Coffee: Systematic Review with ☸️SAIMSARA.

DOI: 10.62487/saimsara648ea100

• Generated: 2026-02-10 10:16:34 CET
• Plan: Pro (expanded craft tokens; source: Europe PMC)
• Source: Europe PMC
• Scope: Titles/Abstracts (tiab)
• Keyword Gate: Fuzzy (≥60% of required terms, minimum 2 terms matched in title/abstract)
• Total Abstracts/Papers: 33626
• Downloaded Abstracts/Papers: 33626
• Included original Abstracts/Papers: 16552
• Total study participants (naïve ΣN): 32917262

• Bias: Qualitatively inferred from study design fields. Cross-sectional studies [12, 36, 548, 862, 1512, 2052, 2073, 2074, 2161, 2177, 2297, 2434, 3240, 3341, 3557, 3735, 3787, 3848, 3868, 3896, 3948, 4042, 4066, 4181, 4196, 4274, 4281, 4301, 4311, 4328, 4449, 4525, 4676, 4696, 5112, 5193, 5264, 5369, 5503, 5735, 5792, 5907, 5913, 6021, 6574, 6696, 6816, 6884, 7033, 7102, 7146, 7402, 7515, 7733, 7906, 8166, 8217, 8316, 8378, 8418, 8428, 8494, 8502, 8525, 8533, 8543, 8586, 8658, 8661, 8693, 8723, 8725, 8742, 8886, 8912, 9000, 9011, 9354, 9564, 9599, 9927, 9978, 9993, 10060, 10115, 10145, 10155, 10156, 10265, 10320, 10386, 10715, 11085, 11602, 11608, 11609, 11711, 11757, 11777, 11849, 11933, 11949, 11960, 12365, 12366, 12516, 13078, 13625, 13626, 13975, 14043, 14908, 15035, 15169, 15404, 15843, 15919, 15964, 16012, 16041, 16177, 16329, 16395, 16521] are susceptible to confounding and cannot establish causality. Cohort studies [22, 24, 42, 53, 58, 60, 118, 119, 159, 198, 218, 224, 240, 261, 271, 292, 318, 337, 341, 347, 350, 368, 453, 527, 548, 588, 705, 728, 758, 785, 84, 862, 101, 109, 1162, 11704, 11714, 11716, 11769, 12078, 12185, 12365, 12366, 1301, 13238, 13252, 13347, 13351, 13364, 13561, 13596, 13737, 13740, 13757, 13842, 13913, 14035, 14125, 14369, 14421, 14435, 14904, 14996, 15015, 15109, 15163, 15180, 15199, 15329, 15348, 15454, 15666, 15767, 15954, 16054, 16098, 16177, 16184, 16275, 16282, 16350, 16362, 16363, 16541, 16543, 16548, 1715, 185, 2026, 2028, 2030, 2047, 2056, 2063, 2068, 2073, 2074, 2077, 2078, 2087, 2112, 2119, 218, 2216, 2259, 2400, 2414, 2434, 2455, 2527, 2561, 2563, 2626, 2698, 2800, 2802, 2808, 2857, 2888, 2892, 2992, 2999, 3016, 3081, 3105, 3131, 3138, 3159, 3178, 3210, 3243, 3265, 3328, 3362, 3363, 3370, 3383, 3387, 3412, 3470, 3516, 3565, 3576, 3601, 3615, 3649, 3652, 3857, 4045, 4080, 4114, 4193, 4221, 4239, 4249, 4262, 4303, 4319, 4379, 4396, 4445, 4475, 4495, 4642, 4643, 4696, 4703, 4717, 4802, 4904, 5184, 5206, 5464, 5673, 6666, 6709, 6828, 6857, 6947, 7016, 7062, 7063, 7070, 7213, 7928, 7937, 8161, 8315, 8338, 8462, 8543, 8693, 9076, 9199, 9381, 9497, 9562, 9603, 10114, 10146, 10274, 10309, 10317, 10716, 10742, 10815, 11606, 11665, 11727, 11769, 11900, 11953, 11971, 12185, 12211, 13351, 13560, 13561, 14904, 15163] offer stronger evidence but can still be affected by unmeasured confounders. Randomized controlled trials (RCTs) [225, 246, 7928, 8098, 8462, 10456, 