CAUTION: This product is not intended for use by individuals who are currently being treated or at risk of being treated for chronic or serious anxiety disorder, panic disorder, social anxiety disorder, or any mental-health condition.

Supercharged Energy for the Mind and Body*

Brain Candy has been formulated to customize brain function. Use it to increase confidence, reduce social anxiety, and improve mood. Or use it to supercharge your brain by increasing its learning and memory retention.*

Athletes love Brain Candy because it allows them to tackle training or competition with increased mental focus and energy. Used as a "pre workout" it increases energy and concentration.*

This great-tasting liquid shot is available in original and caffeine free. All you need is one small bottle per day to experience a clean, long-lasting, no-crash brain and body energy boost.*

When to Use Brain Candy

• Pre workout*
• Before athletic competition or intense practice*
• Before a test, job interview, or any mental task that requires focus and concentration*
• Before going to clubs or parties*
• When your energy is low and your mood is bad*

Five Mind Energizing Ingredients

Here's a rundown of each of Brain Candy's research-backed ingredients:

Acetyl-L-Carnitine

Acetyl-L-carnitine or ALCAR is a naturally occurring amino acid. Some of its effects include:

• Improved social interaction*
• Increased energy production in the mitochondria, thereby boosting physical and mental energy for several hours*
• Improved "processing speed," focus, mood, and memory (including long-term memory)*
• Improved verbal fluency*
• Increased glucose and creatinine levels in the brain, both of which decrease as we age*
• Protecting brain cells from alcohol damage*
• Stimulating brain cells and prompting them to grow more connections to other neurons*
• Increased learning rate*
• Counteracting some forms of depression*
• Improved learning, attention span, and facial recognition*

ALCAR increases levels of norepinephrine and serotonin – neurotransmitters that play an important role in mood and brain function. ALCAR might also work by directly enhancing neural transmission by stimulating synapses or blocking post-synaptic inhibition.*

In short, it appears to increase your electrical "wattage" so you burn brighter and longer. ALCAR also plays well with others. If you combine it with other nootropics, it has a mutually potentiating effect – all the compounds in the combo work better.*

Acetyl-L-Tyrosine

Acetyl-L-tyrosine is a more bioavailable form of the amino acid L-tyrosine, which is used by the brain to make dopamine. Dopamine plays a big part in memory, focus, libido, and sense of well-being. Some of acetyl-L-tyrosine's effects include:*

• Improved mood*
• Reduction of social anxiety*
• Increased positive outlook*
• Improved memory and learning capacity*
• Improved analytical skills*
• Increased energy*
• Improved concentration*
• Reduction of stress*

Acetyl-L-tyrosine leaves people feeling refreshed after training or manual labor by mitigating some of the short-term stress caused by intensive work.

CDP Choline

CDP Choline, also known as citicholine, is a highly bioavailable form of choline, which is an essential nutrient. Some of its effects include:*

• Increased attention span*
• Enhanced production of ATP in brain cells*
• Optimized signaling between brain neurons that enhances learning, cognition, and recall*
• Improved memory*

CDP choline is an ingredient in Brain Candy because it makes you concentrate and focus much better, in addition to enhancing mental alertness.*

DMAE (Dimethylethanolamine)

DMAE is what's known as an amine. It's naturally produced in the brain, but you can also find high levels in certain seafoods. Some of its effects include:

• Improved mood*
• Increased sense of well-being*
• Increased memory*
• Improved alertness*
• Better sleep patterns*
• Increased concentration*

L-Theanine

L-theanine is an amino acid that's considered an analogue of L-glutamine and L-glutamate, both of which are used in the biosynthesis of proteins. Some of L-theanine's effects include:

• Enhanced thinking ability*
• Reduction of anxiety and improved mood*
• Improved cognition*
• Better sense of well-being*
• Improved sleep patterns*

L-theanine adds a calming effect to Brain Candy. However, even though L-theanine calms you, it simultaneously raises energy levels, but without the jitteriness associated with crude stimulants.*

WARNING: DO NOT USE IF YOU ARE UNDER THE AGE OF 18 OR ELDERLY. DO NOT TAKE WITH ANY OTHER STIMULANT OR WEIGHT-LOSS SUPPLEMENT OR ANY PRESCRIPTION OR OVER-THE-COUNTER MEDICINE. Do not use if you are pregnant or nursing or at risk of being treated for high-blood pressure, heart disease, hyperthyroidism, spasms, psychiatric disease, suffer from migraines, have asthma, or are taking asthma medication. Discontinue use if you experience dizziness, headache, nausea, or heart palpitations. If you have trouble sleeping, do not take within 6 hours of bedtime. KEEP OUT OF REACH OF CHILDREN.

Feedback

"With Brain Candy, I can tolerate people I don't like."

It makes such a difference to my day when I have to talk to people I don't like. When on Brain Candy, I'm not annoyed by traffic or roommates or inconsistent energy levels. I'm calm and more focused.

Chigishev

"I can't imagine not taking Brain Candy."

I love Brain Candy! I can't imagine not taking it now. I think I'm hooked! I'm definitely more productive while working on this Modern Warfare downloadable content pack.

Andy, Raven Software Audio Design

"Completed a 2-hour project in 15 minutes."

More Brain Candy goodness: I just completed a task in 15 minutes that I thought would have taken me two hours.

Justin Negrete

"10 minutes later... "Man, I can't wait to train!'"

Second day of Brain Candy, and I was feeling sick this morning before taking it. I thought I was going to have to cancel my training session. Gulp, gulp, gulp, down goes Brain Candy... 10 minutes later I'm like, "Man, I can't wait to train!"

Socrastein

"Reading speed is faster."

When using Brain Candy, I can read anything faster. I'm simply burning through books and articles.

westnole

"I'm buzzing to bust out a project."

Just took my first shot. I honestly have a buzz. Going to bust out a programming project.

tnt2005

"My thoughts become words a lot easier."

Taking Brain Candy, I definitely notice a difference in mood. I'm not the friendliest person, but with Brain Candy, people have noticed that I'm more cheerful. Also, I can talk faster, like my thoughts become words a lot easier. The flow of thoughts to words is constant and uninterrupted. I noticed this while writing a paper the other week.

State Of Psychosis

"I'm so productive it's comical"

I've been so productive today it's comical. I set up a bunch of summer programs and fired my landscaping guy who cheated me, all done with a silly grin on my face. Brain Candy is fantastic!

Weevo

"I may be the happiest college kid taking finals"

I bought a case of Brain Candy specifically for finals week. It's really shocking the difference it makes in my mood and overall feeling. I may be the happiest college kid on campus during finals week!

BuildingUp

"Thanks to Brain Candy I now can have a life"

The last few months, I've been working 15 hours most days. I'm so busy that I actually stopped going to the gym. And after two months at this pace, it was starting to grind me into the dirt -- no energy, grumpy, and completely unproductive.

I'm still working that crazy schedule, with one difference -- I'm taking Brain Candy. With Brain Candy, I'm in the gym six days a week, and I'm smiling and bouncing around all the way up until bedtime. Big difference!

Cold Macaroni

"Amplified pleasures"

One of the biggest advantages I found with Brain Candy is its ability to amplify all the regular things I enjoy. Movies and music are all that much more vivid and exciting. If I start dragging in the afternoon, all I have to do is put my headphones on for five minutes and I'm punch-dancing my way through whatever working on.

For the umpteenth time, Biotest, you walk the walk!

