(If I am not deficient, then supplementation ought to have no effect.) The previous material on modern trends suggests a prior >25%, and higher than that if I were female. However, I was raised on a low-salt diet because my father has high blood pressure, and while I like seafood, I doubt I eat it more often than weekly. I suspect I am somewhat iodine-deficient, although I don’t believe as confidently as I did that I had a vitamin D deficiency. Let’s call this one 75%.
Large scale studies have shown the association between chronic low-grade inflammation and depression (8). For example, in a study that examined data from 14,275 people who were interviewed between 2007 and 2012, they found that people who had depression had 46% higher levels of C-reactive protein (CRP), a marker of inflammatory disease, in their blood samples (9). Studies like these are paving the way towards a new understanding of the pathology of mental health conditions and how diet and stress can alter bodily systems, such as digestive function and consequently impact mental wellbeing. Measuring IgG antibodies in food intolerance tests has been implicated as a popular strategy to tackle symptoms related to sensitivities such as IBS, joint pain, fatigue, migraines, anxiety and depression. A recent survey on 708 people commissioned by Allergy UK, demonstrated how 81% of those with elevated IgG levels, as well as psychological symptoms, reported an improvement in their condition after following a food-specific IgG elimination diet (9). Taking this all into account, health professionals and those with poor mental health may want to consider the potential role of food intolerances in mental well-being and in managing common mood-related disorders, such as depression and anxiety.
We hope you find our website to be a reliable and valuable resource in your search for the most effective brain enhancing supplements. In addition to product reviews, you will find information about how nootropics work to stimulate memory, focus, and increase concentration, as well as tips and techniques to help you experience the greatest benefit for your efforts.
Nor am I sure how important the results are - partway through, I haven’t noticed anything bad, at least, from taking Noopept. And any effect is going to be subtle: people seem to think that 10mg is too small for an ingested rather than sublingual dose and I should be taking twice as much, and Noopept’s claimed to be a chronic gradual sort of thing, with less of an acute effect. If the effect size is positive, regardless of statistical-significance, I’ll probably think about doing a bigger real self-experiment (more days blocked into weeks or months & 20mg dose)

The original magnesium l-threonate caused me no apparent problems by the time I finished off the powder and usage correlated with better days, further supporting the hypothesis that magnesium helps it. But l-threonate would be difficult to cap (and hence blind self-experiment) and is ruinously expensive on a per-dose basis. So I looked around for alternatives for the followup; one of the most common compounds suggested was the citrate form because it is reasonably well-absorbed and causes fewer digestive problems, so I could just take that. Magnesium oxide is widely available it looks cheap, but the absorption/bioavailability problem makes it unattractive: at a 3:5 ratio, an estimate of 4% absorption, a ZMA formulation of an impressive-sounding 500mg would be 500 \times \frac{3}{5} \times 0.04 = 12mg or a small fraction of RDAs for male adults like 400mg elemental. (Calcium shouldn’t be a problem since I get 220mg of calcium from my multivitamin and I enjoy dairy products daily.)


People charged with doing simple tasks did not exhibit much of an increase in brain function after taking Modafinil, but their performance on complex and difficult tasks after taking the drug was significantly better than those who were given a placebo. This suggests that it may affect “higher cognitive functions—mainly executive functions but also attention and learning,” explains study co-author Ruairidh Battleday.

