block sodium-dependent glucose transporters in the gut [37].
  • Suppression of Hepatic Glucose Output: CGAs may directly block sodium-dependent glucose transporters in the gut [37].
  • Insulin Secretion and Uptake: Some polyphenols stimulate pancreatic insulin secretion and enhance glucose uptake by skeletal muscle and adipose tissue via AMPK and other intracellular signaling pathways [37].
  • Anti-inflammatory and Antioxidant Effects: Coffee’s polyphenols dampen chronic inflammation and oxidative stress linked to insulin resistance progression [37].

Key Takeaway

While caffeine acutely reduces insulin sensitivity, regular long-term coffee consumption, particularly due to high CGA and polyphenol content, is associated with improved glucose metabolism and substantially lower diabetes risk- highlighting important differences between short- and long-term metabolic responses [34,36,37].

Clinical Evidence For Diabetes Management

Multiple large-scale clinical studies and meta-analyses provide compelling evidence for coffee’s beneficial role in the primary prevention and management of type 2 diabetes (T2DM). The findings are as follows [34,42,43]:

  • Epidemiological and Meta-analytic Evidence
    • Inverse Association with Diabetes Risk: Systematic reviews and dose-response meta-analyses (aggregating >1 million participants) consistently demonstrate that habitual coffee consumption is linked to a lower risk of developing T2DM, with the risk dropping by about 33% for individuals drinking 6 or more cups per day compared to non-consumers [34,42,43].
    • Caffeinated vs. Decaffeinated: Both caffeinated and decaffeinated coffee intake are associated with reduced diabetes risk, indicating key roles for non-caffeine components (e.g., polyphenols, chlorogenic acids) [34,42,43,44,46].
    • Dose-Response relationship: Risk of T2DM decreases by roughly 12-14% for every additional two cups of coffee consumed per day, and by 11% for decaffeinated coffee, underscoring a robust and consistent inverse relationship [43].
  • Clinical trial and Interventional Evidence
    • Acute vs. Chronic Effects: Short-term intervention trials sometimes show that caffeine coffee acutely impairs insulin sensitivity, but long-term moderate coffee intake improves overall glycemic markers and is associated with lower incidence of diabetes in real-world populations [35,42].
    • Diabetes Management: A controlled trial in people with T2DM found that decaffeinated coffee produced greater improvement in glycemic control (notably HbA1c reduction) than caffeinated coffee. Other studies suggest chronic coffee consumption lowers fasting insulin and C-peptide (a marker of insulin secretion), implying improved insulin sensitivity [42].
    • Glycemic and Cardiovascular Endpoints: Coffee and tea intake have been linked to lower risk of cardiovascular events and death among individuals with diabetes [42].
  • Additional Clinical Nuances
    • Caffeine’s Role: The improved outcomes with decaffeinated coffee and the benefit of both coffee types (caffeinated and decaf) strongly suggest that non-caffeine bioactive compounds drive most of the protective effects [35,42].
    • Moderate Consumption Most Favorable: Regular, moderate consumption (3-4 cups daily, typically 400-600mg caffeine) produces the greatest positive impact; excessive intake has not been shown to confer additional glycemic benefit and may cause other adverse effects [4,42].

Effects of Coffee on Lipid Profile and Cardiovascular Health

Coffee consumption exerts complex, dose-dependent effects on serum lipid profiles and cardiovascular health, with underlying mechanisms shaped by both coffee constituents and preparation methods.

  • Effects on Lipid Profile
    • Total Cholesterol (TC) and LDL Cholesterol (LDL-C):
      • Multiple population analyses and meta-analyses reveal a positive association between increasing coffee intake and rises in TC and LDL-C, especially with unfiltered coffee (e.g., boiled, French press, Turkish), mainly due to the presence of diterpenes cafestol and kahweol.
      • For every additional cup per day, TC may increase by~1.2 mg/dl and LDL-C by ~1.2 mg/dl; those consuming ≥3 cups/day experience larger increases.
      • Filtered coffee, by contrast, has negligible effects on LDL-C or TC since the paper filter removes most diterpenes.
  • HDL Cholesterol (HDL-C) and Triglycerides (TG):
    • Coffee’s impact on HDL-C and TG is nuanced and appears sex- and dose-dependent. In women, moderate consumption (up to ~2.6 cups/day) raises HDL-C but declines at higher intakes; in men, TG increases up to ~3 cups/day, then falls, suggesting non-linear trends [47].
    • Instant and Turkish coffee may slightly elevate TG levels; filtered types are largely neutral [47,48].
  • Cardiovascular Health Outcomes
    • Mortality and Disease Risk:
      • Moderate coffee consumption (2-4 cups daily) is linked to lower risks of all-cause and cardiovascular mortality, reduced incidence of hypertension, arrhythmias, heart failure, and coronary events [49,50].
      • Cardioprotective effects are attributed to anti-inflammatory and antioxidant polyphenols, positive endothelial and metabolic actions, and improved vascular responsiveness [49,50].
  • Mechanisms Affecting Lipid Metabolism
    • Diterpenes (Cafestol, Kahweol):
      • These compounds suppress hepatic LDL receptor activity by posttranscriptional mechanisms, reducing LDL clearance and raising LDL-C levels in blood [20].
      • Filtered coffee contains negligible diterpene levels, mitigating these effects.
    • Polyphenols and Other Bioactives:
      • Chlorogenic acids, caffeine, and trigonelline modulate lipid uptake and transport in the liver and adipose tissue, mainly through CD36, AMPK, and PPARc-dependent signaling, contributing to reduced triglyceride and cholesterol absorption and inflammation.
      • These effects can support favorable lipid profiles over time, especially with regular, moderate consumption.
    • Preparation Modifies Risk:
      • Unfiltered coffee raises cholesterol/TG via diterpenes; filtered or intant coffee has neutral or favorable effects, especially among moderate consumers.
Coffee TypeLDL-C/TC EffectHDL-C/TG EffectCardiovascular RiskKey Mechanism
Unfiltered (boiled)↑↑LDL/TCModest ↑ or neutralAdverse, if excessDiterpene-induced LDL↑ [47,51,52]
FilteredNeutralNeutral/slight ↑HDLLowered mortality riskPolyphenol-mediated [20,48,49]
Moderate intakeMinimal effectFavorable (↓ CVD risk)↓CVD, ↑vascular healthAntioxidant, anti-inflammatory [49,50,53]
Table 4 Coffee Effects on Lipids and Cardiovascular Health

