Many of us rely on coffee to clear morning brain fog — and stay sharp during the day.

In part, that attribute explains why — in addition to its tempting taste — more than half of all Americans drink coffee daily.

Although the near-universal notion that coffee stimulates the brain seems like no-brainer, conventional wisdom often lacks scientific backup.

That’s not the case when it comes to coffee, or its most famous constituent — caffeine — as we reported in Caffeine May Boost Brain Power and Deflect Dementia and Brainy News on Coffee, Tea, & Omega-3s.

And it’s abundantly clear that — unless you’re uncomfortably sensitive to caffeine’s stimulating effects — coffee is actively healthful, largely thanks to its abundance of antioxidants, including caffeine.

For more on this reversal of fortune, see Coffee's Ascent from Demon to Angel.

The underrecognized antioxidants in coffee
Findings in recent years — including confirmation of its antioxidant effects — has put caffeine on something of a pedestal.

As the Italy-based authors of an evidence review said two years ago, “Overall … coffee consumption can increase glutathione levels and improve protection against DNA damage, especially following regular/repeated intake.” Glutathione is a key player in the body’s own antioxidant network.

But caffeine isn’t the only beneficial antioxidant compound in coffee. In fact, polyphenol-type compounds — including ferulic acid, caffeic acid, and chlorogenic acid (CGA) are more responsible for coffee’s potent antioxidant punch.

Chlorogenic acid reduces the rates of liver cancer and colorectal cancer in animal studies, but this hasn’t been tested in people, which would be difficult to do.

More famously, CGA improves blood sugar control — and the blood-sugar-control performance of common diabetes drugs such as Metformin.

Many are surprised to learn that coffee is the biggest single source of antioxidants in the average American’s diet — due in part to his or her meager consumption of antioxidant-rich fruits and vegetables.

Certain fruits and vegetables provide very small amounts of CGA — with blueberries containing more than most — but coffee is by far the richest commonly consumed source.

While roasting lowers the very high levels of CGA in green coffee beans, coffee and espresso brewed from roasted beans still contain unrivaled — albeit varying — amounts.

For example, 16 ounces of brewed coffee (three typical coffee cups’ worth) contain 250 to 400mg of CGA, and the average coffee drinker gets from 0.5 grams to 1 gram of these antioxidants daily.

In contrast, people who don’t drink coffee typically get 80% to 90% less CGA daily (i.e., less than 100mg).

Japanese clinical trial sees big brain boost from coffee’s chlorogenic acids
In prior studies, CGA has shown promise for preventing neurodegenerative disorders.

Routine coffee-drinking reduces the risk of neurodegenerative conditions, and CGA appears largely responsible.

CGA and its metabolites (digestive breakdown products) protect brain cells against oxidative stress and (like dietary omega-3s) promote “neuronal differentiation” — the growth of new brain cells, including in the hippocampus, which is critical to memory.

CGA also appears to exert “neurotrophic” effects, which means that they (also like omega-3s) promote growth of new connections between brain cells.

The results of several studies in rodents have shown that CGA can improve learning and memory functions in those animals.

Now, similar benefits in humans appeared in a small “pilot” clinical trial from Japan, which was randomized and placebo-controlled (Saitou K et al. 2018).

And it found that CGA improved cognitive performance and motor speeds among the participants randomly assigned to consume a beverage that contained these antioxidants.

Importantly, this was the first randomized, double-blind, placebo-controlled study to investigate the effects of CGA on people’s brain performance.

The researchers recruited 38 healthy people and randomly assigned them to receive beverages to which they’d added either 300mg of CGA (extracted from green coffee beans) or an inactive placebo.

Before the trial began, each participant was tested on four key aspects of brain performance:

  1. Motor speed — how quickly someone can make a physical movement.
  2. Shifting attention — how flexibly the brain responds to changes in external stimuli.
  3. Psychomotor speed — how fast the brain translates thoughts into physical movements.
  4. Executive function — planning, creative thinking, impulse control, flexible response to new stimuli, mental focus, working memory, and seeing situations from different perspectives.

After 16 weeks, the CGA group displayed significant improvements in all four measures of brain performance, compared with the placebo group.

The improvement in psychomotor speed is especially valuable because this capacity slows with aging, and is related to other key brain functions, including verbal fluency.

As the Japanese team concluded, “These results suggest that CGAs may improve some cognitive functions, which would help in the efficient performance of complex tasks.”

Importantly, the new findings fit with the results of their previous pilot study, in which people who took supplemental CGA for six months displayed better cognitive function, especially in the prefrontal cortex — a region key to thinking and executive functions.

Better yet, compared to the placebo group, the CGA group showed higher, brain-protective levels of two key proteins — apolipoprotein A1 and transthyretin — low levels of which are linked to early-stage cognitive decline.

The Japanese scientists drew a logical conclusion: “… increased TTR and ApoA1 levels might reflect the improved cognitive functions, as observed in the neuropsychological tests.”

The beauty of this good news is that one out of two Americans already get lots of this good stuff — in a drink they find delicious!


