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Heavy Coffee Drinking and Age-Dependent All-Cause Mortality

      To the Editor:
      The study by Liu et al
      • Liu J.
      • Sui X.
      • Lavie C.J.
      • et al.
      Association of coffee consumption with all-cause and cardiovascular disease mortality.
      reported in the October 2013 issue of Mayo Clinic Proceedings associated heavy coffee drinking with increased all-cause mortality in people younger than 55 years. A previous study,
      • Freedman N.D.
      • Park Y.
      • Abnet C.C.
      • Hollenbeck A.R.
      • Sinha R.
      Association of coffee drinking with total and cause-specific mortality [published correction appears in N Engl J Med. 2012;367(3):285].
      however, associated heavy coffee drinking with a decrease in all-cause mortality. Both studies included large populations with long follow-up and made adjustments for smoking, alcohol consumption, and other potential health effectors. In both studies, a similar effect was attributed to either caffeine or caffeine-free drinks.
      • Liu J.
      • Sui X.
      • Lavie C.J.
      • et al.
      Association of coffee consumption with all-cause and cardiovascular disease mortality.
      • Freedman N.D.
      • Park Y.
      • Abnet C.C.
      • Hollenbeck A.R.
      • Sinha R.
      Association of coffee drinking with total and cause-specific mortality [published correction appears in N Engl J Med. 2012;367(3):285].
      Thus, the agent searched for was not the caffeine.
      Coffee, especially when brewed, contains many antioxidants such as chlorogenic acid, ferulic acid, and various flavonoids. It has been suggested that in a regular American diet, coffee is the main source of antioxidants.
      • Eastman P.
      Research into antioxidants brings good news for coffee and mushrooms.
      Antioxidants neutralize free radicals in the body and curb their potential damage to body cells. However, free radicals also play central active roles in cross-body protection and tissue regeneration.
      Reactive oxygen species (ROS) such as hydrogen peroxide and superoxide are used by the immune system (neutrophils) to attack invading bacteria. Reactive oxygen species also induce apoptosis in cancer cells. At least in part of the cases, cancer cells wield antioxidants to thwart these attacks.
      • Watson J.
      Oxidants, antioxidants and the current incurability of metastatic cancers.
      Watson
      • Watson J.
      Oxidants, antioxidants and the current incurability of metastatic cancers.
      suggested that the ROS produced in anticancer therapies, either ionizing or chemical, are the main effective agents. This potentially explains why resistance to both therapies often occurs simultaneously. Reactive oxygen species also activate after-stress adaptations of skeletal muscles, including their remodeling. They are regularly produced in the muscles to scavenge dead muscle fibers and other tissue debris. This may explain why consumption of powerful antioxidants, such as resveratrol, blocks cardiovascular benefits of physical exercise.
      • Gliemann L.
      • Schmidt J.F.
      • Olesen J.
      • et al.
      Resveratrol blunts the positive effects of exercise training on cardiovascular health in aged men.
      Finally, overconsumption of antioxidants (such as vitamin E) could be related to all-cause mortality.
      • Miller III, E.R.
      • Pastor-Barriuso R.
      • Dalal D.
      • Riemersma R.A.
      • Appel L.J.
      • Guallar E.
      Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality.
      The two faces of ROS suggest that the body, as part of its homeostasis, should maintain an oxidative balance between ROS and antioxidants. The optimal balance may vary from one person to another, depend on an individual's health condition, or vary among distinct tissues. It is common knowledge that ROS levels in the body are elevated with age. Therefore, coffee, a major source of antioxidants, may push the oxidation balance toward ROS deficiency. In such a situation, crucial defense and regenerative processes of the body might become suppressed. Because young people's levels of ROS are already relatively low, they are likely to be more vulnerable to this effect. This explanation could account for the age-dependent effect of coffee consumption in the study by Liu et al.
      • Liu J.
      • Sui X.
      • Lavie C.J.
      • et al.
      Association of coffee consumption with all-cause and cardiovascular disease mortality.
      At old age, however, the extra amounts of ROS should be able to deal with more ingested antioxidants without dropping too low. In the study by Freedman et al,
      • Freedman N.D.
      • Park Y.
      • Abnet C.C.
      • Hollenbeck A.R.
      • Sinha R.
      Association of coffee drinking with total and cause-specific mortality [published correction appears in N Engl J Med. 2012;367(3):285].
      only the good aspects of heavy coffee drinking were observed. This is most likely because more than 75% of the participants in that study were older than 55 years.
      A comparison between ROS levels before and after periods of heavy coffee drinking in people of different ages is required to further support the ROS hypothesis. This research may also help in identifying types of ROS whose levels associate with all-cause mortality, especially in young people.

      References

        • Liu J.
        • Sui X.
        • Lavie C.J.
        • et al.
        Association of coffee consumption with all-cause and cardiovascular disease mortality.
        Mayo Clin Proc. 2013; 88: 1066-1074
        • Freedman N.D.
        • Park Y.
        • Abnet C.C.
        • Hollenbeck A.R.
        • Sinha R.
        Association of coffee drinking with total and cause-specific mortality [published correction appears in N Engl J Med. 2012;367(3):285].
        N Engl J Med. 2012; 366: 1891-1904
        • Eastman P.
        Research into antioxidants brings good news for coffee and mushrooms.
        Oncology Times UK. 2005; 2: 18-19
        • Watson J.
        Oxidants, antioxidants and the current incurability of metastatic cancers.
        Open Biol. 2013; 3: 120144
        • Gliemann L.
        • Schmidt J.F.
        • Olesen J.
        • et al.
        Resveratrol blunts the positive effects of exercise training on cardiovascular health in aged men.
        J Physiol. 2013; 591: 5047-5059
        • Miller III, E.R.
        • Pastor-Barriuso R.
        • Dalal D.
        • Riemersma R.A.
        • Appel L.J.
        • Guallar E.
        Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality.
        Ann Intern Med. 2005; 142: 37-46

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