If you are a slow caffeine metabolizer and consume too much caffeine, you run the risk of mild to severe complications, such as cardiovascular disease. There’s also the sleep disruption problem of having too much caffeine left in your bloodstream late in the day as a result of a longer caffeine half-life, a problem not faced by fast caffeine metabolizers (it’s so unfair if you love your cup of joe, right?). In addition, fast caffeine metabolizers actually run a reduced risk of cardiovascular complications if they consume at least one cup of coffee per day. While anyone can be a slow caffeine metabolizer, there are certain ethnic backgrounds that are indeed associated with slower and faster caffeine metabolisms. For example, it’s known that people with Asian and African ethnic backgrounds generally have slower rates of caffeine metabolism. To find out if you’re a fast or slow caffeine metabolizer, you can have a relatively inexpensive salivary genetic test performed by a company like 23andme and then use the online dashboard to jump straight to your CYP1A2 gene. When you’re there, you type into the search bar “rs762551”. If your rs762551 SNP variant is AA, then you’re a fast caffeine metabolizer, but if your variant is AC or CC, you’re a slow caffeine metabolizer. Fortunately, many genetic testing companies will now simply report directly on your results whether you’re a slow or fast metabolizer, without you needing to go through the SNP searching trouble.


B vitamins are also sold with claims of enhancing memory, usually rationalized by their reduction of homocysteine, a chemical in the blood that may affect circulation in the brain. No benefits from B vitamin intake have been demonstrated when it comes to memory or cognitive function except in the case of people who have high homocysteine levels due to a diet that is very low in B vitamins. There is some concern that folic acid, one of the B vitamins, may spur the growth of polyps in the colon at doses greater than 800 micrograms a day. Phosphatidyl serine is a natural component of nerve cell membranes and its promoters argue that a deficiency leads to impaired communication between nerve cells which in turn impairs cognitive function. Sounds reasonable, except that proper controlled trials have come up empty. The same goes for vinpocetine, a compound originally isolated from the lesser periwinkle plant by Hungarian chemist Csaba Szantay in 1975. It is widely used in Europe to treat strokes and memory problems with claims of increased circulation to the brain. It does indeed increase circulation, much like ginkgo, but there is no compelling evidence for memory improvement.
But according to Professor David Weinshenker of Emory University, most people who take Provigil do not report euphoria or even a level of stimulation close to the effects of caffeine. For Weinshenker, the addiction potential of Provigil is limited, and it’s used in various treatment contexts. Provigil may be an effective medication therapy for depression, ADHD, autism and other disorders.
However, anthropology suggests that paleolithic diets were dependent of where people lived. Close to shores, they ate more fish; within the forest they ate plants; in areas with herbivores they ate more meat. Also, humans ate grains millions of years before the agricultural revolution. And, we can digest those just fine because of an enzyme earmarked to digest grains (amylase). So, paleolithic diets were as varied as they are today.
This supplement is dangerous and should not be sold. I have taken brain supplements for a while and each of them are very similar, EXCEPT for Addium. On the day I took Addium many blood vessels in my hands burst, and two on my face burst. With their "proprietary blend" not being detailed as to the amount of each ingredient (only listed in the aggregate of 500mg Proprietary Blend) you have no way of determining which ingredient may or may not be too much. I can only recommend to stay away from this supplement.
Between midnight and 1:36 AM, I do four rounds of n-back: 50/39/30/55%. I then take 1/4th of the pill and have some tea. At roughly 1:30 AM, AngryParsley linked a SF anthology/novel, Fine Structure, which sucked me in for the next 3-4 hours until I finally finished the whole thing. At 5:20 AM, circumstances forced me to go to bed, still having only taken 1/4th of the pill and that determines this particular experiment of sleep; I quickly do some n-back: 29/20/20/54/42. I fall asleep in 13 minutes and sleep for 2:48, for a ZQ of 28 (a full night being ~100). I did not notice anything from that possible modafinil+caffeine interaction. Subjectively upon awakening: I don’t feel great, but I don’t feel like 2-3 hours of sleep either. N-back at 10 AM after breakfast: 25/54/44/38/33. These are not very impressive, but seem normal despite taking the last armodafinil ~9 hours ago; perhaps the 3 hours were enough. Later that day, at 11:30 PM (just before bed): 26/56/47.
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It’s not clear that there is much of an effect at all. This makes it hard to design a self-experiment - how big an effect on, say, dual n-back should I be expecting? Do I need an arduous long trial or an easy short one? This would principally determine the value of information too; chocolate seems like a net benefit even if it does not affect the mind, but it’s also fairly costly, especially if one likes (as I do) dark chocolate. Given the mixed research, I don’t think cocoa powder is worth investigating further as a nootropic.
If I assume that the coefficient of +1.22 for as.logical(Magnesium.citrate)TRUE’s effect on MP in the previous analysis represents the true causal effect of 0.156g elemental magnesium without any overdose involved and that magnesium would have a linear increase (up until overdose), then one might argue that optimistically 0.078 would cause an increase of ~0.61. Or one could eyeball the graph and note that the LOESS lines look like at the magnesium peak improved by <+0.5 over the long-run baseline of ~3 Then one could do a power estimate with those 2 estimates.
Fitzgerald 2012 and the general absence of successful experiments suggests not, as does the general historic failure of scores of IQ-related interventions in healthy young adults. Of the 10 studies listed in the original section dealing with iodine in children or adults, only 2 show any benefit; in lieu of a meta-analysis, a rule of thumb would be 20%, but both those studies used a package of dozens of nutrients - and not just iodine - so if the responsible substance were randomly picked, that suggests we ought to give it a chance of 20% \times \frac{1}{\text{dozens}} of being iodine! I may be unduly optimistic if I give this as much as 10%.
