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L-tyrosine

L-tyrosine is an amino acid that the body uses to make the neurotransmitters dopamine and noradrenaline. It is found in protein-rich foods; N-acetyl-L-tyrosine is a related form¹.

L-citrulline and citrulline malate

L-citrulline is an amino acid that the body converts to arginine, a precursor of nitric oxide, which widens blood vessels. Citrulline malate combines citrulline with malic acid².

Agmatine sulfate

Agmatine is formed in the body from the amino acid arginine and acts as a signalling molecule in the nervous system. It is sold as agmatine sulfate in sports and nootropic products.

L-arginine and AAKG

L-arginine is an amino acid used by the body to make nitric oxide. AAKG is arginine bound to alpha-ketoglutarate.

Yohimbine (yohimbe bark, rauwolscine)

Yohimbine is an alkaloid from the bark of the African tree Pausinystalia yohimbe. It blocks α2-adrenergic receptors, which increases noradrenaline release. Rauwolscine (alpha-yohimbine) is a closely related alkaloid.

Synephrine (bitter orange, Citrus aurantium)

p-Synephrine is the main protoalkaloid of bitter orange (Citrus aurantium). It is structurally related to adrenaline and is used in weight-loss and pre-workout products³.

Huperzine A

Huperzine A is an alkaloid from the club moss Huperzia serrata. It inhibits acetylcholinesterase, the enzyme that breaks down the neurotransmitter acetylcholine, and it has been used as a medicine for dementia in China⁴.

Magnesium

Magnesium is an essential mineral involved in hundreds of enzyme reactions, including energy metabolism, muscle contraction and nerve function⁵.

EFSA set adequate intakes of 350 mg a day for men and 300 mg a day for women, from all sources⁶. Supplements supply magnesium bound to different partners, such as oxide, citrate or glycinate. Labels should state the amount of elemental magnesium, which is lower than the weight of the compound.

Vitamin D3 (cholecalciferol)

Vitamin D is made in the skin in sunlight and is found in a few foods. It is needed for calcium absorption and bone health. EFSA set an adequate intake of 15 µg (600 IU) a day for adults⁷. 1 µg equals 40 IU.

Calcium

Calcium is the main mineral of bones and teeth and is needed for muscle and nerve function. EFSA based its adult reference values on calcium balance studies⁸.

Caffeine

Caffeine is a stimulant that blocks adenosine receptors in the brain, reducing perceived effort and fatigue. It is found in coffee, tea and energy drinks and is a common ingredient in pre-workout products⁹.

Dicaffeine malate (sold as Infinergy®) is caffeine bonded to malic acid. Its caffeine adds to the total caffeine in a product, but labels do not always state the caffeine equivalent.

L-tyrosine

A review found that tyrosine may support cognitive performance in short-term stressful or cognitively demanding situations, when these neurotransmitters are temporarily depleted, but found no consistent effect on physical exercise performance¹.

L-citrulline and citrulline malate

A review of human studies found that citrulline supplementation raises plasma arginine, and that several studies report improved exercise performance or recovery, but the results are inconsistent².

Agmatine sulfate

Controlled human research on agmatine for exercise performance is very limited. Published human data are mostly small studies and a long-term case report¹⁰.

L-arginine and AAKG

A dose-response meta-analysis of randomised trials found that L-arginine lowered blood pressure in adults¹¹. Evidence for improved exercise performance or "pump" is inconsistent; oral arginine is extensively broken down before reaching the circulation, which is why citrulline is often preferred².

Yohimbine (yohimbe bark, rauwolscine)

A small trial in professional soccer players found reduced body fat with yohimbine but no change in body mass, muscle mass or performance¹². Larger, independent trials are lacking.

Synephrine (bitter orange, Citrus aurantium)

A review of human clinical studies reported small increases in energy expenditure and modest weight loss with bitter orange extract or p-synephrine products over 6–12 weeks, many in combination with other ingredients³.

