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First try at Active Protocol and have questions.

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by JasonUT, Mar 3, 2017.

  1. JasonUT

    JasonUT Senior Member

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    Hello,

    I’d like to thank everyone in advance. I have been reading through this website for several months now. I have been on some form of methylation protocol for 2 years with very small improvement. First attempt was oral 800mcg mB12 and 800 mcg mFolate. About 4 months ago I switched to the SMP and worked up to 2 mg hB12, 2mg adoB12, and 12mg mFolate. I found some small improvement on the SMP, but it seemed to stall.

    About 3 weeks ago I decided to jump straight into the Active Protocol. I can say for sure that changes are happening, but it’s a mixed bag of good things, bad things, and strange things. Over-methylation, start-up, detox, whatever we want to call it. Something is definitely changing.

    The 1st week was a notable improvement in energy and mental clarity. However, this 3rd week symptom pattern has changed to Benzo withdrawal like symptoms. A nervous restlessness, anxiety, depression, jittery, very hard time getting to sleep, mind racing, upset stomach, nausea, low appetite, body aches, tightness in my legs and soles of my feet. It’s a different pattern than my usual CFS symptoms which are mostly dominated by fatigue, body aches, chills, and flu-like symptoms.

    By the way, I have two experiences with Benzo withdrawal. One cold turkey followed by reinstating with longer half-life benzo. Then slow 3 month taper supported by high dose 500mg x4 niacinamide to calm withdrawal symptoms a little. I think the benzo withdrawal was the final blow that sent me into full on CFS.

    My questions:

    1. Does my start-up response seem typical? If not, what needs to be addressed?

    2. Active Protocol seems to suggest 50 mg Zinc per day. Should this be offset by copper to maintain a certain ratio? My current intake of Zinc/Copper is 31mg/3.5mg. By the way, I have some random prostate pain.

    3. I don’t want to stall start-up or healing if that’s what is really happening; however, are there some technics to help get through the symptoms? i.e. CBT, mindfulness, Epsom Salt Bath, etc.

    4. I think I have all Active Protocol Basics covered except Calcium and Vitamin E. Any suggestions on brand, type, dosage? How do these two basics play into Active Protocol process?

    5. I have the Jarrow B-Right Complex for my midday dosing, but haven’t tried it. How does this second dosage play into the Active Protocol process?

    6. For those Active Protocol veterans, what should I change?

    7. Is it possible to take too much methylfolate? Am I just pissing away the extra that my body doesn’t need without any real physical harm? My new nutritionist, who is familiar with methylation, wants me to move up to 15 mg daily. I guess this is in-line with the highest does of Deplin.

    AM Regiment:
    Vitamin D – 2000 IU
    Vitamin C – 500 mg
    Emerald Labs Men’s 1 per day
    Methyl-life AdoB12 – 3 mg
    Jarrow mB12 – 1 mg
    Methylfolate – 5 mg
    Nature’s Lining – 1 pill
    Probiotic – 1 pill
    Colostrum – 1.25 g
    Fish Oil – 1 pill
    Sunflower Lecithin – 7.5 g

    Noon Regiment:
    Vitamin C – 500 mg
    Jarrow mB12 – 1 mg
    Methylfolate – 5 mg
    Copper – 2 mg
    Fish Oil – 1 pill

    Dinner Regiment:
    Vitamin C – 500 mg
    Methylfolate – 1 mg
    Nature’s Lining – 1 pill
    Zoloft – 12.5 mg
    Sunflower Lecithin – 7.5 g

    Bedtime Regiment:
    Vitamin C – 500 mg
    Methyfolate – 1 mg
    Mg Glycinate - 200 mg
    Mg L-Threonate – 48 mg
    Melatonin – 1 mg
    Tryptophan – 500 mg
    L-Orthinine – 500 mg
    Doxylamine succinate (Unisom) – 12.5 mg
     
    Last edited: Mar 3, 2017
  2. JasonUT

    JasonUT Senior Member

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    I made a small change this last Tuesday. Reduced mfolate from 5mg, 5mg, 1mg, 1mg per day to 1mg 4x daily. I was nervous that maybe I was pushing to hard. Any advice or feedback is greatly appreciated.

