Clues for Clinical Treatment Plans

Through Understanding Methylation

By Debby Hamilton, MD, MPH


As an integrative practitioner, my patients typically present with complex medical issues.  Even in pediatrics, this is becoming the norm.  Any tools we can use as practitioners to guide treatment can be beneficial.  Understanding the nutritional biochemistry in methylation can aid treatment plans by creating a protocol more likely to benefit the patient.  Complex illness often needs step-by-step treatment, but knowing which treatment to start first can play a significant role in recovery time and lessen potential adverse reactions.

            Methylation influences multiple mechanisms in the body by adding and subtracting methyl groups. This transfer of methyl groups functions as an on/off switch in the body to control cell activity. The control of gene expression is through the message relayed by the addition or subtraction of a methyl group. Neurotransmitters influencing our mood, sleep patterns, and mental functioning are balanced by methylation. Hormones, which also influence mood and regulate our physiologic homeostasis, rely on proper methylation. Our detoxification system is dependent on this process and its connection with the sulfur pathway, producing one of our main antioxidants—glutathione.

            Even our cellular energy produced by our mitochondria depends on proper functioning of our methylation cycle.  Critical to mitochondrial function is an intact mitochondrial membrane.  Phosphatidylcholine is a key component of this membrane. The PEMT enzyme uses the compound SAMe formed through the methylation cycle to form phosphatidylcholine.  Therefore, if methylation is not functioning well this can lead to problems forming proper cell membranes, negatively impacting cell and mitochondrial function.

            Many practitioners think methylation means a person needs methylfolate.  Yet if this is done as a first step, many people will have a worsening of their symptoms.  Parents are not happy if their hyperactive child has an increase in their hyperactivity from a supplement you have given them.  Understanding that methylation is more than just MTHFR and methylfolate allows a practitioner to identify multiple different genetic SNPs that contribute to how someone will react to a supplement.

            Too many methyl groups in someone who is overmethylated may lead to increased reactions to stress, hyperactivity, anxiety, sleep disorders, food and chemical sensitivities.  Their neurotransmitters such as serotonin, norepinephrine and epinephrine tend to be high.  On the other extreme are people who are undermethylated and have low serotonin levels.  Lower serotonin levels are associated with depression and obsessive-compulsive symptoms.  A high percentage of people who have too few methyl groups may also have decreased levels of calcium, magnesium, methionine, and Vitamin B-6. 

            In addition to the genetic SNP’s we inherit, our environment through epigenetics plays a role in the expression of our methylation genes.  Everything from our diet to infections and toxins can impact genetic stability and alter gene expression. Understanding the interplay of a patient’s methylation genes in addition to genes involving detox pathways and neurotransmitters can help provide a pathway towards treatment in complex illness.  For those practitioners looking for a guidebook, methylation can often provide some insight.


We invite you to learn all this and more at the two-day Methylation 2018 Summit in Chicago, Illinois, July 13-15, 2018.  For more information on this CME-based conference, please go to or contact the Healthy Medicine Academy at (1-303-990-7958).