Am J Physiol Regul Integr Comp Physiol. 2006
Mar;290(3):R546-52.↑ Back To Top
Role of potassium in regulating blood flow and blood
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,
changes in food items and diets?
Karppanen H, Karppanen P, Mervaala E.
Institute of Biomedicine, Pharmacology, University of Helsinki,
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
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.
Comment: The two refs. above
discuss a course of action – simply rebalance the
electrolyte minerals and replace the ones the body tends
to run short of – difficult to find more than these
Mayo Clin Health Lett. 2002 Dec;20(12):8.↑ Back To Top
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
↑ Back To Top
J Neurol. 2004 Mar;251(3):251-60.↑ Back To Top
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.↑ Back To Top
Eccentric muscle work--the unknown side of our movements.
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.↑ Back To Top
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.↑ Back To Top
Managing nocturnal leg cramps--calf-stretching exercises
and cessation of quinine treatment: a factorial randomized
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.↑ Back To Top
Interventions for leg cramps in pregnancy.
Young GL, Jewell D.
Barn Croft Surgery, Temple Sowerby, Penrith, Cumbria, UK,
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.↑ Back To Top
Prevalence and characteristics of muscle cramps in patients
with varicose veins.
Department of Surgery, Aichi Prefectural College of Nursing,
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↑ Back To Top
Leg cramps in the elderly: prevalence, drug and disease
Abdulla AJ, Jones PW, Pearce VR.
Department of Geriatrics, Royal Devon & Exeter Hospital,
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.↑ Back To Top
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
J Clin Pharmacol. 1995 Jun;35(6):588-93.↑ Back To Top
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.↑ Back To Top
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.↑ Back To Top
Unusual cause of hypokalemic paralysis in aged men:
Cheng CJ, Chiu JS, Chen CC, Lin SH.
Division of Nephrology, Department of Medicine, Tri-Service
General Hospital, National Defense Medical Center, Taipei,
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.↑ Back To Top
Potassium chloride supplementation diminishes platelet
reactivity in humans.
Kimura M, Lu X, Skurnick J, Awad G, Bogden J, Kemp F,
Hypertension Research Center, Cardiovascular Research Institute,
University of Medicine and Dentistry of New Jersey, Newark
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
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• References depicting
the difficulty within the Medical Community to Resolve "Cramping"