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Let me introduce myself. My name is Mark Sisson. I’m 63 years young. I live and work in Malibu, California. In a past life I was a professional marathoner and triathlete. Now my life goal is to help 100 million people get healthy. I started this blog in 2006 to empower people to take full responsibility for their own health and enjoyment of life by investigating, discussing, and critically rethinking everything we’ve assumed to be true about health and wellness...

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February 09 2016

Nootropics: Brain Enhancers, Smart Drugs, or Empty Hype?

By Mark Sisson
42 Comments

nootropics finalHang around on nootropic forums where fans and users congregate and you’ll come away with the notion that you’re missing out on a leg up if you’re not taking the latest and greatest nootropic supplement. Nootropics promise vague benefits to “cognition” and “performance,” but what’s really happening? Do nootropics actually work as advertised? Some of them do, absolutely. But others, maybe not so much.

Today’s post will deal solely with compounds, foods, and supplements available over the counter in most countries. Other supplements may have promise, like modafinil and micro-dosed psychedelics, but are unavailable through standard legal means. Plus, their potential benefits may come with some dramatic side effects. So I won’t discuss those. Not today, at least. Instead, I’ll talk about some of the more commonly referred to ways you may (or may not) be able to boost your brain power—some of which are clearly primal approved.

Bacopa monnieri

For thousands of years, Ayurvedic healers have been prescribing bacopa for improved mental health and cognition. The modern evidence suggests they were on to something. Whether you’re a senior citizen suffering from memory impairment, an older person who’s otherwise healthy, or even a young adult with no complaints, bacopa monnieri can increase your focus and working memory.

One downside is the tendency of bacopa to accumulate heavy metals. If you’re going to try bacopa, stick with a company that releases its heavy metal test results. Bacognize bacopa seems to have the lowest levels of heavy metals; Swanson’suses Bacognize in their bacopa product.

Blueberries

Yes, they’re not just delicious. They don’t just go great with yogurt. There’s decent evidence they and their extracts can improve cognitive function, particularly memory.

In older adults with the first inklings of negative changes to their memory, wild blueberry juice improved it.

In 8-10 year olds, a wild blueberry juice drink improved performance on a working memory test.

There seems to be a qualitative difference between the smaller, tarter, bluer wild blueberries and the larger, sweeter, less vibrant blueberries. The wild frozen blueberries from Trader Joe’s turn my entire mouth blue; the frozen organic blueberries from Whole Foods do not. As most of the proposed cognitive benefits come from the polyphenol content, which corresponds to the blueberry pigment, I suspect “makes your mouth turn blue” is a good barometer for nootropic action.

Choline

An entire class of nootropics are the cholinergics: compounds that increase acetylcholine in the brain. In case you’re unaware, acetylcholine acts as a neurotransmitter/neuromodulator that changes how information is processed in the brain. Many nootropics operate under the assumption that increasing available acetylcholine in the brain increases cognitive potential, memory, and performance. This makes sense, particularly if you don’t eat enough choline-rich foods (eggs, liver).

Alpha-GPC is a popular supplementary choline source. Good ol’ egg yolks should work well, too. I notice a distinct (if unscientific) boost to my cognition when I drink a Primal Egg coffee with a few yolks blended in.

Coffee

The original nootropic, coffee remains one of the best. It tastes great. It’s part of the morning ritual, which confers its own advantages (you get up, brew the coffee, and set the tenor for the rest of the day). And it’s a great cognitive enhancer for various populations, such as dialysis patients, extraverts, and infrequent consumers of caffeine.

It may be that once they’re acclimated/addicted, coffee/caffeine just brings a person up to baseline. But that does count for something, as being below baseline is unequivocally bad for performance.

Furthermore, coffee and caffeine consumption is consistently associated with lower rates of age-related cognitive decline. It’s not proven to be causal, but it probably won’t hurt.

Personally, my favorite part of drinking coffee is the burst of productive optimism it confers for an hour, hour and a half. That’s when I can start a project and make huge initial progress, think about and figure out a problem that’s been stumping me, or make headway against writer’s block. It’s also a great way to just come up with new ideas, to brainstorm. A short morning stroll while drinking my coffee is a once or twice weekly occurrence and usually produces something interesting. This quality is probably why the American revolution started in New England coffeehouses.

If coffee gives you the jitters, have some l-theanine (or green tea, the best source of it) alongside to smooth things out. L-theanine is also in Primal Calm, another good choice for better cognition if anxiety and stress are impeding you.