Weight Management

Coffee, particularly through its bioactive compounds like caffeine and chlorogenic acids, supports weight management via multiple metabolic pathways involving energy expenditure, fat metabolism, and appetite regulation. Here is a detailed explanation [20,54,55]:

  • Mechanism of Action
    • Thermogenesis and Increased Energy Expenditure:
      • Caffeine is a potent stimulant of central nervous system, increasing metabolic rate and daily energy expenditure [55,56,57].
      • Human studies show that regular coffee/caffeine intake elevates resting metabolic rate by 3-11%, an effect partly mediated by enhanced sympathetic nervous system activity and increased catecholamine secretion [55,56].
  • Enhanced Fat Oxidation and Lipolysis:
    • Both acute and chronic caffeine intake significantly increase the release of free fatty acids from adipose tissue (lipolysis) and promote their oxidation for energy, especially at rest and during low to moderate intensity exercise [54,55].
    • This effect contributes to greater total fat oxidation, which is linked to lower body fat mass over time [54,58,59].
  • Modulation of Key Metabolic Pathways:
    • Caffeine, chlorogenic acids, and related compounds upregulate the AMP-activated protein kinase (AMPK) pathway and influence PPARc, SREBP, and FOXO signaling, leading to:
      • Suppressed lipogenesis (fat storage),
      • Increased fatty acid b-oxidation,
      • Improved insulin sensitivity [20,60],
    • Coffee bioactives also have epigenetic effects (e.g., upregulation of miR-122 and miR-96) that inhibit enzymes central to fat accumulation [20].
  • Appetite Suppression and Energy Intake Reduction:
    • Caffeine modestly suppresses appetite and can reduce overall calorie intake in the short term, supporting weight maintenance and fat loss [57,61,62].
  • Evidence from Clinical and Observational Studies
    • Fat Mass and Body Composition:
      • Randomized trials and observational studies demonstrate that higher coffee/ caffeine consumption (up to 3-4 cups/day) is associated with reduced risk of obesity, lower body fat percentage, and increased fat-free mass in various populations [58,59,63,64].
      • A trial found that overweight individuals drinking four cups of coffee daily lost ~3.7% of their body fat over several weeks [61].
  • Long-term and Sex-specific Effects:
    • Chronic moderate coffee intake is linked with reduced weight gain overtime [58,64].
    • The effect may be more pronounced in women and varies according to genetic differences in caffeine metabolism (e.g., CYP1A2 genotype) [54,65].
MechanismImpact on Weight/FatMain Bioactives
Increased thermogenesisHigher energy expenditureCaffeine [55,56,57]
Enhanced fat oxidationGreater fat lossCaffeine, CGAs [20,54,59]
Suppressed lipogenesisLess fat storageCaffeine, CGAs [20,60]
Appetite suppressionReduced food intakeCaffeine [57,61]
Table 5. Coffee and Weight Management Mechanisms

Anti Aging and Longevity Management of Coffee

Coffee exerts anti-aging and longevity-promoting effects through a variety of mechanisms, centered around cellular energy regulation, antioxidant actions, and the modulation of stress and inflammation biomarkers. Recent epidemiological and mechanistic studies show that habitual coffee drinkers tend to live longer, with prolonged health span and reduced risk of chronic disease [66,67,68,69,70,71].

  • Mechanism Underlying Anti-Aging and Longevity
    • Cellular Energy Sensing (AMPK and mTOR Pathways):
      • Caffeine and other coffee bioactives activate AMPK (AMP-activated protein kinase), a master cellular “fuel gauge” that promotes DNA repair, autophagy, stress resilience, and metabolic balance [72,73].
      • Caffeine inhibits mTORC1 (mammalian target of rapamycin complex 1), a growth regulator linked with accelerated aging and cellular senescence; mTOR suppression slows cell aging and improves stress resistance [70.72].
      • These molecular switches also drive metabolic health and overlap with interventions like calorie restriction and metformin for lifespan extension [72,73].
  • Antioxidant and Anti-Inflammatory Effects:
    • Coffee polyphenols (mainly chlorogenic acids) and melanoidins enhance activity of key cellular antioxidant enzymes: superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) [74,75,76].
    • Consumption boost endogenous antioxidant defenses and reduces markers of oxidative stress and inflammation, key drivers of aging and age-related disease [74,77,78].
    • CGA specifically extends mean lifespan and delays age-related decline of movement and stress resistance in preclinical models (e.g., elegans, yeast) [75].
  • Protection Against Genomic Instability and Cellular Damage:
    • Regular coffee consumption improves DNA repair capacity, reduces DNA double-strand breaks, and decreases protein/lipid oxidation [69,75].
    • Key pathways modulated include FOXO transcription factors, HSF-1, SKN-1, and HIF-1, which drive stress resilience and healthy aging [75].
  • Human Biomarker Evidence
    • Reduced Biomarkers of Oxidative Stress: Coffee intake consistently lowers serum oxidized LDL, 8-OHdG (DNA oxidative damage marker), and malondialdehyde (lipid peroxidation marker) [75,76,77,78].
    • Enhanced antioxidant enzyme Activity: Higher SOD, catalase, and GPx activities are seen in coffee consumers [75,76].
    • Lower Inflammatory Cytokines: Habitual drinkers show reduced circulating CRP, IL-6, TNF-a, and other pro-inflammatory markers-correlated with lower cardiovascular and all-cause mortality [77,78,79].
    • Relevant Clinical Outcomes: Coffee intake is linked to 1.8-2 extra years of lifespan and healthier aging, with broad reductions in risk for diabetes, heart disease, neurodegeneration, and cancer [69,80].

