Although both findings on the potential health benefits and harmful effects of coffee consumption have historically been reported, the general consensus is that moderate, regular coffee drinking by healthy individuals is either essentially benign or mildly beneficial (George and others 2008 ; Cano‐Marquina and others 2013 ; O'Keefe and others 2013 ; Fardet and Boirie 2014 ). Findings to‐date are largely based on observational data, albeit from large prospective cohort studies and case–control and cross‐sectional data. However, heterogeneity between study populations and designs, and also lack of control for many other confounding factors, add limitations to the existing literature. Moreover, studies or meta‐analyses to‐date typically focus on single disease outcomes or endpoints and few (if any) weigh up the benefits and risks on multiple health outcomes.

Coffee is a widely consumed beverage worldwide and extensive scientific research has been conducted to examine the relationship between coffee consumption and a wide range of chronic diseases and health outcomes, including total mortality, many cancers, cardiometabolic risk, liver disorders, and neurological conditions. Such effects have been attributed to many different bioactive constituents of coffee, including caffeine (methylxanthine), chlorogenic acids (polyphenol), diterpenes, and other phenolics, some of which may also potentially have additive or synergistic effects.

Searches were conducted using coffee as a broad search term, or within 3 words of consumption/consume(r), intake(s), or drink(s) (“coffee” OR “coffee adj3” [consum* or intake* or drink*]). Duplicates were then removed, and remaining studies were screened for eligibility based on set inclusion and exclusion criteria (Table 1 ). To be eligible for inclusion, studies must have been conducted in humans and have reported original data linking the effect of coffee consumption on a specified health outcome(s). All types of coffee were included as relevant (such as instant, filtered, cafetiere, or boiled), although those studies concerned with the effect of caffeine per se were excluded.

A systematic search for the appropriate literature (from 1970, limited to humans and available in English) was conducted using the online electronic databases “OVID” (AMED, FSTA, EMBASE, MEDLINE [PubMED], PSYCinfo), “CINAHL” (academic journals only), and “Web of Knowledge: Web of Science with Conference Proceedings,” together with manual searches of reference lists.

Results

The study selection and screening process is illustrated in Figure 1. Initially, 12329 results were returned following the literature searches. An additional 76 studies were identified by email alerts updating the searches within the Web of Knowledge database (total, n = 12405 studies).

After screening to remove duplicate citations (n = 6047) and exclusion of the studies deemed unsuitable for inclusion (n = 5081) based on the predetermined inclusion/exclusion criteria, a total of 1277 studies were included in the review. This represented approximately 10% of those studies identified by the original search strategy.

For each category of the health conditions/outcome discussed below, example citations are included to highlight the key points. A complete bibliography list of all studies reviewed is included as Supplementary Material.