Of course, before wrapping up this section on psychedelics, I’ll address the topics of where to actually buy the stuff. There are a variety of websites that sell psychedelics, but not all ingredient, chemical or quality sourcing is created equal, nor is there any guarantee that any substance you are purchasing is not laced with undesirable compounds. Heck, I get my psilocybin from a farmer in Wisconsin who is a personal friend, and other ingredients from close acquaintances who have their own sources. I know it may seem unfair, but sometimes sourcing comes down to “who ya know” and doing your own due diligence on that person’s source.
1 PM; overall this was a pretty productive day, but I can’t say it was very productive. I would almost say even odds, but for some reason I feel a little more inclined towards modafinil. Say 55%. That night’s sleep was vile: the Zeo says it took me 40 minutes to fall asleep, I only slept 7:37 total, and I woke up 7 times. I’m comfortable taking this as evidence of modafinil (half-life 10 hours, 1 PM to midnight is only 1 full halving), bumping my prediction to 75%. I check, and sure enough - modafinil.
Past noon, I began to feel better, but since I would be driving to errands around 4 PM, I decided to not risk it and take an hour-long nap, which went well, as did the driving. The evening was normal enough that I forgot I had stayed up the previous night, and indeed, I didn’t much feel like going to bed until past midnight. I then slept well, the Zeo giving me a 108 ZQ (not an all-time record, but still unusual).
For example, a study published in the journal Psychopharmacology in 2000 found that ginkgo improved attention. A 2001 study in the journal Human Psychopharmacology suggested that it improves memory. Nevertheless, in a review of studies on ginkgo in healthy people, researchers found no good evidence that it improved mental abilities, according to a 2002 report in Psychopharmacology Bulletin.

Barbara Sahakian, a neuroscientist at Cambridge University, doesn’t dismiss the possibility of nootropics to enhance cognitive function in healthy people. She would like to see society think about what might be considered acceptable use and where it draws the line – for example, young people whose brains are still developing. But she also points out a big problem: long-term safety studies in healthy people have never been done. Most efficacy studies have only been short-term. “Proving safety and efficacy is needed,” she says.
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.
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 third category was cognitive control - how effectively you can check yourself in circumstances where the most natural response is the wrong one. A classic test is the Stroop Task, in which people are shown the name of a colour (let's say orange) written in a different colour (let's say purple). They're asked to read the word (which is easy, because our habitual response to a word is to read it) or to name the ink colour (which is harder, because our first impulse is to say "orange"). These studies presented a more mixed picture, but overall they showed some benefit "for most normal healthy subjects" - especially for people who had inherently poorer cognitive control.
As it happens, these are areas I am distinctly lacking in. When I first began reading about testosterone I had no particular reason to think it might be an issue for me, but it increasingly sounded plausible, an aunt independently suggested I might be deficient, a biological uncle turned out to be severely deficient with levels around 90 ng/dl (where the normal range for 20-49yo males is 249-839), and finally my blood test in August 2013 revealed that my actual level was 305 ng/dl; inasmuch as I was 25 and not 49, this is a tad low.
This is absolutely fantastic work - Dr. Mosconi's clear, concise prose readily breaks down the science of how we can protect our beloved brains from the horrors of dementia and keep our minds humming beautifully for years. Her mastery of the various key subjects - neurobiology, nutrition, biochemistry - is incredible and her ability to decode complex scientific findings into digestible, easy-to-use advice for the layperson is second to none. This is easily one of the best popular science books I've ever come across and by far the best read on nutrition I know of.
As discussed in my iodine essay (FDA adverse events), iodine is a powerful health intervention as it eliminates cretinism and improves average IQ by a shocking magnitude. If this effect were possible for non-fetuses in general, it would be the best nootropic ever discovered, and so I looked at it very closely. Unfortunately, after going through ~20 experiments looking for ones which intervened with iodine post-birth and took measures of cognitive function, my meta-analysis concludes that: the effect is small and driven mostly by one outlier study. Once you are born, it’s too late. But the results could be wrong, and iodine might be cheap enough to take anyway, or take for non-IQ reasons. (This possibility was further weakened for me by an August 2013 blood test of TSH which put me at 3.71 uIU/ml, comfortably within the reference range of 0.27-4.20.)
An important dietary step to avoid heavy metal toxicity is choosing seafood and fish that has reduced levels of exposure. The Seafood Watch web page is a fantastic resource that has an extensive list of fish, seafood and sushi products that are safe, as well as those that are best to stay away from. For example, choosing wild pacific caught salmon is safer than Atlantic caught salmon.
This would be a very time-consuming experiment. Any attempt to combine this with other experiments by ANOVA would probably push the end-date out by months, and one would start to be seriously concerned that changes caused by aging or environmental factors would contaminate the results. A 5-year experiment with 7-month intervals will probably eat up 5+ hours to prepare <12,000 pills (active & placebo); each switch and test of mental functioning will probably eat up another hour for 32 hours. (And what test maintains validity with no practice effects over 5 years? Dual n-back would be unusable because of improvements to WM over that period.) Add in an hour for analysis & writeup, that suggests >38 hours of work, and 38 \times 7.25 = 275.5. 12,000 pills is roughly $12.80 per thousand or $154; 120 potassium iodide pills is ~$9, so \frac{365.25}{120} \times 9 \times 5 = 137.
The use of cognition-enhancing drugs by healthy individuals in the absence of a medical indication spans numerous controversial issues, including the ethics and fairness of their use, concerns over adverse effects, and the diversion of prescription drugs for nonmedical uses, among others.[1][2] Nonetheless, the international sales of cognition-enhancing supplements exceeded US$1 billion in 2015 when global demand for these compounds grew.[3]
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