Shweta Shah, MD
Assistant Professor
Renal Section, Department of Pediatrics
Texas Children’s Hospital
@nefron1310
I recently came across a tweet about the use of mustard for dialysis cramps.
I had never heard of my patients using this remedy for their muscle cramps on dialysis! I realized I had never actually understood the exact proposed mechanism leading to cramps and was curious how these popular remedies of mustard and pickle juice really work, if at all.
I hope this does not leave my readers in a pickle or give anyone a brain cramp!
The Problem:
Patients with kidney disease who receive chronic hemodialysis experience a multitude of disease related symptoms which affects their quality of life. More prevalent amongst them are fatigue, cramps, pruritus, insomnia, and restless legs. These symptoms are often under-recognized and under-treated and can lead to long term morbidity and poor quality of life in dialysis patients.
One such debilitating symptom is muscle cramps during or after dialysis. Cramps occur when muscles contract on their own and can be quite painful. Dialysis-related muscle cramps are estimated to occur in about 21-74% of dialysis treatments. Muscle cramps can occur during and in between dialysis treatments as well as during sleep, leading to poor quality of sleep,anxiety and depression.The exact pathophysiology of muscle cramp remains unclear and a plethora of treatments are tried with variable success.
What causes cramps?
Although the exact mechanism for muscle cramps is not known, hemodialysis-related fluid and electrolyte shifts are reported as a primary cause. Other contributing factors are vitamin and electrolyte deficiency, muscle fatigue, neurologic dysfunction, and impaired oxygen delivery to the muscles. In sports medicine literature, exercise-associated muscle cramps are reported secondary to excessive sweating, total body volume and sodium deficit as well as muscle fatigue from deconditioning and overuse. Neural mechanisms that normally inhibit muscle contraction are inhibited by muscle fatigue, leading to uninhibited muscle contraction and cramps. This is more prevalent in older age groups, where physical deconditioning and associated metabolic disturbances are common and in the dialysis population.An association of elevated serum leptin levels and muscle cramps was noted in dialysis patients.
How do we treat muscle cramps?
Non-traditional remedies
Besides the traditional methods used to treat cramps in the dialysis unit (summarised in Table 1), non-traditional remedies like mustard, pickle juice have been historically used with limited data on their proposed mechanism of action. The use of pickle juice and mustard for treating muscle cramps in athletes is well documented and most of the literature on these supplements are from exercise biology medicine and not systematically investigated in dialysis patients. Exercise-induced muscle cramps are thought to be caused by salt and fluid loss as was traditionally described but there is recent evidence to suggest the “neuromuscular”pathway leading to muscle fatigue as an important mechanism along with the “dehydration” theory.
Table 1: Summary of known interventions for treatment of muscle cramps in dialysis patients
The National Athletic Trainers’ Association recommends that athletes prone to muscle cramping add 0.3 to 0.7 g/L of salt to their drinks to prevent muscle cramps. This is an attempt to help alleviate cramps through improving salt and fluid balance. For exercise-associated muscle cramps, trainers have used pickle juice and mustard to alleviate cramps. Reported amounts of pickle juice have been ~ 2 oz (60 ml) and typically < 200 ml (2 oz pickle juice= ~1700 mg sodium). No specific dose recommendation for mustard has been cited. In a study by Miller et al, the effect of consuming pickle juice and mustard in hypohydrated trainers was studied and the change in plasma osmolality,sodium and potassium post ingestion were measured. After receiving 1.5 g of sodium with pickle juice (dosed 1ml/kg body weight) or mustard with equivalent sodium, the athletes did not have significant hyperkalemia or hypertonicity, contrary to some clinical concerns with ingesting these supplements. They found that although safe, the amount of pickle juice and mustard ingested in the study will not fully replenish the electrolyte loss caused by exercise-induced sweating. They hypothesized that pickle juice and mustard would not not reduce muscle cramps if it is caused by salt and fluid loss alone because of this. However, this study did not evaluate the effectiveness of pickle juice and mustard in reducing cramping, rather just the safety of these remedies.
