We recognize that eating nose-to-tail provides nutrients and concentrations of certain proteins that we might not get solely from eating muscle meats. Including bones, skin, and organ meats in our diets can give us beneficial compounds that are not as highly concentrated in the parts of animals we more typically consume. There’s a parallel when consuming plant foods: we may be missing out on helpful substances when we consume only a prized fraction of certain plants and discard the rest. Coffee is a prime example: we value the bean, mostly for its caffeine content. (Some of us go far past valuing it and go straight to revering.) But what about the rest of the coffee cherry? What are we leaving behind in the fruit of the coffee tree?  

Concentrate made from coffee fruit is rich in chlorogenic acid (CGA), a “biologically active dietary polyphenol” with numerous health benefits. CGA is also found in green (unroasted) coffee beans but a substantial portion of it is lost during the roasting process. So green coffee bean extract or whole coffee fruit extract may be richer sources of it. In a past article we covered the use of CGA in such applications as metabolic syndrome and mental health. This time let’s focus on neuroprotection.

A study using rat hippocampal neurons showed that pre-treatment with CGA reduced the apoptosis normally induced by beta-amyloid, which could have implications for positively impacting Alzheimer’s disease. Increases were observed in superoxide dismutase and glutathione peroxidase with a decrease in malondialdehyde (a marker of oxidative stress), so the mechanism may be related to increased antioxidant activity. CGA was also shown to reduce cell death and increase antioxidant activity in a rat model of Parkinson’s disease and in cultured human neuroblastoma cells.

Clinical studies support the use of coffee fruit concentrate for stimulating production of brain-derived neurotrophic factor (BDNF). BDNF has powerful effects on the brain and central nervous system. It regulates development and differentiation of new neurons, promotes neuron survival, supports balanced moods, and may even play a role in regulating appetite. BDNF production declines with age and lower levels have been observed in patients with Alzheimer’s disease and are highly suspected in Parkinson’s and Huntington’s diseases. (It is unknown, however, whether reduced BDNF is cause or effect in these conditions.)  

In a study of twenty healthy young subjects (aged 25 to 35), a single dose of encapsulated coffee fruit concentrate (100 mg) increased peripheral serum BDNF by a staggering 91% at 60 minutes and 66% at 120 minutes compared to baseline levels. This was a significant increase compared to placebo and was also significant when compared to the change in BDNF after the same subjects consumed a cup of freshly brewed coffee (approx. 130 mg caffeine). (Brewed coffee increased BDNF slightly but it was not significantly different from placebo.)

One subject from this study was selected at random to receive another dose of coffee fruit concentrate in order to measure BDNF levels localized in exosomes, membrane-bound extracellular vesicles that are believed to cross the blood-brain barrier. At 60 minutes after the dose, this individual showed a 54% increase in serum BDNF and a whopping 206% increase in exosomal BDNF. These levels had declined by 120 minutes but still remained significantly elevated over baseline (32% over for serum and 39% over for exosomes).

Similar findings were seen in a separate study by the same researchers, this one comparing the whole coffee fruit concentrate to grapeseed extract, green coffee bean extract, green coffee caffeine powder, and placebo (silica). These comparisons are interesting because they show that the boost in BDNF stimulated by the coffee fruit concentrate (an average increase of 137%, range 65–222%) wasn’t due to the caffeine: the green coffee caffeine powder (73% caffeine by weight) increased BDNF similarly to grapeseed extract, which is free of caffeine. The green coffee caffeine powder caused only a modest increase in plasma BDNF levels while the whole coffee fruit concentrate led to the largest increase even though it’s only 0.7% caffeine by weight.

The green coffee bean extract didn’t raise BDNF much above placebo, which suggests the most powerful effect is induced by something present in the whole coffee fruit but either not present in the beans or present at a lower concentration. If not the caffeine, the next logical suspect would be CGA, but the increase appeared to be due to something other than CGA as well, because 50 mg of CGA itself did not change BDNF compared to placebo, but 100 mg of coffee fruit concentrate raised blood BDNF level by 148%.

More research remains to be done regarding whether an increase in BDNF might lead to substantial improvements in patients already living with a neurodegenerative disorder. It is well known, however, that BDNF supports synaptic plasticity and neurogenesis, so considering the lackluster efficacy of existing pharmaceutical interventions for conditions like Alzheimer’s and Parkinson’s diseases, natural compounds that increase BDNF have intriguing potential.