Agmatine

Agmatine Sulfate


Summary: Agmatine is an amino acid that offers a wide of cognitive boosting benefits. It also has excellent effects on reducing neuropathic pain, as well as drug addiction habits. It is neuroprotectant and can reduce tolerance built to many medications like benzodiazepines, morphine, and other painkillers. It also synergizes with SSRI’s & cannabis.




Introduction


What is Agmatine?

Agmatine is a form of amino acid that derives from L-Arginine. It has been shown to inhibit receptors for the neurotransmitter acetylcholine, which plays a major role in memory and reasoning.

Agmatine supplement also regulates levels of Nitric Oxide by the affecting nitric oxide synthase enzyme. It controls cellular energy levels by influencing polyamine metabolism and function.

In some studies, it has been shown to enhance the effects of both morphine and fentanyl to increase pain killing, reduce tolerance, and lower addiction, as well as working synergistically with marijuana.

It is also found naturally in every day foods, including beer, wine, coffee, and other fermented foods.

Because it is capable of targeting multiple receptors, agmatine may benefit a spectrum of complex diseases, including diabetes, Alzheimer’s disease, opioid addiction, mood disorders, and even cancer. Furthermore, agmatine may enhance cognitive function, stress resiliency, mood, and athletic performance [R] [R].

The highest levels of agmatine are found in the gut, where it is produced by the microbes living there.

It is also found in dietary form, mainly in fermented foods, and in supplemental form like agmatine sulfate.

Agmatine is also produced in small amounts within the body by the mitochondria in the liver. [R]Self Hacked


Benefits & Effects


Agmatine benefits the body and mind in many different ways and depending on the method it is taken. Some of the most notable agmatine benefits are:

Reduces Pain Sensitivity

In research studies, Agmatine shows to be an effective way for pain relief. Especially in the case of thermal hyperalgesia, a condition where the body is sensitive to changes in temperatures. The body becomes hypersensitive to heat or cold.

Agmatine improves those pain sensations, which is a result of its pro-circulations effect.

In studies looking at pain reduction in neuropathic conditions or inflammatory pain, agmatine was not found to produce a statistically significant effect. However, anecdotal, first-hand reports show that it actually did work for neuropathic conditions. So in this specific situation, it seems to be subjective to each individual.

Reduces Symptoms of Anxiety & Depression

Agmatine exhibits antidepressant effects and promotes mood improvement as well as anxiety reduction and relief. It helps the brain and body manage and overcome stress by reducing anxiety and promoting a sense of well-being.

By increasing NRF2, agmatine prevents depressive behavior by protecting brain cells from high levels of stress hormone cortisol. [R]

Agmatine increases adenylate cyclase in the prefrontal cortex, and decreases levels of adenylate cyclase which associate with depression. [R, R].

Furthermore, it blocks the NMDA receptor, prevents calcium overloading, as well as reverses the decrease of monoamines such as norepinephrine, epinephrine, and dopamine. Depression often associates with a reduction of monoamines in the brain [R, R]

Studies & Research

A small pilot study on three patients suffering depression, Agmatine supplement caused a complete disappearance of depression symptoms in all patients. It most likely did so through NMDA receptor-blocking and not through serotonin pathways. [R]

Agmatine also reduced anxiety in rats when they were put in swimming and maze navigation tests. [R]

Neuroprotection & Longevity

Agmatine acts as an anti-oxidant and is continuously under more research for its anti-aging and longevity potential.

It has been found to exhibit neuroprotective effects against oxidative damage and injuries to the Central Nervous System (CNS).

It is also believed to limit the activity of glutamate receptors and thus, the over-excitation of neurons within the brain.

Additionally, by inhibiting iNOS and nNOS and increasing eNOS, Agmatine protects against brain damage from stroke.

Increasing eNOS protects the brain by dilating the blood vessels to increase blood flow. This prevents damage during times of lack of oxygen from reduced blood flow to the brain (also known as ischemic stroke).

Agmatine decreases iNOS and nNOS, two enzymes that contribute to brain damage from stroke. [R]

A Study on Effects of Agmatine Sulfate on Nerve Injury:

OBJECTIVE:
Evaluate the effect of agmatine sulphate on facial nerve regeneration after facial nerve injury using electron and light microscopy.


METHODS:
The study was performed on 30 male Wistar albino rats split into: a control group, a sham-treated group, a study control group, an anastomosis group, and an anastomosis plus agmatine sulphate treatment group. The mandibular branch of the facial nerve was dissected, and a piece was removed for histological and electron microscopic examination.


RESULTS:
Regeneration was better in the anastomosis group than in the study control group. However, the best regeneration findings were seen in the agmatine sulphate treatment group. There was a significant difference between the agmatine group and the others in terms of median axon numbers (p < 0.004) and diameters (p < 0.004).


CONCLUSION:
Agmatine sulphate treatment with anastomosis in traumatic facial paralysis may enhance nerve regeneration.

PMID: 28122652

Improves Weight Loss & Prevents Weight Gain

Individuals who struggle to gain weight can benefit from Agmatine supplements. In some studies, subjects increased food consumption rates by 44% to 54% in 24 hours.

Moreover, in the following studies, Agmatine shows an increase in fat burning, a decrease in fat composition, and an increase in muscle mass [R], which also contributes to the next benefit of Agmatine:

Supports Muscle Growth

Agmatine stimulates the production of luteinizing hormone (LH). Increasing these hormone levels lead to an increase in testosterone levels.

