The neuroprotective uses of Piracetam

And some backstory about myself...

Piracetam is one of the main parts of my “brain stack”, but I never knew why it is so effective, so I decided to try a little research. For clarity's sake, my “brain stack” is located at the end of the following article, which I will replicate only the stack here.

Things Hidden Since the Foundation of Cognition

For massive cognitive enhancements and healing, this is the best stack I and a friend came up with. The more “fucked up” your brain is, the better its effect, for God's know why.

Morning - 150 mg of Thiamine

Lunch - or with your biggest meal

N Acetyl Cysteine 600 mg to 1200 mg

Niacin (FLUSH) or Niacinamide - 250 mg to 500 mg

Piracetam 400 to 800 mg

Gingko Biloba - 40 mg+

COKE ZERO

Piracetam has synergy with NAC, the first affects cell permeability, the other affects antioxidation, mitochondria, etc. Niacin supercharges the effects, but that isn’t the trick.

A compound inside coke zero acts as a mild calcium blocker.

When you use a calcium blocker with Piracetam, you potentialize its effects by A LOT. So you are compounding each supplement into supercharging your brain. This WILL help you with covid/jab brain fog, and general dementia in old people. Overall focus way up. It is a poor man modafinil.

Old people who used this got their “brains back”. Younger people said it helped a lot, got good positive results, more productivity, and some say “I am more intelligent now”.

This stack will enhance your cognitive capacity.

Thiamine will only make sense in my Thiamine post, it deserves a big article on its own.

First, you need some back history why I am such a massive proponent of this specific “stack”. Stack is nerd slang for a specific combo of compounds and/or supplements to achieve specific goals, often they have to do with cognitive performance. Now to the reasons.

Years ago I was diagnosed with Severe Erosive Gastritis - Grade III, I was basically an inch away from serious ulcerations [open sores that literally bleed] inside my gut. The more severe your gut problems, the more severe every other problem you have, since the gut is quite literally your second brain and a potent modulator of your entire immune system, one thing feeds the other. Allied to that, I was put under a really horrendous (semi-vegetarian) diet by my gastroenterologist, one of the best in the country (and he is shit, so you can gauge how good most gastros are) which compounded every single problem.

Under certain conditions, your body will cannibalize itself, to get what it needs your brain will literally demineralize your bones, so your body can get calcium and sodium, and it will eat your muscles away for proteins and nutrients. I had an aggravating situation that most doctors will not even be aware of even if they are competent. Which is the following.

At 23 years old I was morbidly obese. My weight was over 250 kg (convert to pounds yourself lol). I am a tall guy, still, that is insanely too much. One thing you learn when you start learning about medicine is that fat is not just an “energy deposit”, it is an everything deposit.

3 months after my 24 birthday, I got a “medical scare”, severe high blood pressure (predictable). Here (Brazil) we used to have 3 classes of doctors. Useless (most), the ones that love the profession (the actual good doctors), and Japanese descendants, usually the best in their fields. I ended up with a Japanese doctor with double specialty. From that consult, he stated, “Either you change, or die”. Something clicked. Among other tips, by sheer observation he could see I was interested in medicine, so he told me to go read scientific papers on human metabolism.

Took me 2 weeks to “create a new diet”, at the time I thought it was a novel approach by sheer ignorance. The diet has 120+ years of history. The Ketogenic Diet. What I didn’t know is the following.

The higher your weight, the slower you should lose weight. Otherwise, your body will use your fat stores as fuel and release everything inside. Do you know where every single mammal stores toxins ? Fat. I lost 157 kg in 10 months and 11 days. Also, if you consume too few carbs for your massive weight, your body will eat away your lean mass.

The impact on my body was severe, I harmed (the correct term is taxed) every organ inside me except my heart. The toxins taxed my liver to an insane extent, and my immune system was basically nonexistent for years, for a lack of knowledge and relying on doctor’s stupidity. Most doctors anywhere won’t accept that simple supplementation of vitamins can help you. And only a very small percetange of gastros are aware that gastric lesions affect your ability to absorb nutrients. I also lost a lot of muscle because of going too low carb for my weight and losing it too fast.

