One should note the serious caveats here: it is a small in vitro study of a single category of human cells with an effect size that is not clear on a protein which feeds into who-knows-what pathways. It is not a result in a whole organism on any clinically meaningful endpoint, even if we take it at face-value (many results never replicate). A look at followup work citing Rapuri et al 2007 is not encouraging: Google Scholar lists no human studies of any kind, much less high-quality studies like RCTs; just some rat followups on the calcium effect. This is not to say Rapuri et al 2007 is a bad study, just that it doesn’t bear the weight people are putting on it: if you enjoy caffeine, this is close to zero evidence that you should reduce or drop caffeine consumption; if you’re taking too much caffeine, you already have plenty of reasons to reduce; if you’re drinking lots of coffee, you already have plenty of reasons to switch to tea; etc.
Maddy Heeszel is a 20-something-year-old from Central California. She is a 4.0 GPA graduate from Brandman University with a B.A. in Liberal Studies, Multiple Subjects Teaching. Maddy works full-time as a freelance writer and social media marketer. She also owns a plant nursery. In her spare time, Maddy enjoys cooking, gardening, watching prank videos on YouTube, playing video games, learning new languages, and taking pictures. She also has interests in health, psychology, and nutrition. You can connect with her on Linkedin.

Long story short, aging is your brain’s worst enemy. The same applies to all organs of our body, but the brain suffers the most. Both neurotransmitters and neurons are taking the blow too. As a result, the neuron communication is affected. Now, this may seem like the rocket science to you, but it’s enough to say, serotonin and dopamine are the most important neurotransmitters. Without these components, you can forget about good mood. Serotonin and dopamine levels drop at a rate of approximately 10% for every decade you add to your age.
I find this very troubling. The magnesium supplementation was harmful enough to do a lot of cumulative damage over the months involved (I could have done a lot of writing September 2013 - June 2014), but not so blatantly harmful enough as to be noticeable without a randomized blind self-experiment or at least systematic data collection - neither of which are common among people who would be supplementing magnesium I would much prefer it if my magnesium overdose had come with visible harm (such as waking up in the middle of the night after a nightmare soaked in sweat), since then I’d know quickly and surely, as would anyone else taking magnesium. But the harm I observed in my data? For all I know, that could be affecting every user of magnesium supplements! How would we know otherwise?
Your mileage will vary. There are so many parameters and interactions in the brain that any of them could be the bottleneck or responsible pathway, and one could fall prey to the common U-shaped dose-response curve (eg. Yerkes-Dodson law; see also Chemistry of the adaptive mind & de Jongh et al 2007) which may imply that the smartest are those who benefit least23 but ultimately they all cash out in a very few subjective assessments like energetic or motivated, with even apparently precise descriptions like working memory or verbal fluency not telling you much about what the nootropic actually did. It’s tempting to list the nootropics that worked for you and tell everyone to go use them, but that is merely generalizing from one example (and the more nootropics - or meditation styles, or self-help books, or getting things done systems - you try, the stronger the temptation is to evangelize). The best you can do is read all the testimonials and studies and use that to prioritize your list of nootropics to try. You don’t know in advance which ones will pay off and which will be wasted. You can’t know in advance. And wasted some must be; to coin a Umeshism: if all your experiments work, you’re just fooling yourself. (And the corollary - if someone else’s experiments always work, they’re not telling you everything.)
“Brain-berries” is what Steven Pratt, MD, author of SuperFoods Rx: Fourteen Foods That Will Change Your Life, calls these antioxidant-packed fruits on WebMD.com. This tiny but powerful berry helps protect the brain from oxidative stress and may reduce the effects of age-related conditions such as Alzheimer’s disease or dementia. In a recent study, researchers gave a group of adults with mild cognitive impairment, a risk condition for Alzheimer’s, freeze-dried blueberry powder daily, while another group took a placebo. After 16 weeks, those who ate the blueberry powder (the equivalent of one cup of berries) had improved memory, better cognitive performance, and increased brain activity. Your everyday habits may also reduce your risk of Alzheimer’s.