By increasing testosterone levels, Agmatine contributes to an optimal hormonal environment for muscle growth, enhances athletic performance, and fastens recovery. [R]

Agmatine also increases insulin sensitivity and the uptake of glucose into the muscle. Increasing insulin sensitivity results in more effective shuttling of amino acids as well as glucose into the tissues for growth and repair. [R] [R]

Helps Erectile Dysfunction & Infertility

Studies show that L-arginine is involved in the process of cell replication, in addition to enhancing blood circulation, so it can help improve both sperm production and motility.

Men dealing with cardiovascular issues due to low levels of NO in the blood are more prone to experience erectile dysfunction and fertility problems because an erection requires a relaxation of smooth muscles, which Nitric Oxide triggers.

Although it doesn’t apply to every person, a significant rate of male infertility cases (92%) is treatable with L-arginine supplements in combination with dilators, antioxidants and/or anti-inflammatories. [R]

Research suggests that high-stress levels lower L-arginine levels in the sperm production pathway. Therefore, men with chronic stress specifically can benefit from Agmatine supplement.

According to Dr. Axe, a combination of L-arginine, L-glutamate and yohimbine hydrochloride is a common way of treating erectile dysfunction. And it works better than L-arginine alone. [R]

“In fact,” he says, “many of the most frequently prescribed medications for ED work similarly to L-arginine: by increasing nitric oxide production.”

Furthermore, there’s research suggesting treatment with N-Acetyl Cysteine (NAC) and L-arginine together can help balance hormones naturally and restore normal sexual function in women with polycystic ovary syndrome and estrogen imbalances.

Other studies suggest that L-arginine with herbs such as chasteberry, green tea extract, and antioxidant supplements improve pregnancy rates in women struggling to conceive. [R]

Help’s with Alzheimer’s Disease

Insulin resistance could cause an increase of plaque and neurofibrillary tangles in the brain, which are the signs of Alzheimer’s disease. Agmatine prevents cognitive decline by rescuing insulin signaling and avoiding potential accumulation of those tangles. [R]

Helps Alcohol & Morphine Withdrawal

Agmatine reduces and to an extent, prevents, symptoms of alcohol withdrawal such as “wet dog shakes,” anxiety, flashes, and shakings. [R] [R]

Mechanism of Action


Agmatine has several mechanisms. It can inhibit N-methyl-D-aspartate (NMDA) and nicotinic acetylcholine receptors, as well as activate imidazoline receptors. Agmatine can also inhibit nitric oxide synthase enzymes, which allows it to regulate elevated levels of nitric oxide. Agmatine can inhibit calcium channels and specific serotonin receptors as well. Further research is needed to determine the full extent of agmatine mechanisms. [R]

Agmatine was found to exert modulatory actions directly and indirectly at multiple key molecular targets underlying cellular control mechanisms of cardinal importance in health and disease. It is considered capable of exerting its modulatory actions simultaneously at multiple targets. The following outline indicates the categories of control mechanisms and identifies their molecular targets:

Neurotransmitter receptors and receptor ionophores. Nicotinic, imidazoline I1 and I2, α2-adrenergic, glutamate NMDAr, and serotonin 5-HT2A and 5HT-3 receptors.

Ion channels. Including: ATP-sensitive K+ channels, voltage-gated Ca2+ channels, and acid-sensing ion channels (ASICs).

Membrane transporters. Agmatine specific-selective uptake sites, organic cation transporters (mostly OCT2 subtype), extraneuronal monoamine transporters (ENT), polyamine transporters, and mitochondrial agmatine specific-selective transport system.

Nitric oxide (NO) synthesis modulation. Both differential inhibition and activation of NO synthase (NOS) isoforms is reported.

Polyamine metabolism. Agmatine is a precursor for polyamine synthesis, competitive inhibitor of polyamine transport, inducer of spermidine/spermine acetyltransferase (SSAT), and inducer of antizyme.

Protein ADP-ribosylation. Inhibition of protein arginine ADP-ribosylation.

Matrix metalloproteinases (MMPs). Indirect down-regulation of the enzymes MMP 2 and 9.

Advanced glycation end product (AGE) formation. Direct blockade of AGEs formation.

NADPH oxidase. Activation of the enzyme leading to H2O2 production.

Wikipedia

Dosage


How To Take Agmatine?

There is currently no standard dosage for agmatine sulfate because there haven’t been enough human studies for determination. These numbers are rough estimates to give an idea of typical, experimental dosing:

• For treatment of neuropathic pain: 1,000 to 2,500 mg of agmatine (daily)

• For improving cognitive function: 200 to 500 mg of agmatine (daily)

For vasodilation and enhanced recovery: 500 to 1000 mg of agmatine (30 minutes pre-workout)

Note: Agmatine is not absorbed well when taken with dietary protein, because it uses the same transporters as arginine

The generally accepted daily dosage range for Agmatine Sulfate is between 250 mg and 2.5 grams. Avoid taking higher than necessary dosages to reduce the risk of side effects.

Side Effects


According to studies conducted so far, it appears that Agmatine Sulfate is safe even in relatively high doses. While there have been few studies conducted thus far, they have not shown any side effects to be associated with this supplement.

