The Case of Unrelenting Depression and Anxiety w/ Dr. Loren Marks - Inna Topiler

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Inna Topiler

The Case of Unrelenting Depression and Anxiety w/ Dr. Loren Marks

What role does methylation and the MTHFR gene play in depression and anxiety?

The Case: 

  • Allison is 36 and has been struggling with mood issues since college
  • She feels depressed, anxious, lonely and uncomfortable in social situations.
  • Antidepressant medications and talk therapy worked only temporarily
  • She tried supplement with vitamin B, but that made her feel worse

The Investigation

According to the Anxiety and Depression Association of America, anxiety affects over 18% of the US population and is the most common mental illness in America. They also report that it’s not uncommon for depression and anxiety to be experienced together. The website lists risk factors as genetics, brain chemistry, personality, and life events. I had my suspicions that genetics were at play with Allison. 

My instincts were to test her DNA for the MTHFR gene and determine if there might be a problem with her methylation capacity. To talk more in depth about this, I invite a methylation expert to join me on the show. 

Dr. