zinc and MS

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jimmylegs
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Re: zinc and MS

Post by jimmylegs » Sat Feb 11, 2017 6:20 pm

i just went over copper zinc ratios in an ms study. i was calculating zn:cu vs cu:zn as for that alzheimer's analysis above. thought i would flip the numbers here for the record
Ghazavi, A., Kianbakht, S., Ghasami, K., & Mosayebi, G. (2012). High copper and low zinc serum levels in Iranian patients with multiple sclerosis: a case control study. Clin Lab, 58(1-2), 161-164.
http://bit.ly/2lwAcyR

Table 1
........................MS...:.................SPMS...:...............RRMS...:............Controls
Zn level (µg/dL)....40.17 ±31.89a........23.12 ±10.59c.......42.06 ±32.94.......127.77 ±42.2
Cu level (µg/dL)..114.05 ±42b...........126.14 ±44.20......111.22 ±39.45.........91.3 ±37
note the completely inverted copper zinc ratios, bad for RRMS and TERRIBLE for SPMS
cu:zn
Controls......91.3 / 127.8 = 0.71 (as you head for cu:zn of 1, you're getting close to danger zone; this is unusually good)
RRMS..........111.2 / 42.1 = 2.6 (really high)
MS.............114.1 / 40.2 = 2.8 (splitting the difference between RRMS and SPMS)
SPMS..........126.1 / 23.1 = 5.5 (ouch! makes sense that this one is worst of all)

from other sources, optimal = 0.7-1.0

man. alzheimer's cu:zn ratios got NOTHIN on MS cu:zn ratios. we're a mess.
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2017 review: Zinc in Infection and Inflammation

Post by jimmylegs » Wed Sep 20, 2017 7:10 am

Zinc in Infection and Inflammation (2017)
free full text: http://www.mdpi.com/2072-6643/9/6/624/htm

Abstract: Micronutrient homeostasis is a key factor in maintaining a healthy immune system. Zinc is an essential micronutrient that is involved in the regulation of the innate and adaptive immune responses. The main cause of zinc deficiency is malnutrition. Zinc deficiency leads to cell-mediated immune dysfunctions among other manifestations. Consequently, such dysfunctions lead to a worse outcome in the response towards bacterial infection and sepsis. For instance, zinc is an essential component of the pathogen-eliminating signal transduction pathways leading to neutrophil extracellular traps (NET) formation, as well as inducing cell-mediated immunity over humoral immunity by regulating specific factors of differentiation. Additionally, zinc deficiency plays a role in inflammation, mainly elevating inflammatory response as well as damage to host tissue. Zinc is involved in the modulation of the proinflammatory response by targeting Nuclear Factor Kappa B (NF-κB), a transcription factor that is the master regulator of proinflammatory responses. It is also involved in controlling oxidative stress and regulating inflammatory cytokines. Zinc plays an intricate function during an immune response and its homeostasis is critical for sustaining proper immune function. This review will summarize the latest findings concerning the role of this micronutrient during the course of infections and inflammatory response and how the immune system modulates zinc depending on different stimuli.

related very interesting reference:

Scientific Opinion on Dietary Reference Values for zinc
EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA)
https://www.efsa.europa.eu/sites/defaul ... 14%2C0.pdf

in particular
Table 8: Average dietary zinc requirements depending on phytate intake and body weight

related tables of interest
Table 1: Criteria for categorising diets according to their potential absorption efficiency of zinc (adapted from WHO/FAO (2004))
Table 2: Overview of Dietary Reference Values for zinc for adults (especially the range of daily intake recommendations based on source bioavailability)

really great specifics on how best to manage zinc intakes in a variety of paleo, non paleo, omnivore and vegetarian/vegan settings.

this source gives the thumbs down to serum zinc as a useful indicator of zinc status. however, i've still seen enough studies in which healthy controls had high normal zinc, that it will take a bit more reading before i'm even potentially going to consider the low end of the serum zinc normal range as a desirable place to be. especially when getting serum zinc into the upper teens finally dislodged my serum uric acid level from its recalcitrant low normal level associated with ms (ie 194 in my case) and closer to levels enjoyed by healthy controls (278 in my case).
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Re: zinc and MS

Post by jimmylegs » Fri Oct 27, 2017 12:58 pm

well this one certainly appears to go against the grain. possible connection to elevated copper zinc ratio? we've learned elsewhere that zinc deficit contributes to iron dysregulation/deposition. will bear looking into.

