Creatine is stored as phosphocreatine, which acts as a high-energy reserve. Phosphocreatine decreases rapidly during brain activity. Supplementing with creatine (2 grams per day for 1 month) increased average brain creatine by 9.7%. It acts as an energy source for the brain to focus on learning tasks, as well as an energy source for storing memories.
“Who doesn’t want to maximize their cognitive ability? Who doesn’t want to maximize their muscle mass?” asks Murali Doraiswamy, who has led several trials of cognitive enhancers at Duke University Health System and has been an adviser to pharmaceutical and supplement manufacturers as well as the Food and Drug Administration. He attributes the demand to an increasingly knowledge-based society that values mental quickness and agility above all else.

A fancier method of imputation would be multiple imputation using, for example, the R library mice (Multivariate Imputation by Chained Equations) (guide), which will try to impute all missing values in a way which mimicks the internal structure of the data and provide several possible datasets to give us an idea of what the underlying data might have looked like, so we can see how our estimates improve with no missingness & how much of the estimate is now due to the imputation:


I split the 2 pills into 4 doses for each hour from midnight to 4 AM. 3D driver issues in Debian unstable prevented me from using Brain Workshop, so I don’t have any DNB scores to compare with the armodafinil DNB scores. I had the subjective impression that I was worse off with the Modalert, although I still managed to get a fair bit done so the deficits couldn’t’ve been too bad. The apathy during the morning felt worse than armodafinil, but that could have been caused by or exacerbated by an unexpected and very stressful 2 hour drive through rush hour and multiple accidents; the quick hour-long nap at 10 AM was half-waking half-light-sleep according to the Zeo, but seemed to help a bit. As before, I began to feel better in the afternoon and by evening felt normal, doing my usual reading. That night, the Zeo recorded my sleep as lasting ~9:40, when it was usually more like 8:40-9:00 (although I am not sure that this was due to the modafinil inasmuch as once a week or so I tend to sleep in that long, as I did a few days later without any influence from the modafinil); assuming the worse, the nap and extra sleep cost me 2 hours for a net profit of ~7 hours. While it’s not clear how modafinil affects recovery sleep (see the footnote in the essay), it’s still interesting to ponder the benefits of merely being able to delay sleep19.
Conversely, you have to consider that the long term effects of Modafinil haven’t been studies very well. It significantly upsets sleep cycles, and 50% of Modafinil users report a number of short term side effects, such as mild to severe headaches, insomnia, nausea, anxiety, nervousness, hypertension, decreased appetite, and weight loss. PET scans show it affects the same areas of the brain that are stimulated by substance abuse.

This is not something you notice when you talk to Seltzer. And though our memory is probably at its peak in our early 20s, few 30-year-olds are aware of a deficit. But Seltzer considers himself a transhumanist, in the mould of the Oxford philosopher Nick Bostrom and the futuristic writer and inventor Ray Kurzweil. Transhumanists are interested in robots, cryogenics and living a really, really long time; they consider biological limitations that the rest of us might accept, or even appreciate, as creaky obstacles to be aggressively surmounted. On the ImmInst (Immortality Institute) forums, Seltzer and other members discuss life-extension strategies and the potential benefits of cognitive enhancers. Some members, Seltzer among them, use a drug called piracetam, which was first marketed by a Belgian pharmaceutical company in 1972 and in recent years has become available in the US from retailers that sell supplements. Although not approved for any use by the FDA, piracetam has been used experimentally on stroke patients - to little effect - and on patients with a rare neurological condition called progressive myoclonus epilepsy, for whom it proved helpful in alleviating muscle spasms. Data on piracetam's benefits for healthy people is virtually nonexistent, but many users believe that the drug increases blood flow to the brain.

That it is somewhat valuable is clear if we consider it under another guise. Imagine you received the same salary you do, but paid every day. Accounting systems would incur considerable costs handling daily payments, since they would be making so many more and so much smaller payments, and they would have to know instantly whether you showed up to work that day and all sorts of other details, and the recipients themselves would waste time dealing with all these checks or looking through all the deposits to their account, and any errors would be that much harder to track down. (And conversely, expensive payday loans are strong evidence that for poor people, a bi-weekly payment is much too infrequent.) One might draw a comparison to batching or buffers in computers: by letting data pile up in buffers, the computer can then deal with them in one batch, amortizing overhead over many items rather than incurring the overhead again and again. The downside, of course, is that latency will suffer and performance may drop based on that or the items becoming outdated & useless. The right trade-off will depend on the specifics; one would not expect random buffer-sizes to be optimal, but one would have to test and see what works best.