Cold Macaroni

"Damn, Brain Candy works!"

Damn, Brain Candy works!

fitnessben7500

"I can't imagine going without Brain Candy"

I can't imagine going without Brain Candy.

bbone32

"My coffee craving is nonexistent"

Since I've been on Brain Candy, my coffee craving has been nonexistent. And I used to drink a ton!

emenef

"So calm I didn't even realize it"

The cumulative effect of Brain Candy is really starting to show now. I've been working on some nasty deals at work where everyone is frustrated and hates each other. This week a client told me, "I don't get how you seem so calm through all of this." I didn't even realize I seemed calm.

Brian Candy is Powerful stuff. Really, really enjoying it.

westnole

"I feel 10 years younger!"

As I've gotten older I've lost focus and drive. Lifting had become a drag, house projects were not getting done, etc. Since I started Brain Candy, the early afternoon crash is GONE, and I' able to stay focused 100 % all the way through the night. I'm flat-out productive.

Getting old has been a bitch, but Brain Candy has knocked about 10 years off how I feel. I don't want to be without Brain Candy, ever!

hatda02

"I'm much more even-tempered and patient."

Since starting Brain Candy (one shot per day), I feel better than I ever. My ability to focus is off the charts and I have energy all throughout the day that continues through my long night shifts. The mood enhancement effect is for real, too. I'm much more even-tempered and patient, which is a pretty big deal for me. Others have noticed these differences in me, including the owners of the gym I go to, and have become daily Brain Candy users.

Having used Brain Candy for almost a month now, I have to say that this stuff is the real deal. Hands down my favorite supplement.

Dave-G

"No exasperated feeling at the end of the day."

I've been using Brain Candy for seven days, including three long days at a conference, meeting with executives and lobbyists. I didn't have the urge to fall asleep, throw anyone out a window, or feel the need for coffee. No exasperated feeling at the end of the day, either. I just went right to the gym.

Hip Scar

"Home run, Biotest."

Absolutely loving Brain Candy. Home run, Biotest!

jedalger

"Amazing."

After a long night and only sleeping two hours, I woke up this morning feeling incredibly tired. I rolled over and took a shot of Brain Candy, and 20 minutes later I was going about my morning as if I'd slept like a baby all night. Amazing.

Anthony50

"I don't get it, but Brain Candy works!"

Even though I was initially skeptical, I bought a case of Brain Candy. I took my first bottle on Wednesday and choked out all my Jujitsu training partners at practice. And this is after a two-week spring-break vacation. Thursday I ran the show during an international relations discussion. On Friday I won my first argument ever with my girlfriend. I don't get it, but Brain Candy works!

jjmccue3

"Getting out of bed has never been so easy!"

Taking Brain Candy, getting out of bed has never been so easy!

MontisVerdes

"Amazing day on Brain Candy."

Amazing day on Brain Candy. I worked on a project for my MBA class for six hours straight without taking a break, and that wasn't my intention when I sat down. I just got dialed in and didn't want to get up from the computer. I really wish I had this supplement when I was in undergrad.

MizzouDawg

"Aside from being in a great mood..."

I love this stuff! Aside from being in a great mood and having great workouts, Brain Candy has really helped me focus on my practice sessions (I play bass guitar). I've been breezing through stuff that I had difficulty with before.

setor

"Brain Candy may have been too good."

Day four of Brain Candy may have been too good. I was talking with some friends last night and my wife had to drag me away (to get to bed) because we simply wouldn't stop talking. I've always been the one to see reason and say goodbye, but last night I couldn't do it!

Also, I've definitely had a better time mentally compartmentalizing tasks.

byukid

"Never been more pleased with a supplement."

When I'm on Brain Candy, my "hockey sense" during a game is at a very high and constant pitch. It's the difference between good and great playing. Sometimes it's hard to get "into the groove" and it's all too easy to get out of it.

I've noticed on Brain Candy that I'm in the groove immediately, and I pretty much stay that way. Which is mind-blowingly awesome! It's almost as if Tim Patterson took the concept of "flow" and being "in the zone" and bottled it. Seriously, that's the best way I could describe it.

Katzenjammer

"A winner if there ever was one!"

As an official energy drink junkie, I can say, hands down, Brain Candy blows anything else on the market out of the water. What Spike did to energy drinks, Brain Candy does to nootropic supplements. A winner if there ever was one!

Lonnie123

"Not usually talkative the morning."

The effects on my first day of Brain Candy were good. I was able to stay much more focused during classes, and I was able to joke and laugh much more with classmates than usual (I'm usually not in the mood for that in the morning.)

The effects by the fourth and fifth day were really something. I think Tim Patterson is on to something when he talks about the cumulative effects when taking it routinely in the morning. With Brain Candy, once you're going about your daily routine you'll notice you're much more focused (not jittery) and have a sense of well-being.

ashylaryyku

"Brain Candy is pure gold for social events."

Brain Candy is the real deal guys. I've been quiet all my life and Brain Candy is pure gold for social events. I've never talked so much and said so many smart things in such a short time span.

kjmont

"I couldn't be lazy."

My plan for Sunday was to sit on my butt and watch TV. Well, I took my Brain Candy in the morning and could not be lazy! I had to be productive!

sniper1

"Brain Candy has had a huge impact on my life."

I'm currently taking Brain Candy daily right now and have no plans to stop. I wish I had this stuff when I was in school. I've been struggling with mild depression and anxiety since starting a new job, so this supplement has had a huge impact on my life. My productivity at work in the last week has been unreal.

MizzouDawg

"Just in time..."

Brain Candy showed up at my door just in time! Working on about five hours of sleep right, I was about to take a nap, but once it kicked in I managed to finish the last set of assignments for this semester. It's a nice, clear focus. Can't wait to experience the cumulative effects. This is going to come in handy for finals in the coming weeks!

Dmgctrl

"Alert, aware, effective..,"

I woke up at 4:00 this morning and was out of the house by 5:00. Brain Candy consumed at 6:00 and I was very surprised by the effects: alert, aware, effective and efficient throughout the morning. It was like my sympathetic nervous system was up but under total control. Very cool!

Michael Ranfone, CSCS

"Brain Candy was really working magic...."

I participated in a "strongman" class our gym organized to help promote it. Along with my regular training session, I totaled about 3.5 hours of training in a row. What's crazy is how I was very focused throughout both workouts. Brain Candy was really working its magic tonight!

Anechoic

"Less anxiety about the tough day ahead"

I had Brain Candy this morning. I noticed an elevated mood about 20 minutes after taking on an empty stomach. Getting ready for the day was a more positive experience, with less anxiety about the tough day ahead.

Captain72

"Plus 5 Attitude"

I spent all of last week in sleep deprivation staying up late with friends, but I still managed to train hard and have energy. My attitude (on a - 5 / + 5 scale) has been at a "+ 5" these days. I've even gotten my parents on Brain Candy.

emenef

"Even doing my taxes didn't bother me."

I did my taxes after taking brain candy this weekend, and I didn't break a thing or kick the dog or anything...

westnole

"Love Brain Candy."

Loving this Brain Candy. Going to order another case today!

BradyZ

"Amazing weekend experience"

Ok, Brain Candy update. I took it over the weekend and had a f'n fabulous two days – great mental energy and clarity, good mood, and got all my errands done. Even when I strained my shoulder on overhead press I didn't get pissed like a normally would. Just kind of figured out a way to work around it and make the best of it.

Brain Candy is amazing stuff.

wallstrt

"Awesome!"