10770, 13369, 13913, 15180, 15449] provide the highest level of evidence for causality, but are few. Mixed-design studies [10, 20, 32, 39, 45, 59, 68, 74, 76, 81, 98, 101, 107, 112, 116, 117, 126, 132, 139, 144, 146, 173, 199, 215, 217, 224, 230, 2334, 2348, 2349, 2351, 2377, 2394, 2405, 2408, 2453, 2511, 255, 2586, 2593, 2618, 2640, 2644, 2650, 2674, 2696, 2725, 2768, 2795, 2927, 2977, 2978, 3007, 3008, 3027, 3036, 3058, 3070, 3106, 3137, 3139, 3154, 3205, 3208, 3229, 3306, 3313, 3321, 3325, 3332, 3337, 3339, 3347, 3361, 3377, 3384, 3387, 3391, 3446, 3470, 3493, 3519, 3523, 3528, 3569, 3593, 3596, 3600, 3643, 3648, 3657, 3663, 3679, 3717, 3720, 3723, 3725, 3743, 3746, 3756, 3763, 3779, 3780, 3782, 3788, 3811, 3814, 3816, 3825, 3857, 3898, 3932, 4000, 4009, 4043, 4055, 4062, 4104, 4160, 4262, 4282, 4357, 4404, 4530, 4564, 4590, 4709, 4857, 4967, 4992, 5043, 5170, 5179, 5203, 5208, 5254, 5278, 5300, 5313, 5328, 5339, 5386, 5410, 5425, 5475, 5501, 5505, 5545, 5880, 5896, 6043, 6070, 6104, 6367, 6417, 6433, 662, 6688, 6698, 6700, 6797, 6862, 6872, 6947, 7014, 7131, 715, 7160, 7162, 7202, 7205, 7327, 7397, 748, 7609, 7651, 778, 7841, 7881, 7904, 8010, 8098, 8321, 8327, 8329, 8338, 8436, 8485, 8507, 8593, 8613, 8779, 8879, 9126, 9354, 9417, 9599, 9624, 9944, 9950, 9970, 10010, 10021, 10146, 10170, 10340, 10346, 10473, 10478, 10688, 10810, 11307, 11349, 11473, 11588, 11589, 11591, 11617, 11632, 11665, 11670, 11692, 11774, 11827, 11870, 11900, 11942, 11971, 12108, 12143, 12212, 12262, 12491, 12594, 12597, 12806, 13256, 13328, 13337, 13357, 13372, 13378, 13412, 13523, 13557, 13600, 13603, 13629, 13723, 13769, 13846, 13860, 14115, 14177, 14446, 14515, 14881, 15027, 15092, 15176, 15489, 15559, 15814, 15996, 16138, 16159] combine various methodologies, offering broad insights but sometimes lacking depth in specific areas. Studies with "N/A" for design or population [350, 604, 10291, 10735, 1155, 1164, 1175, 1192, 12108, 12211, 12212, 12597, 12806, 13252, 13256, 13265, 13328, 13337, 13347, 13357, 13372, 13600, 13603, 13629, 13723, 13769, 13842, 13846, 13860, 13975, 14035, 14115, 14177, 14357, 14435, 14446, 14515, 14881, 14904, 14908, 14996, 15015, 15027, 15092, 15109, 15163, 15169, 15176, 15180, 15199, 15329, 15348, 15363, 15404, 15449, 15454, 15489, 15559, 15666, 15767, 15814, 15843, 15919, 15954, 15964, 15996, 16012, 16041, 16054, 16098, 16138, 16159, 16177, 16184, 16275, 16282, 16329, 16350, 16362, 16363, 16395, 16521, 16541, 16543, 16548, 187, 2026, 2035, 2036, 2043, 2065, 2066, 2071, 2079, 2082, 2088, 2096, 2099, 2155, 217, 2203, 2243, 2271, 2315, 2334, 2348, 2349, 2351, 2405, 2408, 2453, 2461, 2511, 255, 2586, 2593, 2618, 2640, 2644, 2650, 2664, 2674, 2696, 2725, 2768, 2795, 2927, 2977, 2978, 3007, 3008, 3027, 3036, 3058, 3070, 3106, 3137, 3139, 3154, 3205, 3208, 3229, 3306, 3313, 3321, 3325, 3332, 3337, 3339, 3347, 3361, 3377, 3384, 3387, 3391, 3446, 3493, 3519, 3523, 