Low potassium theory of autism.

First I'm aware of the massive amount pseudoscience and scam treatments
suggested for autism spectrum conditions. My hypothesis here at best applies to a small number of people on the autism spectrum and benefits will be limited.

High potassium stimulates the release of aldosterone. Aldosterone stimulates the relase of vasopressin. Vasopressin may improve memory, learning,
social recognition ,emotional bonding and reduce repetitive behavior.

I will post some abstracts below.
K= potassium

Kidney Int. 2000 Apr;57(4):1324-8.
Links
Aldosterone and potassium secretion by the cortical collecting duct.
Palmer LG, Frindt G.

Department of Physiology and Biophysics, Weill Medical College of Cornell University, New York, NY 10021, USA. lgpalm@mail.med.cornell.edu

BACKGROUND.: Aldosterone has been implicated in the regulation of both Na and K concentrations in the plasma. Release of the hormone is known to be stimulated by high plasma K, and infusion of aldosterone lowers plasma K. However, the correlation between changes in mineralocorticoid levels and rates of K secretion is not perfect, suggesting that other factors may be involved. METHODS.: Patch-clamp recordings were made of K-channel activity in the split-open cortical collecting tubule of the rat. Estimates of channel density were made in cell-attached patches on the luminal membrane of principal cells of this segment. RESULTS.: Most of the K conductance of the apical membrane is mediated through low-conductance "SK" channels. The number of conducting SK channels is increased when animals are placed on a high-K diet. However, increasing plasma aldosterone levels by infusion of the hormone or by sodium restriction failed to change the number of active channels. CONCLUSIONS.: At least two circulating factors are required for the regulation of renal K secretion by the cortical collecting tubule. Aldosterone mainly stimulates secretion by increasing the driving force for K movement through apical channels. A second, as yet unidentified, factor increases the number of conducting K channels.

PMID: 10760062 [PubMed - indexed for MEDLINE]
1: Am J Physiol Renal Physiol. 2000 Feb;278(2):F246-56.
Links
Decreased vasopressin-mediated renal water reabsorption in rats with chronic aldosterone-receptor blockade.
Jonassen TE, Promeneur D, Christensen S, Petersen JS, Nielsen S.

Department of Pharmacology, the Panum Institute, University of Copenhagen, DK-2200 Copenhagen, Denmark. fitj@farmakol.ku.dk

Previous studies have suggested that mineralocorticoids are needed for a normal action of vasopressin on collecting duct osmotic water permeability. However, the mechanisms behind this are unknown. To investigate if aldosterone-receptor blockade influences vasopressin type 2 receptor (V(2))-mediated renal water reabsorption and the renal expression of the vasopressin-regulated water channel aquaporin-2 (AQP2), rats were treated with the aldosterone-receptor antagonist canrenoate (20 mg/day iv) for 4 wk. Daily urine flow was increased significantly by 44%, and urine osmolality was decreased by 27% in canrenoate-treated rats. Acute V(2)-receptor blockade (OPC-31260, 800 microgram. kg(-1). h(-1)) was performed under conditions in which volume depletion was prevented. In control rats, OPC-31260 induced a significant increase in urine flow rate (V, +25%) and free water clearance (C(H(2)O), -29%). In canrenoate-treated rats, the effect of OPC-31260 was significantly reduced, and semiquantiative immunoblotting demonstrated a significant reduction (45%) in AQP2 expression. Because rats with common bile duct ligation (CBL) have a reduced vasopressin-mediated water reabsorption compared with normal rats (V: -24%; C(H(2)O): -28%, and 86% downregulation of AQP2), the effect of canrenoate combined with OPC-31260 was tested. Canrenoate treatment of CBL rats significantly increased daily urine flow, decreased urine osmolality, and impaired the aquaretic response to OPC-31260 (V: -23%; C(H(2)O): -31%) with maintained suppression of the renal AQP2 expression. Thus canrenoate treatment of normal and CBL rats showed 1) increased urine production, 2) reduced aquaretic effect of acute V(2)-receptor blockade, and 3) a marked reduction in AQP2 expression. This strongly supports the view that aldosterone plays a significant role for vasopressin-mediated water reabsorption.

