312 replies to this topic

[NoopMed]

Thanks for the great writeup! I know I'm new here, but I was wondering if any of these supplements you mentioned interact with Vyvanse? I know Paracetam does, but I want to ensure I dont risk excitotoxcity with the others. Thanks!

I'm not sure, a central goal of my nootropic stack has been to avoid the use of amphetamine derivatives. They are tested in urine screening in 3rd/4th year rotations and they also may lead to state dependent learning.

Out of curiosity, how does Vyvanse and Piracetam lead to excitotoxicity through combination? I was under the impression that amphetamines worked primarily on increasing synaptic dopamine and norepinephrine levels... Generally excitotoxicity is associated with excessive glutamate and calcium levels. Piracetam is thought to increase AMPA/NMDA receptor sensitivity to glutamate, but not necessarily through increasing synaptic levels-- however there is some flexibility to this logic in the potential for excitotoxicity, or at least the risk for it. (Which is why I avoid stuff like spicy Chinese food from the take-out place with a crapton of MSG in it! Also why I would never recommend to a recovering alcoholic or someone with acute head injury!)

[spinward]

Fantastic thread. I love the nitty gritty crazy medical detail (still learning my way through this stuff), though I confess I don't quite grasp all of it. Nonetheless, with regards to your discussion of citicoline:

Citicoline (CDP-Choline) is an intermediate compound that is formed endogenously in the process of synthesizing phosphatidylcholine from choline (12129,12140).
When taken orally, citicoline is metabolized in the gut to cytidine and choline. Both compounds are absorbed independently and taken up by brain cells. Within the brain cell cytidine is converted to cytidine monophosphate, cytidine diphosphate, and cytidine triphosphate. Choline is phosphorylated to form phosphocholine. Phosphocholine combines with cytidine triphosphate to reform citicoline. Citicoline then rapidly combines with diacylglycerol to from phosphatidylcholine (12129,12140,12195).
In animal models, orally administered citicoline increases brain phosphatidylcholine levels by 23% after 42 days and 30% after 90 days. In humans, a single dose of citicoline increases brain choline levels by about 18% in younger adults. But in older adults, brain choline levels don't seem to increase significantly. It's thought that choline uptake in the brain decreases with age, but cytidine uptake does not decrease (12129).

If i understand this study, it appears that as opposed to observations in animals, the circulating elements in citicoline appear to be uridine and choline in humans, not cytidine and choline. (http://web.mit.edu/d...www/pdf/972.pdf). If I remember right, the precursors for synthesizing phosphatidylcholine are choline, uridine, and a PUFA like DHA, so the phosphatidylcholine increasing effect still makes sense. There's also a rather extensive thread on the forum discussing the effects of uridine + choline + DHA (http://www.longecity...ne-uridine-dha/) that might shed some light on other mechanisms of action.

Also, I was wondering your opinion on stimulating nerve growth factor, perhaps with a supplementation regime of lion's mane and ALCAR? Benefits, side effects, etc.

[NoopMed]

Fantastic thread. I love the nitty gritty crazy medical detail (still learning my way through this stuff), though I confess I don't quite grasp all of it. Nonetheless, with regards to your discussion of citicoline:

Citicoline (CDP-Choline) is an intermediate compound that is formed endogenously in the process of synthesizing phosphatidylcholine from choline (12129,12140).
When taken orally, citicoline is metabolized in the gut to cytidine and choline. Both compounds are absorbed independently and taken up by brain cells. Within the brain cell cytidine is converted to cytidine monophosphate, cytidine diphosphate, and cytidine triphosphate. Choline is phosphorylated to form phosphocholine. Phosphocholine combines with cytidine triphosphate to reform citicoline. Citicoline then rapidly combines with diacylglycerol to from phosphatidylcholine (12129,12140,12195).
In animal models, orally administered citicoline increases brain phosphatidylcholine levels by 23% after 42 days and 30% after 90 days. In humans, a single dose of citicoline increases brain choline levels by about 18% in younger adults. But in older adults, brain choline levels don't seem to increase significantly. It's thought that choline uptake in the brain decreases with age, but cytidine uptake does not decrease (12129).

If i understand this study, it appears that as opposed to observations in animals, the circulating elements in citicoline appear to be uridine and choline in humans, not cytidine and choline. (http://web.mit.edu/d...www/pdf/972.pdf). If I remember right, the precursors for synthesizing phosphatidylcholine are choline, uridine, and a PUFA like DHA, so the phosphatidylcholine increasing effect still makes sense. There's also a rather extensive thread on the forum discussing the effects of uridine + choline + DHA (http://www.longecity...ne-uridine-dha/) that might shed some light on other mechanisms of action.

Also, I was wondering your opinion on stimulating nerve growth factor, perhaps with a supplementation regime of lion's mane and ALCAR? Benefits, side effects, etc.

ALCAR:

I did try out 500mg ALCAR BID for several months on its own, and ultimately abandoned it. However, I still take 10mg of it as part of the Spark Energy Drink I mention in previous posts. It seems to work well for many people, but in my case in seemed to acutely cause fatigue at the higher (recommended) doses, and long term seemed to correlate with weight gain and acne. After taking it for about 3 months I noticed those adverse effects, which reversed when I stopped using ALCAR. As I mentioned, I was taking 500mg twice a day, but this was also before I began taking any of the other supplements discussed on this thread besides Ginkgo biloba.

Here is the profile for ALCAR (again, please respond with the associated number if you'd like more info on the publication belonging to the claims listed):


POTENTIAL EFFECTIVENESS:

Age-related cognitive impairment. Taking acetyl-L-carnitine orally seems to improve some measures of cognitive function and memory in elderly people with age-related mental impairment (42,3600,3601).
Age-related testosterone deficiency. Taking acetyl-L-carnitine orally, in combination with propionyl-L-carnitine, seems to help symptoms of androgen decline in older men. The combination taken for 6 months seems to be similar to testosterone for improving sexual dysfunction, depression, and fatigue (12353).
Alzheimer's disease. Acetyl-L-carnitine might slow the rate of disease progression, improve memory, and improve some measures of cognitive function and behavioral performance in some patients with Alzheimer's disease. It is more likely to show some effect in those with early-onset Alzheimer's disease who are less than 66 years of age and have a faster rate of disease progression and mental decline (1594,1595,1596,1597,1598,1599,9105,10391). Acetyl-L-carnitine has not been compared with cholinesterase inhibitors such as donepezil (Aricept).
Chronic cerebral ischemia. Administering a single dose of acetyl-L-carnitine intravenously seems to produce short-term improvements in cerebral blood flow in people with chronic cerebral ischemia (1591,1592).
Cognitive impairment. Taking acetyl-L-carnitine orally seems to improve memory and visuospatial capacity in 30-60 year-old chronic alcoholics with cognitive impairment (1589).
Diabetic neuropathy. Patients with neuropathy related to type 1 or type 2 diabetes seem to have improved symptoms after taking acetyl-L-carnitine 1500-3000 mg daily in divided doses for a year. Acetyl-L-carnitine seems to increase nerve fibers, regenerate nerve fiber clusters, and improve vibratory sensations. However, research is conflicting on whether it can modestly improve nerve conduction velocity. In patients who have neuropathic pain as the most significant symptoms, taking acetyl-L-carnitine 1000 mg two to three times daily also decreases neuropathy-related pain within six months of beginning treatment. Doses of 500 mg three times daily do not seem to reduce pain. Acetyl-L-carnitine also seems more likely to be effective for reducing pain in patients with a shorter duration of diabetes and patients with poorly-controlled type 2 diabetes (1593,12743,12753,13007).
Infertility. Taking acetyl-L-carnitine orally, in combination with L-carnitine for 6 months, seems to increase sperm motility in men with infertility (12352). Some pregnancies occurred after taking these carnitines, but not enough to be statistically significant (12352). Taking acetyl-L-carnitine orally, in combination with L-carnitine and nonsteroidal anti-inflammatory drugs (NSAIDs), seems to improve male infertility caused by abacterial prostatovesiculoepididymitis, an inflammation of the prostate gland, seminal vesicles, and epididymis. The carnitines increase sperm count and motility. The carnitines are used following 2 months of treatment with NSAIDs (9791).
Peyronie's disease. Taking acetyl-L-carnitine orally seems to help treat acute and early chronic Peyronie's disease (10076). Acetyl-L-carnitine appears to be more effective than tamoxifen for reducing pain and inhibiting disease progression.


PROPOSED MECHANISM OF ACTION:


Acetyl-L-carnitine occurs naturally in the body. Endogenous carnitines exist as a "carnitine pool" consisting of L-carnitine and several acetyl-carnitine esters. Intracellular enzymes and cell membrane transporters can rapidly interconvert the carnitines to the needed form and transport them between the tissues and extracellular space. Acetyl-L-carnitine, the most important carnitine ester, is converted to L-carnitine in the body by carnitine acetyltransferase (10395,12744). The body obtains some carnitine from the diet, primarily from red meats and dairy products. The body can also synthesize carnitines from the amino acids, lysine and methionine. The kidney aids in keeping carnitine levels stable. Normally, greater than 90% of filtered carnitine is reabsorbed. If dietary intake of carnitines decreases, carnitine reabsorption becomes even more efficient (12744). Carnitines play an important role in lipid metabolism and energy production. They are essential for normal mitochondrial function, acting as a transporter of long-chain fatty acids into the mitochondria for beta-oxidation (12745,12748,12756,13007). Carnitine deficiency from inborn disorders of carnitine metabolism most often presents with symptoms of progressive cardiomyopathy and skeletal muscle weakness, and less frequently with fasting hypoglycemic coma (12748).
Acetyl-L-carnitine is structurally related to acetylcholine. It also serves as a precursor to acetyl coenzyme A, and contributes acetyl groups to acetylcholine (10395). It also seems to promote acetylcholine release and increases choline acetyltransferase activity (44). These effects have lead to the study of acetyl-L-carnitine in Alzheimer's disease, in which there is substantial cholinergic neuronal loss and acetylcholine depletion (1594). It may also lessen oxidative stress and prevent oxidative damage in the brain better than L-carnitine (12688).
Carnitine levels are lower in people with complications of diabetes (12746). In diabetic neuropathy, there is damage to sensory neuronal membranes. This causes an increase in sodium channels and therefore an increase in spontaneous neuronal firing. Acetyl-L-carnitine is thought to slow neuronal degeneration or help in the regeneration and repair of neurons and therefore decrease excessive excitability and firing. Acetyl-L-carnitine might improve peripheral as well as autonomic neuropathy (12749,12750,12751,12752,13007). Additionally, preliminary clinical research suggests that acetyl-L-carnitine might also improve glucose utilization, possibly by increasing expression of glycolytic and gluconeogenic enzymes (12754).
In HIV patients, acetyl-L-carnitine might slow the loss of CD4 lymphocytes by reducing apoptosis and increasing the serum level of insulin-like growth factor 1 which protects against apoptosis (3605). Lower plasma levels of acetyl-L-carnitine are also associated with neuropathy in people who take HIV drugs (3606). Preliminary research suggests it might increase the activity of nerve growth factor and promote peripheral nerve regeneration. It might also have analgesic properties. However, it doesn't seem to affect viral load or CD4 or CD8 cell counts (12745).
Preliminary research suggests acetyl-L-carnitine might also prevent cisplatin (Platinol) and paclitaxel (Taxol)-induced neuropathy (12755).
Acetyl-L-carnitine and L-carnitine are present in human sperm and seminal fluid (3607). Their levels increase in sperm during the maturation process in the epididymis and coincide with the acquisition of progressive motility (3608,3609). Levels of acetyl-L-carnitine, and the ratio of acetyl-L-carnitine to L-carnitine, have been reported to be lower in infertile semen and sperm samples with low motility (3610,3611), and an increase in sperm motility is seen in vitro when acetyl-L-carnitine or L-carnitine is added to the sample (3612). Preliminary research also suggests acetyl-L-carnitine may increase testosterone production and improve testicular function (12686,12687).
In patients with alcohol-induced cirrhosis, serum levels of L-carnitine and its esters are sometimes increased, possibly due to increased L-carnitine biosynthesis (1931,1948).