3528, 3569, 3593, 3596, 3600, 3643, 3648, 3657, 3663, 3679, 3717, 3720, 3723, 3725, 3743, 3746, 3756, 3763, 3779, 3780, 3782, 3788, 3811, 3814, 3816, 3825, 3857, 3898, 3932, 4000, 4009, 4043, 4055, 4062, 4104, 4160, 4357, 4404, 4564, 4590, 4709, 4857, 4967, 4992, 5043, 5170, 5179, 5198, 5203, 5208, 5254, 5278, 5300, 5313, 5339, 5386, 5410, 5425, 5456, 5475, 5501, 5545, 5880, 5896, 6043, 6070, 6104, 6367, 6417, 6433, 662, 6688, 6698, 6797, 6862, 6872, 7014, 7131, 715, 7162, 7202, 7327, 7397, 748, 7609, 7651, 778, 7841, 7881, 7904, 8010, 8098, 8321, 8327, 8329, 8436, 8485, 8507, 8593, 8613, 8703, 8779, 8879, 9126, 9354, 9417, 9497, 9599, 9600, 9624, 9944, 9970, 10021, 10170, 10340, 10346, 10478, 10614, 10688, 10735, 10810, 11307, 11588, 11589, 11591, 11617, 11632, 11665, 11670, 11692, 11774, 11827, 11870, 11900, 11942, 11971, 12108, 12143, 12262, 12491, 12594, 12597, 13252, 13256, 13328, 13357, 13372, 13378, 13412, 13523, 13557, 13600, 13629, 13723, 13769, 13846, 13860, 14035, 14115, 14177, 14446, 14515, 14881, 15027, 15092, 15176, 15199, 15363, 15489, 15559, 15814, 15996, 16138, 16159, 16282, 16350, 16362, 16521, 16543, 16548] often represent preliminary or highly specific investigations.

• Health Benefits & Disease Prevention: Moderate coffee intake is linked to favorable glucose control, improved body composition, reduced inflammation [12, 36, 119, 186, 218, 548, 1715, 2060, 2073, 3370, 4009, 5369, 5792, 6816, 6857, 8316, 8661, 8725, 9562, 9950, 10274, 10309, 12078], lower risk of cardiovascular disease (CVD), venous thromboembolism (VTE), stroke, and heart failure [84, 198, 2056, 2626, 2888, 3328, 4193, 4643, 5973, 7062], and reduced risk of various cancers (colorectal, renal cell carcinoma (RCC), thyroid, oral, hepatocellular carcinoma) [337, 2047, 2455, 3265, 4045, 4495, 8428, 13723, 14079, 15329, 15348]. It may also protect against Parkinson's disease, dementia, and cognitive decline [588, 758, 1162, 11971, 2056, 2063, 3470, 3516, 4396, 588, 9944, 11953, 2992], and lower risk of kidney stones [2028].
• Adverse Health Outcomes & Risks: Frequent or high coffee consumption is associated with increased risk of ADHD in offspring, pregnancy loss, and low birth weight [58, 2030, 2112, 2400, 3565, 4379, 5430, 6644, 6700, 7063, 7070, 8161, 8543, 9076, 11608, 12185, 13462]. It is also linked to poor sleep quality, insomnia, anxiety, and depression [3240, 3896, 4066, 4274, 6021, 7515, 7733, 8525, 8658, 9000, 9011, 10599, 11711, 15666, 15843, 15964]. Other risks include increased intraocular pressure [984], multiple myeloma [215], esophageal squamous cell carcinoma (ESCC) [2414, 8930], hemorrhoids [2247], and adverse effects on red blood cell storage quality [3363, 4114]. Coffee intake can also be a trigger for interstitial cystitis/bladder pain syndrome (IC/BPS) symptoms [3649], and may exacerbate gastroesophageal reflux disease (GERD) [9599, 10770, 11172, 13668, 15035].
