The Power and Pitfalls of Omics: George Davey Smith’s storming talk at ME/CFS conference
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Discussion in 'Genetic Testing and SNPs' started by paq71, May 15, 2015.

  1. paq71

    paq71

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    Edinburgh UK
    Hi,

    I'm wondering if any one could help giving me some advice on my situation.

    To make a long story short I'm male, 44, I've always been tall, very thin, melancholic, don't seem to be able to light up and have fun. About 13 years ago I reached a point where I couldn't even move as I was feeling completely exhausted and depressed. By almost total chance I had the pyroluria test done which resulted positive. I started taking zinc, B6 and omega oils and I started feeling much better, although I've reached a plateau and never really recovered completely, with long periods of exhaustion and depression and some ok periods.

    In these 13 years I've experimented with all sort of supplements, vitamins, minerals, aminoacids, omega oils etc.

    About 1 year ago I had a complete crash as the consequence of a nasty break up (she went with my best friend and I've lost all my closest affections all at once) and I've physically and mentally felt crumbling down. I've never experienced anything like that before although I had break ups before. I started having huge anxiety and fears, panic attacks, very strong suicidal thoughts, desperation, deep depression, fatigue, catatonic state, chain smoking. I also developed OCD, but I realised that this has been with me all my life.

    My father spent his life sitting on a chair smoking and drinking, which makes me guess he was suffering similar conditions than mine.

    About 2 years ago I did the 23andme test, please see results below. I've been trying to understand what to do according to them but I'm totally overwhelmed by the complexity of the issue.

    Last January I went to see the guys at http://biobalance.ie/ which has performed more testing. I've attached the results and the protocol they've suggested. They've also tested levels of B12 which came back within normal range. They haven't given me any guidance regarding diet.

    I've been on the protocol since the beginning of February. After 5 days I've felt a sharp improvement, especially regarding suicidal thoughts. Since then I've experienced a very slow improvement to today. Despite the improvement I still experience a lot of anxiety, strong depression, ocd, desperation, fear, huge tiredness, difficult sleeping more than 4 hours.

    As far as I can tell my results show that I'm undermethylation but that I'm also very sensitive to methyl donors. I've tried a couple of time since January to add hydroxyB12, but I had the feeling it was massively increasing anxiety. I've also swapped tryptophan for 5-HTP as tryptophan was making me feel extremely sleepy during the day.

    I'm living abroad and I know I've passed the edge and that I'm in a total break down. I'm close to decide to go back home to live with my mum as I just can't continue like this.

    Any advise, opinion or personal experience will be more than welcome. If more information are required I'll be very happy to answer. Anyone with similar genes could please get in touch to share experience? I would be extremely grateful.

    Thank you
    P
     

    Attached Files:

    Last edited: May 15, 2015
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  2. PeterPositive

    PeterPositive Senior Member

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    Hi,
    I am sorry for your situation.
    The problems you're describing are certainly complex and multi-factorial.

    For the specific issue of depression: zinc can play an important role and it's been shown to help. In your labs it is pretty low, although you have mentioned supplementing B6+zinc for pyrlouria.

    What was your kryptopyrrole or HPL value? Are you currently taking zinc and B6? What dosage?

    Also, how much B12 did you take when you had the increasing feeling of anxiety?

    cheers

    EDIT: from your genetic profile the MTRR A66G ++ suggests you may need extra B12 support.
     
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  3. paq71

    paq71

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    Edinburgh UK
    Hi Peter and thank you for your reply.

    When you say 'multifactorial', what factors are you thinking about?

    I've been taking zinc on and off for years, but since January, as you can see from the protocol, I've been on 100mg for the first 4 weeks than down to 50mg/day, my current dose.

    I got tested for pyroluria in the past, sometime being positive, sometimes negative. With the last batch of tests I also got tested for pyroluria, value was 0.02 on a reference unit of up to 0.08 (you can find this in the attached results).

    Since January I'm on a 25mg P-5-P and 200mg B6 per day.

    The dose of hydroxyB12 I've tried was 1,000mcg sublingual.

    Any thoughts?

    Thank you so much.
     
  4. Crux

    Crux Senior Member

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    Hi;

    These symptoms are shared by many here, but the causes can surely be many. I'll just write about some things I've noticed that may or may not apply to your situation.

    The amino acid, Methionine, is a methyl donor. Could be overstimulating for those sensitive to them.