Cancer Coffee consumption has been linked to cancer risk or incidence in virtually every tissue type in the body, with the most commonly reported subsites being colorectal, bladder/urinary tract, pancreatic, and female‐specific and breast cancers. A total of 352 (27.6%) studies have reported links between coffee consumption and cancer, and these are typically observational (Table 2). Only the more mechanistic studies are tested using an intervention study design. Table 2. Number of studies investigating cancer and coffee consumption by outcome and type of study. Benefit Null effect Risk Type of cancer Observationalb Interventionc Observationalb Interventionc Observationalb Interventionc Colorectal 28 30 11 Bladder/urinary tract 3 33 33 Pancreas 5 35 7 Female‐specific (ovarian, endometrial, vulva) 15 17 8 Breast 15 18 5 Prostate 8 14 4 Oral/upper aerodigestive tract 13 5 5 Gastric 6 9 7 Mechanisms (DNA damage, DNA integrity, oxidative damage) 5 9 2 4 Carcinomas (hepatocellular, squamous/basal cell, soft tissue) 14 5 Renal/kidney 2 11 3 Skin 9 3 Lung/respiratory tract 2 4 4 All types (or tobacco‐related) 2 4 Lymphoma's 2 2 1 Leukemia 2 1 1 Liver 4 Brain/glioma 1 1 2 Thyroid 1 1 Gallbaldder/bile ducts 1 Total 138 9 195 0 95 0 Observational findings have for the majority reported a beneficial or null effect of coffee consumption on cancer, with the exception of bladder/urinary tract cancers where the risks of coffee consumption are more commonly reported. An increased risk of bladder/urinary cancer, however, was typically only reported in males, not females (Hartge and others 1983; Marrett and others 1983; Clavel and Cordier 1991; Zeegers and others 2001) and nonsmokers compared to smokers (Pujolar and others 1993). Negative interactions with alcohol (Donato and others 1997) were also evident, together with an influence of certain genetic polymorphisms (such as CYP1A2; Pavanello and others 2010). Moreover, other studies only reported an increased risk of cancer of the urinary system to be evident in consumers of Turkish coffee (Akdas and others 1990), high coffee consumers (40+ cups per week; Slattery and others 1988), or have failed to demonstrate a dose–response (Simon and others 1975; D'Avanzo and others 1992), which suggested that such associations are noncausal. Similar modifiers of risk are also noted in the observational evidence for other types of cancer. Coffee drinking appears to increase the risk of gastric (Galanis and others 1998) and colorectal cancer in men (Slattery and others 1990; Boutron‐Ruault and others 1999; Yamada and others 2014) but not in women (Lee and others 2007), although the authors queried if the former was just a chance finding (Galanis and others 1998). The risk of pancreatic cancer also appears to be higher in smokers (Gorham and others 1988; Harnack and others 1997) and nonconsumers of alcohol (Clavel and others 1989), whilereas genetic polymorphisms (CYP1A2 and GSTM1/GSTT1) can modify the relationship between coffee consumption and risk of breast (Kotsopoulos and others 2007; Bageman and others 2008; Ayari and others 2013), ovarian (Goodman and others 2003), and skin (Fortes and others 2009, 2013) cancer. In some instances, only caffeinated coffee appears to be protective when compared with decaffeinated coffee (for example, in skin, endometrial, and some gastric cancers; Abel and others 2007; Bhoo‐Pathy and others 2015; Sanikini and others 2015) but in other studies, the opposite is true (for example, for ovarian, rectal and lung cancers; Michels and others 2005; Baker and others 2005, 2007). Comparisons between other types of coffee preparations also produce equivocal results within the literature, for example for boiled (not filtered) versus filtered coffee (Nilsson and others 2010; Tverdal 2015) or hot versus iced coffee (Green and others 2014), and risks are also typically associated with heavy coffee consumption (Gullo and others 1995; Efird and others 2004; Luo and others 2007; Lueth and others 2008; Bissonauth and others 2009) or coffee abuse (Uzcudun and others 2002) compared to light/moderate coffee consumption. Finally, for some cancers, risks also appear to be more apparent in younger adults (<60 years; Gallus and others 2007), with a null or beneficial (inverse) effect of coffee consumption on cancer risk becoming apparent only in older adults after more than 35 years coffee consumption (Kokic and others 1996), or in postmenopausal compared to premenopausal females (Kuper and others 2000; Koizumi and others 2008). More consistently, positive or beneficial associations between coffee consumption and cancer risk are evident in the mechanistic studies, and as alluded to above, this evidence more often than not comes from intervention studies. Such research reports a protective or beneficial effect of coffee consumption on antioxidant status (Bakuradze and others 2011), oxidative DNA damage (Steinkellner and others 2005; Hoelzl and others 2010; Misik and others 2010; Bakuradze and others 2011; Hori and others 2014), urine mutagenicity (Aeschbacher and Chappuis 1981), and DNA strand breaks/integrity (Bakuradze and others 2014, 2015). Overall, these data from intervention studies would suggest that coffee can have a beneficial role in terms of reducing the risk of some cancers.

