Bacopa is a supplement herb often used for memory or stress adaptation. Its chronic effects reportedly take many weeks to manifest, with no important acute effects. Out of curiosity, I bought 2 bottles of Bacognize Bacopa pills and ran a non-randomized non-blinded ABABA quasi-self-experiment from June 2014 to September 2015, measuring effects on my memory performance, sleep, and daily self-ratings of mood/productivity. Because of the very slow onset, small effective sample size, definite temporal trends probably unrelated to Bacopa, and noise in the variables, the results were as expected, ambiguous, and do not strongly support any correlation between Bacopa and memory/sleep/self-rating (+/-/- respectively).
Absorption of nicotine across biological membranes depends on pH. Nicotine is a weak base with a pKa of 8.0 (Fowler, 1954). In its ionized state, such as in acidic environments, nicotine does not rapidly cross membranes…About 80 to 90% of inhaled nicotine is absorbed during smoking as assessed using C14-nicotine (Armitage et al., 1975). The efficacy of absorption of nicotine from environmental smoke in nonsmoking women has been measured to be 60 to 80% (Iwase et al., 1991)…The various formulations of nicotine replacement therapy (NRT), such as nicotine gum, transdermal patch, nasal spray, inhaler, sublingual tablets, and lozenges, are buffered to alkaline pH to facilitate the absorption of nicotine through cell membranes. Absorption of nicotine from all NRTs is slower and the increase in nicotine blood levels more gradual than from smoking (Table 1). This slow increase in blood and especially brain levels results in low abuse liability of NRTs (Henningfield and Keenan, 1993; West et al., 2000). Only nasal spray provides a rapid delivery of nicotine that is closer to the rate of nicotine delivery achieved with smoking (Sutherland et al., 1992; Gourlay and Benowitz, 1997; Guthrie et al., 1999). The absolute dose of nicotine absorbed systemically from nicotine gum is much less than the nicotine content of the gum, in part, because considerable nicotine is swallowed with subsequent first-pass metabolism (Benowitz et al., 1987). Some nicotine is also retained in chewed gum. A portion of the nicotine dose is swallowed and subjected to first-pass metabolism when using other NRTs, inhaler, sublingual tablets, nasal spray, and lozenges (Johansson et al., 1991; Bergstrom et al., 1995; Lunell et al., 1996; Molander and Lunell, 2001; Choi et al., 2003). Bioavailability for these products with absorption mainly through the mucosa of the oral cavity and a considerable swallowed portion is about 50 to 80% (Table 1)…Nicotine is poorly absorbed from the stomach because it is protonated (ionized) in the acidic gastric fluid, but is well absorbed in the small intestine, which has a more alkaline pH and a large surface area. Following the administration of nicotine capsules or nicotine in solution, peak concentrations are reached in about 1 h (Benowitz et al., 1991; Zins et al., 1997; Dempsey et al., 2004). The oral bioavailability of nicotine is about 20 to 45% (Benowitz et al., 1991; Compton et al., 1997; Zins et al., 1997). Oral bioavailability is incomplete because of the hepatic first-pass metabolism. Also the bioavailability after colonic (enema) administration of nicotine (examined as a potential therapy for ulcerative colitis) is low, around 15 to 25%, presumably due to hepatic first-pass metabolism (Zins et al., 1997). Cotinine is much more polar than nicotine, is metabolized more slowly, and undergoes little, if any, first-pass metabolism after oral dosing (Benowitz et al., 1983b; De Schepper et al., 1987; Zevin et al., 1997).
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 13 nootropics, along with my thoughts on each.
Somewhat ironically given the stereotypes, while I was in college I dabbled very little in nootropics, sticking to melatonin and tea. Since then I have come to find nootropics useful, and intellectually interesting: they shed light on issues in philosophy of biology & evolution, argue against naive psychological dualism and for materialism, offer cases in point on the history of technology & civilization or recent psychology theories about addiction & willpower, challenge our understanding of the validity of statistics and psychology - where they don’t offer nifty little problems in statistics and economics themselves, and are excellent fodder for the young Quantified Self movement4; modafinil itself demonstrates the little-known fact that sleep has no accepted evolutionary explanation. (The hard drugs also have more ramifications than one might expect: how can one understand the history of Southeast Asia and the Vietnamese War without reference to heroin, or more contemporaneously, how can one understand the lasting appeal of the Taliban in Afghanistan and the unpopularity & corruption of the central government without reference to the Taliban’s frequent anti-drug campaigns or the drug-funded warlords of the Northern Alliance?)
