Need help with methylation and detox SNP analysis

[DownTheRabbitHole]

I'm a 30 year old male and recently had my 23andMe tests done. I then ran them through Genetic Genie (since 23andMe isn't really useful for much else at the moment). Here are my results and I'd be very happy to get any input on what I am doing (or not doing) with regards to treatment.

BTW, sorry for the length....I like to be thorough.

GeneticGenie Methylation SNP profile:
COMT V158M +/+
COMT H62H +/+
VDR Bsm +/-
VDR Taq +/-
MAO-A R297R +/+
MTHFR A1298C +/+
MTRR A66G +/-
MTRR H595Y "no call"
MTRR K350A +/-
MTRR R415T "no call"
MTRR A664A +/-
BHMT-04 "no call"
AHCY-02 "no call"
CBS C699T +/-
CBS N212N "no call"
SHMT1 C1420T "no call"

MTHFRSupport Variant Report V1 (methylation profile only):
ACE Del16 +/+
ADD1 G460W +/-
AGT M235T/C4072T +/-
BHMT R239Q +/+
CBS A13637G +/-
DAO +/-
DHFR +/-
FUT2 +/- (rs492602, rs601338, rs602662)
GAD1 +/- (rs3749034, rs2241165, rs12185692, rs10432420)
GAD1 +/+ (rs2058725, rs3791850)
MTHFS +/+
MTHFD1 C105T +/+
MTHFD1L +/-
MTHFR +/+ (rs1476413, rs3737964, rs4846048, rs4846049, rs6495446)
MTRR-11 A664A +/-
MTRR +/- (rs1532268, rs9332)
NOS2 +/- (rs2297518)
NOS3 +/- (rs1800783, rs1800779, rs3918188)
PEMT +/+ (rs4646406)
SHMT2 +/-
TCN2 C766G +/-

GeneticGenie Detox SNP profile:
CYP1B1 L432V +/-
CYP1B1 N453S +/-
CYP1B1 R48G +/-
CYP2C9*2 C430T +/-
CYP2D6 S486T +/-
CYP2D6 2850C>T +/-
GSTP1 I105V +/-
NAT2 R197Q +/+

GSTT1 "Present"

For most of my life I have had bad ADHD, anxiety, IBS, low blood pressure issues, mood swings, short term memory issues, chronic fungal and bacterial infections, dysrhythmic gait and speech, migraines, chronic brain fog and chronic fatigue. I also recently experienced peripheral neuropathy (PN) due to the buildup of ammonia in my body damaging nerves. Luckily I figured out the cause soon enough to reverse most of the PN damage. The other symptoms have been ameliorated, but I'm not at 100% yet.

Switching to a fairly strict slow carb slightly ketogenic primal/paleo based diet has helped immensely. I'm a celiac so I avoid gluten like the plague. Most of my IBS symptoms and fatigue cleared up when I got off gluten and started eating unpasteurised probiotic rich foods.

My diet is pretty much steady, consisting of the following ingredients ingested almost every day in some form or fashion:

• Spinach (1 cup)
• Cauliflower (1/2 cup)
• Broccoli (1 cup)
• Onions (1/4 cup)
• Sprouted lentils (1 cup)
• Avocado (1 large)
• Baby portabella mushrooms (1/2 cup)
• Kale (1/2 cup)
• Tomatoes (1 small)
• Asparagus (1/2 cup)
• Chia seeds (4 tbsp)
• Dark cherries (1/4 cup)
• Blackberries (1/4 cup)
• Almonds (2 tbsp)
• Brazil nuts (just 1)
• Hazelnuts (2 tbsp)
• Cashews (1 tbsp)
• Sesame seeds (1 tbsp)
• Eggs (4)
• Chicken breast (1-2 large)
• Ground turkey/beef (1/2 cup)
• Coconut oil (1-2 tbsp)
• Black walnut oil (1 tbsp)
• Coffee (1-2 cups half-calf)
• Green/White tea (2-3 cups)
• Iodized salt (1 tsp)
• 85% dark chocolate (10-20 g)
• Almond Breeze Unsweetened Vanilla (1 cup)
• 1 scoop Optimum Nutrition Chocolate Natural Whey Protein (sweetened with stevia)
• 10-20 g L-Glutamine powder (for leaky gut repair and after workout glycogen recovery)

All ingredients are cooked below 225 degrees.

