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C667T homozygous but get depressed on methylfolate (metafolin)

methylfolate mthfr c667t

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#1 Squallor

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Posted 14 July 2017 - 08:20 AM


I recently did a 23andme genetic test and plugged it into genetic genie to get my mutations.

 

A brief history on me; I'm a 29 year old male who has suffered from bipolar depression, OCD and ADHD PI with low motivation despite having hobbies that I love to do. I've struggled with drive despite having such a strong desire to achieve so much and it pains me because I know I'm not lazy. I've had periods of my life where I was firing on all cylinders in regards to my goals. I've got a good growth mindset and thats helped me.

 

I was taking lithium carbonate for 6 years (1200mg) and it helped immensely with my motivation and anhedonia. I was able to pursue my dreams and not feel unmotivated. I've been off lithium for a year now to due me being scared for my kidneys and thyroid and since then my motivation has been stifled and the anhedonia has come back. I've tried lithium orotate and it doesnt seem to work like carbonate did.

 

So I decided to try some genetic testing and see what I can do about it through natural supplementation rather than relying on pharmaceuticals. I've been reading about methylation and decided to get my genes tested through 23andme and lo and behold, I have an mthfr defect (homozygous for C677T). 

 

The issue is though whenever I take methylfolate in higher than 400mcg doses, I get extremely depressed. Like a serotonin deficiency like depression. I feel sad and crave sugar. I've even tried it with methylcobalamin and its worse, and with hydroxyb12. 

 

I do eat a lot of vegetables and my diet is on point for the most part. Do I need to supplement with methylfolate even if I do have this mutation? 

 

So basically my issue is that I don't want to feel anhedonic and low motivation, yet when I try methylfolate, I get worse. Any suggestions?

 

Any help is greatly appreciated. I was thinking about going back on psychiatric medication. 

 

Here are my mutations

 

COMT V158M rs4680 AG +/-
COMT H62H rs4633 CT +/-

COMT P199P rs769224 GG -/-
VDR Bsm rs1544410 CT +/-
VDR Taq rs731236 AG +/-

MAO-A R297R rs6323 TT +/+
ACAT1-02 rs3741049 GG -/-
MTHFR C677T rs1801133 AA +/+
MTHFR 03 P39P rs2066470 GG -/-
MTHFR A1298C rs1801131 TT -/-
MTR A2756G rs1805087 AA -/-

MTRR A66G rs1801394 GG +/+
MTRR H595Y rs10380 __ no call
MTRR K350A rs162036 AA -/-
MTRR R415T rs2287780 __ no call
MTRR A664A rs1802059 AG +/-
BHMT-02 rs567754 CT +/-

BHMT-04 rs617219 __ no call
BHMT-08 rs651852 CT +/-
AHCY-01 rs819147 CT +/-

AHCY-02 rs819134 __ no call
AHCY-19 rs819171 CT +/-
CBS C699T rs234706 AG +/-
CBS A360A rs1801181 GG -/-

CBS N212N rs2298758 __ no call
SHMT1 C1420T rs1979277 __ no call

 

 


Edited by Squallor, 14 July 2017 - 08:22 AM.


#2 monowav

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Posted 14 July 2017 - 12:54 PM

just because you have a predisposition doesn't mean you are expressing it. I'd stop what makes me feel worse.



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#3 jack black

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Posted 14 July 2017 - 01:24 PM

What happens when you take 400mcg or below?

#4 Squallor

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Posted 14 July 2017 - 11:47 PM

I still feel the same. Only slightly less depressed.

#5 airplanepeanuts

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Posted 15 July 2017 - 12:35 AM

I don't have the mutation but have tried MF. It's supposed to induce Methylfolate trap, and I think one can actually feel that it's induces a metabolic cul-de-sac situation. My advise would be to try folinic acid which feels a lot smoother and does not affect mood noticeably.


Edited by airplanepeanuts, 15 July 2017 - 12:36 AM.


#6 Squallor

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Posted 15 July 2017 - 11:30 AM

I've tried folinic acid and feel worse on it. The only time I feel 'normal' is when I have coffee but the effect usually lasts for an hour. Tyrosine helped me as well but it stops working pretty quick.
I also can't handle cholinergics and I can't even eat more than 2 eggs without getting brain fog.

#7 jack black

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Posted 15 July 2017 - 12:31 PM

It's possible your mental problems have nothing to do with methylation. But if your serum homocysteine is elevated, i think you should take methylfolate in low doses even if no subjective benefits.

