• Welcome to Phoenix Rising!

    Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of and finding treatments for complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.

    To register, simply click the Register button at the top right.

Instead of ME/CFS, could some have simple schizophrenia? Its symptoms: anhedonia, blunted emotions, brain fog, apathy, social withdrawal

pattismith

Senior Member
Messages
3,926
Do you have MECFS?
What is” immediately better”
Are you now walking and running all of a sudden a week on?
NO I don't mean it's a cure for ME/CFS but it is very efficient to fix my feeling of internal restlessness or jitteriness that refers to akhatisia.
(I happen to have this feeling from time to time since I started medications for autoimmune/inflammatory diseases.)
 

Wayne

Senior Member
Messages
4,268
Location
Ashland, Oregon
it is very efficient to fix my feeling of internal restlessness or jitteriness that refers to akhatisia.
(I happen to have this feeling from time to time since I started medications for autoimmune/inflammatory diseases.)
Hi @pattismith -- I've been dealing with akathisia after taking a single dose of Promethazine back in 2018. The best things I've discovered that work to calm my system down are coffee enemas (all enemas stimulate the vagus nerve, which activates the calming parasympathetic nervous system); castor oil applications on my abdomen and neck; and some self-acupuncture, with the two primary points being at the top of my head and in a spot between and above the eyes. Two minutes in this video will show you where those two "master" points are, and how easily a person can do this for themselves.

I ran across some historical context on akathisia a couple years ago, with a reference to the first known case being caused by a neuroleptic drug (Promethazine) in 1947. I'll paste it below in case you're interested. -- Best...

Akathisia

R.M.A. de Bie, ... S.H. Fox, in Encyclopedia of Movement Disorders, 2010

Definition and History​

Akathisia is a disorder characterized by a subjective report of inner restlessness with an inability to sit still, relieved by moving about. The patient usually has repetitive movements, which involve primarily the legs and trunk, that occur predominantly when the patient is sitting.

The first documented description of a syndrome resembling akathisia has been attributed to the British physician and anatomist Thomas Willis (1621–1675). The term akathisia (from Greek, literally ‘not to sit’) was coined by Lad Haskovec (1902) to describe two patients with restlessness and an inability to sit still. Haskovec distinguished the disorder from chorea and regarded it as a nonorganic psychiatric disorder, a tradition that continued for the next two decades. Due to the Sicard’s and Bing’s descriptions of akathisia in association with parkinsonism in 1923, akathisia was recognized as a symptom of idiopathic or postencephalitic parkinsonism. An influential statement came from Kinnier Wilson (1940) who wrote that even though Haskovec used the term akathisia for cases of ‘hysterical or psychopathic nature,’ it could be applied to parkinsonian patients.

In 1947, Sigwald reported drug-induced akathisia in a patient with Parkinson’s disease (PD), who developed restlessness when treated with promethazine, a neuroleptic drug. After antipsychotic drugs became generally available, a number of reports appeared in the literature of patients being restless, unable to sit, and marching like soldiers to abate the restless feelings. The similarity with the akathisia syndrome of the preneuroleptic era was recognized. In the early 1960s, akathisia was accepted as an ‘extrapyramidal’ side-effect of neuroleptic medications with dopamine receptor blocking properties. It was demonstrated that akathisia could occur in psychiatrically normal individuals when treated with neuroleptic drugs.

In modern psychiatry, akathisia is used synonymously with drug-induced akathisia, but the term’s origin in the preneuroleptic era makes it clear that the syndrome has multiple causes.

View chapter Explore book
 

Cipher

Senior Member
Messages
806
@Hip

A family member of mine have had problems with restless legs syndrome (RLS), which is due to a dysregulation of dopamine in the brain. This dysregulation seems to be due to a local iron deficiency in the brain:

Research and brain autopsies have implicated both dopaminergic system and iron insufficiency in the substantia nigra.[40] Iron is well understood to be an essential cofactor for the formation of L-dopa, the precursor of dopamine.
Notably, this can be the case even though systemic iron stores are considered non-deficient.

In my family member's case the RLS resolved after receiving intravenous iron. Due to chronic kidney disease, which increases hepcidin, oral iron wasn't effective in her case since increased hepcidin stops oral iron from being absorbed.

From my limited knowledge about these negative symptoms of schizophrenia, it seems like a lack of dopamine could play an important role.