And without those precious nutrients, your brain will start to wither. In a recent Bulletproof Radio podcast episode [iTunes], I talked with neuroscientist Dale Bredesen about why neurodegeneration happens. One of the three most common causes of brain aging is a lack of specific brain nutrients (check out the episode to hear about the other two main causes of brain aging, and what you can do about them).
Began double-blind trial. Today I took one pill blindly at 1:53 PM. at the end of the day when I have written down my impressions and guess whether it was one of the Adderall pills, then I can look in the baggy and count and see whether it was. there are many other procedures one can take to blind oneself (have an accomplice mix up a sequence of pills and record what the sequence was; don’t count & see but blindly take a photograph of the pill each day, etc.) Around 3, I begin to wonder whether it was Adderall because I am arguing more than usual on IRC and my heart rate seems a bit high just sitting down. 6 PM: I’ve started to think it was a placebo. My heart rate is back to normal, I am having difficulty concentrating on long text, and my appetite has shown up for dinner (although I didn’t have lunch, I don’t think I had lunch yesterday and yesterday the hunger didn’t show up until past 7). Productivity wise, it has been a normal day. All in all, I’m not too sure, but I think I’d guess it was Adderall with 40% confidence (another way of saying placebo with 60% confidence). When I go to examine the baggie at 8:20 PM, I find out… it was an Adderall pill after all. Oh dear. One little strike against Adderall that I guessed wrong. It may be that the problem is that I am intrinsically a little worse today (normal variation? come down from Adderall?).
Dr Hart explained how communication between the gut and the brain is controlled via our immune system, our endocrine system (hormones) and our central nervous system, which are all under the influence of the bacteria in our gut. The types and amount of these bacteria, known as our gut microbiome, can be directly impacted by factors such as diet, stress, pollution and medications (2) and the composition of the microbiome is also understood to affect one’s susceptibility to food sensitivities and intolerances (3).  
Alpha Lipoic Acid is a vitamin-like chemical filled with antioxidant properties, that naturally occur in broccoli, spinach, yeast, kidney, liver, and potatoes. The compound is generally prescribed to patients suffering from nerve-related symptoms of diabetes because it helps in preventing damage to the nerve cells and improves the functioning of neurons.

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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
During pregnancy and after pregnancy there is often a concern for the potential depletion of the maternal nutrient reservoir due to the needs of the growing foetus. A nutrient that is particularly important for mental wellbeing and is also essential for the growth of the foetus’s brain, is DHA. This is an omega 3 fatty acid that is found in oily fish and is the primary structural component of brain tissue, as well as playing a crucial role in the maintenance of brain cells and neurotransmitter metabolism (our body can also convert plant sources of omegas 3’s into DHA, such as those found in flaxseeds or chia seeds into DHA, but the conversion can often very poor). Deficiency in this nutrient during pregnancy is common, namely because of lack of seafood intake (the most bioavailable source of DHA) due to poor eating habits and concerns of mercury levels in fish during pregnancy, as well as higher requirements during foetal growth, which can lead to depletion. Due to the role that DHA plays in neurotransmitter metabolism, deficiency in this nutrient has been correlated to symptoms of depression during pregnancy (7). In order, to support your intake of omega 3, aim to have 3 portions of oily fish a week from sources that are low in mercury. These are mainly small fish that have a short life-span such as sardines, mackerel and herring. If you are vegetarian or vegan, although omega 3 is less readily available, it is still possible to get this nutrient from your diet through flax seeds, chia seeds, walnuts and seaweed. If you feel you may not be getting enough through your diet, you may want to consider using a good quality fish oil supplement (or algae based supplement if vegan) as an option. With fish oils, aim to choose a supplement that has been filtered for heavy metals and other pollutants to make sure you're getting the full benefits of the omega 3 oils.
Similarly, Mehta et al 2000 noted that the positive effects of methylphenidate (40 mg) on spatial working memory performance were greatest in those volunteers with lower baseline working memory capacity. In a study of the effects of ginkgo biloba in healthy young adults, Stough et al 2001 found improved performance in the Trail-Making Test A only in the half with the lower verbal IQ.
Flaxseed oil is, ounce for ounce, about as expensive as fish oil, and also must be refrigerated and goes bad within months anyway. Flax seeds on the other hand, do not go bad within months, and cost dollars per pound. Various resources I found online estimated that the ALA component of human-edible flaxseed to be around 20% So Amazon’s 6lbs for $14 is ~1.2lbs of ALA, compared to 16fl-oz of fish oil weighing ~1lb and costing ~$17, while also keeping better and being a calorically useful part of my diet. The flaxseeds can be ground in an ordinary food processor or coffee grinder. It’s not a hugely impressive cost-savings, but I think it’s worth trying when I run out of fish oil.
I posted a link to the survey on my Google+ account, and inserted the link at the top of all gwern.net pages; 51 people completed all 11 binary choices (most of them coming from North America & Europe), which seems adequate since the 11 questions are all asking the same question, and 561 responses to one question is quite a few. A few different statistical tests seem applicable: a chi-squared test whether there’s a difference between all the answers, a two-sample test on the averages, and most meaningfully, summing up the responses as a single pair of numbers and doing a binomial test:
More photos from this reportage are featured in Quartz’s new book The Objects that Power the Global Economy. You may not have seen these objects before, but they’ve already changed the way you live. Each chapter examines an object that is driving radical change in the global economy. This is from the chapter on the drug modafinil, which explores modifying the mind for a more productive life. 

