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Lion’s Mane is an ancient Chinese medicinal mushroom that’s developing a strong following in the world of modern smart drugs. Its ability to enhance overall cognitive function, proven neuroprotective qualities, and linked to the production of NGF, or Nerve Growth Factor, is making Lion’s Mane one of the most promising and popular natural nootropics.
Used for centuries as a general tonic and health treatment, the Lion’s Mane Mushroom (also known as Hericium Erinaceus, Yamabushitake or Satyr’s Beard) is native to China, Japan, North America and Europe. Though it was traditionally prescribed as a general restorative, its effect on the brain has always been recognized, and ancient physicians used it to treat what we would now describe as neurodegenerative diseases.
In recent years the considerable nootropic capabilities of Lion’s Mane have come to the fore, sparked in large part by the discovery of its connection to NGF, a protein that is crucial for the survival and function of nerve cells. Lion’s Mane increases the amount of NGF in the brain, which enhances cognition by reducing inflammation, encouraging neural growth, and improving overall brain health.
But while cognitive enhancement is among the most significant benefits of Lion’s Mane, it’s far from the only one; studies suggest that Lion’s Mane is a powerful neuroprotectant that could be useful in the treatment of a startling variety of conditions ranging from cardiovascular health to obesity and even some types of cancer.
Lion’s Mane is a unique nootropic; just about everything about it, from effects to timeframe to methods of action are quite different from modern nootropics like the racetams. But ongoing research continues to confirm its potency and potential as a brain and cognition enhancer, and many are finding Lion’s Mane to be a valuable addition to their supplementation regimen.
For memory formation and learning, one of the most important brain chemicals is called acetylcholine. This neurotransmitter is derived from a precursor called choline and alpha GPC is among the top sources of this essential nutrient. Unless you’re willing to eat liver and other organs, an alpha GPC supplement might be useful for your brain.
The primary benefit and purpose of alpha GPC is as a prodrug for choline, which it is considered one of the (if not the) most efficient supplement for this purpose . By providing your brain with more raw choline, it can convert that into acetylcholine and this contributes to a host of downstream effects.
Namely, alpha GPC contributes to improved memory formation and learning. Acetylcholine is utilized by the hippocampus to create memories. It is also a powerful tool against cognitive decline and symptoms of Alzheimer’s disease .
Luckily, alpha GPC side effects are few, rare, and mostly positive. Studies suggest one side effect of alpha GPC is increased power output , which shows the supplement can improve physical strength and vitality as well as mental characteristics.
L-theanine is an amino acid extracted from green or black tea. A cup of black tea contains approximately 20 mg theanine. In the brain L-theanine increases dopamine, 98,99 serotonin, 98 and the inhibitory neurotransmitter glycine. 99
Green tea is often used as a relaxing beverage. Although it can contain more caffeine than coffee, theanine appears to counteract its stimulant effect to some degree. In rats, theanine administered intravenously after caffeine dosing, and at approximately the same dose, blunted the stimulant effect of caffeine seen on electroencephalographic recordings. When given by itself in a smaller dose (20-40% of the original dose), theanine administration resulted in excitatory effects, suggesting a dual activity of theanine depending on the dose. 100
Studies show L-theanine induces alpha-brain wave activity, which correlates with a perceived state of relaxation. A small Japanese study of university students showed oral L-theanine administration of 200 mg led to increased alpha-brain waves and a subjective sense of relaxation. Theanine administration caused a dose-dependent relaxed, yet alert, state of mind without sedation, beginning approximately 40 minutes after oral dosing. 101 A study determined more recently that even lower doses of L-theanine can induce alpha-wave production. Electroencephalogram (EEG) tracings were obtained from 54 healthy participants at baseline and 45, 60, 75, 90, and 105 minutes after 50 mg L-theanine (n=16) or placebo (n=19). The theanine group demonstrated a statistically significantly greater increase in alpha-wave production (p<0.05) than the placebo group; both groups sat quietly with eyes closed during the EEG evaluations. 102
The acute stress response elicited by a math test was attenuated by 200 mg theanine – assessed by heart rate and salivary sIgA. 103
(Kathleen A. Head, ND, and Gregory S. Kelly, ND)
The herb withania somnifera, also known as ashwagandha is used with extensive application in traditional Indian and Ayurvedic medicine. The active constituents include withanolides which are steroidal and resemble, in action and appearance, ginsenosides, the active constituents of panax ginseng[i]. Like, Siberian ginseng, ashwagandha is considered to be an adaptogenic herb[ii].
A 2000 review of therapeutic uses of ashwagandha discusses beneficial endocrine, cardiopulmonary and central nervous system effects via various properties for this herb: anti-inflammatory, blood-cell building, anti-tumor, rejuvenating, antioxidant, immune-modulating and anti-stress[iii]. One of the animal studies reviewed found reduction in stress-induced increase of plasma corticosterone and other markers[iv].
