#17

@MAC I went ahead and put up a new topic on nootropics and mushrooms to see if anyone else has experience with it.

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#18

Many people on nootropics sites were saying they would get a headache from taking piracetam if they didn’t also supplement choline. I never suffered from headaches while taking piracetam at various dosages, so I didn’t pay too much attention to it.

Maybe, I will try to up my choline supplement intake and see if there is a subjective improvement. What are the best markers to look at to determine deficiency?

1 Like
#19

I haven’t looked at the norprtopic literature in a year or so, but my guess would be that your choline dependent nootropic would stop working if you don’t supplement with choline. I never have any issues with piracetam either, but preferred phyenlpiracetam.

#20

I really like nicotine as well. It helps my cognition and mood substantially. I was dismayed to learn that theres some evidence (not conclusive, but worth considering) that nicotine per se is causative of atherosclerosis. Would love to be wrong about this. Please post if you have counter-evidence or counter-analysis. Here’s what I’ve found in a few hours of research, presenting evidence in both directions.

  • Nicotine gum chewing has been shown to aggravate regional myocardial hypoperfusion in patients with known coronary artery disease ([65]).

  • Study “Using data from the United Kingdom’s Clinical Practice Research Datalink, this study aimed to evaluate CVD events and survival among individuals who attempted smoking cessation with the support of NRT compared with those aided by smoking cessation advice only.” Hazard ratio was 1.03–1.77 (95%) for ischemic heart disease (heart attack?) and 1.14–1.99 for cerebrovascular disease (?stroke) An explanation for the differences in all-cause mortality between treatment groups in the current study could be prescribing practices, with GPs preferentially prescribing NRT in patients with other smoking-related diseases, such as lung cancer. These patients could be more likely to be prescribed NRT, as this intervention has been shown to increase the likelihood of quitting by 50%–70%.10An alternative explanation is that the NRT cohort consisted of heavier smokers with a greater illness burden, who therefore had higher all-cause mortality compared with those receiving advice only. Both smoking and nicotine treatment have been found to increase heart rate and blood pressure.34–37 The hemodynamic effects of smoking have been linked to nicotine, with heart rate found to increase with intravenous nicotine, nicotine nasal sprays, and nicotine chewing gum.38–40 Nicotine was found to affect coronary artery constriction even at doses as low as 4 mg.41 These effects cause an increase in myocardial work and oxygen demand and result in impaired blood flow and oxygen supply to the heart. However, transdermal nicotine was found to have a lesser acute hemodynamic effect than smoking.42 Although there are not much data available on the effect of transdermal nicotine on coronary blood flow, Benowitz et al42 suggest that transdermal nicotine in smoking cessation treatment of patients with coronary heart disease is likely to be safer than cigarette smoking.

  • A study using the The Health Improvement Network (THIN) general practice database, included 33,247 patients taking NRT, and investigated acute MI, acute stroke, and death for each patient during exposed and unexposed time periods. The authors reported that although the incidence increased before exposure and decreased after exposure to NRT in the period of 56 days before and after first NRT prescription, NRT was not associated with an increase in risk of MI, stroke, or death.21

  • A second database study of 663 smokers with acute coronary syndrome that compared NRT versus no NRT reported no differences after 1 year for death, MI, repeat revascularization, or rehospitalization for angina, congestive heart failure, or arrhythmia.26

  • 2014 Metaanalysis of RCTs Relative Risk: nicotine replacement therapy (RR, 1.95; 95% CI, 0.26-4.30). So the study was rather under-powered.

  • Article 2012 suggest that nicotine, no matter how it’s delivered, can damage blood vessels.In short, nicotine modifies cell structure in a way that facilitates migration and invasion of cells that line the blood vessels. This enables a change in structures called podosomes, which lead to poor vessels and can cause the formation of plaque. Over time, plaque that’s built up can cause the arteries to harden, a form of heart disease called atherosclerosis. It can also block blood flow to the heart or brain, keeping oxygen from reaching those organs and causing heart attack or stroke.