Gut Microbiome And Metabolic Health Mechanism

Coffee influences the gut microbiome and metabolic health via both direct and indirect mechanisms involving its unique array of bioactive compounds- caffeine, polyphenols (especially chlorogenic acids), and fiber-like melanoidins [81,82,83].

  • Gut Microbiome Modulation
    • Altered Microbiota Composition: Human and animal studies show that regular coffee consumption (2-4 cups/day) increases beneficial gut bacteria such as Actinobacteria (notably Bifidobacterium spp.) and some Firmicutes, while reducing potentially harmful bacteria like Proteobacteria and .coli. Some studies show a decrease in Bacteroidetes, others see an increase, with impacts broadly driven by coffee’s non-digestible components [81,82,84].
    • Prebiotic Effects of Coffee Melanoidins: Melanoidins formed during roasting are large, mostly indigestible molecules that reach the colon, where they act as “Mailardized antioxidant dietary fiber” – promoting the growth of probiotic bacteria and production of short chain fatty acids (SCFAs) like butyrate and propionate. These effects mirror those of conventional prebiotic fibers in sustaining healthy gut ecology [81,83].
    • Polyphenols And SCFA Production: Coffee’s abundant polyphenols (notably CGA) are metabolized by the colonic microbiota, driving up SCFA levels, reducing inflammation, enhancing colonic barrier function, and providing antioxidant benefits [82,84,85].
  • Metabolic Health Mechanism
    • Improved Glycemic and Lipid Homeostasis: Coffee-induced microbiome changes (notably more Bifidobacterium and SCFA production) result in improved gut barrier integrity, reduced endotoxin leakage, and lower inflammation- contributing to better insulin sensitivity, glycemic control, and lipid metabolism [82,83].
    • Anti-Inflammatory Pathways: SCFAs and bioactive metabolites from coffee fermentation downregulate pro-inflammatory cytokines (IL-6, TNF-a) and upregulate anti-inflammatory mediators, mitigating obesity0 and diabetes-related inflammation [69,82,86].
    • Gut Motility and Absorption: Both caffeinated and decaffeinated coffee stimulate gut motility/ secretions and may enhance transit time, limit pathogen colonization, and influence nutrient absorption, with additional indirect metabolic benefits [69,82,86].
    • Microbiome Diversity: Moderate coffee use is associated with greater microbiome alpha diversity, a recognized marker of metabolic and overall health [82,85].
  • Biomarker Impacts
    • Higher SCFA Levels: Butyrate, propionate, and acetate are increased, supporting anti-inflammatory and metabolic actions [83,85].
    • Increased Beneficial Bacteria: *Bifidobacterium, Faecalibacterium, Barnesiella,*and others correspond with lower diabetes and obesity risk [82,83,85].
    • Reduced GI Inflammation Markers: CRP, fecal calcprotectin, and other markers are improved after regular coffee use [82,83].

Safety Profile and Contraindications

Coffee is generally safe for most healthy adults when consumed in moderate amounts, with many studies indicating health benefits rather than harm. However, certain populations and conditions require caution due to potential adverse effects primarily attributable to caffeine and other compounds [87,88,89,90,91].

  • Safety Profile
    • Recommended Intake: up to 400mg/day of caffeine (about 3-4 cups of brewed coffee) is considered safe for healthy adults, with no significant adverse effects on cardiovascular health, calcium balance, behavior, cancer risk, or male fertility [90,91,92].
    • Physical Side Effects: High intakes may cause jitteriness, anxiety, insomnia, restlessness, rapid heartbeat, headache, dizziness, and gastrointestinal disturbances (nausea, diarrhea, ulcers) [93].
    • Blood Pressure and Heart Rate: Coffee can temporarily raise blood pressure and heart rate, especially in caffeine-sensitive individuals or those rarely consuming it. For most people, regular moderate coffee isn’t linked to increased blood pressure or arrhythmic risk, but caution is advised in those with uncontrolled hypertension or cardiac arrhythimias [93,94].
    • Bone Health: Caffeine increases calcium loss in urine, possibly raising fracture risk in postmenopausal women with inadequate calcium intake [88,95].
    • Addiction: Chronic high intake may lead to caffeine dependence and withdrawal symptoms (fatigue, irritability, headache) [96].
  • Contraindications
    • Pregnancy: Limit caffeine intake to under 200 mg/day (~2 cups) as even moderate doses cross the placenta, are linked to reduced fetal growth, higher miscarriage and low birth weight risk [88,91,97,98,99].
    • Children and Adolescents: Safe threshold is much lower (~100mg/day), equivalent to ~1 cup, due to lower tolerance and greater sensitivity to caffeine’s effects [91,93].
    • Cardiovascular Disease/ Arrhythmia: Individuals with symptomatic arrhythmia or severe heart disease should avoid high caffeine doses and monitor intake carefully [93,94].
    • Mental Health Conditions: Anxiety disorders, insomnia, panic disorder, and epilepsy are all exacerbated by caffeine [93].
    • GI Disorders: Individuals with IBS, peptic ulcer, reflux, and severe GI symptoms may have worsening of their condition from coffee [95]
    • Medications: Coffee/caffeine can interact with blood thinners (increase bleeding risk), stimulate drug metabolism, and alter the effects of some prescription drugs [100].
  • Special Populations & Cautions
    • Osteoporosis: Caffeine may worsen bone loss, so individuals with osteoporosis should limit intake to <3 cups per day, ensure adequate calcium and vitamin D [88,95].
    • Elderly: Sensitivity to caffeine increases; symptoms like insomnia and arrhythmia may be more common [101].
    • Pregnant/ Breastfeeding Women: Caffeine passes to the fetus/ infant and may disrupt sleep, growth, and neurodevelopment; limit or avoid [97,99].