A swimming endurance study in mice showed ashwagandha prevented the increased adrenal weight and decreased ascorbic acid and cortisol content of adrenal glands induced by stress[v]. And ashwagandha, like panax ginsengshows significant anti-stress and anabolic activity[vi]. Other animal studies have shown antidepressant and anxiety-reducing effect of ashwagandha similar in effect to standard pharmaceutical drugs[vii].
A 2012 placebo-controlled study of 40 elite Indian cyclists showed improved cardiorespiratory endurance with use of Ashwagandha for 8 weeks[viii]. All parameters tested were improved including VO2max and time for exhaustion. The placebo group showed no change with respect to baseline parameters. A 2015 randomized, double-blind, placebo controlled study of 50 healthy athletic adults (performing a shuttle run test ) also found improvements in cardiorespiratory endurance and quality of life[ix].
A 2014 double-blind, multi-dose, placebo-controlled, crossover study of 20 healthy male participants found improved cognitive and psychomotor performance with ashwagandha[x].
Choline is commonly considered to be a B vitamin, but it can be manufactured in the body (vitamins, by definition, cannot). Choline has multiple roles in the body – not least, it is present in all our cell membranes (as phosphatidyl choline), where it is necessary for cell structure and cell signalling (transmission of messages into and out of the cells).
Choline one of the many nutrients needed for healthy brain function and memory. One reason is that it’s a precursor to acetylcholine, a neurotransmitter that has many functions in the nervous system but is most associated with memory and cognitive function. In animal studies, choline has been found to improve learning and memory, and support the release of acetylcholine in the brain. Supplementing with choline has been found to improve memory in people who are deficient in choline at baseline (i.e. at the start of the study) and improve memory and attention in dementia sufferers. There are also lots of studies on the necessity of choline for brain development in the foetus and infant. However, there doesn’t seem to be much research available on the effects of supplemental choline on memory or cognitive function in healthy adults who are not deficient.
Choline is needed for normal muscle function too. It’s been found that a deficiency of choline in the diet can result in muscle damage, by reducing levels of phosphatidyl choline in muscle cell membranes, making them more fragile. Choline may also help to prevent muscle fatigue through acting as a precursor to acetylcholine, which – in addition to its role in memory and cognition – is also required for muscle contraction.
Choline helps to maintain normal levels of a substance called homocysteine. High homocysteine is a risk factor for cardiovascular disease and Alzheimer’s disease, amongst others – so having a healthy intake of choline could help protect against these conditions too.
The amino acid tyrosine is best-known for its role in the production of the thyroid hormones thyroxine (T4) and triiodothyronine (T3), which are made from tyrosine and the mineral iodine. Thyroid hormones govern metabolism, including the production of energy from the food that we eat. As well as directly affecting energy levels, thyroid hormones have an influence on body weight, muscle strength, mood, cognitive function and memory, and heart rate – amongst others.
Tyrosine is also a precursor to adrenaline and noradrenaline – these are hormones involved in the ‘fight or flight’ stress response, and help the body to cope with stress. They also have a role in mood, energy, motivation and drive, and concentration and focus. Because these stress hormones are made from tyrosine, excessive or acute stress can lead to depletion of tyrosine in the brain, which can then have an impact on ability to cope with further stress, as well as a negative effect in all these other areas.
Several studies have found that tyrosine supplements may help to prevent some of the negative effects of stress on the body and mind, including on cognitive performance (reasoning, memory, etc.) and mood. A study carried out at the US Army Research Institute of Environmental Medicine found that people given 100mg/kg tyrosine supplements coped better with exposure to cold and low oxygen levels, including reducing negative effects on mood and performance. Another study carried out on healthy young men who were sleep deprived showed that tyrosine supplements significantly improved cognitive and physical performance when compared to placebo.
In addition to thyroid hormones and adrenaline, tyrosine is also a precursor to another brain chemical: dopamine. Dopamine has important roles in motor control (movement), reward, motivation and pleasure. This includes the feeling of reward that motivates you to continue an activity or behaviour – for example when you’ve had a good session at the gym! Lack of dopamine – including due to a lack of tyrosine – is linked with depression. A study at Cambridge University found that healthy volunteers given a protein drink withouttyrosine or phenylalanine (the precursor to tyrosine) showed more symptoms consistent with depression – including becoming less content and more apathetic – compared to those given a drink containing a balanced amino acid mixture.[6,9]
Acetyl-L-carnitine is one of the forms of carnitine, an amino acid. Carnitines play a vital role in energy production in the body’s cells – specifically, they transport fats (long-chain fatty acids) into the mitochondria of the cells where they are burned for energy. In people who use a lot of energy – athletes for example – carnitine is thought to increase energy production in the muscle cells and improve uptake of oxygen, as well as stimulate the removal of lactic acid to help prevent fatigue.[10,11]
Because of its role in energy production and fat burning, carnitine is a popular supplement for supporting exercise performance. A particularly interesting study investigating this effect was carried out in 2011 at the University of Nottingham on 14 healthy male volunteers. The researchers found that the participants who took 2g of carnitine together with 80g of carbohydrates twice a day for 24 weeks showed an increase in muscle carnitine of 21% (meaning the carnitine they took reached the muscles), 11% greater work output (improved performance), and used 55% less muscle glycogen compared to the control group.