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Neuron Growth:

In regard to Lion's Mane; I've never tried it nor read much about it. I'm also not seeing a lot of information on it in my alternative medicine resources, but the claims on Wikipedia are intriguing. The study on mild cognitive impairment seems to show good potential: http://www.ncbi.nlm....pubmed/18844328


Noopept, a derivative of Piracetam has been shown to increase expression of BDNF and NGF in the rat hippocampus. I have tried Noopept, and found it both pleasant and useful in studying, however; it's a rather new, expensive synthetic chemical and I'm weary of taking it chronically for the longterm as the side effect profile is not likely well known. Subjectively, it makes me feel a little spacey and seems to diminish my recall a bit, so I wouldn't use it for an exam, but I do find that I retain information from study sessions very well when taking it.

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Finally, an update of my current generalized status:
Exams continue to go very well, still performing in the top 1-5% of the class, and stable on my current stack. No new, major adverse effects have presented, however; I have continued to experience some issues with an amplification of the effects of alcohol when taking this stack, and I've also experienced some changes in mood.

Alcohol and Nootropics:

I believe this to primarily stem from the allosteric modification of AMPA glutamate channels by the racetams-- as Alcohol also works on these channels as an inhibitor. Contrary to what you might imagine, my long term memory formation is dramatically reduced when Piracetam is combined with Alcohol when compared to Alcohol alone. Since we frequently have post-exam celebrations, I have to be very cognizant my piracetam and alcohol levels at these events. I don't drink alcohol regularly, but I learned in undergrad that my innate tolerance is remarkably high. ie. I could be drinking with a group of friends at a party, and after 8-12 drinks I'm still fully able to have a very fluent conversation about science, philosophy, etc with someone who is sober and they usually don't even think I've been drinking; meanwhile my friends are starting to blackout. It certainly inhibits my coordination as much as the next man (cerebellum, basal ganglia, brainstem nucleii, etc)-- I just tend to be very resistant to cortical/cognitive inhibition. 3-4 drinks of Alcohol in combination with Piracetam basically brings me to the cognitive state that I would normally experience at 8-12 drinks-- so as you can imagine, 8-12 drinks with piracetam has invariably led to a pretty fragmented memory of the previous evening. Restraint should always be exercised in the use of alcohol, but this can certainly be difficult when literally the entire class is partying like it's New Years Eve after a particularly hard final exam. It's possible that this trend is unique to my school, but I've gotten the impression from medical students at other universities as well. Regardless, I would recommend caution when drinking alcohol with nootropics. Milk Thistle is also a supplement to consider when drinking, as it appears to reduce hepatocyte inflammation and potentially increases the metabolism of alcohol. Many people take it to prevent hangovers and/or reduce the effects of drinking.

Oxiracetam:

I've purchased and tried some oxiracetam in combination with piracetam after reading many positive reviews of this combination. Even the bulk powder is remarkably expensive when compared to piracetam, so I've only used it very sporadically. Subjectively it seems to have stronger stimulant properties than other nootropics. It also seems to take a few hours to feel the effects, but they also seem to last substantially longer than piracetam. I really enjoy it. I used it on my last exam, and my performance was on par with previous exams since starting piracetam. Since I've reached the top echelon, it's hard to continue using the score earned on these exams as an objective measure of performance, but subjectively it did feel like I was doing better and my confidence in answers was improved. Additionally, I did finish the exam about 25% faster than I normally do (they're always the same allotted time and roughly the same number of questions). Many other students complained that this particular exam either took them longer than normal or that they had altogether run out of time to complete the exam, so I guess this could be seen as a somewhat objective measure of performance.

Choline:

Other threads on here discuss the association between brain acetylcholine levels and depression, anxiety, and other mood disorders. I've never considered myself a depressed person or been diagnosed with any permutation of depression, but like many people, I'm susceptible to transient "bad days", "woke up on the wrong side of the bed," etc. In the last month or so I've noticed more of these than usual. The life of a medical student is a tumultuous and ever-changing one, filled with stress, pressure and sleep deprivation. Not to mention our desire to simultaneously maintain some semblance of a "normal" life, ie romance, entertainment/relaxation, and basic activities of daily living. Considering the strain on the latter aspects of life by the prior aspects of med-life, measuring changes in mood while taking nootropics is akin to predicting the weather in the pacific northwest. Regardless, I've been reducing my choline intake. I'm not sure I'll see a change in mood, as I've not encountered a chronically bad mood as of yet, but I'd rather avoid it and find a minimum effective dose of choline.


My Current Stack:

Every Other Day:
300mg CDP Choline (citicoline)
(This actually has a VERY long half-life-- 72 hours. So I've been trying to take citicoline much less often.)

Morning:
1 Scoop Spark Energy Drink from Advocare
800mg Piracetam
120mg Extended Release Ginkgo biloba
1000mg Fish Oil

Average Afternoon:
Large cup of coffee
800mg Piracetam
500mg Choline bitartate


Heavy Study Afternoons:

800mg Piracetam
500mg Choline bitartate
750mg Oxiracetam
120mg Extended Release Ginkgo




That's all for now! Happy Noopin'!

[Justin Garrett Hill]

Nice posts!

I Have been experimenting with quite a few Nootropics for about 3 months....

Sam-e (Nature Made)- 1 x 800mg / morning for 3 months (started August, 1st 2012)
Noopept (HealthSupplelements4less) - 1 x 30mg / morning for 2.5 months (going to stop this for a month now, but started September 10th 2012)
Citicoline (Jarrow) 1 x 500mg morning for 2.5 months (started September 10th 2012)
Piracetam (Serious Nutrition Solutions) 1 x 3g /morning for 2 months (just decided to switch to 2x 2g / morning and then afternoon, started September 20th 2012)
Sulbutiamine (healthsupplements4less) 1 x 500mg /morning for 1.5 months (started October 1st 2012)
Pramiracetam (healthsupplements4less) 1 x 250mg / morning for 1 month (started October 12th 2012)
Oxiracetam (healthsupplements4less) 1 x 750mg / afernoon for 1 month (started OCtober 17th 2012)
Aniracetam (healthsupplements4less) 1x 500mg / morning for 2 weeks (started Novemeber 1st 2012)
Omega-3 (Trader Joes) 1 x 1200 mg / day
AZ energy drink (200mg caffeine+ various typical energy drink blend) 1-2 x day

Yup...I've gone pretty much all in! Long story short, I have felt a very noticeable effect and can say with confidence that the Sam-e, noopept, pramiracetam, and oxiracetam, and the energy drink have nootropic and mood enhancing effects. I could go into more detail about the nuances of my experiences with them, but that would feel like too much detail for right now. I just wanted to point out that I am an experienced nootropic experimenter. As far as side effects, the only 2 things that have happened is that I have had a very small internal eye twitch (not visibly observable). And also, while it may be unrelated, I have either been bitten by mosquitoes or some type of insect, and have had a poor immune response to it ( I have had this once before though where I was bitten by something and bore the mark for 2 months, and was not on any supplements at that time), I mention these two negative issues though because I did read of similar experiences through out this thread. I plan on taking the advice for the eye twitch and trying to eat more regularly, and just last night I applied coconut oil which I purchased from trader joes and applied it to my "bites", and today was the first time I noticed an improvement, so I thought I would pass that along, in case it is helpful to anyone else...

Also notable is that I feel like I may have developed a bit of tolerance to my stack. I am no longer feeling the intensities that I once did from the various supplements. When I first started some of them felt like a very low level psychedelic but with anxiolytic properties and less distortion of senses.

Anyways, I have to get on with my day, just thought I would chime in...
-Justin

[SmittyBrad]

This is a very good thread, OP. It is rather rare in the internet forum world to find someone who is both medically knowledgeable and also willing to write in depth about his trials with a variety of nootropics. Thank you for taking the time.

I have a couple of questions if you don't mind:

1. You mention in the original post and a few times thereafter that you experience crashes throughout the day with some nootropics, including rhodiola and gingko, which cause you to avoid using them on a regular basis (although it appears that you are back to taking gingko daily).

You seem to rely fairly heavily on caffeine, however. I am cognizant (perhaps overly so) of my daily caffeine intake due to the inevitable crashes and up/down experience that it can cause, as well as the tolerance that seems to build with persistent use. I love the effects though and maybe I am being too cautious. Is there some reason that crashing and/or becoming tolerant to caffeine does not pose the same concern to you as it does with other substances?

2. It seems that your performance in medical school has improved drastically from when you first began (~ top 50-60% in your class to top 5%). Subjectively, what % of this improvement do you attribute to "normal" factors (adopting better study methods, studying harder, longer, and more seriously, adjusting to a more demanding schedule, etc) and with what % do you credit nootropics? A hard question to answer, but I'm curious to see what you think.

Thank you again and I wish you continued success.

[NoopMed]

Nice posts!

I Have been experimenting with quite a few Nootropics for about 3 months....

Sam-e (Nature Made)- 1 x 800mg / morning for 3 months (started August, 1st 2012)
Noopept (HealthSupplelements4less) - 1 x 30mg / morning for 2.5 months (going to stop this for a month now, but started September 10th 2012)
Citicoline (Jarrow) 1 x 500mg morning for 2.5 months (started September 10th 2012)
Piracetam (Serious Nutrition Solutions) 1 x 3g /morning for 2 months (just decided to switch to 2x 2g / morning and then afternoon, started September 20th 2012)
Sulbutiamine (healthsupplements4less) 1 x 500mg /morning for 1.5 months (started October 1st 2012)
Pramiracetam (healthsupplements4less) 1 x 250mg / morning for 1 month (started October 12th 2012)
Oxiracetam (healthsupplements4less) 1 x 750mg / afernoon for 1 month (started OCtober 17th 2012)
Aniracetam (healthsupplements4less) 1x 500mg / morning for 2 weeks (started Novemeber 1st 2012)
Omega-3 (Trader Joes) 1 x 1200 mg / day
AZ energy drink (200mg caffeine+ various typical energy drink blend) 1-2 x day

Yup...I've gone pretty much all in! Long story short, I have felt a very noticeable effect and can say with confidence that the Sam-e, noopept, pramiracetam, and oxiracetam, and the energy drink have nootropic and mood enhancing effects. I could go into more detail about the nuances of my experiences with them, but that would feel like too much detail for right now. I just wanted to point out that I am an experienced nootropic experimenter. As far as side effects, the only 2 things that have happened is that I have had a very small internal eye twitch (not visibly observable). And also, while it may be unrelated, I have either been bitten by mosquitoes or some type of insect, and have had a poor immune response to it ( I have had this once before though where I was bitten by something and bore the mark for 2 months, and was not on any supplements at that time), I mention these two negative issues though because I did read of similar experiences through out this thread. I plan on taking the advice for the eye twitch and trying to eat more regularly, and just last night I applied coconut oil which I purchased from trader joes and applied it to my "bites", and today was the first time I noticed an improvement, so I thought I would pass that along, in case it is helpful to anyone else...

