Coffee Fruit(ful) for Cognitive Improvement

by Ari Magill, MD


Our morning cup of joe, a brewed beverage derived from a bean, has been shown to improve cognition, but the coffee fruit, the flesh and skin surrounding the bean (also known as the pulp) has excited scientists because of its high concentration of phenolic antioxidants and phytonutrients,a thus having the potential to prevent or reverse mild cognitive impairment.

The Takeaway:

Coffee fruit’s potential for preventing and reversing cognitive decline has created a great deal of excitement.
A desire to reduce waste stemmed the interest in coffee fruit since bacterial and fungal contamination of the pulp, when thrown away in bulk, presents a health hazard.1

Human Studies

Reyes-Izquierdo et al studied cognitive-enhancing properties of coffee fruit vs. beans,2 comparing blood levels of brain-derived neurotrophic factor (BDNF) in subjects after a single dose of whole coffee fruit concentrate powder (WCFC), green coffee caffeine powder, grape seed extract powder, and green coffee bean extract powder to placebo. They recruited 25 healthy subjects between the ages of 18 and 55, who randomly received a 100-mg dose of one of the treatments or placebo. The single-dose study was repeated only with WCFC and placebo, which verified the results.

BDNF levels were the only significant treatment, increasing by an average of 143%, more than four times that of grape seed extract and green coffee caffeine powder. The authors speculated that the high procyanidinb content of coffee fruit (or its unique combination of polyphenols) is driving BDNF production since grape seed extract contains higher levels of polyphenols but lower levels of procyanidins; the concentrate has only low levels of caffeine, negligible amounts compared to green coffee caffeine powder.

Leal et al highlighted the importance of BDNF in memory formation,3 since it plays a regulatory role in the molecular underpinnings of learning and memory, known as long-term potentiation (LTP). Its action is especially great among hippocampus neurons and plays a central role in the differentiation, health and maintenance, and neurogenesis.4

In a follow-up study, Reyes-Izquierdo et al looked at the effects of WCFC not only on BDNF blood levels but also within exosomesc released into the bloodstream.5 Twenty healthy subjects between the ages of 25 and 35 participated; WCFC were compared to freshly brewed coffee and placebo, with each agent being administered to all subjects on three separate successive days.

Investigators again found that WCFC significantly increased these blood levels compared to placebo and was produced by freshly brewed coffee. Exosomes isolated from blood samples taken from subjects at baseline were shown to carry BDNF. An increased quantity of this was found after subjects took WCFC.

Robinson et al conducted a clinical study on the effects of coffee fruit extract on cognitive function.6 They enrolled 71 subjects with mild cognitive deficits who received either coffee fruit extract (taken in the morning or twice per day) or placebo over 28 days and assessed with working memory tests. Cognitive benefits from coffee fruit extract were demonstrated at one week and maintained during the study. Reaction time was significantly improved, with a trend toward an increase in accuracy.

Animal Study

Because coffee fruit contains modest amounts of caffeine, it can potentially cause arousal of the sympathetic nervous system, with associated symptoms such as fast heart rate and nervousness. Safety evaluation of extremely high doses of the substance on laboratory rats revealed no ill effects, both in terms of toxicity and cancer risk.7


Preliminary studies indicate coffee fruit extract may be a helpful tool to combat cognitive decline. It can be found on Amazon or at health food stores.


a Heeger et al looked at the chemical content of six dried coffee cherry pulp samples and a beverage called Cascara that is derived from coffee cherry pulp;8 They found that the extracts contained high polyphenol and antioxidant content. The former includes chlorogenic acid, which is found in high concentration in whole green coffee bean extract but is partly removed during the roasting process.

They are plant metabolism products that provide defense against insults including ultraviolet light and microbial pathogens. Studies suggest that consistently eating polyphenol-rich diets decreases risk for diseases in humans, including cancers, cardiovascular diseases, diabetes, osteoporosis, and neurodegenerative diseases.9
 Multistep coffee fruit extractions led to higher levels of the chlorogenic acid and greater antioxidant activity (up to 25 times higher) compared to single-step extraction and freeze-dried powders, with lower percentages of caffeine.10

b Procyanidins are another phytonutrient found in plant products (including apples, grapes, and teas) with powerful antioxidant properties.

c Exosomes are tiny vesicles containing lipids, protein, and genetic material released by cells that influence the metabolism and functioning of neighboring cells


  1. Klingel T, et al. A review of coffee by-products including leaf, flower, cherry, husk, silver skin, and spent grounds as novel foods within the European Union. Foods. 2020;9(5):665. doi: 10.3390/foods9050665.
  2. Reyes-Izquierdo T, et al. Modulatory effect of coffee fruit extract on plasma levels of brain-derived neurotrophic factor in healthy subjects. Br J Nutr. 2013;110(3):420-425. doi: 10.1017/S0007114512005338.
  3. Leal G, et al. BDNF and hippocampal synaptic plasticity. Vitam Horm. 2017;104:153-195. doi: 10.1016/bs.vh.2016.10.004.
  4. Numakawa T, et al. Actions of brain-derived neurotrophic factor and glucocorticoid stress in neurogenesis. Int J Mol Sci. 2017;18(11): 2312. doi: 10.3390/ijms18112312.
  5. Reyes-Izquierdo T, et al. Stimulatory effect of whole coffee fruit concentrate powder on plasma levels of total and exosomal brain-derived neurotrophic factor in healthy subjects: An acute within-subject clinical study. Br J Nutr. 2013.
  6. Robinson JL, et al. Cognitive short-and long-term effects of coffee cherry extract in older adults with mild cognitive decline. Neuropsychol Dev Cogn B Aging Neuropsychol Cog. 2020;27(6):918-934. doi: 10.1080/13825585.2019.1702622.
  7. Heimbach JT, et al. Safety studies on products from whole coffee fruit. Food Chem Toxicol. 2010;48(8-9):2517-2525. doi: 10.1016/j.fct.2010.06.025.
  8. Heeger A, et al. Bioactives of coffee cherry pulp and its utilisation for production of Cascara beverage. Food Chem. 2017;221:969-975. doi: 10.1016/j.foodchem.2016.11.067.
  9. Pandey KB, Syed IR. Plant polyphenols as dietary antioxidants in human health and disease. Oxid Med Cell Longev. 2009;2(5):270-278. doi: 10.4161/oxim.2.5.9498.
  10. Mullen W, et al. The antioxidant and chlorogenic acid profiles of whole coffee fruits are influenced by the extraction procedures. J Agric Food Chem. 2011;59(8):3754-3762. doi: 10.1021/jf200122m.

About the Author

Dr. Ari Magill is a holistic neurologist and medical consultant based in Mesa, AZ. He received medical school training at University of Texas Southwestern in Dallas and residency training at the University of Arizona in Tucson. He is passionate about finding innovative treatments for cognitive impairment, emphasizing lifestyle change and natural supplements.