Still, the scientific backing and ingredient sourcing of nootropics on the market varies widely, and even those based in some research won't necessarily immediately, always or ever translate to better grades or an ability to finally crank out that novel. Nor are supplements of any kind risk-free, says Jocelyn Kerl, a pharmacist in Madison, Wisconsin.
On the other metric, suppose we removed the creatine? Dropping 4 grams of material means we only need to consume 5.75 grams a day, covered by 8 pills (compared to 13 pills). We save 5,000 pills, which would have cost $45 and also don’t spend the $68 for the creatine; assuming a modafinil formulation, that drops our $1761 down to $1648 or $1.65 a day. Or we could remove both the creatine and modafinil, for a grand total of $848 or $0.85 a day, which is pretty reasonable.
Took full pill at 10:21 PM when I started feeling a bit tired. Around 11:30, I noticed my head feeling fuzzy but my reading seemed to still be up to snuff. I would eventually finish the science book around 9 AM the next day, taking some very long breaks to walk the dog, write some poems, write a program, do Mnemosyne review (memory performance: subjectively below average, but not as bad as I would have expected from staying up all night), and some other things. Around 4 AM, I reflected that I felt much as I had during my nightwatch job at the same hour of the day - except I had switched sleep schedules for the job. The tiredness continued to build and my willpower weakened so the morning wasn’t as productive as it could have been - but my actual performance when I could be bothered was still pretty normal. That struck me as kind of interesting that I can feel very tired and not act tired, in line with the anecdotes.
Both nootropics startups provide me with samples to try. In the case of Nootrobox, it is capsules called Sprint designed for a short boost of cognitive enhancement. They contain caffeine – the equivalent of about a cup of coffee, and L-theanine – about 10 times what is in a cup of green tea, in a ratio that is supposed to have a synergistic effect (all the ingredients Nootrobox uses are either regulated as supplements or have a “generally regarded as safe” designation by US authorities)
Eat a healthy diet.  While the best nootropic supplements can help fuel your brain, they cannot fill every gap in your diet.  If you want your brain to function at its best, a healthy, nutritious, varied diet is essential.  Make sure that you are eating fatty fish and foods fortified with DHA omega-3 fatty acids.  Get plenty of vitamin E and antioxidants like lutein.
Zack explained that he didn't really like the term enhancement: "We're not talking about superhuman intelligence. No one's saying we're coming out with a pill that's going to make you smarter than Einstein! What we're really talking about is enabling people." He sketched a bell curve on the back of a napkin. "Almost every drug in development is something that will take someone who's working at, like, 40% or 50%, and take them up to 80," he said.
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Gamma-aminobutyric acid, also known as GABA, naturally produced in the brain from glutamate, is a neurotransmitter that helps in the communication between the nervous system and brain. The main function of this Nootropic is to reduce the unnecessary activity of the nerve cells and helps calm the brain. . Thus it helps improve various conditions, like stress, anxiety and depression by decreasing the beta brain waves and increasing the alpha brain waves.  As a result, cognitive abilities like memory power, attention, and alertness also improve. GABA helps drug addicts recover from addiction by  normalizing the brain’s GABA receptors which reduce anxiety and craving levels in the absence of addictive substances.
Last spring, 100 people showed up at a Peak Performance event where psychedelic psychologist James Fadiman said the key to unleashing the cognition-enhancing effects of LSD — which he listed as less anxiety, better focus, improved sleep, greater creativity — was all in the dosage. He recommended a tenth of a “party dose” — enough to give you “the glow” and enhance your cognitive powers without “the trip.”
