What amount of caffeine (caffeine) is required to induce muscle twitching?

From the Guidelines

Caffeine doses exceeding 32 mmol litre−1 are required to guarantee muscle twitching, as this is the highest concentration tested in the static cumulative caffeine test that produces a sustained increase of at least 2 mN in baseline force from the lowest force reached 1. To induce muscle twitching, the amount of caffeine needed can vary significantly between individuals, but research suggests that high doses are typically required.

• The static cumulative caffeine test, as outlined in the European Malignant Hyperthermia Group guidelines, involves increasing caffeine concentrations stepwise to determine the threshold concentration that produces a sustained increase in baseline force 1.
• The test uses caffeine concentrations of 0.5,1.0,1.5,2.0,3.0,4.0, and 32 mmol litre−1, with each successive concentration administered after the maximal contracture plateau induced by the previous concentration has been reached or after exposure for 3 min if no contracture occurs 1.
• The result of this test is reported as the threshold concentration, which is the lowest concentration of caffeine that produces a sustained increase of at least 2 mN in baseline force from the lowest force reached 1.
• It is essential to note that individual sensitivity to caffeine can vary greatly, and factors such as body weight, tolerance, metabolism, and individual sensitivity can influence the dose required to induce muscle twitching.
• Caffeine causes muscle twitching by stimulating the central nervous system and increasing neuronal excitability, leading to spontaneous muscle contractions.
• If muscle twitching persists, reducing caffeine intake is recommended, and symptoms typically resolve within hours as caffeine is metabolized and eliminated from the body.

From the Research

Caffeine and Muscle Twitching

• The amount of caffeine required to induce muscle twitching is not explicitly stated in the provided studies, but some studies suggest that high doses of caffeine can cause muscle twitching as a side effect 2, 3.
• A study on frog single muscle fibers found that 1 mM caffeine can induce twitch potentiation, but the equivalent dose in humans is not specified 4.
• Another study on mouse muscles found that caffeine can convert activity-induced shortening of half-relaxation times into prolongations, but the dose of caffeine used is not specified 5.
• The International Society of Sports Nutrition recommends a caffeine dose of 3-6 mg/kg body mass for exercise performance, but does not mention muscle twitching as a specific effect 6.
• High doses of caffeine (e.g. 9 mg/kg) are associated with a high incidence of side-effects, but it is not clear if muscle twitching is one of them 6.

Caffeine Dosage and Side Effects

• The general consensus is that caffeine doses up to 400 mg/day in healthy adults are not associated with adverse effects, including muscle twitching 2, 3.
• However, individual tolerance to caffeine and sensitivity to its effects can vary greatly, and some people may experience side effects such as muscle twitching at lower doses 2, 3.
• The studies suggest that caffeine can have different effects on different types of muscles, and that the dose and timing of caffeine ingestion can influence its effects on muscle function 4, 5.