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:
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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 Drink800mg Piracetam120mg Extended Release Ginkgo biloba1000mg Fish OilAverage Afternoon:Large cup of coffee800mg Piracetam500mg Choline bitartateHeavy Study Afternoons:800mg Piracetam500mg Choline bitartate750mg Oxiracetam120mg 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).
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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.