After some googling I found this study:

Latent Iron Deficiency as a Marker of Negative Symptoms in Patients with First-Episode Schizophrenia Spectrum Disorder

Iron deficiency may alter dopaminergic transmission in the brain. This study investigated whether iron metabolism is associated with negative symptoms in patients with first-episode psychosis. The study enrolled 121 patients with first-episode schizophrenia spectrum disorder, whose duration of treatment was 2 months or less. Negative symptoms were measured using the Positive and Negative Syndrome Scale (PANSS) and Clinician-Rated Dimensions of Psychosis Symptom Severity (Dimensional) scale of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Prominent negative symptoms were defined as moderate or severe negative symptoms on the Dimensional scale of the DSM-5. Iron deficiency was defined as a serum ferritin ≤ 20 ng/mL. Patients with iron deficiency were significantly more likely to have prominent negative symptoms (45.2 vs. 22.2%; p = 0.014) and a higher PANSS negative symptoms score (p = 0.046) than those with normal ferritin levels. Patients with prominent negative symptoms had significantly lower ferritin levels (p = 0.025). The significance of these results remained after controlling for the duration of illness and other confounding variables. Our finding of an independent association between iron deficiency and negative symptoms in patients at the very early stage of illness implies that iron dysregulation has an effect on negative symptoms in patients with schizophrenia. The possibility of therapeutic intervention with iron should be further investigated.

In this study they define iron deficiency as a serum ferritin ≤ 20 ng/mL. According to Wikipedia, below 30 or 50 ng/mL can be considered deficient:
According to a 2014 review in the New England Journal of Medicine stated that a ferritin level below 30 ng/mL indicates iron deficiency, while a level below 10 ng/mL indicates iron-deficiency anemia.[29]
Some studies suggest that women with fatigue and ferritin below 50 ng/mL see reduced fatigue after iron supplementation.[31][32]

Unfortunately, ferritin is elevated by inflammation and can hence be false-high in the context of iron deficiency.

As I mentioned before, in the case of RLS there is a local iron deficiency in the brain that may coexist with normal systemic iron stores. This can be overcome by increasing systemic iron stores to the higher end of the normal range.

The study above supports the notion that systemic iron deficiency can cause negative symptoms in patients with schizophrenia. I don't know if there's a possibility that a local brain iron deficiency (with normal systemic iron stores) could cause negative symptoms, in a similar fashion to RLS.

It takes a long time (months) until oral iron fully increases iron stores if deficient. Iron bisglycinate is better tolerated than other forms (e.g. ferrous sulfate). For some people oral iron is not absorbed, and IV/IM iron is needed.

While writing this post I realized that I didn't know what my ferritin level was. Upon checking old lab tests, it was 26 µg/L (same as ng/mL). I hadn't taken any notice of this level due to the lab's reference range being 20-375 µg/L. But, as quoted above from Wikipedia, below 50 ng/mL or 30 ng/mL is considered deficient and can induce fatigue without anemia. Guess I'll have to start taking iron supplements and see if I notice any difference!

Related thread: Some CFS patients just have Iron Deficiency Without Anemia, an internist found
 
Last edited:

Cipher

Senior Member
Messages
806
Iron deficiency was common among psychiatric patients (81%) in this study. 58% of the iron deficient patients experienced regression/remission of psychiatric symptoms after iron treatment.

[Iron deficiency: A diagnostic and therapeutic perspective in psychiatry]


[Article in French]

A Kassir 1

Affiliations

Abstract​


Background: Iron plays an essential role in balancing the various metabolism in the body. It is also involved in the synthesis of several neurotransmitters. Nutritional iron deficiency is one of the most widespread worldwide; it poses a great health challenge due to the consequences it entails.

Objectives: The aim of this research study is to explore the percentage of psychiatric patients who have a deficiency in iron. In addition, the study investigates the efficacy of iron administered by oral treatment on psychiatric symptomatology among iron deficient patients. The research study utilized the martial biological results, which involved the observation of the level of iron deficiency among the outpatients of a local psychiatrist and assessor from the period of January 2012 until December 2013.

