Am J Physiol Regul Integr Comp Physiol. 2006 Mar;290(3):R546-52.
Role of potassium in regulating blood flow and blood pressure.
Haddy FJ, Vanhoutte PM, Feletou M.
211 Second St. NW, #1607, Rochester, MN 55901-2896.

Unlike sodium, potassium is vasoactive; for example, when infused into the arterial supply of a vascular bed, blood flow increases. The vasodilation results from hyperpolarization of the vascular smooth muscle cell subsequent to potassium stimulation by the ion of the electrogenic Na(+)-K(+) pump and/or activating the inwardly rectifying Kir channels. In the case of skeletal muscle and brain, the increased flow sustains the augmented metabolic needs of the tissues. Potassium ions are also released by the endothelial cells in response to neurohumoral mediators and physical forces (such as shear stress) and contribute to the endothelium-dependent relaxations, being a component of endothelium-derived hyperpolarization factor-mediated responses. Dietary supplementation of potassium can lower blood pressure in normal and some hypertensive patients. Again, in contrast to NaCl restriction, the response to potassium supplementation is slow to appear, taking approximately 4 wk. Such supplementation reduces the need for antihypertensive medication. "Salt-sensitive" hypertension responds particularly well, perhaps, in part, because supplementation with potassium increases the urinary excretion of sodium chloride. Potassium supplementation may even reduce organ system complications (e.g., stroke).

J Hum Hypertens. 2005 Dec;19 Suppl 3:S10-9.
Why and how to implement sodium, potassium, calcium, and magnesium
changes in food items and diets?
Karppanen H, Karppanen P, Mervaala E.
Institute of Biomedicine, Pharmacology, University of Helsinki, Helsinki, Finland.

The present average sodium intakes, approximately 3000-4500 mg/day in various industrialised populations, are very high, that is, 2-3-fold in comparison with the current Dietary Reference Intake (DRI) of 1500 mg. The sodium intakes markedly exceed even the level of 2500 mg, which has been recently given as the maximum level of daily intake that is likely to pose no risk of adverse effects on blood pressure or otherwise. By contrast, the present average potassium, calcium, and magnesium intakes are remarkably lower than the recommended intake levels (DRI). In USA, for example, the average intake of these mineral nutrients is only 35-50% of the recommended intakes. There is convincing evidence, which indicates that this imbalance, that is, the high intake of sodium on one hand and the low intakes of potassium, calcium, and magnesium on the other hand, produce and maintain elevated blood pressure in a big proportion of the population. Decreased intakes of sodium alone, and increased intakes of potassium, calcium, and magnesium each alone decrease elevated blood pressure. A combination of all of these factors, that is, decrease of sodium, and increase of potassium, calcium, and magnesium intakes, which are characteristic of the so-called Dietary Approaches to Stop Hypertension diets, has an excellent blood pressure lowering effect. For the prevention and basic treatment of elevated blood pressure, various methods to decrease the intake of sodium and to increase the intakes of potassium, calcium, and magnesium should be comprehensively applied in the communities. The so-called 'functional food/nutraceutical/food-ceutical' approach, which corrects the mineral nutrient composition of extensively used processed foods, is likely to be particularly effective in producing immediate beneficial effects. The European Union and various governments should promote the availability and use of such healthier food compositions by tax reductions and other policies, which make the healthier choices cheaper than the conventional ones. They should also introduce and promote the use of tempting nutrition and health claims on the packages of healthier food choices, which have an increased content of potassium, calcium, and/or magnesium and a lowered content of sodium. Such pricing and claim methods would help the consumers to choose healthier food alternatives, and make composition improvements tempting also for the food industry.
 

Mayo Clin Health Lett. 2002 Dec;20(12):8.
Second opinion. I've had trouble sleeping lately because I tend to get cramps in my calf muscles and feet at night. What causes these cramps? What can I do about them? No Abstract

 

Acta Neurol Scand. 2003 Mar;107(3):176-86.
Muscular cramps: proposals for a new classification.
Parisi L, Pierelli F, Amabile G, Valente G, Calandriello E, Fattapposta F, Rossi P, Serrao M.
Dipartimento di Neurologia Clinica, Otorinolaringoiatria, Riabilitazione Motoria, Sensoria e dei Disturbi della Comunicazione, Universita degli Studi di Roma, La Sapienza, Rome, Italy.