Also notable is that I feel like I may have developed a bit of tolerance to my stack. I am no longer feeling the intensities that I once did from the various supplements. When I first started some of them felt like a very low level psychedelic but with anxiolytic properties and less distortion of senses.

Anyways, I have to get on with my day, just thought I would chime in...
-Justin

Sounds like a pretty comprehensive stack. I'm not sure what the AZ energy drink is... is that Arizona Iced Tea's "Rx Energy" drink? Personally, I wasn't a huge fan of Pramiracetam when I tried it... felt pretty "speedy." Oxiracetam did a similar thing for me, but it felt "smoother" in that I didn't feel physical adverse effects, like muscle twitching, jitters, and excess startle reflex. Taking all the racetams at once, it can be pretty hard to distinguish which effects are coming from where, but other people do vouch for synergy between them. I've noticed great synergy between Piracetam and either Aniracetam, Noopept, or Oxiracetam taken independently, in my own experimentation. The only time I've mixed more than 2 is with Piracetam, Aniracetam, and Noopept-- although I've never tried this on a regular enough basis to comment conclusively on the combination.

SAM-e has some wonderful promise in the field of psychiatry with its potential as an antidepressant, and current research is also promising for its potential as a nootropic and anti-senility drug. You may bock at the idea of using an antidepressant, but few things can inhibit mental performance more than depression, and the prevalence of undiagnosed depression is astounding. It's unlikely that taking SAM-e for an extended period of time would produce a Nootropic effect on its own, but once would likely notice a significant improvement in mood and motivation, and this in itself can contribute to the endeavor of a hard working student. Also, SAM-e use shows increased serotonin turnover and elevated dopamine and norepinephrine levels, which should work synergistically with Ginkgo and other nootropics to enhance mental function. Also of note, the prescription atypical antidepressant drug Bupropion (Welbutrin) has been claimed as a Nootropic by many. It blocks the reuptake of Norepinephrine and Dopamine, leading to higher levels in the neuron synapse, which again-- can be associated with heightened mental function. I'll post SAM-e's monograph from Nat Med below, indicating how most physicians currently view the use of SAM-e, then get to your side-effects/concerns:

SAM-e (S-adenosyl-L-methionine):


Effectiveness:

LIKELY EFFECTIVE
Depression. Taking SAMe orally significantly improves symptoms of major depression. Several clinical studies show that taking SAMe is more effective than placebo and appears to be as effective as tricyclic antidepressants in trials lasting up to 42 days (2082,2083,5189,5190,5192,5195,5196,5231,9108,9109,17490). However, some of these studies are limited by small numbers of patients, inconsistent diagnostic criteria, short treatment periods, and potentially flawed study designs (3562,5189,5231,9108).
In patients who don't respond to conventional antidepressants, adding a specific SAMe supplement (SAMe Complete 400 mg, Nature Made) 400 mg to 800 mg twice daily to conventional treatment significantly increases remission rates by about 14% after 6 weeks. About 7 patients need to be treated with SAMe for 6 weeks for one additional non-responding patient to have remission (17490).
Administering SAMe intravenously or intramuscularly, short-term, also significantly improves symptoms of major depression. Several small-scale clinical trials have shown that parenterally administered SAMe is superior to placebo and possibly as effective as intravenous or oral tricyclic antidepressants in studies lasting up to 30 days (2082,3562,5184,5189,5200,5231,9109). In some trials, the antidepressant effect occurred rapidly, within 1-2 weeks of initiation of treatment (5200). This benefit is likely the result of the parenteral route of administration (3562). Parenteral SAMe has been used successfully in combination with an oral tricyclic antidepressant to speed the onset of antidepressant action (5193).
Practice guidelines from the American Psychiatric Association suggest SAMe as a potential alternative to conventional antidepressants (e.g., paroxetine, venlafaxine, etc) for patients with major depression who are interested in using alternative therapies (17491). The Canadian Network for Mood and Anxiety Treatments (CANMAT) also recommends SAMe as an effective option for second line treatment of mild to moderate depression (17123).

Osteoarthritis. Multiple clinical trials show that taking SAMe orally is superior to placebo and comparable to NSAIDs, including the COX-2 inhibitor celecoxib (Celebrex), for decreasing symptoms associated with osteoarthritis. SAMe is associated with fewer adverse effects than NSAIDs and is comparable in reducing pain and improving functional limitation (5188,5199,5203,5204,5205,5206,5207,5208,5209,5215,9108) (9111,12054). Significant symptom relief with SAMe may require up to 30 days of treatment compared to only 15 days with NSAIDs. Some evidence suggests that intravenous loading doses of SAMe given over five days, followed by oral treatment, can speed symptom relief to 14 days (5188).

POSSIBLY EFFECTIVE
AIDS-related myelopathy. Administering SAMe intravenously seems to improve AIDS-related myelopathy. SAMe has investigational orphan drug status for this use (1691,5217,5218).

Fibromyalgia. Taking SAMe orally seems to improve fibromyalgia. Two clinical trials demonstrated significant improvement in symptoms of fibromyalgia compared to placebo (5211,5241). But administering SAMe intravenously doesn't seem to improve symptoms of fibromyalgia (5221).

Intrahepatic cholestasis. Administering SAMe orally or intravenously seems to be helpful for treating intrahepatic cholestasis associated with acute or chronic liver disease and pregnancy-related intrahepatic cholestasis. Multiple clinical trials have shown that short-term SAMe therapy is superior to placebo in decreasing pruritus, fatigue, alkaline phosphatase levels, and total and conjugated bilirubin (5219,5238,5239,5240,9108). Trials have more frequently used injectable dosage forms than oral formulations (5219).

INSUFFICIENT RELIABLE EVIDENCE to RATE
Alcohol-related liver disease. The effect of SAMe in alcohol-related liver disease is inconsistent. Some preliminary clinical research shows that administering SAMe orally or intravenously decreases elevated alanine transaminase (ALT) levels, bilirubin, and some symptoms associated with chronic liver disease (1712,5235,5236,14840). However, SAMe does not significantly affect other measures of liver dysfunction including prothrombin time, albumin, aspartate transaminase (AST), or alkaline phosphatases (ALP) levels. SAMe also does not significantly reduce all-cause mortality, liver-related complications, transplant rates, or alcohol consumption (14840).

Attention deficit-hyperactivity disorder (ADHD). Preliminary research suggests SAMe might lessen ADHD symptoms in adults (9981).
More evidence is needed to rate SAMe for these uses.



Mechanism of Action:

S-adenosylmethionine (SAMe) is a naturally occurring molecule that is distributed throughout virtually all body tissues and fluids (5231). Concentrations are highest in childhood and decrease with age (9114). SAMe plays an essential role in more than 100 biochemical reactions involving enzymatic transmethylation. It contributes to the synthesis, activation and/or metabolism of hormones, neurotransmitters, nucleic acids, proteins, phospholipids, and some drugs (5231,5232,9110). SAMe is produced endogenously from homocysteine and 5-methylene tetrahydrofolate (17490). Its synthesis is closely linked to vitamin B12 and folate metabolism (5231). Deficiencies of these vitamins can result in decreased SAMe concentrations in the central nervous system (5231).
The mechanism for the antidepressant effect is unknown, but SAMe is associated with increased serotonin turnover and elevated dopamine and norepinephrine levels (5196,5232,9110,17490). Low levels of SAMe have been reported in the cerebrospinal fluid (CSF) of severely depressed patients, and these levels can be increased by oral and parenteral administration of SAMe (17122). SAMe supplementation may also work by altering cellular membrane fluidity. Changes in neuronal membrane fluidity might facilitate signal transduction across membranes and increase the efficiency of receptor-effector coupling (5196,9110). Neuroimaging studies indicate that SAMe affects the brain similarly to conventional antidepressants (9114,14841). The onset of action for EEG changes is about 1 hour, with a peak effect after 2 weeks of use. EEG changes might be more pronounced in the elderly (14841).
SAMe supplementation may be beneficial in osteoarthritis due to analgesic and anti-inflammatory effects. After oral administration of 400 mg daily for seven days, SAMe levels in synovial fluid increase by 3 to 4 fold (9110). Preliminary evidence suggests SAMe might stimulate articular cartilage growth and repair, specifically chondrocyte proteoglycan synthesis and proliferation rate (5209,9110). SAMe might also protect against cytokine-induced cell damage by antagonizing the activity of tumor necrosis factor-alpha (TNF-alpha) on synovial cell proliferation and fibronectin mRNA expression (9110).
In liver disease, there appears to be a deficiency in hepatic SAMe. People with acute and chronic liver disease lose the ability to synthesize SAMe from methionine, possibly due to low activity of methionine adenosyl transferase (MAP), the enzyme that converts methionine to SAMe (9115). This can lead to deficiencies in cysteine and choline. It can also lead to depletion of glutathione, which plays a major role in liver detoxification and antioxidant reactions. This depletion may in turn exacerbate liver disease (5198,5219,5236,9116). SAMe supplementation seems to increase the synthesis of glutathione (14840).
In alcoholic liver disease, SAMe may restore levels of glutathione, decrease inflammation, and increase methylation of DNA (10465).
In AIDS-related myelopathy, endogenous SAMe can be depleted. Epidemiological data suggests that people with AIDS have a deficiency of SAMe in their cerebrospinal fluid (CSF), which may lead to myelopathy by impairing SAMe dependent myelin and oligodendrocyte repair mechanisms (1691,5217,5218).
In gastrointestinal stress ulcers there is some evidence that SAMe might have a cytoprotective effect (5213).
SAMe is metabolized to s-adenosylhomocysteine, which can be metabolized to homocysteine (5232). Homocysteine is remethylated to form methionine, which can then form more SAMe, or be converted via transsulfuration to the antioxidant glutathione (5232). These reactions require folate, cyanocobalamin (vitamin B12), and pyridoxine (vitamin B6) (5231). There has been some concern that taking SAMe might increase homocysteine levels. Elevated levels of homocysteine have been linked to cardiovascular and renal disease (1698). However, in a study lasting 4 weeks, administration of SAMe orally in doses titrated up to 1600 mg/day, there was no significant increase in homocysteine levels (12231). In another study, there also was no difference in cardiovascular mortality in people with cirrhosis taking SAMe 1200 mg daily for two years (1712).
Low levels of SAMe have actually been correlated with coronary artery disease (1714). Administration of SAMe to healthy people has shown a positive effect on 5-methyltetrahydrofolate, a key cofactor in homocysteine metabolism. SAMe supplementation has been suggested as a remedy for elevated homocysteine levels (1713). Some research suggests that adequate intracellular SAMe promotes remethylation and transsulfuration of homocysteine (9112).
SAMe can induce symptoms resembling Parkinson's disease in animal models. This effect may be related to the ability of SAMe to add methyl groups to L-dopa. L-dopa has been shown to deplete the concentration of SAMe, which might explain the depression sometimes seen with Parkinson's disease (10466).
Oral SAMe has a low bioavailability, which is presumably the result of rapid and significant first-pass effect. Enteric-coated tablets produce peak plasma concentrations about 3 to 5 hours after ingestion, with a half-life of about 100 minutes. SAMe is excreted in urine and feces (5231). SAMe crosses the blood-brain barrier (5231,9110,17122).