The Emerging Role of Zinc in the Pathogenesis of Multiple Sclerosis
http://www.mdpi.com/1422-0067/18/10/2070/htm
Abstract: Our lab has previously demonstrated that multiple sclerosis-induced spinal cord white matter damage and motor deficits are mediated by the pathological disruption of zinc homeostasis. Abnormal vesicular zinc release and intracellular zinc accumulation may mediate several steps in the pathophysiological processes of multiple sclerosis (MS), such as matrix metallopeptidase 9 (MMP-9) activation, blood-brain barrier (BBB) disruption, and subsequent immune cell infiltration from peripheral systems. Oral administration of a zinc chelator decreased BBB disruption, immune cell infiltration, and spinal white matter myelin destruction. Therefore, we hypothesized that zinc released into the extracellular space during MS progression is involved in destruction of the myelin sheath in spinal cord white mater and in generation of motor deficits. To confirm our previous study, we employed zinc transporter 3 (ZnT3) knockout mice to test whether vesicular zinc depletion shows protective effects on multiple sclerosis-induced white matter damage and motor deficits. ZnT3 gene deletion profoundly reduced the daily clinical score of experimental autoimmune encephalomyelitis (EAE) by suppression of inflammation and demyelination in the spinal cord. ZnT3 gene deletion also remarkably inhibited formation of multiple sclerosis-associated aberrant synaptic zinc patches, MMP-9 activation, and BBB disruption. These two studies strongly support our hypothesis that zinc release from presynaptic terminals may be involved in multiple sclerosis pathogenesis. Further studies will no doubt continue to add mechanistic detail to this process and with luck, clarify how these observations may lead to development of novel therapeutic approaches for the treatment of multiple sclerosis.
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Re: zinc and MS

Post by NHE » Sat Oct 28, 2017 6:07 am

jimmylegs wrote:well this one certainly appears to go against the grain.
Well, after ~ 20 some days of taking 30 mg Zn/day my mobility is noticeably worse. It might be time to give it a break and see what happens.

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Re: zinc and MS

Post by jimmylegs » Sat Oct 28, 2017 10:43 am

sounds like no fun. how have your levels been? for serum zinc and copper, to start?
personally, after testing deficient, adding zinc only did me good. most noticeably in cognitive improvements. this is going back a number of years though. i still take zinc, but more sporadically than per doc's instructions when correcting deficiency.
also worth knowing serum ferritin, if one is planning to add zinc to the regimen.
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Re: zinc and MS

Post by jimmylegs » Fri Aug 10, 2018 10:50 am

earlier this year i had a bad serum zinc result. circling the drain at the bottom of what i consider normal range (11.5-18.5). that level was associated with the worst infection (likely the flu) of my life, a really bad episode cognitively, and cranial lesion activity per MRI.

i've since worked to correct zinc status, matching doc's earlier orders from the first time i tested deficient. the first time, my symptoms (difficulty with spatial info processing, felt as a strain behind left eye) were also consistent with concurrent cranial lesion activity, according to my neuro. the family doc's follow-up prescription for zinc repletion sorted out all my cognitive troubles at the time.

those experiences made me wonder if the following recent study (credit to Petr for the find) included cognitive function among its measures of ability or lack thereof in study subjects. i just ran a search for the term 'cognitive' in this study's full text. results: 0. i have not read in detail, but this early info and a super quick literature search https://bit.ly/2Mabe63 suggests that future studies might do well to look at zinc and ms cognition in more detail.

Lower Serum Zinc Levels in Patients with Multiple Sclerosis Compared to Healthy Controls (2018)
http://www.mdpi.com/2072-6643/10/8/967/htm
"Objective: Diminished blood levels of zinc have been reported to be associated with T-cell-mediated autoimmunity, which has been implicated in multiple sclerosis (MS). We aimed to compare the distribution of serum zinc status in MS patients with that in healthy controls (HCs) and to investigate a potential correlation with clinical state, through analysis of serum zinc concentration in MS patients suffering from different disease subtypes. Methods: Serum zinc concentrations of 133 patients with relapsing (RMS) and 18 patients with the progressive form of MS (PMS), according to the McDonald criteria of 2010, were measured. Clinical status was quantified using the Expanded Disability Status Scale (EDSS). Zinc concentrations were also determined in the sera of 50 HCs, matched for age and sex at a group level. Results: MS patients showed significantly lower zinc concentrations (mean (SD)) than HCs (12.5 (2.1) µmol/L vs. 14.6 (2.3) µmol/L, p < 0.001). In contrast, we did not find any difference between RMS (12.4 (2.0) µmol/L) and PMS (13.0 (3.0) µmol/L) cases (p = 0.8 ). Patients receiving disease-modifying treatment showed lower mean (SD) serum zinc levels than untreated cases (12.3 (1.9) µmol/L vs. 13.5 (3.2) µmol/L, p < 0.03). Zinc levels were not related to disease duration, EDSS, annual relapse rate, or the median number of relapses. Conclusions: The data suggest that a diagnosis of MS is related to lower serum zinc concentrations than in HCs, and concentrations were lower still under disease-modifying therapy. However, zinc levels did not predict disease subtypes or disability status"