Brain Candy is awesome!

jedalger

"Two days without made me understand."

For the first couple of hours I wasn't sure if it was working. Once I realized that it was – and how it was – it started hitting me how amazing Brain Candy is. It took me 4 days to understand it – 2 days with Brain Candy, 2 days without.

BiP

"Mom greeted dad naked..."

I handed my mom a bottle of Brain Candy and told her to drink it... She ended up cleaning the house, greeted my dad naked (he thought he'd share that with me, so now I'll do the same), did laundry, and even took doors off their hinges and helped my dad sand and paint them. And this is from a woman with MS! So all and all, I like Brain Candy and my mom wants to know WTF I gave her.

corstijeir

"I feel this!"

Today when I got to work my Brain Candy had arrived, and here's my report: Well, I can actually feel the blood flow to the brain. In the gym I was able to be more aggressive. It took me back to the intensity I had when I played linebacker with in high school. I was very explosive with every rep. I actually had a sense of my neurons firing more efficiently. It isn't often that I actually feel a supplement working and I'm very critical of such claims. I'm not one to take something and expect it to be "felt." I feel this!

StandTall

"KD ratio is UP!"

As a POV from the gaming community, I've taken Brain Candy for 4 straight days now, and after day 2 I've noticed an improvement in my CoD performance (haha). KD ratio is UP!

diamonddelts59

"I'm finding myself wanting to read more."

This morning I found myself wiping my counter tops before going to class (they weren't even messy). I've also had the sudden urge to read more throughout the day since taking Brain Candy. Just today I brought my Stephen King book to campus, read it before class, and got excited when class let out 30 minutes early because I wanted more reading time (lol). NURD!

ashylarryku

"Mentally focused, energetic, great mood, and the social effect is real."

I'm 3 hours into my first go-around with Brain Candy. It ROCKS!

Starting Tuesday and finishing Wednesday, I worked 36 hours straight (with no sleep) and was totally slammed. Today, even after sleeping nine hours, I should be wiped out. I know a bit about the extremes of mental performance and the effects of no sleep. I'm an anesthesiologist and had to deal with studying and working with no or minimal sleep in residency. So I know how I should feel today.

I took Brain Candy right before 7:00 AM and I feel GREAT! I'm  mentally focused, energetic, in a great mood, and the social effect is real. Instead of dragging and watching the clock, I feel "ON." I know I should be scraping along, but I'm energized and READY TO GO.

This supplement is REAL! I need a palate of Brain Candy delivered, ASAP! I am ready to sign a binding contract for year long auto-ship. I just need my first batch TOMORROW.

DogBiteCat 

"Mentally focused and elevated mood all day"

After taking Brain Candy, my mood was elevated all day. I was able to focus 10 hours after I took it for a great workout. I was also told by two separate people I was funnier. My ability to tolerate people that would otherwise annoy me was heightened. I was refreshed throughout the entire day, even up to the point of when I went to sleep. I went to sleep easily and the sleep quality was great.

corstijeir

"I'm usually in a terrible mood, but..."

Took Brain Candy about an hour ago. Feeling pretty good at the moment. This is highly abnormal as I am usually in a terrible mood when I'm getting ready for work (to the point where I don't even want to respond when my wife talks to me!). I actually found myself singing a song in my head while I was getting ready for work. The fact that I'm even looking forward to my day is weird. I'll report back more later. Oh, and I haven't even had my morning coffee yet, which is usually a requirement for me to function at all.

MizzouDawg

"Brain Candy is friggin' awesome!"

Brain Candy is friggin' awesome! I've never been so happy while in a calorie deficit!

mattyg24

"Less anxiety about the tough day ahead"

I had Brain Candy this morning. I noticed an elevated mood about 20 minutes after taking on an empty stomach. Getting ready for the day was a more positive experience, with less anxiety about the tough day ahead.

Captain72

"Burning through the Wall Street Journal..."

Tried Brain Candy this morning. I usually read the Wall Street Journal and New York Times on the train and just finish as I'm hitting my stop. This morning I burned through both with five minutes to spare.

Westnole

"I could feel the effects 13 hours later!"

I took Brain Candy five minutes after I got up. Within an hour I could feel it. My mind was clear, I seem to have less "ADD," in that I could focus on work e-mails, spreadsheets, and other tasks more effectively. It definitely helped me overcome the sluggishness I had from an uneven night's sleep. I could feel the effects 13 hours later! Amazing. I cannot wait to get on a regular regimen of this!

jkwarsick

"I felt like a genius and a lot more social."

I tried the regular Brain Candy this morning on an empty stomach, around 7:30 AM. I had some breakfast at 8:15 and class started at 8:30. The only effects I really noticed was being more awake for the first hour.

However, at 9:30 I felt like a genius. I was doing class work, while sitting with six other people and listening to two other conversations on the side. For my next class I was wide awake, and paying attention in a class that all year I've never cared about. I was actually talking out loud and referring to questions raised by the professors. I got some weird looks, because the whole quarter I had only talked once before!

So I definitely noticed more awareness, I was a lot more social, and the most impressive part was attention span was highly raised. I can see myself drinking this Nectar of The Gods for the rest of my life.

bassip21

"Mentally fresh, cheerful, carefree, and more talkative"

Overall, I feel more cheerful and carefree with Brain Candy. Mood was noticeably better and I was conversing more with one of my new clients. Energy-wise, I felt pretty fresh mentally the entire day with no afternoon crash or sluggishness. I took the dose on an empty stomach at 8:30 AM and was still noticing these effects around 6:00 PM. It's around 7:15 PM now and I can feel the effects wearing off slightly, but I still feel mentally sharp.

seph89

"Definitely felt more focused on my work"

I took Brain Candy and definitely felt more focused on my work and wanted to get sh*t done!

Cool feeling!

Jud68

"I'm much more confident."

With Brain Candy my thinking is incredibly clear and I'm much more confident.

Quite impressive.

Briansays

"Greater focus and a greater sense of being 'aware' and 'engaged.'"

I took Brain Candy yesterday and felt very "even" all day, no ups or downs. Usually I need a 5-o'clock coffee at work (I work until 2 AM), but yesterday, I just plowed right through with no rundown feeling.

Been on for 3 days solid now. The main thing I notice is a decreased "time to focus" -- meaning I can basically be ready to go in the gym in no time flat (no time needed to psych up or anything like that). I've actually ditched the headphones these last two days. I just don't need them.

There does seem to be an effect with regard to being social, as well. I'm a bit more talkative at work, taking more risks with jokes, things like that. But overall, Brain Candy has given me more of a sharpness of mind, a greater ability to focus, and just a general sense of being "aware" and "engaged."

Lonnie123

"I was super-nice to my coworkers who are idiots."

I had an amazing workout this morning. But what is more amazing is that I was super-nice to my coworkers who are idiots.

Breaux

"I need more time for extra chatting with everyone!"

It's my second day on Brain Candy. I need to allocate more time for extra chatting with everyone!

GreekGodX

"Mental clarity and calmness that I don't think I've felt in years."

I'm really liking Brain Candy. It's a bit more caffeine than I'm used to (in one shot), but that was mostly offset with a kind of mental clarity and calmness that I don't think I've felt in years. Mentally I was ready to GSD (get sh*t done).

wallstrt

"I love this stuff and can't believe how long I can stay focused."