When asked if there’s a discrepancy between Qualia’s claims and that disclaimer, Dr. Stickler points out that products such as OS aren’t promising to treat or cure any diseases. That’s the line these companies can’t cross. They can claim their product makes you smarter or more focused without data from clinical trials, but they can’t claim their pill treats traumatic brain injury, ADHD, or Alzheimer’s.
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.
Not long ago I met Anjan Chatterjee, a neurologist at the University of Pennsylvania, in his office at the labyrinthine Penn hospital complex. Chatterjee's main research interests are in subjects like the neurological basis of spatial understanding, but in the past few years, as he has heard more about students taking cognitive enhancers, he has begun writing about the ethical implications of such behaviour. In 2004 he coined the term "cosmetic neurology" to describe the practice of using drugs developed for recognised medical conditions to strengthen ordinary cognition. Chatterjee worries about cosmetic neurology, but he thinks that it will eventually become as acceptable as cosmetic surgery; in fact with neuroenhancement it's harder to argue that it's frivolous. As he notes in a 2007 paper: "Many sectors of society have winner-take-all conditions in which small advantages produce disproportionate rewards." At school and at work, the usefulness of being "smarter", needing less sleep and learning more quickly is "abundantly clear". In the near future, he predicts, some neurologists will refashion themselves as "quality-of-life consultants" whose role will be "to provide information while abrogating final responsibility for these decisions to patients". The demand is certainly there: from an ageing population that won't put up with memory loss; from overwrought parents bent on giving their children every possible edge; from anxious employees in an efficiency-obsessed, BlackBerry-equipped office culture where work never really ends.
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.
Participants (n=205) [young adults aged 18-30 years] were recruited between July 2010 and January 2011, and were randomized to receive either a daily 150 µg (0.15mg) iodine supplement or daily placebo supplement for 32 weeks…After adjusting for baseline cognitive test score, examiner, age, sex, income, and ethnicity, iodine supplementation did not significantly predict 32 week cognitive test scores for Block Design (p=0.385), Digit Span Backward (p=0.474), Matrix Reasoning (p=0.885), Symbol Search (p=0.844), Visual Puzzles (p=0.675), Coding (p=0.858), and Letter-Number Sequencing (p=0.408).
A picture is worth a thousand words, particularly in this case where there seems to be temporal effects, different trends for the conditions, and general confusion. So, I drag up 2.5 years of MP data (for context), plot all the data, color by magnesium/non-magnesium, and fit different LOESS lines to each as a sort of smoothed average (since categorical data is hard to interpret as a bunch of dots), which yields:

Ampakines bind to AMPARs to block uptake of glutamate, thereby increasing synaptic responses, and this has indeed been shown to minimize the effects of conditions such as Alzheimer’s. Ampakines are also being studied as possible treatments for schizophrenia, depression, ADHD and more. But there is a huge risk associated with ampakine consumption. They are now tightly regulated because if you exceed a safe dosage, you will begin to suffer neuronal damage from glutamate toxicity, which leads to some of the very conditions that ampakines are thought to attenuate. Ampakine consumption can also lead to a decrease in long-term synaptic depression (LTD), a process by which specific synapses (the space between neurons across which information is sent) are intentionally weakened in order to avoid a plateau in the efficiency of your synapses. In other words, it allows your neurons and their connections to continue growing in efficiency. LTD is believed to be necessary for healthy synaptic plasticity (the adaptability of synapses), memory function and motor skills. To be honest, there is debate over whether cognitive functions like motor learning are truly dependent upon LTD, but it is possible that if you were to take a higher-than-recommended dose of an ampakine, the overstimulation that would result may lead to suppressed LTD and consequently to poor memory and motor function.
Green tea is widely drunk in many cultures, especially in Asia, and is known to have potent health benefits. These benefits are attributed to its polyphenol content (particularly the flavanols and flavonols). In cell cultures and animal studies, the polyphenols have been proven to prevent neurotoxin-induced cell injury. Green tea also has anti-inflammatory properties and, according to a study performed on aged mice, may delay memory regression. It’s safe to drink several cups of green tea per day, though it may be more efficacious to take a green tea extract supplement to reach a daily dose of 400 to 500 mg of EGCG, one of the main active components of green tea.
There are a number of smart drugs on the market, the most well-known of which are probably Adderall and Ritalin. Both are technically known as psychostimulants, which means that they stimulate increased activity of the central nervous system: the brain and spinal cord. There are also two other common smart drugs, specifically Modafinil and a class of something called “ampakines”. You’re about to learn how each of them works and the benefits and potential risks therein.
Nicotine absorption through the stomach is variable and relatively reduced in comparison with absorption via the buccal cavity and the small intestine. Drinking, eating, and swallowing of tobacco smoke by South American Indians have frequently been reported. Tenetehara shamans reach a state of tobacco narcosis through large swallows of smoke, and Tapirape shams are said to eat smoke by forcing down large gulps of smoke only to expel it again in a rapid sequence of belches. In general, swallowing of tobacco smoke is quite frequently likened to drinking. However, although the amounts of nicotine swallowed in this way - or in the form of saturated saliva or pipe juice - may be large enough to be behaviorally significant at normal levels of gastric pH, nicotine, like other weak bases, is not significantly absorbed.

After trying out 2 6lb packs between 12 September & 25 November 2012, and 20 March & 20 August 2013, I have given up on flaxseed meal. They did not seem to go bad in the refrigerator or freezer, and tasted OK, but I had difficulty working them into my usual recipes: it doesn’t combine well with hot or cold oatmeal, and when I tried using flaxseed meal in soups I learned flaxseed is a thickener which can give soup the consistency of snot. It’s easier to use fish oil on a daily basis.