If you follow the recommended Agmatine sulfate dosage protocol and do not have any pre-existing contraindications for use, the risk of serious adverse effects is very low.

Minor side effects included nausea, diarrhea, and vomiting in a small percentage of participants, which cleared up after a few days of discontinuing use. [R]

User Experience


Not only does it have varied anti-addiction properties to Opioids, amphetamines, caffeine, nicotine & alcohol, but it also seems to make other drugs, and medicines more potent in their effects. It also shares the properties of Ketamine’s antidepressant effects, via the mTOR AMPA pathway. A small study found a robust antidepressant effect; all patients reported remission of depression. Considering that, shutting down Serotonin production via parachlorophenylalanine, did not reverse the antidepressant effects, shows how punchy this substance is. It’s also a painkiller. I’d recommend this be added to everyone’s stack, provided they aren’t too fond of Alcohol, as I noticed it definitely seems to blunt the good feelings of certain drugs.

Reddit user

Frequently Asked Questions


What is Agmatine Sulfate?

Agmatine Sulfate is a biogenic amine that is derived from the amino acid L-Arginine. This happens by a process called decarboxylation, which is better known as the removal of carboxylic acid group from the amino acid.

Is Agmatine safe?

Yes. And here is a 5 year-long, daily high dosage of Agmatine in order to measure and proof its safety:

Clinical follow-up consists of periodic physical examinations and laboratory blood and urine analyses. All measurements thus far remain within normal values and good general health status is sustained throughout the study period, up to 5 years. This case study shows for the first time that the recommended high dosage of agmatine may be consumed for at least 5 years without evidence of any adverse effects. [R]

How long does Agmatine take to work?

Agmatine starts working as soon as it enters the bloodstream, which is typically 15 – 30 minutes after consumption. Users can expect to experience an increase in muscle pumps, vascularity and muscular endurance within this timeframe. [R]

How much Agmatine should I take?

The generally accepted daily dosage range for Agmatine Sulfate is between 250 mg and 2.5 grams. Avoid taking higher than necessary dosages to reduce the risk of side effects.

Can you take Agmatine with creatine?

This is the reason creatine and protein work so well together, in a nutshell. Bodybuilders can cut out the creatine middle man by supplementing with agmatine sulfate directly. … You take creatine to improve the protein effects. You take nitric oxide to improve the creatine effects.

Further External Readings


Agmatine – Wikipedia

Agmatine – Scientific Review – Examine

N-Acetyl Cysteine (NAC)

N-Acetyl Cysteine


Summary: N-Acetyl Cysteine (NAC) is a prodrug for L-cysteine, a precursor to the antioxidant glutathione, an essential antioxidant in the body. NAC supports glutathione replenishment which has been found to bind to the glutamate recognition sites of the NMDA and AMPA receptors. It also promotes healthy inflammatory responses.




Introduction


What is N-Acetyl Cysteine?

N-Acetyl Cysteine (also known as Acetylcysteine or NAC) is a prodrug for L-cysteine, a precursor to the antioxidant glutathione, an essential antioxidant in the body. NAC supports glutathione replenishment which has been found to bind to the glutamate recognition sites of the NMDA and AMPA receptors. It also promotes healthy inflammatory responses. Acetylcysteine was initially patented in 1960 and licensed for use in 1968. It is on the World Health Organization’s List of Essential Medicines and is easily accessible for a very affordable price.

Acetylcysteine, also known as N-acetylcysteine, is a medication that is used to treat paracetamol overdose, and to loosen thick mucus in individuals with cystic fibrosis or chronic obstructive pulmonary disease. It can be taken intravenously, by mouth, or inhaled as a mist. Some people use it as a dietary supplement.

Wikipedia

Benefits & Effects


N-Acetyl Cysteine Improves Cognitive Function

Combinations of NAC with other antioxidants improve cognition in both healthy older people and those with mild cognitive impairment. (R) (R)

NAC has many studies on enhancing cognitive function in Alzheimer’s, Parkinson’s, and schizophrenia. Currently, it’s under research for boosting cognitive performance after general anesthesia. (R)


N-Acetyl Cysteine Reduces Symptoms of Depression

NAC helps people with depression by balancing glutamate levels within the brain. Doing so, it reduces inflammation and increases the growth of new brain cells. R

In a study of more than 500 participants, NAC shows an improvement in symptoms of depression and overall functionality. At 2000mg per day, it improves mood in people diagnosed with depression. (R), (R)

NAC Helps Symptoms of Bipolar Disorder and Mania

NAC improves chronic health issues such as heart disease and hormonal imbalance in people with Bipolar Disorder. In a 6-month study, NAC indirectly shows to affect overall health, antioxidant and inflammation levels, as well as mood. (R)

Another study on 17 subjects with bipolar disorder, NAC shows improvements in low moods and reduction in overall associating symptoms after six months of supplementation. (R)

In a study of 15 individuals suffering from mania, NAC also shows improvement after a six-month regime. The group receiving NAC had a reduction in symptoms versus the one receiving placebo. However, mood swings seem to worsen as a result. (R)

NAC Reduces Symptoms of OCD (Obsessive Compulsive Disorder)

NAC balances glutamate levels as well as increases antioxidants within the brain. In a study of 44 subjects with OCD, a NAC dose of 2000mg added to standard medication shows to improve symptoms, even in severe cases. R

