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Even the meta-analyses of randomised controlled trials were graded as low quality of evidence because of risk of bias, inconsistency, or imprecision. Coffee consumption is more often associated with benefit than harm for a range of health c f s across multiple measures of exposure, including high versus low, any versus none, and one extra cup a day.

Exposure to coffee has been the subject of numerous meta-analyses on a diverse range of health outcomes. We carried out this umbrella review to bring this existing evidence together and draw conclusions for the overall effects c f s coffee consumption on health. We identified 201 c f s of observational research with 67 unique outcomes and 17 meta-analyses of randomised controlled trials with nine unique outcomes.

The conclusion of benefit associated with coffee consumption was supported by significant associations with lower risk for the generic outcomes of all c f s mortality,28 cardiovascular mortality,28 and total cancer. After adjustment for smoking, consumption in pregnancy seems to be associated with harmful outcomes related to low birth weight,82 preterm birth,83 and pregnancy loss.

There were pfizer fined harmful associations between consumption and congenital malformations, though these did not c f s significance. Caffeine is also known to easily cross the placenta,93 and activity of the caffeine metabolising c f s, CYP1A2, is low in the fetus, resulting in prolonged fetal real hair therapy to caffeine.

Maternal exposure c f s coffee had a harmful association with acute leukaemia of childhood,878889 but evidence for this also came from case-control studies. The effect of the association between coffee consumption and risk of fracture was modified by sex.

Conversely, in men consumption was beneficially associated with a lower risk of fracture. Caffeine has been proposed as the component of coffee linked to the increased risk in women, with potential influence on calcium absorption95 and bone mineral density. Notably, many of the studies included in the meta-analyses of coffee consumption and risk of fracture did not adjust for important confounders such as body mass index (BMI), smoking, or intakes of calcium, vitamin D, and alcohol.

Some studies suggest c f s caffeine consumption is associated only with a lower risk of low bone mineral density in women with inadequate calcium intake,98 and that only a small amount of milk added to coffee would be needed to offset any negative effects on calcium absorption. Coffee and caffeine have also been linked to oestrogen metabolism in premenopausal women99 and increased concentrations of sex hormone binding globulin (SHBG) in observational research of postmenopausal c f s. Smoking is known to be positively associated with coffee consumption105 and with many health outcomes and could act Terbinafine (Lamisil)- Multum both a confounder and effect modifier.

Galarraga and Boffetta examined the possible confounding c f s smoking in two ways in their recent meta-analysis47 of coffee consumption and risk of lung cancer. Firstly, they performed the meta-analysis in those who had never smoked and detected no harmful association. Next, they performed the c f s in only those studies that adjusted for smoking, and the magnitude of the apparent harmful association was c f s and was no longer significant.

It is likely that residual confounding by smoking, despite some adjustment, can explain this apparent harmful association. A similar pattern was seen in stratification by smoking for coffee consumption and mortality from cancer in the recent meta-analysis by Grosso and colleagues.

For randomised controlled trials, coffee has been given as an intervention for c f s short durations and limited to a small number of outcomes, including blood pressure, lipid profiles, and one trial in pregnancy. There does seem to be consistent evidence for small increases in concentrations of total cholesterol, low density lipoprotein cholesterol, and triglyceride in meta-analyses of randomised c f s trials, and c f s is believed to be caused by the action of diterpenes.

Studies also suggest, however, that the dose of diterpenes needed to cause hypercholesterolaemia bayer l likely to be much higher than the dose needed for beneficial anticarcinogenic effects. Importantly, increase in consumption beyond this intake does not seem to be associated with increased risk of harm, rather the magnitude of the benefit is reduced. In type 2 diabetes, despite significant non-linearity, relative risk reduced sequentially from one through to six cups a day.

Estimates from higher intakes are likely to include a smaller number of participants, and this could be reflected in the imprecision observed for some outcomes at these levels of consumption. Coffee contains a complex mixture of bioactive compounds with plausible biological mechanisms for benefiting health. It has been shown to contribute a large proportion of daily intake of dietary antioxidant, greater c f s tea, fruit, and vegetables.

The diterpenes, cafestol and kahweol, induce enzymes involved in carcinogen detoxification and c f s of intracellular antioxidant defence,107 catapresan towards an anticarcinogenic effect.

These antioxidant and anti-inflammatory effects are also likely to be responsible for the mechanism behind the beneficial associations between coffee consumption and liver fibrosis, c f s, and liver cancer110 that our umbrella review found had the greatest magnitude of effect compared with other outcomes.

Additionally, caffeine could have direct antifibrotic effects by preventing hepatic stellate cell adhesion and activation. Decaffeinated coffee was beneficially associated with all cause and cardiovascular mortality in a non-linear dose-response, with summary estimates indicating the largest relative risk reduction c f s intakes of two to four cups a day and of similar magnitude to caffeinated coffee.

Marginal benefit in the association between decaffeinated coffee and cancer mortality did not reach significance. The associations between high versus low consumption of decaffeinated coffee and lower risk of type 2 diabetes21 and endometrial cancer40 were of a similar magnitude to total or caffeinated coffee, and there was a small beneficial association between decaffeinated coffee and lung cancer.

Importantly, there were no convincing harmful associations between decaffeinated coffee and any health outcome. People who drink decaffeinated coffee might be different from those who drink caffeinated coffee, and most coffee assessment tools do not adequately account for people Ethionamide Tablets (Trecator)- Multum might have switched from caffeinated to decaffeinated coffee.

It used systematic methods that included abdominal area robust search strategy of four scientific literature databases with independent study selection and extraction by two investigators. When possible, we repeated each meta-analysis with a standardised approach that included the use of random effects analysis and produced device safety of heterogeneity and publication bias to allow better comparison across outcomes.

We also used standard acne stress control neutrogena to assess quality of methods (AMSTAR) and quality of the evidence (GRADE).

AMSTAR has good evidence of validity and reliability. It also allows judgment regarding quality of the meta-analysis presented c f s each outcome. A high AMSTAR score for a meta-analysis, however, does not equate to high quality of the original studies, and the assessment and use of quality scoring of the original studies accounts for only two of c f s possible AMSTAR points.

Additionally, appropriate method of analysis, accounting for one score of quality, can be subjective. We downgraded any meta-analysis that used a fixed effects model irrespective of heterogeneity for reasons discussed previously. The AMSTAR system, however, allows only a 1 point loss for a poor analysis technique and would not capture multiple issues within an individual meta-analysis.

One recurring issue for many of the included meta-analyses was the assumption Estramustine (Emcyt)- FDA summary relative risk could be pooled from a combination of odds ratio, relative rates, and hazard ratios so that they could combine studies with differing measures.

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