fwiw, while the ms literature has with near uniformity indicated zinc deficit issues in ms patients, in general the research points repeatedly to 18.2 µmol/L as a suitable serum zinc target for optimal health. i know that when my levels head in that direction, that measurable improvements occur, including for example much improved serum uric acid status.

of course, no one should pursue zinc repletion without understanding their own baseline levels and those of important essentials such as copper and iron.

on a somewhat unrelated note, a connection of mine recently showed me zinc bloodwork. brutal levels: 10.3 µmol/L. according to the local lab's disastrous normal range, this result was mid-normal. by my hospital's standards, clearly deficient. over and over the same story. so frustrating.
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Re: zinc and MS

Post by jimmylegs » Tue Aug 21, 2018 3:18 pm

i interpret the title below as follows: within a subject cohort having low variation of their collectively crap dietary and supplemental zinc intake habits, remaining factors shown to influence serum levels include sex (known), age (also known) and time of day of blood draw (also known)

(if you didn't know, morning fasting serum zinc is your best case scenario so if your morning fasting zinc level sucks, it's even worse the rest of the day.

Serum Zinc Concentrations in the US Population Are Related to Sex, Age, and Time of Blood Draw but Not Dietary or Supplemental Zinc
https://academic.oup.com/jn/article/148/8/1341/5045841
"Mean ± SE serum zinc concentrations in males and females were 84.9 ± 0.8 and 80.6 ± 0.6 μg/dL, respectively (P < 0.0001)."

booooooo not good enough.
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36 years of zinc/MS research

Post by jimmylegs » Tue Oct 30, 2018 12:42 pm

a quick zinc meta analysis

1. Lower Serum Zinc Levels in Patients with Multiple Sclerosis Compared to Healthy Controls (2018)
MS patients showed significantly lower zinc concentrations (mean (SD)) than HCs (12.5 (2.1) µmol/L vs. 14.6 (2.3) µmol/L, p < 0.001). In contrast, we did not find any difference between RMS (12.4 (2.0) µmol/L) and PMS (13.0 (3.0) µmol/L) cases (p = 0.8 ).
2. Zinc in Multiple Sclerosis (2016)
The result of the meta-analysis shows a reduction in serum or plasma Zn levels in patients with MS with a 95% CI of [−3.66, −0.93] and a p value of .001 for the difference in Zn concentration in μM. One of six studies measuring cerebrospinal fluid, Zn levels found a significant increase in patients with MS with controls. The studies measuring whole blood and erythrocyte Zn levels found up to several times higher levels of Zn in patients with MS compared with healthy controls with decreasing levels during attacks in relapsing-remitting MS patients.
focusing mostly on serum here. whole blood and RBC can have a turn later.

3. INVESTIGATION THE AMOUNT OF COPPER, LEAD, ZINC AND CADMIUM LEVELS IN SERUM OF IRANIAN MULTIPLE SCLEROSIS PATIENTS (2015)
Table.3.Epidemiologic parameters and concentration of Zinc, Cadmium, Lead and Copper in blood serum (µg/L)

"Significantly higher serum Cu, Zn, and Cd levels were found in MS patients than in the controls (p<0.05)"

Characteristics..Case................Control
......................Mean(±SD)....median....Mean(±SD)....median
Zn..................72.9(±3.76)....73.3.......45.8(±4.28)...42.7
ie patient levels low normal, controls outright deficient. i'm thinking they accidentally reversed the patient and control groups' data here. either that or they did a pretty funky job of selecting controls.

