Evidence in support of the neuroprotective effects of flavonoids has increased significantly in recent years, although to date much of this evidence has emerged from animal rather than human studies. Nonetheless, with a view to making recommendations for future good practice, we review 15 existing human dietary intervention studies that have examined the effects of particular types of flavonoid on cognitive performance. The studies employed a total of 55 different cognitive tests covering a broad range of cognitive domains. Most studies incorporated at least one measure of executive function/working memory, with nine reporting significant improvements in performance as a function of flavonoid supplementation compared to a control group. However, some domains were overlooked completely (e.g. implicit memory, prospective memory), and for the most part there was little consistency in terms of the particular cognitive tests used making across study comparisons difficult. Furthermore, there was some confusion concerning what aspects of cognitive function particular tests were actually measuring. Overall, while initial results are encouraging, future studies need to pay careful attention when selecting cognitive measures, especially in terms of ensuring that tasks are actually sensitive enough to detect treatment effects.
Null results are generally less likely to be published. Consistent with the operation of such a bias in the present literature, the null results found in our survey were invariably included in articles reporting the results of multiple tasks or multiple measures of a single task; published single-task studies with exclusively behavioral measures all found enhancement. This suggests that some single-task studies with null results have gone unreported. The present mixed results are consistent with those of other recent reviews that included data from normal subjects, using more limited sets of tasks or medications (Advokat, 2010; Chamberlain et al., 2010; Repantis, Schlattmann, Laisney, & Heuser, 2010).
Qualia Mind, meanwhile, combines more than two dozen ingredients that may support brain and nervous system function – and even empathy, the company claims – including vitamins B, C and D, artichoke stem and leaf extract, taurine and a concentrated caffeine powder. A 2014 review of research on vitamin C, for one, suggests it may help protect against cognitive decline, while most of the research on artichoke extract seems to point to its benefits to other organs like the liver and heart. A small company-lead pilot study on the product found users experienced improvements in reasoning, memory, verbal ability and concentration five days after beginning Qualia Mind.
When I worked on the Bulletproof Diet book, I wanted to verify that the effects I was getting from Bulletproof Coffee were not coming from modafinil, so I stopped using it and measured my cognitive performance while I was off of it. What I found was that on Bulletproof Coffee and the Bulletproof Diet, my mental performance was almost identical to my performance on modafinil. I still travel with modafinil, and I’ll take it on occasion, but while living a Bulletproof lifestyle I rarely feel the need.

Many of the positive effects of cognitive enhancers have been seen in experiments using rats. For example, scientists can train rats on a specific test, such as maze running, and then see if the "smart drug" can improve the rats' performance. It is difficult to see how many of these data can be applied to human learning and memory. For example, what if the "smart drug" made the rat hungry? Wouldn't a hungry rat run faster in the maze to receive a food reward than a non-hungry rat? Maybe the rat did not get any "smarter" and did not have any improved memory. Perhaps the rat ran faster simply because it was hungrier. Therefore, it was the rat's motivation to run the maze, not its increased cognitive ability that affected the performance. Thus, it is important to be very careful when interpreting changes observed in these types of animal learning and memory experiments.
Also known as Arcalion or Bisbuthiamine and Enerion, Sulbutiamine is a compound of the Sulphur group and is an analog to vitamin B1, which is known to pass the blood-brain barrier easily. Sulbutiamine is found to circulate faster than Thiamine from blood to brain. It is recommended for patients suffering from mental fatigue caused due to emotional and psychological stress. The best part about this compound is that it does not have most of the common side effects linked with a few nootropics.
Starting from the studies in my meta-analysis, we can try to estimate an upper bound on how big any effect would be, if it actually existed. One of the most promising null results, Southon et al 1994, turns out to be not very informative: if we punch in the number of kids, we find that they needed a large effect size (d=0.81) before they could see anything:

Productivity is the most cited reason for using nootropics. With all else being equal, smart drugs are expected to give you that mental edge over other and advance your career. Nootropics can also be used for a host of other reasons. From studying to socialising. And from exercise and health to general well-being. Different nootropics cater to different audiences.


Smart drugs offer significant memory enhancing benefits. Clinical studies of the best memory pills have shown gains to focus and memory. Individuals seek the best quality supplements to perform better for higher grades in college courses or become more efficient, productive, and focused at work for career advancement. It is important to choose a high quality supplement to get the results you want.