• Agricultural & Environmental Aspects: Shaded coffee plantations support dung beetle communities and ecosystem services [22], while coffee agroforestry systems (CAFS) can moderate climate impacts, sequester carbon, and enhance soil fertility [42, 2216]. Climate variability significantly impacts coffee production [224], and population growth is negatively correlated with forest area in coffee regions [159]. Pests and diseases, such as the coffee leaf miner (Leucoptera coffeella), anthracnose (Colletotrichum species), coffee leaf rust, and Xylella fastidiosa, pose significant challenges, with solutions including deep learning for classification, resistant varieties, and improved shade-tree selection [32, 240, 261, 785, 604, 1164, 12806, 13256, 13629, 13842, 14035, 14357, 2394]. Sustainable agricultural practices are preferred by farmers for higher profits and environmental benefits [2077].
• Industrial Processing & Quality Control: Techniques like Fourier Transform Infrared Spectroscopy (FTIR) and Near-Infrared (NIR) spectroscopy enable coffee origin discrimination and authenticity verification [39, 146]. Fermentation processes, especially with native yeast strains, drive flavor metabolic networks and improve beverage quality [60, 76, 117, 1253, 791]. Drying methods can reduce time and energy demand [20, 339]. Roasting can degrade glyphosate residues [173] and influence furan levels [2065], while processing methods affect phenolic content and bioactive compounds [68]. Advanced sensors are being developed for detecting contaminants like ochratoxin A (OTA) [3332], glyphosate [2640], and heavy metals [118, 2618, 4043, 4967, 5170, 8613].
• By-product Valorization: Spent coffee grounds (SCG) and coffee silverskin are rich in dietary fiber, minerals, and phenolic compounds, with potential as functional ingredients [81, 144, 107]. They can be incorporated into biodegradable polymers for packaging [132, 357, 1192, 2593, 348], used for microbial protein production [3588], or converted into biochar for environmental remediation (adsorption of nitrates, heavy metals, diclofenac, tetracycline) [416, 517, 815, 946, 1222, 2203, 3007, 5896]. Coffee pulp extract can enhance growth performance in broiler chickens [463], and coffee mucilage can be enzymatically hydrolyzed for various uses [368].
• Material Science & "Coffee-Ring Effect": Coffee causes significant discoloration and surface roughness changes in various dental and restorative materials, including composite resins, glass-ceramics, and 3D-printed materials [112, 199, 603, 1089, 1163, 1184, 1418, 1506, 1641, 1704, 1716, 1796, 199, 2157, 2377, 2511, 3058, 3137, 3208, 3313, 3321, 3325, 3337, 3339, 3391, 3746, 3779, 4002, 4615, 5278, 5313, 5328, 5505, 5545, 5880, 6104, 6367, 6433, 7397, 7841, 8593, 8879, 9417, 10357, 10447, 10473, 10810, 11473, 12568]. The "coffee-ring effect" in drying droplets is being studied and leveraged for applications like fabricating conductive lines or suppressed for uniform particle deposition in printing and sensing [10, 217, 1175, 1855, 2099, 217, 2433, 2664, 2978, 3139, 3493, 3816, 4104, 5043, 5179, 5198, 7014, 6797, 6872, 2349].

• Moderate Intake Benefits: Clinicians can generally reassure patients about moderate coffee consumption (e.g., 1-4 cups/day) for potential benefits in glucose control, cardiovascular health, and reduced risk of certain cancers [12, 36, 84, 119, 185, 198, 548, 2047, 2056, 337, 4045, 4239, 5973, 7062, 8428, 9497, 10274, 10309].
• Pregnancy & Offspring Risk: Pregnant individuals should be advised on the increased risk of ADHD in offspring, pregnancy loss, and low birth weight associated with frequent maternal coffee consumption [58, 2030, 2112, 2400, 3565, 4379, 5430, 6644, 6700, 7063, 8161, 9076, 11608, 12185, 13462].