In addition to this, privilege also plays an important role in this epidemic. "Not everyone has access to eat healthily", she mentions. In fact, she recalls an anecdote in which a supermarket owner noticed how people living off food stamps rarely use them to buy fruits and vegetables. Curious about this trend, the owner approached someone with food stamps, to which she admitted she didn't buy them because she didn't know the price prior to weighing them and felt ashamed of asking. His solution? Pre-cutting and packaging fruits in order to make them more accessible to those with lower incomes. 
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Elaborating on why the psychological side effects of testosterone injection are individual dependent: Not everyone get the same amount of motivation and increased goal seeking from the steroid and most people do not experience periods of chronic avolition. Another psychological effect is a potentially drastic increase in aggression which in turn can have negative social consequences. In the case of counterfactual Wedrifid he gets a net improvement in social consequences. He has observed that aggression and anger are a prompt for increased ruthless self-interested goal seeking. Ruthless self-interested goal seeking involves actually bothering to pay attention to social politics. People like people who do social politics well. Most particularly it prevents acting on contempt which is what Wedrifid finds prompts the most hostility and resentment in others. Point is, what is a sanity promoting change in one person may not be in another.
Adaptogens are also known to participate in regulating homeostasis through helping to beneficially regulate the mechanisms of action associated with the HPA-axis (think back to the importance of proper HPA-axis function which you learned about in my last article on breathwork), including cortisol regulation and nitric oxide regulation. Through these mechanisms, they can protect against chronic inflammation, atherosclerosis, neurodegenerative cognitive impairment, metabolic disorders, cancer and other aging-related diseases. There are plenty of adaptogens with potent benefits, but the ones you learn about in this article are an excellent start to begin building or expanding your stress-adaptation toolbox.
As far as anxiety goes, psychiatrist Emily Deans has an overview of why the Kiecolt-Glaser et al 2011 study is nice; she also discusses why fish oil seems like a good idea from an evolutionary perspective. There was also a weaker earlier 2005 study also using healthy young people, which showed reduced anger/anxiety/depression plus slightly faster reactions. The anti-stress/anxiolytic may be related to the possible cardiovascular benefits (Carter et al 2013).
Tyrosine (Examine.com) is an amino acid; people on the Imminst.org forums (as well as Wikipedia) suggest that it helps with energy and coping with stress. I ordered 4oz (bought from Smart Powders) to try it out, and I began taking 1g with my usual caffeine+piracetam+choline mix. It does not dissolve easily in hot water, and is very chalky and not especially tasty. I have not noticed any particular effects from it.

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Obviously, as you can see, there are a host of benefits to the better living through science to be had through optimizing your brain with specific compounds. So, putting aside the intriguing topic of psychedelics for the moment (yes, yes, I know you probably want to know how to microdose with LSD or psilocybin), what’s the difference between a smart drug and a nootropic, and how do you choose which to take? You’re about to find out.

Though their product includes several vitamins including Bacopa, it seems to be missing the remaining four of the essential ingredients: DHA Omega 3, Huperzine A, Phosphatidylserine and N-Acetyl L-Tyrosine. It missed too many of our key criteria and so we could not endorse this product of theirs. Simply, if you don’t mind an insufficient amount of essential ingredients for improved brain and memory function and an inclusion of unwanted ingredients – then this could be a good fit for you.

"Herbs will have several different compounds in them, as opposed to, let's say, a drug like amphetamine, which is basically one compound, one molecule," Sahelian says. "Herbs will have a set of several or several dozen compounds in them. It's difficult to pinpoint which one of them is the most active or whether it's the combination of many of them that are producing the result."
The effects of piracetam on healthy volunteers have been studied even less than those of Adderall or modafinil. Most peer-reviewed studies focus on its effects on dementia or on people who have suffered a seizure or a concussion. Many of the studies that look at other neurological effects were performed on rats and mice. Piracetam's mechanisms of action are not understood, though it may increase levels of the neurotransmitter acetylcholine. In 2008 a committee of the British Academy of Medical Sciences noted that many of the clinical trials of piracetam for dementia were methodologically flawed. Another published review of the available studies of the drug concluded that the evidence "does not support the use of piracetam in the treatment of people with dementia or cognitive impairment", but suggested that further investigation might be warranted. I asked Seltzer if he thought he should wait for scientific ratification of piracetam. He laughed. "I don't want to," he said. "Because it's working."
Adderall is composed of a mixture of amphetamine salts – chemical compounds that have numerous potentially positive effects, including increased concentration, awareness and alertness. Amphetamines work, in part, by causing the release of dopamine, a neurotransmitter associated with pleasurable activities like eating. However, an amphetamine-induced release of dopamine occurs automatically – no pleasurable activity needs to occur – but a come-down feeling will likely be experienced eventually, which is associated with feelings of lethargy and mental dullness. Due to this side effect, Adderall cannot be said to be a nootropic.[12]

