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VK's Methyl Cycle Findings and Treatment Program 

To key problem here is ammonia excess and BH4 deficiency due to the joint presence of the CBS up regulation (generates ammonia which wastes BH4) and backward MTHFR abnormalities (blunting the generation of BH4) present. 

To address CBS (which is inappropriately draining methyl cycle intermediates into sulfite, ammonia, and alpha-ketoglutarate) I recommend:

1. Low protein diet (anything with eyes) and avoid sulfur rich foods (see list) and sulfur containing drugs.  DMPS (which contains sulfur) will be put on hold until urine sulfur levels come under control.
2. Monitor urine sulfate with the dipstick methodology every 4-7 days (lower levels will allow an increase in methyl supplementation)
3. To neutralize ammonia, use Ammonia Support RNA ½ dropper with meals and with methyl cycle supplements, along with a charcoal supplement at bedtime (away form other supplements; magnesium citrate may be used as needed to keep the GI tract moving as charcoal may lead to constipation).  Yucca, beginning at ½ capsule twice a day, perhaps sprinkled on protein containing foods, should help with ammonia detoxification. 
4. Molybdenum to help SUOX (sulfite oxidase) break down sulfite.  Homogenized dairy products contain xanthine oxidase, which uses up molybdenum, and are best minimized. 
5. Avoid excitotoxins (see list) and supplement with montiff GABA 500 mg/day.
6. We wish to avoid B6, which stimulates CBS, but a metabolite of B6, P5P, is less of an issue.  The HHC multivitamin, one twice a day, can be used here.  Please stop the folic acid with methy-B12 supplement and switch to the HHC multi instead (OK to stay on your current mineral supplement).
7.  The stress RNA preparation twice a day will help take some of the strain off the urea cycle, the job of which is to detoxify ammonia (this is 2^nd line – the ammonia RNA is more important).
7. In the future we will cautiously add in BH4.

To address MTHFR A1298C (this defect blocks the generation of BH4):
1. All measures to address CBS play a role here; we need to decrease ammonia to spare BH4.
2. Low dose BH4 supplementation after other treatments established.

 We wish to minimize dietary protein, to decrease the production of ammonia, but the protein that VK does take in should be rich in precursors for dopamine and serotonin, such that less BH4 is used up generating these neurotransmitters.  As both COMT and MAO are abnormal, balancing between the dopamine and serotonin precursors (food lists in COMT section) makes sense.

To address MTHFR C677T (this defect blocks the conversion of folic acid into 5-methyl folate):
1. 5-methyl folate supplementation, in the form of Folapro, ¼ tablet per day (after CBS comes under control we may increased the dose.  Stop the folic acid that VK has been taking as he cannot convert it in to 5-methyl-folate.
2. Phosphatidylserine daily and the HHC multi one twice a day to stimulate the backdoor BHMT reaction to detoxify homocysteine (and pull it away from CBS which will convert it in to ammonia, sulfite, and alpha-ketoglutarate).

To address MTRR A66G (this enzyme's job it to  methylate B12 to form methyl-B12), keeping in mind VK's COMT +/+ status, we will use:
1. Hydroxy-B12 2000 mcg sublingual, beginning at once a day, increasing to twice a day in two weeks.
2. Backdoor homocysteine detoxification as above.

To address the three BHMT findings – this acts like the CBS up regulation – same plan.

 Positive COMT status means you are preserving dopamine (and sparing BH4) and SAMe and that methyl supplementation can lead to agitation as it can increase dopamine levels.  This condition is modified somewhat by the VDR positive status.  MAO +/+ means that VK will have trouble breaking down serotonin, and as in the case of VK's COMT +/+ status, this will preserve BH4, a plus, but will leave him more susceptible to mood swings, a minus.

 Helpful testing:

1.  Blood levels of homocysteine and ammonia.
2. 24 hour urine (or first AM void if a 24 hour study is not feasible) for amino acids.
3. 24 hour urine (or first AM void if a 24 hour study is not feasible) for essential and toxic minerals.
4.  We will periodically obtain 24 hour or AM spot urine studies, to monitor toxic metal/mineral status and to watch for the expected reduction in ammonia.  If it appears that VK is taking a turn for the worse, we can obtain a spot urine for toxic metals, and we will likely see an increase in toxic metal excretion, demonstrating that VK is feeling poorly because he is actively detoxifying.
5.  Check the urine sulfate level every 4-7 days; we are looking for a reduction in sulfur burden with the treatments outlined above.

Keep up with the magnetic sleep pad, VK's’s current mineral supplement, Epsom salt baths, homeopathic patch therapy, and singulair.