This continued up to 1 AM, at which point I decided not to take a second armodafinil (why spend a second pill to gain what would likely be an unproductive set of 8 hours?) and finish up the experiment with some n-backing. My 5 rounds: 60/38/62/44/5024. This was surprising. Compare those scores with scores from several previous days: 39/42/44/40/20/28/36. I had estimated before the n-backing that my scores would be in the low-end of my usual performance (20-30%) since I had not slept for the past 41 hours, and instead, the lowest score was 38%. If one did not know the context, one might think I had discovered a good nootropic! Interesting evidence that armodafinil preserves at least one kind of mental performance.
Reason: More than 50 percent of your brain is comprised of DHA! Among a big group of elderly Americans, those with the highest blood levels of DHA were about half as apt to develop dementia and 39% as apt to develop Alzheimer’s as those with lower blood levels of DHA over a nine-year period. The top 25% of those with the highest blood DHA got about 180 mg DHA a day or three servings of fish a week, researchers said. In this study, the other major fatty acid in fish oil. EPA had no effect.
Another traditional Chinese brain booster is Danggui-Shaoyao-San (DSS). It has been suggested that DSS has potent beneficial angiogenesis and neurogenesis effects that may make it a potential treatment for ischemic stroke therapy. DSS is also known to beneficially impact free radical-mediated neurological diseases, exhibit anti-inflammatory and antioxidant activities and reduce cell death in the hippocampus, thereby promoting greater emotional, memory-related and autonomic nervous system function. Currently, there is limited research on proper dosage, but you can learn more about DSS in this fantastic summary article on it’s interplay with Alzheimer’s.
Seriously. Every single thing you experience comes through your brain. It create the fabric of your reality, and by the same token, the energy your brain makes is what allows you to shape that reality. Work, relationships, success, happiness — everything depends on your brain, and building a stronger one will trigger upgrades that extend across every aspect of your life.
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."
I do recommend a few things, like modafinil or melatonin, to many adults, albeit with misgivings about any attempt to generalize like that. (It’s also often a good idea to get powders, see the appendix.) Some of those people are helped; some have told me that they tried and the suggestion did little or nothing. I view nootropics as akin to a biological lottery; one good discovery pays for all. I forge on in the hopes of further striking gold in my particular biology. Your mileage will vary. All you have to do, all you can do is to just try it. Most of my experiences were in my 20s as a right-handed 5’11 white male weighing 190-220lbs, fitness varying over time from not-so-fit to fairly fit. In rough order of personal effectiveness weighted by costs+side-effects, I rank them as follows:
The power calculation indicates a 20% chance of getting useful information. My quasi-experiment has <70% chance of being right, and I preserve a general skepticism about any experiment, even one as well done as the medical student one seems to be, and give that one a <80% chance of being right; so let’s call it 70% the effect exists, or 30% it doesn’t exist (which is the case in which I save money by dropping fish oil for 10 years).
“Over the years, I have learned so much from the work of Dr. Mosconi, whose accomplished credentials spanning both neuroscience and nutrition are wholly unique. This book represents the first time her studies on the interaction between food and long-term cognitive function reach a general audience. Dr. Mosconi always makes the point that we would eat differently and treat our brains better if only we could see what we are doing to them. From the lab to the kitchen, this is extremely valuable and urgent advice, complete with recommendations that any one of us can take.”
A third of participants in clinical trials on Modafinil have reported crippling headaches.  An additional 11% experienced nausea, while others reported an array of other side-effects ranging from nervousness to diarrhea.  Dizziness and insomnia may also result from Modafinil use.   I can attest that the side effects are very real.  In fact, I had to stop using Modafinil after 2 days when my headaches became so intense I ended up at the ER.
Recently I spoke on the phone with Barbara Sahakian, a clinical neuropsychologist at Cambridge University and the co-author of a 2007 article in Nature entitled "Professor's Little Helper". Sahakian, who also consults for several pharmaceutical companies, and her co-author, Sharon Morein-Zamir, reported that a number of their colleagues were using prescription drugs like Adderall and Provigil. Because the drugs are easy to buy online, they wrote, it would be difficult to stop their spread: "The drive for self-enhancement of cognition is likely to be as strong if not stronger than in the realms of 'enhancement' of beauty and sexual function." (In places like Cambridge, at least.)
When comparing supplements, consider products with a score above 90% to get the greatest benefit from smart pills to improve memory. Additionally, we consider the reviews that users send to us when scoring supplements, so you can determine how well products work for others and use this information to make an informed decision. Every month, our editor puts her name on that month’s best smart bill, in terms of results and value offered to users.

