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New Here, Guidance Needed.. 23andMe CBS, MTRR, MTHFR concerns

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by cobain_justinsane, Mar 14, 2013.

  1. cobain_justinsane

    cobain_justinsane

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    Hello all:

    I am looking for some guidance. I fell Ill with CFS/FIBRO/MS symptoms in 2009 after a long course of antibiotics for acne and taking CIPRO (I am well aware of Quinolone toxicity and beleive that it is playing a role in my health problems but feel that Cipro and a very stressful time in my life was the straw that broke the cammels back). On top of that I have depression, anxiety and panic and have dealt with pretty bad acne since I was 18 (Dairy and sugar free controls my acne but it has never truly cleared up). I am not disabled and manage to get by okay but my health challenges are really preventing me from living a normal life.

    I am a 25 year old male and for the past 2 years have been doing ozone saunas, eating a high plant based diet of nuts, seeds, quinoa, buckwheat, brown rice, tones of green vegetables, onions, garlic, no fruit except lemons and limes and red meat, chicken or fish a few times a week.
    I eat no sugar, dairy or gluten except on very and I mean very rare occasions.
    I have seen an alternative MD and am taking 20 mg of Cortef, 10mg DHEA and 60mg of Armour.I have worked on my gut health and feel it is in very good shape. And feel like I have detoxed quite a bit of the junk inside me. I take a digestive enzyme with every meal, chlorella, spirulina and probiotics. I also take magnesium, chromium and COQ10.

    All of this has helped me quite a bit but I have plateaued and then I stumbled onto MTHFR which I think may be the missing piece of the puzzle. My symptoms seem to be worse in winter especially the mental ones.

    23andME results.

    VDR BSM: +/-
    VDR TAQ: +/-

    MAO A R297R: +

    MTHFR C677T: +/-
    MTHFR A1298C: +/-

    MTRR A66G: +/-
    MTRR H595Y: +/-
    MTRR K350A: +/-
    MTRR A664A: +/-

    BHMT-08: +/-

    CBS C699T: +/-

    SHMT1 C1420T: +/-


    My Symptoms:

    -Panic, anxiety, depression (worse in winter, tolerable in summer)
    -Fatigue, though not severe
    -Tinnitus occasionally
    -Raynauds
    -Numbness /tingling
    -Muscle twitching
    -Poor memory/focus
    -Brain fog/derealization
    -Acne (since I was 18)
    -Hair Loss (since I was 18)
    -Gynocymasteia (since I was 15)

    I have a family history of Depression, Alzhimers, Bipolar, Anxiety, Heart Disease and Stroke.

    I received my results and was not at all surprised that I had MTHFR, I was actually releived because It potenntally explains some of my problems.

    I thought I had COMT because I got very hyper and anxious when I took Phosphatidycholine, and aceytl-l-carnatine.
    I also experienced increased depression when taking Zinc and P5P.

    I am concerned about MTRR mutations as I have a lot of those and are wondering how concerned I should be as I realize B12 is extemnely important and wondering if this mutation caused a deficiency in B12

    I am also conerned about the CBS pathway as I seem to tollerate sulfur well. I eat quite a high sulfur diet (onions, some garlic, broccoli, brussel sprouts) and at one point took MSM which I didn’t fell affected me negativly. I beleive I have a high intake of molybdenum as I eat a ton of sprouted Lentils and Mung Beans which are supposedly very high in molybdenum. Does it matter that I am +/- as opposed to +/+ and how should I go about treating the pathway. Also, any Ideas of why P5P could have caused depression or why Phosphatidycholine caused Anxiety?
    Is It possibly because I hadn’t addressed MTHFR at all?

    I would really like to begin treating the MTHFR MTRR as soon as possible but don’t want to cause any problems.Will I have to address CBS first? The CBS is waht confuses me quite a bit as I have educated myself pretty well on all of this but am looking for some guidance.
    If anyone can give me some solid guidance I would really appreciate it.