Another study of 48 subjects who didn’t respond to typical treatment, NAC shows to improve symptoms after a 3-month period safely. (R)

NAC is useful for obsessive-compulsive disorders according to extensive research. It shows promising benefits and has very few side-effects. (R)

Improves Male Fertility

In addition to helping women with PCOS (Polycystic ovary syndrome), NAC may help increase fertility in men. Oxidative stress damages the sperm’s DNA, which results in reducing fertility. (R)

A study done on 120 infertile men receiving NAC, improvements were notable in semen quality and antioxidant status after a period of three months. (R)

Other studies look at the fertility benefits of NAC in combination with other antioxidants such as B vitamins, vitamin C and D. The combination improves the sperm count in those with low sperm count. (R)

In an extensive study of almost 500 infertile men, NAC with selenium show improvement in fertility after a six month period. (R)

Subfertility Conditions

Some men are sub-fertile — they are less fertile without an apparent reason. In 84 of subfertile men trying to conceive, NAC combination supplement called Condensyl (with vitamins, zinc, fig extract, and vitamin E) increased pregnancy rates. It raises the “fertility potential” of subfertile men increasing the rate of successful pregnancy. (R)

The typical NAC dose for improving fertility in those studies was 600 mg/day.

NAC Boosts Skin Health

Interestingly, NAC can be used as a cream or gel to improve skin health. It boosts glutathione in the skin protecting it from damage. Furthermore, NAC reduces skin inflammation and normalizes skin cell division. It’s used for eczema, skin irritation, radiation-induced skin damage, wound healing, and acne. In a study of 100 participants, a 5% NAC gel shows to reduce mild to moderate acne. (R)

Overall, NAC skin formulations are promising and very safe. Case reports and animal studies support this wide range of skin benefits of NAC.

NAC May Improve Autism

NAC seems to benefit children with autism. In a study of 33 autistic children, NAC (900-2,700 mg/day) shows to reduce irritability after three months period. (R)

In 2 different studies with 80 autistic children, those receiving NAC as an add-on to their medication (risperidone) show less irritability and hyperactivity after two months period. (R), (R)

NAC Reduces Muscle Fatigue

Overall, NAC tends to help muscles improve blood flow during intense training as well as recover faster after a workout.

It also seems to help older individuals in improving fitness and enhancing endurance in athletes on the short-term. However, long-term NAC with exercise may prevent muscle recovery.

NAC Reduces Antibiotic Side Effects

Antibiotic side effects arise from free radicals damage. As a potent antioxidant, NAC (1,200 mg/day) reduces side effects, prevents kidney and ear damage from several strong antibiotics in 2 studies of 100 people. (RR)

NAC also protects the liver from the harmful effects of anti-tuberculosis drugs as shown in a study of 60 participants. Those receiving NAC show intact liver after treatment, while 40% of those who didn’t take NAC suffer liver damage. (R)

Reliefs ADHD Symptoms

In a study of nearly 100 ADHD participants, NAC shows to reduce ADHD symptoms in patients with as well as improving cognition, impulsivity, and overall symptoms.

Participants were receiving up to 5g per day during this study. (R)

Other Benefits

According to Health Line, the following are the 9 top benefits of NAC:

  • Essential for Making the Powerful Antioxidant Glutathione
  • Helps With Detoxification to Prevent or Diminish Kidney and Liver Damage
  • May Improve Psychiatric Disorders and Addictive Behavior
  • Helps Relieve Symptoms of Respiratory Conditions
  • Boosts Brain Health by Regulating Glutamate and Replenishing Glutathione
  • May Improve Fertility in Both Men and Women
  • May Stabilize Blood Sugar By Decreasing Inflammation in Fat Cell
  • May Reduce Heart Disease Risk by Preventing Oxidative Damage
  • Ability to Boost Glutathione Levels May Improve Immune Function

Side Effects


N-Acetyl Cysteine is a safe substance with very few known side effects. Although occasionally, it can cause nausea, diarrhea, or constipation.

Large doses in a mouse model showed that acetylcysteine could potentially cause damage to the heart and lungs. They found that acetylcysteine was metabolized to S-nitroso-N acetylcysteine (SNOAC), which increased blood pressure in the lungs and right ventricle of the heart (pulmonary artery hypertension) in mice treated with acetylcysteine.

The effect was similar to that observed following a 3-week exposure to an oxygen-deprived environment (chronic hypoxia).

The authors also found that SNOAC induced a hypoxia-like response in the expression of several important genes both in vitro and in vivo.

Wikipedia

Dosage


How To Take N-Acetyl Cysteine (NAC)?

The typical dose for general wellness and gut health is 500mg per day taken in the morning on an empty stomach.

800 to 2,400mg are the most common across clinical studies. However, for a chronic health condition, consider a higher dose. Studies concerning addiction and mental health issues use doses closer to 3000 mg/day.

Daily doses should be taken at 2-3 times a day.


Acetyl-L-Carnitine

Acetyl-L-Carnitine (ALCAR)


Summary: Acetyl-L-Carnitine is a popular multi-functional nutrient, amino acid type nootropic. It benefits the body and brain. A potent antioxidant and neuroprotectant, and a powerful energizing nootropic that promotes anti-aging and longevity.




Introduction


What is Acetyl L-Carnitine?