Muscle cramps are involuntary, painful, sudden contractions of the skeletal muscles. They are present in normal subjects under certain conditions (during a strong voluntary contraction, sleep, sports, pregnancy) and in several pathologies such as myopathies, neuropathies, motor-neuron diseases, metabolic disorders, hydro-electrolyte imbalances or endocrine pathologies. There has been considerable uncertainty in the literature regarding the classification and nomenclature of muscle cramps, both because the term "cramp" is used to indicate a variety of clinical features of muscles, leading to its use as an imprecise "umbrella" term that includes stiffness, contractures and local pain, and because the spectrum of the diseases in which it appears is wide. The purpose of the present study is to propose a simple classification to provide a framework to better recognize the full spectrum of phenomenology of muscle cramps.

 

J Neurol. 2004 Mar;251(3):251-60.
Role of EMG evaluation in muscle hyperactivity syndromes.
Valls-Sole J, Montero J.
Unitat d'EMG, Servei de Neurologia, Hospital Clinic, Villarroel, 170, 08036, Barcelona, Spain.

Muscle hyperactivity can be a clinical feature on its own or, more commonly, an observation on electromyography (EMG) examinations. Whatever manifestation it takes, muscle hyperactivity always means enhanced excitability of muscle, axons or neurons. Clinical findings may be variable, ranging from fasciculations to muscle cramps. Even though clinical examination may lead in most instances to suggest the diagnosis of the underlying disease, EMG studies are necessary to identify the type of abnormal discharges and suggest the site of their suspected origin. Although in clinical studies, the action potential showing abnormal muscle hyperactivity is practically always recorded from muscle fibers, the site in which the impulse has arisen will determine its shape and firing patterns. In this review, we describe the EMG characteristics observed in syndromes featuring muscle hyperactivity and the pathophysiology underlying the abnormal firing of muscle fibers.

Ther Umsch. 2003 Jul;60(7):425-9.
Eccentric muscle work--the unknown side of our movements.
Steiner R.
Sportmedizinisches Zentrum SMZB, Bern.

Eccentric muscle work is an important part of our everyday activity, i.e. in breaking and preventing falls. Eccentric phases of movements improve the efficiency of cyclic repetitive activities. The molecular function in eccentric work is not understood, however its characteristics are a low metabolic demand and a high power output. Compared to concentric work there are only small differences in the hemodynamics of eccentric work. The muscle capacity for mechanical load is the limiting factor in eccentric work. Unaccustomed eccentric activity leads to damage of the cytoskeleton, which is the reason for delayed onset of muscle soreness. In sports and rehabilitation eccentric training can result in significant strength gain. Its use is today established to improve structures, which are exposed to eccentric loads in everyday activity. The high mechanical power may be promising in the musculoskeletal rehabilitation of patients with cardiopulmonary limitations.

Postgrad Med J. 2002 Oct;78(924):596-8.
Nocturnal leg cramps in older people.
Butler JV, Mulkerrin EC, O'Keeffe ST.
Dept. of Medicine for the Elderly, University College Hospital and Merlin Park Hospital, Galway, Ireland.

Nocturnal leg cramps are common in older people. Such cramps are associated with many common diseases and medications. Physiological methods may be useful for preventing cramps in some people, but there have been no controlled trials of these approaches. Quinine is moderately effective in preventing nocturnal leg cramps. However, there are concerns about the risk/benefit ratio with this drug. In patients with severe symptoms, a trial of 4-6 weeks' treatment with quinine is probably still justified, but the efficacy of treatment should be monitored, for example using a sleep and cramp diary.

Br J Gen Pract. 2005 Mar;55(512):186-91.
Managing nocturnal leg cramps--calf-stretching exercises and cessation of quinine treatment: a factorial randomized controlled trial.
Coppin RJ, Wicke DM, Little PS.
The Surgery, Station Road, Overton, Basingstoke, Hants RG25 3DZ, UK.