Methods: Out of 412 patients, 295 were women and 117 men. The age of the participants ranged from 16 to 89years, with an average age of 45years. The only exclusion criterion was a patient's refusal or inability to take the prescribed iron assessment test. We considered a transferrin saturation coefficient (TSC)<30% and/or a serum ferritin level≤50ng/mL to be "indicative" of obvious iron deficiency, and a ferritin level between 51 and 100ng/mL to be "suggestive" of iron deficiency. A plasma ferritin assay was performed at least once on all of the participants prior to any proposed iron treatment. A calculation of the TSC in 138 patients was requested due to suspected iron deficiency despite a blood ferritin level of>100ng/ml. A single method was utilized in the various laboratories to analyse the blood samples to determine whether there was a deficiency in iron. Only those patients with blood ferritin levels ≤100ng/mL and/or a TSC of<30% (335 patients) were subsequently given exclusively an oral iron treatment prescribed on its own or as a supplement or simultaneously with psychotropic treatment. The daily administered dose of elemental iron varied between 50 and 200mg a day.

Results: About half of the women - 145 (35.19% of the subjects) - and 15 men (3.64% of the subjects) certainly had a deficiency in iron (blood ferritin level≤50ng/mL). Ninety women and 24 men (27.6% of the subjects) had blood ferritin levels between 51 and 100ng/mL indicating iron deficiency, and 28 women and 33 men (14.8% of the subjects) had a TSC of<30% despite a blood ferritin level of>100ng/mL. Overall, 335 patients (81.3% of the subjects) showed an iron deficiency based on the criteria we set. In the remaining 77 patients (18.7% of the subjects), all of them had blood ferritin levels>100ng/mL and some had TSC≤30%, while the remaining patients' TSC was unknown because it was not measured. The results indicated that there is an iron deficiency in 198 out of 240 patients suffering mostly from mood and behavioural disorders, in 101 out of 126 patients suffering mostly from anxiety disorders, in 18 out of 27 patients suffering mostly from sleep disorders, in 14 out of 15 patients suffering mostly from delusions of persecution, and in the 4 patients suffering mostly from burn out. There was evidence of regression/remission of psychiatric symptoms in 193 responsive patients whereas the remaining 142 patients were considered non-responsive. In the responsive patient category, 37 participants were treated with just iron, 52 received iron supplemented to the initial psychotropic treatment which was not fully effective, and 104 patients were treated with iron and prescribed psychotropic drugs simultaneously. The iron treatment seems to bring about a reduction - particularly through its mono-aminergic neurotransmitter synthesis-promoting action - in hyperemotivity, anxiety, irritability, aggressiveness, sadness, anhedonia, apathy, asthenia, sleep disorders, dysautonomia symptoms, eating disorders, restless-leg syndrome, cognitive performance and the likelihood of resorting to psychiatric admission. A daily elemental iron dose intake between 50 and 200mg/day by deficient patients appears to likely enhance the effects of the psychotropic drugs and even to act as an actual antidepressant. Many patients who received a prescription for iron and antidepressants showed few side effects related to antidepressants and a small number required psychiatric hospitalization. Patients considered unresponsive to iron therapy were those who left the study, were not assessed because the study's timeframe ended, still had an iron deficiency because they did not continuously take the medication, or suffered from somatic diseases which explains their resistance to treat the low iron level (nutritional imbalance, digestive or urinary or gynecological or iatrogenic diseases, sleep apnea).

Conclusion: Our clinical observation of two years in a local psychiatrist's clinic revealed that over 80% of patients had iron deficiency. Although the low iron level cannot explain all physical and psychiatric symptoms in patients, it is useful to note that more than half of the iron deficient patients responded favorably after an oral treatment of iron. This result leads to further investigation of the level of iron in psychiatric patients and to reconsider the iron range placed by the laboratories. In addition, it is crucial not to eliminate the possibility of iron deficiency in psychiatric patients. Further research studies are needed to set more specific and detailed criteria to determine the range of iron deficiency in order to support the findings of this study and optimize the care given to patients suffering from various disorders and psychiatric syndromes.
 
Messages
758
Location
Israel
Simple schizophrenia is a type of schizophrenia that does not involve the classic schizophrenia symptoms of hallucinations, delusions, paranoia, false beliefs, incoherent thinking and confused speech (these are the so-called positive symptoms of schizophrenia).

Simple schizophrenia only involves the negative symptoms of schizophrenia, which include:
  • Anhedonia (reduced ability to experience pleasure or reward from normally enjoyable activities)
  • Blunted emotions
  • Apathy
  • Social withdrawal (lack of interest in social interactions and withdrawing from social contact)
  • Reductions in speech
  • Difficulty in concentrating during conversation, and an inability to concentrate on even simple tasks (ie, brain fog)


[/SPOILER]

.
Do these people have physical energy? and if not, do they have worsening of all symptoms, particularly energy after any physical exertion?
The people that I know with schizophrenia are capable of lifting weights at the gym and are very physically strong.