Cardiovascular disease A total of 273 (21.4%) studies have reported links between coffee consumption and cardiovascular disease (CVD), and they are mainly observational, although some evidence from intervention studies is reported, particularly for hyperlipidemias, hypercholesterolemia, and blood pressure (Table 3). Such studies have reported on a number of different outcomes or disease endpoints, ranging from mechanistic studies focusing on individual risk factors (or causes of such) to those reporting adverse events such as myocardial infarction, heart failure, or stroke. Table 3. Number of studies investigating cardiovascular disease (CVD) and coffee consumption by outcome and type of study.a Benefit Null effect Risk Type of CVD/CV outcome Observationalb Interventionc Observationalb Interventionc Observationalb Interventionc Hypercholesterolemia/lipidemia 6 4 29 13 37 14 Blood Pressure/hypertension 9 5 11 7 15 11 Myocardial infarction 1 10 1 13 2 CVD 5 9 7 4 Homocysteine 2 4 3 10 6 CHD 2 8 12 Stroke/blood clot/clotting 7 3 2 6 1 Coronary events 2 1 4 7 Endothelial function 4 1 1 1 2 1 Hemodynamic effects/hemostasis 1 3 2 Gout/uric acid 3 1 2 Heart rate 1 2 1 1 1 CAD 1 1 3 Heart failure 1 2 1 Atherosclerosis 1 1 1 1 IHD 3 CRP (inflammation) 2 1 Aortic/coronary calcification 2 1 Peripheral arterial occlusive disease 2 Haptoglobin levels 1 Myelodysplastic syndromes 1 Total 48 20 88 30 119 42 Within CVD, the majority of evidence has reported negative (or null) associations between coffee consumption and blood cholesterol (that is, an increased risk of hypercholesterolemia). Such inverse associations though are mainly caused by the consumption of cafetiere (Urgert and others 1995, 1996), French‐press (De Roos and others 2000), Arabic (el Shabrawy Ali and Felimban 1993), or boiled coffee (Bonaa and others 1988; Bak and Grobbee 1989; Pietinen and others 1990; Lindahl and others 1991; Ahola and others 1991; Van Dusseldorp and others 1991; Fried and others 1992), as compared to filtered coffee preparations. A direct dose‐dependent effect is also evident (Aro and others 1990; D'Avanzo and others 1993) and another study has quantified a 1.66 and 1.58 mg/dL increase in Low density lipoprotein (LDL)‐cholesterol per daily cup of coffee consumed by men and women, respectively (Berndt and others 1993). Moreover, abstinence from coffee for at least 6 weeks will lower cholesterol concentrations in the general population (Christensen and others 2001) and in hypercholesterolemic patients (Forde and others 1985). This negative effect of coffee on cholesterol concentrations, particularly from boiled coffee, is owing to higher concentrations of diterpenes (kahweol and cafestol) in such coffee preparations (deGroot and others 1996; Gross and others 1997; Naidoo and others 2011). However, 4 randomized controlled trials have shown that diterpenes have lipoprotein(a)‐reducing potential, but the authors concluded that their well‐known adverse side effects on LDL cholesterol preclude their use as such (Urgert and others 1997). Of interest, an inverse relationship has been reported between coffee consumption and triglyceride concentrations (Carson and others 1994; Lancaster and others 1994; Miyake and others 1999), which requires further investigation. Risks of raised blood pressure/hypertension in coffee consumers are also apparent within the literature, and this pressor effect may be caused by a coffee‐induced increase in adrenaline concentrations (Smits and others 1986a,b; Palatini and others 2009). The pressor effect, however, was observed more often than not in coffee naïve individuals, with no effect seen in habitual drinkers (Corti and others 2002) or those who have adapted to heavy coffee consumption (8 cups per day for 4 weeks; Ammon and others 1983). Furthermore, although abstinence from coffee for 9 weeks was able to decrease blood pressure in normotensives (Bak and Grobbee 1990), others have shown no effect on ambulatory blood pressure measurements (Eggertsen and others 1993), nor on the prospective risk of developing hypertension over 33 years (Basile 2002). Indeed, benefits of coffee consumption on blood pressure have also been reported in human intervention studies conducted in both normotensive and mildly hypertensive adults (Awaad and others 2011), and in coffee drinkers with the rapid *1A/*1A genotype, compared to the increased risk observed in those with the slow CYP1A2*1F genotype (rapid vs. slow caffeine metabolizers, respectively; Palatini and others 2009). Coffee consumers also appear to be at an increased risk of higher homocysteine concentrations, an independent risk factor for CVD (Strandhagen and others 2003; Strandhagen and others 2004; Slow and others 2004). This relationship may be driven by the chlorogenic acid (Piters and others 1985) rather than the trigonelline content of coffee (Slow and others 2004), but, can be modified by folic acid (Strandhagen and others 2003), particularly in those with the TT polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene which codes for the MTHFR enzyme. For some outcomes (such as myocardial infarction), the increased risk seen in coffee drinkers is dependent on family history (Azevedo and Barros 2006), CYP1A2 genotype (Cornelis and others 2006) and type of coffee preparation (boiled vs. filtered; Hammar and others 2003), thus highlighting the importance of adequately controlling for these and other confounders in such studies. Although, coffee polyphenols (extracted from green coffee beans and given as a single oral ingestion) have been reported to have a beneficial effect on endothelial function (Ochiai and others 2014), the opposite or at least a null effect is seen when either caffeinated or decaffeinated coffee, respectively, is consumed as a beverage (Buscemi and others 2010). For other outcomes, U‐ or J‐shaped risks of coffee consumption have been reported (Panagiotakos and others 2003; Enga and others 2011). Although such a relationship would suggest that the cardiovascular benefits are achieved by moderate (compared to null/little or heavy/high) coffee consumption, differences in the definition of “moderate consumption” make it difficult to compare and draw adequate conclusions between the studies.