    On another note, my symptom pattern has changed yet again.

    Positives:
    1. Systolic BP has increased from ~100 to ~110. Dystolic is still ~65.
    2. Seems my body temperature is up. I've had this happen before, but hopefully it stays up this time.
    3. Sleep may be improving. I'm not taking unisom the last three days and slept okay.
    4. Jittery, anxiety, restlessness is down.

    Negatives:
    1. Body, muscle, joint pain increased
    2. Abdomen, bladder, prostate pain increased
    3. Increased tiredness. Desire to nap.
    4. Increased urination
    5. Increased irritability
    6. Increased sore throat and pain in arm pits. Lymph nodes maybe?
    7. Still low appetite. Increased nausea
     
  3. JasonUT

    JasonUT Senior Member

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    Potassium observations so far:
    1. Potassium does seem to help my symptoms
    2. Adding organic bottled vegetable juice ~1000mg K+ per day
    3. Adding K+ gluconate ~1000 mg per day in divided doses. About 1/2 tsp per 16 oz water

    However, pre-supplementation serum K+ was 4.6 on Monday, march 6.

    Maybe intracellular K+ and magnesium is what counts.

    I have a lab req for RBC electrolytes and serum basic metabolic panel that I need to complete.
     
  4. Dechi

    Dechi Senior Member

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    You are very brave. I admire anoyone who even contemplates ingesting so many supplements at once. I really hope it works for you.
     
    slysaint likes this.
  5. CCC

    CCC Senior Member

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    Hi @JasonUT : well done for giving it a go. Especially when you have things like zoloft in the mix as well.

    Freddd's approach is not for the fainthearted. The start low and build up verrrry slowly is exactly the right way to go. Everyone has different requirements.

    We (my son) started just over a year ago and it improved a lot of things. So here's a few tips:
    • potassium: we use a headed teaspoon at a time - usually mixed in the a fake chocolate milkshake (cocoa, d-ribose, potassium, almond milk). Potassium gluconate powder mixed in something like milk also won't burn your tummy (might taste disgusting through)
    • vitamin C: we've recently discovered that ascorbate powder stirred into a glass of freshly squeezed orange juice is the most effective way to do it. About 1/3 to 1/2 tspn, in juice, 3 times a day. I've read that you can't absorb more than 500mg at a time (contradicting our experience), and that you absorb more if your body really needs it.
    • copper: don't let it drop too low or go too high. We need only 2mg per week, but zinc every day. In contrast, Freddd takes huge amounts.
    You can absorb quite a bit of stuff through your skin: zinc, magnesium and even B6. We apply 0.7 ml of a metagenics zinc drink on the skin in the mornings, footbath in the evenings of a handful of epsom salt, a pinch of borax and a few drops each of eucalyptus and tea tree oil.

    We also found we could drop some of the supporting supplements: establish a baseline at which you are really stable, then drop something you think you might not need. Tip: people seem to always need B12, folate and potassium on this, so don't drop them. For us, B2 is also crucial. We also can't tolerate SAMe or LCF (induce extreme fatigue). So everyone is different.
     
    Last edited: Mar 12, 2017
  6. JasonUT

    JasonUT Senior Member

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    @CCC

    How long did it take before you started seeing positive results on the Active Protocol?

    How did you discover the correct zinc to copper ratio needs?

    According to this clinic trail from Rich and Dr. Nathan, it took 4-6 weeks to see positive results and normal Methylation Pathway Panel results started around 6 months.

    http://www.prohealth.com/library/showArticle.cfm?libid=16138

    Interestingly, a lot of my current negative symptoms match the "suspect result from die-off and detox" list:

    http://phoenixrising.me/treating-cf...gue-syndrome-cfs-by-rich-van-konynenburg-ph-d

    Interesting you mention B2. I just discovered old OAT's that show B2 deficiency, but this was never brought up by the doctor.
     
  7. JasonUT

    JasonUT Senior Member

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    @CCC

    By the way, can you expand on your Zoloft comment? It sounds like you may know something important.
     
  8. CCC

    CCC Senior Member

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    @JasonUT

    Here's a long answer. I've tried to break it up.