How about restarting Lithium in a smaller dose?. I'm getting some effects from just 150mg a day. Lithium is the only thing I'm aware that protects from brain loss in bipolar. Lamictal is the next best thing. Disclosure: I have no bipolar, at least not in the sense it's defined now.

Edited by jack black, 15 July 2017 - 12:38 PM.


#8 Squallor

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Posted 15 July 2017 - 01:20 PM

I was beginning to think that methylation wasn't causing my mental issues too.
I am considering lithium but would it really be worth taking in such small doses.
Im also worried about my thyroid because I'm prone to hypothyroid as I have been in the past.

#9 jack black

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Posted 15 July 2017 - 03:25 PM

Start lithium, if hypothyroid, switch to lamictal.
It's beneficial even in small doses, but obviously full doses are needed for full blown bipolar.
Maybe there's value in profilactic low dose treatment?

Edited by jack black, 15 July 2017 - 03:28 PM.


#10 Robt800

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Posted 15 July 2017 - 08:38 PM

My advice would be to read up on phoenixrising.me if you haven't already. I'm heterogeneous for c677t and supplement Methylb12 and folate as well as supporting supplements (mainly B6 and b2). My wife has 1 a1298c snp so follows a similar protocol.

We have both found supplementing potassium to be crucial. This is well documented on phoenixrising. The main issue appears to be that as methylation startups, cell replication and division really steps up and potassium seems critical to building proteins.
I eat loads of potatoes, green bananas and plantains and still need some supplemental potassium. My mood drops through the floor without it!

Something for you to look into, hope it helps
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#11 Squallor

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Posted 15 July 2017 - 08:58 PM

I get around 10000 mg of potassium per day according to myfitnesspal just through food alone and I do supplement with lite salt and potassium gluconate on top of that. And I made a similar thread on phoenix rising about a week ago and it was deleted due to me not saying I have me/cfs

Im interested in trying lamictal but hesitant due to me not wanting to be on any prescribed medication and some stories I've read online.

And I've also had my homocystein levels checked and they were normal so I'm not sure if I should be supplementing extra folate. I've also been eating a diet very high in vegetables for the last 5 years. It's almost a paleo type diet but I do allow not paleo food when I feel like it

Edited by Squallor, 15 July 2017 - 09:03 PM.


#12 Squallor

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Posted 16 July 2017 - 11:10 PM

Anyone had experience with lamictal?
I'm looking for something long term

#13 jjnz

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Posted 17 July 2017 - 07:53 AM

"I also can't handle cholinergics and I can't even eat more than 2 eggs without getting brain fog."

 

Stab in the dark but check for rs1799807 and rs1803274 , if you are k variant or likely to produce low butylcholine=>acetylcholine[/size]
then read
https://sites.google...rase-inhibitors
Your com-t genes look ok which is different to the boat im in and still trying to navigate my way out of.
My neurotransmitters hang around for a long time and dont get broken down early enough(comt) and taking cholinesterase inhibitors can make this worse.
 
I went through a major trauma when I gave up smoking and I suspect my vagus nerve was inhibited when my smoking cessation stopped signalling the Nicotinic acetylcholine receptor.

My memory has been crap since . helps when I use tyrosine to increase dopamine despite years of depression made worse by ssnri's

 


Edited by jjnz, 17 July 2017 - 07:58 AM.

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#14 jack black

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Posted 17 July 2017 - 04:23 PM

Anyone had experience with lamictal?
 

 

https://www.drugs.co...ts/lamotrigine/

http://www.everydayh...amictal/reviews

do you need any more?
 



#15 Squallor

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Posted 17 July 2017 - 10:30 PM

Jinz: that's very interesting. I'll post my complete nutrahacker report later. I don't think I found those genes on it though.
It might be a valid theory as I have been eating a lot of nightshades for the past year or so. I have tomatoes virtually everyday. And I have been using nicotine in 2 mg amounts which helps the motivation temporarily.
Apart from giving up nightshades for a while (which is going to be a challenge for me due to me liking them), is there a way to increase the choline breakdown.
I've tried racetams but they didn't really work.

Jack black: thanks for that I'll check it out
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#16 Squallor

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Posted 19 July 2017 - 05:39 AM

This is my nutrahacker report. 

