The abuse liability of caffeine has been evaluated.147,148 Tolerance development to the subjective effects of caffeine was shown in a study in which caffeine was administered at 300 mg twice each day for 18 days.148 Tolerance to the daytime alerting effects of caffeine, as measured by the MSLT, was shown over 2 days on which 250 g of caffeine was given twice each day48 and to the sleep-disruptive effects (but not REM percentage) over 7 days of 400 mg of caffeine given 3 times each day.7 In humans, placebo-controlled caffeine-discontinuation studies have shown physical dependence on caffeine, as evidenced by a withdrawal syndrome.147 The most frequently observed withdrawal symptom is headache, but daytime sleepiness and fatigue are also often reported. The withdrawal-syndrome severity is a function of the dose and duration of prior caffeine use…At higher doses, negative effects such as dysphoria, anxiety, and nervousness are experienced. The subjective-effect profile of caffeine is similar to that of amphetamine,147 with the exception that dysphoria/anxiety is more likely to occur with higher caffeine doses than with higher amphetamine doses. Caffeine can be discriminated from placebo by the majority of participants, and correct caffeine identification increases with dose.147 Caffeine is self-administered by about 50% of normal subjects who report moderate to heavy caffeine use. In post-hoc analyses of the subjective effects reported by caffeine choosers versus nonchoosers, the choosers report positive effects and the nonchoosers report negative effects. Interestingly, choosers also report negative effects such as headache and fatigue with placebo, and this suggests that caffeine-withdrawal syndrome, secondary to placebo choice, contributes to the likelihood of caffeine self-administration. This implies that physical dependence potentiates behavioral dependence to caffeine.
We already knew that rosemary oil has a variety of benefits, but did you know that the herb does, too? Carnosic acid, one of the main ingredients in rosemary, helps protect the brain from neurodegeneration. It does this by protecting the brain against chemical free radicals, which are linked to neurodegeneration, Alzheimer’s, strokes and normal aging in the brain. (10)
Broccoli is great source of vitamin K, which is known to enhance cognitive function and improve brainpower. Researchers have reported that because broccoli is high in compounds called glucosinolates, it can slow the breakdown of the neurotransmitter, acetylcholine, which we need for the central nervous system to perform properly and to keep our brains and our memories sharp. Low levels of acetylcholine are associated with Alzheimer's.

Clinical psychiatrist Emily Deans has a private practice in Massachusetts and teaches at Harvard Medical School. She told me by phone that, in principle, there's "probably nothing dangerous" about the occasional course of nootropics for a hunting trip, finals week, or some big project. Beyond that, she suggests considering that it's possible to build up a tolerance to many neuroactive products if you use them often enough.


Running low on gum (even using it weekly or less, it still runs out), I decided to try patches. Reading through various discussions, I couldn’t find any clear verdict on what patch brands might be safer (in terms of nicotine evaporation through a cut or edge) than others, so I went with the cheapest Habitrol I could find as a first try of patches (Nicotine Transdermal System Patch, Stop Smoking Aid, 21 mg, Step 1, 14 patches) in May 2013. I am curious to what extent nicotine might improve a long time period like several hours or a whole day, compared to the shorter-acting nicotine gum which feels like it helps for an hour at most and then tapers off (which is very useful in its own right for kicking me into starting something I have been procrastinating on). I have not decided whether to try another self-experiment.
“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.
Most people I talk to about modafinil seem to use it for daytime usage; for me that has not ever worked out well, but I had nothing in particular to show against it. So, as I was capping the last of my piracetam-caffeine mix and clearing off my desk, I put the 4 remaining Modalerts pills into capsules with the last of my creatine powder and then mixed them with 4 of the theanine-creatine pills. Like the previous Adderall trial, I will pick one pill blindly each day and guess at the end which it was. If it was active (modafinil-creatine), take a break the next day; if placebo (theanine-creatine), replace the placebo and try again the next day. We’ll see if I notice anything on DNB or possibly gwern.net edits.

