IN DEPTH DESCRIPTION
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 without tyrosine 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.
Vinpocetine is a derivative of apovincamine, an alkaloid compound found in the periwinkle plant.
Studies indicate that vinpocetine can improve cognitive function and memory. A 2014 study on 56 patients with cognitive impairment (epilepsy or dementia) found that taking just 10mg of vinpocetine a day improved patients’ memory and concentration. Other human studies have also found improvement in patients with cognitive impairment[21,14]. Vinpocetine is thought to have this effect by supporting circulation to the brain, enhancing glucose and oxygen utilisation in the brain and exerting a protective effect for the nervous system.
Huperzine A is a natural alkaloid isolated from the plant Huperzia serrata (Chinese club moss), with a long history of use in traditional Chinese medicine.
Like vinpocetine, huperzine A has been extensively studied for its potential to support and improve cognitive function and memory. It is known to inhibit the enzyme acetylcholinesterase, which breaks down acetylcholine, meaning that it can increase levels of acetylcholine in the brain (the neurotransmitter most associated with memory and cognitive function). An early study on rats found that huperzine A could inhibit the action of acetylcholinesterase for three hours, and increased levels of acetylcholine in the brain by 40% after one hour. Huperzine is thought to pass through the blood-brain barrier more easily and have a longer-lasting effect than some acetylcholinesterase-inhibiting drugs that are used for Alzheimer’s. Huperzine is also said to have neuroprotective activity, meaning it helps to protect the nerve cells from injury or degeneration.
Like for vinpocetine and many of the other substances that may support memory, human studies on huperzine have mainly investigated its effects in those already suffering from Alzheimer’s or other forms of dementia or cognitive impairment. In a recent (2014) meta-analysis of 10 randomized controlled trials, the authors concluded that huperzine can significantly improve symptoms for patients with dementia or Alzheimer’s, including in cognitive function and memory. One trial did examine its effects in younger people, however – adolescent students who complained of poor memory. In this double-blind study the researchers gave half (34) of the participants 0.1mg of huperzine twice a day, and the other half a placebo, for four weeks. The group taking the huperzine showed a significant improvement in memory and learning performance. 
Rhodiola rosea is a herb that grows at high altitudes and in colder climates. It has a long history of use in traditional herbal medicine in Europe, Asia and Russia.
Like holy basil, rhodiola has been classed as an adaptogen, as it has been found to increase resistance to a variety of chemical, biological, and physical stressors. (Adaptogens are substances that have a normalising or balancing action in the body including increasing resistance to stress.)
Several human studies have investigated rhodiola’s ability to prevent or reduce stress-induced fatigue, including mental fatigue. One double-blind, placebo-controlled study on 56 physicians tested their levels of mental fatigue including short-term memory and ability to concentrate during night duty, when taking either a rhodiola rosea extract or a placebo. The researchers found a ‘significant improvement’ in those taking the rhodiola versus a placebo, concluding that it ‘can reduce general fatigue under certain stressful conditions’. Another double-blind study on students during exam time found that those taking 100mg of a rhodiola extract showed improvements in hand-eye coordination and mental fatigue, and also general wellbeing. 
Rhodiola may improve exercise performance too. One clinical trial tested the aerobic exercise capacity of 18 men after a 2-week high-altitude training programme when taking either a combination of rhodiola and cordyceps sinensis or a placebo. The researchers found that those taking the rhodiola and cordyceps supplement had a longer exhaustive run time (amongst other measures), concluding that taking the supplement during altitude training ‘provides greater training benefits in improving aerobic performance’.  Another trial published in the Journal of Strength and Conditioning Research tested the effects of rhodiola on endurance exercise performance on 18 subjects. The participants took either rhodiola or a placebo one hour before a 10-minute warm-up followed by a 6-mile cycling time trial. Those taking the rhodiola had significantly decreased heart rate during the warm-up, slightly faster time trial results and a lower ‘rating of perceived exertion’ (perception of effort). The Vikings are said to have used this herb to enhance physical endurance too!
Rhodiola may also support memory and learning. There don’t seem to be any human studies specifically examining this effect, but a study on rats found significant improvements in learning and memory retention – including long-term memory – when the rats were given a 0.1ml extract of rhodiola. 
As part of its activity as an adaptogen, rhodiola may support mood too. One of its traditional uses is in relieving depression. Limited studies have found good results with using rhodiola for mild to moderate depression. A lab study indicated that rhodiola can act as a natural monoamine oxidase inhibitor, meaning it inhibits the breakdown of monoamine neurotransmitters that influence mood such as dopamine, serotonin and noradrenaline, allowing them to be active for longer.
Holy basil – also known as tulsi – is a herb with a long tradition of use in Ayurvedic medicine (Indian herbal medicine). It is one of the most revered herbs within Ayurveda, reflected in the various names it has been given including ‘The Incomparable One’ and ‘The Queen of Herbs’. It is considered a tonic for the body, mind and spirit .