    Instant improvement
    We saw results instantly from methyl B12. That first methylB12 gave instant 'neurological brightening' as Freddd called it.

    Improvement over time

    My son (the patient here) later told me that the effect lessened after about the first week. I happened to stumble across the two mega B2 threads, we added B2, and the improvement kept on happening.

    He started in mid-January last year. Just before the end of January (so a few weeks later), he suddenly - as if someone plugged in a small battery - stopped dragging himself around the house to get around and started walking with a small spring in his step. At the end of March, the brain started working again.

    We slowly worked out way up to about 15 mg of methylB12 before switching to the B12 oil sometime in the middle of the year (this was always the plan if it worked).

    Since then, it's largely been a slow and steady improvement.

    How we discovered copper
    After a year of doing what a doctor said, my son felt more fatigued, had even less appetite, and was more malaised (is that a word?), unable to even leave the house.

    I look up the ingredients list on the practictioner-prescribed supplements and started adding up the B6 and the zinc. Then I googled pyrolia (the reason for those supps), noticed that high levels of zinc (and vitamin C I've since discovered) can deplete copper. Then googled copper deficiency and came to this paper.

    I took that paper to the local GP along with a spreadsheet of supplements and their ingredients, and asked for zinc, copper and b6 tests. He added in selenium. My son had crashed his copper levels and overdone the zinc and b6. His selenium was a bit high, and the local health food shop naturopath managed to find an old paper that said B6 helps retain selenium.

    That's when we started googling, found PR and started the Freddd protocol.

    The dosage of copper we use now is a result of trial and error.

    About B2
    B2 is essential. We saw nothing with cheap B2, so we started FMN - the bioavailable form - as recommended by @ahmo . It took weeks and weeks to see any spillover into the urine. After a while we moved back to the cheap B2. Something had been topped up and it started working (and it's cheaper).

    Towards the end of last year, we ran out of methylfolate and found ourselves only with some mega folinic and B2. So we started taking them together. This led to another improvement. Methylfolate (as 5mg quatrafolic) is taken just before going to bed now.

    About folate
    At first it seemed to be important only because the B12 created a need for it. Now, after several months of treating bartonella (like Lyme disease), it seems to be a need in its own right.

    And about Zoloft
    Sorry, but everything I know about zoloft is from others complained when their doctors changed their meds. I don't even know if that's a big or little dose you're on. Maybe ask your methylation doctor about the interaction between SSRIs and methylation.
     
    LadyDay likes this.
  9. JasonUT

    JasonUT Senior Member

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  10. JasonUT

    JasonUT Senior Member

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    @CCC - Fascinating story. Your story makes me hopeful that this may help me. Please continue to share you and your son's experience.

    Time frame seems consistent with other stories I have read.
    1 week - Instant energy boost
    2+ week - Reduced effect / detox / start-up / die-off / something
    3+ months - Things start to normalize. Apparently, this is supported in Dr. Nathan and Dr. Rich's study. At 3 months, Methylation Pathway Panel results started getting very close to normal.

    It's the 2+ week to 3-6 month range that appears to be hard. Trying to figure out what is happening and how to correct it seems like such a mystery. Is it co-factor depletion, die-off, detox, etc?

    Questions:
    1. What was your sons starting does of mB12 and mFolate?
    2. How did you know you were getting B2 "spillover into the urine"? tests? i.e. I assume this means the body is now saturated with B2 and eliminating excess in urine? It appears that B2 may be important for breaking down food and absorbing nutrients. I wounder if this enables the body to more easily get the additional needed nutrients and co-factors from diet to keep things healing.
    3. What was your sons B2 dosage?
    4. Can you please point me to the mega B2 threads that you reference?
    5. Are there risks in taking excess B2?
    6. Does your son take the two b-complex dosages per day according to Freddd's protocol? What effects does this cause?
    7. Why does you son take the 5mg mFolate at bedtime?
     
  11. CCC

    CCC Senior Member

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    Hi @JasonUT I've beena way from the keyboard.

    1. What was your sons starting does of mB12 and mFolate?

    Sublingually: 250mcg of mB12 and possibly 400mcg of mfolate. first just in the morning, then twice a day, then as needed as he became more confident. It was the adenosylB12 he was very sensitive to - even a crumb gave him extreme nausea for a while.

