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Methylation problems: A case study.

Anthony is a delightful 50 year old gentleman who wanted to avoid heart disease, which runs in his family. His brother, sadly, died at age 48, due to heart disease complicated by poorly controlled Type 2 diabetes.

Anthony's blood work showed an elevated homocysteine at 11.4 on his blood panel. Optimum is below 7. We next ran a Methylation Profile: Plasma through Doctor's Data.

When starting to use a new test, I usually call the customer support for the lab. Doctor's Data has a great customer support team of experts who patiently helped me learn to interpret the methylation profile results when I first started using the test and when I struggle to understand unusual results. I also like to visit with experienced experts to better understand the reasons for changes in retest results. Here are some of the things I learned.

1. Is the methionine result high? If so, think excessive protein intake or low magnesium (or both). Also could be caused by and elevated SAM results (see #3) below.

2. Is the methionine result too low? If so, think insufficient protein, low stomach, leaky gut, or altered MTR or MTRR activity linked to needed more methylated vitamin B12.

3. The SAM to SAH ratio listed at the bottom of the results section is usually the most critical. I was taught to evaluate this using a line between the SAM and SAH results as described below.

4. Put a line from the SAM result bar to the SAH result bar. The line should be close to vertical. A downward slope with SAH higher than SAM is a major problem since elevated SAH creates decreased SAM activity and SAH elevation creates serious increase in oxidative stress. This especially affects the kidney since the kidney is responsible for clearing 40% of SAH. This elevated SAH compared to SAM is caused by downregulation of the SAHH enzyme (also called the AHCY enzyme) often due to genetic SNP's. This is the most challenging of the enzyme defects to help correct with therapeutic nutrition and lifestyle modifications. More on this later in the case study to follow below.

5. An upward slope with SAM higher than SAH is a simpler, less serious problem caused by down-regulation of the MAT (methyltransferase) enzymes. This is a common SNP and easier to support improved function clinically. More on this later.

6. Put a line from the homocysteine result bar to the cystathionine result bar. The bars should be close to vertical. A mismatch with the homocysteine result higher than cystathionine result indicates a problem with the CBS enzyme. This enzyme defect or underactivity is easier to correct clinically.

The first methylation profile on Anthony was done on 05/21/2015. See the copy of his results in figure 1.

My interpretation of the 05/21/2015 test results:

1. His methionine is a bit low suggesting suboptimal Betaine HCL supplemental support and/or speed eating. I instructed Anthony to do 2 minutes of relaxed breathing before meal times.

2. He has a SAM/SAH mismatch with his SAH level in the red range. This concerns me greatly because of SAH creating lots of damaging oxidative stress. This is likely a significant reason for family history of early cardiovascular disease. Because 40% of SAH is cleared by the kidney, I checked his kidney function and was concerned by his dropping GFR over time. Since this is caused by downregulation of the SAHH enzyme (also called the AHCY enzyme), we started with time released niacin (B3). I recommended Anthony minimize pesticide and alcohol exposure and focus on organic eating whenever possible to support improved enzyme function.

3. He has a major Homocysteine/Cystathionine mismatch indicating a CBS enzyme downregulation. We added B6 to support upregulation of CBS. Vitamin B12, serine, zinc, phosphatidl choline, and niacin also help upregulate the CBS enzyme.

4. Our goal from this Methylation Profile is to decrease SAH and decrease Homocysteine.

5. Lastly, I recommended a retest in 8 weeks. Challenges of travel and schedule delayed the re-test to the 10/21/15 profile shown in figure 2.

My interpretation of the 10/21/15 test results:

1. His methionine normalized. No need to add stomach acid support since this lifestyle changes were sufficient.

2. His SAM to SAH conversion improved which unfortunately worsened his SAM/SAH mismatch and his SAH levels worsened. Anthony doesn't appear able to convert niacin (B3) to the active NADH form. We also stopped the time released niacin since, unfortunately, time released niacin does not work as well to boost activity of the SAHH/AHCY enzyme for some patients. We replaced the time released niacin with straight niacin to further support the NADH.

3. His homocysteine improved but his mismatch with cystathionine worsened so we added in the activated form of vitamin B6 in the pyridoxyl 5-phosphate (P-5-P) form.

4. I recommended a re-test in 8 weeks. The 2/03/16 profile retest results are shown in figure 3.

My interpretation of the 02-03-16 test results:

1. His SAM/SAH ratio much improved with his elevated SAH levels starting to drop. Still higher than desired. Continue what we are doing.

2. His homocysteine elevation just slightly better but his mismatch with cystathionine still a problem. We added the free form amino acid serine which we recommended taking 3X/day away from protein.

3. I recommended a retest in 3-4 months. The 6/15/16 profile retest results are shown in figure 4.

My interpretation of the 6/15/16 test results:

1. SAH levels best we have seen, but still higher than desired. The SAM/SAH ratio has worsened somewhat.

2. His homocysteine is stuck in the mid-7's and his mismatch with cystathionine is still a problem. I added a methylation support formulation that I really like from Xymogen called "Methyl Protect" which uses therapeutic doses of activated B5, activated B6, methylated B12, and the activated form of folic acid, methyltetrahydrofolic acid, and trimethylglycine to support homocysteine conversion to methionine. I recommend a retest in 3-4 months.

Summary: As you can see, methylation problems can be complex and simple, easy solutions are not common in these complex, difficult cases. Patience and persistence are important along with consulting with experts like the support docs at the lab you choose to use. Lastly, I mentioned only the supplemental support specific to the methylation profile findings. Based on the patient's history, exam, and labs, he was on a comprehensive supplement support program including a professional grade multi, therapeutic levels of vitamin D3 along with K2, magnesium, vitamin A, zinc, and a phase 2 liver detox support formulation.

My advice to get started, is to run a Methylation Profile: Plasma on yourself, a staff member, or a patient and jump right in. Call the lab's support staff and start learning. While I sometimes feel uncomfortable with my initial ignorance about a test and the results, I have learned to just do the test and get started. My patient does not know what I don't yet know and I love the opportunity to learn and help my patient at the same time.

About the Author:

Dr. Gerhart is the founder and director of Renovare Brain Peak Perfomance and Renovare Wellness by Design Clinic in Peoria, Arizona. In addition to Board Certification in Neurofeedback, Dr. Gerhart is a Board Certified Chiropractic Internist and a Diplomate of the International Academy of Medical Acupuncture. He and his team seek to help those struggling with a long list of chronic health problems through discovering and treating the root causes. By working with both body chemistry, brain wave imbalances, and therapeutic lifestyle change, they have been offering hope and significant improvements for many who have "tried everything" and still suffer.

by: Timothy C. Gerhart, D.C., DABCI, Dipl., Ac., BCN
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Author:Gerhart, Timothy C.
Publication:Original Internist
Article Type:Case study
Date:Dec 1, 2016
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