Acetyl-L-carnitine (ALC) is thought to be the most important carnitine ester (form) in terms of its function and quantity present in the body. It’s also said to be better absorbed than L-carnitine, and to cross the blood-brain-barrier more easily .
ALC may be especially helpful for memory, because it also provides acetyl groups for the production of the neurotransmitter acetylcholine. As we saw when looking at choline, acetylcholine has many functions in the nervous system but is most associated with memory and cognitive function. ALC has been extensively studied for its benefits in dementia and Alzheimer’s disease, with some research finding improvements in memory and attention [15,16] and slower decline in cognitive function and disease progression [17,18]. However, there seems to be little in the way of research on its effects on memory in healthy, younger adults.
Dimethylaminoethanol or DMAE is a precursor to choline. Choline, in turn, is a precursor to acetylcholine, the neurotransmitter that is most associated with memory and cognitive function. Choline itself has been found to improve learning and memory and support the release of acetylcholine in the brain.
DMAE has been investigated for its ability to improve exercise performance. A double-blind trial on 50 healthy male sports teachers found that those taking a combination of DMAE, vitamins, minerals and ginseng performed better in a treadmill exercise test than those taking a placebo, with indications that the supplement improved oxygen utilization in the muscles. However, as several ingredients were used in the supplement, it’s not clear whether all the ingredients contributed to this effect.
Bacopa monnieri, also known as brahmi, is another herb that has been used for centuries in Indian Ayurvedic medicine, including for enhancing memory and learning, and general brain function [50, 51].
Several studies have investigated the potential nootropic (cognitive-enhancing) activity of bacopa. In an Australian study, researchers gave either 300mg of bacopa or a placebo to 81 adults over 55. At the end of the 12-week treatment, those who had taken the bacopa showed improved learning and increased ability to acquire and retain memories . Another similar Australian study on 62 healthy participants found that those taking 300mg of a bacopa extract for 90 days showed improved working memory and better information processing after 12 weeks . It may work in several ways to support cognitive function, including protecting the brain via its antioxidant activity, reducing the breakdown of acetylcholine (the neurotransmitter most associated with memory and cognitive function) and increasing blood flow to the brain. 
Bacopa has also been found to have ‘adaptogenic’ properties , reducing the effects of stress and supporting energy. (Adaptogens are substances that have a normalising or balancing action in the body including increasing resistance to stress.)
Vitamin B12is a water-soluble vitamin with many known roles and many uses as a supplement. Among these, vitamin B12is thought to have a role in regulating the circadian rhythm and sleep-wake cycles. Supplemental vitamin B12has been investigated for helping those with sleep-wake rhythm disorders, with good results in some studies [81,82]. B12is thought to have a direct effect on melatonin levels.[83,84]
Vitamin B12may also have an indirect role in the production of serotonin. Vitamins B12and folate are required for a process called methylation (the donation of methyl groups), which is needed for production of serotonin as well as many other neurotransmitters. Deficiency in B12or folate (and high homocysteine levels, related to poor methylation) are associated with mood disorders such as depression.[86,87]
Vitamin B6(pyridoxine / pyridoxal-5-phosphate)
A primary role of vitamin B6is in production of the neurotransmitter serotonin: it is a co-factor in the pathway for synthesis of serotonin from tryptophan. Because of this role, low levels of vitamin B6in the blood can be linked to depression (often a symptom of low serotonin). Giving vitamin B6supplements was found in an early study to increase serotonin levels in the blood in hyperactive children; and a later observational study – also on children – found that higher intake of vitamin B6and tryptophan at breakfast promoted the synthesis of serotonin when the children were exposed to sunlight for at least 10 minutes.
Vitamin B6can also be said to have a role in sleep, through its part in serotonin production. Serotonin is of course converted to melatonin, the hormone that regulates the circadian rhythm and sleep cycles. However, there don’t seem to be any clinical trials directly examining the effects of vitamin B6supplements on sleep.
There is also some evidence that vitamin B6may have antioxidant effects. A lab study on different forms of B6including pyridoxine and pyridoxal-5-phosphate found that they could reduce the formation of free radicals and damage to cell membrane lipids (fats).