Creatine

Most of you don’t lack creatine in your diet. If you eat fish or meat, you’re probably obtaining it. But vegetarians and vegans and anyone else who eats very little meat obtain little to no dietary creatine. They can definitely benefit from creatine supplementation, which has been shown to improve memory in these populations. Older adult brains can also benefit. Simple, cheap, effective (and will probably boost performance in the gym, too).

Fish oil

Many evolutionary theorists think access to marine foods and marine fats helped spur the growth and complexification of the human brain. That may be why humans have historically gathered on coasts and, if living inland, traded for marine foods from coastal people. Okay, maybe we evolved on fish, but does it actually help living people with already developed brains? Turns out that it is important for in vivo cognition across various age groups.

Healthy young adults who take fish oil (750 mg DHA, 930 mg EPA) can experience improvements in working memory.

Fish oil supplementation can reduce age-related cognitive decline. Both Alzheimer’s disease and mild cognitive impairment are associated with altered DHA levels in the brain, suggesting a deficiency or misallocation. Certain genotypes may need more DHA as they age.

Extra fish oil can help kids with ADHD improve their focus and reduce negative symptoms, especially in kids with generally low fish intake and deficient baseline omega-3 levels. They’re not the typical consumers of nootropics, but maybe the most deserving!

I don’t think drinking a double shot of fish oil every morning will do much for your cognitive performance. I do think correcting a deficiency will almost certainly improve the way your brain works, though.

Nicotine

Nicotine? Sisson, have you finally gone off the deep end? No. I’m talking about pure nicotine consumed sans-smoke and tar, or having to become one of those annoying-and-still-likely-bad-for-you vapers. The actual evidence for the safety of actual nicotine relative to tobacco is quite compelling. So too is the evidence for its cognitive benefits.

Nicotine improves cognition and memory in patients with mild cognitive impairment. It improves reaction time in the short term. Nicotine actually mimics acetylcholine and activates its receptors in the brain. Some scientists are even exploring this mechanism to improve symptoms in animal models of Parkinson’s disease.

Nicotine also acutely increases adrenaline in the brain, which may be partially responsible for the cognitive enhancement. This also means that nicotine should probably be treated as an occasional nootropic, a special occasion for quick bursts of creativity and output. You don’t want chronic adrenaline release.

I’m not suggesting you try nicotine. I’m definitely not suggesting you light up. It is addictive and the research vindicating it has been abused by the tobacco industry. But set aside biases and preconceived notions and the influence of conventional wisdom for just a moment and consider that nicotine may have been unjustly maligned and discarded.

Piracetam

Piracetam may be the most well-known of the nootropics, but there’s actually very little evidence it helps healthy people with healthy brains.

Older people will probably benefit from it, however. It seems to slow cognitive decline. In one study, while piracetam was unable to improve any specific biomarkers related to cognition, clinicians asked to rate either piracetam-takers or placebo-takers on an overall “global” evaluation (how does this patient compare to other similar patients?) rated piracetam-takers more highly.

Combining it with a source of choline may improve its action, as will higher doses (4800 mg/day) versus lower doses (2400 mg/day).

Other -acetams include oxiracetam (promising animal research but no human studies yet) and aniracetam (no human studies). They have large online followings but no solid research in humans as of now.

As I alluded to earlier, there are other potential nootropics that could very well improve the way your brain works, but they’re either of questionable legal status or have yet to undergo human testing. This area will continue to grow and I suspect I’ll be revisiting this topic in the future. For now, though, these are some of the more solid and safe nootropics that you can play around with right now and expect results. Or at the very least, fish burps, a blue tongue, and coffee breath.

Thanks for reading, folks. Do you have any go-to ways to get your mind running at full speed? Feel free to share your own routines in the comments section below.

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42 thoughts on “Nootropics: Brain Enhancers, Smart Drugs, or Empty Hype?”

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  1. Interesting article. Thanks for the research, Mark. I prefer nutrients that came from nature, as opposed to supplements that came from a lab, so it’s always nice to see which foods we should be eating more often (such as blueberries). Coffee doesn’t agree with me at all, but I do find that a cup of green or black tea perks me up just as well without any of the jitters or GI tract upsets.

    1. Definitely an interesting one. I’ve tried it, and it allowed me to focus a bit more on school work. I was a beta tester for Cortex gen 1, and that stuff rocked my world.

      Also love Piracetam.

  2. The evidence for fish oil seems cherry-picked. I might have added tart cherries to this list. I dunno about nicotine. Like many other alkaloids in nightshades, it affects acetylcholine receptors. Nicotinic acetylcholine receptors anyway, the other type of acetylcholine receptor, muscarinic, was named for mushrooms that must not be mentioned here. Nicotine seems to help a lot of schizophrenics focus though. Obviously that’s not what’s going on with this comment.

