Thanks to some threads here and some clicking around in scientific papers I have put together some notes about the subject matter. After the summary below I will just paste them here as I don't have time to edit them.
- Exertion causes ME sufferers to overproduce inflammatory chemicals, such as IL-1 and PGE2.
- These chemicals can produce polyuria of the solute diuresis type, i.e. passing excessive water AND minerals.
- (Not included here) I also found one or more papers stating that lack of sleep causes polyuria - can't remember which type.
- Anti-inflammatory substances can help to reduce levels of inflammatory chemicals and consequently reduce or prevent loss of minerals in urine.
- Mineral deficiency has a range of adverse short-and long-term effects, including tooth and bone damage, vascular pathology, neuronal dysfunction, muscular dysfunction, etc., etc., so may be responsible for many of the symptoms of PEM, and perhaps ME generally, along with the dehydration resulting from uncontrolled polyuria.
Whilst anti-inflammatories (pharmaceutical, supplemental or dietary) are unlikely to be a cure for ME, they may help significantly with symptoms, and may be a useful adjunct to steps taken towards achieving remission/recovery by reducing/preventing the exacerbations that arise from over-exertion.
In a separate blogpost I will paste some info I have found on two very-promising supplements, which I know others have already tried, and I am thinking of doing the same. They are resveratrol and curcumin.
MY NOTES ON INFLAMMATORY CHEMICALS AND SOLUTE DIURESIS:
Polyuria papers of interest
(Study on children)
Am J Physiol Renal Physiol. 2006 Dec;291(6):F1232-40. Epub 2006 Jun 27.
Nocturnal polyuria in monosymptomatic nocturnal enuresis refractory to desmopressin treatment.
Kamperis K1, Rittig S, Jørgensen KA, Djurhuus JC.
The transition from day to night is associated with a pronounced decline in diuresis with reductions in the amount of excreted water, electrolytes, and other end products of our metabolism. Failure to do so leads to a large urine output at night, a condition known as nocturnal polyuria, encountered in a large proportion of children with nocturnal enuresis. The aim of this study was to clarify the mechanisms responsible for the nocturnal polyuria seen in enuretics with inadequate response to desmopressin (dDAVP). Forty-six enuretics (7-14 yr of age) and fifteen age-matched controls were admitted for a 24-h protocol with standardized fluid and sodium intake, comprising urine collections, blood sampling, and blood pressure monitoring. We included patients with severe enuresis (5 +/- 1 wet nights/wk) showing <50% reduction in wet nights on dDAVP. We characterized the patients on the basis of their nocturnal urine production. The children with nocturnal polyuria excreted larger amounts of sodium and urea at night than nonpolyurics and controls. Solute-free water reabsorption as well as urinary arginine vasopressin and aquaporin-2 excretion were normal in polyurics, and no differences were found in atrial natriuretic peptide, angiotensin II, aldosterone, and renin levels. Urinary prostaglandin E2 (PGE2) excretion was significantly higher in polyurics. The nocturnal polyuria in children with dDAVP-resistant nocturnal enuresis seems to be the result of augmented sodium and urea excretion. The high urinary PGE2 levels found in these children point toward a role for increased prostaglandin synthesis in the pathogenesis of enuresis-related polyuria.
Free full text online at http://ajprenal.physiology.org/content/ajprenal/291/6/F1232.full.pdf
(study on children)
J Urol. 2008 Aug;180(2):707-13; discussion 713-4. doi: 10.1016/j.juro.2008.04.047. Epub 2008 Jun 13.
The effect of desmopressin on renal water and solute handling in desmopressin resistant monosymptomatic nocturnal enuresis.
Kamperis K1, Rittig S, Radvanska E, Jørgensen KA, Djurhuus JC.
We sought to evaluate the effect of desmopressin on renal water and solute handling in children with monosymptomatic nocturnal enuresis and desmopressin resistant nocturnal polyuria compared to healthy controls.
