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Mar 17 2013

My Nutrigenomic Analysis

The following post chronicles and details my journey in largely curing myself of Chronic Fatigue Syndrome (CFS). Very recent advances in genetic testing and nutrigenomic analysis have been a tremendous asset and self learning tool.

Genova DetoxiGenomic & MTHFR results:

DetoxiGenomic Profile & MTFR

Genova ImmunoGenomic results:

Selected 23andMe results (converted to Yasko using – Calico13’s spreadsheet):

Yasko Methylation results:

My 23andMe Genetic Ancestral Lineage going back 500 years:

23andMe genetic ancestry composition

Gluten Celiac Markers: HLA-DQA1       rs21787668

Jonathan - Gltuen Celiac SNP result

Analysis of Phase 1 Detox –

Cytochrome P450:

CYP1B1 (up-regulator polymorophsim):
Description – 2 SNPs were measured for this Gene. Specific variants are L432V +/- and N453S negative. This gene is responsible for 4-hydroxylation of estrogen as well as detox of common environmental toxins.

Treatment – Currently supplementing with DIM to support the production of good estrogen

Substrates: Caffeine, Estradiol, Estrone (4-hydroxylation), Resveratrol, Testosterone

This means I metabolize Caffeine quicker. Also not to happy about metabolizing Testosterone faster. Grapefruit juice is an inhibitor of this enzyme….maybe drink more of this?

CYP2C9 (down-regulator polymorphism):
Description – This enzyme helps with the metabolism of certain pharmecutical drugs…..none of which I take anyways.

Treatment – Avoid: N/A
Substrate – Ibuprofen (becomes more potent due to slower metabolization)
Inhibitors – Echinacea, Garlic, Kava kava, Milk thistle, Saw Palmetto, St.John’s wort

Gene SNP Analysis of note via Promethease23andMe & OpenSNP:

Key beneficial genetic traits:

rs8177374(T;T) – A beneficial mutation which provides resistance to several diseases such as invasive pneumococcal disease, bacteremia, malaria, and tuberculosis.

COMT +/+ V158M (rs4680(A;A)) – advantage in memory and attention tasks (worrier strategy) Little or no response to modafinil. You are more difficult to hypnotise.

rs53576(G;G) – optimistic and empathetic. The one in four subjects who inherited a variation in this allele called G/G were significantly better at accurately reading the emotions of others by observing their faces than were the remaining three-quarters of subjects. 10 journal articles explore this Oxytocin Receptor encoding Gene. The empathy gene!

rs10784502(C;C) – (C;C) has higher cranial capacity and over 2% higher IQ.

gs150 – Most likely CYP2C19 normal, i.e. CYP2C19*1, and therefore of the ‘rapid metabolizer’ phenotype. This is based on none of the 11 CYP2C19 variants on the 23andMe v2 chip (out of 19 reported in SNPedia; most are quite rare) being observed.

gs154 – You appear to be a CYP3A5 expressor. This is normal.

gs158 – CYP1A2 normal metabolizer

rs2187668(C;C) – 0.48x average of getting Celiac Disease. (less chance of having issues with gluten) In reference to the HLA-DQA1 protein.

rs2180439(C;C) – reduced risk of baldness
rs1042725(C;C) – ~0.8cm taller

gs182 – CYP2D6*39 normal metabolism

rs25531(G;G) – long form of 5-HTTLPR Seratonin transporter also called the SERT gene. Most efficient form. less sensitive to pain; happier. Significantly reduced risk of depression. Great article in the Atlantic referring to research on this gene. The Science of Success

MCM6 gene (A;G) – Likely to be tolerant due to lactase persistence.Higher adult lactase enzyme levels. (May still be lactose intolerant for other reasons.)

rs1815739(C;T) – One working copy of alpha-actinin-3 (ACTN3 gene) in fast-twitch muscle fiber. Better athletic muscle power performance such as in weightlifting or sprinting. Superior burst strength.

