Samstag, 16. November 2013

Coffee and all-cause mortality and morbidity

A few years ago I was reading a lot about coffee and noticed that recent studies were more and more suggestive of health benefits.
These days I still periodically check the literature, but rarely have the time to read the full text of papers. All in all, I do consider recent data to be consistent with beneficial effects at moderate intakes.

Here, I provide current abstracts and added comments.

Eur J Epidemiol. 2013 Jul;28(7):527-39. doi: 10.1007/s10654-013-9834-7. Epub 2013 Aug 11.
A meta-analysis of prospective studies of coffee consumption and mortality for all causes, cancers and cardiovascular diseases.
Malerba S, Turati F, Galeone C, Pelucchi C, Verga F, La Vecchia C, Tavani A.
Several prospective studies considered the relation between coffee consumption and mortality. Most studies, however, were underpowered to detect an association, since they included relatively few deaths. To obtain quantitative overall estimates, we combined all published data from prospective studies on the relation of coffee with mortality for all causes, all cancers, cardiovascular disease (CVD), coronary/ischemic heart disease (CHD/IHD) and stroke. A bibliography search, updated to January 2013, was carried out in PubMed and Embase to identify prospective observational studies providing quantitative estimates on mortality from all causes, cancer, CVD, CHD/IHD or stroke in relation to coffee consumption.
A systematic review and meta-analysis was conducted to estimate overall relative risks (RR) and 95 % confidence intervals (CI) using random-effects models.
The pooled RRs of all cause mortality for the study-specific highest versus low (≤1 cup/day) coffee drinking categories were 0.88 (95 % CI 0.84-0.93) based on all the 23 studies, and 0.87 (95 % CI 0.82-0.93) for the 19 smoking adjusting studies.
The combined RRs for CVD mortality were 0.89 (95 % CI 0.77-1.02, 17 smoking adjusting studies) for the highest versus low drinking and 0.98 (95 % CI 0.95-1.00, 16 studies) for the increment of 1 cup/day. Compared with low drinking, the RRs for the highest consumption of coffee were 0.95 (95 % CI 0.78-1.15, 12 smoking adjusting studies) for CHD/IHD, 0.95 (95 % CI 0.70-1.29, 6 studies) for stroke, and 1.03 (95 % CI 0.97-1.10, 10 studies) for all cancers.
This meta-analysis provides quantitative evidence that coffee intake is inversely related to all cause and, probably, CVD mortality.
Then I would like to highlight contradictory evidence, perhaps suggesting a non-linear dose-response(?), or more worryingly, something else.
In this case, the authors speculate that coffee may benefit the old while harming the young. Interestingly, a similar hypothesis about the effects of alcohol exists. This does not mean that young people cannot benefit from red wine or coffee, however. Presumably, the benefits on cardiovascular disease would accrue over time, because it is a chronic disease that begins ante- or perinatally (at around birth) and worsens throughout life.