I love this stuff and can't believe how long I can stay focused. I think I finally understood for a moment the distinction Aquinas makes between esse and essentia. It really is a nice calm/warm focus: the kind of focus that seems to expand time, if you know what I mean.

katzenjammer

"Woke up early and was ready to go."

I'm on my third dose of Brain Candy right now. Today I set my alarm clock for 9:00 AM and woke up at 8:50 AM and was up immediately. That never happens.

PB Andy

L-Theanine Research Abstracts

Mood / Anxiety / Cognition / Attention

A combination of green tea extract and l- theanine improves memory and attention in subjects with mild cognitive impairment: a double-blind placebo-controlled study.

J Med Food. 2011 Apr;14(4):334-43. Epub 2011 Feb 8.

Park SK, Jung IC, Lee WK, Lee YS, Park HK, Go HJ, Kim K, Lim NK, Hong JT, Ly SY, Rho SS. LG Household and Health Care Co., Ltd., Daejeon, Korea.

A combination of green tea extract and l- theanine (LGNC-07) has been reported to have beneficial effects on cognition in animal studies. In this randomized, double-blind, placebo-controlled study, the effect of LGNC-07 on memory and attention in subjects with mild cognitive impairment (MCI) was investigated. Ninety-one MCI subjects whose Mini Mental State Examination-K (MMSE-K) scores were between 21 and 26 and who were in either stage 2 or 3 on the Global Deterioration Scale were enrolled in this study. The treatment group (13 men, 32 women; 57.58 ± 9.45 years) took 1,680 mg of LGNC-07, and the placebo group (12 men, 34 women; 56.28 ± 9.92 years) received an equivalent amount of maltodextrin and lactose for 16 weeks. Neuropsychological tests (Rey-Kim memory test and Stroop color-word test) and electroencephalography were conducted to evaluate the effect of LGNC-07 on memory and attention. Further analyses were stratified by baseline severity to evaluate treatment response on the degree of impairment (MMSE-K 21-23 and 24-26). LGNC-07 led to improvements in memory by marginally increasing delayed recognition in the Rey-Kim memory test (P .0572). Stratified analyses showed that LGNC-07 improved memory and selective attention by significantly increasing the Rey-Kim memory quotient and word reading in the subjects with MMSE-K scores of 21-23 (LGNC-07, n = 11; placebo, n = 9). Electroencephalograms were recorded in 24 randomly selected subjects hourly for 3 hours in eye-open, eye-closed, and reading states after a single dose of LGNC-07 LGNC-07 (n = 12; placebo, n = 12). Brain theta waves, an indicator of cognitive alertness, were increased significantly in the temporal, frontal, parietal, and occipital areas after 3 hours in the eye-open and reading states. Therefore, this study suggests that LGNC-07 has potential as an intervention for cognitive improvement.

The combination of L-theanine and caffeine improves cognitive performance and increases subjective alertness.

Nutr Neurosci. 2010 Dec;13(6):283-90.

Giesbrecht T, Rycroft JA, Rowson MJ, De Bruin EA. Sensation, Perception, and Behaviour, Unilever R&D, Vlaardingen, The Netherlands.

The non-proteinic amino acid L-theanine and caffeine, a methylxanthine derivative, are naturally occurring ingredients in tea. The present study investigated the effect of a combination of 97 mg L- theanine and 40 mg caffeine as compared to placebo treatment on cognitive performance, alertness, blood pressure, and heart rate in a sample of young adults (n = 44). Cognitive performance, self-reported mood, blood pressure, and heart rate were measured before L-theanine and caffeine administration (i.e. at baseline) and 20 min and 70 min thereafter. The combination of moderate levels of L-theanine and caffeine significantly improved accuracy during task switching and self-reported alertness (both P < 0.01) and reduced self-reported tiredness (P < 0.05). There were no significant effects on other cognitive tasks, such as visual search, choice reaction times, or mental rotation. The present results suggest that 97 mg of L-theanine in combination with 40 mg of caffeine helps to focus attention during a demanding cognitive task.

L-theanine and caffeine improve task switching but not intersensory attention or subjective alertness.

Appetite. 2010 Apr;54(2):406-9. Epub 2010 Jan 15.

Einšther SJ, Martens VE, Rycroft JA, De Bruin EA. Sensation, Perception Behaviour, Unilever R D Vlaardingen, Vlaardingen, The Netherlands. Suzanne.

Tea ingredients L-theanine and caffeine have repeatedly been shown to deliver unique cognitive benefits when consumed in combination. The current randomized, placebo-controlled, double-blind, cross-over study compared a combination of L-theanine (97 mg) and caffeine (40 mg) to a placebo on two attention tasks and a self-report questionnaire before, and 10 and 60 min after consumption. The combination of L-theanine and caffeine significantly improved attention on a switch task as compared to the placebo, while subjective alertness and intersensory attention were not improved significantly. The results support previous evidence that L-theanine and caffeine in combination can improve attention.

l-Theanine, an amino acid in green tea, attenuates beta-amyloid-induced cognitive dysfunction and neurotoxicity: reduction in oxidative damage and inactivation of ERK/p38 kinase and NF-kappaB pathways.

Free Radic Biol Med. 2009 Dec 1;47(11):1601-10. Epub 2009 Sep 16.

Kim TI, Lee YK, Park SG, Choi IS, Ban JO, Park HK, Nam SY, Yun YW, Han SB, Oh KW, Hong JT. College of Pharmacy and CBITRC, Chungbuk National University, Cheongju, Chungbuk 361-763, Korea.

Amyloid beta (Abeta)-induced neurotoxicity is a major pathological mechanism of Alzheimer disease (AD). In this study, we investigated the inhibitory effect of l-theanine, a component of green tea (Camellia sinensis), on Abeta(1-42)-induced neuronal cell death and memory impairment. Oral treatment of l-theanine (2 and 4 mg/kg) for 5 weeks in the drinking water of mice, followed by injection of Abeta(1-42) (2 microg/mouse, icv), significantly attenuated Abeta(1-42)-induced memory impairment. Furthermore, l-theanine reduced Abeta(1-42) levels and the accompanying Abeta(1-42)-induced neuronal cell death in the cortex and hippocampus of the brain. Moreover, l-theanine inhibited Abeta(1-42)-induced extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase as well as the activity of nuclear factor kappaB (NF-kappaB). l-Theanine also significantly reduced oxidative protein and lipid damage and the elevation of glutathione levels in the brain. These data suggest that the positive effects of l-theanine on memory may be mediated by suppression of ERK/p38 and NF-kappaB as well as the reduction of macromolecular oxidative damage. Thus, l-theanine may be useful in the prevention and treatment of AD.

The effects of L-theanine on alpha-band oscillatory brain activity during a visuo-spatial attention task.

Brain Topogr. 2009 Jun;22(1):44-51. Epub 2008 Oct 9.

Gomez-Ramirez M, Kelly SP, Montesi JL, Foxe JJ. Program in Cognitive Neuroscience and Schizophrenia, The Cognitive Neurophysiology Laboratory, Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, NY 10962, USA.