In regard to your complaints:

1.) Eye Twitching: This is probably a benign "blepharospasm," which is very common with the hat-trick of high caffeine intake, stress, and lack of sleep. HOWEVER, you describe your eye twitching "internally..." Is your eye-ball itself moving if you look in the mirror while it happens? Do you experience blurred vision? Or is it more that you feel your eye twitch, but it's actually the edge of your upper or lower eye lid that moves? (This often feels "internal," but is actually external to the eye itself.) Surprisingly there's a huge difference here in terms of the neuroanatomy involved. (ie Cranial Nerve 7 vs Cranial Nerves 3/4/or 6 and all the optic nucleii...) The latter lid twitching (CN7) is nothing serious to worry about, and will go away if you reduce the caffeine and get more sleep. (Also reducing sulbutiamine, SAM-e, oxi/ani-racetam, or citicoline might help-- as these all have stimulant effects.) If your eyeball itself is actually moving/twitching when this happens, this is called "Nystagmus", and can be related to many things outside the scope of stimulant overuse and could be more serious. I would recommend seeing a doctor (neurologist) if that is the case, as this requires some additional testing and evaluation. They will likely recommend stopping all nootropics.

2.) Insect Bites: Unless you actually saw the insects biting you, I would be more inclined to consider a medication allergy. Can you describe the spots? How many? Color? Size? Discharge/puss? Location? Are they clustered, in a line, evenly distributed, other? Do they itch? Are they flat or raised? Do you even notice other symptoms, like shortness of breath? Increased heart rate? Dizziness? Or a tightness in your throat? (Systemic allergic reaction.) Sometimes skin reactions, either from insect bites, or allergy, can take a long time to heal, but they generally don't have a full inflammation response throughout that time...(Usually will just be spots, without so much redness after the first few days.) Coconut oil may help, as you mentioned. Some hydrocortisone cream/ointment from the pharmacy at your grocer might help even more... However, these are retroactive solutions, and it would be better to find the root of the problem. Aniracetam has been known to cause rashes in some people. Basically anything can cause a rash like this if your unique immune system decides to react, hahaha.

3.) Tolerance: One is bound to build tolerance to all of the nootropics. The racetams generally have the most noticeable effect after the first 3-4 days, and up through the first 2 weeks. After that, there seems to be a reduction in the subjective effect that levels out, but still remains far, far above baseline performance-- at least for me. And, objectively, my performance remains much higher on tests, etc. Caffeine definitely does the same thing. You'll find that if you abruptly remove this stack, you'll drop below your normal baseline performance, but gradually return to normal. This is why one should always TAPER their doses down gradually when they plan to quit using a nooptropic stack. Looking at your stack specifically, it looks like you could use more (or perhaps a difference source of) Choline. Too little choline with all the racetams you're taking will lead to a choline deficit that will feel much worse than simple tolerance. I found that I had to take about 1500mg/day of various sources of choline before I leveled out. Up to 3000mg per day is considered safe experts, however, at high doses you might experience nausea, vomiting, asthma, decreased heart rate, vision blurring etc... since Acetylcholine is also a peripheral neurotransmitter involved heavily in the "Autonomic Nervous System." You should monitor for these effects diligently. Personally, I would reduce the Citicoline down to 1x250mg, as this has additional stimulant effects intrinsically, which are unrelated to its use a precursor to Acetylcholine. Consider introducing Alpha-GPC at breakfast and again at lunch, or perhaps Choline-bitartrate (cheaper, though this is not as likely to be as effective.)

[NoopMed]

This is a very good thread, OP. It is rather rare in the internet forum world to find someone who is both medically knowledgeable and also willing to write in depth about his trials with a variety of nootropics. Thank you for taking the time.

I have a couple of questions if you don't mind:

1. You mention in the original post and a few times thereafter that you experience crashes throughout the day with some nootropics, including rhodiola and gingko, which cause you to avoid using them on a regular basis (although it appears that you are back to taking gingko daily).

You seem to rely fairly heavily on caffeine, however. I am cognizant (perhaps overly so) of my daily caffeine intake due to the inevitable crashes and up/down experience that it can cause, as well as the tolerance that seems to build with persistent use. I love the effects though and maybe I am being too cautious. Is there some reason that crashing and/or becoming tolerant to caffeine does not pose the same concern to you as it does with other substances?

2. It seems that your performance in medical school has improved drastically from when you first began (~ top 50-60% in your class to top 5%). Subjectively, what % of this improvement do you attribute to "normal" factors (adopting better study methods, studying harder, longer, and more seriously, adjusting to a more demanding schedule, etc) and with what % do you credit nootropics? A hard question to answer, but I'm curious to see what you think.

Thank you again and I wish you continued success.

1.) My solution to reintroducing Ginkgo biloba was to begin on a "Time-release" / "Extended-release" formula. I find the effects much less intense, and much longer lasting. I no longer experience a crash when I take it. There are only a few brands that manufacture the extended release formula. Personally, I've tried all sorts of nootropic combinations, and none seem to work as well without Ginkgo, so I keep it around. I recently discovered it is NOT a MAO inhibitor-- I think I claimed this in a recent posting, and this was based on a paper that was later replaced by a more accurate study. Turns out, Ginkgo is a Norepinephrine reuptake inhibitor-- which is doing something very similar in terms of neurotransmitter action as the MAO-I, but without the risk of reacting with certain Tyramine-containing foods. Rhodiola rosea, on the other hand, is indeed a MAO A and MAO B inhibitor-- though its short acting, weak, and reversible, so it's still relatively safe even with tyramine containing foods. Rhodiola is nice, and in combination with Ginkgo biloba, I found it to extend and smooth out the effects... but often it would make me a bit drowsy throughout its duration. It also seemed to stifle my creativity. Unlike caffeine, I find that removing Ginkgo abruptly from my stack produces no side-effects, like headache, etc... However, within a few days, I definitely notice a decrease in mental performance in the absence of ginkgo. Overall, coffee has been shown to have many beneficial collateral effects-- aside from just mental stimulation. ie. Anticancer, antioxidant, antialzheimer's, and more. There's a well known researcher at my university involved in cancer therapies, anti-aging, and nutrition research that swears by 3-5 cups of coffee per day as a sort of "fountain of youth." And, I've found his arguments very convincing. Additionally, caffeine's mode of stimulation is much different than anything else mentioned here-- as it's an adenosine receptor antagonist, and produces alertness instead of stimulation through the catacholamine pathways. Tolerance and crashes from caffeine do not concern me as much because coffee is so readily available, socially accepted (ie. I can be slurping down coffee all day and no one will think twice, but I can't as easily pop various pills all day), and the other benefits from coffee are an added bonus. Strangely, as I've increased my coffee intake from 1 in the morning, to about 3-4 cups throughout the day, I've actually started sleeping better at night... just as long as I don't drink any after 6pm.

2.) It's not really possible to attribute my performance to distinct factors like that. Improvement of the "normal" factors definitely plays a major part in my recent advances, but starting on a nootropic stack is what led to my improvement of the "normal" factors. The two are not mutually exclusive. I study harder, longer, and more seriously, and I'm awake for more hours of the day currently than I've ever been before. For the first year of school, I had tried to maintain these levels of "normal" scholastic behavior, but I was unsuccessful. Now it is no longer a problem. I take the nootropics, and my brain is functions at a higher level when I take the exam itself, but additionally-- I take the nootropics and study better and harder than I ever did before. By this logic, I attribute 100% of my performance increase to the nootropic stack... but if you want to break down how much I've improved the individual components of my grade itself then I'd say my studying has doubled and contributes to about 70% of my grade, while 30% of my grade is raw exam performance (improvisation, logical deduction, speed of answering). These are just estimates, and pretty arbitrary. Anyways, I don't see nootropics as exclusively providing a raw, acute increase in intelligence. They motivate, provide energy, and enhance memory formation. If all you do is take nootropics, hoping to improve exam scores, but don't also improve your studying (or even worse-- study less, under the assumption that increased intellect will negate the need to study), you will most likely find yourself doing the same or worse than before. Nootropics enhance the fertility of the mind, but one must still sow the seed if they want to harvest the crops!

[#1stunna]

great thread, I will add ginko to my basic choline piracetam stack.

[Justin Garrett Hill]

NoopMed thank you for posting the info from Nat Med about Sam-e and also taking the time to consider the rest of my post.

Eye twitch:
In regards to the "eye twitching", I think that most likely the source of that was the combination of the stimulating effects of my supplementation coupled with lack of sleep. My work schedule consistently forced me to get 4 hours of sleep 1 day a week and most of the time only 6-7. It has gone away though since I have a new schedule and have been sleeping much more. I did not ever see the twitch, just felt it, and it felt like it was coming from farther back in my eye area, but because of the way my eyelids sit, it may very well have been my eye and just was hard to tell.

Itchy Skin marks:
The itchy skin marks are slowly going away. I did actually add some hydro-cortisone topical ointment to it, which I think also helps it. I would not rule out some kind of immune response to one of the supplements from this as I do find it awfully peculiar that I was "bitten" on the backs of both of my hands repeatedly over a few nights. It started out as one nasty bite on the first joint of my left pinky, which later scabbed and turned into a blotchy itchy mark about the size of a dime. Although it has been a month and I still see a little redness there. Additionally I had smaller "bites" on my right hand although no where near the ferocity of the initial wound. Lastly about a 1 inch trail of marks perpendicular to my fingers on the backs of both hands. Somewhat similar this picture I thought maybe it could be bedbugs http://0.tqn.com/d/h...alicja_hand.jpg but have not been able to find any bedbugs. But I did find a weird looking spider (only 3 feet direct crawl path, my bed touches the window and it was on the window sill,)from where I sleep. Could have been the spider, maybe bed bugs, maybe allergic reaction. Maybe I will eliminate the aniracetam from my stack for a bit until they are completely gone. Ani was the last and least noticable nootropic I added anyways.

