Bromide exhibits its most significant and well-known interaction with chloride, which in turn is influenced by the patient’s diet. The combination of bromide with levetiracetam did not result in any significant recorded pharmacokinetic interaction. Due to bromide’s long elimination half-life, timing of blood sample collection after oral administration is not critical, although samples collected more than 2 h after dosing should help avoiding peak effect variability (35).
While selenium, probiotics, and iodine all offer valuable support against bromide toxicity, their effectiveness and safety depend on your individual health status. Optimal iodine supplementation has also been linked to improved antioxidant status, particularly in pregnant women and those managing chronic health conditions (Vidal et al., 2014). It is particularly beneficial for thyroid health, an area often compromised by bromide exposure. Iodine, particularly in its iodide form, is another essential nutrient that can combat bromide toxicity by promoting antioxidant activity and reducing oxidative stress. The innovative use of probiotics paired with selenium nanoparticles has recently gained attention for their dual benefits in tackling inflammation and oxidative stress.
A study by Woody et al. (79) showed that, in human patients, the degree of pseudohyperchloremia could be used as an indirect method to assess bromide serum concentration in a quicker manner (79). Prospective dose titrating studies are still currently lacking, and it is possible for adequate seizure control to occur with concentrations below those of the expected therapeutic range. Similarly, Trepanier et al. (27) found serum concentrations between 810 and 2,400 mg/L to be adequate when bromide was used in association with phenobarbital, and 880–3,000 mg/L when bromide was used in monotherapy.
Most analytical methods that are currently used to assess chloride concentrations measure the total halide ion concentration, what includes chloride and bromide. Equally (as previously discussed), concentrations above this range do not necessary result in severe side effects or bromism in all patients (16). It is important to mention that the suggested bromide therapeutic serum concentrations should not be seen as an absolute truth.
On the other hand, Pu/Pd is a commonly reported adverse effect in the clinical experience of one of the authors (GBC). Polyphagia can be severe to lead to garbage and foreign body ingestion, leading to secondary complications (44, 63). Doses between 30 and 40 mg/kg/day can be adequate when using bromide in monotherapy (11, 51, 52). The unchanged halide of bromide is eliminated in the urine after being filtered from the bloodstream at the level of the glomerulus (39). GABA release, binding, transport or metabolism, however, does not appear to be affected by acute or chronic exposure to bromide (34). This facilitates its intracellular accumulation in the neurons and increased gamma-aminobutyric acid (GABA) inhibition due to hyperpolarization of the membrane (29–32).
Bromide Toxicity and the Best Supplements to Combat It
The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article. Studies assessing bromide efficacy are also (and should continue to be) limited due to this (41, 62). The value of monitoring the patient’s triglyceridemia in bromide detox preventing or anticipating signs of pancreatitis is also unknown and could reveal an interesting field for future studies.
Use in monotherapy can be particularly interesting in patients that have a contraindication for the treatment with first line ASM (e.g., phenobarbital in case of hepatic disease; structural epilepsy in case of imepitoin). Since its introduction by Schwartz-Porsche and Jürgens (26) that bromide continued to have an important role in the treatment of epileptic dogs, refractory to phenobarbital therapy. This contrasted with the combination of phenobarbital (alone or in association with bromide) with levetiracetam, which led to an increased clearance and lower levetiracetam plasma concentrations (86). Muñana et al. (86) assessed the possible influence of a combination of phenobarbital and/or bromide in the clearance of levetiracetam of epileptic dogs receiving multidrug treatment. Inspired by these results, Rossmeisl et al. (77) studied the existence of a possible similar relationship between the magnitude of pseudohyperchloremia and bromide serum concentration in bromide treated epileptic dogs.
Peer-reviewed journal articles for bromine (Br)
Despite this, bromide tolerance seems to vary among individuals and, as a result, cases of toxicosis were also reported with low serum concentrations (40). Bromide toxicosis (bromism) appears to be dose-dependent and linked to high serum bromide concentrations (63, 68). Dermatologic adverse effects are only rarely reported in canine patients and do not appear to be a significant problem in patients receiving bromide therapy (63). Podell and Fenner (23) reported Pu/Pd in 13 out of 23 dogs receiving potassium bromide in combination with phenobarbital (23).
It helps the body reduce oxidative stress and inflammation by neutralizing reactive oxygen species (ROS) and protecting cells from damage. This is where detoxification support through targeted supplementation becomes crucial. Exposure to even small amounts over time can accumulate in the body, leading to disruptions in thyroid function, oxidative stress, and hormonal imbalances. Most bromide exposure arises from contaminated food, beverages, and certain consumer products.
Primary Sources of Bromide Exposure
The patient’s maintenance dose should be increased if there is a decrease of more than 10% in bromide serum concentration between these two measurements (76). Bromide serum concentrations should be measured once a steady-state concentration is reached between 6 and 12 weeks after the beginning of treatment with a maintenance dosage (11, 51, 52). In a retrospective study, Boothe et al. (41) reported adverse effects in 8 out of 17 feline patients receiving bromide.