Background/Objectives Ingestion of the non-proteinic amino acid L-theanine (gamma-glutamylethylamide) has been shown to influence oscillatory brain activity in the alpha band (8-14 Hz) in humans during resting electroencephalographic (EEG) recordings and also during cognitive task performance. We have previously shown that ingestion of a 250-mg dose of L-theanine significantly reduced tonic (background) alpha power during a demanding intersensory (auditory-visual) attentional cueing task. Further, cue-related phasic changes in alpha power, indexing the shorter-term anticipatory biasing of attention between modalities, were stronger on L-theanine compared to placebo. This form of cue-contingent phasic alpha activity is also known to index attentional biasing within visual space. Specifically, when a relevant location is pre-cued, anticipatory alpha power increases contralateral to the location to be ignored. Here we investigate whether the effects of L-theanine on tonic and phasic alpha activity, found previously during intersensory attentional deployment, occur also during a visuospatial task. Subjects/Methods 168-channel EEG data were recorded from thirteen neurologically normal individuals while engaged in a highly demanding visuo-spatial attention task. Participants underwent testing on two separate days, ingesting either a 250-mg colorless and tasteless solution of L-theanine mixed with water, or a water-based solution placebo on each day in counterbalanced order. We compared the alpha-band activity when subjects ingested L-Theanine vs. Placebo. Results We found a significant reduction in tonic alpha for the L-theanine treatment compared to placebo, which was accompanied by a shift in scalp topography, indicative of treatment-related changes in the neural generators of oscillatory alpha activity. However, L-theanine did not measurably affect cue-related anticipatory alpha effects. Conclusions This pattern of results implies that L- theanine plays a more general role in attentional processing, facilitating longer-lasting processes responsible for sustaining attention across the timeframe of a difficult task, rather than affecting specific moment-to-moment phasic deployment processes.

The combined effects of L-theanine and caffeine on cognitive performance and mood.

Nutr Neurosci. 2008 Aug;11(4):193-8.

Owen GN, Parnell H, De Bruin EA, Rycroft JA. Unilever Research and Development, Colworth House, Sharnbrook, Bedford, UK.

The aim of this study was to compare 50 mg caffeine, with and without 100 mg L-theanine, on cognition and mood in healthy volunteers. The effects of these treatments on word recognition, rapid visual information processing, critical flicker fusion threshold, attention switching and mood were compared to placebo in 27 participants. Performance was measured at baseline and again 60 min and 90 min after each treatment (separated by a 7-day washout). Caffeine improved subjective alertness at 60 min and accuracy on the attention-switching task at 90 min. The L- theanine and caffeine combination improved both speed and accuracy of performance of the attention-switching task at 60 min, and reduced susceptibility to distracting information in the memory task at both 60 min and 90 min. These results replicate previous evidence which suggests that L-theanine and caffeine in combination are beneficial for improving performance on cognitively demanding tasks.

L-theanine, a natural constituent in tea, and its effect on mental state.

Asia Pac J Clin Nutr. 2008;17 Suppl 1: 167-8.

Nobre AC, Rao A, Owen GN. Unilever Food and Health Research Institute, Olivier van Noortlaan 120, Postbus 114, 3130 AC Vlaardingen, The Netherlands.

Tea is the most widely consumed beverage in the world after water. Tea is known to be a rich source of flavonoid antioxidants. However tea also contains a unique amino acid, L-theanine that may modulate aspects of brain function in humans. Evidence from human electroencephalograph (EEG) studies show that it has a direct effect on the brain (Juneja et al. Trends in Food Science & Tech 1999;10;199-204). L-theanine significantly increases activity in the alpha frequency band which indicates that it relaxes the mind without inducing drowsiness. However, this effect has only been established at higher doses than that typically found in a cup of black tea (approximately 20mg). The aim of the current research was to establish this effect at more realistic dietary levels. EEG was measured in healthy, young participants at baseline and 45, 60, 75, 90 and 105 minutes after ingestion of 50mg L-theanine (n=16) or placebo (n=19). Participants were resting with their eyes closed during EEG recording. There was a greater increase in alpha activity across time in the L-theanine condition (relative to placebo (p+0.05). A second study replicated this effect in participants engaged in passive activity. These data indicate that L- theanine, at realistic dietary levels, has a significant effect on the general state of mental alertness or arousal. Furthermore, alpha activity is known to play an important role in critical aspects of attention, and further research is therefore focussed on understanding the effect of L-theanine on attentional processes.

Psychological effects of dietary components of tea: caffeine and L-theanine.

Nutr Rev. 2008 Feb;66(2):82-90.

Bryan J. School of Psychology, University of South Australia, Adelaide, 5001, South Australia, Australia.

This review summarizes the literature on the association between two dietary components of tea, caffeine and L-theanine, and the psychological outcomes of consumption; it also identifies areas for future research. The studies reviewed suggest that caffeinated tea, when ingested at regular intervals, may maintain alertness, focused attention, and accuracy and may modulate the more acute effects of higher doses of caffeine. These findings concur with the neurochemical effects of L-theanine on the brain. L- theanine may interact with caffeine to enhance performance in terms of attention switching and the ability to ignore distraction; this is likely to be reflective of higher-level cognitive activity and may be sensitive to the detrimental effects of overstimulation. Further research should investigate the interactive effects of caffeine, L-theanine, and task complexity, utilize a range of ecologically valid psychological outcomes, and assess the neuroprotective effects of L-theanine using epidemiological or longer-term intervention studies among individuals at risk of neurodegenerative disease.

The effects of L-theanine, caffeine and their combination on cognition and mood.

Biol Psychol. 2008 Feb;77(2):113-22. Epub 2007 Sep 26.

Haskell CF, Kennedy DO, Milne AL, Wesnes KA, Scholey AB. Human Cognitive Neuroscience Unit, Division of Psychology, Northumbria University, Newcastle upon Tyne NE1 8ST, UK.

L-Theanine is an amino acid found naturally in tea. Despite the common consumption of L-theanine, predominantly in combination with caffeine in the form of tea, only one study to date has examined the cognitive effects of this substance alone, and none have examined its effects when combined with caffeine. The present randomised, placebo-controlled, double-blind, balanced crossover study investigated the acute cognitive and mood effects of L-theanine (250 mg), and caffeine (150 mg), in isolation and in combination. Salivary caffeine levels were co-monitored. L-Theanine increased 'headache' ratings and decreased correct serial seven subtractions. Caffeine led to faster digit vigilance reaction time, improved Rapid Visual Information Processing (RVIP) accuracy and attenuated increases in self-reported 'mental fatigue'. In addition to improving RVIP accuracy and 'mental fatigue' ratings, the combination also led to faster simple reaction time, faster numeric working memory reaction time and improved sentence verification accuracy. 'Headache' and 'tired' ratings were reduced and 'alert' ratings increased. There was also a significant positive caffeine x L- theanine interaction on delayed word recognition reaction time. These results suggest that beverages containing L-theanine and caffeine may have a different pharmacological profile to those containing caffeine alone.

The neuropharmacology of L-theanine(N-ethyl-L-glutamine): a possible neuroprotective and cognitive enhancing agent.

J Herb Pharmacother. 2006;6(2):21-30.

Nathan PJ, Lu K, Gray M, Oliver C. Behavioural Neuroscience Laboratory, Department of Physiology, Monash Center for Brain and Behaviour, Monash University, Australia.

L-theanine (N-ethyl-L-glutamine) or theanine is a major amino acid uniquely found in green tea. L-theanine has been historically reported as a relaxing agent, prompting scientific research on its pharmacology. Animal neurochemistry studies suggest that L- theanine increases brain serotonin, dopamine, GABA levels and has micromolar affinities for AMPA, Kainate and NMDA receptors. In addition has been shown to exert neuroprotective effects in animal models possibly through its antagonistic effects on group 1 metabotrophic glutamate receptors. Behavioural studies in animals suggest improvement in learning and memory. Overall, L-theanine displays a neuropharmacology suggestive of a possible neuroprotective and cognitive enhancing agent and warrants further investigation in animals and humans.