Caveats aside, if you do want to try a nootropic, consider starting with something simple and pretty much risk-free, like aromatherapy with lemon essential oil or frankincense, which can help activate your brain, Barbour says. You could also sip on "golden milk," a sweet and anti-inflammatory beverage made with turmeric, or rosemary-infused water, she adds.
Speaking of addictive substances, some people might have considered cocaine a nootropic (think: the finance industry in Wall Street in the 1980s). The incredible damage this drug can do is clear, but the plant from which it comes has been used to make people feel more energetic and less hungry, and to counteract altitude sickness in Andean South American cultures for 5,000 years, according to an opinion piece that Bolivia’s president, Evo Morales Ayma, wrote for the New York Times.
We recently held an informative event in London with Dr Gill Hart, a biochemist and expert in the field of food intolerances and their global effect on health and we wanted to share some of the highlights of what Dr Hart covered. Based on some of her recent research (1), the talk offered some interesting insights into how food intolerances may have a role to play in our mental health. It honed in on the differences between food allergies and food intolerances within our immune system; some of the ways that our immune system, gut and brain are believed to influence each other, and how food intolerances, therefore, can play a role in mental health symptoms. She also spoke about how to go about testing and managing these intolerances through elimination diet strategies.

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.
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.
Choline is very important for cognitive function because it is a precursor to Acteylcholine. Your body needs enough choline to convert into Acteylcholine to keep your brain healthy. For this reason, choline supplements are often considered great nootropics, even by themselves. CDP-Choline and Alpha GPC are the best sources for supplemental Choline.
After I ran out of creatine, I noticed the increased difficulty, and resolved to buy it again at some point; many months later, there was a Smart Powders sale so bought it in my batch order, $12 for 1000g. As before, it made Taekwondo classes a bit easier. I paid closer attention this second time around and noticed that as one would expect, it only helped with muscular fatigue and did nothing for my aerobic issues. (I hate aerobic exercise, so it’s always been a weak point.) I eventually capped it as part of a sulbutiamine-DMAE-creatine-theanine mix. This ran out 1 May 2013. In March 2014, I spent $19 for 1kg of micronized creatine monohydrate to resume creatine use and also to use it as a placebo in a honey-sleep experiment testing Seth Roberts’s claim that a few grams of honey before bedtime would improve sleep quality: my usual flour placebo being unusable because the mechanism might be through simple sugars, which flour would digest into. (I did not do the experiment: it was going to be a fair amount of messy work capping the honey and creatine, and I didn’t believe Roberts’s claims for a second - my only reason to do it would be to prove the claim wrong but he’d just ignore me and no one else cares.) I didn’t try measuring out exact doses but just put a spoonful in my tea each morning (creatine is tasteless). The 1kg lasted from 25 March to 18 September or 178 days, so ~5.6g & $0.11 per day.
Nootropics still exist largely in an unregulated gray area, which makes users somewhat hesitant to discuss their regimens. But I did speak to several people who told tales of increased productivity and sharpened focus. Bob Carter, a financial analyst for a start-up called LendingHome, says that nootropics have replaced his other morning stimulant. “I basically think of it as a substitute for coffee,” he says. “I think the problem with a cappuccino from Starbucks is that it gives you the feeling of being jittery. Whereas with this particular supplement, I feel more calm.”
I can test fish oil for mood, since the other claimed benefits like anti-schizophrenia are too hard to test. The medical student trial (Kiecolt-Glaser et al 2011) did not see changes until visit 3, after 3 weeks of supplementation. (Visit 1, 3 weeks, visit 2, supplementation started for 3 weeks, visit 3, supplementation continued 3 weeks, visit 4 etc.) There were no tests in between the test starting week 1 and starting week 3, so I can’t pin it down any further. This suggests randomizing in 2 or 3 week blocks. (For an explanation of blocking, see the footnote in the Zeo page.)

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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.).
I was contacted by the Longecity user lostfalco, and read through some of his writings on the topic. I had never heard of LLLT before, but the mitochondria mechanism didn’t sound impossible (although I wondered whether it made sense at a quantity level14151617), and there was at least some research backing it; more importantly, lostfalco had discovered that devices for LLLT could be obtained as cheap as $15. (Clearly no one will be getting rich off LLLT or affiliate revenue any time soon.) Nor could I think of any way the LLLT could be easily harmful: there were no drugs involved, physical contact was unnecessary, power output was too low to directly damage through heating, and if it had no LLLT-style effect but some sort of circadian effect through hitting photoreceptors, using it in the morning wouldn’t seem to interfere with sleep.
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).
This is why it was so refreshing to stumble across Dr. Lisa Mosconi's new book "Brain Food: The Surprising Power of Eating for Cognitive Power" . "Our brains aren't keeping up with the historical change in dietary consumptions", says Dr. Lisa. And it's quite evident in her book when she does a historical overview and draws an important relationship between what our ancestors were eating and the concept of longevity. Her contribution to the fascinating new world of "neuro-nutrition" differs drastically from the diet culture we are all so used to and can help us understand why including (and excluding) certain foods, will actually boost our brain health. 
Provigil may well confer a temporary advantage on healthy people, but this doesn't mean that it's ready to replace your morning espresso. Anjan Chatterjee told me that there "just aren't enough studies of these drugs in normal people". One study, published recently in the Journal of the American Medical Association, suggests that Provigil can be habit-forming. A group led by Nora Volkow, the director of the National Institute on Drug Abuse, scanned the brains of 10 men after they had been given a placebo, and also after they had been given a dose of modafinil. The modafinil appeared to lead to an increase in the brain chemical dopamine. "Because drugs that increase dopamine have the potential for abuse," Volkow's report concluded, "these results suggest that risk for addiction in vulnerable persons merits heightened awareness." (Cephalon, in a response to the report, notes that Provigil's label urges physicians to monitor patients closely, especially those with a history of drug abuse.) On the website Erowid, where people vividly and anonymously report their experiences with legal and illegal drugs, some modafinil users have described a dependency on the drug. One man, who identified himself as a former biochemistry student, said that he had succeeded in kicking cocaine and opiate habits but couldn't stop using modafinil. Whenever he ran out of the drug, he said, "I start to freak out." After "four to five days" without it, "the head fog starts to come back".