Huperzine A

A Cochrane review found some benefit on cognitive function in people with Alzheimer's disease, but only one study was of adequate quality and size, so there was inadequate evidence to recommend its use⁴. A Cochrane review in mild cognitive impairment found the evidence insufficient¹³.

There is no good evidence that huperzine A improves focus or performance in healthy people.

Magnesium

Authorised EU claims include that magnesium contributes to a reduction of tiredness and fatigue, to normal muscle function and to normal functioning of the nervous system, for foods that are a source of magnesium¹⁴.

For exercise performance, a review found that supplementation may help people with low magnesium status or older adults, but found no clear benefit in people who already have enough magnesium¹⁵.

Vitamin D3 (cholecalciferol)

Authorised EU claims include that vitamin D contributes to the maintenance of normal bones, muscle function and immune function¹⁴.

In the large VITAL trial, 2000 IU (50 µg) a day of vitamin D3 did not lower the incidence of invasive cancer or major cardiovascular events compared with placebo¹⁶. A meta-analysis found that vitamin D supplements did not prevent fractures or falls, or have clinically meaningful effects on bone density¹⁷.

Calcium

Authorised EU claims include that calcium is needed for the maintenance of normal bones and teeth and contributes to normal muscle function¹⁴.

Caffeine

The International Society of Sports Nutrition concludes that caffeine consistently improves exercise performance when consumed in doses of about 3–6 mg per kg of body mass, with benefits for muscular endurance, movement velocity, strength, sprinting, jumping and aerobic exercise⁹.

L-tyrosine

Most studies are small and use single doses in laboratory settings¹.

L-citrulline and citrulline malate

Studies differ in dose, form (citrulline or citrulline malate, often with an unverified ratio) and exercise test, and many are small. The mechanism behind any performance effect is not established².

Agmatine sulfate

There are no large randomised trials showing a performance benefit from agmatine in healthy people. Claims of better "pump" or focus are not established.

L-arginine and AAKG

Studies vary in dose and population¹¹.

Yohimbine (yohimbe bark, rauwolscine)

Evidence for fat loss or performance is limited to small studies. Supplement labels are often inaccurate: of 49 US yohimbine supplements tested, only 2 gave accurate information on both the quantity and the known adverse effects¹⁸.

Synephrine (bitter orange, Citrus aurantium)

Most studies are small, short and use multi-ingredient products, and longer studies are needed to establish efficacy and safety³.

Huperzine A

The trials are mostly small, of limited quality and in people with cognitive disease, so they do not apply to healthy users⁴¹³.

Magnesium

Many studies on magnesium and health are observational or involve people with low magnesium status, so their findings do not show that extra magnesium helps people who are not deficient¹⁵⁵.

Vitamin D3 (cholecalciferol)

Benefits are clearest for correcting deficiency. Trials in people with adequate vitamin D status show little benefit for bone, cancer or heart outcomes¹⁶¹⁷.

Calcium

Benefits beyond adequate intake are not established.

Caffeine

Responses vary widely between people, partly because of genetics and habitual caffeine use. Many studies use pure caffeine, so results do not automatically apply to multi-ingredient products⁹.

• Not recommended for beginners or caffeine-sensitive users.

L-tyrosine

People taking MAO inhibitors or thyroid medication should not use tyrosine supplements without medical advice.

L-citrulline and citrulline malate

Citrulline is generally well tolerated in the doses studied. Digestive discomfort has been reported, and people taking blood-pressure or erectile-dysfunction medication should ask a doctor, because citrulline raises arginine and nitric oxide production².

Agmatine sulfate

A case report described 5 years of high daily agmatine intake without detected adverse effects¹⁰. One case report cannot establish safety for the wider population.

L-arginine and AAKG

A risk assessment identified an observed safe level of 20 g a day¹⁹. Because it lowers blood pressure, people taking blood-pressure or erectile-dysfunction medication should ask a doctor first¹¹.

Yohimbine (yohimbe bark, rauwolscine)

A review of poison-centre cases found that adverse events with yohimbine products had more serious outcomes than average exposures, including rapid heart rate, anxiety, high blood pressure and agitation²⁰. People with heart conditions, high blood pressure, anxiety disorders or taking antidepressants should not use yohimbine.