 

Attached File  nuhack1.jpg   302.61KB   1 downloadsAttached File  nuhack2.jpg   232.67KB   1 downloadsAttached File  nuhack3.jpg   298.41KB   1 downloadsAttached File  nuhack5.jpg   220.81KB   1 downloadsAttached File  nuhack6.jpg   202.49KB   1 downloadsAttached File  nuhack7.jpg   229.92KB   1 downloadsAttached File  nuhack8.jpg   160.61KB   0 downloadsAttached File  nuhack9.jpg   248.6KB   1 downloads


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#17 jjnz

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Posted 19 July 2017 - 10:22 AM

Cool ! Havent seen nutrihacker before

You have the rs 578776 as me, the smoking buzz gene :) I assume you don't smoke but if you do it might pay to give up slowly rather than all in one go.

your rs2236225 and rs6922269 should have you needing more choline so your reaction is interesting. I dare say there's a lot more to it than we see in your genes though.

if you go to your 23and me data you should be able to see your rs1799803 status, else try promethiase which I think is still free if you use their desktop version

 

 

 

 


Edited by jjnz, 19 July 2017 - 10:24 AM.

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#18 Squallor

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Posted 19 July 2017 - 11:23 AM

So for my rs1799807 its:

 

BCHE rs1799807 165548529 C or T

T / T

And my rs1803274 is:

 

 

BCHE rs1803274 165491280 C or T C / T
 

 

 

 

 

 

 

 

 

I don't smoke but I use nicotine in 2mg lozenge form a day. I never go over 2mg a day. And yes, I do get a huge buzz from nicotine itself; makes me feel 'normal' and happy, if only for a while (30 minutes)

 

I also recently tried inositol and it made me feel very depressed. I tried also taking fish oil again due to its health benefits but I get extreme brain fog the next day. Everything is pointing to choline intolerance or too much of it. A few years back, I did supplement with choline for a while but you'd think that wouldnt matter now.

Also, I am an extremely empathetic person, something that I read acetylcholine dominant types are.



#19 jjnz

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Posted 20 July 2017 - 03:17 AM

Your 1799803 is good but you do have the BUche K variant which is still being researched but worth keeping an eye on the research for that.

I have the empathy issue too :) it's a good thing , even if no one else gets it.

I can't get nootropics here in NZ but I occasionally take 5htp or tyrosine to mix things up a bit, tried ashwaganda ,ginkgo, schisandra, theanine, taurine, honestly I can't say it makes much difference. It seems the more wired I get the harder it is to stay focussed on one thing. Coffee seems to be the best thing.

Off topic but where do you get your nicotine lozengers?


Edited by jjnz, 20 July 2017 - 03:17 AM.


#20 Squallor

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Posted 20 July 2017 - 08:50 AM

I get them from chemist warehouse, they're 2mg nicorette lozenges.

 

Tyrosine works for me sometimes but its unpredictable. But when it does work, its AMAZING. 

I don't know about 5htp though. I feel lousy the next day when I take 50mg at night before bed, I wonder if theres a "right" amount and balance I can take of these supplements to help balance my neurochemistry. 

I've heard of the 10 to 1 ratio of tyrosine to 5htp but i think i might be different.

 

Edit: I should also add that I half the lozenge so its 1mg. Taking 2mg all at once makes me spacey and wired because my tolerance is low and I intend to keep it that way. I barely feel caffeine so I'm not going down that way with nicotine.


Edited by Squallor, 20 July 2017 - 08:52 AM.

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#21 Iuvenale

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Posted 20 July 2017 - 04:53 PM

If caffeine makes you feel better, you might want to check this SNP, which increases adenosine (caffeine decreases it).

rs73598374
The T (minor) allele is associated with:
* 35% lower levels of ADA. People with the T allele show a higher level of both circulating adenosine and adenosine inside cells ®.
* Reduced conversion of adenosine to inosine , which serves as an antioxidant and stimulant. Only 5% of the alleles in the global population are T, so it's relatively rare. More adenosine translates into increased slow-wave sleep in individuals with the T allele ®.
* Worsened performance on a test of attention among right-handed carriers ®.
* Reduced attention and vigor when awake. Also, EEG alpha activity (8.5-12 Hz), sleepiness, fatigue, and α-amylase in saliva were enhanced ®.
* Significantly higher deep sleep and EEG 0.75- to 1.5-Hz oscillations in non-REM sleep. When awake, attention and vigor were reduced. EEG alpha activity (8.5-12 Hz), sleepiness, fatigue, and Œ-amylase in saliva were enhanced ®.
* Better sleep, but more fatigue in the day due to higher adenosine levels.
* Lower telomerase activity ®, which will cause shorter telomeres.
* A higher likelihood for males to live between 66-88 years, but a lower likelihood for men to live longer than 88 years ®. It’s believed that elevated cellular concentrations of adenosine reduce heart disease risk, as well as help during a stroke ®.
* Higher rates of glycolysis, which may increase the number of metabolic calories and, in turn, reduce activation of Sirtuin genes ®.