    The zinc is still low, but the dosage is plenty high. ( I would guess absorption is poor. underweight. )
    RBC magnesium is low. Most people feel calmer and sleep better with some type of magnesium.
    The B6 dose looks very high, though the blood test is normal. ( malabsorption again?)
    Copper is low normal.

    Histamine is elevated.

    Your snps could possibly increase the need for some B12 and folate supps., but since they can increase anxiety,that's not good. Many folks here experiment with very low starting doses.

    I wonder if working on improving absorption, gut issues, may help with the symptoms?

    In my own case, dietary changes have helped, but I still take some supps. B12 helped with my ocd, suicidality, depression, etc. This, of course, varies per individual.
     
  5. paq71

    paq71

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    Good advices, thank you.

    I'm taking plenty of calcium/magnesium as per protocol.

    I've experimented in the past with 5-mthf and I felt great for a few months, then it was making me feel worse and had to stop it.

    What form of b12 would you advise?

    What kind of dietary changes have you noticed improvements with? At the moment I'm trying to avoid sugars and refined carbs as candida has been an issue and probably still is.

    I didn't mention on my post that I'm also trying inositol, I'm on 12gr/day at the moment.

    Thanks
    p
     
  6. PeterPositive

    PeterPositive Senior Member

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    Well, typically it's not just one thing causing issues like those we discuss here. Depression is not even fully understood by experts... in any case some of those causes can be due to lifestyle, nutritional imbalances, gut issues, genetics, drugs, toxins...

    It seems weird that you have low zinc at those dosages. Maybe there's an absorption problem as @Crux suggested.
    Zinc methionine (Optizinc) is usually well absorbed. Probably better than other forms, such as sulfate.

    Sorry I didn't notice. So this time was negative.
    Anyways zinc is needed anyways, while B6 seems to be absorbed ok.

    Do you have any digestive issues, IBS or similar?

    This could be too high a dose for starting up. B12 can be tricky at the beginning so it's best to keep it low and slow. I would suggest to try again at a 1/10th of that dose, even less if necessary, and find an amount that doesn't cause issues.

    B12 can help the mood significantly and a generic serum test won't tell you very little about your B12 status.

    It just takes some patience and time. I started very low after trying a high-ish dose and getting super wired. I got scared and dropped it entirely. Then my doc suggested to crush the lozenge and take just a few crumbs. It worked. Now I can tolerate higher doses with no side effects.

    cheers
     
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  7. Crux

    Crux Senior Member

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    The suggestions I make are only from a personal point of view, not professional, so, I'm just guessing.

    I believe that calcium supplementation is usually not necessary. It's a buffer against acidity, but it tends to 'clog the works'.

    With B12, the hydroxocobalamin may be less stimulating than the methylcobalamin, if you're sensitive to methyl donors.

    Not everyone will need folate, though many folks here do really well with it. There are RBC folate tests and others you can try if there is concern. Also, how's your homocysteine? It may be a little bit telling of how folate, B12, and B6 are doing,along with methyl donors.

    I remember trying inositol years ago for insomnia. It's also supposed to be good for anxiety. It only worked mildly, so I moved on.

    With diet, reduced carbs has helped enormously. This is another highly individualized regimen, but it's really improved energy, mood, sleep, and digestion for me. I have suspected SIBO, and reduced carbs keeps the gut bug population in check.

    (Also, I have an odd theory that tobacco, and nicotine addictions may be associated with acidic conditions. They are strong alkaloids, maybe they buffer against the acidosis that sugars and carbs can cause in some people? I have a history of smoking.)
     
  8. paq71

    paq71

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    Thanks a lot, very interesting insights here.

    @PeterPositive: Digestive issues: probably. I've been on anti-candida diet some years ago and I believe it has never been eliminated. I'm trying to eat as little sugars as possible. I'm also not eating a great diet in general lately so surely there's room for improvement there.

    Your suggestion about taking much smaller dose of hydroxyB12 is really interesting. I'll try that tomorrow morning and let you know. Did you notice improvements pretty soon when you've started taking it?

    @Crux: I've never tested homocysteine I think. If it's relevant my bilirubin was high some time ago. I've been tested back in 2012 for Serum Folate, which was within range (13.6uh/L on a range 2.8-20).

    I've the same feeling about inositol, but I'm giving it a try especially for OCD. And yes, I've been smoking A LOT in the last year. Sometimes I've night sweats, when I drink fresh veg juices, and the morning after the white bed sheets are yellow. Heavy detox?

