Beta‐Alanine Relieves Symptoms in Primary Orthostatic Tremor

Primary orthostatic tremor (POT) is a rare neurological disease manifested as a fast tremulous muscle activity of 13–18 Hz in a standing position. ¹ The condition brings an intense feeling of instability and muscle fatigue. Ultimately patients become severely limited in their ability to stand and develop walking difficulties. Patients describe a feeling of inability to remain standing, difficulties in initiating walking after a period of standing (freezing of gait), and painful cramping of the lower extremities. ¹ The leg tremor is induced immediately when standing up and persists at a stable frequency in each individual patient. ² Symptoms of unsteadiness are usually delayed for some minutes in the earlier stages of the disease but are evoked sooner after standing up as the disease progresses. ¹ , ² Medical treatment options (propranolol, benzodiazepines, anti‐epileptic drugs) are limited and treatment effects are often unsatisfactory and/or diminish over time. ² This letter describes four female patients (Table 1) with electromyography (EMG)‐verified POT who experienced a pronounced positive effect from the dietary supplement beta‐alanine, an amino acid commonly used by athletes to enhance muscle performance. ³ These four patients all reported significant improvement in disabilities related to POT after commencing regular intake of beta‐alanine. The reported improvements included prolonged standing time, improved gait initiation, improved balance, less fatigue, and less muscle pain. The presence of tremor activity was reported to remain unchanged. Detailed case reports are available as supplementary material S1.

TABLE 1.

Clinical characteristics and beta‐alanine treatment outcome

Patient	Age (years)	Disease duration (years)	Comorbidity	Previous tremor treatments	Present tremor treatments	Beta‐alanine dosage, follow‐up period	Patient‐reported effects of beta‐alanine
1	64	30	None	Valproic acid, clonazepam, gabapentin, propranolol	None	3 g/day, 10 weeks	Increased stability, decreased muscle pain
2	60	12	Hypertonia, hypothyroidism, hyperhidrosis, type 1 diabetes	Gabapentin, propranolol	Primidone, benserazide/levodopa, clonazepam	4 g/day, 8 weeks	Increased stability and physical endurance, decreased muscle pain
3	55	13	B12‐deficiency	Clonazepam	Propranolol	4 g/day, 13 weeks	Increased physical endurance, prolonged tolerated standing time, decreased muscle stiffness, less violent shaking
4	64	7	None	Gabapentin, propranolol, clonazepam	None	5–6 g/day, 8 weeks	Prolonged tolerated standing time, less freezing of gait

It is hypothesized that symptoms of POT could partly be due to muscle fatigue, and remedies for improving muscle endurance could thus be beneficial in POT.

Beta‐alanine is a nonessential amino acid and, together with histidine, a precursor of the cytoplasmic dipeptide carnosine. Both carnosine and beta‐alanine may have implications on the central nervous system and tremor generation through enhancing GABAergic activity and also have proposed neuroprotective properties. ⁴ However, carnosine is highly abundant in muscle tissue where it acts as a buffer regulating intracellular pH. ⁵ The level of carnosine is dependent on the concentration of beta‐alanine, and intake of dietary supplements containing beta‐alanine increases levels of carnosine. ⁶ The frequency spectrum of POT (13–18 Hz) tangents the upper limit of possible muscle tremor frequency, where stimulations above 20 Hz are known to induce tetanic muscle force. ⁷ The slow‐twitch muscle fibers in postural muscles are less flexible to fast turnover activity like the high frequency tremor in POT, which is why the involvement of type 2 fast‐twitch muscle fibers is likely to be recruited but these are also more prone to fatigue. The severity of POT symptoms, like reduction in tolerated standing time, may be related to muscle fatigue. Patients with POT also frequently describe their incapacity to stand as being like a feeling of leg stiffness, painful leg cramps, a fear of falling, and a sense of leg weakness. Treatments intended to enhance muscle endurance, like beta‐alanine, could be an alternative approach to treating POT. However, placebo‐controlled trials and long‐term follow‐up are necessary to confirm this effect.

Financial Disclosure

Employment as a consultant in neurology at the neurological clinics of Danderyds Sjukhus and Neuroenheten Sabbatsberg, Stockholm, Sweden.

Ethics Statement

All patients reported on approved their participation. No approval from the Swedish Ethical Review Authority was required for this work. This report is consistent with the Journal's guidelines concerning ethical publication.

Supporting information

Data S1. Supporting information.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.