  3. About blueberries painting your mouth blue. My impression is that frozen blueberries paint everything while fresh do not. Why would that be? I guessed that for freezing and preserving they need to be “prepared”, washed, treated, maybe even scrubbed. My bias would be for fresh rather than frozen.

    1. Freezing blue berries releases more juice because the ice crystals break the cell walls. So the Blue in Blueberries is up front in frozen while on the back end with fresh. I think you can’t go wrong with either. Theoretically, blue in the the mouth or the gut all goes to the same place. The caveat is are fresh blueberries really fresh or have they been altered for shelf life? Does source frozen lock in the goodness(whatever that is) or not? My solution is to use half fresh and half frozen then does it matter?

    1. Or take exogenous ketones, directly

      There is mct power, too. I understand some people who have “upset stomach,” when running, from MCT oil don’t have the issues with the powder form

  4. Paul Jaminet at The Perfect health Diet has consistently stated that commercially available fish oil is invariably oxidized during manufacture and storage to the point where it can cause more harm than good. Does anyone know of any studies to either support or refute this claim. Thanks!

    1. Ray Pit has a good piece on fish oil with references to studies. He is not a fish oil fan

  5. WildGrok simple grok
    He groks that coffee is good
    Going now to the magic place where it appears (*)
    WildGrok smart, knows to do the proper rituals for coffee to manifestate,
    no need to ask shaman

    (*) coffee maker at workplace

  6. Great, I always start the day with some cups of coffee, krill oil, and a pipe or two of tobacco. Now, if only I could remember why I do this 🙂

  7. I have been using a various mix of supps to improve cognitive function. GLA and Taurine plus turmeric with bioprene and vit D in the mornings as well as a complex vit B are my deafults. WHen I had to get out of an exam whole for cramming I also added in some Noopept with Lions mane. That worked quite well as a combo.

    I have as an experiment half a 2mg tried nicotine lozenge, I am not a smoker or have been, I had a huge boost in cognitive function and also had a increase in mood which I found interesting. I did find that it was a bit upsetting on my stomach and this lasted from about 2pm the day before until about midday the next.

    I will try a spray next as the aspartame and nicotine lozenge was a bit harsh for my liking. I will also only do this very rarely as I think your sensitivity will decrease with more usage.

    1. Heck yea. Noopept is a favorite of mine. I always feel way more into what I’m doing while using it.

      My favs are noopept, Aniracetam, and Cortex gen 1.

  8. Grow your own Bacopa, avoid the heavy metals. It is native to warmer areas of North America.

  9. By the way you left off niacinamide, the alkaline form of niacin.

  10. My husband sells PRN brand Omega 3 ever since seeing a presentation at an Optometric conference in November. With our clean paleo diet, introducing this wonderful brand of Omega 3 has rendered my dry eye & joint pains things of the past. Even though my orthopaedic surgeon says my knee’s ready for replacement, I have no knee pain while on this supplement. I no longer have to take aleve 500mg twice daily for full-body arthritis. GONE! Ask you local Optometrist if they have this supplement for sale. It’s head and shoulders better then any other Omega 3 supplement.

  11. Interesting and informative as always, thanks Mark. Aside from a primal diet I take fish oil capsules, just started drinking a couple of cups of oolong tea daily, and take a supplement that is a very concentrated extract of blueberries.

  12. Re: Bacopa monnieri

    The article Mark references on this for evidence that “young adult with no complaints, bacopa monnieri can increase your focus and working memory” actually doesn’t say this in the abstract:

    “No significant changes were found on any of the tests. The findings suggest that Bacopa monniera, at least for the dose administered, has no acute effects on cognitive functioning in normal healthy subjects”

    Re: DHA and ApoE4

    The article referenced for “certain genotypes may need more DHA as they age” doesn’t say this; it only speculates that ApoE4 “possibly, in part” affects Alzheimer’s risk through DHA homeostasis. This is basically just a reference to a speculation.

    Sorry, I know it’s easier to criticize than to create, but it’s important to check on these things…

  13. Fasting was not mentioned. After 48 hours with nothing but water your mind opens wide and asks why the F#&^%$ am I starving myself???

  14. The “nicotine may have been unjustly maligned and discarded” link leads to the article about furikake…unless you are suggesting people put tobacco leaves in their furikake, please fix the link, I am interested in reading more about it!!