BACKGROUND: Quinine is a common treatment for nocturnal leg cramps but has potential side effects. An uncontrolled study suggested that calf-stretching exercises could prevent nocturnal leg cramps (night cramps) but these findings have never been confirmed. AIM: To assess the effect of calf-stretching exercises and cessation of quinine treatment for patients with night cramps taking quinine. DESIGN OF STUDY: Randomised controlled trial. SETTING: Twenty-eight general practices in southern England. METHOD: One hundred and ninety-one patients prescribed quinine for night cramps were randomised to one of four groups defined by two "advice" factors: undertake exercises and stop quinine. After 6 weeks they were advised that they could take quinine and undertake the exercises freely. Documentation of cramp at 12 weeks was achieved in 181 (95%) patients. Main outcome measures were: symptom burden score, and frequency of night cramps and quinine usage. RESULTS: At 12 weeks there was no significant difference in number of cramps in the previous 4 weeks (exercise = 1.95, 95% confidence interval [CI] = -3.01 to 6.90; quinine cessation = 3.45, 95% CI = -1.52 to 8.41) nor symptom burden or severity of cramps. However, after 12 weeks 26.5% (95% CI = 13.3% to 39.7%) more patients who had been advised to stop quinine treatment reported taking no quinine tablets in the previous week (odds ratio [OR] = 3.32, 95% CI = 1.37 to 8.06), whereas advice to do stretching exercises had no effect (OR = 0.73, 95% CI = 0.27 to 1.98). CONCLUSIONS: Calf-stretching exercises are not effective in reducing the frequency or severity of night cramps. Advising those on long-term repeat prescriptions to try stopping quinine temporarily will result in no major problems for patients, and allow a significant number to stop medication.

Cochrane Database Syst Rev. 2002;(1):CD000121.
Interventions for leg cramps in pregnancy.
Young GL, Jewell D.
Barn Croft Surgery, Temple Sowerby, Penrith, Cumbria, UK, CA10 1RZ.

BACKGROUND: Many women experience leg cramps in pregnancy. They become more common as pregnancy progresses and are especially troublesome at night. OBJECTIVES: The objective of this review was to assess methods of preventing and treating leg cramps in pregnancy. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register (October 2001). SELECTION CRITERIA: Randomised trials of treatments for leg cramps in pregnancy. DATA COLLECTION AND ANALYSIS: Trial quality was assessed and data were extracted independently by two reviewers. MAIN RESULTS: Five trials involving 352 women were included. The trials were of moderate quality. The only placebo-controlled trial of calcium treatment showed no evidence of benefit. Trials comparing sodium chloride with placebo (odds ratio 0.54, 95% confidence interval 0.23 to 1.29) and calcium with sodium chloride (odds ratio 1.23, 95% confidence intervals 0.47 to 3.27 ) showed no evidence of benefit. Placebo controlled trials of multivitamin with mineral supplements (odds ratio 0.23, 95% confidence intervals 0.05 to 1.01) and magnesium (odds ratio 0.18, 95% confidence intervals 0.05 to 0.60) provided some suggestion of benefit. REVIEWER'S CONCLUSIONS: The evidence that calcium reduces cramp is weak and seems to depend on placebo effect. The evidence for sodium chloride is stronger but the results of the sodium chloride trial may no longer be relevant because of dietary changes which include an increased sodium intake in the general population. It is not possible to recommend multivitamins with mineral supplementation, as it is not clear which ingredient, if any, is helping. If a woman finds cramp troublesome in pregnancy, the best evidence is for magnesium lactate or citrate taken as 5mmol in the morning and 10mmol in the evening.

Vasa. 2000 Nov;29(4):269-73.
Prevalence and characteristics of muscle cramps in patients with varicose veins.
Hirai M.
Department of Surgery, Aichi Prefectural College of Nursing, Nagoya, Japan.

BACKGROUND: It has been suggested that limb circulation may be disturbed in patients with muscle cramps due to leg venous hypertension. The aim of this study was to examine the incidence and characteristics of muscle cramps from venous insufficiency. PATIENTS AND METHODS: The incidence and characteristics of muscle cramps, which were investigated by a questionnaire, were compared between 288 patients with incompetence of the long or short saphenous vein and 550 age-matched individuals from the general population. RESULTS: The patient group showed a significantly higher incidence of muscle cramps in the last year than the general population group, 67% and 53%, respectively (p < 0.001). The incidence of calf cramps was significantly higher in the patient group than in the general population group, 91% and 75%, respectively (p < 0.001). Although most subjects reported symptoms occurring only at night, the incidence was significantly higher in the patient group than in the general population group, 78% and 52%, respectively (p < 0.001). There was no significant difference in the duration or severity of muscle cramps between the groups. The patient group showed a significantly higher incidence of more than 12 episodes per year than the general population group (p < 0.001). CONCLUSIONS: Muscle cramps in patients with varicose veins occur more frequently and more often at night and in the calf in comparison with those from the general population.