These events plus other variables led to the cascade which became my severe erosive gastritis, severe systemic inflammation and the lack of proper supplementation and nutrients led to my brain degrading so much, that by 2019 I had a possible diagnosis of Early Onset Alzheimer’s Disease. That is how bad my nervous system and brain were.

Thiamine comes in about late 2019. Thiamine helped my brain a lot. Within months I got back at a “nice” level, not what I used to be, but functional. I could learn properly, remember days, etc. The longer I took thiamine, the more my brain recovered, it is slow, but the improvements within 6 months are perceptible.

I knew about Piracetam, but for years was afraid to try, because every single time I tried, it hurt my stomach pretty bad (this is not the fault of the Piracetam btw, but mine). A good friend prompted me to test it again, and since I was taking NAC with food, I decided “I will just take everything with food, I don’t trust these people with these crappy designed papers anyway”. (this is in reference to how scientists measure bioavailability)

By sheer coincidence, I was taking 125 mg of Niacin at the time, and 600 mg of NAC. I added 400 mg of Piracetam + 20 mg of Gingko Biloba (a reliable place here that sells it like this). Within one week, the changes in cognition were perceptible. Within 2 weeks, I already commented with said friend on the improvements, and it boggled his mind. I was getting the enhancing effects of Piracetam at 10x LOWER dosage.

Within 2 months this is what happened to my brain and physiology :

• My memory got back to the level it used to be when I was 20 years old, meaning I have a degree of eidetic memory

• My cognition also got back to what used to be, hyper-fast, parallel thinking, I could once again connect dots at a speed few can

• Learning became easy again

• Here gets weird. In a small subset of users, you can get other types of enhancements at high dosages of Piracetam, I got some of my hearing back, and my vision which was never bad got enhanced

These effects happen at 4 grams+ per day, and people will often stack a lot of other supplements to achieve even parts of it. All of these effects have literature and case reports on them. Piracetam is sometimes used in certain countries as a late-stage treatment (treat symptoms) for CJD (Creutzfeldt-Jakob Disease). Now to understand some of the science on why this work the way it does.

Up until a few years ago, calcium blockers were seen as one of the possible causative agents of Alzheimer’s (doesn’t make sense even when I was a layman). Now ?

At some level, some of the old people addicted to Coke Zero are literally self-medicating…

New therapeutic activity of metabolic enhancer piracetam in treatment of neurodegenerative disease: Participation of caspase-independent death factors, oxidative stress, inflammatory responses and apoptosis
Highlights

• Piracetam ameliorates the LPS induced adverse effects in rat brain regions.

• Piracetam exerts antioxidative, anti-inflammatory and anti-apoptotic activity.

• Piracetam induced neuroprotective involve caspase independent pathway.

• Piracetam prevents the AIF and endonuclease G translocation and apoptosis.

LPS [Lipopolysacharides] are parts of the outer (the part outside) of some bacteria, they are highly toxic inside us, and a very used model to study inflammation or anti-inflammatory/antioxidant mechanism of many compounds, among many other uses. The entire paper is worth reading, but this part is the one that jumps the eye very early on.

Piracetam treatment offered significant protection against LPS induced oxidative and inflammatory parameters and inhibited astrocytes activation. LPS administration caused augmented level of reactive oxygen species and depleted mitochondrial membrane potential which were attenuated with piracetam treatment.

From my perspective, the Mitochondrial Membrane Potential attenuation is one of the best things you could achieve with a supplement because SARS-CoV-2 does exactly that and more.