rs2542052(C;C) – Higher odds of living to 100.
rs1800497(G;G) – Learns quicker from mistakes. (source)

rs1861046(G;G) – Conduct disorder (CD) gene. I consider this a benefit! hahaha

Key Not-so beneficial Genetic Traits:

rs1021737(T;T) +/+ – Homozygotes for this variant allele in the CTH gene had significantly higher plasma homocysteine levels than other genotypes in a cohort of 496 Caucasian individuals. (Hyperhomocysteinemia)

rs5186(C;C) – 7.3x increased risk of Hypertension

rs17070145(C;C) – reduced memory abilities

gs157 – You appear to have a common genotype in the gene CYP1A2 which metabolizes coffee more slowly than some other forms. The same amount of caffeine will tend to have more stimulating effect on slow metabolizers than on fast metabolizers.

gs161 – CYP2C9 intermediate metabolizers are 30% of the population. May require slightly different dosages for drugs such as tamoxifen, warfarin, fluvastin, and many nonsteroidal anti-inflammatory agents such as aspirin, ibuprofen and naproxen.

rs762551(A;C) – carrier of one CYP1A2*1F allele; slow metabolizer more strongly affected by drinking coffee

rs4654748(C;T) – 1.45 ng/mL lower Vitamin B6 blood concentration

rs2282679(A;C) – somewhat lower vitamin D levels

rs12934922(A;T) – Reduced conversion of beta-carotene to retinol Associated with Rs7501331 and reduced BCMO1, lower ability to convert beta-carotene to retinyl esters and higher serum beta-carotene levels.

rs7501331(C;T) – Reduced conversion of beta-carotene to retinol Reduced BCMO1 activity results in 32% lower ability to convert Beta-carotene to retinyl esters and higher serum beta-carotene levels.

Complete Roadmap Guide for the following analysis: (click for larger image)

Yasko Method interpretation of results:

COMT V185M +/+ & H62H +/+

The combo on this enzyme leads me to have a “Super COMT +/+” status. This is a rather serious mutation. It means I have a 3-4 fold reduced clearance neurotransmitters dopamine, epinepherine (adrenaline), and norepinephrine from neural synapses. Thus leading to naturally elevated levels of dopamine and adrenaline. This makes a lot of sense because naturally I am a fairly happy person. In some ways its like I am permanently on anti-depressants making me more resilient to depression. Another plus to this particular polymorphism is that with higher dopamine levels it leads to higher intelligence than average due to how these neurotransmitters interact with the pre-frontal cortex of the brain. Many savants have this defect.

The down side however is the higher levels of adrenaline which leads to heightened anxiety and stimulation of the SNS system. In times of stress adrenaline levels can build quickly, creating a negative feedback loop, due to the fact nor-epinephrine is one of the few neurotransmitters that doesn’t inhibit it’s own production when levels become abnormally high. This is a survival fight or flight mechanism and can quickly lead to adrenal burnout & chronic fatigue if stress/anxiety isn’t properly managed.

This enzyme also processes the colours red & purple. That means ingesting fruits or dyes with those colours can cause an even further slow down of the COMT enzyme. The chemical responsible for this is a Phenol. Dr. Rosemary Waring is the pioneer in research of this. Thus avoiding a lot of the colourful fruits and vegetables is recommended, and when eating them supplementing with a digestive enzyme that breaks down phenols such as No-Fenol by Houston Enzymes is beneficial.

COMT also metabolizes estrogen.

COMT also shares a promoter site with another enzyme called thioredoxin reductase, which helps regulate oxidative stress utilizing lithium. Hence lithium supplementation has been found by Dr.Yasko to be helpful.

VDR Taq status is important to fully understand the ramifications of this defect. Awaiting test result.

Further testing: Get tested for phenol-sulphotransferase-P deficiency?

Treatment:

SHMT +/+

SHMT - Methylation

SHMT is considered a priority mutation by Dr. Amy Yasko. It seems that a defect here has a tendency to lead to gut dysbiosis and imbalanced flora. I have a double defect here and have not surprisingly found much help from taking probiotics. Gut issues is something I have had life long issues with and the SHMT mutation in a way compounds gut issues resulting from the reduced breakdown of nor-epinephrine due to COMT mutations.