    So to recap: my protocol seems fairly ok for the test results I got. I might benefit from slow B12 supplementation and certainly from diet and lifestyle changes?

    I really appreciate your help guys.
    P
     
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  9. PeterPositive

    PeterPositive Senior Member

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    Going low and slow usually yields results after some time, you may feel some changes after a few days, for other people it may take several weeks. Be patient :)
     
  10. Kitty_Cat

    Kitty_Cat

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    So sorry you're feeling that way. It really sucks.

    Just a few more thoughts on what the issues that you've mentioned (and in no particular order):
    1. Be very careful about the brand of calcium that you use to supplement with. Calcium supplements are commonly contaminated with lead, among other things. Search around for a brand which tests for contaminants.
    2. Pyroluria is often a congenital condition (a tendency to develop it based upon your genetics and epigenetic factors), however it can also be acquired at any point in your life without having that tendency, given the right extreme oxidative stress conditions. In either case the urine tests will usually come back positive when you are more stressed, but there appear to be occasions when the pyroles clear from the urine. Often this might be because stressors are under control, and you are doing well. However, I've also read that sometimes, when a person is particularly low and their body clock is screwed up, the pyroles might not actually appear in the urine until a couple of hours after the evening meal, so a mid morning urine sample might miss this.
    3. Oxidative stress is a huge thing if you are zinc deficient. You really want to control your exposures to stress as much as possible. Stressors can be hiding on all sorts of places. I'm afraid smoking does huge amounts of oxidative damage. Withdrawing from nicotine can also be stressful for a lot of people, but I can't help but think that not addressing that might be slowing down your progress a bit. Sorry. Any chance you could look into quitting? Interestingly Julia Rucklidge in New Zealand has been doing a lot of research on nutrition for mental health disorders, and she believes she has found a correlation between micronutrient deficiencies and addictions. She has done a TED talk, although there is also a longer, more detailed discussion recorded on her work website. I think she works for the university of Christchurch.
    4. Other sources of oxidative stress include dietary things, including processed, sugary foods and drinks, alcohol, pesticide residues, and there are a lot of whole foods which can irritate people. Pyrolurics tend not to do well on gluten, but other cereal grains can be just as problematic. Modern soy products can be awful for a lot of people. Other legumes and certain other foods and food groups can be problematic, depending on the individual.
    5. Microbial exposures can cause stress. Often the gut can harbour nasty bugs, or even good bugs in the wrong location (eg SIBO as mentioned above). Altering your gut flora might be necessary. However, you might also have to think about the health of your teeth, gums, sinuses, lungs, skin, etc. Gingivitis might be masked in smokers because the blood supply to the gums might be compromised so they don't bleed on brushing. Make sure you're brushing under the gum line and cleaning in between the teeth too.
    6. Sometimes there can be environmental exposures that could be irritating you. Hopefully not, but have a think about it. Are you exposed to damp and molds? Are there lots of chemicals in your personal care products? (Toothpaste, mouthwash, shower gel, shampoo, etc) are you exposed to toxins through your work or in your house? All sorts of chemicals in the air can be breather in or absorbed through the skin. If you're really sensitive then even something like laying a new carpet or being exposed to paint fumes could annoy you.
    7. Exercise is generally a good thing, but if you're really stressed then high intensity exercise can act as a stressor. Try to get outside for exercise, eg walking, and get into nature. Some people even have access to things like yoga or qi gong on the beach or in the park.
    8. Vitamin D is really important, so regular safe sun exposure to build up vitamin D is important. Do not get sunburned, but (unless you have some unusual photosensitive condition) do try to get outside during the summer without sunscreen for short periods of time, exposing as much of your skin as possible. But do not get burned! Get your vitamin D levels checked. If you need to supplement use the D3 form. Recent scientific studies suggest the RDI for vitamin D was miscalculated. The statistical error seems to have underestimated our requirements by tenfold.
    9. Try to develop techniques for dealing with stress. This can be hard to implement, but please do try to do this regularly throughout the day. Mindfulness seems to be really popular, but you can use other techniques like heart math, yoga, art, massage, music therapy etc.
    10. Do things that you enjoy. Try to have fun.
    11. Spend time with supportive people who care about you and who you care about. Good quality human contact is really important.
    12. There are a number of superfoods that can help you to heal. They maximize micronutrients while minimizing antinutrients: Liver and organ meats, bone broths, fermented foods, seaweed and some others. All animal proteins are best obtained from grass fed, pastured organic or wild animals if possible. Conventional animal bones might contain more lead, and their fats might contain other heavy metals, pesticides and less omega 3 fats.
    13. A lot of people with pyroluria report improvements with evening primrose oil. It might be possible to test your fatty acid profile to look at your omegas. This is different from a standard cholesterol test.
    14. If you're not sleeping watch out for caffeine. Probably an idea to cut out coffee, tea, energy drinks and maybe even chocolate.