I have 1-2 glasses of wine or a gluten free beer once per month (sometimes twice).

I am currently taking the following supplements daily to correct for these genetic conditions:

• 1 cap Vitacost Synergy Optimized B-100 Complex (importantly contains 100 mcg methylcobalimin and 800 mcg (6s)-5-methyltetrafolic acid)
• 350 mg Jarrow Formulas N-Acetyl Tyrosine (CBS and NAT2 have me questioning this)
• 150 mcg Country Life Chelated Molybdenum
• 4,000 IU Vitamin D3 (questionable whether it helps VDR)
• 10 mg Albion Manganese Glycinate Chelate
  
• 400 mg Swanson Triple Magnesium Complex (350 mg magnesium oxide, 40 mg magnesium citrate, 10 mg magnesium aspartate)
  
• 15 mg Zinc + 1 mg Copper complex

Some other supplements I take that may or may not have an impact on the activity on these SNPs but help with other issues:

• Vitacost KriaXanthin (2,000 mg Antarctic krill oil, 3 mg astaxanthin)
• Vitacost Mega EFA (2,126 mg fish oil, 800 mg EPA, 400 mg DHA)
• 2200 mcg LifeExtension Super K with Advanced K2 Complex (1000 mcg K1, 1000 mcg K2 MK-4, 200 mcg K2 MK-7)
• 1000 mg SerinAid (200 mg phosphatidylserine, 90 mg phosphatidylcholine, 20 mg phosphatidylethanolamine) (questionable if it helps boost serine levels, which SpectraCell shows I am low on)
• 300 mg LifeExtension Super R-Lipoic Acid (Na-RALA; supports glutathione production)
• 350 mg Rhodiola Rosea Extract (250 mg rhodiola rosea root extract, 100 mg rhodiola rosea root)
• 600 mg Kyolic Aged Garlic Extract (For my ApoE cholesterol levels. Debatable if it really helps.)

While the above have helped, they aren't working as well as I would like so I believe further tweaking (or a complete revision) is necessary.

I keep reading that taking hydroxycobalamin is important with COMT++, but that has been almost impossible to find. I keep finding hydroxocobalamin instead. Are they the same thing? Does this form of B12 have to be taken sublingually for proper absorption?

I also take the following for my back pain caused by disc degeneration (works great) but I am concerned about the sulphur content affecting me unfavorably due to these genes (should I be?):

• 1,500 mg Glucosamine Sulfate
• 1,200 mg Chondroitin Sulfate
• 1,000 mg MSM

Tests have shown I have slightly elevated ALT (43 IU/L) and below normal ALP (39 IU/L), both of which suggest my liver is stressed by the extra work it is doing thanks to these genes. What's worse, I have the ApoE variant meaning my liver has a hard time clearing cholesterol from my blood. I was taking 150 mg of Milk Thistle daily to help with this, but I found out it could potentially cause an increase in estrogen so now I'm not so sure about it. I was also taking 600 mg NAC for my liver but realizing I am CBS C699T+- and NAT2 R197Q++ has made me rethink that due to the sulphur and acetylation pathways this can interact with.

The biggest problem I am facing is how to reconcile the interplay of these genes because some seem "opposed" (for lack of a better term) to each other in some respects, especially when it comes to their effects on methylation.

I really need to find an optimal balanced solution for all my genes involved, so any input on my supplement regimen and diet as it relates to my genetics would be very much appreciated!

 

[IpadAddict]

Hi DownTheRabbitHole

Your diet looks pretty amazing and I respect your dedication.

Things I personally avoid

Cashews. These are legumes and no-no Paleo. I recently found this out. I seem to handle a few raw cashews but the roasted ones with the cheap vegetables oils really muck up my digestion.

Coffee. This can be cross reactive to gluten for people sensitive. Also there are issues with mold and mycotoxins. Also true of dark chocolate and possible chia seeds but google cyrex labs and cross reactivity to check.

