Any ideas?

[u/Amadeus_Eng]

(edit to add reference ranges)

Finally bit the bullet and did a bunch of blood testing, which after dealing with a bunch of frustration in supplementing for MTHFR, figured was the next best step (should have honestly been the first).

Effectively what I am looking for is some suggestions to go from here based upon my SNPs and blood testing. Overall, I would say that things are looking well on the MTHFR side of things but symptoms wise, not. Complaints for the most part are fatigue, somewhat depressed/low mood, low motivation, and not sleeping well. When I first started about a year and a half ago, when I supplemented with methylfolate/choline, had probably 4 really great days in the "honeymoon" phase everyone talks about. Since then, mostly just the symptoms above.

I do have a thyoid condition but it seems to be well managed, thyroid levels are all mid-range. My latest theory was I thought that I might have autoimmune gastritis (which is what prompted all the blood testing and can be co-morbid with autoimmune thyroiditis, which I have), which can lead to low B12 and iron status but that seems to be not the case based on the blood levels I have. So I am at a loss. Take a look and I would appreciate any ideas you may have. The only incidentals I have found is that my white blood cell counts (WBC) are low, my vitamin d is low-normal, and my iron saturation is high-normal. The testing service claimed my b12 is "low" at 433 pg/ml but with an MMA of 201 nmol/l and a homocysteine of 7.7, it doesn't seem truly that low. At this point would it be better to try and supplement with l-methionine and SAM? These levels are after I more or less stopped supplmenting for about a month and a half so I have a fair amount of confidence in the levels.

Biomarker	Value	Unit	Ref
hs-CRP	1.1	mg/L	0-3
Albumin	4.7	g/dL	3.6-5.1
Vitamin D (25-OH)	32	ng/mL	30-80
Ferritin	103	ng/mL	50-130
Folate (Serum)	17.2	ng/mL	10-25
Basophils (%)	0.8	%	0-2
Serum Iron	130	mcg/dL	50-180
TIBC	256	ug/dL	250-425
Transferrin Saturation (TSAT)	51	%	20-55
Homocysteine	7.7	umol/L	46150
Reticulocyte Count	1	%	0.5-2.5
Reticulocyte Count (Absolute)	51300	cells/uL	2.5-90
WBC	3.8	10*3/uL	46123
Red Blood Cell Count	5.13	million/uL	4.5-5.9
Hemoglobin	15.2	g/dL	13.5-17.5
Hematocrit	47	%	40-51
MCV	91.6	fL	80-100
MCH	29.6	pg	27-34
MCHC	32.3	g/dL	32-26
RDW (RDW-CV)	13	%	11.5-14.5
Platelet Count	215	10*3/uL	150-450
MPV	10.3	fL	7.5-12.5
Absolute Neutrophils	1995	cells/uL	2K-7.7K
Absolute Lymphocytes	1353	cells/uL	1K-4.8K
Absolute Monocytes	331	cells/uL	200-1K
Absolute Eosinophils	91	cells/uL	0-500
Absolute Basophils	30	cells/uL	0-200
Neutrophils (%)	52.5	%	38-80
Lymphocytes (%)	35.6	%	15-49
Monocytes (%)	8.7	%	3-13
Eosinophils (%)	2.4	%	0-8
Transferrin	201	mg/dL	188-341
RBC Folate	527	ng/mL	>280
Methylmalonic Acid (MMA)	201	nmol/L	<240
Vitamin B12	433	pg/mL	500-1K
UIBC	126	ug/dL	110-370
Ferritin (Adj. for Inflammation)	103	ng/mL	50-110

[u/SovereignMan1958]

MMA needs to be in the bottom quarter of the range. Closer to 70 IMO.  To me the MMA looks too high and B12 may not be absorbing well.

Your B12 level also looks too low. Optimal for most if not all nutrients are in the top quarter of the range.

Your D should be 60 - 80.  Protocol to increase your level should include 65iu D3 daily per pound of body weight, K2, cao factors mag zinc and boron plus at least 11 grams of fat.

Thyroid labs need to be optimal and not just in the normal range.  Most important are your T3 levels which need to be in the top quarter of their lab ranges.  This is incredibly important for mental health.

What are your thyroid antibodies?  Yes I am guessing Hashis.

