Zinc

[Ghost]

Just thought I'd give an update. It's been two months now that I've been taking a consistent dose of zinc, and my PSSD is pretty much gone 90% of the time! Things are still constantly improving too. I don't know if it's because it's been so long (I've been dealing with this for almost seven years), but things are better than I remember. I'd forgotten how good it's supposed to feel! There is still a little anhedonia, but that seems to be going away too.

I'm still taking 15 mg, but I had to switch from Optizinc to zinc gluconate after a month. With Optizinc I noticed pretty rapid improvement, but during the fourth week I started getting headaches, nausea, anxiety and had trouble sleeping. It felt similar to when I was taking zinc picolinate last year, so I think I may have started to get too much zinc. My theory is that these chelates bypass the zinc transporter in the intestines, and instead are absorbed through a different pathway. As a result, they bypass one of the main regulatory mechanisms of zinc homeostasis. Once I switched to zinc gluconate, the problems went away. Three weeks after switching (seven weeks overall) things really started improving. Pretty excited to see where this goes.

Glad you are feeling well!

I've only ever tried Picolinate. Maybe I'll look at getting some Gluconate...

[PeterSv]

Just thought I'd give an update. It's been two months now that I've been taking a consistent dose of zinc, and my PSSD is pretty much gone 90% of the time! Things are still constantly improving too. I don't know if it's because it's been so long (I've been dealing with this for almost seven years), but things are better than I remember. I'd forgotten how good it's supposed to feel! There is still a little anhedonia, but that seems to be going away too.

I'm still taking 15 mg, but I had to switch from Optizinc to zinc gluconate after a month. With Optizinc I noticed pretty rapid improvement, but during the fourth week I started getting headaches, nausea, anxiety and had trouble sleeping. It felt similar to when I was taking zinc picolinate last year, so I think I may have started to get too much zinc. My theory is that these chelates bypass the zinc transporter in the intestines, and instead are absorbed through a different pathway. As a result, they bypass one of the main regulatory mechanisms of zinc homeostasis. Once I switched to zinc gluconate, the problems went away. Three weeks after switching (seven weeks overall) things really started improving. Pretty excited to see where this goes.

Really nice to hear you are improving, great job! Now I am considering testing a low dose of Zinc. But my testosteron numbers from blood work is actually pretty high. S-FSH and S-LH is on the low side though. Do you know if it is still a good thing to do?

[gatogordito]

Yeah, I still think it would be worth giving it a shot. Zinc is cheap and as long as you don't take too much it shouldn't cause any harm. Just be patient and give it at least a month.

[PeterSv]

Thanks, I will try for a period and see what happens!

[gatogordito]

I've done a lot of research over the past year on zinc trying to figure out why it is so effective for me, and I thought I'd share some of my findings.

First off, people who are depressed tend to have lower levels of serum zinc (http://www.ncbi.nlm.nih.gov/pubmed/23806573). This makes me think many with PSSD have some sort of zinc deficiency.

Plenty of studies have shown that antidepressants have an effect on serum and brain levels of zinc:

http://www.ncbi.nlm.nih.gov/pubmed/10065601

We have studied the effect of chronic treatment with imipramine, citalopram and electroconvulsive shock (ECS) on serum and brain zinc levels in rats. Chronic treatment with citalopram (but not with imipramine or ECS) significantly (approx 20%) increased the serum zinc level. Chronic treatment with both drugs slightly (by approx 10%) increase the zinc level in the hippocampus and slightly decreased it in the cortex, cerebellum and basal forebrain. Calculation of the ratio hippocampus/brain region within each group demonstrated a significantly (approx 20%) higher value after treatment with either imipramine or citalopram. Moreover, chronic ECS induced a significant increase (by 30%) in the zinc level in the hippocampus and also a slight increase (by 11-15%) in the other brain regions. Thus, these different antidepressant therapies induced an elevation of the hippocampal zinc concentration, which indicates a significant role of zinc in the mechanism of antidepressant therapy.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3016009/

Zinc exhibits antidepressant-like activity in preclinical tests/models. Moreover, zinc homeostasis is implicated in the pathophysiology of affective disorders. The aim of the present study was to examine the effect of chronic zinc, citalopram and imipramine intraperitoneal administration on the presynaptic and extracellular zinc concentration in the rat prefrontal cortex and hippocampus. We used two methods: zinc–selenium histochemistry (which images the pool of presynaptic-vesicle zinc) and anodic stripping voltammetry (ASV) for zinc determination in microdialysate (which assays the extracellular zinc concentration). We report that chronic (14×) zinc (hydroaspartate, 10 and 65 mg/kg) and citalopram (20 mg/kg) administration increased the pool of presynaptic zinc (by 34, 50 and 37%, respectively) in the rat prefrontal cortex. The 21% increase induced by imipramine (20 mg/kg) was marginally significant. Likewise, zinc (hydroaspartate, 65 mg/kg), citalopram and imipramine increased the extracellular zinc (although with a different pattern: time point, area under the curve and/or basal level) in this brain region. Furthermore, zinc induced an increase in presynaptic (by 65%) and extracellular zinc (by 90%) in the hippocampus, while both citalopram and imipramine did not. These results indicate that all of the treatments increase presynaptic/extracellular zinc concentrations in the rat prefrontal cortex, which may then contribute to their antidepressant mechanisms. Alterations induced by zinc (but not antidepressants) administration in the hippocampus may be related to specific zinc mechanisms. All the data (previous and present) on the effect of antidepressant treatments on the presynaptic/extracellular zinc concentrations suggest the involvement of this biometal presynaptic/synaptic homeostasis in the antidepressant mechanism(s).