References

  1. Mohamed AI, Erukainure OL, Salau VF, Islam MS. Impact of coffee and its bioactive compounds on the risks of type 2 diabetes and its complications: A comprehensive review. Diabetes & Metabolic Syndrome: Clinical Research & Reviews [Internet]. 2024 Jul 1;18(7):103075. Available from: https://www.sciencedirect.com/science/article/pii/S187140212400136X
  2. Wong THT, Wong CH, Zhang X, Zhou Y, Xu J, Yuen KC, et al. The Association Between Coffee Consumption and Metabolic Syndrome in Adults: A Systematic Review and Meta-Analysis. Advances in Nutrition. 2020 Oct 28;12(3):708–21.
  3. Zoltan Ungvari, Kunutsor SK. Coffee consumption and cardiometabolic health: a comprehensive review of the evidence. GeroScience. 2024 Jul 4;
  4. Effects of coffee consumption on glucose metabolism: A systematic review of clinical trials. Journal of Traditional and Complementary Medicine [Internet]. 2019;9(3):184–91. Available from: https://www.sciencedirect.com/science/article/pii/S2225411018300014
  5. Semiz S, Serdarevic F. Prevention and Management of Type 2 Diabetes and Metabolic Syndrome in the Time of COVID-19: Should We Add a Cup of Coffee? Frontiers in Nutrition [Internet]. 2020 Oct 6;7. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7573071/
  6. Corbi-Cobo-Losey MJ, Miguel Ángel Martínez‐González, Anne Katherine Gribble, Fernández-Montero A, Navarro AM, Domínguez LJ, et al. Coffee Consumption and the Risk of Metabolic Syndrome in the “Seguimiento Universidad de Navarra” Project. Antioxidants. 2023 Mar 10;12(3):686–6.
  7. Liang N, Kitts D. Antioxidant Property of Coffee Components: Assessment of Methods that Define Mechanisms of Action. Molecules. 2014 Nov 19;19(11):19180–208.
  8. Freitas VV, Lorrane L, Teixeira C, Henrique M, Stringheta PC. Coffee: A comprehensive overview of origin, market, and the quality process. Trends in Food Science and Technology. 2024 Feb 1;146:104411–1.
  9. Saud S, Salamatullah AM. Relationship between the Chemical Composition and the Biological Functions of Coffee. Molecules. 2021 Dec 16;26(24):7634.
  10. Vieira AJSC, Gaspar EM, Santos PMP. Mechanisms of potential antioxidant activity of caffeine. Radiation Physics and Chemistry. 2020 Sep;174:108968.
  11. Ősz BE, Jîtcă G, Ștefănescu RE, Pușcaș A, Tero-Vescan A, Vari CE. Caffeine and Its Antioxidant Properties-It Is All about Dose and Source. International Journal of Molecular Sciences [Internet]. 2022 Oct 28;23(21):13074. Available from: https://pubmed.ncbi.nlm.nih.gov/36361861/
  12. Bjarnadottir A. Coffee and Antioxidants: Everything You Need to Know [Internet]. Healthline. 2019. Available from: https://www.healthline.com/nutrition/coffee-worlds-biggest-source-of-antioxidants
  13. Watson D. The Top Coffee Antioxidants and Their Health Benefits [Internet]. Tea-and-Coffee.com. 2025. Available from: https://www.tea-and-coffee.com/blog/coffee-antioxidants
  14. Yeager SE, Batali ME, Guinard JX, Ristenpart WD. Acids in coffee: A review of sensory measurements and meta-analysis of chemical composition. Critical Reviews in Food Science and Nutrition [Internet]. 2021 Sep 23;63(8):1–27. Available from: https://pubmed.ncbi.nlm.nih.gov/34553656/
  15. Yashin A, Yashin Y, Wang J, Nemzer B. Antioxidant and Antiradical Activity of Coffee. Antioxidants. 2013 Oct 15;2(4):230–45.
  16. Iriondo-DeHond A, Ramírez B, Escobar FV, Dolores del Castillo M. Antioxidant properties of high molecular weight compounds from coffee roasting and brewing byproducts. Bioactive Compounds in Health and Disease. 2019 Mar 29;2(3):48.
  17. Antioxidant capacity of coffees of several origins brewed following three different procedures. Food Chemistry [Internet]. 2007 Jan 1;102(3):582–92. Available from: https://www.sciencedirect.com/science/article/abs/pii/S0308814606004304
  18. Liao YC, Kim T, Silva JL, Hu WY, Chen BY. Effects of roasting degrees on phenolic compounds and antioxidant activity in coffee beans from different geographic origins. LWT. 2022 Oct;168:113965.
  19. Markos Makiso Urugo, Tola YB, Onwuchekwa Ogah, Fitsum Liben Endale. Bioactive compounds in coffee and their role in lowering the risk of major public health consequences: A review. Food Science and Nutrition. 2023 Nov 22;12(2).
  20. Farias-Pereira R, Park CS, Park Y. Mechanisms of action of coffee bioactive components on lipid metabolism. Food Science and Biotechnology. 2019 Aug 12;28(5):1287–96.
  21. Sandeep PM, Mandappa IM. Bioactive components in coffee and their health aspects. Coffee Science. 2022 Jul 7;293–302.
  22. Rebollo-Hernanz M, Aguilera Y, Martín-Cabrejas MA, Gonzalez de Mejia E. Activating Effects of the Bioactive Compounds From Coffee By-Products on FGF21 Signaling Modulate Hepatic Mitochondrial Bioenergetics and Energy Metabolism in vitro. Frontiers in Nutrition. 2022 Mar 22;9.