Metabolic health The vast majority of evidence investigating coffee consumption and metabolic health (Table 4) consistently shows a beneficial (inverse) association with the risk of type 2 diabetes (n = 126; 9.9% studies). These associations are at least in part mediated by a decreased insulin resistance (or improved insulin sensitivity) and/or improved glucose tolerance. Direct effects on glucose tolerance appear to be caused by the antagonistic effect of chlorogenic acid (with/without caffeine) on glucose transport, shifting glucose absorption to more distal parts of the intestine (Johnston and others 2003), rather than acting through the incretin hormones. Other mechanisms of action suggested include associations with low‐grade systematic inflammation (C‐reactive protein and sCD163; Arsenault and others 2009; Chacon 2014), oxidative stress (Bakuradze and others 2011), and sex‐hormone binding globulin (Goto and others 2011, 2014). Results may also be different depending on the range of body mass index categories included within the study (Arsenault and others 2009; Otake and others 2014), and the use of hormone replacement therapy (HRT; Catalano and others 2008; Arsenault and others 2009), again highlighting these as important confounders. Table 4. Number of studies investigating metabolic health and coffee consumption by outcome and type of study.a Benefit Null effect Risk Metabolic outcome Observationalb Interventionc Observationalb Interventionc Observationalb Interventionc Type 2 diabetes 33 1 4 1 Obesity/body weight/fat 8 10 8 1 3 IGT 9 5 1 3 2 4 Insulin resistance/sensitivity 6 3 4 Metabolic syndrome 6 3 2 Diabetes (all) 7 Inflammation/oxidative stress 2 2 1 Metabolic health 2 1 1 1 Type 1 diabetes 3 Satiety regulation 1 2 Exercise performance/fitness 1 1 Gestational diabetes 1 Total 72 24 22 10 10 5 Coffee intake (3 × 250 mL/day for 4 weeks) can also decrease energy intake, by improving satiety hormones (ghrelin and serotonin) and therefore decreasing levels of body fat (Bakuradze and others 2014). Moreover, others have shown that either the mannooligosaccharides (Kumao and Fujii 2006) or polyphenols (chlorogenic acid; Soga and others 2013) in coffee can increase or stimulate postprandial fat utilization, thus promoting excretion of fat in the feces. Although some studies have shown an adverse effect on the risk of metabolic syndrome, this has only been shown, for example, for higher coffee consumption (>3 cups/day), particularly of instant coffees with excess sugar and powdered creamer (Kim and others 2014), and therefore these results must be interpreted with caution.