You would need to read some of my recent articles or my Twitter to understand this part. A summary, and oversimplification for misfolded protein/plaque diseases to develop and take hold, they need somewhat stringent conditions, and among a lot of the autopsies, the same trend can be observed. Hyperglycemia, and always higher levels of TNF-Alpha and downregulation of Interleukin-10 (not mentioned in this paper), and the low availability or outright deficiency of Glutathione (GSH). The main effect of NAC is antioxidation, raising your GSH levels, anti-inflammation being secondary, now you can get how they have synergy, and why they are so effective together with “brain stuff”.

Piracetam attenuates cyclophosphamide-induced hepatotoxicity in rats: Amelioration of necroptosis, pyroptosis and caspase-dependent apoptosis

Key findings

Cyclo administration resulted in deterioration of serum liver function tests and elevation of hepatic tissue concentration of P53, Nf-kβ, apoptosis-inducing factor-1, NLRP3 inflammasome, Bax; gene expression of receptor-induced protein-1 along with reduction of hepatic Bcl-2 concentration. Bax/Bcl-2 ratio headed for apoptosis. Cyclo administration also resulted in a severe deterioration of the hepatic histopathological picture and significant immunohistochemical expression of caspase-3, tumor necrosis factor-alpha (TNF-α) and Cyclooxygenase-2 (COX-2) in hepatic tissues versus the normal group. Pira significantly improved all the aforementioned parameters, reallocating the Bax/Bcl-2 ratio to anti-apoptosis. Moreover, Pira treatment amended Cyclo-induced histopathological abnormalities and significantly reduced caspase-3, TNF-α plus COX-2 immunoreactivity in hepatic tissues.

These are but a few of the extensive recent research on Piracetam, the literature, and use is quite extensive, it goes beyond these, there are quite a few papers on HIV, neurodegeneration, and how Piracetam is a really good option as a prophylactic treatment to slow this down. Now we have a mechanistic understanding of why and how Piracetam is acting in the stack, it is acting as not only as an anti-inflammatory but also as a minor immunomodulator.

The entire stack [Piracetam, Niacin, NAC, Coke Zero, the compounds inside Coke like Phenylalaline and caffeine] are modulating your bioenergy in the brain, severely diminishing inflammation, chelating whatever extra unnecessary metals you have (see down below), rescuing some of the immune cells towards the proper function, and not being overactive driving inflammation, among other not so clear mechanisms (why it gives you such a broader focus and literally makes you think faster ? The list goes on.

As a side note, I went to check some of the fancy brands of Nootropics (smart drugs), and many are now adding Piracetam with Phenyl…FYI…

With a decent diet (fasting or low carb), proper nutrition, a common multivitamin, and the “stack”, cognitive recovery and subsequent enhancement are not merely achievable, it is factual, to the degree of recovery each person will go, only testing will know. I can talk from experience, the worst your brain is, the more effective the stack becomes, probably because you can clearly measure the before and after when things are working at above optimum levels.

As a final note on this subject and for full disclosure, I don’t have the paper only my paper notes, but some Alzheimer’s researchers looking into the effects of Piracetam and neurodegeneration and memory loss argue that the same genes that make one propensity to develop AD, are the same genes that make Piracetam super-effective in some people. My paternal side of the family had half a dozen Alzheimer’s cases, therefore part of the massive benefit I get might be from my cursed genetics.

For last since we are into a neurodegeneration veneer lately, a lot of people ask why I stay away from Zinc besides whatever comes inside my multivitamin, I abhor Iron, and avoid calcium (the calcium by now should be self-evident).

Neurometals in the Pathogenesis of Prion Diseases

Abstract

Prion diseases are progressive and transmissive neurodegenerative diseases. The conformational conversion of normal cellular prion protein (PrPC) into abnormal pathogenic prion protein (PrPSc) is critical for its infection and pathogenesis. PrPC possesses the ability to bind to various neurometals, including copper, zinc, iron, and manganese. Moreover, increasing evidence suggests that PrPC plays essential roles in the maintenance of homeostasis of these neurometals in the synapse. In addition, trace metals are critical determinants of the conformational change and toxicity of PrPC. Here, we review our studies and other new findings that inform the current understanding of the links between trace elements and physiological functions of PrPC and the neurotoxicity of PrPSc.