PMID: 10662729 [PubMed - indexed for MEDLINE]
1: Experientia. 1986 Sep 15;42(9):1012-4.
Links
High potassium intake increases the plasma concentration and urinary excretion of vasopressin in the rat.
Brooks DP, Crofton JT, Share L, Nasjletti A.

The effect of alterations of dietary potassium intake on the plasma concentration and the urinary excretion of vasopressin was studied in male rats. Ingestion of a high potassium diet resulted in increases in the plasma concentrations of potassium and vasopressin, systolic blood pressure, urine flow, and urinary vasopressin excretion. Ingestion of a low potassium diet had little effect on the plasma vasopressin concentration and systolic blood pressure but caused decreases in the plasma potassium concentration and urinary vasopressin excretion. The results indicate that physiological changes in the plasma potassium concentration or some other consequence of altered dietary potassium intake can affect vasopressin release and excretion.

PMID: 3758299 [PubMed - indexed for MEDLINE]
1: Biol Trace Elem Res. 2006 Jun;110(3):193-209.
Links
Analyses of toxic metals and essential minerals in the hair of Arizona children with autism and associated conditions, and their mothers.
Adams JB, Holloway CE, George F, Quig D.

Arizona State University, Tempe, AZ 85287-6006, USA.

The objective of this study was to assess the levels of 39 toxic metals and essential minerals in hair samples of children with autism spectrum disorders and their mothers compared to controls. Inductively coupled plasma-mass spectrometry was used to analyze the elemental content of the hair of children with autism spectrum disorders (n=51), a subset of their mothers (n=29), neurotypical children (n=40), and a subset of their mothers (n=25). All participants were recruited from Arizona. Iodine levels were 45% lower in the children with autism (p=0.005). Autistic children with pica had a 38% lower level of chromium (p=0.002). Autistic children with low muscle tone had very low levels of potassium (-66%, p=0.01) and high zinc (31%, p=0.01). The mothers of young children with autism had especially low levels of lithium (56% lower, p=0.005), and the young children (ages 3-6 yr) with autism also had low lithium (-30%, p=0.04). Low iodine levels are consistent with previous reports of abnormal thyroid function, which likely affected development of speech and cognitive skills. Low lithium in the mothers likely caused low levels of lithium in the young children, which could have affected their neurological and immunological development. Further investigations of iodine, lithium, and other elements are warranted.

PMID: 16845157 [PubMed - indexed for MEDLINE]
1: Philos Trans R Soc Lond B Biol Sci. 2006 Dec 29;361(1476):2187-98.
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Oxytocin, vasopressin and pair bonding: implications for autism.
Hammock EA, Young LJ.

Department of Psychiatry and Behavioural Sciences, Centre for Behavioural Neuroscience, Yerkes National Primate Research Centre, Emory University, Atlanta, GA 30329, USA.

