The Facts Behind Nootropics
/What are Nootropics?
Our household is definitely in the early-adopter group when it comes to trying out new “health” trends. I had the lid of my blender melted trying to make steaming hot Bulletproof Coffee, we invested a small fortune in bone broth and grass-fed pastured organic protein when we chose to go Paleo (that one lasted almost an entire year, and I learned how to make falafel out of cauliflower), and one weekend I spent a total of 21 hours chopping and juicing about 100 pounds of fruits and vegetables to make my own 5-day juice cleanse for two. While it may sound strange to hear a physician admit to being amenable to these sorts of fads, I can assure you that most of our prior health trend bandwagon jumping has been after a fair amount of research and data corroboration on my part (which I will happily share in future posts).
You can imagine, then, my surprise when my husband came home a couple of weeks ago with a tiny gold canister with the word “Nootro” on the lid, which is apparently one of several commercially available brands of Nootropics, the most recent trend in self-optimization. Of course, when I saw this, my first question was, “What are Nootropics?” (My second question was, “How much did that cost?!”). But really, I was simply very uncomfortable with the idea of these new supplements that I knew nothing about and needed to put on my Sherlock hat to do some investigating.
Nootropics are cognitive enhancers. They have historically been studied to improve memory function in patients with conditions that lead to memory and concentration deficiencies (think Alzheimer’s disease and progressive vascular dementia from multiple cerebral micro-infarcts). Like many pharmacologic agents, however, Nootropics were also recognized as potentially having some very beneficial side effects in the form of cognitive enhancement and increased concentration in patients without preexisting dementia. Of course, this opens the door for the use of nootropics in non-medical settings - cerebral cosmesis if you will, or Viagra for the brain. It’s the same vein of mental doping that happens on college campuses with the illegal sale and distribution of prescription stimulants (ie. Ritalin and Adderal). This is not a use that has been approved by the FDA, nor is it likely that the FDA would approve the elective use of nootropics in the foreseeable future. Nevertheless popularity has been growing not only on college campuses, but in the workplace as well.
This illustration says it all, showing the trend in Google searching for “nootropics” in the past 10 years.
My research into the topic has led to 2 issues: I am concerned regarding some of the ingredients in these commercially available nootropics and the lack of proven efficacy and, more importantly, long term safety; and I am concerned regarding the ethical dilemma surrounding the use of nootropics in a non-medically indicated manner.
The Ingredients
This ingredient list comes directly from the website for Nootroo. I’ve tried to look up data from peer reviewed scientific literature, with a focus on proven medical benefits, and any medical concerns.
CDP-Choline
Cytidine 5’-diphosphocholine is an essential intermediary involved primarily in the biosynthesis of phosphotidylcholine, a component in biological membranes in many organ systems, including the brain. Choline is also involved in the synthesis of Acetyl-choline, a neurotransmitter. Because it is involved in both cell repair/regeneration and neurotransmission, the potential for cognitive improvement from choline supplementation has been studied since the 1950s. The good news is that in the 60+ years of data including human studies, albeit small and not necessarily well designed, no significant adverse effects of the drug have been reported. On the other hand, almost all data suggesting improvement in memory, cognitive function, and attention has been from studies involving elderly patients with vascular dementia, Alzheimer’s or Parkinson’s, or younger patients after stroke or traumatic brain injury. The two studies I was able to identify in young healthy volunteers provide us with 2 pieces of information: (1) Choline supplementation can enhance sensory gating (the ability to tune out extraneous sensory stimuli); and (2) choline supplementation affects brain oscillations on EEG, though the clinical significance of this finding is uncertain. Bare in mind, though, that given the study design, both of these tidbits of data are applicable only to young, healthy, right-handed men. (Sources: 1, 2, 3)
L-Theanine