    Thanks a Million

    Andy

    PS if any more information is needed just ask.
  2. Red04

    Red04 Senior Member

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    My wife has a very similar symptom set (everything the same except no tinnitus and she had severe fatigue) and saw an amazing recovery in a few short months with the active b12 protocol (freddd's protocol). We didn't do any testing and just followed the symptoms and reactions to the supplements. I believe you can never read too much and learn too much but I see some people get wrapped up in theories and crazy vocabulary. Don't lose sight of the fact that several people have been effectively cured by the SMP and Active B12 protocol.

    I would recommend you consider learning the protocols and give them a shot before you over analyze everything. Read up on them, research them and see what you agree with. Pick one and try it, post any problems/questions up here, try the other if you aren't seeing major improvement.
  3. ahmo

    ahmo Senior Member

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    Northcoast NSW, Australia
    Hi Cobain. Your +/- variants are less severe than +/+. My profile is very similar to yours. (see at bottom of my post) I am pasting in a list I got, I believe, from heartfixer, which is a short-hand version of Amy Yasko's protocol. Also, do you have Yasko's free ebook?

    http://www.holisticheal.com/autism-pathways-to-recovery-book-and-workbook.html
    http://www.heartfixer.com/AMRI-Nutrigenomics.htm

    You're taking p5p. Does that mean you've tested for pyroluria? If not, here's a pyroluria questionnaire:
    http://www.hputest.nl/evraag.htm

    And MTHFR sites: http://www.mthfrsupport.com/ http://mthfr.net/mthfr

    Re CBS, sulfur. Yes, it's important to clear this first, as it interrupts methylation. I'd been on the GAPS diet 3-4 months, which had drastically reduced my anxiety symptoms by Day 3. I developed an outbreak on my face, which I eventually labelled rosacea. When I consulted a cosmetologist, who was dubious about this dx, I looked at my diet. First I eliminated histaminic foods (pyroluria), and got a 50% decrease in symptoms. Then I took out sulfur, which cleared the condition within 24 hrs. This was before I tested for and found the CBS. Since then I've been thiol-free, except for whatever the B vits might be contributing. I recalled that I'd had excitotoxic reactions some years earlier to MSM, SAMe. I've been sulfur-free (except small amts of meat) for 5-6 months, in no hurry to put it back in. I bought sulfate strips, not cheap, and have been at the next to lowest each time I've tested, which started several months after eliminating sulfur. this is considered an acceptable level.

    Once I'd been off sulfur for a couple months I began implementing the B12 protocol, methylB12, methylfolate. I've recently added adb12, as recommended by Freddd. I tried AL-Carnitine, with no results. When I switched to carnitine fumarate, again per
    Freddd's protocol, I felt an immediate lift. I've now increased that to 3 caps/day, and am staying with my current levels of these 4 substances, Freddd's "Deadlock Quartet", for a month before making any other alterations.

    It is extremely likely that you have bacterial overgrowth and metals, which are interfering with methylation and everything else. This was validated for me when I got my results from Metametrix urine testing for metals and comprehensive. I've been using high doses of other minerals to counter the toxic metals, + raw juice daily, as per the GAPS protocol, rather than using a more aggressive protocol. High doses of zinc, molybd, selenium, + manganese and magnesium are all appropriate for thyroid, pyroluria, and detoxxing metals. There's no telling whether you're actually absorbing what you need in molybd from your foods. If you were to do one test, it might well be the toxic and elemental metals, just to see how much of the minerals you're absorbing.