In fact one of them did go regularly to the gym.
I disagree with this and can not relate to the idea that this is 100% in the brain stem or brain chemicals. Those organs are definitely affected but I suspect that is not the cause. That Abilify helps a bit says nothing, as any brain chemical abnormalities might be downstream from something else.....plus the weakness in this illness is so harsh.
 
Last edited:

Hip

Senior Member
Messages
17,790
A family member of mine have had problems with restless legs syndrome (RLS), which is due to a dysregulation of dopamine in the brain. This dysregulation seems to be due to a local iron deficiency in the brain:

Very interesting. I did try some iron supplementation years ago (ferrous sulphate 200 mg daily = 65 mg iron), but without noticing much benefit. However, I only took it for a few weeks, which may not be long enough. And that was before catching COVID, which has worsened mental health.

It might be worth trying iron supplementation again.

I also have a family member with RLS, so will mention the iron connection to them.



In schizophrenia, it is the dopamine D2 receptors which are implicated. It is believed too much activation of the D2 receptor leads to schizophrenic symptoms. Antipsychotics often antagonise D2, reducing dopamine stimulation at this receptor.

I use very low-dose amisulpride to treat some of the schizophrenia-like symptoms I have. This drug works in a interesting way on the D2 and D3 receptors, as a dopamine system stabiliser rather than a simple dopamine D2 antagonist.

A dopamine system stabiliser is a bit like an audio compressor unit used by musicians: it boosts the dopamine signal when the signal is weak, but attenuates the signal when it is strong. Abilify is another dopamine system stabiliser drug, although Abilify's dopamine stabilisation mechanism works in a different way to amisulpride's.

Prof Gottfries has a patent about using dopamine system stabiliser drugs to treat ME/CFS (or fibromyalgia, I cannot remember which). This was years before the Abilify treatment of ME/CFS appeared.


But in spite of high activation of the D2 receptor leading to schizophrenic symptoms, dopamine boosting drugs or supplements do not seem to worsen my schizophrenic-like symptoms. For example, I can take MAO inhibitors such as moclobemide (to treat my depression symptoms) without noticing any worsening of the mild psychosis-type symptoms I get.

Likewise with Spanish saffron, a pretty effective dopamine boosting antidepressant, which I often take to boost mood.
 
Last edited:

Hip

Senior Member
Messages
17,790
Do these people have physical energy? and if not, do they have worsening of all symptoms, particularly energy after any physical exertion?


See the first post, where it says:
One recent study found that a subset of both simple schizophrenia and regular schizophrenia patients displayed symptoms reminiscent of ME/CFS and fibromyalgia — including fatigue, muscle pain, muscle tension, autonomic symptoms, and a flu-like malaise.

The study also found that such somatic symptoms in schizophrenia patients were associated with inflammatory cytokines like IL-1beta, TNF-alpha and CCL11.

So it's possible that a very small number of ME/CFS patients may be misdiagnosed, and might instead have simple schizophrenia. Alternatively, there may be a small number of ME/CFS patients who have simple schizophrenia on top of their ME/CFS.

I have some simple schizophrenia symptoms, so might be one of these people with ME/CFS and simple schizophrenia; or simple schizophrenia instead of ME/CFS.
 

L'engle

moogle
Messages
3,167
Location
Canada
Sounds like if people have me/cfs and simple schizophrenia they are likely to have their me/cfs symptoms rolled into the schizophrenia diagnosis as symptoms of that. Since its a diagnosis of exclusion, whatever other condition a person has takes precedence. So a lot of mental illnesses end up having mc/cfs symptoms tacked onto them as a subset, muddying the diagnosis further.
 

L'engle

moogle
Messages
3,167
Location
Canada
Another angle is that schizophrenia must be pretty exhausting. Processing the extra 'stuff' your mind is sending you and sorting out what is real. So they probably do have fatigue, and probably crashes after episodes, but perhaps not the PEM, that we get from 'normal' activity.
 

Hip

Senior Member
Messages
17,790
Another angle is that schizophrenia must be pretty exhausting. Processing the extra 'stuff' your mind is sending you and sorting out what is real. So they probably do have fatigue, and probably crashes after episodes, but perhaps not the PEM, that we get from 'normal' activity.