Treatment:

MTHFR C677T +/-

This means I have a 30-40% reduced rate of converting folate into the active form called 5-Methyltetrahydrofolate which is needed primarily for methylating B12 in order to convert homocystine into methionine in the methylation cycle which then is converted into SAMe. This has knock on effects for thousands of reaction in the body involving methylation with SAMe including DNA & RNA synthesis, epigenetics as well as eventually leading down to glutathione production.

Treatment:

MTHFR A1298C +/-

This is the more serious of the two MTHFR mutations. This mutation affects the Tetrahydrobiopterin (BH4) cycle which is responsible for the production of dopamine, seratonin, nor-epinephrine as well as a co-factor in the production of nitric oxide (NO) which detoxifies ammonia.

In this case I am not to concerned about how this affects dopamine and nor-epinephrine production due to a compromised COMT, however this can greatly reduce seratonin production which is a concern due to a normal working MAO A which breaks serotonin down. This defect also impacts detoxification of ammonia via NO. I have a CBS up-regulation meaning ammonia production is increased 10-15x making this even more of a problem. The NO cycle further impacts the Citric Acid cycle compromising energy production leading to cellular fatigue.

Treatment:

  • MTHFR A1298C + Liver Support – chiefly for L-biopterin to support BH4 production
  • Apple Pectin & Malic Acid – Potent Aluminum detoxifer

MTRR A66G +/- & MTRR-11 AGG4A +/+

This enzyme is responsible for the re-methylation and recycling of vitamin B12. Fortunately the MTRR A66G +/- is a fairly minor defect considering all other possible MTRR defects. The MTRR 11 +/- is more serious leading to faster detoxification as well as amino acid dumping enhancing the need for more protein and perhaps supplementation with BCAA’s. Because of my COMT +/+ status and the supposed abundance of methyl groups in addition to a normally functioning MTR enzyme supplementing with hydroxyb12 instead of methylb12 is more desirable.

Treatment:

BHMT-08 +/-
This enzyme is the “shortcut” from homocysteine to methionine. This defect appears to be one of the more insignificant ones, and the best thing to do is make sure MTR/MTRR is working properly and efficiently.
CBS C699T +/-

This is one of the most serious defects. This defect is an up-regulation operating at 10-15x normal rate. This means homocystine is rapidly drained from the methylation cycle down the transulfation pathway producing toxic ammonia and sulfites in addition to negatively impacting glutathione production.

Ammonia is a potent excitotoxin. It binds to glutamate/NMDA receptors causing over-activation of neuronal cells. This is one of the key factors in causing feelings of  tired but wired, anxiety, excess muscle tension along the spine and neck, brain fog, psychological fatigue, memory loss and a whole host of other nervous system disorders. It will also cause microglia activation (the brains immune system) as it cleans up neurons that died form over-stimulation.

The CBS defect is compounded by defects with MTHFR A1298C & NOS. BH4 and Nitrous Oxide are used to help clean up ammonia, and if those systems are compromised it will exacerbate ammonia detoxification issues. It requires two BH4 molecules to detoxify one ammonia molecule.

Bacteria in the gut that produce ammonia will also compound the CBS problem. Thus taking things like Yucca root to help soak up ammonia int he gut so it doesn’t leak into the body and start affecting the brain is beneficial. Dr.Yasko often recommends a low protein diet in order to reduce intake of nitrogen based amino acids, however I don’t this is particularly wise. Amino acids form protein are far to essential for most bodily functions. Amino acids from protein in your diet are required for almost every process in the body and all your tissues, fibers, muscles, organs are composed of them. As well as your neurotransmitters, hormones and your detox “components”!

According to Metabolic type theory those with SNS dominance will have a higher protein turnover in the muscle leading to yet more ammonia buildup further necessitating the need for ammonia detox support.

