Submission Science ECA KO 60 caps

Ephedra and ephedrine

Ephedra (Ephedra sinica, ma huang) contains ephedrine alkaloids, which stimulate the sympathetic nervous system. Ephedrine is also a licensed medicine in some indications¹.

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.

White willow bark (salicin)

White willow bark contains salicin, a natural precursor of salicylic acid, chemically related to aspirin. Some stimulant products also contain aspirin itself.

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.

Higenamine

Higenamine is a plant alkaloid that stimulates β2-adrenergic receptors, the same receptor family targeted by asthma bronchodilators. It is found in plants such as Nandina domestica⁴.

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.

Piperine (black pepper extract, BioPerine®)

Piperine is the pungent alkaloid of black pepper, added to supplements as a "bioavailability enhancer".

Ephedra and ephedrine

A meta-analysis of clinical trials found that ephedra or ephedrine produced modest short-term weight loss of about 0.9 kg a month more than placebo, with no data on long-term weight loss and insufficient evidence for athletic performance¹.

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.

White willow bark (salicin)

A review found evidence of pain-relieving effects of willow bark extracts, with fewer adverse effects than non-steroidal anti-inflammatory drugs including aspirin⁵.

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.

Higenamine

There are no controlled human trials showing that higenamine improves exercise performance or weight loss. Analyses of US supplements found up to about 62 mg per serving, with labels that often did not state the amount⁴.

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 performance⁶. Larger, independent trials are lacking.

Piperine (black pepper extract, BioPerine®)

A 2026 review of 22 human pharmacokinetic studies found that reports of enhanced nutrient absorption come mainly from manufacturer-affiliated studies, and that independent trials did not confirm enhancement for curcumin or resveratrol at supplement doses⁷.

Ephedra and ephedrine

The trials were short and did not assess long-term outcomes¹.

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.

White willow bark (salicin)

Trials are few and use different extracts⁵.

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.

Higenamine

Published research concerns supplement analysis rather than effects in humans⁴.

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 effects⁸.

Piperine (black pepper extract, BioPerine®)

Piperine raises blood levels of other compounds mainly by inhibiting drug-metabolising enzymes (CYP3A4, CYP2C9) and P-glycoprotein, not by improving absorption⁷.

Ephedra and ephedrine

Use of ephedra or ephedrine with caffeine was associated with an increased risk of psychiatric, autonomic and gastrointestinal symptoms and heart palpitations¹.

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 infant⁹.

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 intake⁹².

White willow bark (salicin)

People sensitive to salicylates or aspirin, with stomach ulcers or bleeding disorders, or taking blood thinners should avoid it⁵. Aspirin is a medicine and is not suitable in pregnancy or for children.

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.

Higenamine

As a β2-agonist, higenamine may raise heart rate and cause palpitations, and its safety at supplement doses has not been established⁴.

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 agitation¹⁰. People with heart conditions, high blood pressure, anxiety disorders or taking antidepressants should not use yohimbine.

Piperine (black pepper extract, BioPerine®)

Because it inhibits drug-metabolising enzymes, piperine can raise blood levels of prescription medicines, including drugs with a narrow therapeutic index. People taking medication should ask a pharmacist first⁷.

Contains an ingredient listed as "Eph" (ephedra/ephedrine). Ephedra species and their preparations are prohibited in foods, including food supplements, in the EU (Regulation (EC) No 1925/2006, Annex III, Part A). Contains yohimbine. Isolated yohimbine is classified as a medicinal substance in several EU member states; its legal status depends on the country of sale.

Ephedra and ephedrine

Ephedra species and their preparations are prohibited in foods, including food supplements, in the EU (Regulation (EC) No 1925/2006, Annex III, Part A)¹¹. Ephedrine is prohibited in competition by the World Anti-Doping Agency above a urinary threshold¹².

Caffeine

Caffeine is permitted in EU foods and food supplements, subject to labelling rules. It is not on the World Anti-Doping Agency Prohibited List¹².

White willow bark (salicin)

Aspirin (acetylsalicylic acid) is a medicinal substance and is not permitted in food supplements in the EU¹³. No health claim for this ingredient is authorised in the EU¹⁴; it is sold under national food-supplement rules¹⁵.

Synephrine (bitter orange, Citrus aurantium)

Bitter orange extracts are used in EU food supplements under national rules, which differ between Member States¹⁵.

Higenamine

Higenamine is not an authorised food supplement ingredient in the EU¹⁶ and is prohibited at all times by the World Anti-Doping Agency as a β2-agonist¹⁷¹².

Yohimbine (yohimbe bark, rauwolscine)

Yohimbine is a pharmacologically active substance. Its use in food is regulated under Regulation (EC) No 1925/2006 and national rules¹¹, and several EU Member States treat it as a medicinal substance¹³.

Piperine (black pepper extract, BioPerine®)

No health claim for this ingredient is authorised in the EU¹⁴; botanical ingredients are sold under national food-supplement rules¹⁵.