Neurological disorders Coffee consumption has been positively linked to improvements in (or a decreased risk of) a number of neurological disorders, with the most commonly reported being Parkinson's disease, cognitive decline/function, and mental health. A total of 94 (7.4%) studies have reported links between coffee consumption and neurological outcomes, and they are typically observational (Table 5). Table 5. Number of studies investigating neurological disorders and coffee consumption by outcome and type of study.a Benefit Null effect Risk Type of neurological outcome Observationalb Interventionc Observationalb Interventionc Observationalb Interventionc Parkinson's disease 23 9 1 Cognitive function/decline 12 3 7 Depression/anxiety 6 3 1 Headache/migraine 3 6 Sucide 2 3 Pain 1 1 2 Mental health/disease 2 2 Restless leg syndrome 3 Mood 1 2 Stress 1 2 Blepharospasm 2 Sympathetic nerve activity 1 1 Multiple sclerosis 1 Amyotrophic lateral sclerosis 1 Multiple system atrophy 1 Total 51 5 22 1 23 1 Overall, coffee has been shown to be beneficially associated with the risk of Parkinson's disease (Ross and others 2000; Tan and others 2003; Hosseini Tabatabaei and others 2013; van der Mark and others 2014), with a dose–response protective relationship apparent (Tan and others 2003), but possibly only in males (Savica and others 2013; Ascherio and others 2001) and female non‐HRT users (Ascherio and others 2004; Ascherio and others Mar 2003). Additive effects were also apparent with preceding diabetes (D'Amelio and others 2009) and smoking (Grandinetti and others 1994; Powers and others 2008). Although some studies reported an effect of certain genetic polymorphisms (for example, adenosine A2A receptor, CYP1A2, and AP06; Tan and others 2006; McCulloch and others 2008; Popat and others 2011), others have shown no such generic–environmental interactions (Facheris and others 2008; Chung and others 2013). The protective effect of coffee on the risk of Parkinson's disease is at least in part due to certain alkaloid compounds within coffee acting as monoamine oxidase inhibitors (Herraiz and Chaparro 2006). The protective effect of coffee on cognitive decline/function may be more apparent in females compared to males (Johnson‐Kozlow and others 2002; Arab and others 2011) and such effects on psychomotor/cognitive performance (Natu and Agarwal 1997) are more likely to be due to caffeine consumption (Johnson‐Kozlow and others 2002), rather than the chlorogenic acids within coffee (Camfield and others 2013). Furthermore, it has been postulated that antioxidants in coffee capable of decreasing reactive oxygen species may give rise to a reduction in the risk of Alzheimer's disease (Kotyczka and others 2011).

Gastrointestinal conditions Gastrointestinal (GI) complaints have been traditionally linked in the literature with coffee consumption, with null/adverse associations with reflux, ulcers, heartburn, and dyspepsia most commonly reported. A total of 73 (5.7%) studies have reported links between coffee consumption and GI conditions, the majority being observational studies (Table 6). Table 6. Number of studies investigating gastrointestinal (GI) conditions and coffee consumption by outcome and type of study.a Benefit Null effect Risk Type of GI outcome Observationalb Interventionc Observationalb Interventionc Observationalb Interventionc Reflux 1 9 6 Peptic ulcer disease 8 1 1 Bowel/colon symptoms 1 1 4 2 1 1 Duodenal ulcer 5 1 Dyspepsia 4 2 Helicobacter pylori 4 1 Gastric acid secretion 1 1 2 Gastric emptying 2 2 Gut microbiotia/colonic fermentation 4 Inflammatroy conditions (gastritis, duodenitis, ulcerative colitis, IBD) 2 1 Pancreatic function 1 1 1 Heartburn 3 Proximal stomach function 1 2 Gastric ulcer 1 1 Anal fisure 1 1 Intraoesophageal tempature 1 Postoperative ileus 1 Total 4 10 40 7 14 8 Although negative findings are apparent, suggesting an increased risk of GI complaints in coffee consumers, such negative associations are weak at best, and are only reported in univariate, not multivariate analyses (Bhatia and others 2011); for (unusually) high coffee consumption (Schlemper and others 1996); they are perceived side effects by the consumer or patient rather than being tested/diagnosed (Ostensen and others 1985; Eisig and others 1989; Sihvo and Hemminki 1999); or they are only reported in coffee‐sensitive/susceptible individuals (Cohen 1980; DiBaise 2003). Moreover, some of the adverse effects are from acute feeding studies, where coffee is either directly instilled into the stomach or given intra‐ or orogastrically (Cohen 1980; Coffey and others 1986; Boekema and others 2001), so results are not comparable to normal habitual coffee consumption. Others have suggested that variability in coffee‐induced gastric responses may be caused by differences in bean processing (Van Deventer and others 1992; DiBaise 2003; Rubach and others 2014), such as dark or light roasting. Finally, beneficial effects of moderate coffee consumption on gut health offer some promise for additional benefits of coffee drinking among the general population. Such effects have been reported by 4 intervention studies to‐date and include improvements in the fecal microbiota (Umemura and others 2004; Jaquet and others 2009; Walton and others 2010), and improved colonic fermentation (Scazzina and others 2011). These positive findings warrant confirmation in larger and longer‐term studies.