  23. Pokorná J, Venskutonis PR, Kraujalyte V, Kraujalis P, Dvořák P, Tremlová B, et al. Comparison of different methods of antioxidant activity evaluation of green and roastC. ArabicaandC. Robustacoffee beans. Acta Alimentaria [Internet]. 2015 Sep;44(3):454–60. Available from: https://core.ac.uk/download/pdf/42945738.pdf
  24. Nemzer B, Kalita D, Abshiru N. Quantification of Major Bioactive Constituents, Antioxidant Activity, and Enzyme Inhibitory Effects of Whole Coffee Cherries (Coffea arabica) and Their Extracts. Molecules. 2021 Jul 16;26(14):4306.
  25. Souza L dos S de, Carrero Horta IP, de Souza Rosa L, Barbosa Lima LG, Santos da Rosa J, Montenegro J, et al. Effect of the roasting levels of Coffea arabica extracts on their potential antioxidant capacity and antiproliferative activity in human prostate cancer cells. RSC Advances. 2020;10(50):30115–26.
  26. Sánchez-González I, Jiménez-Escrig A, Saura-Calixto F. In vitro antioxidant activity of coffees brewed using different procedures (Italian, espresso and filter). Food Chemistry. 2005 Mar;90(1-2):133–9.
  27. Morais SL, Rede D, Maria João Ramalhosa, Correia M, Maria, Delerue‐Matos C, et al. Assessment of the Antioxidant Capacity of Commercial Coffee Using Conventional Optical and Chromatographic Methods and an Innovative Electrochemical DNA-Based Biosensor. Biosensors. 2023 Aug 24;13(9):840–0.
  28. Duarte SM da S, Abreu CMP de, Menezes HC de, Santos MH dos, Gouvêa CMCP. Effect of processing and roasting on the antioxidant activity of coffee brews. Ciência e Tecnologia de Alimentos. 2005 Jun;25(2):387–93.
  29. Rahmawati I, Purnamasari Y. Effect of Light, Medium, and Dark Roasting on Antioxidant Activity of Gununghalu Arabica Coffee (Coffea arabica L.). International Journal of Business, Economics, and Social Development [Internet]. 2024 Feb 29;5(1):78–83. Available from: https://www.journal.rescollacomm.com/index.php/ijbesd/article/view/586
  30. Melliyanti SN, Afandi FA, Giriwono PE, Herawati D. A meta analysis: the effects of types, roasting degrees and origins on antioxidant properties of coffee. International Journal of Food Science & Technology. 2023 Apr 10;
  31. Odžaković B, Džinić N, Kukrić Z, Grujić S. Effect of roasting degree on the antioxidant activity of different Arabica coffee quality classes. Acta Scientiarum Polonorum Technologia Alimentaria [Internet]. 2016 Oct 1 [cited 2020 Dec 14];15(4):409–17. Available from: https://pubmed.ncbi.nlm.nih.gov/28071018/
  32. Kocadağlı T, Gökmen V. Effect of roasting and brewing on the antioxidant capacity of espresso brews determined by the QUENCHER procedure. Food Research International. 2016 Nov;89:976–81.
  33. TERRA S, MELENGATI J, ROSADO CP, ALVES EA, ROCHA RB, Teixeira A, et al. ANTIOXIDANT ACTIVITY AND TOTAL PHENOLIC CONTENT OF AMAZONIAN ROBUSTA COFFEE HUSK: THE INFLUENCE OF SELF- INDUCED ANAEROBIOSIS FERMENTATION | Galoá Proceedings. Proceedingsscience [Internet]. 2023 [cited 2025 Sep 15]; Available from: https://proceedings.science/slacan-2023/trabalhos/antioxidant-activity-and-total-phenolic-content-of-amazonian-robusta-coffee-husk?lang=pt-br
  34. Ding M, Bhupathiraju SN, Chen M, R. M. van Dam, Hu FB. Caffeinated and Decaffeinated Coffee Consumption and Risk of Type 2 Diabetes: A Systematic Review and a Dose-Response Meta-analysis. Diabetes Care [Internet]. 2014;37(2):569–86. Available from: http://care.diabetesjournals.org/content/diacare/37/2/569.full.pdf
  35. Effects of coffee consumption on glucose metabolism: A systematic review of clinical trials. Journal of Traditional and Complementary Medicine [Internet]. 2019;9(3):184–91. Available from: https://www.sciencedirect.com/science/article/pii/S2225411018300014
  36. ‌Moon SM, Joo MJ, Lee YS, Kim MG. Effects of Coffee Consumption on Insulin Resistance and Sensitivity: A Meta-Analysis. Nutrients. 2021 Nov 8;13(11):3976.
  37. Effects of coffee consumption on glucose metabolism: A systematic review of clinical trials. Journal of Traditional and Complementary Medicine [Internet]. 2019;9(3):184–91. Available from: https://www.sciencedirect.com/science/article/pii/S2225411018300014
  38. Shi X, Xue W, Liang S, Zhao J, Zhang X. Acute caffeine ingestion reduces insulin sensitivity in healthy subjects: a systematic review and meta-analysis. Nutrition Journal [Internet]. 2016 Dec;15(1). Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5192567/
  39. van Dam RM, Pasman WJ, Verhoef P. Effects of Coffee Consumption on Fasting Blood Glucose and Insulin Concentrations: Randomized controlled trials in healthy volunteers. Diabetes Care. 2004 Nov 23;27(12):2990–2.
  40. Alperet DJ, Rebello SA, Khoo EYH, Tay Z, Seah SSY, Tai BC, et al. Abstract 040: The Effects of Coffee Consumption on Insulin Sensitivity and Other Risk Factors for Type 2 Diabetes. Circulation. 2018 Mar 20;137(suppl_1).
  41. MD T. News-Medical [Internet]. News-Medical. 2025 [cited 2025 Sep 15]. Available from: https://www.news-medical.net/news/20250504/Black-coffee-improves-insulin-sensitivity-in-women-study-finds.aspx