Because Ammonia is such a potent excitotoxin, it is reasonable to assume that excess glutamates from processed flavored food will be even more of a burden. Thus limiting MSG, hydrolyzed-anything and the food additive such as “Natrual Flavors”, “Spices” would be prudent because they often contain hidden glutamate. (source)

Treatment:
  • CBS/NOS – Kidney Support
  • Small amounts of B-6 (P5P form) – CBS uses this as a cofactor and a CBS upreg can lead to depletion
  • Molybdenum & Manganese to help eliminate sulfites
  • Yucca & Charcoal to soak up excess ammonia – (only use charcoal on an empty stomach separated from meals by a couple of hours, otherwise it will also catch valuable nutrients)
  • CBS RNA
  • L-Carnatine Fumarate – Fumarate is used in the Urea cycle to help eliminate Ammonia
  • Apple Pectin – Helps detoxify aluminum which then frees up glutamine synthetase to help transport ammonia out of the brain
  • Other possible Urea Cycle supports: L-Ornithine, Citruline Malate, L-Arginine

Preamble

I came down with CFS/Fibromyalgia/ME when I was 15 years old with no know/remembered trigger. I am 28 now, so I have been battling this for almost half my life. My primary symptoms are chronic fatigue, tired but wired, anxiety, excessive high body temperature…especially at night, full body muscle achiness but primarily neck and spine, brain fog, poor concentration, poor memory, headaches, no appetite for 3 hours after waking- nausea associated with this, IBS, allergies & very poor recovery after exercise. I am textbook ME/CFS/Fibromyalgia.

I have other problems that I have had since birth which indicate issues with Methylation prior to the onset of CFS/Fibromyalgia. My mother used thyroid meds to get pregnant with me, her mother died of thyroid cancer, my grandpa on my dad’s side has prostate issues and his mother had b12 issues, my dad and his mother both got grey hair in their late 20’s, my cousin on my dad’s side has CFS….all of these things are linked with polymorphisms in methylation. So thus I have a sneaking suspicion I inherited issues from both my parents in regards to this. I was a colicky baby, had dry bleeding skin, numerous allergies, anxiety, and nightmares since I was born. All this got worse with the onset of CFS. As a child I also apparently reacted violently to MMR vaccinations.

What has worked so far & my theories on why

I have tried a gazillion supplements over the last decade or so, and been to countless doctors/Naturopath’s and tried many therapies & diets. I even went to the Mayo clinic and after $10,000 worth of work they told me I was perfectly healthy according to their tests and to go home and learn to live with it. Yea right!

30% -> 70%

  • L-Glutamine
  • High Protein Diet

For me being at 30% was, flunking out on half my courses at school, needing to nap 3+ hours a day, unable to exercise, extreme muscle tension, full body aches and pains, severe anxiety, insomnia, fatigue, felling like vomiting every morning and more. This state persisted for about 5 years.

What worked was, large doses of Micronized L-Glutamine 10-20g a day. This increased my energy from about 30% to 60% and a high protein diet took me to about 70%. The glutamine was a magic bullet in terms of the insane catabolism I had experienced with the associated achy muscular pain which had been virtually debilitating. L-Glutamine is a conditionally essential amino acid. Meaning if you are on a low protein diet (which I was for those 5+ years) it can cause serious problems.

Leaky gut and irritable bowel are particularly nasty situations and Glutamine also has implications here. Let me breifly describe how I think this works.

When the gut/ intestinal lining develops holes undigested food particles/molecules, particularly proteins leak into your body/bloodstream. These could be from ‘normal’ food, however, in a undigested/not-completely broken down form, your body thinks they are foreign invaders and attacks these molecules mounting an immune system response against them. Also bacteria will leak in as well. Had these food molecules/proteins originally been broken down properly your body wouldn’t be attacking them.
But now, your body is mounting a full fledged assault, exacerbating the ‘allergy/intolerance’ problem.

Slowly it seems like you become allergic to everything you eat, and technically you are. What this does is it severely taxes your bodies detox components namely glutathione and your white blood cells/killer T cells. Now the production of glutathione as well as white blood cells is DEPENDENT on you having a whole range of amino acids that support the methylation cycle and all it’s subsidiary cycles. Remember glutathione and white blood cells are made up of amino acids from protein. If you don’t have adequate methionine, cystine, glycine, etc. your body won’t be able to make glutathione and white blood cells. This is basic math!