Acetyl-L-Carnitine, also known as ALCAR and ALC, is an amino acid naturally produced in your body to generate energy. It’s also found in animal proteins such as red meats. Many people supplement with acetyl-L-carnitine because of its potential benefits. Acetyl-L-Carnitine is a more bioavailable form of amino acid l-carnitine, a derivative of amino acid lysine. The body continuously produces L-carnitine, and furthermore gets it from the foods you eat.

Although research shows actual carnitine insufficiency is uncommon in healthy people with no metabolic disorders, supplementation with addition of it is proven to be beneficial in many different ways. Ranging from improving heart health (R) to enhancing brain function (R).

Acetyl-L-Carnitine is L-carnitine with the addition of an acetyl group, thereby making it the most bioavailable form of L-carnitine and it readily crosses the blood-brain barrier. Its primary actions work towards brain functionality. Its nootropic properties seem to magnify when taken with other nootropics. The combination makes it a potentiating agent allowing nootropics to work more effectively.

Other forms of L-carnitine include L-carnitine L-tartrate (LCLT) which is typically assessing physical performance, and Glycine Propionyl L-carnitine (GPLC), which relieves blood flow issues. The only L-carnitine form that possesses nootropic properties is Acetyl L-carnitine, and it furthermore provides both L-carnitine and acetyl groups (molecule) that act towards the development of the learning neurotransmitter, acetylcholine.


Benefits & Effects


What Are Acetyl-L-Carnitine Benefits?

  1. Enhances Brain Function and Stamina
  2. Provides Neuroprotection Against Brain Cell Death
  3. Restores Cognitive Function and Repairs Impairment
  4. Support Mitochondrial Function and Nervous System
  5. Regulates Sexual Infertility and Erectile Dysfunction

Research proves ALCAR beneficial to the brain and body in many ways. From enhancing cognitive abilities (R) to increasing energy (R), reducing pain, and even preventing damage from alcohol consumption. (R)

Enhances Brain Function and Stamina

Studies show that it successfully lowers mental exhaustion and improves cognitive function as well as learning capability. In a placebo-controlled, randomized, double-blind, 2-phase study, 66 participants with fatigue were given 2 g of L-carnitine once a day. By the end of the study, the group taking L-carnitine showed significant improvements in physical fatigue, mental fatigue, fatigue severity amongst other physical enhancements, as compared to those receiving a placebo.

Moreover, the study confirms that oral supplementation of L-carnitine reduces the total of fat mass, increases muscular mass, increases capacity for physical and cognitive activity, improves cognitive functions, all while reducing fatigue as well. (R)

Provides Neuroprotection Against Brain Cell Death

Due to its potent antioxidant attributes, ALCAR acts as a neuroprotectant, blocking and restoring damage from free radicals that injure brain cells. It also helps the brain clear itself of other toxins and decreases cell death due to excitotoxicity, a neurotic process that triggers by the over-activation of glutamate receptors. It enhances the neural network by stimulating nerves and signal receptors and additionally protects the brain against the damaging influences of drinking alcohol. (R)

Restores Cognitive Function and Repairs Impairment

One of Acetyl-L-Carnitine’ many exciting prospects is as a treatment for age-related neurological disorders, including Alzheimer’s disease. It has been confirmed to dramatically slow decline in Alzheimer’s patients and decreases age-related recall failure. Other studies showed that ALCAR supports repair ambulatory capability in the elderly and functions as a mood lifter as well as working as an anti-depressant in the elderly. (R)

Support Mitochondrial Function and Nervous System

ALCAR promotes mitochondrial function and serves to support the nervous system overall performance. Especially in the case where an individual is subject to neurodegenerative disease. It can be of significant benefit to people with physical disorders typically correlated with aging, including high blood pressure, diabetes, and metabolic syndrome. It has shown to be efficient in managing nerve pain, enhancing kidney function, and improving heart health. (R) (R)

Regulates Sexual Infertility and Erectile Dysfunction

ALCAR regulates men’s infertility and improves signs of andropause and erectile dysfunction. It is also in use to fight Peyronie’s disease, an inflammatory disease that affects the penis. (R) (R) Additionally, it is under clinical trials as a possible treatment for chronic fatigue.


Mechanism of Action


ALCAR synthesizes primarily in the liver and kidneys, after which it travels to other tissues. ALCAR has excellent bioavailability. The gastrointestinal tract quickly digests it. Its actions differ considerably from other forms of L-carnitine, which don’t cross the blood-brain barrier. The acetyl groups that make ALCAR unique, enable it to cross the blood-brain barrier readily and rapidly. Its most effective role is within the cerebellum.

Another one of ALCAR’s nootropic benefits involves the acetyl groups, which produce the support for the synthesis of the neurotransmitter acetylcholine. Often referred to as “the learning neurotransmitter,” acetylcholine is accountable for learning, memory, and cognitive function. Increased levels of acetylcholine result in an improvement in cognitive function, and low levels of that essential neurotransmitter risks neurological complications similar to Parkinson’s and Alzheimer’s.

Acetyl-L-Carnitine on Neurotransmitters

ALCAR resumes showing increasing levels of norepinephrine and serotonin. They are vital neurotransmitters that play an essential part in mood and brain function. The capacity to improve neurotransmitter production is one of the principal techniques that ALCAR complements nootropics attributes. Similar to those of the racetams, which enhance the action of neurotransmitter receptors in the cerebellum.