Chicken/Turkey. These are not great sources of protein and they are usually fed non paleo foods such grains such as wheat, corn etc. Should avoid

Recommendations
Head over to www.jackKruse.com his epi-paleo diet favours shellfish, crustaceans, fish, offal, grass fed lamb, pork, beef for quality protein.
He also looks at other factors than just diet such as circadian biology, emf reduction, good water, earthing, hormone balancing, good sleep etc. From my experience diet and supplements get you perhaps 30% better.
You should also consider hooking up with Tim Jackson who is an expert on 23andMe and hormones.

 

[Critterina]

@DownTheRabbitHole ,

I can't comment on most of this, but with your MTHFR A1298C +/+ and ADHD, anxiety, mood swings, short term memory issues, and migraines, you could probably do with substantially more methylfolate. Also, I know that many - but not all - people do better on hydroxyB12 than methylB12 when they have COMT mutations - but - if what you're taking doesn't bother you, you may be one of those that are less sensitive.

 

[joshi81]

Hi the thing do not understand is this, yoi told to have high ammonia which caused peripheral neuropathy... but... your paleo diet, full of meat, eggs and vegetables from the cabbage family (at least in amy yasko's opinion) is the worst you can do for high ammonia in particular because of your hetero CBS.
So i am curious to know how did you lower your ammonia? how did you test that effectively it was lowered?
Thanks

 

[DownTheRabbitHole]

Cashews. These are legumes and no-no Paleo. I recently found this out. I seem to handle a few raw cashews but the roasted ones with the cheap vegetables oils really muck up my digestion.

You can solve the primary problem (phytic acid) by soaking and/or sprouting them so you keep more of the beneficial minerals found therein. I go one further and grind them then boil to make a cream for use in my cauliflower mash (recipe found in 4 Hour Chef).

Coffee. This can be cross reactive to gluten for people sensitive. Also there are issues with mold and mycotoxins. Also true of dark chocolate and possible chia seeds but google cyrex labs and cross reactivity to check.

I'm pretty skeptical about the coffee/gluten cross reactivity and agree with Gluten Dude on his (kind of amusing) analysis of the research.

With or without coffee doesn't seem to make much difference, although I try to steer away from the caffeine. For a while I was mixing in ground roasted chicory root with my coffee which added a robust flavor and some prebiotic fiber to help cut back on caffeine. Stopped just because it is hard to find around here.

As for the myco toxins, I'm guessing you have read material from the BP Exec. I try to stick to locally roasted single origin coffee just as a precaution, but I'm not sold on it being a big issue. I don't have either of the mold sensitivity MLA genes, so it is probably a non-issue with me.

Luckily my insides feel fantastic when I consume chia so I'm clearly not having a reaction. I work 16 - 18 hour days, so I can't really imagine making it through without chia to start my day.

Chicken/Turkey. These are not great sources of protein and they are usually fed non paleo foods such grains such as wheat, corn etc. Should avoid

Unfortunately I don't have much choice. Any time I eat beef it has to be in small portions or diluted with another meat and lots of salad. Tears up my digestive tract. Chicken and turkey are the only ones I can handle. No idea why that is yet.

Head over to www.jackKruse.com his epi-paleo diet favours shellfish, crustaceans, fish, offal, grass fed lamb, pork, beef for quality protein.
He also looks at other factors than just diet such as circadian biology, emf reduction, good water, earthing, hormone balancing, good sleep etc. From my experience diet and supplements get you perhaps 30% better.

Looks like it might be helpful. Thanks!

You should also consider hooking up with Tim Jackson who is an expert on 23andMe and hormones.

I'll see if I can get ahold of him. Thanks!

 

[DownTheRabbitHole]

I can't comment on most of this, but with your MTHFR A1298C +/+ and ADHD, anxiety, mood swings, short term memory issues, and migraines, you could probably do with substantially more methylfolate. Also, I know that many - but not all - people do better on hydroxyB12 than methylB12 when they have COMT mutations - but - if what you're taking doesn't bother you, you may be one of those that are less sensitive.

I haven't noticed any real benefit from taking more methylfolate. Just yesterday I made the decision to order some B12 in the form of 2,000 mcg of Hydroxocobalamin and 3,000 mcg of Adenosylcobalamin. Both as lozenges. Will try each independently over next 2 weeks to see the effects and report back.