The easiest way to use 2mg was to use half a gum; I tried not chewing it but just holding it in my cheek. The first night I tried, this seemed to work well for motivation; I knocked off a few long-standing to-do items. Subsequently, I began using it for writing, where it has been similarly useful. One difficult night, I wound up using the other half (for a total of 4mg over ~5 hours), and it worked but gave me a fairly mild headache and a faint sensation of nausea; these may have been due to forgetting to eat dinner, but this still indicates 3mg should probably be my personal ceiling until and unless tolerance to lower doses sets in.
The power calculation indicates a 20% chance of getting useful information. My quasi-experiment has <70% chance of being right, and I preserve a general skepticism about any experiment, even one as well done as the medical student one seems to be, and give that one a <80% chance of being right; so let’s call it 70% the effect exists, or 30% it doesn’t exist (which is the case in which I save money by dropping fish oil for 10 years).
Manually mixing powders is too annoying, and pre-mixed pills are expensive in bulk. So if I’m not actively experimenting with something, and not yet rich, the best thing is to make my own pills, and if I’m making my own pills, I might as well make a custom formulation using the ones I’ve found personally effective. And since making pills is tedious, I want to not have to do it again for years. 3 years seems like a good interval - 1095 days. Since one is often busy and mayn’t take that day’s pills (there are enough ingredients it has to be multiple pills), it’s safe to round it down to a nice even 1000 days. What sort of hypothetical stack could I make? What do the prices come out to be, and what might we omit in the interests of protecting our pocketbook?

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.)
The advantage of adrafinil is that it is legal & over-the-counter in the USA, so one removes the small legal risk of ordering & possessing modafinil without a prescription, and the retailers may be more reliable because they are not operating in a niche of dubious legality. Based on comments from others, the liver problem may have been overblown, and modafinil vendors post-2012 seem to have become more unstable, so I may give adrafinil (from another source than Antiaging Central) a shot when my modafinil/armodafinil run out.
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The table below does not include all companies or all available products in the market but those that we promote as their affiliates. In full compliance with the FTC guidelines, please assume that any and all links on the table are affiliate links, and we may receive compensation if you click one of these and make a purchase. We are independently owned and the opinions expressed here are our own. All editorial content is written without prejudice or bias, regardless of sponsor or affiliate associations.
The Lynches said that Provigil was a classic example of a related phenomenon: mission creep. In 1998, Cephalon, the pharmaceutical company that manufactures it, received US government approval to market the drug but only for "excessive daytime sleepiness" due to narcolepsy; by 2004, Cephalon had obtained permission to expand the labelling so that it included sleep apnoea and "shift-work sleep disorder". Net sales of Provigil climbed from $196m in 2002 to $988m in 2008.
Can brain enhancing pills actually improve memory? This is a common question and the answer varies, depending on the product you are considering. The top 25 brain enhancement supplements appear to produce results for many users. Research and scientific studies have demonstrated the brain boosting effects of nootropic ingredients in the best quality supplements. At Smart Pill Guide, you can read nootropics reviews and discover how to improve memory for better performance in school or at work.
Nicotine has been shown to improve working memory, and research has also demonstrated that oral consumption of nicotine enhances memory consolidation in perceptual learning by enhancing the efficacy of nicotinic acetylcholine receptors and thereby enhancing the overall cholinergic system, which modulates memory formation. In other words, nicotine consumption improves the efficiency of acetylcholine (a neurotransmitter) receptors and, thus, improves the part of the nervous system that regulates healthy memory function. Some research also indicates that psychiatric populations suffering from cognitive deficits (such as patients suffering from schizophrenia) may enjoy even greater neuroprotection from nicotine consumption than healthy individuals. You may be concerned about using nicotine given its potential as an addictive substance. Well, nicotine plays a dual role in the brain by simultaneously promoting addiction and enhancing cognition. In fact, the processes are closely linked through the pathways by which they work. That means that when it comes to dosing nicotine, it’s all about moderation. Because nicotine can be easily abused and has high addictive potential, when using nicotine for cognitive enhancement, you must be precise with dosage and conscious of the amount you use. Studies have shown that moderate doses of nicotine typically produce cognitive enhancement, but very high doses can actually impair cognitive performance. A moderate dose would look something like 2-4 milligrams administered over 20-30 minutes, a dose easily available in the form of nicotine gum or spray. Later in this article, I’ll fill you in on my own personal dosage and use of nicotine.