Folic acid (folate)
Like vitamin B12, folate may have an indirect role in the production of serotonin. Vitamins B12and folate are required for a process called methylation (the donation of methyl groups), which is needed for production of serotonin as well as many other neurotransmitters. Deficiency in B12 or folate (and high homocysteine levels, related to poor methylation) are associated with mood disorders such as depression.[86,87]
Folate may have antioxidant activity. Folate deficiency is associated with oxidative stress, perhaps due a build-up of homocysteine as a result of poor methylation. And several human studies have found that folate supplementation can reduce markers of oxidative stress in the body – although often using high doses.[94,95]
Niacin and niacinamide (also known as nicotinamide) are two forms of vitamin B3 that are used in the body – and can be consumed in food or supplements.
Like the other B vitamins, B3has an important role in metabolism. It is the precursor to nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP), coenzymes that are required for over 400 enzymatic reactions in the body, including those involved in energy production.
Vitamin B3is thought to have antioxidant activity. Several studies have examined this link, including a trial that found reduced DNA damage to lymphocytes (white blood cells) after 8 weeks of supplementation with 100mg of B3(as niacin).; and a study on 127 older adults that found a link between higher dietary niacin intake and reduced oxidative stress.
There is some suggestion that vitamin B3could also encourage growth hormone production. A laboratory study using rat pituitary cells found that vitamin B3 (as niacinamide) and its derivatives increased the synthesis of growth hormone in the cells, including in response to triiodothyronine (T3 – a thyroid hormone). While there seem to be few human studies on this, one double-blind trial on 42 adults tested a combination of glycine, glutamine and niacin for its effects on memory, growth hormone secretion and insulin-like growth factor-I (IGF-1), finding that those taking the supplement showed a 70% increase in serum growth hormone levels.
Ensuring the body has adequate levels of vitamin B3may also support serotonin synthesis. This is because in situations of vitamin B3deficiency, B3can be manufactured in the body from tryptophan, the precursor to serotonin. Hence, more of the tryptophan is being used for manufacture of B3 instead of being converted to serotonin. However, again there seems to be little in the way of studies directly examining intake of vitamin B3in diet or supplements and its effect on serotonin levels.
Evidence indicates adrenal cortex function is compromised in the event of a deficiency of vitamin B 5 derivatives and metabolites. On the other hand, administration of pantethine (active vitamin B 5 ) in several experimental animal models appeared to enhance adrenal cortex function. 211-213 Administration of pantethine to humans with a variety of clinical conditions buffered the rise in urinary cortisol metabolites expected to occur secondary to a loading dose of ACTH, 214 suggesting pantethine can down-regulate hypersecretion of cortisol secondary to high stress conditions.
Men receiving 10 g pantothenic acid daily for six weeks had a less pronounced drop in white blood cell counts and vitamin C levels subsequent to cold-water immersion stress, compared to pre-supplementation values. 215
(Kathleen A. Head, ND, and Gregory S. Kelly, ND)
Summary (taken from http://lpi.oregonstate.edu/mic/vitamins/pantothenic-acid)
- Pantothenic acid — also known as vitamin B5— is a water-soluble vitamin that is a precursor in the synthesis of coenzyme A. Coenzyme A is essential to many biochemical reactions that sustain life. Also, the phosphopantetheinyl moiety of coenzyme A is required for the biological activity of several proteins, including the acyl-carrier protein involved in fatty acid (More information)
- Pantothenic acid is essential to all forms of life. It is ubiquitously found in foods of plant and animal origin, and dietary deficiency is very rare.(More information)
- The Food and Nutrition Board of the US Institute of Medicine set an adequate intake (AI) of 5 milligrams (mg)/day for adults based on the estimated daily average intake of pantothenic acid.(More information)
- Evidence from limitedintervention studies suggests that pantothenic acid and/or pantothenol (alcohol analog) might improve the healing process of skin wounds. Yet, additional larger studies are warranted. (More information)
- Treatment with high-dose pantethine — a pantothenic acid derivative — has been shown to lowerserum cholesterol and lipid Although pantethine therapy appears to be well tolerated, medical supervision is indispensable. (More information)
- Foods rich in pantothenic acid include animal organs (liver and kidney), fish, shellfish, milk products, eggs, avocados,legumes, mushrooms, and sweet potatoes. (More information)
- Little or no toxicity has been associated with dietary andsupplementalpantothenic acid such that no tolerable upper intake level (UL) has been set. (More information)
Pantothenic acid, also known as vitamin B5, is essential to all forms of life (1). Pantothenic acid is found throughout all branches of life in the form of coenzyme A, a vital coenzyme in numerous chemical reactions (2).
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