If you’re a coffee or tea drinker, keep sipping: Caffeine may help protect against age-related cognitive decline. “Studies have indicated that caffeine—for example, roughly 500 milligrams daily, the equivalent of about five cups of coffee—may help stave off memory issues in humans,” says Bruce Citron, PhD, a neuroscientist at Bay Pines VA Healthcare System and the USF Morsani College of Medicine in Florida. (Experts warn against taking caffeine supplements, which flood your body with a lot of caffeine all at once.)
Looking at the prices, the overwhelming expense is for modafinil. It’s a powerful stimulant - possibly the single most effective ingredient in the list - but dang expensive. Worse, there’s anecdotal evidence that one can develop tolerance to modafinil, so we might be wasting a great deal of money on it. (And for me, modafinil isn’t even very useful in the daytime: I can’t even notice it.) If we drop it, the cost drops by a full $800 from $1761 to $961 (almost halving) and to $0.96 per day. A remarkable difference, and if one were genetically insensitive to modafinil, one would definitely want to remove it.
Noopept is a Russian stimulant sometimes suggested for nootropics use as it may be more effective than piracetam or other -racetams, and its smaller doses make it more convenient & possibly safer. Following up on a pilot study, I ran a well-powered blind randomized self-experiment between September 2013 and August 2014 using doses of 12-60mg Noopept & pairs of 3-day blocks to investigate the impact of Noopept on self-ratings of daily functioning in addition to my existing supplementation regimen involving small-to-moderate doses of piracetam. A linear regression, which included other concurrent experiments as covariates & used multiple imputation for missing data, indicates a small benefit to the lower dose levels and harm from the highest 60mg dose level, but no dose nor Noopept as a whole was statistically-significant. It seems Noopept’s effects are too subtle to easily notice if they exist, but if one uses it, one should probably avoid 60mg+.

I have elsewhere remarked on the apparent lack of benefit to taking multivitamins and the possible harm; so one might well wonder about a specific vitamin like vitamin D. However, a multivitamin is not vitamin D, so it’s no surprise that they might do different things. If a multivitamin had no vitamin D in it, or if it had vitamin D in different doses, or if it had substances which interacted with vitamin D (such as calcium), or if it had substances which had negative effects which outweigh the positive (such as vitamin A?), we could well expect differing results. In this case, all of those are true to varying extents. Some multivitamins I’ve had contained no vitamin D. The last multivitamin I was taking both contains vitamins used in the negative trials and also some calcium; the listed vitamin D dosage was a trivial ~400IU, while I take >10x as much now (5000IU).


Choline is a nootropic: it enhances your ability to pay attention and learn efficiently,[18] probably because you use a lot of acetylcholine during mentally-demanding tasks, and choline helps you synthesize enough to work harder and go longer.[19] Choline also links to decreased brain inflammation in a dose-dependent manner — the more choline you eat, the less inflamed your brain tends to be.[20]

Is lifestyle truly important, though? According to Dr. Lisa, "genes load the gun, but lifestyle pulls the trigger." As someone who grew up very aware of my genetic predisposition (diabetes, cardiovascular diseases, breast cancer — you name it and someone in my family has it), I always thought that this weighed heavily on whether or not someone manifests an illness. But, groundbreaking research on epigenetics actually states the contrary. 


Apkarian and colleagues imaged the brains of 68 participants and gave them personality tests. The researchers then randomly assigned the participants to groups that either received no treatment, sugar pills or a pain-killing drug. Those given pills were not told if they received a placebo or an active drug. Participants took the treatment for two weeks, stopped for one week and then repeated this cycle.
…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.
Dark chocolate. Let's end with the good stuff. Dark chocolate has powerful antioxidant properties, contains several natural stimulants, including caffeine, which enhance focus and concentration, and stimulates the production of endorphins, which helps improve mood. One-half ounce to 1 ounce a day will provide all the benefits you need, says Kulze. This is one "superfood" where more is not better. "You have to do this one in moderation," says Kulze.
Results: Women with high caffeine intakes had significantly higher rates of bone loss at the spine than did those with low intakes (−1.90 ± 0.97% compared with 1.19 ± 1.08%; P = 0.038). When the data were analyzed according to VDR genotype and caffeine intake, women with the tt genotype had significantly (P = 0.054) higher rates of bone loss at the spine (−8.14 ± 2.62%) than did women with the TT genotype (−0.34 ± 1.42%) when their caffeine intake was >300 mg/d…In 1994, Morrison et al (22) first reported an association between vitamin D receptor gene (VDR) polymorphism and BMD of the spine and hip in adults. After this initial report, the relation between VDR polymorphism and BMD, bone turnover, and bone loss has been extensively evaluated. The results of some studies support an association between VDR polymorphism and BMD (23-,25), whereas other studies showed no evidence for this association (26,27)…At baseline, no significant differences existed in serum parathyroid hormone, serum 25-hydroxyvitamin D, serum osteocalcin, and urinary N-telopeptide between the low- and high-caffeine groups (Table 1⇑). In the longitudinal study, the percentage of change in serum parathyroid hormone concentrations was significantly lower in the high-caffeine group than in the low-caffeine group (Table 2⇑). However, no significant differences existed in the percentage of change in serum 25-hydroxyvitamin D
Zack and Casey Lynch are a young couple who, in 2005, launched NeuroInsights, a company that advises investors on developments in brain-science technology. (Since then, they've also founded a lobbying group, the Neurotechnology Industry Organization.) Casey and Zack met as undergraduates at UCLA; she went on to get a master's in neuroscience and he became an executive at a software company. Last summer I had coffee with them in San Francisco and they both spoke with casual certainty about the coming market for neuroenhancers. Zack, whose book, The Neuro Revolution, was published in July, said: "We live in an information society. What's the next form of human society? The neuro-society." In coming years, he said, scientists will understand the brain better, and we'll have improved neuroenhancers that some people will use therapeutically, others because they are "on the borderline of needing them therapeutically" and others purely "for competitive advantage".
The main concern with pharmaceutical drugs is adverse effects, which also apply to nootropics with undefined effects. Long-term safety evidence is typically unavailable for nootropics.[13] Racetams — piracetam and other compounds that are structurally related to piracetam — have few serious adverse effects and low toxicity, but there is little evidence that they enhance cognition in people having no cognitive impairments.[19]
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