MATERIALS AND METHODS:
A total of 12 patients with enuresis and nocturnal polyuria, normal bladder reservoir function and no response to desmopressin, and 10 age matched controls were enrolled in the study. Children were admitted to the hospital for a 48-hour protocol comprising urine collections and blood sampling. Sodium and water intake was standardized. During the second night children received 40 mug intranasal desmopressin. Parameters characterizing the renal water and solute handling were measured and compared between baseline nights and nights with desmopressin.
Desmopressin markedly reduced nocturnal urine output in patients with enuresis, minimizing sodium, urea and overall solute excretion, despite the fact that these children were unresponsive to desmopressin at home. This effect on renal sodium handling was not mediated by atrial natriuretic peptide, angiotensin II, aldosterone or renin. Desmopressin did not influence urinary prostaglandin E(2) excretion. The antinatriuretic effect was seen only in patients with enuresis, and it was directly correlated with the reduction in urine output.
Children with nocturnal enuresis and nocturnal polyuria who do not exhibit adequate response to desmopressin at home seem to respond well to the agent at the clinic. The effect of desmopressin in children with enuresis seems largely dependent on reductions in the amount of sodium excreted. Sodium regulating hormones remained unaffected by desmopressin, indicating a possible direct effect of the agent on renal sodium handling.
(study on children)
J Urol. 2012 Nov;188(5):1915-22. doi: 10.1016/j.juro.2012.07.019. Epub 2012 Sep 19.
Effect of indomethacin on desmopressin resistant nocturnal polyuria and nocturnal enuresis.
Kamperis K1, Rittig S, Bower WF, Djurhuus JC.
We evaluated the acute effect of indomethacin on renal water and solute handling in children with coexisting monosymptomatic nocturnal enuresis and desmopressin resistant nocturnal polyuria, and in healthy controls.
MATERIALS AND METHODS:
A total of 23 subjects were recruited, consisting of 12 children with monosymptomatic nocturnal enuresis and nocturnal polyuria with partial or no response to desmopressin, and 11 age matched controls. Children completed a 48-hour inpatient study protocol consisting of fractional urine collections and blood samples. Sodium and water intake were standardized. During the second night a dose of 50 mg indomethacin was administered orally before bedtime. Diuresis, urine osmolalities, clearances and fractional excretions were calculated for sodium, potassium, urea, osmoles and solute-free water. Renin, angiotensin II, aldosterone and atrial natriuretic peptide were measured in plasma. Prostaglandin E(2) was measured in urine.
Indomethacin markedly decreased the nocturnal sodium, urea and osmotic excretion in children with enuresis and controls. The overall effect on nocturnal urine output was inconsistent in the group with enuresis. Subjects in whom nocturnal diuresis was decreased following administration of indomethacin remained dry.
Prostaglandin inhibition leads to antidiuresis, reducing the amount of sodium, urea and osmotic excretion in children with monosymptomatic nocturnal enuresis and desmopressin resistant nocturnal polyuria. The sodium regulating hormones do not seem to mediate these processes. The overall effect in desmopressin nonresponders with nocturnal polyuria is variable. The extent to which indomethacin can be applied in the treatment of enuresis needs further evaluation.
(adolescents and adults)
Clin Endocrinol (Oxf). 1998 Dec;49(6):793-801.
The efficacy of DDAVP is related to the circadian rhythm of urine output in patients with persisting nocturnal enuresis.
Hunsballe JM1, Hansen TK, Rittig S, Pedersen EB, Djurhuus JC.
Desmopressin may be a useful treatment in some, but not all, patients with nocturnal enuresis. We have evaluated a relation between nocturnal urine output in patients with primary monosymptomatic nocturnal enuresis and the treatment response to synthetic vasopressin.
Adolescent or adult enuretics and normal subjects were enrolled in the study and admitted to hospital for a 24 hour investigation of the diurnal variation in urine output, plasma vasopressin (AVP) and plasma atrial natriuretic peptide (ANP). The enuretics were characterized prior to investigation as either 1-desamino-8-D-arginine vasopressin (DDAVP) responders or non-responders. During admission the fluid intake was restricted to 25 ml/kg per day.
Twenty-four patients (15-37 years) with primary monosymptomatic nocturnal enuresis and 9 normal subjects (24-31 years).