  15. According to “https://examine.com/supplements/Oxiracetam/”, there is some research on oxiracetam in humans. Although it doesn’t look particularly useful for young, healthy minds like you noted for piracetam, there are a few studies indicating it could help with cognitive decline.

  16. Regarding the choline supplement you mentioned, Alpha-GPC , is it sourced from soy? I couldn’t find out from reading the bottle, but most choline supplements are. From what I understand, the soy-based choline are typically in a phospholipid form, so the general negativity associated with soy and estrogen mimicking is not an issue. My daughter has some sensory issues and choline (along with fish oil and vitamin E) supplementation seems to help, but I’ve been hard pressed to find Choline that isn’t derived from soy. If it IS soy-based, is it organic (to avoid the glyphosate/round-up contamination)? Just curious.
    FYI – My daughter’s sensory issues are ultimately what led me to MDA. One day, I’ll write a success story for you. Thanks!

  17. I prescribe Bacopa Complex occasionally with good effect (for cognitive function, memory, easing the effects of environmental stressors, and even supporting physical endurance). Like all the supplements and herbs I work with, it comes from a company that puts everything through rigorous testing.

    I also prescribe and take various cognition-boosting herbs, including a couple types of ginseng–typically combined with complementary herbs in formulas, which tend to enhance the effects (making it very different from taking a single herb or isolated compound).

    But…I find that for myself and with clients, getting a nutrient-rich diet is really the most important thing for focus and brain health…including plenty of pasture-raised eggs, coconut oil and other healthy fats, fish and other high-quality animal proteins…and, yes, blueberries:)

  18. I recently started taking supplemental lithium orotate, which I have noticed has great effects on my mood but is also supposed to have nootropic effects and actually regenerate atrophied gray matter in the brain. So maybe not just for crazies, not making any claims about myself not being crazy though. Wondering if anyone else had experience with this.

  19. Franzdude, is that you? You know im skeptical about everything but a couple drags of my morning cigarette unfogs my brain most mornings. Im trying to cut down to a completely recreational use for these cancer sticks but i think its best without. Related: Ecigs with buttery flavor are supposedly more harmful than other flavors. I cant recall the chemical that harms you but its connected to the fake butter popcorn industry. Lung failure and butter popcorn flavor. Look it up.

  20. Great article Mark, fascinating stuff.

    What’s your view on Alpha Brain from Onnit?

  21. Seems like a decent overview for those who have a bit of a basic understanding, but I want to point out that just because something is NATURAL does not mean that it is good (in the nootropics world).

    This is probably well-known, but bacopa monnieri is a great example of this you mentioned above. It isn’t that heavy metals collect in bacopa the plant, it’s that our modern mechanisms of production add this kind of thing into the products.

    Using the bacopa example, the active psychoactive ingredients are called bacosides. This particular element must be standardized and thus distilled in the products. Most cheap, short-cut oriented nootropics manufacturers will opt for methods that include ethyl acetate and a host of other ingredients (rather than ethanol or water, which is safe).

    Just wanted to bring this clearly to the attention of any reader thinking that natural is better (as many in the primal world do!)

  22. What are your thoughts on Huperzine A? I saw a study mentioned on braintropic.com in which the students taking huperzine A saw significant improvements to memory over placebo.

    1. I’m taking it right now and it’s almost scary how focused and fast my thinking is becoming (I’ve been taking it for about a week (also added Coffee Fruit, MCT oil, L-cittruline/arginine complex, phosphytidylserine, and choline/inisotal complex)… meaning I’m a little worried it may push me overboard on acetylcholine. However for now I feel more focused, quicker thinking and smarter than ever. I’m actually taking it for brain recovery (it’s been tested for that in alzheimers patients) Mine is for apnea recovery. But my baseline was so bad, it’s hard for me to tell. I may be at my ‘normal’ level of intelligence now with the help of Hup A. Long story short, it does seem to be effective. I wouldn’t take it without choline supplementation though because since it’s a acetylcholine reuptake inhibitor theoretically it could cause you to overutilze your choline reserves an leave you with a chloline deficit. Even though I’m taking a bunch of other supportive supplements (mostly nutritional except the coffee fruit which is supposed to raise BDNF, I did skip a couple days of the Hup A and I could definitely tell the difference.

      1. Note, results may vary, I may be have a dramatic reaction to it due to my brain damage from apnea.

  23. Great article! Are there any specific vitamins that can serve as natural brain supplements? Also I noticed that you only mentioned eggs and liver under choline – broccoli is another good source for any vegans who want to boost their levels!