Liver disorders A total number of 72 (5.6%) studies have investigated the effect of coffee consumption on liver disorders, namely, liver function/enzymes in general and gallstones/gallstone disease (Table 7). Overall, this evidence, largely from observational studies, is showing coffee to have a protective effect on the liver. In general, coffee may offer protection against alcohol‐induced liver damage/impairment (Corrao and others 1994; Tanaka and others 1998; Honjo and others 2001; Klatsky and others 2006; Ikeda and others 2010; Marotta and others 2013) and alcohol‐induced hepatic inflammation (Maki and others 2010), which does not appear to be related to the caffeine content (Corrao and others 2001; Xiao and others 2014), or antioxidant activity (Gutierrez‐Grobe and others 2012). In some studies, such beneficial effects are more evident in males (Pintus and Mascia 1996; Danielsson and others 2013) and smokers (Kono and others 1994), compared to females and nonsmokers, respectively. Strong cafetiere (vs. filtered) coffee, however, may show the opposite effect. Drinking 5 to 6 cups per day negatively affected the integrity of liver cells in a 24‐week randomized‐controlled intervention study (Urgert and others 1996). There is debate in the literature, however, if the compounds which might be responsible for such effects are the diterpenes, for example kahweol within coffee oil (Urgert and others 1996; Boekschoten and others 2004). Table 7. Number of studies investigating liver disorders and coffee consumption by outcome and type of study. Benefit Null effect Risk Liver outcome Observationalb Interventionc Observationalb Interventionc Observationalb Interventionc Liver enzymes/function 25 1 3 1 3 Gallstones/gallstone disease 8 1 10 3 Cirrhosis 6 Fibrosis 4 1 NAFLD/fatty liver disease 4 1 Hepatitis C 2 2 Liver disease 1 1 Cholangitis 1 Choledocholithiasis 1 Hepatic drug metabolism 1 Hepatic inflammation 1 Total 52 4 17 2 3 3

Mortality Overall, coffee consumption has been associated with a reduced risk of total/all‐cause and cause‐specific mortality, particularly for CVD and coronary heart disease (CHD; n = 62; 4.9% studies; Table 8). In contrast, in some of the earlier studies conducted 20+ years ago, CHD or ischemic heart disease (IHD) mortality was inversely associated with coffee consumption (Heyden and others 1976; Hennekens and others 1976; Hemminki and Pesonen 1977; LeGrady and others 1987; Tverdal and others 1990; Klatsky and others 1993). In these studies, however, risks were related to sale of coffee, not consumption (Hemminki and Pesonen 1977), none/very low (0 to 1 cups), or very high (6 to 9+ cups) daily consumption (LeGrady and others 1987; Tverdal and others 1990) or associated risks were minimal (Hennekens and others 1976) and therefore results should be interpreted with caution. Similar to the discussion previously for other conditions, the link between coffee consumption and mortality seems to vary inconsistently by gender (Tverdal and others 1990; Jazbec and others 2003; Leurs and others 2010; Liu and others 2013), HRT users versus nonusers (Ascherio and others 2004), and smoking status (Rosengren and Wilhelmsen 1991; Odegaard and others 2015), but remains beneficial in the majority of evidence, when populations are considered as a whole. Table 8. Number of studies investigating mortality and coffee consumption by outcome and type of study. Benefit Null effect Risk Mortality outcome Observationala Interventionb Observationala Interventionb Observationala Interventionb Total/all‐cause 14 13 3 CVD/CHD 10 10 6 Cirrhosis 6 1 Cancer (all types) 5 1 Pancreatic cancer 3 3 Prostate cancer 3 Breast/overian cancer 2 1 Respiratory disease 2 Infection/inflammatory disease 2 Parkinson's disease 1 1 Hepatocellular carcinoma 2 Urinary bladder cancer 1 1 Diatetes 1 Injuries/accidents 1 Oral/pharyngeal cancer 1 Suicide 1 Colon cancer 1 Total 41 0 39 0 16 0