    RE the psychological/emotional symptoms: Yasko recommends v low dose lithium orotate especially for MAO defects, due to the overly rapid recycling of neurotransmitters. I have always been emotionally labile, far too reactive, easy to cry, and in fact worked through all manner of modalities to deal with these in my life pre-GAPS. The diet itself helped with these, as did pyroluria supps. But lithium has been a quantum shift. 1/4 cap a day has made a big difference, truly stabilised my emotional life. OK, that's enough for today, hope there's something useful for you here. Best wishes, ahmo






    rs4680 - COMT V158M (Risk Allele: A)
    s4633 - COMT H62H (Risk Allele: T)

    This gene helps break down dopamine and norepinephrine. A defect will cause higher dopamine due to slower breakdown. Implicated in ADD/ADHD. More susceptible to dopamine fluctuations, therefore mood wings. People without COMT mutations are generally more even tempered.

    rs1544410 - VDR Bsm (Risk Allele: T)
    rs731236 - VDR Taq (Risk Allele: G)

    Vitamin D receptor. VDR Fok is involved with Blood sugar regulation. [Fok Not Tested] VDR mutations oppose COMT mutations in the regulation of dopamine levels. A VDR mutation means that a person is less sensitive to methyl group supplement levels. (Mood swings.) A VDR mutation can result in behaviors opposite to a COMT mutation. See Dr. Roberts comments at http://www.heartfixer.com/AMRI-Nutrigenomics.htm#VDR Taq: Vitamin D Receptor Taq Abnormality

    rs6323 - MAOA R297R (Risk Allele: T)

    Slower breakdown of Serotonin. Can lead to high/low cycling of neurotransmitter. Mood swings, aggressive behaviors. ACE deletions will also increase anxiety and lower frustration thresholds.

    rs1801133 - MTHFR C677T (Risk Allele: A)
    rs1801131 - MTHFR A1298C (Risk Allele: G)

    MTHFR mutations are the centerpiece of the work by Yasko, Rawlins and others, and is the most important to understand. An MTHFR mutation can starve the entire methylation cycle, which has some very large health impacts.
    The C677T mutation is associated with a general set of problems: elevated homocysteine, increase in heart disease, increased stroke, increased deep vein thrombosis, peripheral neuropathy, placental vascular problems (stillbirth), preeclampsia, neural tube defects, cleft lip.
    The A1298C mutation is assoicated with a second set of problems: depression, anxiety, irritable bowel syndrome, fibromyalgia, chronic fatigue, migraines, dementia, nerve pain, schizophrenia, parkinson’s, tetrahydrobiopterin (BH4) problems. Although not addressed by Yasko, if your Promethease report includes Gs223 or Gs224, you may have additional BH4 impairment.
    A person who is compound heterozygous (a single C677T mutation and a single A1298C mutation, each on a different strand) will see symptoms from both defects, but the symptoms tend to be more severe. Rawlins also believes that blood clots are more prevalent. As bad as that is, a person with a single mutation on one gene and a double mutation on the other can be worse. A person who is compound homozygous (double mutation on both genes) is also worse.
    rs1801394 - MTRR A66G (Risk Allele: G)
    rs10380 - MTRR H595Y (Risk Allele: T)
    rs162036 - MTRR L350A (Risk Allele: G) [my chart reads K350A rs162036]

    Necessary to regenerate Methyl-B12 for use by MTR. Mutation can cause shortage, suggesting a need for more B12.

    rs567754 - BHMT-02 (Risk Allele: T)
    rs617219 - BHMT-04 (Risk Allele: C)
    rs651852 - BHMT-08 (Risk Allele: A, 23andMe: T)

    The product the BHMT gene is central to the ‘short cut’ through the methylation cycle, again helping to convert homocysteine to methionine. The activity of this gene product can be affected by stress, by cortisol levels and may play a role in ADD/ADHD by affecting norepinephrine levels.
    Yasko believes that believes BHMT-02 and BHMT-04 play a role in the gut environment. Yasko also believes that BHMT-08 is related to the impact that psychological stress has on a patient’s attention levels.
    rs234706 - CBS C699T (Risk Allele: A)

    Limits homocystine into downstream path. People with CBS mutations will need to be careful with sulfur containing supplements. Increased risk for ammonia detoxification issues. Puts a burden on SUOX.