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. 
Recently I spoke on the phone with Barbara Sahakian, a clinical neuropsychologist at Cambridge University and the co-author of a 2007 article in Nature entitled "Professor's Little Helper". Sahakian, who also consults for several pharmaceutical companies, and her co-author, Sharon Morein-Zamir, reported that a number of their colleagues were using prescription drugs like Adderall and Provigil. Because the drugs are easy to buy online, they wrote, it would be difficult to stop their spread: "The drive for self-enhancement of cognition is likely to be as strong if not stronger than in the realms of 'enhancement' of beauty and sexual function." (In places like Cambridge, at least.)
Consider something as simple as a phone call. You hear the phone ring – your auditory capacity kicks in. Next, you decide whether to answer – decision-making comes into play. You reach for the phone – calling your motor skills to work. You answer – using your voice – all controlled by your brain, all done in mere moments, without conscious thought. Your brain works non-stop, consuming mental energy and physical resources.

In 2011, a story surfaced that struck fear into many: A woman was being treated for brain and memory disorders, when in reality she was just incredibly low in B12 stores. Turns out, this isn’t uncommon; many physicians don’t run routine blood tests for the nutrient, which is especially troublesome considering that our ability to absorb B12 is dramatically reduced with age. Over time, low vitamin B12 can do a number of your cognition.
It wasn't always helpful, but it does work sometimes. The first two days gave me stomach and head pain, so I began to test with taking before or after food, and with or without food. The bottle says to take before food, but I preferred taking this with food, more food is better. This doesn't go well in the stomach with something like chocolate, so take this with something like bread or a meal. More importantly, stay very hydrated unless you want a headache, these pills are very hydro-demanding. The pills also work better if you get your blood moving, just a short walk is fine. Energy drinks and coffee go very well with these, as I had a very clear minded experience when taking these with a Monster Java, it was like a cool breeze blowing away the mental fog.
Woo understands that when selling brain drugs, skepticism comes with the territory. "The typical first reaction is, this is bullshit, you guys are snake-oil salesmen," he says. "We're not medical doctors nor biochemistry experts, but we are experts in building teams and building products. Like how Elon Musk attacks rockets and electric cars from 'first principles,' we see ourselves as applying Silicon Valley aesthetics and operational know-how to the murky world of nootropics."
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".
The placebos can be the usual pills filled with olive oil. The Nature’s Answer fish oil is lemon-flavored; it may be worth mixing in some lemon juice. In Kiecolt-Glaser et al 2011, anxiety was measured via the Beck Anxiety scale; the placebo mean was 1.2 on a standard deviation of 0.075, and the experimental mean was 0.93 on a standard deviation of 0.076. (These are all log-transformed covariates or something; I don’t know what that means, but if I naively plug those numbers into Cohen’s d, I get a very large effect: \frac{1.2 - 0.93}{0.076}=3.55.)
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).
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Dallas Michael Cyr, a 41-year-old life coach and business mentor in San Diego, California, also says he experienced a mental improvement when he regularly took another product called Qualia Mind, which its makers say enhances focus, energy, mental clarity, memory and even creativity and mood. "One of the biggest things I noticed was it was much more difficult to be distracted," says Cyr, who took the supplements for about six months but felt their effects last longer. While he's naturally great at starting projects and tasks, the product allowed him to be a "great finisher" too, he says.