The psychosis component of schizophrenia that you are talking about, involving things that are not real (such as delusions, visual and auditory hallucinations) is not present in simple schizophrenia.

Simple schizophrenia does not involve psychosis, so in that respect is a milder version of schizophrenia.


Simple schizophrenia involves symptoms such as anhedonia, blunted emotions, apathy, social withdrawal, reductions in speech, difficulty in concentrating (brain fog).

ME/CFS patients will usually have at least two of these symptoms, namely blunted emotions and brain fog.

And a few ME/CFS patients report having anhedonia.


Interestingly, although simple schizophrenia can be considered milder than schizophrenia, it is much harder to treat. Antipsychotics are often successful in addressing the psychosis symptoms of schizophrenia. But neither antipsychotics nor any other drugs can help the symptoms of simple schizophrenia much. So simple schizophrenia is a harder challenge to treat.
 

datadragon

Senior Member
Messages
389
Location
East Coast, USA
Hi Hip and all,

It might be worth trying iron supplementation again.
Vitamins C and/or B6 and vitamin A may often be required to correct iron deficiency anemia which would not respond to iron supplementation. B6 and A both use zinc in their metabolism. Typically A and Zinc are the culprits due to their lowering through inflammation/infection. Zinc is required for mobilization of stored vitamin A from the liver and conversions to active metabolites so again taking retinol Vitamin A might still require the zinc and magnesium for utilization. vitamin A also enhances potassium and phosphorus absorption. iron and copper are synergistic in that sufficient copper is required for iron utilization, and dependent on ceruloplasmin which needs zinc, vitamin A, magnesium for example. https://cancercelltreatment.com/2015/01/31/mineral-vitamins/

lets start here with Iron, Dopamine, Glutamate:

Iron is required for the healthy functioning of dopamine receptors. More specifically, brain iron is required for these receptors to communicate properly. If there is a lack of brain iron, it doesn’t matter how many neurotransmitters are being produced, there just isn’t going to be proper functioning of these receptors. Brain iron deficiency produces increased sensitivity of the cortico-striatal terminals to release glutamate, Dr. Ferré has found that low levels of receptors of adenosine, a chemical in the brain that regulates neurochemicals, lead to abnormally high levels of glutamate and dopamine. https://rlsfoundation.blogspot.com/2018/07/new-research-identifies-adenosine-role.html
https://seratame.com/what-causes-rls-restless-leg-syndrome-and-the-dopamine-connection/

I mentioned earlier that Dopamine binding to D1 receptors enhances the excitatory effects that result from glutamate’s interaction with a specific glutamate receptor subtype (i.e., the NMDA receptor). Conversely, activation of D2 receptors normally inhibits the effects induced by glutamate’s binding to another glutamate-receptor subtype (i.e., the AMPA receptor https://www.sciencedirect.com/science/article/abs/pii/S0006899312005112 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826820/

I mentioned here that Zinc deficiency potently decreases the activities of extracellular adenine-nucleotide-hydrolyzing ectoenzymes, delaying both extracellular ATP clearance and adenosine generation, Findings indicate that the activity of ENPP1, ENPP3, NT5E/CD73, and TNAP, which are involved in the regulation of purinergic signaling, decreased under zinc-deficient conditions.. https://forums.phoenixrising.me/threads/role-of-dysfunctional-glycolysis.91264/post-2449814

In other posts, I have previously mentioned zinc (and Vitamin As) roles in sleep and ceruloplasmin production needed to make copper and iron bioavailable (usable) we could revisit. I've also been discussing how zinc becomes less available to utilize and zinc uptake is reduced under inflammation/infection conditions. Earlier also mentioned the PPAR's like PPAR-a need for zinc which are involved with depression.