    2. How did you know you were getting B2 "spillover into the urine"? tests? i.e. I assume this means the body is now saturated with B2 and eliminating excess in urine? It appears that B2 may be important for breaking down food and absorbing nutrients. I wounder if this enables the body to more easily get the additional needed nutrients and co-factors from diet to keep things healing.

    The colour. The urine goes a colour that is close to dutch boy chartreuse (google it) when the metabolic byproducts spillover into the urine.

    The big reason we got onto it was my son's OATs (organic acids test - a urine test) that showed a block at the succinate dehydrogenase step in his Krebs cycle, and B2 is an important vitamin at that point. See this post for more of an explanation.

    3. What was your sons B2 dosage?
    Varied. The trick is that you can't absorb more than 25mg at a time, so he just took 25mg at a time (first as 18mg sublingually, and then as 25mg orally because that's how the tablets came). He would have been up to 100 to 200 mg total at the peak.

    4. Can you please point me to the mega B2 threads that you reference?
    It's worth reading both threads, because they end up agreeing with each other in the end! It's these long threads, and the sometimes heated discussions, that helped us learn how to pick up the micro effects of different things on the body.

    Since then, the need for extra B2 has been independently proposed by a few people, including the B12oils.com inventor (a B vitamin biochemist).

    5. Are there risks in taking excess B2?

    Theoretically, you wee out the excess, but I have heard that you can unbalance your vitamins, especially B1. Some people have found it uncovered a need for manganese as well. My son just takes a good mutli, and a manganese tablet every few days. That seems to be enough for him.

    There was a suggestion that he is MTR/MTRR, which results in a huge demand for B2 until there's enough mb12 in the system.

    We did find that the higher dose of B2 reduced his demand for mfolate and mB12.

    6. Does your son take the two b-complex dosages per day according to Freddd's protocol? What effects does this cause?
    He takes just one as a precaution. He doesn't need the second. Half the time I can't get him to take even one these days, but he did for the first year.

    7. Why does you son take the 5mg mFolate at bedtime?
    He has worked out he needs it. He otherwise wakes up in the morning (he has hypersomnia - so he sleeps all night) with massive folate cravings. This just lessens that a little bit.
     
  12. JasonUT

    JasonUT Senior Member

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    @CCC Thanks for your reply. Hopefully, continued discussion, debate, and collaboration on patient experience is good for everyone.

    My OAT Analysis for B2 factors from 2015:
    Succinic Acid was high: 6.0 (Range is less than 5.3) (Mitochondrial Krebs metabolite)
    3-Methylglutaric was high: 0.62 (Range is 0.02 - 0.38) (Mitochondrial Amino Acid Metabolite)
    Glutaric Acid was high: 0.43 (Range is less than 0.45) (Nutritional Marker)

    My MTR/MTRR Status:
    MTR A2756G is AA -/-
    MTRR is AG +/-
    I don't know what this means for me. Anyone have any knowledge of MTR/MTRR?

    Brainstorming Next Steps:
    1. OAT
    2. Methylation Pathway Panel
    3. NutrEval or SpectraCell Nutrient Panel
    4. Try FMN (B2)
    5. Try CoQ10
    6. Try Carnitine
     
    Last edited: Mar 16, 2017
  13. JasonUT

    JasonUT Senior Member

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    Homework note to self: read up on elevated BUN. My BUN is consistently in the 19-25 mg/dl range. Reference range is 8-20 mg/dl.

    There is an old quote from Rick Van K here in post #5:
    "That all makes sense to me. Your creatine production may be low because of a methylation deficit that that would raise the BUN/creatinine ratio. B6 is needed to synthesize neurotransmitters, and B2 is needed to help break them down, so a balance between the two is necessary to maintain normal neurotransmitter levels."

    How did we jump from BUN/creatinine ratio straight into B6 and B2's role in neurotransmitters? Nevertheless, old OAT's show low B2 and B6. So this is probably something I need to figure out.