    [Not tested for NOS, SUOX; NOS Helps in the formation of nitric oxide which has a role in ammonia detoxification, oxidative stress, and chemical production. Mutations here are made worse by MTHFR A1298C mutations and CBS mutations. A mutation here is also made worse by a lack of mutations in SUOX. SUOX This gene product helps to detoxify sulfites in the body. Sulfites are a natural byproduct of the methylation cycle and are also ingested from foods. Made worse with CBS and NOS mutations.]
    Christopher likes this.
  4. Victronix

    Victronix Senior Member

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    I noticed you are taking Armour. I take Synthroid. When my TSH gets too high (i.e., 6 - 8), I can get fairly extreme anxiety and panic. Have you had levels tested recently? It's amazing how many things can interfere with thyroid absorption, even strawberries. Some thyroid doctors have also reported that patients seem to need more thyroid in the winter months. I'm worse in the winter also in terms of everything.

    Kaiser tried to force Cipro on me -- even when I would tell doctors I didn't want to take it and they would say okay, as though they would then choose a different antibiotic, when I would get to the pharmacy I would find that they had ordered it anyway. So I told them I was allergic to it and made up some symptoms. When I saw that it was the drug of choice for dealing with the Antrax attacks (I seem to recall Cheney had some role in the company that made it), and the postal workers ended up with horrible side effects, I decided to avoid it at all costs. Later, I did some research and saw that there were lawsuits because of permanent damage done to people from it.
  5. cobain_justinsane

    cobain_justinsane

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    Thanks a lot for the reply Red!

    I am very happy for you and your wife, that's awesome that she's come so far!

    I'm just wondering what some of the doseages of supplements she was on, was she on very high doses or lower doses. I have read through some of your posts but have not got through all of them yet.

    Thanks a lot

    Andy
  6. Kir

    Kir

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    I am currently awaiting my 23andme results. Looking at other people's results, it's very hard to interpret. So I'm guessing that -/- means you don't have it, +/- means you have it, but not strongly and +/+ means you have it strongly? Is that correct? I just want to make sure, so that once my results come in (4 1/2 weeks in and STILL waiting), I will know how to interpret them. I'm in So. Cal. and have been trying to find preferably a naturopath who is both MTHFR and Lyme literate. I have been to the practitioner list on mthfrsupport.com and they have only one listed in my area, however, I don't want to go to her. Any other suggestions? I also have Lyme, EBV, HHV-6, candida, parasites, adrenal fatigue, sluggish liver, hormonal imbalances, a clotting disorder, etc. The adrenal fatigue and sluggish liver are making my life a living hell right now. Thanks.
  7. Red04

    Red04 Senior Member

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    She followed Freddd's protocol which would be considered high doses of methylfolte by some. In comparison with deplin doses she was probably a low dose. Her nomral dose now is 2400mcg. I went down to 800mcg when she was at her best and it just wasn't enough for her to maintain. When she started the protocol, she would take dosages of 6400-8000mcg of methlylfolate. 4-5 solgar pills 2X a day. Deplin dosages of methylfolate are 15000 mcgs. So, depending on your prospective 8000 mcgs could be high or low.

    Her b12 is 5mg methylcobalamin and 3mg adb12. 855 mcg LCF.

    The important thing if you want to follow the protocol is to titrate. Don't just take 8000mcg of methylfolate. Start with 200mcg (1/4 of a pill) or less. Freddds post can help you titrate everything. Follow the symptoms...

    Get the basics in place for a few weeks A,D,E,C,potassium, calcium, magnesium, zinc, Omega 3, Multi B, then titrate in the B12's, Methylfolate, and LCF. Watch low potassium symptoms, watch low potassium symptoms, and watch low potassium symptoms. Keep some on hand at all times.

    She does NOTHING in regards to diet. She eats whatever, whenever. Terrible diet. Processed foods. Fast foods. Skips meals. etc.....So if you have a more controlled diet it could be different.
  8. thegiantess

    thegiantess

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    Hi all,
    Sorry to jump in here, but am a little confused. I have a 23andMe test and have been staring at it all morning and can't even figure out where y'all are seeing the MTHFR info? Where should I be looking? Help!