Although PrPC and PrPSc have the same chemical characteristics and primary sequence, PrPSc differs from PrPC in terms of its high content of β-sheet secondary structure, propensity to form insoluble amyloid fibrils, and resistance to protease digestion. When misfolded PrPSc enters the body via the ingestion of contaminated food or iatrogenic contamination, the protease-resistant PrPSc invades the brain, forms aggregates and amyloid fibrils, and in turn promotes neighboring PrPC molecules to misfold and aggregate.

There are at least two possible pathogenic pathways of prion diseases; the first supports “the loss of the normal, protective functions of PrPC”, and the second supports “the gain of toxic functions of PrPSc” [6]. Normal PrPC consists of a 30–35 kDa glycoprotein anchored at the plasma membrane with a glycosylphosphatidylinositol (GPI) domain and is widely distributed throughout the body, including the liver, heart, and brain. Although the physiological roles of normal cellular PrPC are not yet fully understood, knockout mice lacking PrPC exhibit several neurological disfunctions, including the death of Purkinje neurons in the cerebellum, synaptic function disorder, and memory loss [7,8]. PrPC reportedly regulates N-methyl-D-aspartate (NMDA)-type and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors [9].

Increasing evidence suggests that PrPC is a metal-binding protein and plays critical roles in the maintenance of metal homeostasis [10]. In the brain, various trace elements including iron (Fe), zinc (Zn), copper (Cu), and manganese (Mn) exist at different concentrations and distributions across various brain regions [11]. These trace elements, termed “neurometals”, play significant roles for brain functions as well as ubiquitous elements such as calcium (Ca) and magnesium (Mg). Recent studies supported that “neurozinc” acts as an intracellular messenger and modulates neural information [12,13]. Neurometals are essential for normal brain functions; however, their excess is neurotoxic, and therefore, their concentration and chemical form are strictly regulated. Thus, the depletion of PrPC and the resulting metal dyshomeostasis may trigger neurodegenerative processes. Interestingly, PrPC, APP, and α-synuclein are co-localized at the synapse, which is a narrow space filled with metals and the major target of these neurodegenerative diseases. APP and α-synuclein also possess metal-binding abilities and are involved in the regulation of metal homeostasis [14].

Molecular Mechanism of PrPSc-Induced Neurotoxicity: Disruption of Ca Homeostasis

The apoptotic pathways induced by PrP106–126 are of great interest. PrP106–126 reportedly causes various adverse effects, such as the proliferation of microglia, induction of proinflammatory responses, ROS production, and activation of ER stress. However, the precise mechanism of neurodegeneration induced by PrP106–126 is still unclear.

We focus here on the formation of Ca2+-permeable pores by the PrP106–126 peptide and the consequent Ca2+ dyshomeostasis. It is widely accepted that the disruption of neuronal Ca2+ homeostasis and alteration of the intracellular Ca2+ concentration ([Ca2+]i) activate various apoptotic proteins such as calpain and caspase, leading to neuronal death, and they trigger various adverse effects that are also associated with prion diseases.

Ca2 is calcium. Ignore the terms you don’t understand, everything else is somewhat straightforward to understand if you simplify it in your mind. Too much free neurometals = fuel for neurodegeneration. I could go on further but then, I would get abruptly off-topic, but you can search calcium, zinc, and iron accumulation + mitochondrial dysfunction and you can get a pretty clear picture of where this is going. This is already addressed in my stack by both my dietary tips and NAC, a known mild chelating agent.

Off-topic. Tomorrow my mother will go through surgery, so I may be fairly inactive for 2 to 4 days, I will still try to write and publish things, but in case I go full radio silent, this is the reason why.

Thanks to everyone who bought me a coffee and is a paying subscriber, up until a few weeks ago, all the money I went to this. Thanks to everyone who shares or just appreciates the work and finds helpful “anything” here.

Deep appreciation for all the supporters!