Int J Clin Pract. 1999 Oct-Nov;53(7):494-6
Leg cramps in the elderly: prevalence, drug and disease associations.
Abdulla AJ, Jones PW, Pearce VR.
Department of Geriatrics, Royal Devon & Exeter Hospital, Exeter, UK.

To determine the prevalence of leg cramps in elderly outpatients and their association any underlying diseases and concomitant drug intake, we conducted a cross-sectional study using an in-depth questionnaire. A total of 365 patients aged 65 years and over (mean 78.5 years) attending our outpatient clinic participated in the study. The prevalence of leg cramps was 50%. Cramps were commoner in females (56%) than in males (40%). Although reported to occur anytime throughout the 24 hours, cramps were most prevalent at night (62%). In many patients, leg cramps were a long-standing complaint: 20% had been suffering with them for more than 10 years, whereas only 9% of patients reported them first starting within the last six months. Only 73 (40%) sufferers had informed their practitioner; of these, 39 (53%) received treatment, of whom 26 gained benefit. Leg cramps were strongly associated with peripheral vascular disease (odds ratio 2.9, 95% CI 1.89-4.55, p < 0.00001), arthritis (odds ratio 2.26, 95% CI 1.48-3.45, p = 0.0001) and female gender (odds ratio 1.96, 95% CI 1.28-3.03, p = 0.002). Heart failure, hypertension, diabetes mellitus and stroke were not significantly associated. Except for a causal association with analgesic use, no positive association could be shown with any other class of drugs, including diuretics.

Tidsskr Nor Laegeforen. 1999 Apr 30;119(11):1589-90.
Leg cramps in pregnancy--how common are they?    [Article in Norwegian]
Valbo A, Bohmer T.
Kvinneklinikken Baerum sykehus.

Leg cramps in pregnancy, defined as painful spasms of the calf, were investigated among women giving birth at the maternity ward at Baerum Hospital from 1 October to 20 October 1997. A questionnaire distributed to 120 women three days after parturition revealed that 45% had suffered from leg cramps during pregnancy. Among 54% of them the cramps appeared after the 25th week of pregnancy. 76% of the women had experienced the symptoms twice per week or less often; 81% of them suffered from painful cramps only during night-time. We conclude that leg cramps are still a common symptom in pregnancy and may compromize sleep and hence the ability to work.

J Clin Pharmacol. 1995 Jun;35(6):588-93.
Is quinine effective and safe in leg cramps?
Mandal AK, Abernathy T, Nelluri SN, Stitzel V.
Department of Medicine, Wright State University, VA Medical Center, Dayton, OH 45428, USA.

Muscle cramp is a recurrent and painful condition and a common complaint among elderly subjects and patients treated with hemodialysis. It is commonly nocturnal and can disturb a good night's sleep. No specific cause can be identified; therefore, therapy is mostly symptomatic. Quinine sulfate, an antimalarial drug, is widely used as an effective therapy for idiopathic leg cramps. Several double-blind, randomized, placebo-controlled studies have questioned the effectiveness of quinine in leg cramps; whereas other studies have shown significantly more benefit with use of quinine in reducing the frequency and severity of cramps compared with placebo or vitamin E. The mechanism of this beneficial effect is obscure, however. Quinine appears to decrease the excitability of the motor end plate, thereby reducing the muscle contractility. Most patients consider quinine beneficial for their leg cramps, which is difficult to refute by scientific data. More important, cramp is a subjective symptom, therefore difficult to measure objectively. Consequently, scientific studies designed to prove or disprove the effectiveness of quinine can be subject to flaws. Further, a dosage of 200 to 300 mg of quinine every night has not been shown to cause significant side effects. Nevertheless, quinine should be used in a small dose and cautiously, especially in the elderly and patients with renal failure, and should be avoided in patients with liver disease.