    Further down the same thread in post #6, Rich states:
    "The urine organic acids panel, together with the urine amino acids panel, will give indirect information on the status of methylation. In the urine organic acids panel, if the methylmalonic acid and the formiminoglutamic acid are both elevated, that is usually a good indication of a partial methylation cycle block. If pyroglutamic acid is high or low on this panel, it indicates glutathione depletion. If there is a large drop between citric acid and either of the next two citric acid metabolites, that also suggests glutathione depletion. On the amino acids panel, the sulfur-containing amino acids (methionine, cystathionine, cysteine, cystine and taurine) will give information about the status of the sulfur metabolism in general, and glycine, serine and sarcosine will give information about the methylation cycle and the transsulfuration pathway."

    Breaking this down for me:
    Methylmalonic Acid and Formiminoglutamic Acid - MMA is elevated on 3/21/2015 and 5/26/2015 test. I can't find Formiminoglutamic Acid.

    Pyroglutamic Acid - High but in range on 3/21/2015. High out of range on 5/26/2015. Conclusion - Glutathione Depletion (CPL Lab 11/5/2015 shows Glutathione Total 593 Range 544 - 1228uM)

    Citric Acid and Citric Acid Metabolites - I am having trouble figuring this one out.

    methionine, cystathionine, cysteine, cystine and taurine - I can't find these on my OAT

    glycine, serine and sarcosine - I can't find these on my OAT
     
    Last edited: Mar 20, 2017
  14. JasonUT

    JasonUT Senior Member

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    My BUN/Creatinine Ratio Analysis: First column is date, second column is symptoms bad Yes/No/?, third column is ratio). There seems to be a pattern. Higher than 20 means bad symptoms equals Yes.

    What does this mean? Does this help me in anyway?

    Date Flare Ratio
    12/23/2014 Yes 25.0
    5/4/2015 ? 21.0
    9/8/2015 ? 23.3
    10/27/2015 ? 22.7
    2/11/2016 Yes 22.9
    3/9/2016 No 18.3
    5/4/2016 No 19.6
    6/1/2016 No 19.1
    7/1/2016 Yes 20.7
    7/11/2016 Yes 23.3
    9/22/2016 No 16.8
    3/6/2017 Yes 16.5
    3/8/2017 Yes 23.4

    This site suggests some relationship between BUN, ammonia, sulfate, and CBS gene SNP.

    Orotic Acid is the Ammonia indicator on the OAT and mine is in range.
     
    Last edited: Mar 20, 2017
  15. JasonUT

    JasonUT Senior Member

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    Unfortunately, post #9 above can't be edited anymore. I was hoping to maintain a single source of reference for all my links. I am going to try the blog post function and hope that can become my single source of reference links.

    JasonUT - Possibly Useful Links and Info
     
  16. JasonUT

    JasonUT Senior Member

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    OAT and Krebs Cycle Analysis Post: The post will focus on my layman's analysis of my OAT in relation to a possible Krebs Cycle dysfunction.

    Per my OAT from May 2015, I appear to have some dysfunction in the Succinate and Funarate Steps. My Succinic Krebs Metabolite is high at 6.0 and the 2SD range is less than 5.3. Also, my Fumaric level is within the 2SD range but low. My CoQ10 levels are in 1SD, but a little bit low.

    1SD = 1 standard deviation
    2SD = 2 standard deviation

    There seems to be few reactions that occur at these two step in the Krebs Cycle. [Source]
    1. FAD -> FADH2
    2. Succinate + Q -> Fumrate + QH2

    What conclusions can I try to derive from the above?
    1. FAD is Vitamin B2. Maybe this is why some people have such good reactions to supplementing with extra FMN/R5P. FMN + ATP <-> FAD + PP. Supposedly FMN can cross into the cell and/or mitochondria without extra work. Maybe this is why FMN is so good, because it is very easily converted to FAD?

    2. CoQ10: Q is converted to QH2. i.e. ubiquinone is converted to ubiquinol. Apparently, the reaction can happen both ways. Maybe some people have a breakdown or deficiency in this reaction. Therefore, supplementing with one or both of the forms of CoQ10 may be helpful.

    3. My Succinic level is high, but my Fumaric level is low. Since Fumaric is low, could this suggest that L-Carnitine Fumarate is the correct form for me?