Fortunately for me, the FDA decided Smart Powder’s advertising was too explicit and ordered its piracetam sales stopped; I was equivocal at the previous price point, but then I saw that between the bulk discount and the fire-sale coupon, 3kg was only $99.99 (shipping was amortized over that, the choline, caffeine, and tryptophan). So I ordered in September 2010. As well, I had decided to cap my own pills, eliminating the inconvenience and bad taste. 3kg goes a very long way so I am nowhere close to running out of my pills; there is nothing to report since, as the pills are simply part of my daily routine.
The research literature, while copious, is messy and varied: methodologies and devices vary substantially, sample sizes are tiny, the study designs vary from paper to paper, metrics are sometimes comically limited (one study measured speed of finishing a RAPM IQ test but not scores), blinding is rare and unclear how successful, etc. Relevant papers include Chung et al 2012, Rojas & Gonzalez-Lima 2013, & Gonzalez-Lima & Barrett 2014. Another Longecity user ran a self-experiment, with some design advice from me, where he performed a few cognitive tests over several periods of LLLT usage (the blocks turned out to be ABBA), using his father and towels to try to blind himself as to condition. I analyzed his data, and his scores did seem to improve, but his scores improved so much in the last part of the self-experiment I found myself dubious as to what was going on - possibly a failure of randomness given too few blocks and an temporal exogenous factor in the last quarter which was responsible for the improvement.
"More and more of our young people are using these drugs to help them work. They've got their laptop, their iPhone, and their Adderall. This rising generation of workers and leaders may have a subtly different style of thinking and working, because they're using these drugs or because they learned to work using these drugs, so that even if you take the drugs away they'll still have a certain approach. I'm a little concerned that we could be raising a generation of very focused accountants."
Professor David O Kennedy published a book in 2014 called Plants and the Human Brain. In his book he summarizes the last 15 years of research into cognitive nutrition, including the work he's done with colleagues at the Brain Performance Nutrition Research Center at Northumbria University. It's a great read and a good guide to what sorts of herbs and other plants to include in our weekly diet and it is all based on hard science rather than mere assertion or trendy but unsubstantiated beliefs.

After we had ordered beers he said: "One of the most impressive features of being a student is how aware you are of a 24-hour work cycle. When you conceive of what you have to do for school, it's not in terms of nine to five but in terms of what you can physically do in a week while still achieving a variety of goals - social, romantic, extracurricular, CV-building, academic."

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A total of 330 randomly selected Saudi adolescents were included. Anthropometrics were recorded and fasting blood samples were analyzed for routine analysis of fasting glucose, lipid levels, calcium, albumin and phosphorous. Frequency of coffee and tea intake was noted. 25-hydroxyvitamin D levels were measured using enzyme-linked immunosorbent assays…Vitamin D levels were significantly highest among those consuming 9-12 cups of tea/week in all subjects (p-value 0.009) independent of age, gender, BMI, physical activity and sun exposure.
One idea I’ve been musing about is the connections between IQ, Conscientiousness, and testosterone. IQ and Conscientiousness do not correlate to a remarkable degree - even though one would expect IQ to at least somewhat enable a long-term perspective, self-discipline, metacognition, etc! There are indications in studies of gifted youth that they have lower testosterone levels. The studies I’ve read on testosterone indicate no improvements to raw ability. So, could there be a self-sabotaging aspect to human intelligence whereby greater intelligence depends on lack of testosterone, but this same lack also holds back Conscientiousness (despite one’s expectation that intelligence would produce greater self-discipline and planning), undermining the utility of greater intelligence? Could cases of high IQ types who suddenly stop slacking and accomplish great things sometimes be due to changes in testosterone? Studies on the correlations between IQ, testosterone, Conscientiousness, and various measures of accomplishment are confusing and don’t always support this theory, but it’s an idea to keep in mind.