Understanding the neurobiological substrates regulating normal social behaviours may provide valuable insights in human behaviour, including developmental disorders such as autism that are characterized by pervasive deficits in social behaviour. Here, we review the literature which suggests that the neuropeptides oxytocin and vasopressin play critical roles in modulating social behaviours, with a focus on their role in the regulation of social bonding in monogamous rodents. Oxytocin and vasopressin contribute to a wide variety of social behaviours, including social recognition, communication, parental care, territorial aggression and social bonding. The effects of these two neuropeptides are species-specific and depend on species-specific receptor distributions in the brain. Comparative studies in voles with divergent social structures have revealed some of the neural and genetic mechanisms of social-bonding behaviour. Prairie voles are socially monogamous; males and females form long-term pair bonds, establish a nest site and rear their offspring together. In contrast, montane and meadow voles do not form a bond with a mate and only the females take part in rearing the young. Species differences in the density of receptors for oxytocin and vasopressin in ventral forebrain reward circuitry differentially reinforce social-bonding behaviour in the two species. High levels of oxytocin receptor (OTR) in the nucleus accumbens and high levels of vasopressin 1a receptor (V1aR) in the ventral pallidum contribute to monogamous social structure in the prairie vole. While little is known about the genetic factors contributing to species-differences in OTR distribution, the species-specific distribution pattern of the V1aR is determined in part by a species-specific repetitive element, or 'microsatellite', in the 5' regulatory region of the gene encoding V1aR (avpr1a). This microsatellite is highly expanded in the prairie vole (as well as the monogamous pine vole) compared to a very short version in the promiscuous montane and meadow voles. These species differences in microsatellite sequence are sufficient to change gene expression in cell culture. Within the prairie vole species, intraspecific variation in the microsatellite also modulates gene expression in vitro as well as receptor distribution patterns in vivo and influences the probability of social approach and bonding behaviour. Similar genetic variation in the human AVPR1A may contribute to variations in human social behaviour, including extremes outside the normal range of behaviour and those found in autism spectrum disorders. In sum, comparative studies in pair-bonding rodents have revealed neural and genetic mechanisms contributing to social-bonding behaviour. These studies have generated testable hypotheses regarding the motivational systems and underlying molecular neurobiology involved in social engagement and social bond formation that may have important implications for the core social deficits characterizing autism spectrum disorders.

PMID: 17118932 [PubMed - indexed for MEDLINE]

http://www.usc.edu/uscnews/stories/13992.html


Brinton showed that animals lacking vasopressin exhibit strikingly similar symptoms to a subgroup of autistic children. The symptoms include impaired memory and learning, decreased social recognition and emotional bonding, repetitive behavior and abnormal kidney function.



She suggested that such children might respond to vasopressin therapy. Of the approximately 300,000 autistic patients in the United States, Brinton estimated that 10 to 20 percent might be responsive to vasopressin therapy.

Potassium salts are hard on the stomach and large amounts might have other
dangers. So eating a diet high in potassium and low in sodium would be the
safe way to supplemnet potassium. I've taken 1000-3000 mg of potassium at
one time in the form of a potassium citrate solution and on all doses I experience a major clearing up of the mind. Though the effect may last only and hour or so and I have not tried repeated dosing.
I've used 2.5 grams of potassium bicarbonate (1000 mg potassium) with the same results.

Thanks for posting about this theta. This is very interesting. ;)

I thought I would mention various anecdotal bits of information. First a person
eating the typical Western diet likely is eating a high ratio of sodium to potassium the opposite of what my hypothesis suggest would be helpful. The
body (kidneys)will release aldosterone when potassium is high to conserve sodium. So having high sodium intake will be a problem. I have saw mention else where of persons on the autism spectrum craving sodium. Since its so common It likely does not mean much but one thing very common with people
on the autism spectrum is they often eat highly restrictive odd diets. In my case it would be impossible to get enough potassium from foods alone.

Since vassopressin will lower urine production consuming the correct but not too much water maybe a factor in optimal vassopressin secretion.

Potassium citrate and presumable other potassium salts can lower urine pH. Potassium citrate is prescribe for that purpose to treat kidney stone problems.
There is a popular quack health fad in which its recommended people maintain
somewhat basic urine. I saw a Internet site that mentioned people on the
autism spectrum had acidic urine but I could not find any studies to back that
up. Its a warning on various ADHD meds that pH increasing substance (like possible potassium citrate(salts of weak acids and strong bases are basic))can increase absorption of the ADHD meds. Also I have mentioned else where
that lower urine pH might even increase the half-life of various ADHD drugs as much as 100%. So people on such drugs should be aware of potential drug
interactions.

I would STRONGLY caution against medicating oneself with potassium supplements.