Moreover, ALCAR targets brain metabolism, promoting cellular energy and serving as a potent neuroprotectant. Its critical antioxidant qualities combat the impressions of cellular oxidation. It further decreases the number of damaged cells in an individual brain, thereby becoming a useful longevity tool.

Damaged fat cells identified as lipofuscin (age spots) also happen in the brain and are actively correlated amidst age-related neurological dysfunctions, lack of energy, and weak memory. By supporting the brain excrete those damaged cells. ALCAR increases brain function and significantly lessens the risk of neurodegenerative disorders. It has also been shown to limit brain deterioration during times of stress.


Dosage


How to Take Acetyl-L-Carnitine?

Typical ALCAR dosage is 500 mg per day once in the morning, and up to 1,500 mg split into three doses of 500 mg. From there, adjust dosage to your need without exceeding 1,500 mg. At least not during trial period.

It is water-soluble, therefore it can be taken with or without food. However, taking ALCAR late in the evening can result in disruption of sleep.

Recommended dosage, active amounts, other details:

The standard dose for L-carnitine is between 500-2,000mg.


There are various forms of carnitine supplementation available.

Acetyl-L-Carnitine (ALCAR) is used for cognitive enhancement. L-Carnitine L-Tartrate (LCLT) is typically used for physical performance and power output.

Glycine Propionyl L-Carnitine (GPLC) is used to alleviate intermittent claudication and blood flow issues.

L-carnitine is supplemented daily. The equivalent dosage range for other forms of L-carnitine are as follows: 630-2,500mg (ALCAR), 1,000-4,000mg (LCLT) and 1,000-4,000mg (GPLC).

Examine.com

Side Effects


Side effects are uncommon. If they occur, it is usually in in the cases of consuming high doses before allowing the body to adapt to the additional amount of Acetyl-L-Carnitine that it is receiving.

Nausea is the most common side effect. It is easily preventable by taking ALCAR alongside food rather than on an empty stomach.

Headaches are the second most common side effect, which may imply an excessive amounts of choline.

Users report that headaches from ALCAR use decrease when they reduce the amount of choline in their stacks and diets.


Conclusion


ALCAR is an outstanding amino acid nootropic. It offers many benefits to both the body and the brain. In addition to its potent  brain boosting effect, it is also a healthy nutrient.

Acetyl-L-Carnitine is safe, affordable, very tolerable, and easily accessible in department and drug stores. It enhances cognitive function, supports ant-aging and longevity, which makes it a nootropic worth adding to any stack.


User Experiences


To be fair in sharing the Reddit community experiences, I will add the first 3 that I see whether the experience is positive or negative. Three Acetyl-L-Carnitine reddit experiences:

First Experience

As the title says, it’s been a game changer. Old stack was citicoline 300mg b.id with centrophenoxine 350mg one to two times daily. Switched Centro to ALCAR 500 one daily just to try and damn it’s been really good. Mornings are good, everything is really clear. Honestly this feels a lot like amphetamine. So much so that I cancelled my pdoc appt to get a refill. I was basically off the meds but wanted to have a few around but now I really don’t think I need them. Very glad people on here have posted about alcar before!skibenz

Second Experience

Funny enough I get a stronger response from ALCAR then I do racetams in regards to mental performance. It seems to make me really smart. Your mileage may vary though. To OP: I get results in a day. Be careful for not overdoing it. I’ve posted before that acetylcholine overload tends to make you depressed and function worse.eastmangoboy

Third Experience

I have been taking Acetyl for about 17yrs. For the last 2 yrs or so it has affected me less and less (no idea why) but before that, I noticed a MASSIVE positive boost from taking it. I experienced a huge uptick in word retrieval and overall brain function. used to always say that when I took Acetyl, it was like an electric switch was turned on, as that’s what it felt like … electric..I always bought it in bulk powder and almost always used 1 gram in my morning shake (180lb Male). DO NOT use it after noon …. you will NOT sleep !!!! You should notice a difference within 3-4 days. As I did mention, I am noticing now that I am affected by Acetyl less and less. If I miss a few days, I don’t really notice it like I did years ago and I don’t really get that electric charge feeling. I don’t know why this is, as I’ve purchased a few different brands.German_Mafia

Further Reading & External References


Acetylcarnitine – Wikipedia

Acetyl-L-Carnitine: Uses and Risks


L-Theanine

L-Theanine


Summary: L-theanine is a natural amino acid, often called the “natural xanax”. It almost only exists in green tea leaves. It works brilliantly in unwinding and relaxing the body and brain without causing drowsiness, while reducing stress and increasing cognitive function. Due to not causing drowsiness, it is the perfect choice to combine with stimulants of any sort to take the edge off.




Introduction


What is L-Theanine?

L-theanine is a relaxing, non-sedating amino acid that is synergistic with stimulants to ‘take the edge off.’ Especially with coffee, it synergizes so well resulting in clean energy, furthermore preventing the nasty caffeine crash that many people experience after caffeine intake. It is also useful on its own, promoting relaxation and minimizing stress without causing drowsiness. A combination of L-theanine with caffeine at a 2:1 ratio is increasing in popularity as a remarkably synergetic combination that boosts cognition and attention.

