The powder totals 227g of magnesium citrate, hence there is ~0.945g per magnesium citrate pill. The nutritional information states that it contains 119 servings of 0.315g magnesium elemental = 37.485g elemental, as expected, and so likewise there is 0.156g elemental magnesium per pill. This is the same dosage as the second half of the first magnesium citrate experiment (249 gel capsules there, 240 here), where the overdose effect seemed to also happen; so to avoid the overdosage, I will take one pill every other day to halve the dose to an average of ~0.078g/78mg elemental per day (piggybacking on the morning-caffeine experiment to make compliance easier).
The above are all reasons to expect that even if I do excellent single-subject design self-experiments, there will still be the old problem of internal validity versus external validity: an experiment may be wrong or erroneous or unlucky in some way (lack of internal validity) or be right but not matter to anyone else (lack of external validity). For example, alcohol makes me sad & depressed; I could run the perfect blind randomized experiment for hundreds of trials and be extremely sure that alcohol makes me less happy, but would that prove that alcohol makes everyone sad or unhappy? Of course not, and as far as I know, for a lot of people alcohol has the opposite effect. So my hypothetical alcohol experiment might have tremendous internal validity (it does prove that I am sadder after inebriating), and zero external validity (someone who has never tried alcohol learns nothing about whether they will be depressed after imbibing). Keep this in mind if you are minded to take the experiments too seriously.
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.
We can read off the results from the table or graph: the nicotine days average 1.1% higher, for an effect size of 0.24; however, the 95% credible interval (equivalent of confidence interval) goes all the way from 0.93 to -0.44, so we cannot exclude 0 effect and certainly not claim confidence the effect size must be >0.1. Specifically, the analysis gives a 66% chance that the effect size is >0.1. (One might wonder if any increase is due purely to a training effect - getting better at DNB. Probably not26.)
Another prescription stimulant medication, modafinil (known by the brand name Provigil), is usually prescribed to patients suffering from narcolepsy and shift-work sleep disorder, but it might turn out to have broader applications. “We have conducted at the University of Cambridge double-blind, placebo-controlled studies in healthy people using modafinil and have found improvements in cognition, including in working memory,” Sahakian says. However, she doesn’t think everyone should start using the drug off-label. “There are no long-term safety and efficacy studies of modafinil in healthy people, and so it is unclear what the risks might be.”
At this point I began to get bored with it and the lack of apparent effects, so I began a pilot trial: I’d use the LED set for 10 minutes every few days before 2PM, record, and in a few months look for a correlation with my daily self-ratings of mood/productivity (for 2.5 years I’ve asked myself at the end of each day whether I did more, the usual, or less work done that day than average, so 2=below-average, 3=average, 4=above-average; it’s ad hoc, but in some factor analyses I’ve been playing with, it seems to load on a lot of other variables I’ve measured, so I think it’s meaningful).
So, I have started a randomized experiment; should take 2 months, given the size of the correlation. If that turns out to be successful too, I’ll have to look into methods of blinding - for example, some sort of electronic doohickey which turns on randomly half the time and which records whether it’s on somewhere one can’t see. (Then for the experiment, one hooks up the LED, turns the doohickey on, and applies directly to forehead, checking the next morning to see whether it was really on or off).
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.
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Since the discovery of the effect of nootropics on memory and focus, the number of products on the market has increased exponentially. The ingredients used in a supplement can tell you about the effectiveness of the product. Brain enhancement pills that produce the greatest benefit are formulated with natural vitamins and substances, rather than caffeine and synthetic ingredients. In addition to better results, natural supplements are less likely to produce side effects, compared with drugs formulated with chemical ingredients.
When Giurgea coined the word nootropic (combining the Greek words for mind and bending) in the 1970s, he was focused on a drug he had synthesized called piracetam. Although it is approved in many countries, it isn’t categorized as a prescription drug in the United States. That means it can be purchased online, along with a number of newer formulations in the same drug family (including aniracetam, phenylpiracetam, and oxiracetam). Some studies have shown beneficial effects, including one in the 1990s that indicated possible improvement in the hippocampal membranes in Alzheimer’s patients. But long-term studies haven’t yet borne out the hype.