  • “In Dr. Hai’s experiments, nicotine appeared to drive the formation of a kind of cellular drill called podosome rosettes, which are members of the invadosome family, consisting of invadopodia, podosomes and podosome rosettes. These specialized cell surface assemblies degrade and penetrate the tissue during cell invasion. Invasion of vascular smooth muscle cells from the middle layer of the arterial wall (media) to the inner layer of the arterial wall (intima) contributes substantially to plaque formation in atherosclerosis.”

  • Chi-Ming Hai, a molecular pharmacology professor at Brown University, believes the answer lies in nicotine. Hai exposed heart cells to nicotine and found that after 6 hours, podosome rosettes formed and ate through the tissue. The nicotine acted as “a kind of cancer of the blood vessel, which is waking up these cells and breaking them away from their surrounding matric [sic] and then migrating having an effect like it is almost like digging a hole through the wall,” he said.

  • Article found that the odds of a heart attack increased by 42% among people who used e-cigarettes. This increase in risk was on top of the increases in risk due to any smoking that the e-cigarette users were doing.

  • 2021 review “Although the initial presentations of nicotine-induced vascular dysfunction may be insidious (changes in vasoreactivity and vascular remodelling as discussed in this review), these changes contribute to the pathogenesis of serious medical conditions including atherosclerosis, abdominal aortic aneurysm, coronary artery disease and myocardial infarction.123–125”

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#21

desertshores, I’ve been researching piracetam, noopept, and alpha-gpc for some time. Do you mind telling me where you source the products you use, including the type of choline you prefer at this time? Thanks for any response you can give.

#22

There is growing evidence that apart from direct mechanisms of SGLT2 inhibitors in the central nervous system, they also exert a beneficial pleiotropic effect. In silico studies indicate that flozins have the molecular ability to inhibit acetylcholinesterase. Canagliflozin was even called a ‘dual inhibitor of SGLT2 and AChE’ as its estimated inhibition constant K i (i.e., the concentration required to produce half-maximum inhibition) against AChE was 0.12859 µM [58]. It is clinically relevant as patients taking canagliflozin reach a serum drug concentration of 10µM, and the brain/serum ratio of canagliflozin is 0.3. Therefore, the amount of canagliflozin penetrating the brain (3 µM) is enough to inhibit AChE [17,59]. As for other SGLT2i, the K i for inhibiting AChE is 0.177 µM for empagliflozin and 25.02 µM for dapagliflozin, and brain concentrations are 0.5 µM and 0.3 µM, respectively, so out of those two, only in the case of empagliflozin, brain concentration is enough to inhibit AChE (Table 1) [17,30,60]. Patients with Alzheimer’s disease have a reduced amount of acetylcholine neurotransmitters in the brain, and acetylcholinesterase inhibitors including donepezil, rivastigmine, galantamine are commonly used to increase the acetylcholine level and improve cognition [61]. In a rat model of cognitive impairment induced by scopolamine, canagliflozin, similarly to galantamine, decreased AChE activity, increased acetylcholine M1 receptor (M1 mAChR) and monoamines levels. It also improved cognitive functions in the Y maze task and water maze task [62]. Canagliflozin has the greatest potential of inhibiting AChE and may be a preferable solution in patients with T2DM who would also benefit from the inhibition of acetylcholinesterase.

Canagliflozin - Another Top Longevity Drug
#23

Currently I am not taking piracetam, I am only taking Noopept.
I normally buy from

They say some people get headaches of taking racetams, but I have never experienced this. Some also say racetams deplete choline and this is what causes the headaches
I tried almost everyone of the choline supplements, citicoline etc., but actually noticed no effect from any of them. Now I just take plain choline from Walmart.

2 Likes
#24

Here is a side effect many may welcome.

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#25

I read many Chinese studies on Huperzine which is an acetylcholinesterase inhibitor and cognition more than 20 years ago. I have been taking Huperzine ever since. The paper that convinced me showed an effect equal to Tacrine but with fewer side effects. Here is a review on Huperzine.