Dopamine receptor D2 short, vesicular monoamine transporter (VMAT2) and DAT mRNAs were significantly decreased in schizophrenia, with no change in DRD3 mRNA, DRD3nf mRNA and DAT protein between diagnostic groups. However, DAT protein was significantly increased in putatively treatment-resistant cases of schizophrenia compared to putatively treatment-responsive cases. Midbrain monoamine oxidase A (MAOA) mRNA was increased, whereas MAOB and catechol-O-methyl transferase mRNAs were unchanged in schizophrenia. https://www.nature.com/articles/tp2016257 The dopamine transporter (DAT) is regulated by Zinc which directly interacts with the protein. https://pubmed.ncbi.nlm.nih.gov/19000913/ Additional cations able to influence MAO-A function include Zinc (Zn2+), which inhibits MAO-A activity. Monoamine oxidase A (MAO-A) is an enzyme that breaks down neurotransmitters such as serotonin (5-HT), norepinephrine (NE), and dopamine (DA), tyramine (and other less clinically relevant chemicals). https://bmcneurosci.biomedcentral.com/articles/10.1186/1471-2202-8-73
 
Last edited:
Messages
44
In schizophrenia, it is the dopamine D2 receptors which are implicated. It is believed too much activation of the D2 receptor leads to schizophrenic symptoms. Antipsychotics often antagonise D2, reducing dopamine stimulation at this receptor.

I use very low-dose amisulpride to treat some of the schizophrenia-like symptoms I have. This drug works in a interesting way on the D2 and D3 receptors, as a dopamine system stabiliser rather than a simple dopamine D2 antagonist.

A dopamine system stabiliser is a bit like an audio compressor unit used by musicians: it boosts the dopamine signal when the signal is weak, but attenuates the signal when it is strong. Abilify is another dopamine system stabiliser drug, although Abilify's dopamine stabilisation mechanism works in a different way to amisulpride's.

Prof Gottfries has a patent about using dopamine system stabiliser drugs to treat ME/CFS (or fibromyalgia, I cannot remember which). This was years before the Abilify treatment of ME/CFS appeared.


But in spite of high activation of the D2 receptor leading to schizophrenic symptoms, dopamine boosting drugs or supplements do not seem to worsen my schizophrenic-like symptoms. For example, I can take MAO inhibitors such as moclobemide (to treat my depression symptoms) without noticing any worsening of the mild psychosis-type symptoms I get.

Likewise with Spanish saffron, a pretty effective dopamine boosting antidepressant, which I often take to boost mood.

HI @Hip ,
Hope you are improving from the long covid.
I’m trying amisulpride again in order to remove the last of the clozapine
My meds are
10mg olanzapine
5mg about of clozapine
And some stelazine
50mg amisulpride
I’ve put up the olanzapine to help sleep as the amisulpride is very stimulating which I take at night.
I assumed it was the stimulant affect but now I think it’s akathinsia
I’ve research a bit and mirtazapine is supposed to help akathinsia with amisulpride.
The other issue is the prolactin elevation.
D2 partial agonists don’t work with amisulpride because amisulpride works king of outside the brain and doent cross the blood brain barrier I read as explaination.
I’ve heard metformin can reverse the hyperprolactination and get your testosterone up.
Plus I’ve got the Pantathene you recommended which mops up the prolactin and should work as it’s not tweeting the dopamine receptors.
If you have any ideas on how to reduce the akathinsia I would be very greatful.
Hers the links I’ve been looking at

https://www.cambridge.org/core/jour...ia-revisited/BF5042E428267A0D22A12C1C1A22FE13

https://bmcpsychiatry.biomedcentral.com/articles/10.1186/s12888-022-03721-9

https://ncbi.nlm.nih.gov/pmc/articles/PMC3153714/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3664784/

Their May be a supplement that may have an anti akathinsia effect
Thought it was worth putting past you as you have get me successes in the past like the Pantathene
Thanks again
Greg Morley
 
Last edited by a moderator:
Messages
44
also I’m getting the hang of the different types of kava now
Got on order
KELIA
MELO MELO
PACIFIC ELIXIR
KELIA IS SUPOSED to be the best cultivar ever created acording to kave experts
I’m getting them from kava society New Zealand
I’ve checked them and ordered from them before.
A bit pricy but at least you know your getting the best
Thanks @Hip
 
Last edited by a moderator:

hapl808

Senior Member
Messages
2,003
I mentioned earlier that Dopamine binding to D1 receptors enhances the excitatory effects that result from glutamate’s interaction with a specific glutamate receptor subtype (i.e., the NMDA receptor). Conversely, activation of D2 receptors normally inhibits the effects induced by glutamate’s binding to another glutamate-receptor subtype (i.e., the AMPA receptor https://www.sciencedirect.com/science/article/abs/pii/S0006899312005112 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826820/

I wonder if some of this could be involved in the stimulating aspects of PEM - where an enjoyable stimulating activity later leads to an awful crash. Is D1 or D2 more involved in activity versus recovery or something else? With the success of LDA in some people, it definitely seems like a lever that's involved somehow.