It is an amino acid that naturally exists in green tea leaves as its main active ingredient, and that is the only source that provides it. It is famous for its fantastic nootropic features such as improving memory, expanding learning capacity, as well as providing a calming, zen-like effect.

L-Theanine, for the most part, is a relaxing but not sedating amino acid that is synergistic with stimulants such as caffeine as it can ‘take the edge off’. It is effective by itself in the standard supplemental dosages as well, and although it can be attained via a diet high in green tea ingestion that is the only dietary source of L-Theanine

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Benefits & Effects


L-Theanine Reduces Anxiety & Stress

A review by researchers of a small set of trials concluded that there are benefits of L-theanine in reducing acute stress and anxiety in people with stressful conditions. [R]

Oral intake of L-theanine in rats at feasible dosages reduces circulating biomarkers of stress with or without an actual stressor being present. Therefore, it reduces the adverse effects of stress such as memory impairment. Reductions of perceived stress reported in human subjects given oral theanine at the standard dosages. [R] [R] [R]

L-Theanine Improves Memory, Attention, and Cognition

In a 16-week long study on individuals with mild cognitive impairment, supplementing with l-theanine shows an improved delayed recognition as well as immediate recall comparing to those receiving a placebo during a mental exercise. Furthermore, attention span and alertness levels increased during the memory test. [R]

Theanine Enhances Sleep Quality

Theanine enhances sleep quality. In a study measuring sleep time with individuals supplementing with L-theanine, sleep time increases by 11 and up to 21%, therefore making it a valuable compound for achieving better nighttime sleep. (R)

Promotes Longevity and Increases Lifespan

In a study using the model organism C. elegans, L-theanine shows to promote longevity and promote healthy and increased lifespan. Due to those findings, the study suggests that the compound might have similar effects on mammals and humans (R)

Reduces Symptoms of Depression

L-Theanine intake for a period of eight weeks during an open-label study helped easing depressive symptoms, anxiety, sleep disturbance, as well as cognitive impairments in subject suffering major depressive disorder. (R)

Promotes Relaxation without causing Drowsiness

Theanine is proving to be a great agent in promoting relaxation without the accompanying effect of drowsiness. The company developing ‘suntheanine’, l-theanine supplement, won the 1998’s Food Ingredient Research Award for the outstanding research and findings. (R)

Significantly Reduces Symptoms of Schizophrenia

In persons diagnosed schizophrenia receiving 400mg L-theanine in addition to antipsychotic medication for eight weeks were able to reduce anxiety as well as psychopathology symptoms significantly. (R)

Enhances Blood Flow and Stimulates Nitric Oxide Production

Theanine appears to promote nitric oxide formation at relatively low concentrations and is likely practically relevant following oral ingestion. (R)

Reduces Negative Effects of Caffeine & Improves Cognitive Boosting Effects

Theanine and caffeine are typically found together in tea. A combination of caffeine and theanine together significantly improves alertness, reduce fatigue, and improves task-switching accuracy.

High dose caffeine (250 mg, equivalent to 2.5 cups of coffee) has some negative effects, such as jitters and increased blood pressure. Theanine was able to mitigate the increase in blood pressure.

L-Theanine decreases the negative and jittery effects of caffeine in rats.

However, human studies found that L-Theanine helps reduce caffeine jitters, although the changes were not significant.

L-Theanine changes the pharmacological profile of caffeine in humans, as the combination of caffeine and L-Theanine have somewhat different cognitive enhancement effects.

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Additional Benefits

Large studies in humans have not been undertaken; however, several smaller-scale studies (fewer than 100 participants) have shown increased alpha wave generation and lowered anxiety, along with benefits to sleep quality in people with ADHD. [R]


Mechanism of Action


L-theanine has a comparable chemical composition to glutamate, an amino acid that assists in the transmission of nerve impulses in the brain. Thereby, providing a host of benefits for the mind. It has a remarkable ability of crossing the blood-brain barrier, which means that it reaches the brain directly. Furthermore, it has positive effects on stress levels proving to increase both dopamine and serotonin levels in brain; which are two of the brain’s feel-good chemicals. Green tea is known to be effective at helping people relax due to the positive impact on those neurotransmitters.

Theanine is an antagonist of the NMDA receptors (albeit with fairly weak efficacy) and can inhibit synaptic release of glutamate via blocking the transporter competitively. Theanine may also reduce glutamate levels, but this is also a fairly weak mechanism requiring a high concentration of theanine

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Dosage


How to Take L-Theanine?

The effective l-theanine dose is 200mg.

For optimal nootropic results, take l-theanine with caffeine (coffee or supplement, whatever suits you) at a 2:1 ratio. As a stack, it would be:

  • L-Theanine 200mg
  • Caffeine 100mg

For those interested, you can actually purchase a supplement pre-made that has 200 mg Theanine & 100 mg Caffeine pressed into one capsule. I’ve personally used and still use Nootropic Depot’s.

Note: if you have anxiety or hypertension, you may want to skip caffeine entirely as it aggravates the symptoms.

Experimenting is the best way to find out how you react to it.


Side Effects


L-theanine is very safe as very high doses have failed to cause toxicity. However, that doesn’t mean you should go for such high dosage. (R)

L-theanine is exceptionally reliable. Furthermore, it is classified Generally Recognized as Safe by the Fraud and Deception FDA in the US.