L-Theanine reduces psychological and physiological stress responses.

Biol Psychol. 2007 Jan;74(1):39-45. Epub 2006 Aug 22.

Kimura K, Ozeki M, Juneja LR, Ohira H. Nagoya University Department of Psychology, Chikusa-ku, Nagoya, 464-8601, Japan.

L-Theanine is an amino acid contained in green tea leaves which is known to block the binding of L-glutamic acid to glutamate receptors in the brain. Because the characteristics of L-Theanine suggest that it may influence psychological and physiological states under stress, the present study examined these possible effects in a laboratory setting using a mental arithmetic task as an acute stressor. Twelve participants underwent four separate trials: one in which they took L-Theanine at the start of an experimental procedure, one in which they took L-Theanine midway, and two control trials in which they either took a placebo or nothing. The experimental sessions were performed by double-blind, and the order of them was counterbalanced. The results showed that L-Theanine intake resulted in a reduction in the heart rate (HR) and salivary immunoglobulin A (s-IgA) responses to an acute stress task relative to the placebo control condition. Moreover, analyses of heart rate variability indicated that the reductions in HR and s-IgA were likely attributable to an attenuation of sympathetic nervous activation. Thus, it was suggested that the oral intake of L- Theanine could cause anti-stress effects via the inhibition of cortical neuron excitation.

CDP Choline Research Abstracts

Memory / Social Anxiety / Cognition / Mental Energy / GH

CDP-choline increases plasma ACTH and potentiates the stimulated release of GH, TSH and LH: the cholinergic involvement.

Fundam Clin Pharmacol. 2004 Oct;18(5):513-23.

Cavun S1, Savci V. Department of Pharmacology and Clinical Pharmacology, Uludag University Medical Faculty, 16059 Bursa, Turkey.

In the present study, we investigated the effect of intracerebroventricular (i.c.v.) administration of cytidine-5'-diphosphate (CDP) choline on plasma adrenocorticotropin (ACTH), serum growth hormone (GH), thyroid stimulating hormone (TSH), follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels in conscious rats. The involvement of cholinergic mechanisms in these effects was also determined. In basal conditions, CDP-choline (0.5, 1.0 and 2.0 micromol, i.c.v.) increased plasma ACTH levels dose- and time-dependently, but it did not affect the TSH, GH, FSH and LH levels. In stimulated conditions, i.c.v. administration of CDP-choline (1 micromol, i.c.v.) produced an increase in clonidine-stimulated GH, thyrotyropin-releasing hormone (TRH)-stimulated TSH, LH-releasing hormone (LHRH)-stimulated LH, but not FSH levels. Injection of equimolar dose of choline (1 micromol, i.c.v.) produced similar effects on hormone levels, but cytidine (1 micromol, i.c.v.) failed to alter plasma levels of these hormones. Pretreatment with hemicholinium-3, a neuronal high affinity choline uptake inhibitor, (20 microg, i.c.v.) completely blocked the observed hormone responses to CDP-choline. The increase in plasma ACTH levels induced by CDP-choline (1 micromol, i.c.v.) was abolished by pretreatment with mecamylamine, a nicotinic receptor antagonist, (50 microg, i.c.v.) but not atropine, a muscarinic receptor antagonist, (10 microg, i.c.v.). The increase in stimulated levels of serum TSH by CDP-choline (1 micromol, i.c.v.) was blocked by atropine but not by mecamylamine pretreatment. However, CDP-choline induced increases in serum GH and LH levels were greatly attenuated by both atropine and mecamylamine pretreatments. The results show that CDP-choline can increase plasma ACTH and produce additional increases in serum levels of TSH, GH and LH stimulated by TRH, clonidine and LHRH, respectively. The activation of central cholinergic system, mainly through the presynaptic mechanisms, was involved in these effects. Central nicotinic receptors solely mediated the increase in plasma ACTH levels while the activation of central muscarinic receptors was involved in the increase in TSH levels. Both muscarinic and nicotinic receptor activations, separately, mediated the increases in serum GH and LH levels after CDP-choline.

Effects of cytidine 5'-diphosphocholine administration on basal and growth hormone-releasing hormone-induced growth hormone secretion in elderly subjects.

Acta Endocrinol (Copenh). 1991 May;124(5):516-20.

Ceda GP(1), Ceresini G, Denti L, Magnani D, Marchini L, Valenti G, Hoffman AR.

The basal and GH-releasing hormone-stimulated secretion of GH declines in the elderly. We tested the ability of cytidine 5'-diphosphocholine, a drug used in the treatment of stroke and Parkinson's disease, to alter GH secretion in 11 healthy elderly volunteers, aged 69-84. Each subject received an iv infusion of 2 g of cytidine 5'-diphosphocholine or normal saline. GHRH and TRH were also administered during cytidine 5'-diphosphocholine infusions. The infusion of cytidine 5'-diphosphocholine induced a 4-fold (p less than 0.05) increase in serum GH levels over basal values. A small increase in GH was seen after GHRH administration. However, the addition of GHRH to the cytidine 5'-diphosphocholine infusion resulted in a GH response which was significantly greater than that seen after GHRH alone; the integrated concentration of GH was more than 2-fold greater in the cytidine 5'-diphosphocholine treated group (706.85 +/- 185.1 vs 248.9 +/- 61.4 micrograms.l-1.(120 min)-1; p = 0.01). The PRL and TSH responses to TRH were not significantly affected by cytidine 5'-diphosphocholine infusion, indicating that dopaminergic mechanisms are not involved. These studies demonstrate that cytidine 5'-diphosphocholine can enhance basal and GHRH-stimulated GH release in the elderly, but the mechanism of action of the drug remains unclear.

Citicoline: pharmacological and clinical review, 2006 update.

Methods Find Exp Clin Pharmacol. 2006 Sep;28 Suppl B:1-56.

Secades JJ, Lorenzo JL. Medical Department, Grupo Ferrer S.A., Barcelona, Spain.