Manually mixing powders is too annoying, and pre-mixed pills are expensive in bulk. So if I’m not actively experimenting with something, and not yet rich, the best thing is to make my own pills, and if I’m making my own pills, I might as well make a custom formulation using the ones I’ve found personally effective. And since making pills is tedious, I want to not have to do it again for years. 3 years seems like a good interval - 1095 days. Since one is often busy and mayn’t take that day’s pills (there are enough ingredients it has to be multiple pills), it’s safe to round it down to a nice even 1000 days. What sort of hypothetical stack could I make? What do the prices come out to be, and what might we omit in the interests of protecting our pocketbook?
The fish oil can be considered a free sunk cost: I would take it in the absence of an experiment. The empty pill capsules could be used for something else, so we’ll put the 500 at $5. Filling 500 capsules with fish and olive oil will be messy and take an hour. Taking them regularly can be added to my habitual morning routine for vitamin D and the lithium experiment, so that is close to free but we’ll call it an hour over the 250 days. Recording mood/productivity is also free a sunk cost as it’s necessary for the other experiments; but recording dual n-back scores is more expensive: each round is ~2 minutes and one wants >=5, so each block will cost >10 minutes, so 18 tests will be >180 minutes or >3 hours. So >5 hours. Total: 5 + (>5 \times 7.25) = >41.
The methodology would be essentially the same as the vitamin D in the morning experiment: put a multiple of 7 placebos in one container, the same number of actives in another identical container, hide & randomly pick one of them, use container for 7 days then the other for 7 days, look inside them for the label to determine which period was active and which was placebo, refill them, and start again.
Some nootropics are more commonly used than others. These include nutrients like Alpha GPC, huperzine A, L-Theanine, bacopa monnieri, and vinpocetine. Other types of nootropics ware still gaining traction. With all that in mind, to claim there is a “best” nootropic for everyone would be the wrong approach since every person is unique and looking for different benefits.
Several studies have assessed the effect of MPH and d-AMP on tasks tapping various other aspects of spatial working memory. Three used the spatial working memory task from the CANTAB battery of neuropsychological tests (Sahakian & Owen, 1992). In this task, subjects search for a target at different locations on a screen. Subjects are told that locations containing a target in previous trials will not contain a target in future trials. Efficient performance therefore requires remembering and avoiding these locations in addition to remembering and avoiding locations already searched within a trial. Mehta et al. (2000) found evidence of greater accuracy with MPH, and Elliott et al. (1997) found a trend for the same. In Mehta et al.’s study, this effect depended on subjects’ working memory ability: the lower a subject’s score on placebo, the greater the improvement on MPH. In Elliott et al.’s study, MPH enhanced performance for the group of subjects who received the placebo first and made little difference for the other group. The reason for this difference is unclear, but as mentioned above, this may reflect ability differences between the groups. More recently, Clatworthy et al. (2009) undertook a positron emission tomography (PET) study of MPH effects on two tasks, one of which was the CANTAB spatial working memory task. They failed to find consistent effects of MPH on working memory performance but did find a systematic relation between the performance effect of the drug in each individual and its effect on individuals’ dopamine activity in the ventral striatum.
“I cannot overstate how grateful I am to Cavin for having published this book (and launched his podcast) before I needed it. I am 3.5 months out from a concussion and struggling to recover that final 25% or so of my brain and function. I fully believe that diet and lifestyle can help heal many of our ills, and this book gives me a path forward right now. Gavin’s story is inspiring, and his book is well-researched and clearly written. I am a food geek and so innately understand a lot of his advice — I’m not intimidated by the thought of drastically changing my diet because I know well how to shop and cook for myself — but I so appreciate how his gentle approach and stories about his own struggles with a new diet might help people who would find it all daunting. I am in week 2 of following his advice (and also Dr. Titus Chiu’s BrainSave plan). It’s not an instantaneous miracle cure, but I do feel better in several ways that just might be related to this diet.”
Take quarter at midnight, another quarter at 2 AM. Night runs reasonably well once I remember to eat a lot of food (I finish a big editing task I had put off for weeks), but the apathy kicks in early around 4 AM so I gave up and watched Scott Pilgrim vs. the World, finishing around 6 AM. I then read until it’s time to go to a big shotgun club function, which occupies the rest of the morning and afternoon; I had nothing to do much of the time and napped very poorly on occasion. By the time we got back at 4 PM, the apathy was completely gone and I started some modafinil research with gusto (interrupted by going to see Puss in Boots). That night: Zeo recorded 8:30 of sleep, gap of about 1:50 in the recording, figure 10:10 total sleep; following night, 8:33; third night, 8:47; fourth, 8:20 (▇▁▁▁).

Table 3 lists the results of 24 tasks from 22 articles on the effects of d-AMP or MPH on learning, assessed by a variety of declarative and nondeclarative memory tasks. Results for the 24 tasks are evenly split between enhanced learning and null results, but they yield a clearer pattern when the nature of the learning task and the retention interval are taken into account. In general, with single exposures of verbal material, no benefits are seen immediately following learning, but later recall and recognition are enhanced. Of the six articles reporting on memory performance (Camp-Bruno & Herting, 1994; Fleming, Bigelow, Weinberger, & Goldberg, 1995; Rapoport, Busbaum, & Weingartner, 1980; Soetens, D’Hooge, & Hueting, 1993; Unrug, Coenen, & van Luijtelaar, 1997; Zeeuws & Soetens 2007), encompassing eight separate experiments, only one of the experiments yielded significant memory enhancement at short delays (Rapoport et al., 1980). In contrast, retention was reliably enhanced by d-AMP when subjects were tested after longer delays, with recall improved after 1 hr through 1 week (Soetens, Casaer, D’Hooge, & Hueting, 1995; Soetens et al., 1993; Zeeuws & Soetens, 2007). Recognition improved after 1 week in one study (Soetens et al., 1995), while another found recognition improved after 2 hr (Mintzer & Griffiths, 2007). The one long-term memory study to examine the effects of MPH found a borderline-significant reduction in errors when subjects answered questions about a story (accompanied by slides) presented 1 week before (Brignell, Rosenthal, & Curran, 2007).