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:
These days, young, ambitious professionals prefer prescription stimulants—including methylphenidate (usually sold as Ritalin) and Adderall—that are designed to treat people with attention deficit hyperactivity disorder (ADHD) and are more common and more acceptable than cocaine or nicotine (although there is a black market for these pills). ADHD makes people more likely to lose their focus on tasks and to feel restless and impulsive. Diagnoses of the disorder have been rising dramatically over the past few decades—and not just in kids: In 2012, about 16 million Adderall prescriptions were written for adults between the ages of 20 and 39, according to a report in the New York Times. Both methylphenidate and Adderall can improve sustained attention and concentration, says Barbara Sahakian, professor of clinical neuropsychology at the University of Cambridge and author of the 2013 book Bad Moves: How Decision Making Goes Wrong, and the Ethics of Smart Drugs. But the drugs do have side effects, including insomnia, lack of appetite, mood swings, and—in extreme cases—hallucinations, especially when taken in amounts the exceed standard doses. Take a look at these 10 foods that help you focus.
One of the most popular legal stimulants in the world, nicotine is often conflated with the harmful effects of tobacco; considered on its own, it has performance & possibly health benefits. Nicotine is widely available at moderate prices as long-acting nicotine patches, gums, lozenges, and suspended in water for vaping. While intended for smoking cessation, there is no reason one cannot use a nicotine patch or nicotine gum for its stimulant effects.
Mercury, as well as other heavy metals such as lead, can accumulate in brain tissue, as well as in the spinal cord, as they are fat-soluble - meaning that they can hide itself in fat tissue, which is abundant in both the brain and the spine. Once there, they can displace important nutrients for brain health such as zinc and iron, which are needed for neurotransmitter production, as well as induce an inflammatory process called oxidative stress among other things.
I eventually met Seltzer in an underground food court not far from the Pentagon. He's slim, with a shaved head, and he spoke precisely, rarely stumbling over his words. I asked him if he had any ethical worries about smart drugs. After a pause, he said that he might have a concern if somebody popped a neuroenhancer before taking a licensing exam that certified him as, say, a brain surgeon, and then stopped using the drug. Other than that he couldn't see a problem. He said that he was a firm believer in the idea that "we should have a fair degree of liberty to do with our bodies and our minds as we see fit, so long as it doesn't impinge on the basic rights, liberty and safety of others". He argued: "Why would you want an upward limit on the intellectual capabilities of a human being? And, if you have a very nationalist viewpoint, why wouldn't you want our country to have the advantage over other countries, particularly in what some people call a knowledge-based economy?" He went on: "Think about the complexity of the intellectual tasks that people need to accomplish today. Just trying to understand what Congress is doing is not a simple thing! The complexity of understanding the gamut of scientific and technical and social issues is difficult. If we had a tool that enabled more people to understand the world at a greater level of sophistication, how can we prejudice ourselves against the notion simply because we don't like athletes to do it? To me it doesn't seem like the same question. And it deserves its own debate."
According to McCabe's research team, white male undergraduates at highly competitive schools are the most frequent student users of neuroenhancers. Users are also more likely to belong to a fraternity or a sorority, and to have a grade point average (GPA) of 3.0 - ie satisfactory - or lower. They are 10 times as likely to report that they have smoked marijuana in the past year and 20 times as likely to say that they have used cocaine. In other words, they are decent students at schools where to be a great student you have to give up a lot more partying than they're willing to give up.
Adderall is a mix of 4 amphetamine salts (FDA adverse events), and not much better than the others (but perhaps less addictive); as such, like caffeine or methamphetamine, it is not strictly a nootropic but a cognitive enhancer and can be tricky to use right (for how one should use stimulants, see How To Take Ritalin Correctly). I ordered 10x10mg Adderall IR off Silk Road (Wikipedia). On the 4th day after confirmation from seller, the package arrived. It was a harmless looking little padded mailer. Adderall as promised: 10 blue pills with markings, in a double ziplock baggy (reasonable, it’s not cocaine or anything). They matched pretty much exactly the descriptions of the generic I had found online. (Surprisingly, apparently both the brand name and the generic are manufactured by the same pharmacorp.)
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50 pairs of active/placebos or 100 days. With 120 tablets and 4 tablets used up, that leaves me 58 doses. That might seem adequate except the paired t-test approximation is overly-optimistic, and I also expect the non-randomized non-blinded correlation is too high which means that is overly-optimistic as well. The power would be lower than I’d prefer. I decided to simply order another bottle of Solgar’s & double the sample size to be safe.