4. Serum level of iron, zinc and copper in patients with multiple sclerosis (2013)

"Mean serum zinc levels were significantly decreased in MS patients (10.92 ± 2.114) as compared to these levels in the control group (14.05 ± 3.2)."
this study isn't indexed anywhere good. for starters, not specifying units is a disqualifier. looks like umol/l, if so numbers are consistent w Pawlitzski et al 2018

5. High copper and low zinc serum levels in Iranian patients with multiple sclerosis: a case control study. (2012)
"Significantly lower serum Zn and higher serum Cu levels were found in the MS patients compared with the controls (p < 0.0001 and p = 0.002, respectively). The serum Zn level of the secondary-progressive MS patients was significantly lower compared with the relapsing-remitting MS patients (p = 0.009)."

..............................pwMS................pwSPMS............pwRRMS..........Controls
Zn level (µg/dL)...40.17 ±31.89a...23.12 ±10.59c...42.06 ±32.94...127.77 ±42.2
makes sense to me. esp controls 127.77


6. Assessment of serum magnesium, copper, and zinc levels in multiple sclerosis (MS) patients (2007)
"Mean serum level of magnesium was 1.87 ± 0.37, copper 110.7 ± 19.5, and zinc 85.4 ± 13.5 in patients (control group), and 2.22 ± 0.24, 133.7 ± 13.4, and 110 ± 8.3 respectively in case group.

Conclusion: We found that serum level of magnesium, copper, and zinc is significantly decreased in patients inflicted with MS."
aaaand that's why you can't get indexed. methods specify "Thirty-five MS patients with definite diagnosis of MS" with "Control group was selected
from matched people of the same age and sex without diseases affecting serum copper, zinc, and magnesium levels."
results characterize the patients as the control group. that's not confusing 7:\
not to mention, even though the raw numbers look appropriate, again no units included. research fail.

7. Zinc in muliple sclerosis (1983)
"Plasma zinc levels were slightly increased in patients with multiple sclerosis and significantly increased in those with other neurological impairments (p <0.01), compared with control subjects. Albumin‐bound as well as protein‐bound zinc levels were normal in all groups tested. The α2 macroglobulin‐bound zinc level was significantly lower (p < 0.01) in patients with multiple sclerosis than in control subjects. Erythrocyte‐bound zinc levels were significantly increased (p < 0.05) in patients with multiple sclerosis when compared with control subjects. Erythrocyte‐bound zinc was normal in patients with other neurological impairments. Because erythrocyte‐bound zinc levels are relatively independent of daily fluctuations in dietary zinc intake, an increase in these values may suggest alterations in the control mechanisms governing zinc compartmentalization in patients with multiple sclerosis."
methods:
patients: clinically definite MS, no drugs, no treatments for any other medical problems
control subjects were healthy volunteers from within the university population
other neuro group included myasthenia gravis, guillain-barre syndrome, dementia, huntington's, etc.
Table I. Mean Values of Zn variables in PwMS, Controls and other neuro patients
group..........plasma zn (ug/dl)...serum zn (ug/dl).
pwms..........84.5......................83.1
controls.......78.8......................81.7
other neuro..96.2......................91.1
nobody's anywhere close to 120 ug/dl; as with Ghoreishi et al above, it is odd that the controls manifest lowest zinc levels. maybe the 'university population' is not the best representation of optimal zinc status in truly healthy controls

8. Trace Elements in Whole Blood of Multiple Sclerosis (1983)
"Zn values are greatly increased in MS patients (by 25-75%). The increase is higher in the relapsing form of MS than in the chronic form, suggesting some connection with the activity of the disease."
i have no access to this one, in order to check their numbers.

9. Zinc and copper in multiple sclerosis (1982)
"The serum concentrations of zinc and copper were measured in 50 patients with multiple sclerosis. Lower serum zinc levels were found compared to age- and sex-matched controls."

................Male wMS.....Male Controls.... Female wMS....Female Controls
Zn (umol/l) 13.0 ...........14.8 ................12.1 ..............13.2
i like 18.2 umol/l

and now for the tally:

.........................................low zn in ms ........ 'high'(ER) zn in ms
good data access and quality......#1 #4 #5 #9........#3 #7 (control levels deficient or low)
poor data access....................#2.......................#8 (can't access specifics for 8 )
poor data quality....................#6

conclusions:
in 4 of 4 studies with good data access and quality, zinc levels are low normal in pwms
in 8 of 9 studies regardless of access/quality, zinc levels are low normal in pwms
in 2 of 3 studies which suggest higher zinc in ms, reported control levels are either deficient or low normal
can't check the data for the third of three studies suggesting high zinc in ms.

so overall as regards serum, we have agreement with the 2016 analysis and further support given this year's findings.