    4. Maybe the correct combo of L-Carnitine Fumarate, FMN, and CoQ10 will be enough to nudge my Krebs cycle back into more efficient operation?

    Note: L-Carnitine is a dipeptide derived from Lysine and Methionine. L-Carnitine's main function is to transfer fat to energy. [Source] Does this mean a break down in the methylation cycle affecting methionine will cause deficiencies in L-Carnitine output? So does L-Carnitine Fumarate have a double function to help the krebs cycle and provide some relief to the methylation output?

    This seems to tie a lot of things together for me. So what to do next?
     
    Last edited: Mar 20, 2017
  17. CCC

    CCC Senior Member

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    @JasonUT - It looks like you have the same issue as my son: a block at succinate dehydrogenase.

    B2 solved that for us, initially as the source naturals FMN, and then as the cheaper B2 once we could.

    COQ10 did nothing for us (regardless of price or form) . Even once FMN/B2 was on board, it worked a tiny bit then ran out of steam. LCF just makes my son very tired. ALCAR did nothing, but looking back, it might have helped him retain his muscle mass, which he has now lost.
     
    sb4 likes this.
  18. JasonUT

    JasonUT Senior Member

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    Appointment with Nutritionist seemed to go well. He agreed with the logic in post #16 above.
    We are in a wait and see period to find out if this methylation and mitochondrial support will work. He says minimum of 12 weeks before we can expect to see results. This aligns with Dr. Nathan and Dr. Rich Van K's clinical study here.

    Overall, based on OAT, glutathione serum, and BUN/creatinine tests, Doc seems to think there could be a detox dysfunction at the cellular level. Methylation, mitochondrial, and Kreb cycle support may help.

    He also thinks there may be a pathogen component to this.

    Actions for me:

    1. Potassium Gluconate supplementation 700-1000 mg is good, but should be offset with 400 mg Magnesium Orotate per day. I need to research this in greater detail.

    2. Per OAT and Glutahione Tests. Supplement extra FMN B2 with no risk. Watch urine color for B2 saturation level.

    3. Experiment with L-Carnitine Fumarate and Ubiquinol dosing. These should work synergistically with low risk. Could help Succinic dehydrogenase enzyme step in Krebs cycle.

    4. Consider Acetyl L-Carnitine; however, we both agreed that this may cause an unpleasant excitatory response. Medium Risk.

    5. Complete new OAT test through M.D.

    6. Stop taking colostrum for now. He is nervous about over-driving the immune response.

    7. Request SpectraCell Micro Nutrient Test by M.D. Test will check cell level nutrients.
    https://www.spectracell.com/patients/patient-micronutrient-testing/

    8. Request SED Rate, Homocysteine, and Ferriten test by M.D.

    9. Complete Methylation Pathway Panel.
     
  19. JasonUT

    JasonUT Senior Member

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    OAT and Krebs Cycle Analysis Post 2: The post will focus on my layman's analysis of my OAT in relation to a possible Krebs Cycle dysfunction.

    Looking at my OAT in greater detail I noticed that my 2-oxoglutaric is low in the 2SD range and Aconitic is slightly elevated, but still in the 1SD range. Looking at the Krebs cycle it appears that cis-Aconitate goes to D-Isocitrate and then to a-ketoglutarate (aka 2-oxoglutaric).

    Water and NAD+ appear to be the only two inputs into these steps in the process. So NAD (aka B2) pops up again.

    Is this even more evidence that I am deficient in B2 and FMN supplementation will help?
     
  20. JasonUT

    JasonUT Senior Member

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    @CCC
    Thanks so much for taking the time to answer my questions. I have a few more. My current B2 dosage is:

    Breakfast:
    R5P, Ribofavin - 25 mg via Emerald Labs Mens 1-day Multi +
    FMN - 18 mg via Source Naturals Sublingual

    Lunch:
    Riboflavin - 25 mg via B-Right

    Questions:
    1. So your son was taking 100-200 mg FMN per day? I am guessing this was in multiple 25 mg doses throughout the day.

    2. Did you notice any difference between the sublingual and oral tablet? Which was more effective?

    3. What brands are recommended?
     

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