One of the primary uses for holy basil is as an anti-stress or ‘adaptogenic’ herb. Adaptogens are substances that can be said to have a normalising or balancing action in the body (i.e. promoting homeostasis), including increasing resistance to stress. Holy basil has been found to protect against physical stress such as physical exertion and cold exposure, mental stress, and stress to the body from toxins and infections . Notable among the studies on holy basil and stress is a double-blind placebo-controlled human study carried out in 2011. Researchers gave 150 participants either a holy basil capsule or a placebo for six weeks. At the end of the six weeks, self-rated stress symptoms such as forgetfulness, frequent feeling of exhaustion, and frequent sleep problems decreased significantly in the group taking the holy basil compared to the placebo group. The overall improvement in control of stress symptoms was 39% greater in those taking the holy basil. Holy basil has also been found to reduce symptoms of anxiety in both human and animal studies.[37,38]
Holy basil may also be helpful for memory and cognitive function. In one study, holy basil was found to reduce symptoms of experimentally induced dementia in rats. Like huperzine A, it was found to inhibit the enzyme acetylcholinesterase which breaks down acetylcholine (the neurotransmitter most associated with memory and cognitive function). However, there don’t seem to have been any human studies carried out to specifically examine this effect.
Pine bark extract
Pine bark extract is most often included in supplements for its antioxidant and anti-inflammatory activity. It contains many individual active constituents including catechins (like those found in green tea), procyanidins and phenolic acids, all of which can act as antioxidants.
Pine bark extract may support exercise performance and help prevent injury through improving the body’s antioxidant defences. This is because one of the contributing factors to muscle fatigue and damage during exercise is the production of reactive oxygen species (free radicals), which are a natural by-product of energy metabolism in the cells. One clinical trial published in Research in Sports Medicine gave nine trained cyclists either an antioxidant supplement containing pine bark extract or a placebo then tested their time to fatigue in a cycling trial. When taking the pine bark extract, the cyclists rode on average 80 seconds longer than when taking the placebo. Another similar trial published in the journal Nutrients found that both trained and untrained participants had an average of 17% increased time to fatigue when taking the pine bark-based antioxidant extract. The researchers concluded that their results indicated “lower oxidative stress-induced suppression of aerobic respiration” with the pine bark extract – in other words, it reduced the effects of free radicals in suppressing energy production .
Pine bark extract may also improve performance and endurance by increasing nitric oxide levels. Nitric oxide is a signalling molecule in the body has a vasodilatory effect – meaning it dilates the blood vessels, enhancing blood flow so more nutrients and oxygen can reach the muscle tissues. Several studies have examined this vasodilatory effect of pine bark extract [43, 44] but not in relation to exercise performance specifically.
Pine bark has also been reported to reduce cramping in athletes. A human study giving 50mg of pycnogenol (a patented pine bark extract) to athletes and other participants found that the average frequency of cramps in the athletes decreased from 8.6 per week before the trial to just 2.4 per week after 4 weeks of taking the supplement.
Pine bark extract may also support cognitive function and mood. In one study published in the Italian medical journal Panminerva Medica, 53 students undergoing university exams took a pine bark extract for eight weeks, with an equivalent control group who were not taking the supplement. The students taking the pine bark extract were found to have improved sustained attention, memory and mood ratings and had a higher average test score (26.1 versus 23.8 in the control group – an improvement of 7.6%).
Beetroot / Nitrates
The effect of beetroot extracts and juices on exercise performance has been the subject of much research over the last four to five years. Beetroot naturally contains nitrates, which can convert to nitrites in the body and then nitric oxide. Nitric oxide has a vasodilatory action, meaning it dilates the blood vessels, enhancing blood flow.
Some studies examining this effect show small benefits to exercise performance. In a 2015 study published in the European Journal of Applied Physiology, researchers gave either a nitrate-rich beetroot juice or a nitrate-depleted beetroot juice to 16 male team sport players for seven days, then gave them an intermittent sprint test on a cycle ergometer. They found a small but significant increase in ‘total work’ during the sprint test and an improved reaction time to cognitive tasks in the nitrate-rich group compared to the nitrate-depleted group. Another randomised, placebo-controlled study published in 2015 gave seven participants a beetroot juice containing 8.4 mmol of nitrates or a placebo for nine days, then subjected them to a cycling test at 35rpm and 115rpm. Although there was no difference in results for the lower-intensity test (35rpm), when doing the higher-intensity test (115rpm) those taking the beetroot juice showed increased muscle oxyhaemoglobin (indicating muscle oxygenation), faster oxygen uptake from the lungs (Vo2) and greater exercise tolerance than when taking the placebo.
A 2013 review and meta-analysis of 17 earlier human studies investigating nitrates on exercise performance found that overall there was a “significant moderate benefit … of nitrate supplementation on performance for time to exhaustion tests”. They found a “small but insignificant beneficial effect” on performance for time trials and graded exercise tests, but concluded that “this effect may be meaningful in an elite sport context”.
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