The Best Nootropic Ingredients to boost focus, mood, motivation and memory!Lloyd Siewert
In this article we take our own anecdotal experience (we use this stuff a lot) and also pull information from some of our favourite research sites (listed at the end) to give you the top one or two safe natural nootropic ingredients currently available in the categories of: Focus, Mood, Motivation & Memory.
Feel free to watch the associated YouTube video or read on for more detailed info on each of these readily available and cost effective ingredients that could have you firing on all mental cylinders daily!
Cognizin / CDP-Choline & Alpha GPC
How It Works
Sufficient levels of CDP-choline preserve phosphatidylcholine and sphingomyelin, which build the protective nerve sheet called myelin. Citicoline also inhibits the inflammatory enzyme phospholipase A2 and boosts the master antioxidant glutathione [7, 8].
What is Alpha-GPC?
Alpha-GPC (L-alpha-glycerylphosphorylcholine or choline alphoscerate) is a phospholipid essential for brain health. It provides choline for cell membranes and myelin production, and thus nourishes the nervous system [1, 2].
- Beef liver
- Whole grains
In some European countries, alpha-GPC is a prescription drug for Alzheimer’s disease (Gliatilin, Delecit). In the US, it’s sold as a dietary supplement for memory enhancement. Supplement and drug manufacturers usually derive alpha-GPC from egg or soy lecithin [6, 7].
CDP-Choline vs. Alpha-GPC
Let’s start with the basics. CDP-choline or citicoline is made of choline (with two phosphate groups) and cytidine, while alpha-GPC is made of choline (with one phosphate group) and glycerol. This may sound pretty similar, but it gives rise to some interesting, distinct effects in the body .
For one, alpha-GPC raises choline blood levels to a greater extent than CDP-choline. As a result, it has a more powerful impact on age-related cognitive decline and physical performance. Secondly, alpha-GPC may stimulate fat burning and growth hormone production, giving it an edge over CDP-choline among bodybuilders [9, 10, 11, 12, 13].
Alpha-GPC has gained popularity among weightlifters, athletes, and bodybuilders due to its supposed ergogenic properties.
Lower doses of alpha-GCP (200 mg) enhanced vertical jump power by 8.5% in 22 people .
In seven male volunteers, pre-workout supplementation with alpha-GPC (600 mg) caused a staggering 44-times spike in growth hormone (short-term). It delivered a 14% higher bench press force but didn’t impact power or recovery .
Rhodiola is also known as arctic root or golden root, and its scientific name is Rhodiola rosea.
Its root contains more than 140 active ingredients, the two most potent of which are rosavin and salidroside.
People in Russia and Scandinavian countries have used rhodiola to treat anxiety, fatigue and depression for centuries.
It found significant improvements in symptoms of stress, such as fatigue, exhaustion and anxiety, after just three days. These improvements continued throughout the study.
In a similar study, 100 people with chronic fatigue symptoms received 400 mg of rhodiola every day for eight weeks. They experienced significant improvements in stress symptoms, fatigue, quality of life, mood and concentration (6Trusted Source).
These improvements were observed after only one week of treatment and continued to improve through the final week of the study.
In one six-week study on the effectiveness of rhodiola on symptoms of depression, 89 people with mild or moderate depression were randomly assigned to receive either 340 mg or 680 mg of rhodiola or a placebo pill daily (12Trusted Source).
Both rhodiola groups experienced significant improvements in overall depression, insomnia and emotional stability, whereas the placebo group showed no improvements.
Interestingly, only the group receiving the larger dose showed improvements in self-esteem.
Another study compared the effects of rhodiola to the commonly prescribed antidepressant sertraline, which is sold under the name Zoloft. It randomly assigned 57 people diagnosed with depression to receive rhodiola, sertraline or a placebo pill for 12 weeks (13).
While rhodiola and sertraline both reduced symptoms of depression, sertraline had a greater effect. However, rhodiola produced fewer side effects and was better tolerated.
The physicians were randomly assigned to receive either 170 mg of rhodiola or a placebo pill per day for two weeks.
Rhodiola reduced mental fatigue and improved performance on work-related tasks by 20%, compared to the placebo.
Another study looked at the effects of rhodiola in military cadets performing night duties. The cadets consumed either 370 mg or 555 mg of rhodiola, or one of two placebos daily for five days (18Trusted Source).
Both doses were found to improve the cadets’ capacity for mental work, compared to the placebos.
In another study, students experienced significantly reduced mental fatigue, improved sleep patterns and increased motivation to study after taking rhodiola supplements for 20 days. Their exam scores were also 8% higher than those in the placebo group (19Trusted Source).
be sure to look at the labels of these supplements to ensure they contain a standardized amount of 3% rosavins and 1% salidrosides. These are the naturally occurring proportions of these compounds in rhodiola root.