Likewise with Spanish saffron, a pretty effective dopamine boosting antidepressant, which I often take to boost mood.

Can't say I've noticed anything with saffron, although I haven't taken higher dosages.
 

Cipher

Senior Member
Messages
806
If you have any ideas on how to reduce the akathinsia I would be very greatful.
Since akathinsia is very similar to restless legs syndrome, you might find this post interesting. After a quick google search I found this case-report:

Improvement in neuroleptic‐induced akathisia with intravenous iron treatment in a patient with iron deficiency​

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2117825/


Iron deficiency may play a role in the pathogenesis of drug‐induced akathisia, but the evidence is conflicting.1,2,3 There have been no reports of the effect of iron treatment in this condition. We report the case of a patient with iron deficiency whose akathisia had not responded to standard interventions but did respond dramatically to intravenous iron treatment.

A 68‐year‐old man with schizophrenia had been well controlled for 10 years on thioridazine 150 mg/day. His treatment was changed to respiridone 1 mg twice daily. Within 2 weeks, he had developed a severe sensation of inner restlessness and anxiety associated with increased leg movements and body rocking. No depressive or psychotic symptoms were noticed, although the patient was greatly distressed. Acute drug‐induced akathisia was diagnosed.

No improvement in akathisia symptoms was noticed when the dose of respiridone was reduced or when respiridone was discontinued and thioridazine restarted. Therapeutic trials of alprazolam, benztropine and propranolol failed to alleviate his symptoms and led to side effects.

When seen in our clinic, the patient had had symptoms for >6 months. He reported a “terrible feeling” of restlessness and anxiety “gnawing inside me” each day. Symptoms were present throughout the day, with no worsening at night, and no limb paraesthesias were noticed. There was no personal or family history suggestive of restless legs syndrome (RLS). Neurological examination was normal apart from reduced facial expressiveness. The Barnes Akathisia Rating Scale (BARS), a well‐validated scale of akathisia severity comprising objective and subjective components, was 11/14, which is consistent with severe akathisia.2

Electrolytes, serum urea, creatinine and glucose, thyroid function tests, erythrocyte sedimentation rate, C reactive protein, vitamin B12, and folate levels were normal. Haemoglobin was 13.1 g% (abnormal in our laboratory <13 g%), transferrin saturation 12% (abnormal <15%), serum ferritin 36 μg/l (abnormal <12 μg/l), total iron‐binding capacity 490 μg/l (abnormal >400 μg/l) and serum iron 520 μg/l (abnormal <600 μg/l). A diagnosis of iron deficiency was made on the basis of the abnormal transferrin saturation combined with a serum ferritin <50 μg/l.4 Gastrointestinal examination was normal and serial tests for faecal occult blood were negative. He had a distant history of peptic ulcer disease. Dietary history showed inadequate intake of iron‐containing foods. His dentition was poor. The patient refused endoscopic investigation of the intestinal tract. Screening tests for coeliac disease were negative.

Oral iron supplements caused unacceptable nausea and epigastric discomfort. The patient was given 400 mg intravenous ferrous sucrose in divided doses (100 mg in 100 ml normal saline on days 1 and 3, and 200 mg on day 5). On day 7, the patient reported that he felt normal for the first time in months. The BARS score was now 3/14 (corresponding to mild or questionable akathisia); haemoglobin was 13.8 g%, ferritin 52 μg/l and transferrin saturation 17%. Dietary advice was given to increase the intake of iron‐containing food. Subsequently, he was able to tolerate 300 mg ferrous gluconate (containing 35 mg of elemental iron) every second day. Clinical (BARS score 3/14) and haematological (haemoglobin 13.7 g% and ferritin 68 μg/l) improvement were maintained on review at 5 months.