next, to unpack the CNS and RBC pieces. not today mind you.
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Re: 36 years of zinc research

Post by jimmylegs » Tue Oct 30, 2018 5:56 pm

one more bit before getting into the other analyses

summary with units conversions
....patients....controls


1...12.5........14.6 umol/l /.153 v
.....81.7........95.4 ug/dl

2. no specifics

3. study units actually say ug/L. if they mean it, then conversions are as follows:
......1.1...........0.7 umol/l
......7.29.........4.58 ug/dl x.153 ^
so everyone is massively deficient. if they mean ug/dl, then this:
.....11.2..........7.0 umol/l
.....72.9........45.8 ug/dL x.153 ^
in this case, everyone's either very deficient (controls) or nearly so (patients).

4....10.9.........14.1 umol/l /.153 v
......71.2.........92.2 ug/dl

5......6.2.........19.6 umol/l
......40.2.......127.8 ug/dl x.153 ^
kinda makes it look like they got #3 patients and controls reversed doesn't it. it happens. i've confirmed that exact error in a breast cancer meta analysis.

6....13.1.........16.8 umol/l
......85.4.......110.0 ug/dl x.153 ^

7....12.9.........12.1 umol/l
......84.5........78.8 ug/dl x.153 ^
again, just because control levels suck too, doesn't mean pwms levels aren't

8. no data

9....13.0.........14.8 umol/l
......85.0.........96.7 ug/dl

......12.1.........13.2 umol/l
......79.1.........86.3 ug/dl

SO
patient range..........control range (not counting #3's errors and #7's odd 'controls')
..6.2 - 13.1 umol/l......13.2 - 19.6 umol/l
40.2 - 85 ug/dl............86.3 - 127.8 ug/dl

i'm actually kind of amazed the means didn't overlap
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Re: 36 years of zinc research

Post by NHE » Sat Nov 10, 2018 11:55 pm

jimmylegs wrote:3. INVESTIGATION THE AMOUNT OF COPPER, LEAD, ZINC AND CADMIUM LEVELS IN SERUM OF IRANIAN MULTIPLE SCLEROSIS PATIENTS (2015)
https://www.jchps.com/issues/Volume%208 ... 040-45.pdf
You can fix the broken link by substituting %29 for ) as discussed below in the FAQ.

http://www.thisisms.com/forum/site-supp ... ml#p139024

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Re: zinc and MS

Post by jimmylegs » Sat Dec 01, 2018 6:11 am

so i figure out years and years and years ago that the jimmylegs are a zinc deficit thing.

then recently they resurface. what the heck.*then* i get zinc tested. not 'deficient', but circling the drain. then i take a bunch of my newest zinc product which i have been using since my preferred local vendor closed up shop (and doesn't sell them online either hellooo...!?). three a day. retest. level hardly budges. legs are still intermittently jimmyesque.

then, i switch to plain old zinc citrate and THEN for once i actually find zinc picolinate. i have not been retested yet but at this point i do notice that the jimmylegs are gone.

so. the zinc product that seemingly resulted in jimmylegs stays in the mix, not least because it contains some copper. there is none in my zinc citrate, my zinc picolinate, OR my multi. it also stays because maybe it's partly my fault. maybe i let things go so long that the more recent zinc inputs got into serum but were immediately dropped off somewhere important.

the take home message for me, my diet is short on high zinc foods and it is not what you'd call low in things that can interfere with zinc absorption and utilization. i eat phytate laden leafy greens and i eat legumes. i eat normal bread. all in a limited way, but my status quo intake of zinc rich foods is not up to it.

i am trying to gear myself up for a regular trip to happy hour at a local oyster bar, but haven't managed it yet. can't handle the tinned ones. in the meantime, last night's chores included mixing up 8 quarter pound beef-venison patties (all local). i couldnt help it and added some phytates too - spinach and kale. soon it'll be time for another retest and i expect good news at last!
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Re: zinc and MS

Post by THX1138 » Sun Dec 23, 2018 10:39 pm

so i figure out years and years and years ago that the jimmylegs are a zinc deficit thing.
What (or who) are the jimmylegs :?:

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Re: zinc and MS

Post by jimmylegs » Mon Dec 24, 2018 10:49 am

no idea. maybe sporadic focal myoclonus or similar.
take control of your own health
pursue optimal self care at least as actively as a diagnosis
ask for referrals to preventive health care specialists eg dietitians
don't let suboptimal self care muddy any underlying diagnostic picture!

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