Synephrine (bitter orange, Citrus aurantium)

The reviewed studies did not report serious adverse effects at the doses tested³, but combining synephrine with caffeine and other stimulants increases cardiovascular stress. People with high blood pressure, heart-rhythm disorders or taking stimulant or antidepressant medication should avoid it.

Huperzine A

As an acetylcholinesterase inhibitor, huperzine A can cause nausea, diarrhoea, sweating and a slow heart rate, and it may interact with medicines that affect acetylcholine or heart rate. Anyone taking medication or with heart, lung or digestive conditions should ask a doctor first.

Magnesium

The EU Scientific Committee on Food set a tolerable upper intake level of 250 mg a day for magnesium from supplements and fortified foods (readily dissociable salts and compounds such as magnesium oxide), based on mild, reversible diarrhoea as the most sensitive effect. Magnesium in normal food is not included²¹.

People with impaired kidney function can accumulate magnesium and should only supplement under medical advice. Magnesium can reduce the absorption of some antibiotics and osteoporosis medicines, so separate them by several hours or ask a pharmacist⁵.

Vitamin D3 (cholecalciferol)

EFSA set a tolerable upper intake level of 100 µg (4000 IU) a day for adults, based on persistent hypercalciuria (excess calcium in the urine) as an early sign of excess vitamin D²². Long-term intakes above this level can raise blood calcium and harm the kidneys. High-dose products should only be used on medical advice.

Calcium

The EU Scientific Committee on Food set an upper level of 2500 mg a day from all sources²¹.

Caffeine

EFSA concluded that single doses of up to 200 mg, and daily intakes of up to 400 mg from all sources, do not raise safety concerns for healthy adults. For pregnant and breastfeeding women, daily intakes up to 200 mg do not raise concerns for the foetus or infant²³.

Higher intakes can cause anxiety, sleep disturbance, raised heart rate and blood pressure, and digestive upset. Combining several caffeine sources (coffee, energy drinks, pre-workouts) raises total intake²³⁹.

Contains yohimbine. Isolated yohimbine is classified as a medicinal substance in several EU member states; its legal status depends on the country of sale.

L-tyrosine

Amino acids such as L-tyrosine are used in EU food supplements under national rules. No health claim is authorised¹⁴.

L-citrulline and citrulline malate

L-citrulline is used in EU food supplements under national rules. No health claim for citrulline is authorised in the EU¹⁴.

Agmatine sulfate

Agmatine sulfate is used in some EU food supplements under national rules. No health claim is authorised¹⁴. Whether a product needs novel food authorisation depends on its history of use²⁴.

L-arginine and AAKG

No health claim for this ingredient is authorised in the EU¹⁴; botanical ingredients are sold under national food-supplement rules²⁵.

Yohimbine (yohimbe bark, rauwolscine)

Yohimbine is a pharmacologically active substance. Its use in food is regulated under Regulation (EC) No 1925/2006 and national rules²⁶, and several EU Member States treat it as a medicinal substance²⁷.

Synephrine (bitter orange, Citrus aurantium)

Bitter orange extracts are used in EU food supplements under national rules, which differ between Member States²⁵.

Huperzine A

Huperzine A is a pharmacologically active substance. Its status as a food ingredient is not harmonised in the EU, and some Member States treat it as a medicinal substance²⁷²⁴.

Magnesium

Magnesium is a permitted mineral in EU food supplements²⁵. Authorised claims may only be used in their approved wording¹⁴.

Vitamin D3 (cholecalciferol)

It is a permitted nutrient in EU food supplements²⁵; authorised claims may only be used in their approved wording and when the product is at least a source of the nutrient¹⁴.

Calcium

It is a permitted nutrient in EU food supplements²⁵; authorised claims may only be used in their approved wording¹⁴.

Caffeine

Caffeine is permitted in EU foods and food supplements, subject to labelling rules. It is not on the World Anti-Doping Agency Prohibited List²⁸.