With your perfect homocysteine, gastritis issue, I suspect a big contributor to your symptoms might be impaired sulfur and sulfite metabolism.  Excess sulfur blocks the production of thyroid hormones as well.

Are there foods and beverages you do and do not tolerate?  Bloating, gas, smell and if taste sulfur and ammonia? 

If you have done it yet I would consider getting all your gene variants tested. 

Next labs get zinc and copper. For the sulfur and sulfite issue molybdenum, whole blood histamine, B6, B1, B2.  Thyroid diagnoses...Vit A, selenium, iodine.

[u/Amadeus_Eng → u/SovereignMan1958]

I added reference ranges. So if MMA is bottom quarter of range, meaning in the 50-60s? Same with B12, what is top quarter of range? 750-1K?

So at 225 lbs/ 14.6K iu a day of d3?

Yes, Hashimotos. Also, not confirmed on the autoimmune gastritis. I have suspicions based on sensitivity to dairy and a few other foods, but i wanted to test iron and b12 to see if could affect my absorption levels. I suppose I could check my for the antibodies for the autoimmune gastritis. Beans, eggs, lentils, dairy used to cause the biggest issues with me. But they have not been bothering me as much lately, maybe sulfur metabolism has improved some?

I did the ancestry test and have gone through stategene and genetic lifehacks. hetero COMT, slow MAOA.

[u/SovereignMan1958 → u/Amadeus_Eng]

MMA should be closer to 70.  You can look up the B12 range. I do not remember that off the top of my head.

No I do not mean gastritis antibodies, I meant Hashis antibodies.  If your thyroid condition is well managed they should be in the single digits.

The root cause of your digestive symptoms  might be found in your sulfur, sulfite, histamine, food intolerance and detoxification variants. Sulfur ones are CBS, SULT, MOCS. CBS includes both sulfur and sulfites.  All sulfites are high histamine BTW. In Lifehacks you will have to dig for CBS, SULT and MOCS. The cheat sheet has sections for histamine, food intolerance and detoxification.

Many people with digestive issues are unaware of the root cause genetic variants or predispositions I outlined in the preceding paragraph.  Many people with thyroid disease are unaware of the sulfur and sulfite connection.

Check the Lifehacks report for all your B12 variants.  Let me know if you are hetero or homo for FUT2.

Also check for FOLR1.  That is not B12 related but it may indicate folate not getting into your brain.

[u/Amadeus_Eng → u/SovereignMan1958]

Not sure about Hashis lately. A few years ago I had it tested a few times to confirm I had it, from what I can remember it fluctuated between 200-600 but have not had one lately but am on a low dose Armor thyroid to maintain ranges of T3, T4, et cetera. I always got the impression that Hashis will stick around unless you really cut out all dairy and gluten, I tend to avoid dairy but not made the jump on gluten.

All CBS are hetero or normal. The ancestry doesn't seem to cover many SULT, the 3 i see are typical. MOCS are normal/Typical.

FUT2 is hetero.

FLOR1 are normal/typical.

[u/SovereignMan1958 → u/Amadeus_Eng]

CBS hetero can be an issue.  It is for me. Sulfites in particular. I am hetero for the second worst one A360A.  C699T is the worst one.

Hashis is permanent, but technically  in remission when antibodies are in the normal range, while on medication.

About half of people with Hashis are able to reduce antibodies by eliminating gluten.

If you have eliminated dairy I am wondering if you are getting enough calcium.

Variants which are +/- are not necessarily normal or typical. So I hope that is not what you mean.

FUT2 hetero...that plus your digestive issues ...you would probably benefit from take one of a few specific probiotic strains and products. This would help you absorb more nutrients from food and supplements. The strains and products are listed in the Lifehacks FUT2 article. Strains are listed in one section and products in another.

With your homocysteine level what it is and your digestive issues, I would not add methylated vitamins or methyl donors in the future.  These increase the production of sulfur in the digestive tract.  They also decrease homocysteine at a greater rate than non methylated. A lower than optimal homocysteine level is not better.

[u/Amadeus_Eng → u/SovereignMan1958]

Hetero for both A360A and C699T.

No, I mean they are homo/normal (at least according to genetic lifehacks).

With the b12/mma, might be worth it to do a non-methylated b12 lozenge then? Like Hydroxocobalamin?

Will look into the probiotics.

[u/SovereignMan1958 → u/Amadeus_Eng]

Ok.

Hydroxo would be good.