Encouraged by TruBrain’s magnesium & my magnesium l-threonate use, I design and run a blind random self-experiment to see whether magnesium citrate supplementation would improve my mood or productivity. I collected ~200 days of data at two dose levels. The analysis finds that the net effect was negative, but a more detailed look shows time-varying effects with a large initial benefit negated by an increasingly-negative effect. Combined with my expectations, the long half-life, and the higher-than-intended dosage, I infer that I overdosed on the magnesium. To verify this, I will be running a followup experiment with a much smaller dose.
10:30 AM; no major effect that I notice throughout the day - it’s neither good nor bad. This smells like placebo (and part of my mind is going how unlikely is it to get placebo 3 times in a row!, which is just the Gambler’s fallacy talking inasmuch as this is sampling with replacement). I give it 60% placebo; I check the next day right before taking, and it is. Man!

Piracetam (known also by the name Nootropil) is one of the best known Nootropics and makes up part of the Racetam family along with Aniracetam, Phenylpiracetam, Pramiracetam, Oxiracetam, Nefiracetam, Coluracetam and Nebracetam. These are all synthetic compounds that have been created in the lab, but there are also a number of effective herbal and natural nootropic supplements.
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.”
Of course, work pressure, post-Christmas financial constraints and time away from family and friends can make us all feel low, however, this can happen on any date depending on our own personal circumstances. Rather than taking a ‘duvet day’ to bail out of commitments on Blue Monday, as the media is suggesting, why not take a more positive stance and engage in some activities that are tried and tested tools to help support better mood? After all, as the evidence suggests, the date or day of the week is unlikely to change these worries for the majority of us. For example, doing some exercise and eating a healthy meal with good company are both scientifically proven to support our mental wellbeing. Low-intensity exercise such as walking sustained over an extended period can help release proteins called neurotrophic factors that improve brain function and support mood, and nutrients such as B12 and Omega 3, are just two of many that have been shown to improve symptoms associated to depression. Our Nutrition Solutions offers more information on nutrition for depression if you want to know more about practical actions you can take yourself through nutrition to prevent or tackle depression.
To make things more interesting, I think I would like to try randomizing different dosages as well: 12mg, 24mg, and 36mg (1-3 pills); on 5 May 2014, because I wanted to finish up the experiment earlier, I decided to add 2 larger doses of 48 & 60mg (4-5 pills) as options. Then I can include the previous pilot study as 10mg doses, and regress over dose amount.
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.
…The first time I took supplemental potassium (50% US RDA in a lot of water), it was like a brain fog lifted that I never knew I had, and I felt profoundly energized in a way that made me feel exercise was reasonable and prudent, which resulted in me and the roommate that had just supplemented potassium going for an hour long walk at 2AM. Experiences since then have not been quite so profound (which probably was so stark for me as I was likely fixing an acute deficiency), but I can still count on a moderately large amount of potassium to give me a solid, nearly side effect free performance boost for a few hours…I had been doing Bikram yoga on and off, and I think I wasn’t keeping up the practice because I wasn’t able to properly rehydrate myself.
The problems with our mental functions begin if the blood flow to the brain cells is disrupted regardless of the reasons. There are countless capillaries in the head, which supply the brain with essential nutrients and oxygen. If the blood doesn’t get to these capillaries, your optimal mental performance is compromised. Here’s a term worth remembering – hypoperfusion. If you’re suffering from hypoperfusion, then this means you are having problems with the blood flow to your brain. Here’s a quick overview of the factors that most commonly cause hypoperfusion:
The different ADHD medications like Adderall and Ritalin are classified as stimulants, and deal with these symptoms by increasing the neurotransmitters known as dopamine and norepinephrine, which are associated with pleasure, movement, and attention. They have a calming and focusing effect on people affected with ADHD, and are helpful for the inattentiveness, poor memory, impulsiveness, and mood swings experienced by those people.
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)