Amongst the brain focus supplements that are currently available in the nootropic drug market, Modafinil is probably the most common focus drug used by people, and it’s actually touted to be the best nootropic available today. It is a powerful cognitive enhancer that is great for boosting your overall alertness with least side effects. However, to get your hands on this drug, you require a prescription.
Nootropics can also show signs of neuro-preservation and neuro-protection. These compounds directly affect the levels of brain chemicals associated with slowing down the aging process. Some nootropics could in an increase in the production of Nerve Growth Factor and Brain-Derived Neurotrophic Factor to stimulate the growth of neurons and neurites while slowing down the rate of damage as well.
Lisa Mosconi has a web and media presence and a book Brain Food: The Surprising Science of Eating for Cognitive Power. She claims, “There is increasing evidence that implementing the lifestyle changes described in this book has the potential to prevent Alzheimer’s from developing and also to help slow down or even halt progression of the disease.” What’s more, “eating for your brain…actually helps you achieve peak performance in every part of your life.”
Ngo has experimented with piracetam himself (“The first time I tried it, I thought, ‘Wow, this is pretty strong for a supplement.’ I had a little bit of reflux, heartburn, but in general it was a cognitive enhancer. . . . I found it helpful”) and the neurotransmitter DMEA (“You have an idea, it helps you finish the thought. It’s for when people have difficulty finishing that last connection in the brain”).
Artichoke + Forskolin: There is plenty of evidence that suggests artichoke extract supplements (made from the leaves of artichokes) offer strong neural antioxidant properties. Additionally, Forskolin (Coleus forskohlii) is one of the few studied compounds known to naturally boost cAMP (Cyclic Adenosine Monophosphate) in your brain and is also important for neural signaling within brain cells (291m 292). I’ve experienced noticeably enhanced memory and word recall when consuming this combo. Tim Ferriss talked about this one a bit in my podcast with him, particularly referencing its presence in the somewhat popular cognition supplement “CILTEP”. Made primarily from artichoke extracts and forskolin, CILTEP is a stack that also contains vitamin B6, L-phenylalanine and acetyl-L-carnitine. It is recommended to take two to three capsules at the beginning of each day and to skip dosage one or two days per week to achieve optimal results.
Like caffeine, nicotine tolerates rapidly and addiction can develop, after which the apparent performance boosts may only represent a return to baseline after withdrawal; so nicotine as a stimulant should be used judiciously, perhaps roughly as frequent as modafinil. Another problem is that nicotine has a half-life of merely 1-2 hours, making regular dosing a requirement. There is also some elevated heart-rate/blood-pressure often associated with nicotine, which may be a concern. (Possible alternatives to nicotine include cytisine, 2’-methylnicotine, GTS-21, galantamine, Varenicline, WAY-317,538, EVP-6124, and Wellbutrin, but none have emerged as clearly superior.)
In addition to diet, there are many other things you can also do related to lifestyle, such as stress management through mindfulness (8) or gentle movement such as pre or post natal yoga (9), which have both shown to be incredibly helpful in encouraging mental wellbeing. If you feel you need extra support, personalised nutritional therapy can be very helpful as there can often be other drivers such as nutrient deficiencies and digestive complaints that can play a significant role in mental health and will need to be addressed in a way that is tailored to the individual.
Farah questions the idea that neuroenhancers will expand inequality. Citing the "pretty clear trend across the studies that say neuroenhancers will be less helpful for people who score above average", she said that cognitive-enhancing pills could actually become levellers if they are dispensed cheaply. A 2007 discussion paper published by the British Medical Association (BMA) also makes this point: "Selective use of neuroenhancers among those with lower intellectual capacity, or those from deprived backgrounds who do not have the benefit of additional tuition, could enhance the educational opportunities for those groups." If the idea of giving a pill as a substitute for better teaching seems repellent - like substituting an IV drip of synthetic nutrition for actual food - it may be preferable to a scenario in which only wealthy kids receive a frequent mental boost.