  42. Pimentel GD, Zemdegs JC, Theodoro JA, Mota JF. Does long-term coffee intake reduce type 2 diabetes mellitus risk? Diabetology and Metabolic Syndrome [Internet]. 2009 Sep 16;1:6. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2761298/
  43. Jiang X, Zhang D, Jiang W. Coffee and caffeine intake and incidence of type 2 diabetes mellitus: a meta-analysis of prospective studies. European Journal of Nutrition. 2013 Oct 23;53(1):25–38.
  44. Impact Of Caffeine and Decaffeinated Coffee on Blood Glucose Levels in Healthy Individuals And Type 2 Diabetes Patients on Antidiabetic Medication [Internet]. Jneonatalsurg.com. 2025 [cited 2025 Sep 15]. Available from: https://www.jneonatalsurg.com/index.php/jns/article/view/7415
  45. Ding L, Wang HP, Zhao JY, Zhao X, Sha Y, Qin LQ, et al. Coffee and tea consumption and cardiovascular disease and all-cause and cause-specific mortality in individuals with diabetes mellitus: a meta-analysis of prospective observational studies. Frontiers in Nutrition. 2025 Jun 2;12.
  46. Impact Of Caffeine and Decaffeinated Coffee on Blood Glucose Levels in Healthy Individuals And Type 2 Diabetes Patients on Antidiabetic Medication [Internet]. Jneonatalsurg.com. 2025. Available from: https://www.jneonatalsurg.com/index.php/jns/article/view/7415
  47. Mo C, Duan X, Pu J, Zhou X, Zheng Y, Wang S. Coffee consumption as a double-edged sword for serum lipid profile: findings from NHANES 2005-2020. Frontiers in nutrition [Internet]. 2025 Sep;12:1606188. Available from: https://pubmed.ncbi.nlm.nih.gov/40704303/
  48. KARABUDAK E, TÜRKÖZÜ D, KÖKSAL E. Association between coffee consumption and serum lipid profile. Experimental and Therapeutic Medicine. 2015 Mar 11;9(5):1841–6.
  49. Mendoza MF, Sulague RM, Posas-Mendoza T, Lavie CJ. Impact of Coffee Consumption on Cardiovascular Health. Ochsner Journal [Internet]. 2023 Mar 16;23(2):152–8. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10262944/
  50. Dewland TA, Rob, Marcus GM. Coffee and cardiovascular disease. PubMed [Internet]. 2025 Jul 8 [cited 2025 Sep 15]; Available from: https://academic.oup.com/eurheartj/advance-article-abstract/doi/10.1093/eurheartj/ehaf421/8193215?redirectedFrom=fulltext&login=false
  51. Urgert R, Essed N, van der Weg G, Kosmeijer-Schuil TG, Katan MB. Separate effects of the coffee diterpenes cafestol and kahweol on serum lipids and liver aminotransferases. The American Journal of Clinical Nutrition. 1997 Feb 1;65(2):519–24.
  52. Rustan AC, Halvorsen B, Huggett AC, Ranheim T, Drevon CA. Effect of Coffee Lipids (Cafestol and Kahweol) on Regulation of Cholesterol Metabolism in HepG2 Cells. Arteriosclerosis, Thrombosis, and Vascular Biology. 1997 Oct;17(10):2140–9.
  53. Rodríguez NB, Rico DC, Marin JC. Protocolo para una revisión de revisiones: efecto del consumo de café en el perfil lipídico y el riesgo de dislipidemia. Universitas Médica [Internet]. 2022 Aug 25;63(1). Available from: http://www.scielo.org.co/scielo.php?script=sci_arttext&pid=S2011-08392022000100005
  54. Gutiérrez-Hellín J, Del Coso J, Espada MC, Hernández-Beltrán V, Ferreira CC, Varillas-Delgado D, et al. Research Trends in the Effect of Caffeine Intake on Fat Oxidation: A Bibliometric and Visual Analysis. Nutrients [Internet]. 2023 Jan 1;15(20):4320. Available from: https://www.mdpi.com/2072-6643/15/20/4320
  55. Acheson KJ, Zahorska-Markiewicz B, Pittet P, Anantharaman K, Jéquier E. Caffeine and coffee: their influence on metabolic rate and substrate utilization in normal weight and obese individuals. The American Journal of Clinical Nutrition. 1980 May 1;33(5):989–97.
  56. Dulloo AG, Geissler CA, Horton T, Collins A, Miller DS. Normal caffeine consumption: influence on thermogenesis and daily energy expenditure in lean and postobese human volunteers. The American Journal of Clinical Nutrition [Internet]. 1989 Jan 1;49(1):44–50. Available from: https://academic.oup.com/ajcn/article-abstract/49/1/44/4716276/
  57. Harpaz E, Tamir S, Weinstein A, Weinstein Y. The effect of caffeine on energy balance. Journal of Basic and Clinical Physiology and Pharmacology [Internet]. 2017 Jan 1;28(1):1–10. Available from: https://www.degruyter.com/document/doi/10.1515/jbcpp-2016-0090/html
  58. Westerterp-Plantenga MS, Lejeune MPGM, Kovacs EMR. Body Weight Loss and Weight Maintenance in Relation to Habitual Caffeine Intake and Green Tea Supplementation. Obesity Research. 2005 Jul;13(7):1195–204.
  59. Cao C, Liu Q, Abufaraj M, Han Y, Xu T, Waldhoer T, et al. Regular Coffee Consumption Is Associated with Lower Regional Adiposity Measured by DXA among US Women. The Journal of Nutrition. 2020 May 3;150(7):1909–15.
  60. Gamboa-Gómez CI, Barragán-Zúñiga LJ, Guerrero-Romero F, Martínez-Aguilar G, José Luis Gónzalez, Valenzuela-Ramírez AA, et al. Effects of coffee with different roasting degrees on obesity and related metabolic disorders. Journal of functional foods. 2023 Dec 1;111:105889–9.