He first took up the game in 1995, when he was in college. He recalled: "It was very mathematical, but you could also inject yourself into the game and manipulate the other guy with words" - more so than in a game like chess. Phillips soon felt that he had mastered the strategic aspects of poker. The key variable was execution. At tournaments he needed to be able to stay focused for 14 hours at a stretch, often for several days, but he found it difficult to do so. In 2003, a doctor gave him a diagnosis of ADHD and he began taking Adderall. Within six months, he had won $1.6m at poker - far more than he'd won in the previous four years. Adderall not only helped him concentrate, it also helped him resist the impulse to keep playing losing hands out of boredom. In 2004, Phillips asked his doctor to give him a prescription for Provigil, which he added to his Adderall regimen. He took 200-300mg of Provigil a day, which he felt helped him settle into an even more serene and objective state of mindfulness; as he put it, he felt "less like a participant than an observer - and a very effective one". Though Phillips sees neuroenhancers as essentially steroids for the brain, they haven't yet been banned from poker competitions.
The evidence? A 2012 study in Greece found it can boost cognitive function in adults with mild cognitive impairment (MCI), a type of disorder marked by forgetfulness and problems with language, judgement, or planning that are more severe than average “senior moments,” but are not serious enough to be diagnosed as dementia. In some people, MCI will progress into dementia.
I take my piracetam in the form of capped pills consisting (in descending order) of piracetam, choline bitartrate, anhydrous caffeine, and l-tyrosine. On 8 December 2012, I happened to run out of them and couldn’t fetch more from my stock until 27 December. This forms a sort of (non-randomized, non-blind) short natural experiment: did my daily 1-5 mood/productivity ratings fall during 8-27 December compared to November 2012 & January 2013? The graphed data29 suggests to me a decline:
70 pairs is 140 blocks; we can drop to 36 pairs or 72 blocks if we accept a power of 0.5/50% chance of reaching significance. (Or we could economize by hoping that the effect size is not 3.5 but maybe twice the pessimistic guess; a d=0.5 at 50% power requires only 12 pairs of 24 blocks.) 70 pairs of blocks of 2 weeks, with 2 pills a day requires (70 \times 2) \times (2 \times 7) \times 2 = 3920 pills. I don’t even have that many empty pills! I have <500; 500 would supply 250 days, which would yield 18 2-week blocks which could give 9 pairs. 9 pairs would give me a power of:
A randomized non-blind self-experiment of LLLT 2014-2015 yields a causal effect which is several times smaller than a correlative analysis and non-statistically-significant/very weak Bayesian evidence for a positive effect. This suggests that the earlier result had been driven primarily by reverse causation, and that my LLLT usage has little or no benefits.
We’d want 53 pairs, but Fitzgerald 2012’s experimental design called for 32 weeks of supplementation for a single pair of before-after tests - so that’d be 1664 weeks or ~54 months or ~4.5 years! We can try to adjust it downwards with shorter blocks allowing more frequent testing; but problematically, iodine is stored in the thyroid and can apparently linger elsewhere - many of the cited studies used intramuscular injections of iodized oil (as opposed to iodized salt or kelp supplements) because this ensured an adequate supply for months or years with no further compliance by the subjects. If the effects are that long-lasting, it may be worthless to try shorter blocks than ~32 weeks.
Microdosing with Iboga: Native to the rainforests in Central Africa, Iboga is an evergreen shrub, with high concentrations found in the root bark. It has a rich history amongst practitioners in the indigenous Bwiti religion in Africa and has recently found its way into Western practices, primarily for extremely effective therapy for drug addictions, but also for physical energy, cognitive performance in smaller microdoses, and a surge in positive emotions (See additional studies here and here.).  To microdose with Iboga, you will want to find it in tincture or root bark form (the root bark form is typically encapsulated). If using a tincture, find a source that has the root bark extracted into its purest form, combined with Iboga alkaloids, which keeps the full spectrum of the plant untouched. Just a single drop of an Iboga tincture equates to about 0.5 milligrams and suffices as a microdose. For the root bark of Iboga, a dose of 300-500 milligrams is also an effective dose. I’ve personally found Iboga to be most useful prior to a workout or an effort that combines both brain and body demands, such as tennis or basketball – but it makes you hyperactive and jittery if taken prior to a day of desk work. This makes sense when you consider that African tribes traditionally whipped themselves into a frenzied pre-battle state on Iboga.