But there’s a surprising lack of skepticism in the room. That’s because this is a weekly meetup of amateur biohackers. In fact, positivity is one of their ground rules. Members share experiences with ketogenic diets, biofeedback apps, sensory-deprivation tanks, and, lately, a class of smart drugs known as “nootropics.” Their primary obsession is brain enhancement.
Not that everyone likes to talk about using the drugs. People don’t necessarily want to reveal how they get their edge and there is stigma around people trying to become smarter than their biology dictates, says Lawler. Another factor is undoubtedly the risks associated with ingesting substances bought on the internet and the confusing legal statuses of some. Phenylpiracetam, for example, is a prescription drug in Russia. It isn’t illegal to buy in the US, but the man-made chemical exists in a no man’s land where it is neither approved nor outlawed for human consumption, notes Lawler.

The compound has great nootropic properties that includes memory enhancement and protection against brain aging. There are studies that suggest that the compound is an effective treatment for disorders like vascular dementia, Alzheimer’s, brain stroke, anxiety and depression. However, there are some side effects associated with Alpha GPC, like headache, heartburn, dizziness, skin rashes, insomnia, and confusion.
Maca root has been used by indigenous people groups in South America for thousands of years. It’s part of the mustard family found primarily in Andean regions and some of its primary uses include improving sexual function, memory and learning as well as reducing the effects of osteoporosis. The standard effective dose ranges from 1,500 to 3,000 mg.
Qualia: Like TianChi, the nootropic blend Qualia is a “shotgun” approach, providing over forty-two different ingredients, including a host of herbal adaptogens, brain vitamins, amino acids, choline donors, anti-inflammatories and antioxidants too long to list here (you can view the full ingredient profile here). Unlike TianChi, it also contains synthetic nootropic “noopept”, which has about 1,000 times the potency of piracetam, along with a few other helpful ingredients, including curcumin and bioperine, and slightly higher amounts of caffeine. It also requires two daily dosing protocols: with the first dose taken on an empty stomach and the second with a meal (for those compounds better absorbed with food). For those who prefer to skip on the synthetic nootropic, get most of the compounds at slightly lower price point (Qualia is admittedly quite expensive at $150 for the two dosing bottles), and also get the addition of the Indian plant you learned about earlier called “Celastrus paniculatus”, there is a very similar supplement made by the same manufacturer called “Qualia Mind”.
-Raw cacao is rich in theobromine, a powerful antioxidant known to support cellular aging and reduce the risk of heart disease. Its effects are similar to those of caffeine, as they both are vasodilators and improve blood flow to the brain [except cacao won’t give you jitters]...You can use raw cacao to make cacao tea, or in your smoothies. Dark chocolate with cocoa content of 80% or higher is also rich in theobromine and natural antioxidants. Besides, chocolate makes you happy. I have a small piece of high-quality dark chocolate, like 85% or 90% dark, every day.
Paul McHugh, a psychiatrist at Johns Hopkins University, has written sceptically about cosmetic neurology. In a 2004 essay he notes that at least once a year in his private practice he sees a young person - usually a boy - whose parents worry that his school performance could be better and want a medication that will assure it. In most of these cases "the truth is that the son does not have the superior IQ of his parents", though the boy may have other qualities that surpass those of his parents - he may be "handsome, charming, athletic, graceful". McHugh sees his job as trying to get the parents to "forget about adjusting him to their aims, with medication or anything else".
(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%.
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