  • Azam S, Hadi N, Khan NU, Hadi SM. Antioxidant and prooxidant properties of caffeine, theobromine and xanthine. Med Sci Monit. 2003 Sep;9(9):BR325-30.
  • Bourne LC, Rice-Evans C. Bioavailability of ferulic acid. Biochem Biophys Res Commun. 1998 Dec 18;253(2):222-7.
  • Eskelinen, M.H., Ngandu, T., Tuomilehto, J., Soininen, H., Kivipelto, M. Midlife coffee and tea drinking and the risk of late-life dementia: A population-based CAIDE study. J. Alzheimer’s Dis. 2009, 16, 85–91.
  • Farah A, Monteiro M, Donangelo CM, Lafay S.Chlorogenic acids from green coffee extract are highly bioavailable in humans. J Nutr. 2008 Dec;138(12):2309-15. doi: 10.3945/jn.108.095554
  • Hall S, Desbrow B, Anoopkumar-Dukie S, Davey AK, Arora D, McDermott C, Schubert MM, Perkins AV, Kiefel MJ, Grant GD. A review of the bioactivity of coffee, caffeine and key coffee constituents on inflammatory responses linked to depression. Food Res Int. 2015 Oct;76(Pt 3):626-636. doi: 10.1016/j.foodres.2015.07.027. Epub 2015 Aug 4. Review.
  • Heitman, E., Ingram, D.K. Cognitive and neuroprotective effects of chlorogenic acid. Nutr. Neurosci. 2017, 20, 32–39.
  • Ito, H., Sun, X.L., Watanabe, M., Okamoto, M., Hatano, T. Chlorogenic acid and its metabolite m-coumaric acid evoke neurite outgrowth in hippocampal neuronal cells. Biosci. Biotechnol. Biochem. 2008, 72, 885–888.
  • Johnston KL, Clifford MN, Morgan LM. Coffee acutely modifies gastrointestinal hormone secretion and glucose tolerance in humans: glycemic effects of chlorogenic acid and caffeine. Am J Clin Nutr. 2003 Oct;78(4):728-33.
  • Kay CD, Pereira-Caro G, Ludwig IA, Clifford MN, Crozier A. Anthocyanins and Flavanones Are More Bioavailable than Previously Perceived: A Review of Recent Evidence. Annu Rev Food Sci Technol. 2017 Feb 28;8:155-180. doi: 10.1146/annurev-food-030216-025636. Epub 2017 Jan 11.
  • Kim, J., Lee, S., Shim, J., Kim, H.W., Kim, J., Jang, Y.J., Yang, H., Park, J., Choi, S.H., Yoon, J.H., et al. Caffeinated coffee, decaffeinated coffee, and the phenolic phytochemical chlorogenic acid up-regulate NQO1 expression and prevent H2O2-induced apoptosis in primary cortical neurons. Neurochem. Int. 2012, 60, 466–474.
  • Kwon, S.H., Lee, H.K., Kim, J.A., Hong, S.I., Kim, H.C., Jo, T.H., Park, Y.I., Lee, C.K., Kim, Y.B., Lee, S.Y., et al. Neuroprotective effects of chlorogenic acid on scopolamine-induced amnesia via anti-acetylcholinesterase and anti-oxidative activities in mice. Eur. J. Pharmacol. 2010, 649, 210-217.
  • Lila MA, Burton-Freeman B, Grace M, Kalt W. Unraveling Anthocyanin Bioavailability for Human Health. My Annu Rev Food Sci Technol. 2016;7:375-93. doi: 10.1146/annurev-food-041715-033346. Epub 2016 Jan 11. Review.
  • Martini D, Del Bo' C, Tassotti M, Riso P, Del Rio D, Brighenti F, Porrini M. Coffee Consumption and Oxidative Stress: A Review of Human Intervention Studies. Molecules. 2016 Jul 28;21(8). pii: E979. doi: 10.3390/molecules21080979. Review.
  • Nakajima, Y., Shimazawa, M., Mishima, S., Hara, H. Water extract of propolis and its main constituents, caffeoylquinic acid derivatives, exert neuroprotective effects via antioxidant actions. Life Sci. 2007, 80, 370–377.
  • Olthof MR, Hollman PC, Katan MB. Chlorogenic acid and caffeic acid are absorbed in humans. J Nutr. 2001 Jan;131(1):66-71.
  • Saitou K et al. Effect of Chlorogenic Acids on Cognitive Function: A Randomized, Double-Blind, Placebo-Controlled Trial. 2018, 10 (10), 1337; doi: 10.3390/nu10101337
  • Tajik, N., Tajik, M., Mack, I., Enck, P. The potential effects of chlorogenic acid, the main phenolic components in coffee, on health: A comprehensive review of the literature. Eur. J. Nutr. 2017, 56, 2215–2244.
  • Van Gelder, B.M., Buijsse, B., Tijhuis, M., Kalmijn, S., Giampaoli, S., Nissinen, A., Kromhout, D. Coffee consumption is inversely associated with cognitive decline in elderly European men: The FINE Study. Eur. J. Clin. Nutr. 2007, 61, 226–232.