The principal metric would be mood, however defined. Zeo’s web interface & data export includes a field for Day Feel, which is a rating 1-5 of general mood & quality of day. I can record a similar metric at the end of each day. 1-5 might be a little crude even with a year of data, so a more sophisticated measure might be in order. The first mood study is paywalled so I’m not sure what they used, but Shiotsuki 2008 used State-Trait of Anxiety Inventory (STAI) and Profiles of Mood States Test (POMS). The full POMS sounds too long to use daily, but the Brief POMS might work. In the original 1987 paper A brief POMS measure of distress for cancer patients, patients answering this questionnaire had a mean total mean of 10.43 (standard deviation 8.87). Is this the best way to measure mood? I’ve asked Seth Roberts; he suggested using a 0-100 scale, but personally, there’s no way I can assess my mood on 0-100. My mood is sufficiently stable (to me) that 0-5 is asking a bit much, even.

One of the most popular legal stimulants in the world, nicotine is often conflated with the harmful effects of tobacco; considered on its own, it has performance & possibly health benefits. Nicotine is widely available at moderate prices as long-acting nicotine patches, gums, lozenges, and suspended in water for vaping. While intended for smoking cessation, there is no reason one cannot use a nicotine patch or nicotine gum for its stimulant effects.


There are a variety of substances to get magnesium from. Considerable enthusiasm for the new compound magnesium l-threonate was stirred by 2 small animal rat studies finding that magnesium l-threonate was able to increase magnesium levels in the brain and improve learning/memory tasks. (There are no published human trials as of October 2015, and evidence of publication bias, which I take as evidence against there being large effects in humans.) Animal studies mean very little, of course (see the appendix), but I thought it’d be interesting to try using l-threonate, so I bought the $30 Life Extension Neuro-Mag Magnesium L-Threonate with Calcium and Vitamin D3 (205g), which according to the LEF product page works out to ~60g of Magtein™ magnesium L-threonate and ~4.31g elemental magnesium inasmuch as LEF claims 2000mg of threonate powder provides 144mg elemental magnesium or a 14:1 ratio. (I don’t need the calcium or vitamin D3, but this was the only magnesium l-threonate on Amazon.) Experiment-wise, I’ll probably look at sleep metrics and Mnemosyne performance; I put off designing a blind self-experiment until after trying some.
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”.
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?
One of the most popular legal stimulants in the world, nicotine is often conflated with the harmful effects of tobacco; considered on its own, it has performance & possibly health benefits. Nicotine is widely available at moderate prices as long-acting nicotine patches, gums, lozenges, and suspended in water for vaping. While intended for smoking cessation, there is no reason one cannot use a nicotine patch or nicotine gum for its stimulant effects.
I've started taking the addium in conjunction with another supplement that I'm using for focus NootropX - 90 caps - Mental Focus and Concentration Supplement With Memory Enhancement For Extreme Clarity and Alertness - Instant Brain and Memory Power Boost From Patented AES® Absorption System - The Ultimate Brain Vitamins and the combination of the two is really changing my whole life. With the nootropx I'm able to really focus on a task and completed, and the addium gives me the motivation to work, and work alot. My productivity at work has increased so much, and it's really amazing. I cannot believe it. I recommend both of these products, they will definitely change the way that you attempt projects.
Jump up ^ EFSA Panel on Dietetic Products, Nutrition and Allergies; European Food Safety Authority (EFSA), Parma, Italy (2011). "Scientific Opinion on the substantiation of health claims related to L-theanine from Camellia sinensis (L.) Kuntze (tea) and improvement of cognitive function (ID 1104, 1222, 1600, 1601, 1707, 1935, 2004, 2005), alleviation of psychological stress (ID 1598, 1601), maintenance of normal sleep (ID 1222, 1737, 2004) and reduction of menstrual discomfort (ID 1599) pursuant to Article 13(1) of Regulation (EC) No 1924/2006". EFSA Journal. 9 (6): 2238. doi:10.2903/j.efsa.2011.2238.
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