Cytidine 5'-diphosphocholine, CDP-choline, or citicoline is an essential intermediate in the biosynthetic pathway of structural phospholipids in cell membranes, particularly phosphatidylcholine. Following administration by both the oral and parenteral routes, citicoline releases its two main components, cytidine and choline. Absorption by the oral route is virtually complete, and bioavailability by the oral route is therefore approximately the same as by the intravenous route. Once absorbed, citicoline is widely distributed throughout the body, crosses the blood-brain barrier and reaches the central nervous system (CNS), where it is incorporated into the membrane and microsomal phospholipid fraction. Citicoline activates biosynthesis of structural phospholipids of neuronal membranes, increases brain metabolism, and acts upon the levels of different neurotransmitters. Thus, citicoline has been experimentally shown to increase norepinephrine and dopamine levels in the CNS. Owing to these pharmacological mechanisms, citicoline has a neuroprotective effect in hypoxic and ischemic conditions, decreasing the volume of ischemic lesion, and also improves learning and memory performance in animal models of brain aging. In addition, citicoline has been shown to restore the activity of mitochondrial ATPase and membrane Na+/K+ATPase, to inhibit activation of certain phospholipases, and to accelerate reabsorption of cerebral edema in various experimental models. Citicoline has also been shown to be able to inhibit mechanisms of apoptosis associated to cerebral ischemia and in certain neurodegeneration models, and to potentiate neuroplasticity mechanisms. Citicoline is a safe drug, as shown by the toxicological tests conducted, that has no significant systemic cholinergic effects and is a well tolerated product. These pharmacological characteristics and the action mechanisms of citicoline suggest that this product may be indicated for treatment of cerebral vascular disease, head trauma (HT) of varying severity, and cognitive disorders of different causes. In studies conducted in the treatment of patients with HT, citicoline was able to accelerate recovery from post-traumatic coma and neurological deficits, achieving an improved final functional outcome, and to shorten hospital stay in these patients. Citicoline also improved the mnesic and cognitive disorders seen after HT of minor severity that constitute the so-called post-concussional syndrome. In the treatment of patients with acute ischemic cerebral vascular disease, citicoline accelerates recovery of consciousness and motor deficit, achieves a better final outcome, and facilitates rehabilitation of these patients. The other major indication of citicoline is for treatment of senile cognitive impairment, either secondary to degenerative diseases (e.g. Alzheimer disease) or to chronic cerebral vascular disease. In patients with chronic cerebral ischemia, citicoline improves scores in cognitive rating scales, while in patients with senile dementia of the Alzheimer type it stops the course of disease, and neuroendocrine, neuroimmunomodulatory, and neurophysiological benefits have been reported. Citicoline has also been shown to be effective in Parkinson disease, drug addictions, and alcoholism, as well as in amblyopia and glaucoma. No serious side effects have occurred in any series of patients treated with citicoline, which attests to the safety of treatment with citicoline.

Effect of CDP-choline on senile mental deterioration. Multicenter experience on 237 cases.

Minerva Med. 1990 Jun;81(6):465-70.

Serra F, Diaspri GP, Gasbarrini A, Giancane S, Rimondi A, Tam MR, Sakellaridis E, Bernardi M, Gasbarrini G. Scuola di Specializzazione in Geriatria e Gerontologia, 1a Cattedra di Patologia Speciale Medica e Metodologia Clinica, Universitˆ degli Studi di Bologna.

The efficacy of CDP-choline (1000 mg/die) administered for two 21-day treatment cycles, with a one-week wash-out period between them, was evaluated in out and in-patients suffering from mild to moderate brain aging. The study was performed on 237 fully evaluable patients with the use of the reduced geriatric scale of Plutchik and al., for clinical evaluation of the symptomatology. The clinical data obtained demonstrate that treatment with CDP-choline is able to determine an improvement of symptomatology since the 1st cycle of therapy (p less than 0.001), and a further improvement in the 2nd cycle (p less than 0.001). Particularly, the therapeutic effect of the 1st cycle is persistent in the intermediate wash-out period (suspension of treatment) with a further decrease, of symptomatology regarding some items of Plutchik's scale (p less than 0.01). Finally, treatment with CDP-choline 1000 mg/die for two 21-day cycles in 237 patients suffering from brain aging determined a statistically significant improvement of the cognitive and behavioural parameters taken into consideration: independence/autonomous life; human relations/social life; interest and attentive capacity; individual behaviour. Therefore citicoline is confirmed as a valid therapeutic remedy for the clinical, functional and social recovery of these patients.

Citicoline in the treatment of cognitive and behavioral disorders in pathologic senile decline.

Clin Ter. 1991 Jun 30;137(6):403-13.

Di Trapani G, Fioravanti M. Clinica Neurologica, Universitˆ Cattolica del Sacro Cuore di Roma.

A three months study was performed on 150 aging patients with primary memory deficits in order to verify the effectiveness of CDP-Choline, administered in repeated cycles of four weeks, with an interval of one week between cycles, in improving patients' cognitive and behavioral efficiency and in stabilizing their cognitive decline. Objective measures of memory and attention, and a behavioral rating scale were used to assess treatment effects. CDP-Choline treatment demonstrated both symptomatic efficacy and a long lasting effect on cognition and behavior of these patients. Level of activation and attention responsiveness improved during treatment cycles and no further changes were identified of these variables in the follow-up period. Measures related to specific memory functioning showed, besides improvements during treatment, after-effects still active in the follow-up period, suggesting a long lasting change of the cognitive decline trend characteristic of these patients.

Effect of CDP-choline on learning and memory processes in rodents.

Methods Find Exp Clin Pharmacol. 1992 Oct;14(8):593-605.

Petkov VD, Mosharrof AH, Kehayov R, Petkov VV, Konstantinova E, Getova D. Institute of Physiology, Bulgarian Academy of Sciences, Sofia.

The effects of cytidine (5') diphosphocholine (CDP-choline) on learning and memory were studied using conditioned reflex methods for passive avoidance and active avoidance with punishment reinforcement (step-through, step-down, shuttle box and maze), for active avoidance with alimentary reinforcement (staircase maze), and the Morris water maze. The majority of experiments involved comparative studies of the nootropic drugs meclofenoxate and/or piracetam. CDP-choline was administered orally, in some of the experiments also intraperitoneally, at doses of 10-500 mg/kg body weight once or twice daily for 5 or 7 days. In separate cases only single doses were administered. Trainings started one hour after the last dose of the drugs. Retention tests were given 3 h, 24 h, 7 days or 10 days after training. The results obtained with the different methods document CDP-choline's ability to improve learning and memory in rats and mice. No essential differences in the effects of CDP-choline were established upon oral and intraperitoneal administration of the drug. The learning- and memory-facilitating effects of CDP-choline were similar to those of meclofenoxate and piracetam. The results of the present study permit us to define CDP-choline as a substance capable of improving cognitive levels.

Citicoline improves verbal memory in aging.

Arch Neurol. 1996 May;53(5):441-8.

Spiers PA, Myers D, Hochanadel GS, Lieberman HR, Wurtman RJ. Clinical Research Center, Massachusetts Institute of Technology, Cambridge, USA.

OBJECTIVE: To test the verbal memory of older volunteers given citicoline.

DESIGN: A randomized, double-blind, placebo-controlled, parallel group design was employed in the initial study. After data analysis, a subgroup was identified whose members had relatively inefficient memories. These subjects were recruited for a second study that used a crossover design. The subjects took either placebo or citicoline, 1000 mg/d, for 3 months in the initial study. In the crossover study, subjects took both placebo and citicoline, 2000 mg/d, each for 2 months.

SUBJECTS: The subjects were 47 female and 48 male volunteers 50 to 85 years old. They were screened for dementia, memory disorders, and other neurological problems. Of the subjects with relatively inefficient memories, 32 participated in the crossover study.

MAIN OUTCOME MEASURE: Verbal memory was tested at each study visit using a logical memory passage. Plasma choline concentrations were measured at baseline; at days 30, 60, and 90 in the initial study; and at day 60 of each treatment condition in the crossover study. Plasma choline concentrations and memory scores were analyzed using repeated-measures analysis of variance and covariance, followed by planned comparisons when appropriate.

RESULTS: In the initial study, citicoline therapy improved delayed recall on logical memory only for the subjects with relatively inefficient memories. In the crossover study, the higher dosage of citicoline was clearly associated with improved immediate and delayed logical memory.

CONCLUSIONS: Citicoline therapy improved verbal memory functioning in older individuals with relatively inefficient memories. Citicoline may prove effective in treating age-related cognitive decline that may be the precursor of dementia.

Cytidinediphosphocholine (CDP-choline) for cognitive and behavioural disturbances associated with chronic cerebral disorders in the elderly.