    Thanks!
  9. Victronix

    Victronix Senior Member

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    You can upload your 23andme zip file to programs online that will produce those results. The main one that I know of is:

    Genetic Genie - Automated methylation and detox analysis from 23andme results

    There is also another one, Promethease, but that's mainly similar to the report from 23andme -- http://snpedia.com/index.php/Promethease

    One person on here, Caledonia, has several links on his signature that are helpful as well:

    Rich Van Konynenburg - Methylation Block/Glutathione Depletion Hypothesis, Simplified Methylation Protocol, HDRI Methylation Panel interpretation
    Heartfixer - Dr. Robert's excellent summary of the Yasko protocol
    Autism: Pathways to Recovery - Dr. Amy Yasko's protocol - the "gold standard"
    Methylation and MTHFR Defects - excellent video by Ben Lynch
    Nutreval Interpretation Guide - a summary of Rich Vank's Interpretations
  10. caledonia

    caledonia

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    You have the First Priority mutations SHMT and CBS. If these are expressed, you need to take care of them first before diving into folate and B12 supplementation.

    I have CBS +/- and tolerated sulfur foods and supplements well. However, it was still expressed and was a big problem. Starting out, I could only tolerate 200mcg of methylfolate and 0.5mcg methylcobalamin. I did the CBS protocol for 6 months. Now I can tolerate somewhat larger amounts of B12 (limited by the Zoloft I'm on, but that's a whole other story). I no longer need several of the CBS supplements and a few of my other supplement needs are reducing too.

    MTRR recycles B12. So it would be like if you had a little garden waterfall that ran with a pump. If it ran correctly, you would pour a bucket of water in and it would recycle over and over. Well, it's like your pump is broken. You add a bucket of water, the waterfall runs once, then it stops. Similarly, you add B12 into your body and it doesn't get recycled well. So you're likely deficient in B12 and will need continuous supplementation.

    MTHFR converts dietary folate into methylfolate. The methylfolate combines with B12 to make methyl groups. The methyl groups attach to a substrate to make DNA, neurotransmitters, etc. So that's likely not working well for you.

    MAO+ for males is like saying MAO+/+ for females because you only have one copy. So I'm not surprised with the mental health issues.

    Warning: If you're on any psych drugs, you only want to crank up methylation enough to fix any breakthrough symptoms. If you want to go further, you may need to discontinue the drug, however, this can't be done suddenly or you can get a horrible "discontinuation syndrome". This happened to me and took me almost a year to get straightened out. The solution is to taper 10% of your previous dose every 6 weeks or so, and gradually ramp up methylation as you taper off the drug. It's going to take me 2-3 years to get off Zoloft.

    ps. If you're having a winter worsening of depression, that sounds like SAD or possibly vitamin D deficiency.
    Victronix likes this.
  11. thegiantess

    thegiantess

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    Thanks for the response! I spent most of the afternoon yesterday converting my 23andMe into an analysis. Looks like I am compound hetero for MTHFR. Awesome. :(. It is nice when you have confirmation that it is not all in your head though, huh?! I also have the less bad CBS hetero, but am extremely reluctant to follow this whole eliminate sulfur and protein thing. That seems excessive to me. I am sure that for some people who are very ill it is necessary, but I am not very ill. I don't have infections, or CFS or MS or anything of that nature. I have a clean stool profile, have spent 3 previous months fixing some gut issues with a Naturopath, etc. I think in my case I will just continue to supplement...and should have never stopped. The same naturopath that helped me repair my gut was insightful enough to figure out that I had a functional B12 deficiency despite my serum test being high. So, in tandem with the gut protocol he had me on 5methyl folate and B12 drops. I felt better in the matter of 2 weeks. Then I got distracted and decided to cut back because I got what I think was a severe potassium crash. Anyway... within a week the tingling and itchy skin and irritability is back! So, that is what led me to forums and inspired me to check with my 23andMe just to see if I might have this mysterious MTHFR issue that I have heard people reference. And low and behold!