In cell studies, rhodiola extract directly activated four important neurotransmitters: norepinephrine, serotonin, dopamine, and acetylcholine. Low dopamine, in particular, is strongly associated with depression and often overlooked; this plant’s effect on dopamine may explain its mood-lifting effects [22, 23].
In one study, salidroside from Rhodiola significantly decreased inflammatory cytokines and returned neurotransmitter levels to normal in rat brains. These two effects are probably linked; inflammation often contributes to depression [20, 24].
Monoamine oxidase is also the target of some antidepressant drugs like selegiline, phenelzine, and isocarboxazid. This class of drugs may interact dangerously with rhodiola; see the section on drug interactions below [26, 27].
What Is Tryptophan?
Tryptophan is one of many amino acids found in foods that contain protein.
For example, they are necessary to produce several important molecules that help transmit signals.
Overall, tryptophan and the molecules it produces are essential to the optimal functioning of your body.
Motivation or sometimes referred to as “mental drive” is seen to be largely associated with the neurotransmitter Dopamine. Although motivation is no doubt far more complex then serum levels of dopamine in the brain, supporting this neurotransmitter when trying to optimise our mental drive from biohacking standpoint does make some logical sense. One of the best ways to ensure we are at optimum dopamine levels (and some of his close catecholamine pals) is to leverage supplementation of the amino acid Tyrosine.
What is Tyrosine?
Tyrosine is a large non-essential neutral amino acid (LNAA), naturally present in food. Tyrosine is the precursor of the catecholamines, converted to dopamine via L-Dopa and the enzymes tyrosine hydroxylase (TH) and aromatic l-amino acid decarboxylase and to noradrenaline by dopamine β-hydroxylase (Molinoff and Axelrod, 1971). Research in rodents showed that orally administered tyrosine reaches the brain (Glaeser et al., 1983).
Tyrosine helps make several important substances, including (4):
- Dopamine: Dopamine regulates your reward and pleasure centers. This important brain chemical is also important for memory and motor skills (5Trusted Source).
- Adrenaline and noradrenaline: These hormones are responsible for the fight-or-flight response to stressful situations. They prepare the body to “fight” or “flee” from a perceived attack or harm (5Trusted Source).
- Thyroid hormones: Thyroid hormones are produced by the thyroid gland and primarily responsible for regulating metabolism (6Trusted Source).
- Melanin: This pigment gives your skin, hair and eyes their color. Dark-skinned people have more melanin in their skin than light-skinned people (7Trusted Source).
It’s also available as a dietary supplement. You can purchase it alone or blended with other ingredients, such as in a pre-workout supplement.
Supplementing with tyrosine is thought to increase levels of the neurotransmitters dopamine, adrenaline and norepinephrine.
By increasing these neurotransmitters, it may help improve memory and performance in stressful situations (4).
It May Improve Mental Performance in Stressful Situations
Stress is something that everyone experiences.
However, when these rodents were given a tyrosine supplement, the decline in neurotransmitters was reversed and their memory was restored.
While rodent data does not necessarily translate to humans, human studies have found similar results.
In one study in 22 women, tyrosine significantly improved working memory during a mentally demanding task, compared to a placebo. Working memory plays an important role in concentration and following instructions (12Trusted Source).
In a similar study, 22 participants were given either a tyrosine supplement or placebo before completing a test used to measure cognitive flexibility. Compared to the placebo, tyrosine was found to improve cognitive flexibility (13Trusted Source).
Cognitive flexibility is the ability to switch between tasks or thoughts. The quicker a person can switch tasks, the greater their cognitive flexibility.
Additionally, supplementing with tyrosine has been shown to benefit those who are sleep deprived. A single dose of it helped people who lost a night’s sleep stay alert for three hours longer than they otherwise would (14Trusted Source).
Tyrosine and its effect on Dopamine
Tyrosine administration increases dopamine metabolites in CSF, like homovanillic acid (HVA), in rats (Scally et al., 1977) and in patients with Parkinson’s disease (Growdon et al., 1982). In young adults, tyrosine administration improved cognitive control functions such as response inhibition, task switching, and working memory, especially in demanding circumstances (for review, see Deijen, 2005; Jongkees et al., 2015). In the aging brain, tyrosine may similarly improve cognitive functioning.
Stress or demanding circumstances increase neuronal firing and thereby catecholamine metabolism (Bliss et al., 1968), making these neurons more sensitive to precursor availability such as tyrosine (Scally et al., 1977). For this reason, a relatively high dose may be optimal in a high neuronal firing situation, but suboptimal during basal neuronal firing, even in young adults.
Mechanistically, the conversion of tyrosine to L-dopa by the rate-limiting enzyme TH is inhibited by its final end products, i.e., the catecholamines dopamine and noradrenaline, present in the cytoplasm (Daubner et al., 2011). Indeed, a very high dose of phenylalanine, the conditional precursor of tyrosine, reduced dopamine release in the rat striatum, whereas lower doses increased dopamine release (During et al., 1988). The authors speculated that TH inhibition resulted in net reduced dopamine synthesis due to sudden high amounts of cytoplasmic catecholamines.