So back to the leaky gut/holes in your intestine. We now have a serious negative feedback loop. Any protein/amino acids you are digesting properly are being used to make the stuff to mount an imuune response against the other protein/food particles leaking into your blood that weren’t digested properly. Your glutathione/white blood cells will be used up so fast, you won’t have enough to produce the stomach acid needed to break down the food particles in the first place. Now things just got from bad to worse. And there in lies the negative feedback loop.

You can forget about detoxing, mercury, ammonia, etc. your body is busy detoxing every meal you eat.
This is why large quantities of glutamine are so very helpful for leaky gut. They rebuild the “screen/filter” in your small intestine, that prevents the undigested protein molecules from leaking into your blood. So now your preventing your body from trying to detox all the food you eat. Which takes a humongous load off your immune system.

Now your body is still in a depleted state, so supporting glutamine with digestive enzymes can be very beneficial as well. The goal is to provide support breakdown of food so your body dosent have to expend precious resources to do it. Once your body’s basic system are back online, and your tissues more or less healed, you can begin to worry about detox of chemicals.

Consuming easily digestible proteins such as PeptoPro, a Whey protein isolate with protein enzymes can be very beneficial. Eating red meat, or veggie fiber-dense proteins is NOT effective, it requires too much work from an already taxed body.

What I did was start on large doses of glutamine (20g a day), then slowly ramped up protein intake to 60g with lots of digestive enzyme support over a few months. Once my health was at 50% I decreased glutamine to maybe 5g a day, and stopped the digestive enzymes and then started detoxing heavy metals, etc. It’s important to not put the cart before the horse here.

My theory here is that as an SNS dominant my body tends towards a catabolic state. This means that often it breaks down muscle tissue for energy in an almost preferentially version over fat. Contrary to SNS dogma I now eat a high protein diet in order to compensate for this…however it is currently from a raw vegan sprouted brown rice protein powder source. My body digests it easily and I can fuel my muscles keeping them in a slight anabolic state. This has really helped me preserve energy and alleviated many CFS symptoms. I am now 6ft tall at 190lbs and I eat almost 175g of protein a day. I am eating 35g of protein minimum every 3 waking hours. That’s 5 meals a day. This provides a steady steam of amino-acids to my muscles and body keeping it nourished and from going catabolic.

I also find that pumping iron, really helps balance my SNS. I work out 1x a week for 45mins, and have been building solid muscle mass and strength. Pumping iron appears to force my body and especially my muscles to strive for an anabolic state most of the time, provided I fuel them with adequate protein. The workout is inherently catabolic, however the 4day to 1week rest period in between sessions is where the muscles repair & rebuild and is anabolic. It really grounds out that SNS dominance.

Because my citric acid cycle is compromised due to methylation issues, mitochondrial factories are not working great. Intense Cardio is out of the question so thus I have resorted to a minimalist bodybuilding program instead. Cardio is based on how long your mitochondrial factories can pump out energy. Weightlifting on the other hand is more about rebuilding muscle fibers to become stronger and bigger. That said I do a bit of minor very low impact cardio.

70 -> 75%

Within 24 hours of taking DIM, I had a huge burst of energy, significant portions of brain fog cleared up, concentration improved and muscle achiness diminished. My emotions felt more stable and waking up in the morning I felt somewhat rejuvenated and not like I had been hit by a semi- truck which was the norm for me. The reason this worked was it ties in with the COMT +/+ defect as well as CYP1B1 up-regulation. (for additional info see my Xeno/estogen thread)

75 -> 80%

  • SNS support Supplements: Beta Carotene, Thaimin (B1), Riboflavin (B2), Niacin, Pyridoxine (B6), Folic Acid, Vitamin D, Magnesium, Potassium, Manganese, Chromium, Alpha-linolenic acid
For more information about this see my: Metabolic Diet & Supplements thread

I started the whole list of SNS supplements, and started having improvements in my health within 12 hours. I would say it has boosted my overall health and well being by about 5-10%, but then again I am already on a mostly SNS diet…which really is the most important part.

80 ->90%+

  • Yasko Supports, biopterin, RNAs, Yucca, etc.
I feel the methylation cycle stuff is the last leg for me in terms of overcoming CFS. The Yucca has really diminished the muscle tension I feel along my spine and neck. I seem to have a lot less brain fog and better concentration as well. I’m also waking up more rejuvenated. The anxiety & Stress RNA’s appear to be helping as well.