The AC-11 that Marcus mentioned for health is an extract from the Amazon jungle vine una de gato, and has been shown in laboratory and clinical trials to encourage DNA repair. The Mucuna pruriens he named for motivation is a legume that's a concentrated source of L-Dopa, which the body converts to the neurotransmitter dopamine. The Huperzia serrata Marcus selected for hunting is the same substance that induces lucid dreaming. This seems appropriate. While I felt the Alpha Brain helped my hunting, maybe I was dreaming. Or maybe a dream state of mind is good for hunting.
I had tried 8 randomized days like the Adderall experiment to see whether I was one of the people whom modafinil energizes during the day. (The other way to use it is to skip sleep, which is my preferred use.) I rarely use it during the day since my initial uses did not impress me subjectively. The experiment was not my best - while it was double-blind randomized, the measurements were subjective, and not a good measure of mental functioning like dual n-back (DNB) scores which I could statistically compare from day to day or against my many previous days of dual n-back scores. Between my high expectation of finding the null result, the poor experiment quality, and the minimal effect it had (eliminating an already rare use), the value of this information was very small.
Participants (n=205) [young adults aged 18-30 years] were recruited between July 2010 and January 2011, and were randomized to receive either a daily 150 µg (0.15mg) iodine supplement or daily placebo supplement for 32 weeks…After adjusting for baseline cognitive test score, examiner, age, sex, income, and ethnicity, iodine supplementation did not significantly predict 32 week cognitive test scores for Block Design (p=0.385), Digit Span Backward (p=0.474), Matrix Reasoning (p=0.885), Symbol Search (p=0.844), Visual Puzzles (p=0.675), Coding (p=0.858), and Letter-Number Sequencing (p=0.408).
In fact, when combined into a variety of different supplement “stacks” and taken in the correct dosage, these compounds – usually referred to as either smart drugs or nootropics (but now also including the category of psychedelics) – can completely change how your brain performs, including impacting receptor sites for neurotransmitters, altering levels of enzymes that break down specific neurotransmitters, changing cell membrane structures and thus controlling the movement of molecules inside and outside of the cell, increasing cerebral perfusion, which improves blood flow to the brain, affecting what are called “biogenic processes”, including neuronal cell creation or “neurogenesis”, and neuroendocrine regulation, regulating hormonal processes of the body specifically related to cognition (See additional studies here, here, here and here.).
Green tea is widely drunk in many cultures, especially in Asia, and is known to have potent health benefits. These benefits are attributed to its polyphenol content (particularly the flavanols and flavonols). In cell cultures and animal studies, the polyphenols have been proven to prevent neurotoxin-induced cell injury. Green tea also has anti-inflammatory properties and, according to a study performed on aged mice, may delay memory regression. It’s safe to drink several cups of green tea per day, though it may be more efficacious to take a green tea extract supplement to reach a daily dose of 400 to 500 mg of EGCG, one of the main active components of green tea.
If this is the case, this suggests some thoughtfulness about my use of nicotine: there are times when use of nicotine will not be helpful, but times where it will be helpful. I don’t know what makes the difference, but I can guess it relates to over-stimulation: on some nights during the experiment, I had difficult concentrating on n-backing because it was boring and I was thinking about the other things I was interested in or working on - in retrospect, I wonder if those instances were nicotine nights.
Jesper Noehr, 30, reels off the ingredients in the chemical cocktail he’s been taking every day before work for the past six months. It’s a mixture of exotic dietary supplements and research chemicals that he says gives him an edge in his job without ill effects: better memory, more clarity and focus and enhanced problem-solving abilities. “I can keep a lot of things on my mind at once,” says Noehr, who is chief technology officer for a San Francisco startup.

According to the US Food and Drug Administration, "Piracetam is not a vitamin, mineral, amino acid, herb or other botanical, or dietary substance for use by man to supplement the diet by increasing the total dietary intake. Further, piracetam is not a concentrate, metabolite, constituent, extract or combination of any such dietary ingredient. [...] Accordingly, these products are drugs, under section 201(g)(1)(C) of the Act, 21 U.S.C. § 321(g)(1)(C), because they are not foods and they are intended to affect the structure or any function of the body. Moreover, these products are new drugs as defined by section 201(p) of the Act, 21 U.S.C. § 321(p), because they are not generally recognized as safe and effective for use under the conditions prescribed, recommended, or suggested in their labeling."[33]
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