“The phase IV clinical trials in China have demonstrated that HupA significantly improved memory deficits in elderly people with benign senescent forgetfulness, and patients with Alzheimer disease and vascular dementia, with minimal peripheral cholinergic side effects and no unexpected toxicity. HupA can also be used as a protective agent against organophosphate intoxication.”

https://www.nature.com/articles/aps20061

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#26

I worked in a neurologist’s office during graduate school doing EEG assessment and brainwave biofeedback. A woman had an orgasm, her first in years, during one of the biofeedback sessions. Jon, the doc asked excitedly, “What protocol were you using?” Unfortunately for us, it only worked for her.

#27

Might not have been the biofeedback. Maybe the technician was her type.

It is not the pistol, but the pistolero.

2 Likes
#28

I’m posting my nootropics stack again. I’ve taken piracetam in the past and as it is water soluble vs phenylpiracetam which is fat soluble the effect is pretty short lived (1hr tops) . Also you need to continue taking piracetam multiple times in a day so 800mg to 1200mg 3-4 times a day. It gets pretty annoying.

Also, you probably know the TMAO related stroke risk of choline supplementation with alpha gpc or cdp choline. But, I don’t really consider it something that should be focused on because in reality most of the foods you eat contain TMAO and it can be offsetted.

Anyways,my nootropics stack:

  1. Phenylpiracetam (Nanotropil) - 100mg
  2. Vinpocetine - 10mg
  3. Mexidol (Emoxypine) - 125mg
  4. Picamillon 20mg and/or Selank
  5. Ocassionally Semax - (note: anything that increases BDNF anectodally increases hair loss (although reversable when stopped). I noticed that so I don’t take it much.)
    Highly recommend Semax 0.1 % for those with a higher risk of stroke or age related cognitive decline. For example, in Eastern europe Semax is carried on every ambulence and is admistered in the ER immediately to Stroke patients.
  6. Several eggs a day (must be pasture raised and corn and soy free) or Ocassional Alpha GPC - 300mg
  7. L-theanine - 200mg if I ever drink caffeine. I don’t tend to drink much coffee.
  8. Lithium Orotate - 1mg
  9. Have tried Zyn’s but stopped after a week. Nicotine decreases thiamine (B1) big time hence why the energy drain after it. Only way I would take Zyn’s is with large doses of thiamine.
5 Likes
#29

Hi Genja,

I have been doing some research on a7 nicotinic receptor agonists searching for an effective and safe way to improve cognition via nicotinic receptors. This article is a treasure with tables of agonists and positive allosteric modulators (PAM ). The alpha 4 receptor also improves cognition.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8318519/.

1 Like
#30

it sounds pretty scary, consider how many supplements contains alpha gps or choline esp. those for energy or brain focus. Are the effect dose dependent?

1 Like
#31

Exactly. dose and time dependent. Large doses (600-1200mg daily) over years. But keep in mind if you have a predisposed condition that you may or may not be aware of, your risk obviously goes up. Such as hypertension, clotting disorders etc…So it’s not for everyone, and definitely not something I would do everyday.

Eat a couple of eggs instead for the choline. Even though they have high choline levels similar to the supplements they seem not to cause the same degree of risk with TMAO as the supplements.

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#32

Participants’ plasma TMAO levels increased significantly in all 3 intervention arms containing choline bitartrate (all P < .0001), but daily ingestion of 4 large eggs (P = .28) or phosphatidylcholine supplements (P = .27) failed to increase plasma TMAO levels

People just need to give up on choline bitartrate and switch to phosphatidylcholine instead. I don’t take any of those nootropics nor am I about to anytime soon but just wanted to chime in that basically lecithin supplements are much better anyway.

3 Likes
#33

Also Nefiracetam which is an Agonist for Alpha 7 nicotine receptors and also Alpha 4B.

Nefiracetam, a pyrrolidone derivative developed as an anti-dementia drug, persistently potentiated currents through neuronal nicotinic acetylcholine (ACh) receptors (α7, α4β2)

https://www.sciencedirect.com/science/article/abs/pii/S0169328X00001170

#34

I broke down my stack (the one from above) in great detail if anyone is interested. It’s a must read imo.

3 Likes
#35

Huperizine is great. Didn’t have a chance to take it for an extended period of time. But will try to add it in.

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#36

I understand CDP choline does not have that stroke risk.