Fioravanti M, Yanagi M. Department of Psychiatric Science and Psychological Medicine, University of Rome "La Sapienza", P.le A. Moro, 5, Rome, Italy, 00185.

BACKGROUND: CDP-choline (cytidine 5'-diphosphocholine) is a precursor essential for the synthesis of phosphatidylcholine, one of the cell membrane components that is degraded during cerebral ischaemia to free fatty acids and free radicals. Animal studies suggest that CDP-choline may protect cell membranes by accelerating resynthesis of phospholipids. CDP-choline may also attenuate the progression of ischaemic cell damage by suppressing the release of free fatty acids. CDP-choline is the endogenous compound normally produced by the organism. When the same substance is introduced as a drug it can be called citicoline.CDP-choline is mainly used in the treatment of disorders of a cerebrovascular nature. The many years of its presence in the clinical field have caused an evolution in dosage, method of administration, and selection criteria of patients to whom the treatments were given. Modalities of the clinical studies, including length of observation, severity of disturbance, and methodology of evaluation of the results were also heterogeneous. In spite of uncertainties about its efficacy due to these complexities, CDP-choline is a frequently prescribed drug for cognitive impairment in several European countries, especially when the clinical picture is predominantly one of cerebrovascular disease, hence the need for this review. Due to its effects on the adrenergic and dopaminergic activity of the CNS, CDP-choline has also been used as an adjuvant in the treatment of Parkinson's disease.

OBJECTIVES: To assess the efficacy of CDP-choline (cytidinediphosphocholine) in the treatment of cognitive, emotional, and behavioural deficits associated with chronic cerebral disorders in the elderly.

SEARCH STRATEGY: The trials were identified from a last updated search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 22 April 2004 using the terms CDP-choline, CDP, citicoline, cytidine diphosphate choline or diphosphocholine. The Register contains records from all major health-care databases and many ongoing trials databases and is updated regularly.

SELECTION CRITERIA: All relevant unconfounded, double-blind, placebo-controlled, randomized trials of CDP-choline for cognitive impairment due to chronic cerebral disorders were considered for inclusion in the review.

DATA COLLECTION AND ANALYSIS: Two reviewers independently reviewed the included studies, extracted the data, and pooled it when appropriate and possible. The pooled odd ratios (95% Confidence Interval (CI)) or the average differences (95% CI) were estimated. No intention-to-treat data were available from the studies included.

MAIN RESULTS: Fourteen studies were included in this review. Some of the included studies did not present numerical data suitable for analysis. Description of participants varied over the years and by type of disorders and severity, and ranged from aged individuals with subjective memory disorders to patients with Vascular Cognitive Impairment (mild to moderate), Vascular Dementia or Senile Dementia (mild to moderate). Seven of the included studies observed the subjects for a period between 20 to 30 days, one study was of 6 weeks duration, four studies used periods extending over 2 and 3 months, one study observed continuous administration over 3 months and one study was prolonged, with 12 months of observation. The studies were heterogeneous in dose, modalities of administration, inclusion criteria for subjects, and outcome measures. Results were reported for the domains of attention, memory testing, behavioural rating scales, global clinical impression and tolerability. There was no evidence of a beneficial effect of CDP-choline on attention. There was evidence of benefit of CDP-choline on memory function and behaviour. The drug was well tolerated.

AUTHORS' CONCLUSIONS: There was some evidence that CDP-choline has a positive effect on memory and behaviour in at least the short to medium term. The evidence of benefit from global impression was stronger, but is still limited by the duration of the studies. Further research with CDP-choline should focus on longer term studies in subjects who have been diagnosed with currently accepted standardised criteria, especially Vascular Mild Cognitive Impairment (VaMCI) or vascular dementia.

Citicoline (CDP-choline): mechanisms of action and effects in ischemic brain injury.

Neurol Res. 1995 Aug;17(4):281-4.

D'Orlando KJ, Sandage BW Jr. Interneuron Pharmaceuticals Inc., Lexington, MA 02173, USA.

Citicoline is approved in Europe and Japan for use in stroke, head trauma and other neurological disorders. It is presently being evaluated in phase II/III stroke trials in the United States. Exogenous administration of CDP-choline provides both choline and cytidine which access the brain and serve as substrates for the synthesis of phosphatidylcholine, a primary neuronal membrane component; the choline also enhances brain acetylcholine synthesis. Membrane repair and regeneration is necessary for recovery from stroke. Furthermore, citicoline may alleviate free fatty acid-induced toxicity which accompanies ischemic insult. Data from many pre-clinical and clinical trials support the hypothesis that citicoline may be a safe and effective treatment for stroke.

DMAE References

Mood / Well-Being / Cognition / Attention

Efficacy of dimethylaminoethanol (DMAE) containing vitamin-mineral drug combination on EEG patterns in the presence of different emotional states.

Eur J Med Res. 2003 May 30;8(5):183-91.

Dimpfel W, Wedekind W, Keplinger I. Pro Science, Private Research Clinic GmbH - med. Forschung und Entwicklung -, Kurt-Schumacher-Str. 9, D-35440 Linden, Germany.

The psychophysiological model of provoking different emotional states by watching film excerpts with various emotional contents was used to characterize drug action in 80 subjects (male/female=50%) with threshold emotional disturbance within a randomized, group-parallel, double-blind, placebo-controlled study. Analyzing the brain's electrical reaction during presentation of 5 videoclips of 7 min duration followed by 3 minutes pause revealed a content specific representation of topographical frequency changes. This procedure was repeated after 6 and 12 weeks of daily intake of a vitamin-mineral drug combination containing dimethylaminoethanol (DMAE) (Vitagerin Geistlich N) or placebo. Subjects taking the active drug for 3 months developed significant less theta and alpha1 power in sensomotoric areas of the cortex. The grade of change and statistical significance was dependend on the content of the excerpt, but the pattern of changes in general remained the same. Since decreases in theta and alpha1 electrical power have been associated with increased vigilance and attention, subjects taking the drug combination obviously were more active and felt better. - Analysis of the emotional change in mood profile as induced by the TV session was achieved by completing two different quenstionaires (POMS and Bf-S). Both scores revealed a better mood for the active drug group thus corroborating the results from EEG analysis. Therefore the vitamine-mineral drug combination containing DMAE can be interpreted to induce a psychophysiological state of better feeling of wellbeing on both levels of analysis mood and electrical pattern of brain activity in subjects suffering from borderline emotional disturbance.

The influence of 2-dimethylaminethanol (DMAE) on the mental and physical efficiency in man.

Act Nerv Super (Praha). 1967 Nov;9(4):417.

Danysz A, Smietański J, Panek W.

Effects of dimethylaminoethanol acetyl glutamate on the attentive capacity of a group of soccer players.

Arch Maragliano Patol Clin. 1974 Jul-Dec;30(2):189-98.

Rugginenti A.

Dimethylaminoethanol and personality disorders of the young adult. Electro-clinical correlations.

Ann Med Psychol (Paris). 1966 Apr;124(4):579-84.

Sabourin H, Rigal J, Savelli A, Yeghicheyan A.

Apropos of some cases of personality and behavior disorders in children treated by dimethylaminoethanol.

Gaz med fr. 1963 oct 10;70:2929-33.

Boutillier H, Corsetti R, Ducamin Jp, Rayboud M.

2-Dimethylaminoethanol in behavior disorders of childhood.

Sem Med. 1961 Sep 18;119:939-44.

Knobel M, Abramovsky H.