…Phenethylamine is intrinsically a stimulant, although it doesn’t last long enough to express this property. In other words, it is rapidly and completely destroyed in the human body. It is only when a number of substituent groups are placed here or there on the molecule that this metabolic fate is avoided and pharmacological activity becomes apparent.
The surveys just reviewed indicate that many healthy, normal students use prescription stimulants to enhance their cognitive performance, based in part on the belief that stimulants enhance cognitive abilities such as attention and memorization. Of course, it is possible that these users are mistaken. One possibility is that the perceived cognitive benefits are placebo effects. Another is that the drugs alter students’ perceptions of the amount or quality of work accomplished, rather than affecting the work itself (Hurst, Weidner, & Radlow, 1967). A third possibility is that stimulants enhance energy, wakefulness, or motivation, which improves the quality and quantity of work that students can produce with a given, unchanged, level of cognitive ability. To determine whether these drugs enhance cognition in normal individuals, their effects on cognitive task performance must be assessed in relation to placebo in a masked study design.
I can test fish oil for mood, since the other claimed benefits like anti-schizophrenia are too hard to test. The medical student trial (Kiecolt-Glaser et al 2011) did not see changes until visit 3, after 3 weeks of supplementation. (Visit 1, 3 weeks, visit 2, supplementation started for 3 weeks, visit 3, supplementation continued 3 weeks, visit 4 etc.) There were no tests in between the test starting week 1 and starting week 3, so I can’t pin it down any further. This suggests randomizing in 2 or 3 week blocks. (For an explanation of blocking, see the footnote in the Zeo page.)
Perceptual–motor congruency was the basis of a study by Fitzpatrick et al. (1988) in which subjects had to press buttons to indicate the location of a target stimulus in a display. In the simple condition, the left-to-right positions of the buttons are used to indicate the left-to-right positions of the stimuli, a natural mapping that requires little cognitive control. In the rotation condition, the mapping between buttons and stimulus positions is shifted to the right by one and wrapped around, such that the left-most button is used to indicate the right-most position. Cognitive control is needed to resist responding with the other, more natural mapping. MPH was found to speed responses in this task, and the speeding was disproportionate for the rotation condition, consistent with enhancement of cognitive control.
28,61,36,25,61,57,39,56,23,37,24,50,54,32,50,33,16,42,41,40,34,33,31,65,23,36,29,51,46,31,45,52,30, 50,29,36,57,60,34,48,32,41,48,34,51,40,53,73,56,53,53,57,46,50,35,50,60,62,30,60,48,46,52,60,60,48, 47,34,50,51,45,54,70,48,61,43,53,60,44,57,50,50,52,37,55,40,53,48,50,52,44,50,50,38,43,66,40,24,67, 60,71,54,51,60,41,58,20,28,42,53,59,42,31,60,42,58,36,48,53,46,25,53,57,60,35,46,32,26,68,45,20,51, 56,48,25,62,50,54,47,42,55,39,60,44,32,50,34,60,47,70,68,38,47,48,70,51,42,41,35,36,39,23,50,46,44,56,50,39
You have the highest density of mitochondria in your brain’s prefrontal cortex, which helps to explain why I feel Unfair Advantage in my head first. You have the second highest density in your heart, which is probably why I feel it in the center of my chest next. Mitochondrial energizers can have profound nootropic effects! At higher doses mitochondrial energizers also make for an excellent pre-workout supplements.
Some critics argue that Modafinil is an expression of that, a symptom of a new 24/7 work routine. But what if the opposite is true? Let’s say you could perform a task in significantly less time than usual. You could then use the rest of your time differently, spending it with family, volunteering, or taking part in a leisure activity. And imagine that a drug helped you focus on clearing your desk and inbox before leaving work. Wouldn’t that help you relax once you get home?
Not included in the list below are prescription psychostimulants such as Adderall and Ritalin. Non-medical, illicit use of these drugs for the purpose of cognitive enhancement in healthy individuals comes with a high cost, including addiction and other adverse effects. Although these drugs are prescribed for those with attention deficit hyperactivity disorder (ADHD) to help with focus, attention and other cognitive functions, they have been shown to in fact impair these same functions when used for non-medical purposes. More alarming, when taken in high doses, they have the potential to induce psychosis.
I’m wary of others, though. The trouble with using a blanket term like “nootropics” is that you lump all kinds of substances in together. Technically, you could argue that caffeine and cocaine are both nootropics, but they’re hardly equal. With so many ways to enhance your brain function, many of which have significant risks, it’s most valuable to look at nootropics on a case-by-case basis. Here’s a list of 9 nootropics, along with my thoughts on each.
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