Also I was wondering if you could post the Nat Med info for Sulbutiamine?

I think I will add Alpha GPC to my stack.

Any thank you! It's definitely nice to know someone is doing their homework. I look forward to your next postings and learning more about nootropics.

[NoopMed]

NoopMed thank you for posting the info from Nat Med about Sam-e and also taking the time to consider the rest of my post.

Eye twitch:
In regards to the "eye twitching", I think that most likely the source of that was the combination of the stimulating effects of my supplementation coupled with lack of sleep. My work schedule consistently forced me to get 4 hours of sleep 1 day a week and most of the time only 6-7. It has gone away though since I have a new schedule and have been sleeping much more. I did not ever see the twitch, just felt it, and it felt like it was coming from farther back in my eye area, but because of the way my eyelids sit, it may very well have been my eye and just was hard to tell.

Itchy Skin marks:
The itchy skin marks are slowly going away. I did actually add some hydro-cortisone topical ointment to it, which I think also helps it. I would not rule out some kind of immune response to one of the supplements from this as I do find it awfully peculiar that I was "bitten" on the backs of both of my hands repeatedly over a few nights. It started out as one nasty bite on the first joint of my left pinky, which later scabbed and turned into a blotchy itchy mark about the size of a dime. Although it has been a month and I still see a little redness there. Additionally I had smaller "bites" on my right hand although no where near the ferocity of the initial wound. Lastly about a 1 inch trail of marks perpendicular to my fingers on the backs of both hands. Somewhat similar this picture I thought maybe it could be bedbugs http://0.tqn.com/d/h...alicja_hand.jpg but have not been able to find any bedbugs. But I did find a weird looking spider (only 3 feet direct crawl path, my bed touches the window and it was on the window sill,)from where I sleep. Could have been the spider, maybe bed bugs, maybe allergic reaction. Maybe I will eliminate the aniracetam from my stack for a bit until they are completely gone. Ani was the last and least noticable nootropic I added anyways.

Also I was wondering if you could post the Nat Med info for Sulbutiamine?

I think I will add Alpha GPC to my stack.

Any thank you! It's definitely nice to know someone is doing their homework. I look forward to your next postings and learning more about nootropics.

The bite on your left pinky does sound more like an insect bite than an allergy. The bites on your right hand sound more like a possible allergy or could be bed bugs. Spiders don't tend to bite multiple times, from my understanding. Bed bugs tend to leave bites in a distinct line, but are more common on the torso than the hands. Bed bugs are pretty hard to get rid of from what I hear, but I'm not certain of the technique.

Unfortunately Nat Med only has information on natural supplements, vitamins, minerals, etc. There's nothing available regarding synthetics like Sulbutiamine, Piracetam, or prescription drugs. Sulbutiamine is a synthetic dimer of Thiamine, and I can post the info for that vitamin (B1) below, but the info will not be an accurate parallel to Sulbutiamine, since Sulbutiamine was specifically invented to act as a FAR more blood brain barrier soluble version of the vitamin, and the brain levels achieved are likely much higher than is ever possible with just Thiamine.

here is is:


Thiamine (Vitamin B1)

Effectiveness:

EFFECTIVE
Metabolic disorders. Taking thiamine orally helps to temporarily correct metabolic disorders associated with genetic diseases such as subacute necrotizing encephalopathy (SNE, Leigh's disease), maple syrup urine disease (branched-chain aminoacidopathy), and lactic acidosis associated with pyruvate carboxylase deficiency and hyperalaninemia (15).
Thiamine deficiency. Taking thiamine orally helps to prevent and treat thiamine deficiency syndromes including beriberi and peripheral neuritis associated with pellagra or neuritis of pregnancy. Thiamine deficiency can occur in people with malabsorption conditions such as alcoholism, cirrhosis, and gastrointestinal (GI) diseases; and in those with inadequate intake due to anorexia, nausea, and vomiting; and in those with increased requirements, including pregnancy, increased carbohydrate intake, increased physical activity, hyperthyroidism, infection, and hepatic disease; however, deficiency is rare with these conditions (15). The elderly might also be at increased risk for subclinical thiamine deficiency (11076).
Wernicke-Korsakoff syndrome (WKS). Parenteral administration of thiamine seems to help decrease the risk of developing WKS and decrease symptoms of WKS in acute alcohol withdrawal. Between 30% and 80% of alcoholics are suspected to have thiamine deficiency (11075). An optimal dose for treating WKS has not been established, however, a 200 mg IM dose may be more effective than lower doses (11075).
POSSIBLY EFFECTIVE
Cataracts. A high dietary intake of thiamine is associated with a reduced risk of nuclear cataracts (6378). Higher dietary intake of thiamine also seems to be associated with a reduced risk of age-related lens opacification (14301).
Diabetic nephropathy. Preliminary clinical research shows that taking high-dose thiamine 100 mg three times daily for three months significantly decreases urinary albumin excretion in patients with type 2 diabetes compared to placebo (16556).
POSSIBLY INEFFECTIVE
Mosquito repellent. Some clinical research shows that taking B vitamins orally, including thiamine, does not significantly improve mosquito repellency (18016).
INSUFFICIENT RELIABLE EVIDENCE to RATE
Athletic performance. Some clinical research suggests that thiamine (given as allithiamin), in combination with pantethine and pantothenic acid (vitamin B5) does not improve muscular strength or endurance in well-trained athletes (10432).
Cervical cancer. Epidemiological evidence suggests that increasing intake of thiamine from dietary and supplement sources, along with folic acid, riboflavin, and vitamin B12, might decrease the risk of precancerous cervical lesions (11074).
More evidence is needed to rate thiamine for these uses.


Mechanism of Action:

Thiamine is required for carbohydrate metabolism. It combines with adenosine triphosphate (ATP) to form thiamine diphosphate, a coenzyme in carbohydrate metabolism, wherein the decarboxylation of pyruvic acid and alpha-ketoglutaric acid occurs. This coenzyme is also a part of transketolation reactions. Thiamine is also a coenzyme in the utilization of pentose in the hexose monophosphate shunt (15).
Thiamine deficiency leads to decreased transketolase activity in erythrocytes and increased pyruvic acid concentration in the blood (15). Pyruvic acid is converted to lactic acid. Therefore, lactic acidosis can also occur in patients with thiamine deficiency (15).
Thiamine might also be involved in neuromuscular transmission (10541).
Syndromes associated with thiamine deficiency are beriberi and Wernicke-Korsakoff syndrome (3041). Beriberi is characterized by anorexia; abdominal discomfort; constipation; peripheral neurologic changes; sleep disturbance; poor memory; and, sometimes, cardiovascular symptoms, including dyspnea, edema, palpitations, vasodilation, warm extremities, and high output cardiac failure.
Wernicke-Korsakoff syndrome is characterized by confusion, aphonia, ataxia, nystagmus, ophthalmoplegia, and coma. It's often associated with chronic alcoholism. In alcoholism thiamine deficiency occurs due to decreased intake, impaired absorption, and decreased storage of thiamine (11075). Ethanol also decreases the phosphorylation of thiamine, reducing its conversion to the active form (11077).
In Crohn's disease, decreased serum thiamine levels have been reported (6269). Preliminary animal data also suggests thiamine deficiency in diabetics may exacerbate the development of diabetic nephropathy (11467).
In diabetic nephropathy, it is thought that dysfunction of glomerular endothelial cells, podocytes, and tubular epithelial cells, may be reversed by increasing the plasma concentration of thiamine. This might improve glomerular and tubular structure and function and vascular inflammation thereby decreasing urinary albumin excretion (16556).
There is interest in using thiamine and other B vitamins as a repellent for mosquitos and other insects. The theory is that oral ingestion of thiamine produces an odor detectable by mosquitos that repels them. However, there is no reliable evidence that thiamine works for this use (18016).

[Justin Garrett Hill]

NoopMed,
I am wondering what your thoughts are about the histamine / acetylcholine connection, and their possible connection to hives. My "whatever they are on my hands (hives?)" flared up last night night after almost disappearing. There are other factors I am considering still as the cause for this which I will list below, but I find it curious that if they are indeed hives, one of the common treatments for chronic hives is taking an anti-histamine. I am wondering if my stack due to its affects on acetylcholine is in turn affecting my histamine levels which could be causing the hives. I don't know nearly enough about intricacies of these systems and thought that I would bounce this article off you and ask for your thoughts. http://learnmem.cshl...ent/11/1/1.full

As far as other causes for my "hives" I am considering also that my chronic breakfast diet of Pure Protein Bars could also be an allergen. I realized today that it has peanuts in it, and while I do no know if I have a peanut allergy maybe eating it every day for months has compounded a slight allergy I have to it...I have been off my supplement stack for about 4 days now to see if that was might be causing the hives, but last nights flare up must be related to diet (AZ energy drink or Pure protein bar, or wheat) or handling a bunch of cash and receipts (I am working as a cashier presently).
Anyways, just thought I would add that info.

[jjtitus]

NoopMed,
I am wondering what your thoughts are about the histamine / acetylcholine connection, and their possible connection to hives. My "whatever they are on my hands (hives?)" flared up last night night after almost disappearing. There are other factors I am considering still as the cause for this which I will list below, but I find it curious that if they are indeed hives, one of the common treatments for chronic hives is taking an anti-histamine. I am wondering if my stack due to its affects on acetylcholine is in turn affecting my histamine levels which could be causing the hives. I don't know nearly enough about intricacies of these systems and thought that I would bounce this article off you and ask for your thoughts. http://learnmem.cshl...ent/11/1/1.full

As far as other causes for my "hives" I am considering also that my chronic breakfast diet of Pure Protein Bars could also be an allergen. I realized today that it has peanuts in it, and while I do no know if I have a peanut allergy maybe eating it every day for months has compounded a slight allergy I have to it...I have been off my supplement stack for about 4 days now to see if that was might be causing the hives, but last nights flare up must be related to diet (AZ energy drink or Pure protein bar, or wheat) or handling a bunch of cash and receipts (I am working as a cashier presently).
Anyways, just thought I would add that info.

I noticed you mentioned that you handle a lot of receipts so I just thought I'd mention that they contain high levels of Bisphenol A, which could be causing some issues, although a lot of research is inconclusive... it's probably food related, but who knows:

Free BPA is found in high concentration in thermal paper and carbonless copy paper, which would be expected to be more available for exposure than BPA bound into resin or plastic.^{[28][164][165]} Popular uses of thermal paper include receipts, event and cinema tickets, labels, and airline tickets. A Swiss study found that 11 of 13 thermal printing papers contained8 – 17 g/kgBisphenol A (BPA). Upon dry finger contact with a thermal paper receipt, roughly 1 μg BPA (0.2 – 6 μg) was transferred to the forefinger and the middle finger. For wet or greasy fingers approximately 10 times more was transferred. Extraction of BPA from the fingers was possible up to 2 hours after exposure.^[166] Further, it has been demonstrated that thermal receipts placed in contact with paper currency in a wallet for 24 hours cause a dramatic increase in the concentration of BPA in paper currency, making paper money a secondary source of exposure.^[167] Also, other paper products, such as toilet paper, newspapers and napkins, become contaminated with BPA during the recycling process.^[168] Free BPA can readily be transferred to skin, and residues on hands can be ingested.^[9] Bodily intake through dermal absorption (99% of which comes from handling receipts) has been shown for the general population to be 0.219 ng/kg bw/day (occupationally exposed persons absorb higher amounts at 16.3 ng/kg bw/day)^[168] whereas aggregate intake (food/beverage/environment) for adults is estimated at 0.36–0.43 μg/kg bw/day (estimated intake for occupationally exposed adults is 0.043–100 μg/kg bw/day).^[169]

[Justin Garrett Hill]

Thanks for that point JJTitus. I had also considered the BPA from handling receipts as something that could be aggravating my immune system (crappy occupational bi-product), however the first and largest mark on my finger appeared a couple of weeks before starting this job. I am looking for another job though...