What’s next?

I still seem to have issues with my cirtic acid cycle due to lack of muscle endurance type energy. Also I still do experience diminished forms of brain fog & anxiety. I wake up feeling somewhat exhausted although it’s not nearly as bad as before.

Louise Hay has put forth the idea that CFS develops in individuals that are highly disconnected from their emotions. This is a pattern that begins early in childhood when a child receives messages from it’s parents that it is not okay to express certain emotions. This causes patterned subconscious repression of emotions and often results in something known as freeze response when novel stress situations are presented. For me personally this makes a lot of sense and I have begun using Self Regulation therapy as an effective tool to remedy this issue and empower myself emotionally and thus energetically. Emotions have an all-powerful effect on the biochemistry of our body and if the free-flow of them is impeded in any way it will lead to health issues.

Great Resources:

The journey continues!

*Note: This post originally appeared on the Phoenix Rising forum.

    • Paul

      I am currently suspecting Methylation problems in myself. Have been diagnosed with OCD for about 12 years (Half my life). Have been suffering from a lot of things in relation to that. I also do have physical issues with fatigue (absolutely hate excersizing) even though I was competitive in sports I had problems getting in shape even though I ran 3 miles a day like anyone else (and this for me was torture). Tomorrow I am going to have my histamine levels checked and I am doing a little homework in preparation for either a high or low histamine level (as that indicates under or overmethylation) I am suspecting undermethylation on my behalf. This comprehensive test is amazing, how much does something like this cost? Have you seen significant results due to the treatment recomended by this test? Any tips and pointers for a beginner wanting to look into his methyl cycle to find any problems? Thanks in advance.

    • Gestalt

      You can get most of the results from the 23andMe test which is $99. The yasko Methylation is about $500 and the genova tests are also in that range. And yes the results have been extremely useful. Check out my post on Nutrigenomics here. As a beginner I would start there. http://www.gestaltreality.com/2013/03/17/nutrigenomics/

    • Paul

      Prior to your glutamine supplementation and protein diet did you have any problems with excersize or experience anything like asthma? I have a feeling I will do the 23 and me test regardless of my histamine test results, it seems like the most cost effective test.

    • Paul

      As you mentioned, I think you said that you experienced the feeling of being “tired but wired”. I was wondering if you experienced any negative reactions to glutamine as it is a precursor to glutamate production. I suppose if you don’t have any glutamate/ GABA imbalance (resulting in panic or anxiety) it wouldn’t have a profound impact on you, but that is one thing I would be concerned about if supplementing with glutamine. Do you think that glutamine could have negative impacts on me since I suffer form anxiety and have had panic attacks in the past?

    • Gestalt

      No, never had asthma. I did have issues with exercise from a muscle repair and endurance perspective prior to glutamine and high protein diet.

      Regarding glutamine & glutamate you can read my response on phoenix rising starting at post#16 here: http://forums.phoenixrising.me/index.php?threads/gestalts-genova-23andme-yasko-methylation-genetic-results.18309/

      Short Answer; No I have not had any issues with glutamine supplementation even at very large doses 20g+, and I wouldn’t worry about it converting to excess glutamate. I think this study proves it for most people. http://www.ncbi.nlm.nih.gov/pubmed/17001467

    • I see Gestalt that you are using DIM with good effect. Have you thought of using sulforaphane instead of – or as well as DIM? It is derived from the broccoli sprouts (not the mature vegetable as is DIM) and is far more effective in nutrigenomically upregulating the genes which code for glutathione synthesis, the antioxidant enzymes and the detoxification enzymes as just a few of the literally hundreds of genes it upregulates. It also downregulates many of the genes coding for inflammatory cytokines.

      Sulforaphane will activate the enzymes needed to synthesise your own glutathione; this is different from the pathway you describe which is affected by a variant of the CBS gene. You need both pathways working well to optimise your glutathione levels.