Taking potassium supplements and creating a state of Hyperkalemia -- can stop the heart.

I guess you probably know that potassium OD is part of how they 'stop the heart' in the "lethal injection" protocol.

I guess you probably know that potassium OD is part of how they 'stop the heart' in the "lethal injection" protocol.

http://ptcl.chem.ox.ac.uk/MSDS/PO/potassium_chloride.html

IVN-MUS LD50 117 mg kg-1

KCl is 52.4% K so thats 61.4 mg K per /kg or in my case since I'm 73 kg
4482 mg K IV would be LD50. Thats pretty shocking as I have taken orally
3000 mg at one time. Yeah be safe and stick with food high in potassium and eat them over the entire day.

The thought occurred to me that lab animals are likely to be on a low sodium
diet. Which would likely lower the dose of potassium needed for a LD in those lab animals. I've read suggestions that people's diets have any where from 3-6 times the ratio of potassium to sodium. If you consider people maybe eating
anywhere from 2500-7500 mg of sodium a day and eating a similar amounts
(or less) of potassium it may mean the actual danger level of potassium supplementation is quite high in the average person. Anyway 1000 mg dose of potassium has shown utility in my 73 kg body. That works out to be slightly more than two medium bananas.

due to the condtion i have i have >>>Vasopressin<<< 3 to 4times a day for life i have not notic ny befrits in menrony in anyways so far and ive been on it for 26years myself

maybe a few case it could work but ive never seen init so far

dorm

due to the condition i have i have >>>Vasopressin<<< 3 to 4times a day for life i have not notic ny befrits in menrony in anyways so far and ive been on it for 26years myself

maybe a few case it could work but ive never seen init so far

dorm

Yeah I wish there was away to narrow down who may respond to vassopressin
(assuming it does have benefits in 10-20%).

I thought a family or personal history of high blood pressure might indicate a
person low in potassium. Oh my first thought was the mechanism of action
of my potassium induced mental effects was lowering blood pressure but I can not find solid information backing up cognitive benefits in lowering blood pressure.

The study showing low potassium in tissues of autistics with low muscle tone
got me thinking dyspraxia might be a common factor to but I read dyspraxia
might in fact be very common with autism spectrum.

Its possible the mechanism of high potassium intake in me is not vassopressin
secretion to.

Interesting another thread on the forum has mentioned potassium and ADHD.

http://www.addforums.com/forums/showthread.php?p=531239&posted=1#post531239

Here is the abstract of a study it was referencing.

1: J Child Neurol. 2007 Dec;22(12):1408-10.
Links
Hypokalemic sensory overstimulation.
Segal MM, Rogers GF, Needleman HL, Chapman CA.

SimulConsult, Inc, Chestnut Hill, Massachusetts. jcn@simulconsult.com.

This report describes 2 generations of a family with symptoms of sensory overstimulation that exhibit a potassium sensitivity similar to that seen in hypokalemic periodic paralysis. The sensory overstimulation is characterized by a subjective experience of sensory overload and a relative resistance to lidocaine local anesthesia. The sensory overload is treatable with oral potassium gluconate, with onset of the therapeutic effect in ~20 minutes. The effect of potassium is reminiscent of its effect in the channelopathies underlying hypokalemic periodic paralysis, and the resistance to lidocaine applied peripherally suggests a peripheral sensory localization to the abnormality. The phenotype overlaps with that of attention deficit disorder, raising the possibility of subtypes of attention deficit disorder that have a peripheral sensory cause and novel forms of therapy.

PMID: 18174562 [PubMed - in process]

Not sure how I respond to lidocaine. I had two wisdow teeth removed and one hurt being removed. Anyway it suggest another mechanism of action for potassium. Oh and the "sensory overstimulation" sounds related autism spectrum.

Here is another hypothesis that may have a relationship to potassium and autism.

http://www.autism-world.com/index.php/2007/03/30/lower-testosterone-cure-autism/


Hypothesis

Spironolactone is an aldosterone antagonist - potassium sparing diuretic that possesses potent immune and hormone modifying properties which may make it ideally suited for use as an intervention in autism spectrum disorders.