  61. How Caffeine Affects Your Metabolism [Internet]. www.henryford.com. 2024. Available from: https://www.henryford.com/blog/2024/02/effects-of-caffeine-on-metabolism-what-you-should-know
  62. Wang Q, Hu GL, Qiu MH, Cao J, Xiong WY. Coffee, tea, and cocoa in obesity prevention: mechanisms of action and future prospects. Current Research in Food Science. 2024 Apr 1;100741–1.
  63. Tian YL, Liu X, Yang MY, Wu YH, Yin FQ, Zhang ZT, et al. Association between caffeine intake and fat free mass index: a retrospective cohort study. Journal of the International Society of Sports Nutrition [Internet]. 2024 Dec 20 [cited 2025 Apr 3];22(1). Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC11703537/
  64. Shadia Hamoud Alshahrani, Atia YA, Raheem Atiya Badir, Almalki SG, Nahla Tayyib, Shahab S, et al. Dietary caffeine intake is associated with favorable metabolic profile among apparently healthy overweight and obese individuals. BMC Endocrine Disorders. 2023 Oct 20;23(1).
  65. Mattioli AV. Sex-specific impacts of caffeine on body composition: commentary on a retrospective cohort study. Journal of the International Society of Sports Nutrition [Internet]. 2025 Dec;22(1):2454633. Available from: https://pubmed.ncbi.nlm.nih.gov/39825466/
  66. StudyFinds Analysis. 2 extra years of life: Drinking coffee daily shows benefits for aging [Internet]. Study Finds. 2024 [cited 2025 Sep 15]. Available from: https://studyfinds.org/2-extra-years-drinking-coffee/
  67. Francisco H. News-Medical [Internet]. News-Medical. 2025 [cited 2025 Sep 15]. Available from: https://www.news-medical.net/news/20250819/Review-finds-coffee-linked-to-longer-life-and-lower-disease-risk.aspx
  68. com. Cumulative Research Suggests Coffee Prolongs Life by 1.8 Years [Internet]. Nad.com. 2024 [cited 2025 Sep 15]. Available from: https://www.nad.com/news/cumulative-research-suggests-coffee-prolongs-life-by-1-8-years
  69. New Study Links Coffee Consumption to Reduced Type 2 Diabetes Risk via Anti-Inflammatory Effects [Internet]. Coffeeandhealth.org. 2024. Available from: https://www.coffeeandhealth.org/health/media-content/news-alerts/daily-coffee-consumption-for-healthy-aging
  70. Takahashi K, Ishigami A. Anti-aging effects of coffee. Aging. 2017 Aug 29;9(8):1863–4.
  71. Lopes CR, Cunha RA. Impact of coffee intake on human aging: Epidemiology and cellular mechanisms. Ageing Research Reviews [Internet]. 2024 Nov 16;102:102581. Available from: https://www.sciencedirect.com/science/article/pii/S1568163724003994?via%3Dihub
  72. New Research Suggests Longevity from Coffee Tied to Ancient Cellular Trigger [Internet]. Daily Coffee News by Roast Magazine. 2025 [cited 2025 Sep 15]. Available from: https://dailycoffeenews.com/2025/08/19/new-research-suggests-longevity-from-coffee-tied-to-ancient-cellular-trigger/
  73. Caffeine Flip-Flops a 500-Million-Year-Old Switch to Slow Aging [Internet]. SciTechDaily. 2025 [cited 2025 Sep 15]. Available from: https://scitechdaily.com/caffeine-flip-flops-a-500-million-year-old-switch-to-slow-aging/
  74. Moshtagh M, Moodi M, Moezi SA, Sharifi F, Khazdair MR. Inflammatory and Oxidative Stress Biomarkers in the Elderly, the Birjand Longitudinal Aging Study. Aihara K, editor. BioMed Research International [Internet]. 2023 Jan [cited 2025 Aug 13];2023(1). Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC9974246/
  75. Kobylińska Z, Biesiadecki M, Kuna E, Galiniak S, Mołoń M. Coffee as a Source of Antioxidants and an Elixir of Youth. Antioxidants [Internet]. 2025 Feb 27;14(3):285. Available from: https://www.mdpi.com/2076-3921/14/3/285
  76. Dludla PV, Cirilli I, Fabio Marcheggiani, Silvestri S, Orlando P, Ndivhuwo Muvhulawa, et al. Potential Benefits of Coffee Consumption on Improving Biomarkers of Oxidative Stress and Inflammation in Healthy Individuals and Those at Increased Risk of Cardiovascular Disease. Molecules. 2023 Sep 5;28(18):6440–0.
  77. Anese M, Alongi M, Cervantes-Flores M, Simental-Mendía LE, Martínez-Aguilar G, Valenzuela-Ramírez AA, et al. Influence of coffee roasting degree on inflammatory and oxidative stress markers in high-fructose and saturated fat-fed rats. Food Research International [Internet]. 2023 Mar 1 [cited 2023 Apr 23];165:112530. Available from: https://www.sciencedirect.com/science/article/abs/pii/S0963996923000753
  78. Kempf K, Herder C, Erlund I, Kolb H, Martin S, Carstensen M, et al. Effects of coffee consumption on subclinical inflammation and other risk factors for type 2 diabetes: a clinical trial. The American Journal of Clinical Nutrition. 2010 Feb 24;91(4):950–7.
  79. Davinelli S, Medoro A, Hu FB, Scapagnini G. Dietary Polyphenols as Geroprotective Compounds: From Blue Zones to Hallmarks of Ageing. Ageing Research Reviews. 2025 Mar 1;102733–3.