#22 Squallor

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Posted 20 July 2017 - 11:09 PM

If caffeine makes you feel better, you might want to check this SNP, which increases adenosine (caffeine decreases it).

rs73598374
The T (minor) allele is associated with:
* 35% lower levels of ADA. People with the T allele show a higher level of both circulating adenosine and adenosine inside cells ®.
* Reduced conversion of adenosine to inosine , which serves as an antioxidant and stimulant. Only 5% of the alleles in the global population are T, so it's relatively rare. More adenosine translates into increased slow-wave sleep in individuals with the T allele ®.
* Worsened performance on a test of attention among right-handed carriers ®.
* Reduced attention and vigor when awake. Also, EEG alpha activity (8.5-12 Hz), sleepiness, fatigue, and α-amylase in saliva were enhanced ®.
* Significantly higher deep sleep and EEG 0.75- to 1.5-Hz oscillations in non-REM sleep. When awake, attention and vigor were reduced. EEG alpha activity (8.5-12 Hz), sleepiness, fatigue, and Œ-amylase in saliva were enhanced ®.
* Better sleep, but more fatigue in the day due to higher adenosine levels.
* Lower telomerase activity ®, which will cause shorter telomeres.
* A higher likelihood for males to live between 66-88 years, but a lower likelihood for men to live longer than 88 years ®. It’s believed that elevated cellular concentrations of adenosine reduce heart disease risk, as well as help during a stroke ®.
* Higher rates of glycolysis, which may increase the number of metabolic calories and, in turn, reduce activation of Sirtuin genes ®.




I checked that gene and I'm C/T for it. So does that mean it's a mutated gene?

Took 500 mg tyrosine and 50 mg 5htp this morning on an empty stomach.
Felt a little drowsy and had a little brain fog, a bit spaced out, but I noticed my social anxiety decreased. I was able to interact with co workers with less of the negative 'theyll judge me' self talk.
Apart from that, I don't notice too much of mood lift.
Today I'm seeing my doctor to refer me to a psychiatrist so I can sort this out.
I've been really hesitant to see a shrink because I don't want to be put on meds and rely on them. I feel like it's covering up a nutritional issue that I might have but I take my vitamins and eat very clean and I still suffer from this anhedonic low motivation state.

#23 iseethelight

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Posted 20 July 2017 - 11:53 PM

 

If caffeine makes you feel better, you might want to check this SNP, which increases adenosine (caffeine decreases it).

rs73598374
The T (minor) allele is associated with:
* 35% lower levels of ADA. People with the T allele show a higher level of both circulating adenosine and adenosine inside cells ®.
* Reduced conversion of adenosine to inosine , which serves as an antioxidant and stimulant. Only 5% of the alleles in the global population are T, so it's relatively rare. More adenosine translates into increased slow-wave sleep in individuals with the T allele ®.
* Worsened performance on a test of attention among right-handed carriers ®.
* Reduced attention and vigor when awake. Also, EEG alpha activity (8.5-12 Hz), sleepiness, fatigue, and α-amylase in saliva were enhanced ®.
* Significantly higher deep sleep and EEG 0.75- to 1.5-Hz oscillations in non-REM sleep. When awake, attention and vigor were reduced. EEG alpha activity (8.5-12 Hz), sleepiness, fatigue, and Œ-amylase in saliva were enhanced ®.
* Better sleep, but more fatigue in the day due to higher adenosine levels.
* Lower telomerase activity ®, which will cause shorter telomeres.
* A higher likelihood for males to live between 66-88 years, but a lower likelihood for men to live longer than 88 years ®. It’s believed that elevated cellular concentrations of adenosine reduce heart disease risk, as well as help during a stroke ®.
* Higher rates of glycolysis, which may increase the number of metabolic calories and, in turn, reduce activation of Sirtuin genes ®.