Mayo Clin Proc. 2013 Oct;88(10):1066-74. doi: 10.1016/j.mayocp.2013.06.020. Epub 2013 Aug 15.
Association of coffee consumption with all-cause and cardiovascular disease mortality.
Liu J, Sui X, Lavie CJ, Hebert JR, Earnest CP, Zhang J, Blair SN.
During the 17-year median follow-up, 2512 deaths occurred (804 [32%] due to cardiovascular disease). In multivariate analyses, coffee intake was positively associated with all-cause mortality in men. Men who drank more than 28 cups of coffee per week had higher all-cause mortality (hazard ratio [HR], 1.21; 95% CI, 1.04-1.40). However, after stratification based on age, younger (<55 years old) men and women showed a significant association between high coffee consumption (>28 cups per week) and all-cause mortality after adjusting for potential confounders and fitness level (HR, 1.56; 95% CI, 1.30-1.87 for men; and HR, 2.13; 95% CI, 1.26-3.59 for women).
In this large cohort [n=43 727], a positive association between coffee consumption and all-cause mortality was observed in men and in men and women younger than 55 years. On the basis of these findings, it seems appropriate to suggest that younger people avoid heavy coffee consumption (ie, averaging >4 cups per day). However, this finding should be assessed in future studies of other populations.
And a verbal summary:
J Am Coll Cardiol. 2013 Sep 17;62(12):1043-51. doi: 10.1016/j.jacc.2013.06.035. Epub 2013 Jul 17.
Effects of habitual coffee consumption on cardiometabolic disease, cardiovascular health, and all-cause mortality.
O'Keefe JH, Bhatti SK, Patil HR, DiNicolantonio JJ, Lucan SC, Lavie CJ.
Coffee, after water, is the most widely consumed beverage in the United States, and is the principal source of caffeine intake among adults. The biological effects of coffee may be substantial and are not limited to the actions of caffeine. Coffee is a complex beverage containing hundreds of biologically active compounds, and the health effects of chronic coffee intake are wide ranging. 
From a cardiovascular (CV) standpoint, coffee consumption may reduce the risk of type 2 diabetes mellitus and hypertension, as well as other conditions associated with CV risk such as obesity and depression,
but it may adversely affect lipid profiles depending on [preparation technique]
Regardless, a growing body of data suggests that habitual coffee consumption is neutral to beneficial regarding the risks of a variety of adverse CV outcomes including coronary heart disease, congestive heart failure, arrhythmias, and stroke.
Moreover, large epidemiological studies suggest that regular coffee drinkers have reduced risks of mortality, both CV and all-cause.
The potential benefits also include protection against neurodegenerative diseases, improved asthma control, and lower risk of select gastrointestinal diseases.
A daily intake of ∼2 to 3 cups of coffee appears to be safe and is associated with neutral to beneficial effects for most of the studied health outcomes.
However, most of the data on coffee's health effects are based on observational data, with very few randomized, controlled studies, and association does not prove causation. Additionally, the possible advantages of regular coffee consumption have to be weighed against potential risks (which are mostly related to its high caffeine content) including anxiety, insomnia, tremulousness, and palpitations, as well as bone loss and possibly increased risk of fractures.
As alluded to a few things still need sorting out: contradictory studies, absence of RCTs, preparation technique, genotype effects, age-dependence of effects and risk-benefit dose-response.

Sonntag, 3. November 2013

Folic acid supplementation in primary prevention?

Increased cancer incidence could be a potential side-effect from supplementation, because folate is involved in purine and pyrimidine synthesis. What do controlled trials say?

Simply put: no risk, no benefit in recent analyses (1, 2). An earlier (now outdated?) meta-analysis suggested increased risk of cancer (3). Perhaps some time I can read the full papers:

"Our analyses suggest that cancer incidences were higher in the folic acid-supplemented groups than the non-folic acid-supplemented groups (relative risk=1.21 [95% confidence interval: 1.05-1.39]). Folic acid-supplementation trials should be performed with careful monitoring of cancer incidence" (3)

 Almost the same holds true for CVD (4). Folic acid's useless.

1. Lancet. 2013 Mar 23;381(9871):1029-36.
Effects of folic acid supplementation on overall and site-specific cancer incidence during the randomised trials: meta-analyses of data on 50,000 individuals.
Vollset et al.

Int J Cancer. 2013 Sep 1;133(5):1033-41. doi: 10.1002/ijc.28038. Epub 2013 Feb 15.
Folic acid supplementation and cancer risk: a meta-analysis of randomized controlled trials.
Qin X, Cui Y, Shen L, Sun N, Zhang Y, Li J, Xu X, Wang B, Xu X, Huo Y, Wang X.

3.  Cancer Epidemiol. 2012 Feb;36(1):78-81. doi: 10.1016/j.canep.2011.05.003. Epub 2011 Oct 21.
Meta-analysis of cancer risk in folic acid supplementation trials.
Baggott JE, Oster RA, Tamura T.

4. Eur J Intern Med. 2012 Dec;23(8):745-54. doi: 10.1016/j.ejim.2012.07.004. Epub 2012 Aug 11.
Efficacy of folic acid supplementation in cardiovascular disease prevention: an updated meta-analysis of randomized controlled trials.
Yang HT, Lee M, Hong KS, Ovbiagele B, Saver JL.