The use of antiseizure medications (ASMs) is the current mainstay for the treatment of epilepsy. In addition to this, seizure frequency might increase overtime in untreated patients suffering from idiopathic epilepsy, emphasizing another possible advantage of initiating treatment in a timely fashion (Table 1) (7, 10). In veterinary medicine, bromide continues to be used in the management of epileptic patients for over 30 years, yet adverse effects can impact owners and patients alike. When potassium bromide is dissolved in water, it has a sweet flavour at low concentrations, a bitter flavour at medium concentrations, and a salty flavour at high concentrations. It has been the only anticonvulsant medication for certain humans and canine patients with hepatic impairment in recent years. This combination offers a unique and promising approach to reducing the adverse effects of bromide toxicity by addressing both gut health and oxidative stress.
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Since bromide is still used in veterinary medicine in the United States, veterinary diagnostic labs can routinely measure blood bromide levels. The half-life of bromide in the human body (12 days) is long compared with many pharmaceuticals, making dosing challenging to adjust. This use gave the word “bromide” its colloquial connotation of a comforting cliché.
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- This combination offers a unique and promising approach to reducing the adverse effects of bromide toxicity by addressing both gut health and oxidative stress.
- A response rate (decrease of at least 50% in monthly seizure frequency) of 69% (9/13) was reported with the addition of bromide to the treatment of imepitoin-refractory epileptic dogs (61).
- Royaux et al. (61) described possible benefits of the addition of bromide to epileptic dogs receiving imepitoin.
- Studies assessing the risk of pancreatitis in bromide treated dogs are limited (65–67) and although this still appears to be a possible complication of the use of this medication, evidence for a causal effect has not yet been obtained.
- Hundreds of organobromine compounds are generated by this process.
It seeks to raise awareness about both the positive and negative aspects of this substance, empowering clinicians to make more informed decisions when utilizing this well-established ASM. Although the exact point prevalence is not known, this was estimated to be between 0.6 and 0.75% in the general dog population (1). A systematic review and metanalysis by Fiest et al. (2) identified a point prevalence of active epilepsy of 6.38 per 1,000 people. The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice.
Final Thoughts on Bromide Detoxification
- Hypobromite is produced via eosinophil peroxidase, an enzyme that can use chloride but preferentially uses bromide.
- It’s also our endeavor to discuss the current use as an alternative or add-on with other known antiseizure medications and potential future studies that might enhance our understanding and use of this medication.
- Medications like barbiturates (e.g., phenobarbital), which boost chloride conductance through GABA-ergic activity, may work together with bromide to elevate the seizure threshold (29).
- A loading dose of 125 mg/kg, divided into two daily administrations over 5 days, has been previously suggested.
- The dose for NaBr is approximately 15% less of that of KBr, since potassium has a higher molecular weight than sodium, making 1 g of NaBr to contain more bromide than 1 g of KBr (28, 44, 51).
Care should be taken while administering intravenous fluid therapy and this should be performed in association with serial monitoring of serum bromide concentrations (68). In cases where bromide is given in association with phenobarbital, a decrease of 10–30% of the dosage of phenobarbital can reduce the severity of neurological adverse effects in a few days. Serum bromide concentrations should be regularly assessed to identify possible changes in concentration trends and allow intervention before the development of signs of bromism or breakthrough seizures (68).
What Is Bromide? Its Natural Presence and Common Uses
Evidence regarding the frequency of polyuria and polydipsia (Pu/Pd) in dogs treated with bromide is controversial. However, cats may develop an eosinophilic bronchitis which makes bromide use in cats not advisable, what also limits the current available studies in this species (62). Longer loading periods with more fractioned dosages might reduce the risk of gastrointestinal signs (44). Only 5% of the patients in this study vomited during the loading period, without this being impeditive to finish the loading protocol (14). This approach results in a total loading dose of 625 mg/kg by the end of the 5-day period (51). Due to bromide’s long elimination half-life, dosing can be performed only once daily, what might help increasing owner’s compliance (44).
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Although Trepanier (28) reported doses between 50 and 80 mg/kg/day to be possibly needed in some patients treated with bromide alone, the authors believe these doses are most likely excessively high and not indicated in most patients. Sodium bromide (NaBr) constitutes an alternative, less common formulation that can also be used in veterinary patients. As with any medication, a steady-state serum concentration is reached after about four to five eliminations half-lives of regular administration (43). Elimination half-life is variable and reported between 15 (40) and 46 days in dogs (35), approximately 11 days in cats (41) and 12 days in humans (42).
Adverse effects affecting the patient’s skin also became well recognized, with the development of cutaneous eruptions (bromoderma) that added significant morbidity to human patients treated with this medication (22). Despite the lack of any randomized studies at that time, the available clinical data is considered enough to name bromide as the first effective ASM, marking the beginning of the modern treatment of human epilepsy (19). In the United States potassium bromide (KBroVet-CA1) and phenobarbital (Fidoquel-CA1) are currently the only two medications that received conditional approval by the Food and Drug Administration (FDA) in January 2021 and September 2023, respectively (9, 12).