We don't really know how these drugs modify zinc levels, but could it be possible that in some cases PSSD could be a result of zinc dysregulation in the brain?

Zinc plays such an important role in the brain, modulating many neurotransmitters:

http://www.ncbi.nlm.nih.gov/pubmed/15723351

Antidepressants partially inhibit the uptake of 5-hydroxytryptamine (5-HT; serotonin) in the rat corpus callosum (CC), a white matter commissure involved in interhemispheric brain communication. It is also known that zinc modulates many proteins, including neurotransmitter transporters. We examined the effects of zinc on the uptake of 5-HT into slices of the adult rat CC, in the absence or presence of some antidepressants. Zinc increased 5-HT uptake in a concentration-dependent manner when the CC slices were incubated in a solution buffered with sodium bicarbonate; however, zinc exerted no effect on 5-HT transport when HEPES was the buffer. Potentiation of 5-HT uptake by zinc was maximal with 1 microM (45% over the control uptake). Moreover, 1 microM zinc potentiated 5-HT uptake in the cingulate cortex by 58% and in the Raphe nucleus by 65%. The antidepressants fluoxetine and imipramine inhibited 5-HT uptake in the CC by approximately 50%, whereas 6-nitroquipazine, a potent 5-HT uptake blocker, inhibited uptake by only 23%. Interestingly, inhibition of 5-HT uptake by all three substances, fluoxetine, imipramine, and 6-nitroquipazine, was counteracted by the presence of 1 microM zinc. Free zinc may thus contribute to modulation of extracellular levels of 5-HT and its removal. These actions should be considered in the treatment of mental depression with antidepressants.

It even acts as a neurotransmitter. There is a receptor called GPR39 which is activated by zinc. We don't know much about what its role is, but interestingly enough antidepressants have an effect on this receptor:

http://www.ncbi.nlm.nih.gov/pubmed/26481532

The administration of acute antidepressants induced diverse effects in the proteins that were examined (namely, GPR39 down-regulation and a reduction in CREB protein after administration of all ADs; a decrease in BDNF after administration of imipramine and escitalopram; an increase in BDNF after administration of reboxetine; no change in BDNF following administration of bupropion; and a decrease in TrkB following the administration of all ADs except bupropion). On the other hand, chronic treatment (which is required for depression relief) with all antidepressants increased the levels of all these proteins.

On a seperate note, I remember I had temporary success with St. John's Wort, which only lasted for a couple days. It turns out one of the active ingredients, hyperforin, induces the release of zinc stored in the mitochondria of neurons (http://www.ncbi.nlm.nih.gov/pubmed/19845832). Could this be why I felt some relief? There is only so much zinc stored in the mitochondria, so this could explain why the positive effects only lasted a short time.

[dark_knight]

gatogordito, are you still feeling well? I have recently discovered that Zinc/P-5-P/Vitamin K combo works great for me! I guess Zinc played a huge part in my improvement. I also noticed that my results are much better when I combine Zinc with Vitamin K. I am happy to say that I am at 100% improvement so far. I hope my results will stick long term.

[Zero]

So what kind of Zinc do you recommend ultimately and how much? Gluconate or Picolinate? with or without Magnesium?

[gatogordito]

gatogordito, are you still feeling well? I have recently discovered that Zinc/P-5-P/Vitamin K combo works great for me! I guess Zinc played a huge part in my improvement. I also noticed that my results are much better when I combine Zinc with Vitamin K. I am happy to say that I am at 100% improvement so far. I hope my results will stick long term.

That's great to hear!

The past few months have been pretty rough for me and I'm having a hard time figuring out what exactly is going on. I was doing great with 15 mg of zinc, but things started to stagnate and my anhedonia wasn't improving. I tried upping it to 30 mg and after a few days I felt even worse. I stopped taking it and the next day I had a rebound effect where I felt great, much like when I was taking zinc picolinate last year. This lasted for a couple days then I started feeling worse again. So from there I kept lowering the dose and taking it less often. Whenever I lowered the dose, things would improve for about a week, and then I would start to feel worse again. It got to the point where I could only take about 5 mg every few days. But it sucks because I've lost a lot of the benefits from the higher doses of zinc, and from what I can tell my testosterone levels have plummeted.

So now I'm starting to think I may have low copper levels and the zinc is pushing it even lower, causing these bad reactions. When I started zinc over a year ago, I was taking 50 mg of zinc picolinate for nearly 5 months. That's a pretty high dose, especially with zinc picolinate, which I've found to be highly absorbed. I think some of the bad effects I experienced could be explained by low copper:

-I started to experience bad insomnia, where I'd wake up about every 1.5 hour. Sometimes I would wake up with my heart racing. An enzyme called superoxide dimutase (SOD) is low in people with sleep apnea. SOD requires both zinc and copper, so it's possible this is the cause of my insomnia.