      By upregulating the cell’s own antioxidant enzymes such as superoxide dismutase, glutathione peroxidase and other lesser known enzymes such as thioredoxin reductase and haemoxygenase-1, you have a good chance of enhancing mitochondrial function. In CFS, it is as if the mitochondria go into a holding pattern with various energy-producing enzymes blocked. The first enzyme in the Kreb’s Cycle, aconitase is easily blocked by the superoxide radical and using a product called GliSODin (a nutrigenomic superoxide dismutase activator), you should be able to remove the block here as well as several of the blocks elsewhere in the mitochondria preventing energy production.

      To do this, I would suggest you try GliSODin (you need to buy the genuine one which originates in France as there are useless copies available) plus a broccoli sprout-derived sulforaphane such as EnduraCell. Avoid products marked as broccoli sprout ‘extracts’ as they are inactive and also avoid those marked as ‘sulforaphane glucosinolate’ or branded ‘SGS’ as they too are inactive. They are inactive because of the way they are processed, the essential enzyme, myrosinase has been removed.

      I’ll go back and read your blog in more detail as you have obviously done plenty of research in trying to understand your own situation.

    • Gestalt

      Christine, yes I have tried sulforaphane as did my girlfriend, and we seemed to get some negative results with it. Symptoms got worse all around…. We tried the BroccoGen from http://www.organicteatreeoil.com/

      My chief concern with Sulforophane is that it inhibits/decreases CYP1A1 as well as a few other CYP detoxification enzymes. If I am increasing Glutathione levels by inhibiting detoxification pathways is that a good thing? Will it just cause more toxins to build up? My concern is that it may be like making a deal with the devil.

      Thanks for the info on GliSODin. I would like to try it. Do you have a good source on where to get it?

      • Gestalt, BroccoGen is a myrosinase-INactive broccoli sprout product (as are most of those originating in the U.S.) All this provides is the inactive precursor, so I suspect that your negative results may have been coincidental. Such supplements are virtually worthless. You will find the EnduraCell online if you do a search and they can also advise on GliSODin.

        Although sulforaphane inhibits modestly CYP1A1 in the Phase 1 detoxification pathway, it very actively upregulates the Phase 2 pathways which are necessary for synthesis of glutathione and several other cyroprotective enzymes. This is the ideal way in which to increase your own glutathione synthesis and a whole host of other valuable compounds necessary to modulate oxidative stress.

      • Gestalt, how do I know when comments appear on your blog? I didn’t realise that you had replied to my comments back in May and just again ‘stumbled’ on your blog.

    • Paul

      I posted my 23andMe results on Phoenix Rising. We both share the double COMT variations: http://forums.phoenixrising.me/index.php?threads/my-genetic-profile.23423/

    • Roxie60

      Just discussed taking lyposomal glutamine with my Dr a couple of weeks ago but have been concerned. I just went to the health food store to discuss glutamine and the young man suggested the micronized version. I so sick of no energy I guess I’m willing to try it. They are not open till Monday so have to wait. Thanks for all the info, great job! and thanks for sharing this, makes me willing to try another supplement:

      large doses of Micronized L-Glutamine 10-20g a day. This increased my energy from about 30% to 60%

    • annie

      Hi Gestalt,

      Thanks for all of this great information! Like others I had wondered about the possible relationship between glutamine and glutamate and the links you posted have really cleared this up.

      I was wondering if you might know how the body works with glutamic acid? Im keen to try the raw vegan rice protein however i’ve noticed that each serve has over 4g’s of glutamic acid. In your experience what impact did this have on the glutamate/ GABA balance?

      • annie

        interesting . . .

        i tried it and within 15 minutes starting experiencing pounding heart and increased mental agitation . . .
        its a shame as its such a digestible form of protein

    • Ken

      Calico13’s spreadsheet has been taken down. Would it be possible for you to update the link, or send it to me. Thanks so much.

    • Suz

      What interesting results… would you now have further testing, particularly around other MTHFR defects?

    • Guest

      Interesting that Gestalt said his ammonia levels went down with yucca, even though he used the stalk and not the root that Yasko recommends…

    • Megan

      Hi Eric – how are you doing now? My son has similar SNP’s to you – I am very keen to hear what your current regime is (and what didn’t work). You have done an amazing job with all this! Thanks so much, Megan