Both akathisia and RLS are characterised by motor restlessness and sleep disturbances, and RLS can be precipitated by dopamine‐blocking drugs. There is convincing evidence that iron status is an important factor in the pathogenesis of RLS, and correction of iron deficiency improves symptoms in RLS.5 The balance of evidence from previous studies does not suggest that iron deficiency plays a similarly critical role in the development of drug‐induced akathisia in most patients. However, many studies either focused on serum iron,1,2 which is not a good guide to iron status, or used an inappropriately low cut‐off for normal serum ferritin.4 Nevertheless, studies that examined ferritin levels reported that patients with akathisia had lower levels than controls without akathisia.3

Studies comparing blood tests with bone marrow examination have shown that serum ferritin at a cut‐off of 50 μg/l is the best screening test for iron deficiency in patients with and without anaemia.4 Furthermore, serum ferritin <50 μg/l has also proved useful for predicting responsiveness to iron supplementation in people with RLS.5

The patient in this report had several haematological indices suggestive of iron deficiency and several risk factors for iron deficiency. His serum ferritin of 36 μg/l is also consistent with mild iron deficiency. His haemoglobin level of 13.1 g% was at the low end of normality for a man. As a general rule, 8 mg of storage iron corresponds to 1 μg/l ferritin. Thus, in an iron replete person, 400 mg of intravenous iron would lead to a rise in serum ferritin of about 50 μg/l; the relatively small rise in ferritin levels in our patient suggests that the iron supplement was indeed used to correct a tissue deficiency in iron.

It is unlikely that this patient had an atypical RLS. No night‐time worsening of symptoms (a necessary diagnostic feature in RLS) was noticed. The feeling of inner restlessness and body rocking are characteristic of acute drug‐induced akathisia. It is not uncommon for akathisia, once provoked, to fail to resolve when the precipitating drug change is reversed.

The close temporal relationship between administration of intravenous iron and resolution of hitherto resistant symptoms in our patient suggests that iron deficiency can contribute to the development or persistence of akathisia in some patients. Iron repletion may be valuable in such cases, although this requires further evaluation. There are, of course, other potential benefits to treating and identifying the cause of iron deficiency. We suggest that haemoglobin, serum ferritin and transferrin saturation should be checked in patients with akathisia, and that patients with iron deficiency should be treated until haemoglobin is normal and serum ferritin is more than 50 μg/l. Although the use of intravenous iron formulations may facilitate examination of the potential effects of iron repletion on akathisia in future studies, biochemical improvement is usually seen within 2–4 weeks of starting oral iron supplements in patients with deficiency and this should remain the initial treatment.
 

Hip

Senior Member
Messages
17,790
Hi Hip and all,

Unfortunately I am not able to read long and complicated posts; my brain fog has become worse since getting COVID, so I am more limited in what I can read.

I can only read simple posts where someone says "treatment X can help ME/CFS; here is a link to some anecdotal / published study evidence of it working for ME/CFS; and here is a brief explanation of why it works".

Also, long paragraphs detailing how certain vitamins or supplements affect multiple metabolic pathways does not mean much; most vitamins have hundreds of effects in the body.
 
Last edited:

datadragon

Senior Member
Messages
389
Location
East Coast, USA
Also, long paragraphs detailing how certain vitamins or supplements affect multiple metabolic pathways does not mean much; most vitamins have hundreds of effects in the body.
That is the point... so what happens when a specific nutrient (zinc) is made unavailable to utilize and made deficient intentionally during inflammation/infection and then it becomes prolonged? ...potentially hundreds of downstream effects all at the same time that can explain most of what people are experiencing with me/cfs. Interferon-y (intensive exercise also is ifn-y), Interferon-α (IFN-a) and inflammatory cytokines IL-1β, IL-6 and TNF-a, have all been shown to induce metallothioneins which do this. If you can read the below its just a bit more.

Interferon-y also increases WASF3 levels while reducing zinc availability and uptake at the same time. https://forums.phoenixrising.me/thr...s-chronic-fatigue-syndrome.90582/post-2443910

The cytokine interleukin 6 (IL6) induces the expression of Metallothionein and α2-macroglobulin (A2M) and consequently reduces zinc availability. IL-6 is released during the acute phase of an inflammatory response. This mechanism is beneficial to the acute immune response, however, a long-term decrease in zinc availability may contribute to pathological processes in conditions of chronic inflammation

Interleukin-6 (IL-6) up-regulates the ZIP14 gene expression, which in turn, is responsible for an excess of intracellular zinc and, at the same time, for hypozincemia that accompanies the acute phase response to inflammation and infection. Infection and inflammation produce systemic responses that include hypozincemia and hypoferremia. Interleukin-6 regulates the zinc transporter Zip14 in the liver and contributes to the hypozincemia of the acute-phase response. https://www.pnas.org/doi/10.1073/pnas.0502257102
 
Last edited: