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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 acid¹.

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.

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 products².

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.

Choline (choline bitartrate, alpha-GPC)

Choline is an essential nutrient used to make cell membranes and the neurotransmitter acetylcholine. EFSA set an adequate intake of 400 mg a day for adults³. Supplements supply it as choline bitartrate, alpha-GPC or citicoline.

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 form⁴.

Beta-alanine

Beta-alanine is an amino acid that combines with histidine in muscle to form carnosine, which helps buffer acid during intense exercise⁵.

Taurine

Taurine is an amino sulfonic acid made by the body and found in meat and fish. It is involved in bile acid formation and cell volume regulation, and it is a common energy-drink ingredient⁶.

Betaine (trimethylglycine)

Betaine (trimethylglycine) occurs naturally in beetroot, spinach and wheat. It acts as an osmolyte and as a methyl donor in homocysteine metabolism.

Vitamin C (ascorbic acid)

Vitamin C is a water-soluble vitamin needed for collagen formation, immune function and iron absorption. EFSA set population reference intakes of 110 mg a day for men and 95 mg a day for women⁷.

Grape seed extract (OPC)

Grape seed extract is rich in oligomeric proanthocyanidins (OPCs), polyphenolic antioxidants.

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 inconsistent¹.

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 report⁸.

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 exercise².

Choline (choline bitartrate, alpha-GPC)

The EU authorises claims that choline contributes to normal lipid metabolism, homocysteine metabolism and liver function for foods that are a source of choline⁹. Claims that choline improves focus or exercise performance are not authorised.

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 performance⁴.

Beta-alanine

The International Society of Sports Nutrition concludes that 4–6 g a day for at least 2–4 weeks raises muscle carnosine and improves performance in exercise lasting about 1–4 minutes⁵.

A meta-analysis found a significant overall ergogenic effect, with the size of the benefit depending on the type and duration of exercise¹⁰.

Taurine

There is no authorised EU health claim for taurine, and evidence that taurine on its own improves exercise performance in healthy people is limited.

Betaine (trimethylglycine)

A meta-analysis found that betaine supplementation for at least 7 days improved muscular strength, especially lower-body strength, and may improve jumping performance¹¹. The EU authorises a claim that betaine contributes to normal homocysteine metabolism at 1.5 g a day⁹.

Vitamin C (ascorbic acid)

Authorised EU claims include that vitamin C contributes to normal collagen formation, normal immune function, the reduction of tiredness and fatigue, and increased iron absorption⁹.

Grape seed extract (OPC)

A meta-analysis of 16 randomised controlled trials examined the effect of grape seed extract on blood pressure¹².

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 established¹.

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.

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 products².

Choline (choline bitartrate, alpha-GPC)

Evidence on cognitive or performance effects in healthy adults is limited.

L-tyrosine

Most studies are small and use single doses in laboratory settings⁴.

Beta-alanine

Effects on strength and on endurance exercise beyond about 25 minutes are not established⁵. A single serving taken before training does not reproduce the daily supplementation used in research.

Taurine

Most of the research uses taurine in combination with caffeine or other ingredients.

Betaine (trimethylglycine)

The studies are small and differ in dose and duration¹¹.

Vitamin C (ascorbic acid)

Intakes above needs are largely excreted; extra benefit from high doses is not established.

Grape seed extract (OPC)

Trials are small and use different extracts and doses¹².

• Do not exceed the recommended daily dose.
• Food supplements should not be used as a substitute for a varied and balanced diet and a healthy lifestyle.
• Keep out of the reach of young children.
• Contains stimulants. Not recommended for children, or for pregnant or breastfeeding women.

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 production¹.

Agmatine sulfate

A case report described 5 years of high daily agmatine intake without detected adverse effects⁸. One case report cannot establish safety for the wider population.

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 infant¹³.

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 intake¹³².

Choline (choline bitartrate, alpha-GPC)

High intakes can cause a fishy body odour, sweating and digestive upset.

L-tyrosine

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

Beta-alanine

The only commonly reported side effect is paraesthesia, a harmless tingling of the skin that is more likely with larger single doses⁵.

Taurine

A risk assessment identified an observed safe level of 3 g a day of supplemental taurine¹⁴, and EFSA did not raise safety concerns for the amounts used in energy drinks⁶.

Betaine (trimethylglycine)

Betaine is generally well tolerated; high intakes may raise blood cholesterol in some people.

Vitamin C (ascorbic acid)

No tolerable upper intake level has been set; high doses can cause digestive upset. People with a history of kidney stones or iron overload should ask a doctor before taking high doses.

Grape seed extract (OPC)

Generally well tolerated; it may add to the effect of blood-thinning medicines.

Sold as a food supplement. No health claims are made for this product.

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 EU⁹.

Agmatine sulfate

Agmatine sulfate is used in some EU food supplements under national rules. No health claim is authorised⁹. Whether a product needs novel food authorisation depends on its history of use¹⁵.

Caffeine

Caffeine is permitted in EU foods and food supplements, subject to labelling rules. It is not on the World Anti-Doping Agency Prohibited List¹⁶.

Choline (choline bitartrate, alpha-GPC)

Choline is a permitted nutrient source in EU food supplements¹⁷⁹.

L-tyrosine

Amino acids such as L-tyrosine are used in EU food supplements under national rules. No health claim is authorised⁹.

Beta-alanine

Beta-alanine is used in EU food supplements under national rules. No health claim is authorised⁹.

Taurine

Taurine is used in EU foods and food supplements. No health claim is authorised⁹.

Betaine (trimethylglycine)

Betaine is used in EU food supplements; the homocysteine claim may be used only in its authorised wording and conditions⁹.

Vitamin C (ascorbic acid)

It is a permitted nutrient in EU food supplements¹⁷; authorised claims may only be used in their approved wording and when the product is at least a source of the nutrient⁹.

Grape seed extract (OPC)

No health claim for this ingredient is authorised in the EU⁹; it is sold under national food-supplement rules¹⁷.