 

[DownTheRabbitHole]

Hi the thing do not understand is this, yoi told to have high ammonia which caused peripheral neuropathy... but... your paleo diet, full of meat, eggs and vegetables from the cabbage family (at least in amy yasko's opinion) is the worst you can do for high ammonia in particular because of your hetero CBS.
So i am curious to know how did you lower your ammonia? how did you test that effectively it was lowered?

I have not yet investigated Yasko's diet recommendations so I can't comment on that. All I know is that the highly unhealthy "All American" style diet I was on was making me feel like crap so I did paleo just to see what happened after I got the Celiac diagnosis. Perhaps modifying to account for ammonia causing foods will improve things further. I will give it a try.

As for what I've done so far to lower ammonia, I have been supplementing with 100 mcg Biotin in my b-complex and taking an extra dose of straight d-biotin at 1,000 mcg every other day (which I failed to mention in my original post). I also eat hazelnuts (rich in manganese) and supplement with 10 mg manganese daily, which my SpectraCell report showed was depleted and is known to lower ammonia (can't locate my source to cite, sorry).

The biggest results I saw though on the ammonia front were from taking methylfolate to support the BH4 cycle and cutting WAY back on my drinking. Was having a glass of wine or beer once every night and would occasionally drink even more with friends on the weekend. While this may not be a lot for most people, it was more than my body could handle and I never realized. Just changing my drinking habits made an enormous difference in ammonia levels. I've lost the blood test #'s but I'm actually scheduled to get another draw next week to test my levels again.

Rehabbing the PN was just a matter of retraining the nerves after I alleviated the source of the damage. Switched to Vibram Five Fingers to engage my toes to a greater degree and every time I go out I try to feel every interesting texture I can find to engage the nerves in my hands (hand sanitizer is my friend). Took nearly 6 months, but the alternating numbness, tingling and pain in my hands and feet have almost completely disappeared.

I'm considering trying yucca root before bed to see if it helps with my liver's detox process. I still wake up achy and feeling like I didn't sleep (even at my lightest sleep cycle), which does not make for a productive morning.

I may also give L-Citrulline and L-Ornithine a try before my workouts to see if they help. Jonathan Zerbin at Gestalt Reality appears to have been trying this so I'm curious how well it works given that exercise (especially the tabata routines I do) produces a spike in ammonia.

I do know that supplementing with 10-15 g of L-Glutamine powder right after an intense workout significantly improves my mental clarity and relieves the overall weakness I feel rather quickly. I've been doing this for years and thought this was due simply to glycogen replenishment. I never considered before that this might be due in part to it's role in detoxifying ammonia.

 

[DownTheRabbitHole]

I have added my methylation profile from version 1 of my MTHFRSupport Variant Report in case that will be helpful to anyone trying to cross-correlate gene activity. I also included the affected hetero/homo rsID #s when that was the only differentiating factor in the report.

Does anyone know a good way to raise my glutathione that won't disrupt other processes caused by my genes? My SpectraCell report shows it is predictably low.

 

[Critterina]

Raising glutathione...did your SpectraCell report say anything about B6? I know you're taking a boatload of supplements, but B6 (or in my case P5P, since I tested deficient while taking regular B6) should help glutathione production, theoretically at least, and I don't think it is contraindicated by any of your SNPs. I don't know, though...maybe someone else will comment?

 

[DownTheRabbitHole]

Raising glutathione...did your SpectraCell report say anything about B6? I know you're taking a boatload of supplements, but B6 (or in my case P5P, since I tested deficient while taking regular B6) should help glutathione production, theoretically at least, and I don't think it is contraindicated by any of your SNPs. I don't know, though...maybe someone else will comment?

B6 was deficient at the time of the test. My B-complex I'm now taking contains B6 in the forms of 50 mg pyridoxine HCL and 50 mg P5P.

I also had the following deficiencies: B1, biotin, glutathione, selenium, vitamin E

The following were borderline deficiencies: B12, folate, pantothenate, serine, glutamine, manganese, fructose, lipoic acid

Of all the deficiencies, glutathione and vitamin E were the worst. Almost bottomed out on both.

 

[martincollins]

If you're working that much...how much quality sleep are you getting? The body really needs to have consistency in sleep patterns to work optimally. Do you take your magnesium supplement right before bed? Some people benefit from 5-HTP as well for sleep.