Age Aging. 1994 Sep;23(5):418-20.
A general population survey of rest cramps.
Naylor JR, Young JB.
St Luke's Hospital, Bradford.

Two hundred and eighteen subjects, out of 250 individuals taken from a general practice register, returned completed questionnaires giving details about rest cramps, and a further 15 were contacted by telephone. The overall prevalence of rest cramps in the survey population was 37%. The symptom was more prevalent in older subjects. Rest cramps were most commonly experienced in the muscles of the leg, in 83% of the 86 cramp sufferers. Symptoms were usually present at night (73%). On average cramp episodes lasted for 9 min (95%CI 6.7-11.2). Most cramps sufferers experienced symptoms infrequently, but 40% had cramp episodes more than three times per week and 6% complained of at least one episode per day or night. Twenty-one per cent of cramp sufferers described their symptoms as very distressing. A minority, 32% of the 86 cramp sufferers, had reported the symptoms to a general practitioner although the 86 subjects self-rated their health more negatively than the individuals without muscle cramps. There was a significant, positive association between rest cramps and symptoms of angina or intermittent claudication although these two factors only accounted for 12% of the variance, suggesting that peripheral vascular disease may play a relevant but limited role in the aetiology of rest cramps.

 

South Med J. 2005 Dec;98(12):1212-5.
Unusual cause of hypokalemic paralysis in aged men: Sjogren syndrome.
Cheng CJ, Chiu JS, Chen CC, Lin SH.
Division of Nephrology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.

Hypokalemic paralysis is a less recognized but reversible disorder in elderly patients. This report describes two elderly Chinese males (age 74 and 78 years) who had progressive muscle weakness and eventually paralysis. Physical examination showed symmetrical flaccid paralysis of extremities. Both had the major biochemical abnormality of profound hypokalemia (1.4 and 1.8 mmol/L) accompanied by high urine K+ excretion and hyperchloremic metabolic acidosis. A positive urine anion gap and alkaline urine pointed to the diagnosis of distal renal tubular acidosis. Large doses of potassium chloride supplementation were required to restore muscle strength. Pertinent investigations, including elevated titers of antinuclear antibody and rheumatoid factor, positive anti-Ro antibody, low serum C3 and C4 levels, and delayed saliva excretion on salivary scintigraphy suggested Sjogren syndrome. Despite the lack of sicca syndrome at the initial presentation, both had development of typical sicca syndrome and positive Schirmer test at the 5-month and 1-year follow-up, respectively. Potassium citrate supplement and prednisolone therapy completely corrected the hypokalemia and metabolic acidosis. Extraglandular involvement with distal renal tubular acidosis preceding the typical sicca syndrome may induce hypokalemic paralysis and unveil Sjogren syndrome in elderly males.

Hypertension. 2004 Dec;44(6):969-73. Epub 2004 Oct 25.
Potassium chloride supplementation diminishes platelet reactivity in humans.
Kimura M, Lu X, Skurnick J, Awad G, Bogden J, Kemp F, Aviv A.
Hypertension Research Center, Cardiovascular Research Institute, University of Medicine and Dentistry of New Jersey, Newark 07103, USA.

The prevalence of occlusive stroke is inversely correlated with potassium intake. We explored the hypothesis that a high potassium intake attenuates platelet reactivity, as expressed in ADP-evoked platelet aggregation. We studied healthy men (n=31) and women (n=42), blacks (n=33) and whites (n=40). In this cohort, we supplemented the habitual intake of 17 men and 21 women with 60 mmol KCl/70 kg body weight per day for 3 days and maintained 14 men and 21 women on their habitual intake. We then compared the change in ADP concentration causing 50% of the maximal initial rate (EC50) of platelet aggregation in the potassium-supplemented versus control groups. Potassium supplementation attenuated platelet reactivity, expressed by an increase in EC50 of platelet aggregation (P=0.0005), which was primarily attributable to an increase in EC50 in whites (P=0.0004). Urinary potassium excretion was significantly lower in blacks than in whites under basal conditions and after potassium supplementation. We conclude that potassium supplementation diminishes platelet reactivity, a phenomenon that provides a link between platelet biology and occlusive stroke.