Foods with pungent tastes like vinegar,mustard,or pickle juice can stimulate an oropharyngeal neural reflex that inhibits hyperactive α-motor neurons. This can lead to muscle relaxation and relief of cramps, and may explain why these nontraditional methods help with muscle cramping The key agent stimulating the reflex in these remedies is thought to be acetic acid Acetic acid can also acts via the acetylcholine neurotransmitter action at the neuromuscular junction. Spectroscopic analysis and enzymatic assay, used to measure the acetic acid content, revealed that yellow mustard, sweet relish, all pickle juices, and the pickle juice products were composed of moderate amounts of acetic acid. Miller et al showed that about 74 ml of pickle juice resulted in alleviation of muscle cramps in 85 secs, this amounts to 0.32-0.62 g of acetic acid. This amounts to a 1.5-3 packets of yellow mustard or 3-5.5 packets of sweet relish to achieve the same effect, thus making that option impractical. The amount of pickle juice used in study (78.9 ml ± 14.2 ml) contained 1.51 ± 0.27 g Na and this was equivalent to 135.24 ± 22.8 g of mustard. One serving of commercially available PJ Sport® (240 ml) or PJ Shot® (75 ml) should achieve the same effect. Interestingly, 1-2 tbsp of apple cider vinegar contains 5 times higher acetic acid content than was shown to be effective in Miller’s study.A review of commercially available products shows low potassium content 1-2% of daily value per serving, an important fact to note for our dialysis patient population.
Other remedies may have varied purported mechanisms. Some help reduce the pain from muscle cramping rather than alleviating the cramping. Another compound, allyl isothiocyanate, found in mustard is thought to induce sensory nerve stimulation through the TRP ion channel ANKTM1. Of note, tetrahydrocannabinol (THC), an active ingredient in marijuana and capsaicin, present in cayenne pepper, also act through this channel to relax muscles. Some studies show that it is the turmeric in yellow mustard that helps with leg cramps due to its anti-inflammatory property.
Traditional treatment
Below is a brief review of the traditional modalities used to treat cramps during dialysis and purported mechanism of action for each.
Cramps during dialysis are associated with intra-dialytic hypotension and often improves with small bolus of normal saline and correction of hypotension. Reducing the ultrafiltration rate is necessary to prevent further cramping. The 2005 KDOQI guidelines recommended the use of cool-dialysate in patients on dialysis with frequent intradialytic hypotension. Sodium and ultrafiltration profiling during dialysis has shown to reduce hemodialysis associated symptoms including cramps. has been shown to be associated with lower rates of intra-dialytic hypotension and muscle cramps associated with dialysis. L-carnitine may also be effective with cramping associated with intradialytic hypotension if given in doses of 2,100-14,000 mg/week for 8-24 weeks by reducing oxidative stress.
Sometimes cramps are thought to be due to electrolyte changes or low vitamin levels.. Ensuring the dialysate calcium and magnesium is ≥ 2.5 mEq/L and ≥1.0 mEq/L respectively, as lower calcium and magnesium baths have been associated with intra-dialytic hypotension and cramps. Combination of vitamin C and E supplement has shown greater benefits than each used alone
Cramping in dialysis patients may be due to deconditioning and muscle fatigue rather than the dialysis treatment itself. Patients on dialysis have a higher tendency for muscle fatigue and exercise based intervention may be effective in reducing fatigue-induced cramping and improving physical conditioning.
Beyond these patient and dialysis characteristics, traditional medications have been prescribed to help with intradialytic cramping. Gabapentin, when compared to placebo, has shown favorable results to reduce cramps during hemodialysis, when administered prior to session.Quinine is no longer used in dialysis associated cramps due to boxed warning for hematological side effects like TTP and HUS as well as QT prolongation. Verapamil, a calcium channel blocker, has been shown to reduce nocturnal cramps when compared to quinine.
As is apparent, there is a lot we still do not know about this common affliction in our dialysis patients. It is in fact one of the top 3 patient reported symptoms. Because of this, Kidney Health Initiative (KHI) workgroup, a public-private partnership between ASN and FDA summarized the knowledge gaps and barriers in management of these symptoms and provided a strategic action plan to study effectiveness of treatment options for muscle cramps.In addition to clear understanding of its etiology, there are no definitive scoring systems or questionnaires to elucidate a comprehensive cramp history which will aid in documenting prevalence, severity, and compare efficacy of intervention. The pathophysiology of cramps remains poorly understood and results of current treatment are variable. These low-cost readily available interventions like pickle juice and mustard, that are seemingly low-risk, necessitate wide scale safety and efficacy testing in pragmatic clinical trials.
Reviewed by Matthew A. Sparks and Amy Yau
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