We speculate that administrating extra precursor to a system with already high dopamine synthesis capacity may result in its inhibition.
So it would seem that if you are stressed, sleep deprived or dopamine depleted then a larger dose of Tyrosine is potentially beneficial (2g -10g), however if you are at a good baseline smaller doses are best (250mg – 500mg). Further research would be needed to solidify this hypothesis but it looks to be a logical approach for the average nootropic enthusiast to take.
What is Huperzine A?
Huperzine A acts as a cholinesterase inhibitor — a type of medication that works by improving the levels of neurotransmitters in the brain. Small early studies suggest that huperzine A might improve memory and protect nerve cells, which could slow the cognitive decline associated with Alzheimer’s.
Mechanism of Action
There are two forms of huperzine A: ‘(+)’ and ‘(-)’. The ‘(-)’ form is found naturally in the huperzia moss, and is believed to be more potent than the ‘(+)’ form.
Although the effects of huperzine A are still being actively studied by scientists, there are a few mechanisms that have been identified so far which may be responsible for some of its reported effects.
Huperzine A has been reported to be a potent, reversible, and specific inhibitor of the enzyme acetylcholine esterase (ACHE). This enzyme breaks down the major neurotransmitter acetylcholine, suggesting that some of huperzine A’s effects may come from generally increased levels of acetylcholine throughout the brain .
For example, according to one animal study, huperzine A was reported to increase acetylcholine levels in rat brains for up to 6 hours after administration .
Several animal studies have reported that huperzine A may result in a more prolonged increase in acetylcholine in the whole brain when compared to other compounds that raise acetylcholine levels, such as tacrine, physostigmine, and metrifonate [5, 6, 7].
Huperzine-A’s most renowned action is that of an acetylcholinesterase inhibitor. Specifically, it can inhibit the G4 isoform of acetylcholinesterase which is highly prevalent in mammalian brains. It is of greater or equal potency to other acetylcholinesterase inhibitors such as Tacrine or Rivastigmine. It has a high affinity for acetylcholinesterase as an inhibitor, and a slow dissociation constant which enables a long active half-life.
It may be preferable for usage as a cholinergic since it has been reported to have less cholinergic-related side-effects, possibly through its high affinity for brain G4 acetylcholine resulting in less availability for systemic butrylcholine inhibition, which leads to various systemic effects which may be seen as side effects.
In addition to acetylcholinesterase inhibition, it can also be seen as neuroprotective against glutamate, beta-amyloid pigmentation, and H2O2-induced toxicity.
Huperzine-A can also block the NMDA receptor ion channel without psychomimetic side-effects.
Huperzine-A is able to promote proliferation of hippocampal neural stem cells (NSCs) at a concentration of 1μM for 48 hours (which is more potent than 10-100μM) to 125% of control secondary to activating the ERK pathway, and this neurogenesis was confimed in vivo with injections of 0.2mg/kg of huperzine-A for 4 weeks (about a 25% increase in BrdU stained cells, affecting both newborn and adult mice).
Could Protect Against Dementia
Additionally, animal studies have found that lion’s mane may help protect against Alzheimer’s disease, a degenerative brain disease that causes progressive memory loss.
In fact, lion’s mane mushroom and its extracts have been shown to reduce symptoms of memory loss in mice, as well as prevent neuronal damage caused by amyloid-beta plaques, which accumulate in the brain during Alzheimer’s disease (5Trusted Source,6Trusted Source, 7Trusted Source, 8Trusted Source).
While no studies have analyzed whether lion’s mane mushroom is beneficial for Alzheimer’s disease in humans, it appears to boost mental functioning.
A study in older adults with mild cognitive impairment found that consuming 3 grams of powdered lion’s mane mushroom daily for four months significantly improved mental functioning, but these benefits disappeared when supplementation stopped (9Trusted Source).
Depression and Anxiety
While there are many causes of anxiety and depression, chronic inflammation could be a major contributing factor.
May Speed Recovery from Nervous System Injuries
The nervous system consists of the brain, spinal cord and other nerves that travel throughout the body. These components work together to send and transmit signals that control almost every bodily function.
Injuries to the brain or spinal cord can be devastating. They often cause paralysis or loss of mental functions and can take a long time to heal.
However, research has found that lion’s mane mushroom extract may help speed recovery from these types of injuries by stimulating the growth and repair of nerve cells (16Trusted Source, 17Trusted Source, 18Trusted Source).
Lion’s mane extract may also help reduce the severity of brain damage after a stroke.
In one study, high doses of lion’s mane mushroom extract given to rats immediately after a stroke helped decrease inflammation and reduce the size of stroke-related brain injury by 44% (20Trusted Source).