    Don't try to make lots of changes at once. If I had to prioritize things to do, I'd probably focus on the smoking first, then the diet, then have a look at the other things.

    I see you're already taking some amino acids. There might be some others you could try. I would recommend Trudy Scott's website, everywoman over 29 and her book, the anti-anxiety food solution. They're not just for women.

    Best regards.
     
  11. paq71

    paq71

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    Wow @Kitty_Cat, amazing, amazing help, thank you so much! I'll reply following your points

    1. Good advice. I've been taking this, any idea if it is any good?
    [​IMG]
    2. I'm aware of the volatile nature of the test results for KP. I've never really taken them as defined indicators. To tell you the truth I think I was positive only 12 years ago, on my first test. All the following tests over the years returned negative.

    3. Stress is a huge thing for me. I get stressed a lot, even for a remark from a friend I start sweating and get agitated. I got a little better over the years, but mainly in masking it. A few years ago I've tried Transcendental Meditation and it did good to me. I've recently tried to do it again, but I had panic attacks and it was impossible to sit still for 20 minutes. Now I might be able to do it as I'm a little calmer and not suicidal all the time. Unfortunately life has reserved me a lot of very stressing traumas, especially regarding relationships, especially the last one. It's 1 year now and I'm still obsessively thinking about what has happened every moment, and I dream about it too every night. When anxiety flared up 1 year ago with panic attacks I started chain smoking and I believe it has saved my life somehow. I know I'm killing myself with cigarettes, I know I'm stressing my system and loading it with nasties. I know I've to quit asap. Right now I'm on about 5-10 a day. On good days maybe 3. I'm doing my best. Before this break down I stopped for 5 years, this time seems impossible.

    4. Diet. Certainly since the break down my diet has degraded as I find very difficult eating regularly and cooking. Again, I'm trying to do my best. Most of the time I can avoid sugars and if I eat carbs they're wholemeal. I'm finding unthinkable to be able to get organised to have a sound diet. I know I need to try all these things, but I don't have the energy/motivation (=deep depression).

    5. I'm trying to keep my teeth clean flossing each night. I've about 20 fillings (white) and I think 1 root canal done ages ago.

    6. I've tried to minimise chemical exposure as much as possible. To clean the house I use baking soda, I've painted the walls with water based paint, I don't use chemicals, no WiFi, herbal toothpaste with no fluoride, soap with no parfumes and fragrances. The house should be pretty mould free.

    7. Exercise: I've been going at the gym for 20 years, until the breakdown. I remember in the last couple of years of gym I was feeling flu-like symptoms for days after a session. I've now lost 12Kg, all muscles. I'm very skinny. Now I'm starting to feel like I could try something gentle. I need to get organised which seems to be a big issue for me right now.

    8. I'm trying to stay in the sun as much as I can, although it's not easy in Scotland (I'm Italian) and yes, I do burn very easily so I need to be careful. Regarding supplementing D3 at the moment I'm trying not to add any other supps on the top of the protocol the doctor gave me (attached above) as he clearly stated not to take any other supps. I don't want to screw up the protocol.

    9. Yes, but somehow I just can't do anything. I spend my days walking around with the dog, smoking, browsing the Internet. Can't work, can't exercise, can't meditate, can' read, all things I was used to do before.

    10. This is an interesting point. I seem to be completely unable to even think of 1 single thing that I would enjoy doing. Isn't that strange? It's as if all the interest, all life, all energy, all motivation had left me. I don't see the point in anything.

    11. That's difficult as all my closest affections have left/betrayed me. I've a few friends here but not as close as the others were and, again, I don't feel motivated to get closer or to create new friendships. I'm making an effort, but it's a huge one each time and I can only talk about how miserable I feel.

    12. I'll look into these superfoods.

    13. I'm taking evening primrose at the moment.

    14. I do drink coffee but I feel awful and incredibly sleepy if I try to cut.

    Really great advices, thanks so much!
    p
     
  12. paq71

    paq71

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    UPDATE: About 1 week ago I've introduced 5mg of Lithium Orotate into my protocol. I had an immediate huge overall improvement especially regarding anxiety and depression. I've noticed huge improvement in general mood, obsessive thoughts, desperation, fear, energy, brain fog, tiredness, sleep.

