Nutrigenomics: Addressing CBS & BHMT mutations

In this post, I compile a list of six clues to determine if CBS & BHMT mutations are an issue for those of us who have heterozygous CBS & BHMT mutations and, therefore, aren't sure if we are up-regulators.  This list is compiled from Dr. Yasko's book and the Methylation section of the Heartfixer website, where each clue is mentioned in different areas, but never compiled as a list .

For those of us that decide to go the nutrigenomics route to treating ME/CFS, one of the first problems we encounter is deciphering whether CBS & BHMT mutations are problematic. These two mutations are up-regulations, leading to high levels of sulfate and ammonia.  As Dr. Yasko puts it, this up-regulation leaves the "drain open" meaning that any other methylation supports will go "down the CBS drain" if the CBS mutation is not addressed first.

If you are homogygous (+/+) for any CBS mutation, there is no question that you are affected.  But there's ambiguity for those of us who are heterozygous (+/-) for the CBS mutation, especially if it's the lesser of the two mutations: CBS A360A.  (Note there are also some people who believe that Dr. Yasko is incorrect and that CBS mutations are not important.  See posts #17-19 in this PR thread.)

Six Clues

Urine sulfate levels:  Urine sulfate levels can be tested at home using these urine sulfate test strips.  Ideally, you want your urine sulfate levels below 400, but if that's not possible, then below 800 is apparently acceptable. (Heartfixer, see Overview, #2).  Mine is testing around 800.  CONCLUSION: SLIGHT PROBLEM.

Blood ammonia levels:  If blood ammonia levels are high or high-normal, it tends to indicate CBS or BHMT issues.  Mine tested at the highest possible number without being out of range: 47 (normal range is ≤47 µmol/L.  CONCLUSION: PROBLEM

Sulfur Tolerances:  If someone has a CBS and/or BHMT mutation, supposedly they will not tolerate sulfur well.  This means they will have an adverse reaction to foods or supplements containing high sulfur.  For me, I have never noticed any adverse affects from eating eggs, broccoli, and other foods high in sulfur.  (It's not clear what the adverse reaction would be).  Also, I underwent a heavy metal detoxification protocol last September using DMSA, which contains high amounts of sulfur.  I did not have any adverse reactions.  CONCLUSION: NO PROBLEM

Blood homocysteine levels:  Supposedly, the CBS mutations usually lead to low or low-normal levels of homocysteine.  I've never seen "low" defined, but optimal levels are considered to be around 6 to 7, so "low" is obviously below that.   Mine, when tested last in December, 2011, was 9.1, which is within range, but above optimal.  (Reference range is <14.4)  This might suggest that I don't have CBS or BHMT mutation issues, except for the fact that I have other mutations SHMT (+/-), MTR A2756G (+/-), and MTRR A664A (+/+) which lead to high levels of homocysteine.  So it's possible that these other mutations are counterbalancing the CBS up-regulation.   CONCLUSION:  UNCLEAR

Which CBS mutation?:  As mentioned above, the CBS A360A is the least severe of the CBS mutations, leading to only about 1/40th the amount of up-regulation as the CBS C699T.  Further, if you are heterozygous (+/-) like me, it's not clear if that particular mutation is "turned on."  CONCLUSION: UNCLEAR

Combinations of mutations:  Someone who only has a CBS mutation or only has a BHMT mutation is less likely to have a problem than someone who has both.  Personally, I am heterozygous for CBS A360A and 3 of the 4 BHMT mutations: 2, 4, and 8.  (1 is not tested by 23andMe).  CONCLUSION: LIKELY PROBLEM

Conclusion

It's still a little unclear, but to be safe, I'm going to assume that I have a slight to moderate issue with CBS up-regulation, and cut down a little on the highest sulfur foods, but I won't radically change my diet.  I will also supplement with Yucca and charcoal flushes before proceeding to the next phase of the methylation protocol.

[updated 5/23/13]

[5/28/13]  This thread from Phoenix Rising provides some interesting feedback from other users trying to   treat CBS and BHMT mutations.