Hives update: I did a huge fruit smoothie (2 cups organic blueberries, 2 cups organic rasberries, 1 bannana, 2 scoops mtrx whey protein powder) and giant salad yesterday (half bag arugula, half a beet, handful of carrots, walnuts (hope I'm not allergic to this!), and ended the day with 4oz of organic wheatgrass and some hydro-cortisone applied topically to the hives. Woke up and once again they look much flatter and better. I am going to try and continue this mostly raw diet (2 meals out of 3) and hope that solves it.

I feel like fresh fruit, vegetables, water, exercise and rest can solve most things!


Also, I did read an interesting article I happened upon in my continued perusal into the histamine / acetylcholine axis. The article is about Serotonin NOT being the anti-depressant neurotransmitter that people think it is, and in fact plays more negative roles. I thought it interesting http://raypeat.com/a...ggression.shtml
I tend to give more credence to folks who are educated but also see the pharmaceuticals motivations in altering information to suit their financial goals...However a couple of things that also came to mind is that I think that seretonin does not cross the blood brain barrier and plays much different roles in the brain than it does circulating the rest of the body.

Just more food for thought.

[jjtitus]

Just came across this thread on Lion's Mane today, thought you might be interested in reading it if you haven't already:

http://www.longecity...timulating-ngf/

NoopMed, seems like adding this to your current stack might further improve memory/senses even further...? I'm definitely considering adding it in, and from what I've read the easiest/most effect product is Fungi Perfecti by Host Defense.

Also, while reading over a "Newbie Guide to Nootropics" the OP suggested adding these additional supplements to a basic piracetam/choline stack:

Picamilon
Aniracetam
Lion's Mane
Fish Oil
PhosphatidylSerine
Bacopa

Picamilion is a designer drug. GABA is a neurotransmitter that plays a role in reducing nervous excitement. However, taking GABA orally is ineffective because GABA cannot cross the blood-brain barrier. Picamilion is a synthesis of niacin (vitamin B3) and GABA that was designed to cross the blood-brain barrier. After crossing the blood-brain barrier picamilion is broken down to niacin and GABA.

I especially like the effect of the three neuroenhanced B vitamins. Sulbutiamine is broken down to two thiamine parts (vitamin B1) after crossing the blood-brain barrier. Picamilon is broken down to niacin (vitamin B3) and GABA after it crosses the blood-brain barrier. Pyritinol is enhanced B6. The combination of brain specific B1, B3 and B6 is greater than any of them alone. They are highly synergistic.

Aniracetam is a supplement derived from piracetam. It is much more potent that piracetam and has entirely different types of effects. I take 750 mg of aniracetam and 4000 mg of piracetam daily. The effects are synergistic. Aniracetam is another supplement that you should probably research for yourself. Any supplement in the -racetam family is entirely non-toxic, has cumulative effects, and impacts almost every known measure of mental performance.

Lion's mane is a mushroom that has been used for centuries in the east to enhance the nervous system. Recently it has been discovered that this is because lion's mane increases the production of Nerve Growth Factor. NGF is responsible for determining the rate at which new brain cells are produced. A Nobel Prize was awarded for this discovery because no other substance is known to cross the blood-brain barrier and stimulate the production of NGF. Six months of supplementation with lion's mane is proven to produce a significant improvement in nearly every measure of mental function in people with dementia. In a literal sense, you have more brains when you supplement with lion's mane. NOBEL-FREAKING-PRIZE. Don't underestimate it.

Phosphatidylcholine is synthesized from uridine, choline, and DHA. Fish Oil has two omega-3 fatty acids: EPA and DHA. CDPCholine is broken down and converted into uridine and choline. Thus, phosphatidylcholine can be produced from supplementation with CDPcholine and fish oil. Both phosphatydlcholine and phosphatidylserine are essential components of every nerve cell membrane. Increasing the levels of phosphatidylcholine and phosphatidylserine improve nearly every measure of mental performance.


Bacopa is a herbal supplement long used in India to enhance memory. It has unique chemicals that have a mechanism of action distinct from every other supplement in this regimen. Even alone it has a powerful effect on memory recall. It also repairs old and damaged neurons and dendrites. An interesting side effect is that it is as effective at reducing anxiety as prescription anti-anxiety medicines. This effect cannot be underestimated on stressful tests.

It sounds like the synergy of these supplements could be really beneficial at reaching the "next level"... the only one I'm a little hesitant to include is Bacopa due to some of the side effects I've come across. What are your thoughts?

[agedman]

Is there a reason why you chose Spark Energy Drink from Advocare?

[#1stunna]

Noopmed your input on this thread would be appreciated:
http://www.longecity...794#entry552794

[bradsmitty]

Noopmed, if you happen to have a free moment, I would love to hear an update. I would imagine you are just finishing up with finals. Are you still maintaining similar levels of cognition with your stack? Have you noticed any changes since you lowered your choline intake? Still getting the same effects from piracetam?

If you would like to discuss any recent changes in your stack, that would be appreciated also.

I hope things are going well.

[NoopMed]

Is there a reason why you chose Spark Energy Drink from Advocare?

I was introduced to Spark by a friend a very long time ago and have enjoyed using it as a coffee substitute. It is easier on my stomach and contains many useful vitamins and minerals in addition to a substantial amount of caffeine. If you refer to the ingredients you'll see that it covers several neurotransmitters or precursors to NTs like choline, tyrosine, gaba, and glycine. It also has several critical vitamins. I also like the taste and its easy to mix piracetam or other noop powders into for breakfast. It's also a convenient way of incorporating low levels of these vitamins and NTs. Buying them all separately and mixing them on your own would be an option. Dosing them all independently every day at the low levels I prefer would be arduous and a waste of my time. I definitely do not want to megadose most of these, no point, and just more work for my kidneys and liver.

That said... Coffee and a standard multivitamin would probably be a suitable substitute if you're already taking other sources of choline and tyrosine.

[NoopMed]

Noopmed, if you happen to have a free moment, I would love to hear an update. I would imagine you are just finishing up with finals. Are you still maintaining similar levels of cognition with your stack? Have you noticed any changes since you lowered your choline intake? Still getting the same effects from piracetam?

If you would like to discuss any recent changes in your stack, that would be appreciated also.

I hope things are going well.

Things have been going great. I actually had a pretty significant discovery very recently! Many of the motor side effects I had been experiencing/describing in previous posts appear to be from a mild magnesium deficiency. (I later found that I had very few sources of Mg in my diet, aside from occasional almonds, and it wasn't in the vitamin drink I usually take. I'd been learning about this particular deficiency in lecture and it felt pretty familiar. I read up on it in various piracetam and nootropic reports and eventually found someone explaining that a mild magnesium deficiency can go undetected for a very long time, but can be exposed in a hyperstimulated state generated from nootropic substances. Started taking a 500mg Magnesium supplement at bedtime, and the tremors and twitches disappeared within about 3 days. I now take that every few days at night.

Other than that, I've purposefully been avoiding any recent updates because I've been trying out a few new things and I'm not entirely satisfied with them. I still feel that my last stack was the most balanced and sustainable... However, I do have some potential changes, removals, and additions in the near future which I've been trying out and will discuss in an "in progress" sense below.

This was the last primary stack:
-------------------------------------------------------------------
Every Other Day:
300mg CDP Choline (citicoline)
(This actually has a VERY long half-life-- 72 hours. So I've been trying to take citicoline much less often.)

Morning:
1 Scoop Spark Energy Drink
800mg Piracetam
120mg Extended Release Ginkgo biloba
1000mg Fish Oil

Average Afternoon:
Large cup of coffee
800mg Piracetam
500mg Choline bitartate

Heavy Study Afternoons:

800mg Piracetam
500mg Choline bitartate
750mg Oxiracetam
120mg Extended Release Ginkgo

----------------------------------------------------------------------

OK, so recent stuff...

ALCAR:

Over and over again I keep running into research and anecdotes regarding the benefits of ALCAR (see previous post for datasheet), so I finally decided to give it another shot. I took it consistently for two weeks. 500mg BID (once at breakfast and once at lunch). Same damn thing happened again that happened the first time I tried it (quite some time ago). Within two weeks, I broke out in significant amounts of Acne and body weight increased significantly (~10 lbs). It's hard to tell if it was water weight or fat, but my inclination is fat because I noticed a fairly obvious increase in central and peripheral abdominal mass. I also noticed a significant decline in my declarative memory (names, identifications, rote factoids, etc), and a marked slowing of my cognition. On the plus side, I did experience an increased general sense of well-being and libido... haha, but that's not really what I'm trying for at the moment. Once I stopped the ALCAR, I returned to my normal cognitive state after a few days, but noted a major downturn in my mood-- verging on depression. I have a strong suspicion that the most significant effect it has on me in an increase in pituitary LH and FSH, thereby increasing testosterone. Excess testosterone moves right along to aromatase enzymes and gets converted to dihydrotestosterone, estrogen, estradiol , etc.... sex hormones. Not something I need to mess around with, personally. Also, I think it may imbalance what is probably my "normal" and "good enough" mitochondrial metabolism. Leading increased glucose usage and decreased fat usage for energy. Also not something I particularly want. Bottom line, it may work for some people, particularly people who have moved well past their endocrine peak (ie Men older than 45-50+ or so... and for women, thoroughly well past menopause? Not entirely sure on this.)




Panax Ginseng:

This is showing promise. The primary item of interest is the synergistic effects on memory and cognition with ginkgo biloba. I've been taking it once in the morning, along with my Ginkgo and have felt a subjective improvement. At times I feel a little TOO amped up, and I definitely drink less coffee while taking it. Also, it seems to inhibit the increased appetite that I seem to experience from all the choline. OF NOTE: There are two types of Ginseng commonly available. "American Ginseng" and "Korean Ginseng." They do contain some synonymous compounds, but also several different ones. Most of the promising research regarding cognition has been found in KOREAN GINSENG (Panax ginseng) ONLY. Here is the data sheet:


Panax Ginseng (Korean Ginseng):

Effectiveness:

POSSIBLY EFFECTIVE

Chronic obstructive pulmonary disease (COPD). A meta-analysis of clinical trials evaluating the use of Panax ginseng orally in patients with stable COPD shows that Panax ginseng significantly improves pulmonary function tests and quality of life compared to placebo after 3-6 months of treatment. However, Panax ginseng only modestly improved forced expiratory volume 1 (FEV1). Panax ginseng improved COPD symptoms by approximately 53% compared to placebo (17736).