Adderall is a mix of 4 amphetamine salts (FDA adverse events), and not much better than the others (but perhaps less addictive); as such, like caffeine or methamphetamine, it is not strictly a nootropic but a cognitive enhancer and can be tricky to use right (for how one should use stimulants, see How To Take Ritalin Correctly). I ordered 10x10mg Adderall IR off Silk Road (Wikipedia). On the 4th day after confirmation from seller, the package arrived. It was a harmless looking little padded mailer. Adderall as promised: 10 blue pills with markings, in a double ziplock baggy (reasonable, it’s not cocaine or anything). They matched pretty much exactly the descriptions of the generic I had found online. (Surprisingly, apparently both the brand name and the generic are manufactured by the same pharmacorp.)
However, they fell short in several categories. The key issue with their product is that it does not contain DHA Omega 3 and the other essential vitamins and nutrients needed to support the absorption of Huperzine A and Phosphatidylserine. Without having DHA Omega 3 it will not have an essential piece to maximum effectiveness. This means that you would need to take a separate pill of DHA Omega 3 and several other essential vitamins to ensure you are able to reach optimal memory support. They also are still far less effective than our #1 pick’s complete array of the 3 essential brain supporting ingredients and over 30 supporting nutrients, making their product less effective.
For this batch, I tried out NOW Foods Magnesium Citrate Powder ($7 for 227g); the powder was still a bit sticky but much easier to work with than the Solgar pills, and the 227g made 249 gel capsule pills. The package estimates 119 serving of 315mg elemental magnesium, so a ratio of 0.315g magnesium for 1.9g magnesium citrate, implying that each gel cap pill then contains 0.152g magnesium (\frac{(119\times315)}{249}=150) and since I want a total dose of 0.8g, I need 5 of the gel cap pills a day or 35 per block.
Eliminating foggy-headedness seems to be the goal of many users of neuroenhancers. But can today's drugs actually accomplish this? I recently posed this question to Chatterjee's colleague Martha Farah, who is a psychologist at Penn and the director of its Center for Cognitive Neuroscience. She is deeply fascinated by, and mildly critical of, neuroenhancers, but basically in favour - with the important caveat that we need to know much more about how these drugs work. While Farah does not take neuroenhancers, she had just finished a paper in which she reviewed the evidence on prescription stimulants as neuroenhancers from 40 laboratory studies involving healthy subjects. Most of the studies looked at one of three types of cognition: learning, working memory, and cognitive control. A typical learning test asks subjects to memorise a list of paired words; an hour, a few days, or a week later, they are presented with the first words in the pairs and asked to come up with the second. Neuroenhancers did improve retention, especially where subjects had been asked to remember information for several days or longer.
Oxidative stress refers to a biochemical process that occurs as a result of an accumulative everyday exposure to toxic burdens such as chemicals in cosmetics, furniture, paints, cars, and pollution. Our body has its own way of armouring itself from the damage that exposure to toxins can create through its production of endogenous antioxidants, which is nature’s way of neutralising oxidative stress. Although we have our own production of these wonder molecules, when we are continuously overloaded with toxins in our environment and have problems detoxifying, the liver can become overwhelmed. Research shows that over time oxidative stress can lead to an increase in inflammatory molecules such as cytokines, which have been shown to correlate with depression (5).This is why it is important to have a high intake of nutrients that support the liver in metabolising and removing toxins from the body, as well as regulating the inflammatory response. There are a few things we can change in our diet to support this area, for example eating foods such as the cruciferous family of vegetables which includes kale, cauliflower, broccoli and cabbage. These are particularly effective at supporting the liver in ushering out toxins as they all share an antioxidant compound called indole-3 Carbinol, which plays an important role in liver health (6). In addition, bitter greens such as collard greens, rocket, chicory and swiss chard are also great for supporting the liver’s own antioxidant defence system.
Hericium erinaceus (Examine.com) was recommended strongly by several on the ImmInst.org forums for its long-term benefits to learning, apparently linked to Nerve growth factor. Highly speculative stuff, and it’s unclear whether the mushroom powder I bought was the right form to take (ImmInst.org discussions seem to universally assume one is taking an alcohol or hotwater extract). It tasted nice, though, and I mixed it into my sleeping pills (which contain melatonin & tryptophan). I’ll probably never know whether the $30 for 0.5lb was well-spent or not.