    Anyway, thanks again, and best of luck.
  12. caledonia

    caledonia

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    I know two people with the minor CBS mutation and it doesn't seem to be much of a problem for them. If you're tolerating a decent amount of methyl donors (methylfolate and methylcobalamin) then you're probably ok. A cortisol/stress/anxiety response would be a sign that you need to look at CBS. You can get urine sulfate strips and if it's high, that would be another indication. Another one would be a high ammonia test, but that one's more expensive.

    I'm not sure what a potassium deficiency response is like. I lean towards needing more magnesium instead of potassium.
  13. Victronix

    Victronix Senior Member

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    A cortisol/stress/anxiety response would be a sign that you need to look at CBS.

    I have that type of response to methylfolate, but my CBS is -/-.

    My BHMT 08, COMT V158M & H62H, and MAO A are +/+. I haven't read up enough yet to understand whether sulfate might be an issue for me. Overstimulation has been an issue for me overall. And magnesium makes a big difference for me in general. I had been taking a Carlson's Albion Cal Mag but they apparently lost their Albion license so now am having to experiment all over again with new brands with Albion. It's been the only one my gut could handle.

    Potassium deficiency for me has been mainly muscle pains, waking up every 1 - 2 hrs at night, exhaustion, stomach cramping, etc.
  14. antherder

    antherder Senior Member

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    I only have the CBS C699T +/- mutation, but I definitely have major problems with sulfur foods and supplements, and don't tolerate methylcobalamin well at all.
  15. Victronix

    Victronix Senior Member

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    My experience with methylcobalamin was that it was really hard at the start, but over the course of 2 weeks, the side effects all went away. Each time I increased it, it was very difficult, but over time, that decreased. Now if I take an extra dose or something by accident, there are almost no side effects at all. And I'm COMT++.
  16. antherder

    antherder Senior Member

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    Thanks for mentioning that. Good to know. I will try to brave...
  17. thegiantess

    thegiantess

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    Yah, it doesn't seem to be much of a problem. I do handle methyl pretty well and am going to start Fredd's full protocol soon, because other SNPs indicate that a combo supp might be better for me. Potassium deficiency for me is hell. The first time it happened was about 2 weeks after supplementing. I was nauseated, non-stop and had a pounding headache.. I was also tired and irritable. I backed off a little, drank tons of coconut water and it evened out. This more recent episode was extreme exhaustion and itchy skin. Like pins and needles and crawling. If I pay attention to food intake (tracked in fit day) and aim for about 5000 mg of potassium for the day then I feel better, if not, worse.

    A really good test for me is just to drink coconut water. In regular life I think it tastes pretty horrible, but when I am low in potassium it tastes like liquified unicorns. I also think that just re-starting the protocol has contributed somewhat to itchy skin.. it is almost like I can feel methylation happening.
  18. caledonia

    caledonia

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    Lol! :thumbsup: That's what my homemade electrolyte solution (salt/magnesium) tastes like to me too. Like I can't get enough of it.

    I can't do much coconut water due to the potassium content. It's funny how we can all be so different.
  19. thegiantess

    thegiantess

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    Huh, interesting. What sort of low Mag symptoms do you experience? And are they brought by the same B12 wasting it sorting of thing that is happening with Pot?

    Also, I am at least somewhat interested in those sulfate strips.. I guess it is better safe than sorry. Do you use them? Is there a particular brand or source that is good?
  20. caledonia

    caledonia

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    Hi Andy,
    I was just reviewing Yasko's Vimeo video on CBS and noticed that she said that B6 (P5P) increases CBS activity. This would cause any methyl groups to go shooting down the CBS drain. So you would actually want to mostly limit your intake of P5P. (a little bit is apparently desired). So if the methyl groups are shooting down the drain, they won't be available to make neurotransmitters, thus depression.

    I'm not sure about the phosphatidylcholine or zinc, but it sounds like you're just not ready for them yet or you're possibly taking too much.

    It really sounds like CBS is an issue for you.

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