• Timing of Consumption: Delaying coffee intake after meals is recommended to reduce anemia risk in pregnant women and improve iron absorption [3159, 5430, 8586, 10688, 16275].
• Specific Patient Populations: Patients with globus pharyngeus may benefit from coffee cessation [3243], and individuals with interstitial cystitis/bladder pain syndrome (IC/BPS) should be aware of coffee as a potential trigger [3649]. Patients with cirrhosis are recommended to consume 2 or more cups daily [3576].
• Dental Health & Aesthetics: Patients should be informed that coffee significantly discolors dental restorative materials and natural teeth, and discuss strategies for mitigation or material selection [112, 199, 603, 1089, 1163, 1184, 1418, 1506, 1641, 1704, 1716, 1796, 2157, 2377, 3058, 3137, 3313, 3321, 3325, 3337, 3339, 3391, 3746, 3779, 4002, 4615, 5278, 5313, 5328, 5505, 5545, 5880, 6104, 6367, 6433, 7397, 7841, 8593, 8879, 9417, 10357, 10447, 10473, 10810, 11473, 12568].

• Dose-Response Characterization: Future studies should precisely define "moderate" and "high" coffee intake thresholds for specific health outcomes across diverse populations, using standardized metrics [185, 198, 2030, 215, 2414].
• Mechanistic Pathways: Further research is needed to elucidate the exact biological mechanisms underlying coffee's diverse effects, particularly concerning gut microbiota interactions, inflammatory pathways, and cellular responses [12, 139, 186, 2800, 2808, 3387, 341, 347, 5475, 7881, 9562].
• Longitudinal Studies on Adverse Outcomes: More long-term prospective cohort studies are required to confirm and quantify the causal links between coffee consumption during pregnancy and childhood developmental/health issues [58, 2030, 2112, 2400, 3565, 4379, 6644, 6700, 7063, 8161, 13462].
• Personalized Nutrition: Research should explore genetic variations influencing caffeine metabolism and individual responses to coffee, to enable personalized dietary recommendations [1512, 2802, 3016, 3363, 8338, 11665, 15169].
• Sustainability & Valorization Efficacy: Studies should focus on scaling up the valorization of coffee by-products and assessing the long-term environmental and economic impacts of these solutions in real-world settings [20, 81, 132, 187, 348, 357, 416, 517, 605, 662, 715, 778, 815, 835, 946, 953, 1192, 1222, 2203, 2348, 2586, 2795, 2941, 3007, 3588, 4160, 439, 5456, 5896, 6043, 6070, 7162, 7904, 8010].

• Study Design Heterogeneity — The diverse range of study designs, including many cross-sectional and mixed studies, limits the ability to infer causality and synthesize results uniformly.
• Lack of Standardized Intake — Definitions of "moderate" or "frequent" coffee consumption vary significantly across studies, complicating direct comparisons and dose-response analysis.
• Confounding Factors — Many observational studies may not fully account for all lifestyle, genetic, and dietary confounders, potentially biasing reported associations.
• Self-Report Bias — Relying on self-reported coffee intake can introduce inaccuracies due to recall bias or under/over-estimation [5673].
• Population Specificity — A substantial number of studies focus on specific populations or settings, which may limit the generalizability of findings to broader global populations.

• Standardized Intake Protocols — Develop and implement consistent definitions for coffee consumption levels in research to improve comparability.
• Longitudinal Cohort Studies — Conduct more long-term prospective cohort studies with detailed dietary assessments to establish causality for health outcomes.
• Mechanistic Pathway Elucidation — Investigate specific molecular and physiological pathways, including gut microbiome interactions, mediating coffee's effects.
• Real-World Intervention Trials — Design and execute randomized controlled trials to test the efficacy of coffee consumption interventions for specific health endpoints.
• Waste Valorization Scale-Up — Focus on pilot and industrial-scale projects for coffee by-product utilization to assess economic viability and environmental impact.