Cognitive function. Taking Panax ginseng orally might improve abstract thinking, mental arithmetic skills, and reaction times in healthy, middle-aged people (2064). Panax ginseng alone does not seem to improve memory (2064), but there is some evidence that a combination of Panax ginseng and ginkgo leaf extract can improve memory in otherwise healthy people ages 38 to 66 years (8591,9759).

Erectile dysfunction (ED). Taking Panax ginseng orally seems to improve sexual function in men with erectile dysfunction (8813).

Premature ejaculation. Applying a multi-ingredient cream preparation containing Panax ginseng, angelica root, Cistanches deserticola, Zanthoxyl species, torlidis seed, clove flower, asiasari root, cinnamon bark, and toad venom (SS Cream) to the glans penis one hour prior to intercourse and washing off immediately before intercourse seems to improve ejaculatory latency in men with premature ejaculation (2537).


POSSIBLY INEFFECTIVE

Athletic performance. Taking Panax ginseng orally doesn't seem to improve aerobic exercise performance (1427,4230,4231,4236).

Menopausal symptoms. Taking Panax ginseng orally doesn't seem to help vasomotor symptoms such as hot flashes in postmenopausal women (10981). In postmenopausal women, some preliminary clinical research suggests that panax ginseng might improve quality of life, and menopausal symptoms such as fatigue, insomnia, and depression (3863,10981).

Quality of life. Taking Panax ginseng orally doesn't seem to be helpful for improving mood, sense of well being and overall quality of life. Although some research suggests that Panax ginseng might improve self-rated quality of life (6254), other studies show no benefit (8601,10314). Tell patients not to rely on Panax ginseng to improve mood or sense of well being.


INSUFFICIENT RELIABLE EVIDENCE to RATE

Breast cancer. Population research in China suggests that breast cancer patients who regularly take any form of ginseng, including either Panax ginseng or American ginseng, have higher quality of life scores and have a lower risk of overall mortality, breast cancer-related mortality, and breast cancer recurrence compared to patients who do not take ginseng (14466); however, ginseng users were also significantly more likely to have been treated with tamoxifen.

Bronchitis. Taking a specific Panax ginseng extract (G115) orally might be beneficial when used adjunctively for treating acute exacerbations of chronic bronchitis. Panax ginseng, combined with antibiotic therapy, might reduce bronchial bacterial counts more than antibiotic therapy alone (8814).

Cancer. Epidemiological data suggests that taking ginseng orally might decrease the incidence of cancer, specifically stomach cancer, lung cancer, liver cancer, ovarian cancer, and skin cancer (2063,3122).

Common cold. There is some evidence that taking a specific Panax ginseng extract (G115) orally can decrease the chance of catching a cold (589).

Congestive heart failure (CHF). An intravenous formulation of ginseng seems to increase ejection fraction in patients with congestive heart failure. Ginseng might improve hemodynamics and might work synergistically with digoxin (4243,8604).

Diabetes. There is contradictory evidence about the effects of Panax ginseng on diabetes. Some clinical research shows that taking Panax ginseng orally, 200 mg daily, can decrease fasting blood glucose levels and hemoglobin A1C (HbA1C) in patients with type 2 diabetes (4225). However, other clinical research suggests the use of Panax ginseng ginsenosides (AIPOP, Gangdown-Do, Korea) orally, 250-500 mg daily, or Korean red ginseng extract (Spectrum Laboratories, Gardena, CA) orally, 3-8 grams daily does not significantly improve postprandial glucose concentrations, beta-cell function or insulin sensitivity compared to placebo (17734).

Influenza. There is some preliminary evidence that suggests taking a specific Panax ginseng extract (G115) orally four weeks prior to influenza vaccination and continued for eight more weeks can decrease the risk of getting the flu (589).

(More evidence is needed to rate Panax ginseng for these uses.)


Mechanism of Action:

The applicable part of Panax ginseng is the root. Panax ginseng contains several active constituents. The constituents thought to be of most importance are triterpenoid saponins referred to collectively as ginsenosides or panaxosides. Ginsenosides is the term developed by Asian researchers, and the term panaxosides was developed by early Russian researchers. Numerous subtypes of ginsenosides have been identified. Other constituents include pectin, B vitamins, and various flavonoids (11). Panax ginseng also contains the peptidoglycans, panaxans, which have hypoglycemic effects (12536). The ginsenosides have a wide range of pharmacological activity and effects. In some cases, these isolated constituents seem to counteract each other's activity. For example, ginsenoside Rg1, raises blood pressure and acts as a central nervous system (CNS) stimulant. Ginsenoside Rb1 lowers blood pressure and acts as a CNS depressant (11). They also seem to interfere with platelet aggregation and coagulation (1522). Ginsenosides also potentiate nerve growth factor (11) and might confer neuroprotection through nicotinic activity (3109). There is also evidence that ginsenosides can relax human bronchial smooth muscle by stimulating the release of nitrous oxide from airway epithelium which may account for the potential anti-asthmatic effect of Panax ginseng (11007). However, research on related ginseng species, Panax pseudoginseng, suggests these ginsenosides may not be pharmacologically significant. Rb1 has a low oral bioavailability, and Rg1 is rapidly eliminated from the blood in animal models (11153).
Ginseng is widely used as a general tonic or "adaptogen" for fighting stress. There is some evidence that it might work against stress by affecting the hypothalamic-pituitary-adrenal (HPA) axis. Panax ginseng saponins seem to increase serum cortisol concentrations (3256,3257). Panax ginseng might also increase dehydroepiandrosterone sulfate (DHEA-S) levels in women (3863).
Panax ginseng might affect immune function and might have anticancer effects. Panax ginseng appears to stimulate natural-killer cell activity and possibly other immune-system activity. It might also have some antitumor activity (3122). Extracts of Panax ginseng decrease the production of tumor necrosis factor (TNF), diminish DNA strand breakage, and inhibit the formation of induced skin tumors (11006). There is conflicting research about the antioxidant and free radical scavenging activity of panax ginseng (4227,8602). Ginsenosides have been shown to inhibit tumor cell invasion and suppress sister chromatid exchanges in human lymphocytes (11006). Panax ginseng also contains water insoluble polyacetylenic constituents such as panaxynol, panaxydol, and panaxytriol. Panaxydol seems to have antiproliferative effects on various types of cancer cells by inhibiting cancer cell growth at the cell cycle G1 to S transition phase (11005). In peptic ulceration, Panax ginseng has shown inhibitory activity on Helicobacter pylori-induced hemagglutination (3121). Samgyetang, a soup made from chicken, panax ginseng, garlic, jujube, and chestnuts, appears to offer protection from experimentally induced peptic ulcers (10249).
Panax ginseng may lower serum cholesterol and triglycerides, possibly by increasing lipoprotein lipase activity, which enhances lipid metabolism (12538). However, panax ginseng appears to have negligible effects on cardiovascular function (4322).
Some ginsenosides have structural similarities to cardiac glycosides and can interfere with measurement of serum digoxin levels by some assay methods (15585,15587). It is not clear whether panax ginseng has any of the pharmacological effects of cardiac glycosides.
Panax ginseng may affect blood glucose. Preliminary evidence that Panax ginseng might reduce tissue insulin resistance and changes in gene expression in Type II diabetes (8605). Ginsenosides in Panax ginseng might also directly stimulate insulin release (6461). The effect of various ginsengs on glucose appears to be related in part to the mix of ginsenosides. Other nonginsenoside constituents likely affect blood glucose as well. Panax ginseng and other ginsengs contain protopanaxadiol (PPD) ginsenosides, Rb1, Rb2, Rc, and Rd. They also contain protopanaxatriol (PPT) ginsenosides, Rg1, Re, and Rf. A higher ratio of PPD ginsenosides to PPT ginsenosides is related to greater blood glucose and insulin lowering potency of the ginseng product. Compared with American ginseng, panax ginseng appears to have a lower PPD to PPT ratio and may have less blood glucose. Some research suggests Panax ginseng may actually increase postprandial blood glucose and lower preprandial insulin levels. However, ginsenoside content varies among batches, plant parts, and preparation methods (12536).
The estrogenic effects of ginseng are controversial. Some clinical evidence suggests it doesn't have estrogen-mediated effects such as increasing follicle-stimulating hormone (FSH), estradiol levels, or endometrial thickness (10981). However, case reports of ginseng side effects such as postmenopausal vaginal bleeding suggest estrogen activity (590,591,592,10982,10983). Panax ginseng extract has been shown to increase serum ceruloplasmin oxidase activity (a measure of estrogenic activity in the liver) in animal models when ovaries are removed (6180). In vitro research also shows estrogen activity. Studies on human breast cancer cells indicate that ginseng, specifically its constituent ginsonside-Rb1, acts as a phytoestrogen (10984).
Panaxagin, a protein isolated from unprocessed ginseng root, seems to have antiviral and antifungal activity, according to preliminary research. It appears to inhibit HIV reverse transcriptase and ribosomal activity of some fungi (8603).
A multi-ingredient cream preparation containing Panax ginseng is thought to work in premature ejaculation by increasing the penile vibratory threshold and reducing the amplitude of penile somatosensory evoked potentials (2537). Some people try ginseng for cystic fibrosis because there is preliminary evidence that it has activity against Pseudomonas aeruginosa lung infections, but this effect has not yet been demonstrated in humans (3095,3096).
There is some evidence that a Panax ginseng root extract can mildly inhibit cytochrome P450 2D6 (CYP2D6) activity by approximately 6% in humans. However, contradictory research suggests Panax ginseng might not significantly inhibit CYP2D6. Panax ginseng appears to have no effect on CYP1A2 and CYP3A4 activity (1303,10847).


OK so there's Ginseng. Stimulating, mimetic, and despite research showing it did not help exercise performance... I certainly felt like it did.



Finally, last one.

Phosphatidylserine


This has been mentioned in many other posts and other locations, so I thought I'd research it a bit. From what I can ascertain it seems like a fairly benign supplement for significant long term maintenance of brain health. Benefits appear to show themselves slowly. Side effects show themselves quickly however. I purchased 100mg pills, and as you'll see in the data sheet below, "flatulence" was noted at 300mg. YUP! haha. Tried it 3 times per day the first two days, and incurred very significant flatulence. Stepped down to twice a day, and I'm doing just fine. Not really noticing anything yet in terms of benefit, but the concept behind it should be fairly "background" with the hope of preventing degradation and supplying my neurons with the raw membrane materials to stay strong and healthy. An added benefit is the noted reduction in serum cortisol (the primary stress hormone). This can be increased with CDP-Choline, which was something I was substantially worried about. I had considered stopping CDP-Choline altogether because of that possible side effect (and not wanting to get Cushing's Disease... wiki if you like). This will potentially reduce that risk, while providing many other added benefits. Notably, that cortisol is also toxic to the hippocampus and reduced levels of it should help with development of perhaps the most important center of memory activity. As another added benefit, it appears to be work synergistically with DHA (found in Fish Oil, and the primary molecule of interest with that supplement). DHA helps to concentrate PS in cell membranes, which in turn reduces their propensity for death via apoptosis (cellular suicide.. a complex topic-- perhaps worth a wiki review, but perhaps requiring a lot of context to grasp.).