Mentions dose.

Levels of immunoglobulins were measured immediately prior to treatment with spirolactone 100 mg daily (approximately 2 mg/kg/day).

Some observations they made.

prior to and following implementation of spironolactone indicated a 21% improvement in irritability, a 17% decrease in lethargy, a 40% reduction of stereotypy, a 28% reduction of hyperactivity and a 33% decrease in inappropriate speech.

1: J Clin Endocrinol Metab. 2007 May;92(5):1863-70. Epub 2007 Feb 13.
Links
Down-regulation of D2 dopamine receptor and increased protein kinase Cmu phosphorylation in aldosterone-producing adenoma play roles in aldosterone overproduction.
Chang HW, Chu TS, Huang HY, Chueh SC, Wu VC, Chen YM, Hsieh BS, Wu KD.

Department of Internal Medicine, National Taiwan University Hospital, 7 Chung-Sun South Road, Taipei, Taiwan 100.

CONTEXT: The mechanism associated with the overproduction of aldosterone by aldosterone-producing adenomas (APA) is unknown. OBJECTIVE: The objective of the study was to explore the role of the D2 dopamine receptor (D2R) on aldosterone synthesis and secretion and clarify the clinical importance of this role on aldosterone overproduction in APA. RESULTS: D2R expression in APA was examined in 24 patients and was much less than that in the nontumorous adrenal cortex. D2R mRNA levels in APA were inversely correlated with CYP11B2 mRNA levels and the patient's plasma aldosterone concentration. Angiotensin II (AII)-stimulated aldosterone secretion and CYP11B2 mRNA expression in human adenocarcinoma cells (H295R) was attenuated by the D2 agonist, bromocriptine (BMC). BMC selectively attenuated AII-induced protein kinase C (PKC)-mu phosphorylation and its translocation to the cell membrane. PKCmu-specific short-hairpin RNA significantly decreased AII-induced CYP11B2 mRNA expression and aldosterone secretion. BMC also attenuated the AII-induced increase in cytoplasmic calcium, partially through an inhibition of cytoplasmic inositol 1,4,5 triphosphate production. Despite similar total PKCmu levels in APA and the nontumorous adrenal cortex, expression of phosphorylated PKCmu in APA was much higher. CONCLUSION: This is the first study to demonstrate that the D2R modulated aldosterone secretion and synthesis through a specific attenuation of PKCmu activity, as well as the intracellular calcium level. Down-regulation of the D2R in APA, in turn, increased PKCmu activity and led to overproduction of aldosterone in affected patients. The D2R may thus serve as a potential treatment target for primary aldosteronism.

PMID: 17299068 [PubMed - indexed for MEDLINE]

This study got me thinking how chronic elevated levels of aldosterone will
lower potassium levels. That study mentions D2 dopamine receptor down-regulation may play a role in elevated aldosterone in some people.
Downregulation of D2 receptors is typical of ADHD drugs. Which might effect
the aldosterone-producing adenomas. Which I assume are located in some glands outside of the brain. That would mean a drug that was a D2 antagonist and could not cross the blood brain-barrier might be useful to treated chronic elevated aldosterone. It could mean that ADHD drugs would lower potassium levels in some people.

One effect I notice from large dose potassium supplementation is a tautness of the muscle/skin in my face. Its something I feel like in 15-30 minutes after oral intake of the potassium and it passes quickly. I notice and it maybe completely unrelated when I hold my face in front of an electric heater I get a similar sensation. I hold my face in front of the heater when I'm stressed, have a headache, etc. Anyway they maybe related to. I was trying to find a link months ago but gave up. I did find some patent that suggest potassium cation and chloride anion both have an anti-irritation effect on the skin (an hence they could be used in cosmetic for sensitive people, etc).