Other conditions/health outcomes In addition to all of the health relationships outlined above, a number of other conditions or health outcomes have also been linked to coffee consumption. A total of 155 (12.1%) studies are listed in Table 9 and corresponding conditions within each category are listed in Table 10. Table 9. Number of studies investigating other conditions and coffee consumption by outcome and type of study. Benefit Null effect Risk Health condition/outcome Observationalb Interventionc Observationalb Interventionc Observationalb Interventionc Bone health 3 22 18 Renal (Kidney/Urinary) 7 1 9 1 6 Hormonal conditions/disturbance 5 4 2 3 Nutritional status 3 2 1 7 1 Fertility 1 6 6 Eye health/vision 1 2 2 2 Sleep conditions 2 1 1 3 Respiratory health 3 2 1 Prostate conditions 1 5 Skin conditions 1 3 1 Ageing 1 2 1 Pancreatic health 1 2 1 Female health 3 1 Other 8 1 4 4 Total 37 2 67 5 54 3 Table 10. Details of other conditions related to coffee consumption within the literature. Category List of conditions Bone health Risk for osteoporosis; bone mineral density; bone fragility; bone loss; hip fracture; fracture risk; fracture prevalence; perimenopausal fractures; markers of bone metabolism; T‐score variability; risk of rheumatoid arthritis; musculoskeletal pain Renal (kidney/urinary) Interstitial cystitis; urinary incontinence; urinary/kidney stones; nephrolithiasis; chronic kidney disease; nocturia; dehydration; estimated glomerular filtration rate; glomerular function (urinary hydrogen peroxide); hypokalemia; bladder pain syndrome; IgA nephropathy; Hormonal Menstrual disturbances; premenstrual syndrome; menstrual function (menstrual pattern, dysmenorrhea); menopausal/climacteric symptoms (hot flashes and night sweats); onset of menopause; salivary cortisol; sex hormone and other hormone levels (estradiol, testosterone); erectile dysfunction; anterior pituitary hormones Nutritional status Iron status/stores; prenatal zinc deficiency; total antioxidant capacity; iron deficiency anemia; B‐vitamin status; tocopherol (adipose tissue content); selenium levels (toenail); serum β‐carotene and α‐tocopherol; dietary/nutritional behaviours Fertility Sperm progressive motility; semen quality; male infertility (azoospermia or oligospermia); sperm aneuploidy; fecundity; time to pregnancy Eye health/vision Intraocular pressure; exfoliation glaucoma/glaucoma suspect; macular edema; cataract; age‐related maculopathy; choroidal thickness Sleep conditions Insomnia; drowsiness; sleep problems; alertness, sleep onset and sleep quality; alertness and performance Respiratory health MRSA nasal carriage; pulmonary function; bronchial asthma; Prostate conditions Benign prostatic hyperplasia; prostatic hypertrophy Skin conditions Psoriasis; dermatoses; skin photoprotection Aging Skin aging; frailty; health‐related quality of life; reaching 90 years of age Pancreatic health Pancreatitis; chronic calcific pancreatitis of the tropics; pancreatic ductal adenocarcinoma Female health Fibrocystic breasts; benign breast disease; endometriosis Other Thyroid disease; serum uric acid/hyperuricemia; acute hyperammonemia; urinary vanilmandelic acid levels; tinnitus; hearing function; periodontal health/disease; oral clefts Overall, the other most frequently reported condition associated with coffee consumption is poor bone health. Although approximately half of the studies included in the current review have shown a null effect on bone outcomes (22 out of 43), a similar proportion has also reported adverse effects (18 out of 43). These adverse effects are reported only in lean compared to overweight/obese individuals (Korpelainen and others 2003), and in females, not males (Meyer and others 1997), with high daily coffee consumption (Meyer and others 1997; El Maghraoui and others 2010). Nevertheless, others have shown that the adverse effects on bone mineral density can be offset by milk, typically consumed with coffee (Barrett‐Connor and others 1994), and are only evident in those with the rapid CYP1A2 CC genotype (Hallstrom and others 2010), and may not translate into an increase in fracture risk in the longer‐term (Trimpou and others 2010; Hallstrom and others 2013). Additional research is clearly warranted to elucidate the effect of coffee consumption on bone health. Finally, for all other categories of health outcomes identified, results are equivocal and therefore conclusions on the benefit, risk, or null effect of coffee consumption cannot be determined based on the current literature.