But Baldino may have been overly modest. In 2002, researchers at Cambridge University gave 60 healthy young male volunteers a battery of standard cognitive tests. One group received modafinil, the other a placebo. The modafinil group performed better on several tasks, such as the "digit span" test, in which subjects are asked to repeat increasingly longer strings of numbers forwards, then backwards. They also did better in recognising repeated visual patterns and at a spatial-planning challenge known as the Tower of London task. (It's not nearly as fun as it sounds.) Writing in the journal Psychopharmacology, the study's authors said the results suggested that "modafinil offers significant potential as a cognitive enhancer".

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.


Coconut oil was recommended by Pontus Granström on the Dual N-Back mailing list for boosting energy & mental clarity. It is fairly cheap (~$13 for 30 ounces) and tastes surprisingly good; it has a very bad reputation in some parts, but seems to be in the middle of a rehabilitation. Seth Robert’s Buttermind experiment found no mental benefits to coconut oil (and benefits to eating butter), but I wonder.
With this experiment, I broke from the previous methodology, taking the remaining and final half Nuvigil at midnight. I am behind on work and could use a full night to catch up. By 8 AM, I am as usual impressed by the Nuvigil - with Modalert or something, I generally start to feel down by mid-morning, but with Nuvigil, I feel pretty much as I did at 1 AM. Sleep: 9:51/9:15/8:27

Why? Just think for a moment how much visual, auditory, and sensory information you’re exposed to and required to process every day.  From constant background sounds to big city noise pollution, the phone ringing, artificial lighting, chemical-laden air fresheners circulating smells of fresh linen, electromagnetic fields piercing through your brain, the new procedure you have to learn at work, and a host of other sensory stimuli, the human brain has to organize and deal with this information all while keeping you upright and going. Although the brain has incredible skills and unimaginable capabilities, modern living creates unprecedented stress and sensory overload from all of the information that must be processed every single day.  Sensory overload has even been shown to cause irritability, anxiety, mood swings, depression, ADHD, fibromyalgia, PTSD and chronic fatigue syndrome. The ability of your brain to continue learning, processing, and forming new neural connections is key to maintaining optimal brain health and longevity.

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.


Reason: More than 50 percent of your brain is comprised of DHA! Among a big group of elderly Americans, those with the highest blood levels of DHA were about half as apt to develop dementia and 39% as apt to develop Alzheimer’s as those with lower blood levels of DHA over a nine-year period. The top 25% of those with the highest blood DHA got about 180 mg DHA a day or three servings of fish a week, researchers said. In this study, the other major fatty acid in fish oil. EPA had no effect.

The task of building a better mousetrap just got a lot harder. Scientists at Princeton University recently created a strain of smarter mice by inserting a gene that boosts the activity of brain cells. The mice can learn to navigate mazes and find or recognize objects faster than run-of-the-mill rodents. The news, announced in the Sept. 2, 1999 issue of the journal Nature, raises the possibility that genetic engineers may someday be able to help humans learn and remember faster, too.
[…] The 7 Best Brain Boosting Supplements | Live in the Now … – Indeed the right type of brain food can help our brains overcome any potential damaging … Know about the Foods and Supplements for Good Brain Health | Health Way … […] medicines, dietary supplements and organic food products. Justin has also been writing on best brain supplements for … […]
Another factor to consider is whether the nootropic is natural or synthetic. Natural nootropics generally have effects which are a bit more subtle, while synthetic nootropics can have more pronounced effects. It’s also important to note that there are natural and synthetic nootropics. Some natural nootropics include Ginkgo biloba and ginseng. One benefit to using natural nootropics is they boost brain function and support brain health. They do this by increasing blood flow and oxygen delivery to the arteries and veins in the brain.
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