-I noticed that I would get depressed and feel stressed after eating a large meal, especially if it was carb heavy. Copper is involved in glucose metabolism, and a deficiency can lead to glucose intolerance (http://www.ncbi.nlm.nih.gov/pubmed/6363640).

-I may have been mildly anemic. My body temperature has been pretty low (~97.0), I get cold hands and feet, and have pretty bad cold intolerance. Sometimes I'd experience shortness of breath while working out, and have been struggling with cardio. Copper is critical in the conversion of ferrous to ferric iron, which is the form needed for it to be transported into the blood.

I think I may setup an appointment with my doctor this week and get some blood work done. I definitely need to get serum copper, zinc and ceruloplasmin levels checked. Maybe iron levels too.

I've got to get this fixed. It sucks knowing how good it is to feel 100% again, but then having that taken away again. I don't know if vitamin K will help prevent the issue I'm having, but it wouldn't hurt to try! I just hope you don't run into the same issue as me.

[dark_knight]

gatogordito, are you still feeling well? I have recently discovered that Zinc/P-5-P/Vitamin K combo works great for me! I guess Zinc played a huge part in my improvement. I also noticed that my results are much better when I combine Zinc with Vitamin K. I am happy to say that I am at 100% improvement so far. I hope my results will stick long term.

That's great to hear!

The past few months have been pretty rough for me and I'm having a hard time figuring out what exactly is going on. I was doing great with 15 mg of zinc, but things started to stagnate and my anhedonia wasn't improving. I tried upping it to 30 mg and after a few days I felt even worse. I stopped taking it and the next day I had a rebound effect where I felt great, much like when I was taking zinc picolinate last year. This lasted for a couple days then I started feeling worse again. So from there I kept lowering the dose and taking it less often. Whenever I lowered the dose, things would improve for about a week, and then I would start to feel worse again. It got to the point where I could only take about 5 mg every few days. But it sucks because I've lost a lot of the benefits from the higher doses of zinc, and from what I can tell my testosterone levels have plummeted.

So now I'm starting to think I may have low copper levels and the zinc is pushing it even lower, causing these bad reactions. When I started zinc over a year ago, I was taking 50 mg of zinc picolinate for nearly 5 months. That's a pretty high dose, especially with zinc picolinate, which I've found to be highly absorbed. I think some of the bad effects I experienced could be explained by low copper:

-I started to experience bad insomnia, where I'd wake up about every 1.5 hour. Sometimes I would wake up with my heart racing. An enzyme called superoxide dimutase (SOD) is low in people with sleep apnea. SOD requires both zinc and copper, so it's possible this is the cause of my insomnia.

-I noticed that I would get depressed and feel stressed after eating a large meal, especially if it was carb heavy. Copper is involved in glucose metabolism, and a deficiency can lead to glucose intolerance (http://www.ncbi.nlm.nih.gov/pubmed/6363640).

-I may have been mildly anemic. My body temperature has been pretty low (~97.0), I get cold hands and feet, and have pretty bad cold intolerance. Sometimes I'd experience shortness of breath while working out, and have been struggling with cardio. Copper is critical in the conversion of ferrous to ferric iron, which is the form needed for it to be transported into the blood.

I think I may setup an appointment with my doctor this week and get some blood work done. I definitely need to get serum copper, zinc and ceruloplasmin levels checked. Maybe iron levels too.

I've got to get this fixed. It sucks knowing how good it is to feel 100% again, but then having that taken away again. I don't know if vitamin K will help prevent the issue I'm having, but it wouldn't hurt to try! I just hope you don't run into the same issue as me.

I really doubt you have copper deficiency. You were taking "Zinc Balance" which already contains 100% DV of copper, so there's no way you are deficient in copper. Even if you didn't take Zinc Balance, you still wouldn't be copper deficient, because copper is abundant in American diet.

Unless you have blood tests to prove you have copper deficiency, stay away from it. Copper is a very tricky and dangerous supplement.

I am looking forward to how your blood tests turn out though.

About Vitamin K, I am not 100% sure if it will help you, but it wouldn't hurt to try. Obviously it's too early to tell if my results will start to stagnate like yours did. I really hope not.
I really wish you recover man!

[HalfPerson]

Coincidentally, I started taking 25mg of Zinc Gluconate yesterday. I tried 50mg this time last year but it seemed to give me insomnia and 'the dribble' after I peed. 25mg seems tolerable. I also started supping with a Vit B Complex tab yesterday, too. I don't know if it'll be a good combo but I'm only two days in and will report back if I notice any marked negs or positives.

I don't know if it's better to just use one supplement at a time. This time last year I was supping too much in an attempt to find a cure for my PSSD as quickly as possible, about 6 or 7 different ones daily. I never felt any benefits, I just felt weird and had a bad stomach most of the time!