To me, it sounds like you have a pretty good grasp of nutrition and supplementation. Maybe some foods high in beta-carotene. I also like sardines for the mineral and omega-3 content. Maybe some more prebiotic foods as well. You mentioned probiotic rich foods but are you eating yogurt, kefir, sauerkraut, kimchi, or taking a supplement? In the morning, I make a blender smoothie to make less work for the GI tract. I alternate days with red smoothies and green smoothies. They are not sweet smoothies necessarily which comes to mind for some. They are more veggie based and include prebiotic foods.

We often work on our strengths and overlook our weaknesses. I often have to evaluate what I'm working on for my health and ask myself if it's where I should be focusing. Often, I focus on nutrition and overlook sleep and stress management. Lately, I've worked on sleep and it has helped a lot. Anyways, just thought I would throw that out as a reminder...

 

[DownTheRabbitHole]

If you're working that much...how much quality sleep are you getting? The body really needs to have consistency in sleep patterns to work optimally. Do you take your magnesium supplement right before bed? Some people benefit from 5-HTP as well for sleep.

I'm a super light sleeper and only do 4.5 to 6 hours a night (timed for sleep cycles), so I have to take a 25 min siesta at midday to keep going. I really don't think when I do sleep that it is quality...especially this past month. I do take the magnesium at bedtime, but it doesn't seem to help as much as 5 g of glycine combined with 200 mg L-theanine. I really don't like to take supplements to go to sleep though. Makes me nervous I will become dependent so those are only for emergencies when I know I must get a good night's sleep.

5-HTP makes me light headed and dizzy and my back muscles tense up a lot even on just 100 mg. Not sure what to make of that.

To me, it sounds like you have a pretty good grasp of nutrition and supplementation. Maybe some foods high in beta-carotene. I also like sardines for the mineral and omega-3 content. Maybe some more prebiotic foods as well. You mentioned probiotic rich foods but are you eating yogurt, kefir, sauerkraut, kimchi, or taking a supplement? In the morning, I make a blender smoothie to make less work for the GI tract. I alternate days with red smoothies and green smoothies. They are not sweet smoothies necessarily which comes to mind for some. They are more veggie based and include prebiotic foods.

I don't do yogurt due to the milk (I have an unexplained reaction to casein) but I do eat homemade sauerkraut and kimchi at least once a week to keep my gut happy. I mostly eat onion for prebiotic fiber. I also take Align and S. Boulardii in pill form (sometimes kombucha).

We often work on our strengths and overlook our weaknesses. I often have to evaluate what I'm working on for my health and ask myself if it's where I should be focusing. Often, I focus on nutrition and overlook sleep and stress management. Lately, I've worked on sleep and it has helped a lot. Anyways, just thought I would throw that out as a reminder...

It's a good reminder! I need to work on my sleep. I had it all together and then something went wrong a little over a month ago and I've been brain fog + CFS central. The only thing I can think of that I changed is that I started eating a LOT more asparagus, kale, spinach, broccoli, cauliflower and onions....all high sulfur, high ammonia foods. I'm phasing most of those out to see if the increased intake was the cause. Sucks, because those are some of my absolute favorite foods and generally some of the healthiest foods (not to mention easily acquired in bulk at Costco).

 

[martincollins]

Dan Pardi (of dansplan.com) might be a good resource on sleep. He has a couple of podcast interviews out there...one with Chris Kresser. I think he recently was interviewed by Joel Fuhrman. I believe Ameer Rosic's podcast with Chris Kresser talks about sleep and methylation...possibly another option for you. Sounds like you exercise, I believe I remember one of them saying to exercise around 6 hours before bedtime. I've heard some say to stay off tablets/PC's to avoid artificial light for 2 hours prior to bed.

As you probably know, spinach and kale both have oxalic aicd so that could be something to consider if you're eating a lot raw. Chard does too but generally most people cook that and cooking removes it to the point it's generally not a problem. I generally alternate days with my green smoothies so I haven't had a problem so not sure how it would manifest. Asparagus is a pretty high in prebioitics I think and has a super low glycemic index so I'm bummed to hear it's high sulfur/high ammonia. Thanks for that info. Good luck!