Circulating levels of AVP, ANP, plasma electrolytes and plasma osmolality were measured (1400, 2000, 2300, 0200, 0500 and 0800 hours) together with urine volume, urine osmolality and urine electrolytes during daytime and nighttime. Tubular reabsorptive capacity for water, osmoles and creatinine were assessed as well as urinary and fractional excretion rates of sodium and potassium.
Controls and DDAVP non-responders had a significant decrease in urine output at night concomitant with a significant plasma AVP amplitude in peak/nadir values although both groups lacked a significant nocturnal increase in AVP. In contrast, in DDAVP responders there was no circadian variation in urine output and thus a nocturnal polyuria together with no oscillation in plasma AVP. The DDAVP responding group had a nocturnal urine production significantly larger than the two other groups. However, the mean 24 hour AVP levels were similar in all groups. The excessive urine production at night in DDAVP responders was accompanied by nocturnal natriuresis due to an increased fractional excretion of sodium. In contrast, nocturnal antidiuresis in controls and DDAVP non-responding enuretics coincided with diminished sodium excretion. Average ANP levels were elevated in both enuretic groups compared to normals, whereas a circadian variation was detected only in the latter.
It is concluded that DDAVP responsiveness is linked to the nocturnal urine production and that no pathophysiological role can be ascribed to AVP or ANP in DDAVP refractory adolescent and adult enuretics. Moreover, it is suggested that an abnormal tubular handling of sodium may contribute to the nocturnal polyuria seen in DDAVP responders.
J Urol. 1997 Sep;158(3 Pt 1):830-6.
Single dose imipramine reduces nocturnal urine output in patients with nocturnal enuresis and nocturnal polyuria.
Hunsballe JM1, Rittig S, Pedersen EB, Olesen OV, Djurhuus JC.
We investigated the effect of imipramine on nocturnal urine output in patients with nocturnal enuresis.
MATERIALS AND METHODS:
There were 15 monosymptomatic enuretic patients 15 to 37 years and 8 control subjects 25 to 32 years old. We measured nocturnal urine output, urine osmolality, creatinine clearance, osmolal clearance, free water clearance, excretion of solutes, fractional excretion of sodium, fractional excretion of potassium and plasma vasopressin with and without a single oral dose of imipramine (1 mg./kg. of body weight) taken at 8 p.m.
Baseline studies showed significantly larger and less concentrated nocturnal urine among enuretics compared with controls. We observed a marked antidiuretic effect of imipramine in 6 enuretics with severe nocturnal polyuria. The imipramine induced decrease in urine output was accompanied by reduced osmolal clearance. Approximately a third of the observed decrease in solute excretion was attributed to lower excretion of sodium and potassium. The remaining two-thirds were most likely caused by an increased tubular reabsorption of urea, which may be secondary to a sympathomimetic effect of imipramine tubules, possibly because of altered adrenal medullary function with an increase in proximal tubular sodium and water reabsorption. The resultant lower tubular flow rate facilitates tubular reabsorption of urea in the distal part of the nephron.
Imipramine has a vasopressin independent antidiuretic effect if nocturnal polyuria is present. The antidiuretic effect of imipramine can be attributed primarily to increased alpha-adrenergic stimulation in the proximal tubules with a secondary increased urea and water reabsorption more distally in the nephron.
Journal of Chronic Fatigue Syndrome 2000; 6(3/4): 69-107.
Review: Immunology of Chronic Fatigue Syndrome
Roberto Patarca, Timothy Mark, Mary Ann Fletcher and Nancy Klimas
E. M. Papper Laboratory of Clinical Immunology
Department of Medicine (R-42)
University of Miami School of Medicine
P.O. Box 016960
Miami, Florida 33101
IL-1 induces prostaglandin (PGE2, PGI2) synthesis by endothelial and smooth muscle cells (140). These substances are potent vasodilators, and IL-1 administration in animals and humans produces significant hypotension. IL-1 has a natriuretic effect (141) and may affect plasma volume.
Inflammatory cytokines and mineral loss in urine
Blog entry posted by MeSci, Jun 18, 2014.