As I am not any of the latter, I didn’t really expect a mental benefit. As it happens, I observed nothing. What surprised me was something I had forgotten about: its physical benefits. My performance in Taekwondo classes suddenly improved - specifically, my endurance increased substantially. Before, classes had left me nearly prostrate at the end, but after, I was weary yet fairly alert and happy. (I have done Taekwondo since I was 7, and I have a pretty good sense of what is and is not normal performance for my body. This was not anything as simple as failing to notice increasing fitness or something.) This was driven home to me one day when in a flurry before class, I prepared my customary tea with piracetam, choline & creatine; by the middle of the class, I was feeling faint & tired, had to take a break, and suddenly, thunderstruck, realized that I had absentmindedly forgot to actually drink it! This made me a believer.

Pop this pill and improve your memory. Swallow that one and reduce your cognitive decline. We see ads for such products all the time and I suspect they will increase as the baby boomers reach senior citizenhood. The most popular brain boosting supplements are fish oil pills and they are also probably the best studied ones. The results are not encouraging. When all the studies are pooled, we are left with the possibility of a barely significant improvement in recalling lists of words soon after they have been learned, but the effect does not last. Extracts of the ginkgo biloba tree are also popular, and here the prospects are even dimmer. There is no impact on memory, despite claims of increased circulation in the brain. And ginkgo can interfere with the action of anticoagulants and has also been shown to be an animal carcinogen.
After we had ordered beers he said: "One of the most impressive features of being a student is how aware you are of a 24-hour work cycle. When you conceive of what you have to do for school, it's not in terms of nine to five but in terms of what you can physically do in a week while still achieving a variety of goals - social, romantic, extracurricular, CV-building, academic."
There are a variety of substances to get magnesium from. Considerable enthusiasm for the new compound magnesium l-threonate was stirred by 2 small animal rat studies finding that magnesium l-threonate was able to increase magnesium levels in the brain and improve learning/memory tasks. (There are no published human trials as of October 2015, and evidence of publication bias, which I take as evidence against there being large effects in humans.) Animal studies mean very little, of course (see the appendix), but I thought it’d be interesting to try using l-threonate, so I bought the $30 Life Extension Neuro-Mag Magnesium L-Threonate with Calcium and Vitamin D3 (205g), which according to the LEF product page works out to ~60g of Magtein™ magnesium L-threonate and ~4.31g elemental magnesium inasmuch as LEF claims 2000mg of threonate powder provides 144mg elemental magnesium or a 14:1 ratio. (I don’t need the calcium or vitamin D3, but this was the only magnesium l-threonate on Amazon.) Experiment-wise, I’ll probably look at sleep metrics and Mnemosyne performance; I put off designing a blind self-experiment until after trying some.
…The Fate of Nicotine in the Body also describes Battelle’s animal work on nicotine absorption. Using C14-labeled nicotine in rabbits, the Battelle scientists compared gastric absorption with pulmonary absorption. Gastric absorption was slow, and first pass removal of nicotine by the liver (which transforms nicotine into inactive metabolites) was demonstrated following gastric administration, with consequently low systemic nicotine levels. In contrast, absorption from the lungs was rapid and led to widespread distribution. These results show that nicotine absorbed from the stomach is largely metabolized by the liver before it has a chance to get to the brain. That is why tobacco products have to be puffed, smoked or sucked on, or absorbed directly into the bloodstream (i.e., via a nicotine patch). A nicotine pill would not work because the nicotine would be inactivated before it reached the brain.
All clear? Try one (not dozens) of nootropics for a few weeks and keep track of how you feel, Kerl suggests. It’s also important to begin with as low a dose as possible; when Cyr didn’t ease into his nootropic regimen, his digestion took the blow, he admits. If you don’t notice improvements, consider nixing the product altogether and focusing on what is known to boost cognitive function – eating a healthy diet, getting enough sleep regularly and exercising. "Some of those lifestyle modifications," Kerl says, "may improve memory over a supplement."
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