    I've noticed that it was producing its effects after about 3 hours from ingestion of the pill and that the effect would last about 4 hours. So I've tried to take 10mg and then 15mg, split in 5mg doses after breakfast, lunch and before bed. This dosage seem to work well for me.

    I still don't feel 100% but really huge improvement.

    Any thoughts?
    p
     
  13. pogoman

    pogoman Senior Member

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    I see you are double heterozygous for mthfr and heterozygous for tcn2.
    I won't say "compound" heterozygous ;)
    Lithium orotate is supposed to help plasma B12 convert into cellular B12, the tcn2 c677g mutation can block that.
    http://ghr.nlm.nih.gov/gene/TCN2

    I am homozygous for both, I found taking a good brand of lithium orotate and tons of B12 has helped immensely.
    I found the Seeking Health brand of LO was not effective as the Swanson brand, I went back on Swanson a couple days ago and I had immediate improvement.
     
  14. paq71

    paq71

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    Yes, that's the brand I'm using. How much lithium are you taking? What form of B12? Can you tell me a little bit more about my mutations? Do you think I'm taking the right supps?
     
    Last edited: Jun 7, 2015
  15. pogoman

    pogoman Senior Member

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    here is a starter on the two main mthfr mutations, c677t and a1298c.
    http://mthfr.net/
    its been well documented and has to do with folate issues.
    but like with all mutations good or bad, not all will have symptoms especially if heterozygous.

    tcn2 c677g is also been researched.
    http://www.ncbi.nlm.nih.gov/pubmed/15941899

    google will find a lot more on both of the above.

    I take one of the Swanson's LO about 3 times a day.
    I also take a bunch of methyl and hyd B12 with them, usually 5 to 10 mgs at a time.
    I also take 400mcg of methyl folate about 3 to 4 times a day.
    The methyl B12 and methyl folate are Jarrows brand plus a health store's brand of liquid methyl B12.
    also adeno B12 from Seeking Health altho I have doubts now about it.

    for me, I can take tons of methyl supplements and not get over stimulated.
    however, sulfur compounds will cause fatigue and brain fog like crazy.
    so no sam-e, msm, methionine and the like for me.

    I also take coq10 as ubiquinol, riboflavin B2, L-carnitine and choline as they help my muscle pain and energy.
    I also take various others of the B vitamins except niacin, I haven't noticed they helped but just in case they do help methylation issues.

    also, I have hypergonadism and night sweats can be a symptom.
    inositol lowers testosterone levels so be aware.
    I am taking dhea short term to get my levels back up, I tried inisitol a couple months ago and I started getting sweating and energy issues from it.
     
    Last edited: Jun 7, 2015
  16. paq71

    paq71

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    Thanks a lot for the info! Quite different from my protocol. for sure I know I don't tolerate SAMe as it gives me huge anxiety and I feel like I'm going insane.

    Do you've a practitioner following you?
     
  17. pogoman

    pogoman Senior Member

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    I added more as you typed lol.
    I am seeing an endocrinologist and neurologist right now, saw a genetic doctor last year but he was not helpful.
    but the endo wants me to contact the genetic doc and let him know how the methylation supplements have helped.
    all they could diagnose me so far is a "noninflammatory myopathy".
     
  18. pogoman

    pogoman Senior Member

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    oh, one more thing about tcn2 while I'm here.
    from what I found if its an issue, you can have normal B12 blood levels but be low in the cells which causes symptoms.
    so starting lithium orotate helps it convert to the cells and you have to start or increase B12 supplements to feed the process and keep B12 blood levels from dropping.
     
  19. paq71

    paq71

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    I've started taking tiny amounts of hydroxyB12. Any tips on the right form to take?
     
  20. pogoman

    pogoman Senior Member

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    only thing I can offer is preferrably sublingual or liquid.
    hyd B12 is kinda rare where I live, stores offer just methyl or cyo B12 and even the local NP that offers shots at a health food store chain does not offer hyd B12 anymore.

    this is what I bought off of Amazon, it has no sugar so I can just take one sublingually when going to sleep without worrying about teeth issues.

    http://www.amazon.com/gp/product/B00P1O8SLS?psc=1&redirect=true&ref_=oh_aui_detailpage_o00_s01
     

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