  80. Nield D. Giant Study Links Drinking Coffee With Almost 2 Extra Years of Life [Internet]. ScienceAlert. 2024. Available from: https://www.sciencealert.com/giant-study-links-drinking-coffee-with-almost-2-extra-years-of-life
  81. Machado M, Ferreira H, Oliveira MBPP, Alves RC. Coffee by-products: An underexplored source of prebiotic ingredients. Critical Reviews in Food Science and Nutrition. 2023 Feb 27;1–20.
  82. Saygili S, Hegde S, Shi XZ. Effects of Coffee on Gut Microbiota and Bowel Functions in Health and Diseases: A Literature Review. Nutrients [Internet]. 2024 Sep 18;16(18):3155–5. Available from: https://www.mdpi.com/2072-6643/16/18/3155
  83. Iriondo-DeHond A, Rodríguez Casas A, del Castillo MD. Interest of Coffee Melanoidins as Sustainable Healthier Food Ingredients. Frontiers in Nutrition. 2021 Oct 12;8.
  84. Jaquet M, Rochat I, Moulin J, Cavin C, Bibiloni R. Impact of coffee consumption on the gut microbiota: a human volunteer study. International Journal of Food Microbiology [Internet]. 2009 Mar 31;130(2):117–21. Available from: https://pubmed.ncbi.nlm.nih.gov/19217682/
  85. Bhandarkar NS, Mouatt P, Goncalves P, Thomas T, Brown L, Panchal SK. Modulation of gut microbiota by spent coffee grounds attenuates diet-induced metabolic syndrome in rats. FASEB journal: official publication of the Federation of American Societies for Experimental Biology [Internet]. 2020 Mar 1;34(3):4783–97. Available from: https://pubmed.ncbi.nlm.nih.gov/32039529/
  86. Hegde S, Shi DW, Johnson JC, Geesala R, Zhang K, Lin YM, et al. Mechanistic Study of Coffee Effects on Gut Microbiota and Motility in Rats. Nutrients [Internet]. 2022 Nov 18;14(22):4877. Available from: https://pubmed.ncbi.nlm.nih.gov/36432563/
  87. Kim SA, Tan LJ, Shin S. Coffee Consumption and the Risk of All-Cause and Cause-Specific Mortality in the Korean Population. Journal of the Academy of Nutrition and Dietetics. 2021 Nov;121(11):2221-2232.e4.
  88. The Nutrition Source. Coffee [Internet]. The Nutrition Source. 2019. Available from: https://nutritionsource.hsph.harvard.edu/food-features/coffee/
  89. Research I of M (US) C on MN. Safety of Caffeine Usage [Internet]. www.ncbi.nlm.nih.gov. National Academies Press (US); 2001. Available from: https://www.ncbi.nlm.nih.gov/books/NBK223789/
  90. Poole R, Kennedy OJ, Roderick P, Fallowfield JA, Hayes PC, Parkes J. Coffee consumption and health: umbrella review of meta-analyses of multiple health outcomes. BMJ [Internet]. 2017 Nov 22;359(8131):j5024. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5696634/
  91. Temple JL, Bernard C, Lipshultz SE, Czachor JD, Westphal JA, Mestre MA. The safety of ingested caffeine: A comprehensive review. Frontiers in Psychiatry [Internet]. 2017 May 26;8(80). Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC5445139/
  92. Wikoff D, Welsh BT, Henderson R, Brorby GP, Britt J, Myers E, et al. Systematic review of the potential adverse effects of caffeine consumption in healthy adults, pregnant women, adolescents, and children. Food and Chemical Toxicology. 2017 Nov;109(1):585–648.
  93. Evans J, Battisti AS, Richards JR. Caffeine [Internet]. National Library of Medicine. StatPearls Publishing; 2024. Available from: https://www.ncbi.nlm.nih.gov/books/NBK519490/
  94. Caffeine and arrhythmias: A critical analysis of cardiovascular responses and arrhythmia susceptibility. Journal of the Saudi Heart Association [Internet]. 2024 Dec 3;36(4):335–48. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC11648991/
  95. Coffee: Uses, Side Effects, Interactions, Dosage, and Warning [Internet]. Webmd.com. 2019. Available from: https://www.webmd.com/vitamins/ai/ingredientmono-980/coffee
  96. Spritzler F. 9 Side Effects of Too Much Caffeine [Internet]. Healthline. 2023. Available from: https://www.healthline.com/nutrition/caffeine-side-effects
  97. Effects of restricted caffeine intake by mother on fetal, neonatal and pregnancy outcomes [Internet]. www.who.int. Available from: https://www.who.int/tools/elena/review-summaries/caffeine-pregnancy–effects-of-restricted-caffeine-intake-by-mother-on-fetal-neonatal-and-pregnancy-outcomes
  98. Chen B, Zhang M, He Y, Si Y, Shi Y, Jiang K, et al. The association between caffeine exposure during pregnancy and risk of gestational hypertension/preeclampsia: A meta‐analysis and systematical review. Journal of Obstetrics and Gynaecology Research. 2022 Sep 25;
  99. Lakin H, Sheehan P, Varun Soti. Maternal Caffeine Consumption and Its Impact on the Fetus: A Review. Cureus. 2023 Nov 4;15(11).
  100. 10 Medications That Don’t Mix Well With Coffee [Internet]. Uhhospitals.org. University Hospitals; 2025 [cited 2025 Sep 15]. Available from: https://www.uhhospitals.org/blog/articles/2025/06/10-medications-that-dont-mix-well-with-coffee
  101. Is It Okay to Drink Coffee Every Day? [Internet]. Gwsmedika.id. GWS Medika; 2024. Available from: https://gwsmedika.id/en/news-articles/is-it-okay-to-drink-coffee-every-day