(Of important NOTE: Traditionally PS was manufactured from "bovine cortex." It can also be produced from Soy, and this has be come more readily available. Many of the original studies were done using PS from a Bovine Cortex source, so in the forums and from several distributors there is strong encouragement for using the bovine source, and say things like, "Not from Soy." etc... Recent studies are also coming out, which I found elsewhere on PubMed showing that the Soy product is also effective. I GREATLY PREFER SOY! Bovine cortex is notorious for impurities-- the most horrific being prions that contribute to Bovine spongiform encephalopathy-- AKA Mad Cow Disease, or Cruetzfeld-Jakob disease in humans. The risk of this is probably very low, however; having been to cattle processing plants personally, I prefer to avoid any bovine "byproduct" when I can. I'm happy to eat a steak, but I'll pass on the gelatins, cortexes, etc.)

Here is the data sheet for Phosphatidylserine:


Phosphatidylserine:

Effectiveness:

POSSIBLY EFFECTIVE

Age-related cognitive impairment. Clinical studies show that phosphatidylserine improves attention, arousal, verbal fluency, and memory in aging people with cognitive deterioration (2440,2441,7119,7120,15539). Most clinical studies have used phosphatidylserine derived from bovine cortex. However most supplements now use soy or cabbage derived phosphatidylserine. There is also preliminary evidence that plant derived phosphatidylserine improves memory in people with age-associated memory impairment (15539).

Alzheimer's disease. Taking phosphatidylserine orally can increase cognitive function, global improvement rating scales, and improve behavioral rating scales over 6-12 weeks of treatment (2255,2437,2438,2439,7114,7118). Phosphatidylserine seems to be most effective in patients with less severe symptoms (2437,2439). Phosphatidylserine might lose its effectiveness with extended use. After 16 weeks of treatment, progression of Alzheimer's disease seems to overcome any benefit of phosphatidylserine (2255).


INSUFFICIENT RELIABLE EVIDENCE to RATE

Depression. There is some preliminary evidence that phosphatidylserine might improve depression in geriatric patients (7113).

Exercise-induced stress. There is some evidence that athletes taking phosphatidylserine orally during over-training might have the perception of well being and reduced muscle soreness (2264). Some research also suggests that non-athletically trained healthy men might benefit from both acute and chronic phosphatidylserine administration (8851,8852).

(More evidence is needed to rate phosphatidylserine for these uses.)


Mechanism of Action:

Phosphatidylserine is a fat-soluble phospholipid that occurs endogenously in humans. It is the most abundant phospholipid in the human brain and is important in neuronal membrane functions such as maintenance of the cell's internal environment, signal transduction, secretory vesicle release, cell-to-cell communication, and cell growth regulation (2437,7115). Phosphatidylserine is also a component of the mitochondrial membrane, where it might function as a metabolic reservoir for other phospholipids (7121). Although the body is able to synthesize phosphatidylserine through an elaborate series of reactions and substantial energy expenditure, the body obtains most phosphatidylserine from dietary sources. Phosphatidylserine is present in small quantities in most foods (7116).
It is not clear how phosphatidylserine works for dementia such as Alzheimer's disease and age-related memory impairment. However, one theory is that patients with dementia or age-related memory impairment have structural or functional abnormalities in neuronal membranes that cause changes in neurotransmitter functioning. People with cognitive dysfunction often have changes in acetylcholine, norepinephrine, and serotonin levels. Some researchers think the abnormal neuronal function can be attributed to changes in lipid composition of the brain. It is thought that exogenous administration of phosphatidylserine might then normalize brain lipid content and return neuronal function to normal (2441). Phosphatidylserine has been shown to increase acetylcholine, norepinephrine, serotonin, and dopamine levels in animal models and patients with Alzheimer's disease (2437,8857,8858).
In animal models, levels of phosphatidylserine in the brain decline with age (15539).
In animal models, phosphatidylserine improves spatial memory and passive avoidance (8858).
Phosphatidylserine also appears to minimize age-related neuronal dendrite loss and atrophy of cholinergic neurons (2437,8857). The fatty acid docosahexaenoic acid (DHA), which is readily present in neuronal cells, appears to further promote the accumulation of phosphatidylserine in cell membranes, which in turn prevents apoptotic cell death (8857).
Evidence shows that high levels of procoagulant endothelial particles containing phosphatidylserine are present in patients with acute coronary syndromes. Although these increased levels are hypothesized to contribute to plaque disruption and thrombosis, the exact mechanisms are not yet understood (8855).
There is also interest in phosphatidylserine for decreasing exercise-induced stress. Some preliminary evidence shows that phosphatidylserine might blunt the rise in cortisol and adrenocorticotropin following strenuous training (2264,8851,8852). Very preliminary clinical laboratory research suggests that phosphatidylserine 300 mg per day might improve mood and subjective feelings of stress (11963).
In animal models of multiple sclerosis, phosphatidylserine reduces tremor, spasticity, and urinary incontinence, possibly by suppressing the release of the cytokine tumor necrosis factor (8853,8854).



---------------------------------------------


I'd like to give things some time before I figure out an official stack with these new supplements. I'm also considering changes to the previous stack. For example, I sometimes feel pretty burnt out after use of Oxiracetam. I'm not sure how often I'll be using this in the future, it's also very expensive to maintain. (If anyone knows a cheap, good quality source, do let me know.) I may also step CDP-Choline back up to daily with Phosphatidyl serine. I'm also hoping to try out Lion's Mane Mushroom, but it's hard to find a consolidated body of evidence regarding it at this point. I'm also considering stepping down the Piracetam, or at least experimenting with a wash-out protocol. This will likely wait until I'm satisfied with the stack. I've been taking it long enough now, that I'm curious how things will go if I stop or at least begin reducing to much lower doses.

[Nickthedevil]

This truly is a great conversation mostly maintained by NoopMed, theres something for everyone, my question with all these supplements how much is this costing you?

[NoopMed]

Hahaha... well, I've got a truly impressive medicine cabinet at my disposal, of which I actively use only maybe 15%.

I'm currently stocked on everything I use daily for the next 6 months, at least.

All told, I've spent somewhere around $1000-$1200, but it probably costs about $100 to get setup for a several month trial.
Daily, the supplements are less expensive than what I would spend on coffee if I didn't get it for free.

There are students in my class that would probably be happy to pay $1000 per exam for the scores I've earned since starting things up... though class test scores and class ranks still come far behind performance on THE BOARDS...

[Nickthedevil]

That begs the question were you a great student before you started using nootropics, and do you think your getting value for money?

[#1stunna]

He must have been assuming he is from the US. Not easy getting in med school here.

[leftside]

One of my favorite supplements is American Ginseng. I buy it by the pound direct from a farmer in BC, Canada. It lasts me about 1 year. I break off a small chunk and add it to my tea in the morning. Very minor stimulant, but I mainly take it for immune system properties.

[Crankshaft]

NoopMed,

Quick question about the beginning and tailoring a personal stack.
I'm starting the process step-wise so i can learn what my individual needs are.

I have begun with Alpha GPC and Piracetam.
How quickly should i notice a cognative change?
Also, is the increase in performance cumulative, and over what initial time period?

I gave Alpha GPC, Vinpocetine and Huperzine A a try for a couple weeks last month.
I seemed to have an initial improvement in what I would call visual memory...(pathways etc.) but that seemed to diminish after 3 or 4 days and it left me with a bit of pressure in the head... hmmm?

I am in the throws of Board Study myself right now.
Good luck to ya!
and Thanks

[jjtitus]

I gave Alpha GPC, Vinpocetine and Huperzine A a try for a couple weeks last month.
I seemed to have an initial improvement in what I would call visual memory...(pathways etc.) but that seemed to diminish after 3 or 4 days and it left me with a bit of pressure in the head... hmmm?

I followed the exact same process, but ended up dropping the Huperzine A because of similar "pressure in the head". After a couple weeks, I kept up the Alpha GPC/Vinpocetine regimen and added 1 tsp Piracetam BID, which I noticed initially as an increased clarity of thought and is now a little more subtle... every now and then I notice minor improvements in memory, vocabulary and reasoning/logic. Like most people say though, it's not a huge difference, just a steady improvement over the last few weeks. I have Aniracetam and Lion's Mane that just came in, so I plan to add those into my afternoon stack (offset by at least a week, Lion's Mane first), should be interesting to see if there's any difference. Just my 2 cents, I'll leave it to Noopmed to fill in the rest.

[Nickthedevil]

I did think that noopmed was from the USA; though I didn't assume because assumptions are the brother of all fuck-ups (I'm sure that my referring to lock-stock will be frowned upon in here)
If you clikc on a user name there is an attribute that says: Location, either he was being honest and he's from the USA or he's one of those kooky Canadians and he's being ironic. either way, great student is relative, med students despite being intellectual monsters amoung brick layers have a pecking order of their own, noopmed seems to be a bit of an intellectual but he might still think he's a sub par intellect where par is Steven Hawking or Da vinci.

I've always wanted to know if smart people could raise the bar through supplementation.

[#1stunna]

it is a great question and you put it in perspective well

[#1stunna]

noopmed consider trying this as your before bed mag supplement.
http://www.amazon.co...rds=calm me mag


My wife has a high stress job, eats bad, has RLS, and trouble winding down after work so I put this in her stocking. We will see if it helps her.

[NoopMed]

noopmed consider trying this as your before bed mag supplement.
http://www.amazon.co...rds=calm me mag


My wife has a high stress job, eats bad, has RLS, and trouble winding down after work so I put this in her stocking. We will see if it helps her.

Is this a pure magnesium supplement? If so, the price seems rather high. I got 500mg pills from my neighborhood CVS for $5. For RLS, I can see a potential NDMA glutamate channel mechanism playing a part in helping to aid with sleep... however, I doubt these will help with sleep in people who have simple insomnia. RLS has a whole treatment protocol that involves the dopamine pathway, primarily employing dopamine agonists. Honestly, most of us don't have enough dopamine in our lives... but that's more a lifestyle issue than a medical solution... The best thing she can do find something outside of work in her life to focus on that helps relieve stress. Something she enjoys, that she can invest herself in and not experience displeasure or stress. Generally something meaningful, call it a hobby if you like, but something that she can really focus on that interests her.

Also, most critically--I probably don't emphasize this enough... A healthy diet usurps any of the shit in these "Nootropic Stacks." If you don't feed your brain well, nothing here will make a difference. A balanced, healthy diet is by far the most important element. This forum isn't really geared towards that, but the resources are everywhere... http://lmgtfy.com/?q=healthy+diet