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.
l-theanine (Examine.com) is occasionally mentioned on Reddit or Imminst or LessWrong33 but is rarely a top-level post or article; this is probably because theanine was discovered a very long time ago (>61 years ago), and it’s a pretty straightforward substance. It’s a weak relaxant/anxiolytic (Google Scholar) which is possibly responsible for a few of the health benefits of tea, and which works synergistically with caffeine (and is probably why caffeine delivered through coffee feels different from the same amount consumed in tea - in one study, separate caffeine and theanine were a mixed bag, but the combination beat placebo on all measurements). The half-life in humans seems to be pretty short, with van der Pijl 2010 putting it ~60 minutes. This suggests to me that regular tea consumption over a day is best, or at least that one should lower caffeine use - combining caffeine and theanine into a single-dose pill has the problem of caffeine’s half-life being much longer so the caffeine will be acting after the theanine has been largely eliminated. The problem with getting it via tea is that teas can vary widely in their theanine levels and the variations don’t seem to be consistent either, nor is it clear how to estimate them. (If you take a large dose in theanine like 400mg in water, you can taste the sweetness, but it’s subtle enough I doubt anyone can actually distinguish the theanine levels of tea; incidentally, r-theanine - the useless racemic other version - anecdotally tastes weaker and less sweet than l-theanine.)
Power times prior times benefit minus cost of experimentation: (0.20 \times 0.30 \times 540) - 41 = -9. So the VoI is negative: because my default is that fish oil works and I am taking it, weak information that it doesn’t work isn’t enough. If the power calculation were giving us 40% reliable information, then the chance of learning I should drop fish oil is improved enough to make the experiment worthwhile (going from 20% to 40% switches the value from -$9 to +$23.8).
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).
Of course, as you can probably imagine, the antioxidant content of coffee (which you’ll learn how to maximize below) may not be the only smoking savior here. And no, it’s not the tobacco and nasty chemicals in a cigarette that’s working the magic: as other studies have gone on to prove, it’s the nicotine folks – and the nicotine is pretty powerful stuff, not only enhancing locomotor and cognitive performance when combined with coffee but also ramping up exercise performance by 18-21% all on its own!
There are many books about nutrition and cognitive functions. The authors ground their nutrition protocol on what humans ate during the paleolithic era. Often these authors contradict each other. For some, we were better hunters than gatherers so we ate mostly meat. For others, we were better gatherers and ate primarily nuts, plants, fruits. Others advance our digestive system can’t tolerate grains because it was a modern invention of the first agricultural revolution (about 10,000 years ago).
Some suggested that the lithium would turn me into a zombie, recalling the complaints of psychiatric patients. But at 5mg elemental lithium x 200 pills, I’d have to eat 20 to get up to a single clinical dose (a psychiatric dose might be 500mg of lithium carbonate, which translates to ~100mg elemental), so I’m not worried about overdosing. To test this, I took on day 1 & 2 no less than 4 pills/20mg as an attack dose; I didn’t notice any large change in emotional affect or energy levels. And it may’ve helped my motivation (though I am also trying out the tyrosine).
Traditional Chinese medicine also has a long, well-established relationship with nootropic herbs and plants. One of the most popular and well-known is ginkgo biloba, derived from the Chinese maidenhair tree, a relic of the ancient world. The maidenhair tree is the last living species of the division Ginkgophyta>. Some believe that the name ginkgo is a misspelling of the original Japanese gin kyo, meaning “silver apricot”. It’s seen as a symbol of longevity and vitality and is known to be effective at stimulating the growth of new neurons. Researchers have demonstrated that ginkgo flavonoids, the main constituents in ginkgo extract, provide potent anti-Alzheimer’s effects via antioxidant activity in the brains of mice and also stabilize and improve the cognitive performance of Alzheimer patients for 6 months to 1 year. Effective doses range from 120 to 240 mg one to four hours before performance, and for older adults, doses range from 40 to 120 mg three times a day.
Methylphenidate – a benzylpiperidine that had cognitive effects (e.g., working memory, episodic memory, and inhibitory control, aspects of attention, and planning latency) in healthy people. It also may improve task saliency and performance on tedious tasks. At above optimal doses, methylphenidate had off–target effects that decreased learning.