I checked that gene and I'm C/T for it. So does that mean it's a mutated gene?

Took 500 mg tyrosine and 50 mg 5htp this morning on an empty stomach.
Felt a little drowsy and had a little brain fog, a bit spaced out, but I noticed my social anxiety decreased. I was able to interact with co workers with less of the negative 'theyll judge me' self talk.
Apart from that, I don't notice too much of mood lift.
Today I'm seeing my doctor to refer me to a psychiatrist so I can sort this out.
I've been really hesitant to see a shrink because I don't want to be put on meds and rely on them. I feel like it's covering up a nutritional issue that I might have but I take my vitamins and eat very clean and I still suffer from this anhedonic low motivation state.

 

 

Tyrosine doesn't really increase dopamine. 

 

When it comes to the topic of actually increasing dopamine and adrenaline outright, L-tyrosine does not seem to hold much promise. The synthesis of catecholamines is highly regulated in the body and in particular the one enzyme that converts L-tyrosine into the next metabolite, L-DOPA, so simply increasing the amount of L-tyrosine in your body does not necessarily increase catecholamine production.

 

https://examine.com/...nts/l-tyrosine/



#24 Squallor

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Posted 21 July 2017 - 12:13 AM

Whether it increases dopamine or not I'm not really well versed to say on the matter, but I do notice improvement in focus and motivation but it's inconsistent. It might be an increase in thyroid production too.

#25 Iuvenale

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Posted 21 July 2017 - 03:26 AM

Yes, it means that you have the relatively rare T allele (5%). You should experiment with caffeine, theophylline, and theobromine (both found in cocoa). Also, take inosine, as we C/Ts are low in it.

#26 Squallor

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Posted 21 July 2017 - 06:19 AM

I'm all over caffeine. 

 

Never heard of inosine before so thanks for the suggestion. 



#27 jjnz

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Posted 21 July 2017 - 11:01 AM

I too suffer from self talk but it's only occasional and usually 2 things have to happen.

1/ I'm doing something where I don't have to think too much, weeding a garden/ pushing a lawnmower.

2/My observation is that Tyrosine and methylfolate ( ie truckloads of spinach) will take me over that way, where as vit b2 /or b3 niacin will seem to calm me down.

I think this is tied up with methylation rather than neurotx's but I'm never sure how much to read into methylation, every quack on the internet is an expert on it, I do wonder though because I have severe osteoporosis and no one can find a cause  

 

If I take tyrosine I take it on an empty stomach and with b6, never with htp because thats driving both neurotransmitters up.

I wonder if the effect is gut mediated because I agree there is an effect. I see people saying the same thing about GABA, it dosent cross the BBB, yet there definitely an effect to be had, parasympathetic feedback from gut ganglia or leaky BBB, who knows.

 

For me I'd relate self talk to too much dopamine rather than not enough serotonin but I dont know. I get pretty hyper on beer and that usually a GABA promotor , Have you tried theanine ? 



#28 Squallor

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Posted 21 July 2017 - 01:17 PM

Tried theanine. Don't remember the experience but it wasn't a good one.
I've also been a little withdrawn and timid. Used to be funny and quirky and I enjoyed talking to the others but now I have this air of distrust to people and I have pretty bad avoidant personality disorder which makes me look weak and overly agreeable.
I feel like I can't disagree with anything.

#29 Iuvenale

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Posted 21 July 2017 - 01:30 PM

I have been drinking coffee for years, but when I found out I was C/T for rs73598374 I started taking caffeine pills and it has made a HUGE difference. I am less irritable and I actually want to do things, rather than be lazy. I don't feel like I have to force myself to perform tasks even though I'd rather just lie down and sleep. I also have more energy in the afternoon (adenosine builds up over the course of the day, and in C/Ts it builds up much faster). Caffeine also, paradoxically, helps people who are C/T sleep better. 

 

Also, as a C/T, caffeine might help prolong your lifespan. Adenosine reduces the length of telomeres. See this video: https://chrismasterj...can-save-life/ 

 


Edited by Iuvenale, 21 July 2017 - 01:33 PM.


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#30 Squallor

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Posted 21 July 2017 - 09:37 PM

I do notice that I get more depressed when I try to lower my caffeine intake. Explains why.

I'll be jumping on lithium carbonate again and see how I go. I just hope my thyroid remains well so I'll continue making sure my iodine and selenium levels are good.




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