Conclusion


L-Theanine is a natural safe amino acid offering many benefits. It’s a popular choice for individuals wanting a simple and effective way to boost their mental performance. Alone, with caffeine, or even with an advanced nootropic stack; L-theanine is worth trying.


Further Reading



N-Acetyl L-Tyrosine (NALT)

N-Acetyl L-Tyrosine (NALT)


Summary: N-Acetyl L-Tyrosine (NALT) is a more bioavailable form of Tyrosine, an amino acid that’s also a nootropic. It improves mood, memory, and enhances cognitive abilities in many ways. It has great effects of reducing stress and maintaining mental performance during sleep deprivation.




Introduction


What is N-Acetyl-L-Tyrosine? (NALT)

Tyrosine is an amino acid the body produces from various dietary sources. Some of its primary functions are maintaining brain chemistry. A result of providing the necessities for the formation of dopamine, norepinephrine, and epinephrine; which are vital neurotransmitters that profoundly affect energy levels, moods motivation, and brain function. It works as the buffer delivering the necessary materials for the brain to produces them. Particularly under conditions where stress has depleted them. Another feature is its protein synthesis and the regulation of hormones required in the creation of melanin; supporting skin, hair, and eyes.
Moreover, Tyrosine is related to the thyroid hormones.

It also supports weight maintenance and loss by suppressing appetite and helping the body’s ability to burn fats. Although the body produces sufficient amounts of L-Tyrosine on its own, studies suggest that additional supplementation provide physical and mental benefits especially under the circumstances of environmental stress.


Benefits & Effects


N-Acetyl L-Tyrosine Enhances Cognition Under Stress

A recent study found that Tyrosine effectively impacts memory and information processing decline under stressors such as extreme weather or extreme cognitive demand. The study hypothesizes that this effect is because tyrosine grants substance from which the brain can produce neurotransmitters. Thereby neutralizing the depletes caused by stress. The report concludes that individuals are facing demanding requirements, whether mountain climbing or meeting job deadline, can benefit from L-Tyrosine. (R), (R)

Improves Memory Under Pressure and Challenges

A study investigating L-Tyrosine’s impact on individuals doing challenging mental tasks shows that those receiving L-Tyrosine perform better at the more difficult levels of the job. The study confirms L-Tyrosine to provide most benefits at higher levels of demand. (R)

Increases Dopamine in the Brain and Boosts Cognitive Flexibility

A study of 22 individuals shows L-Tyrosine supplementation enhances cognitive flexibility as well as the ability to switch between tasks and thoughts. This result is attributed to L-Tyrosine’s capability to increase dopamine in the brain, which further enhances mental versatility.

Increases Focus and Supports ADHD Treatment

A study on ADHD patients shows 77% of participants receiving L-Tyrosine alone showed significant improvement over a period of 10 weeks. Further studies indicate that the simultaneous use of L-Tyrosine especially boosted the effect of ADHD medication such as Ritalin and Adderall. Non-ADHD nootropic users report that tyrosine improves focus. Therefore it is commonly added in nootropic stacks for that purpose. (R)


Mechanism of Action


L-Tyrosine forms in the body from a range of high dietary sources such as meats, fish, seeds, milk, yogurt, and cheese. It develops as a result of the precursor aminoalkanoic acid, known as essential amino acid, metabolizing within the liver. After metabolizing into L-Tyrosine, it further metabolizes by an associate protein known as hydroxylase, which prepares L-Tyrosine to be in use for the creation of different neurotransmitters. Once the protein hydrolyzes it, L-Tyrosine is carried in plasma and may metabolize into catecholamines in various membranes.

The discharge is activated by stimulation of adrenergic neurons within the brain, creating a restrictive interior system that maintains adequate internal secretion levels when the body is experiencing stress. Once there’s a high demand on the body’s stores of the vasoconstrictor, the brain responds with the release of adrenergic transmitters. The release, therefore, increases the quantity of the modifying protein discharged. A lot of L-Tyrosine transforms into catecholamines, thereby preventing deficits. This process is associating evidence in favor of L-Tyrosine supplement.

Once the discharge multiplies over a sustained amount, internal secretion synthesis is assumed to be addicted to concentrations of amino acid. Moreover, supplementation could increase internal secretion synthesis and unleash by making a certain sufficiency of amino acid throughout prolonged periods of stimulation.


Dosage


How To Take N-Acetyl L-Tyrosine?

The standard dose of L-Tyrosine is 500-1000 mg daily, divided into 2 to 3 doses, half-hour before meals. The dose for NALT is lower, with 300 mg being the regular daily dose.


Conclusion


L-Tyrosine is highly effective at improving cognition in situations involving intense stress. A robust body of research indicates that L-Tyrosine prevents cognitive decline in these situations. Furthermore, studies show that it enhances memory, increases cognitive flexibility, and improves mental performance under stress and cognitive demand.

The clinical studies, as well as anecdotal data from the nootropic community, indicate that L-Tyrosine is useful to everyone; not necessarily limited to those experiencing military-grade stress.

Working or studying long hours, struggling with anxiety, and even intense exercise are all stressors that impact cognition. Because L-Tyrosine is available through familiar dietary sources, supplementation is a choice rather than a health necessity. In situations that involve acute environmental stressors, it is a wise choice that will boost cognition. Therefore, tyrosine is worthy of consideration as a day to day supplement.