L-Theanine is an amino acid almost exclusively found in green tea, and while the effective isolate wasn’t identified as L-Theanine until much later, the mental clarity and calming benefits of green tea have been heralded since the eighth century. L-Theanine appears to increase the levels of neurotransmitters generally associated with positive responses (dopamine, serotonin, and GABA). A large proportion of the existing body of data on L-Theanine comes from studies in rat and gerbil models, showing that L-Theanine supplementation is associated with positive effects on learning and memory, and that it functions as an antidepressant. Again, amongst human studies, high quality data in young healthy individuals is lacking. The few studies discoverable show that L-Theanine, like CDP-Choline, can also enhance sensory-motor gating in young adults, that it affects brain wave oscillations on EEG, and that it can decrease stress responses. While overall the message is positive, the studies are small and the data remains mixed. There is, however, no obvious health concern with use of L-Theanine supplementation. (Sources: 1, 2, 3, 4)
Caffeine
Caffeine, the stimulant in your morning cup of Jo, is naturally occurring in 60 different plants, and evolutionarily probably came into existence as a pesticide. It is one of the most studied nootropes, with mention of medical use of caffeine documented as far back as 1025 AD. Epidemiologic studies show a link between chronic caffeine consumption and reduced risk of subsequent neurodegenerative diseases (ie Alzheimer's), reduced memory impairment, and reduction in motor symptoms in Parkinson's patients. Interestingly, while studies have shown that caffeine is certainly associated with an increased perception of alertness and awakeness, the benefits on cognitive function actually remain up for debate (there is a question whether benefits seen in studies are true benefits of caffeine versus the masking of sleep deprivation and/or caffeine withdrawal). On the downside, there is a laundry list of bad side effects that can come with caffeine consumption, including anxiety, agitation, restlessness, insomnia, gastrointestinal disturbances, tremors, tachycardia, psychomotor agitation; there are also sporadic case reports that consistently appear over the years of death from caffeine overdose. (Sources: 1, 2, 3, 4, 5)
Noopept
Noopept is the Russian developed analog of prescription cognitive enhancer, piracetam. The bulk of data on Noopept is from mice and rat studies, which suggest improvements in cognition, exploratory and locomotive activity in maze studies, and reversal in oxidative and ischemic brain injury in rodents. The only human studies I was able to find are available only in Russian, which precludes me from being able to analytically assess the study merits and results. Only one study evaluates Noopept in healthy adults, also in Russian, and follows the similar pattern of proving EEG activity differences in adults with Noopept, again with questionable clinical significance (Obviously the individuals designing these studies have a theory as to the significance of the different EEG wave patterns, but given how inconsistently these EEG findings translate into actual clinical findings I would not consider them significant until they are replicated in a clinical study looking at clinically relevant outcomes). (Sources: 1, 2, 3, 4, 5)
Phenylpiracetam
Also with roots in Russia, this member of the piracetam family was developed for its faster absorption and its higher bioavailability (the amount actually available for use in your body after consumption). In encephalopathic patients and those with brain injury, it has been shown to decrease depression and anxiety, as well as increase cognitive function. Phenylpiracetam has not, however, been studied in healthy individuals and clinical trials of this particular drug are limited. Beware, too, that it makes an appearance on the list of drugs banned by the World Anti-Doping Agency. (Sources: 1, 2)
Take Home Message
While overall there is no evidence of harm with these ingredients, noopept and phenylpiracetam are relatively new compounds and it will likely take years to detect any adverse effects, if any exist. In addition, though there is evidence to suggest that these drugs are beneficial in mice, rats, gerbils, and a subset of humans with preexisting cognitive dysfunction, there is very little evidence that they have a positive effect in young, healthy adults. Of course, one option would be to just increase your intake of coffee, green tea, and foods rich in choline (hint: egg yolks and liver).
The Ethical and Moral Side of Things
When considering cognitive enhancers, groups on either side of the fence are happy to wax on poetically about the benefits or lack thereof of nootropic agents, but the elephant in the room remains the ethics behind their use. At what point are we crossing the threshold from self-enhancement to cognitive-doping and potentially even cheating? And with the current price point, is this new phenomenon only perpetuating Gladwell’s “accumulative advantage?” This is not a question that will ever find a satisfactory answer, but definitely one that deserves consideration (1, 2, 3).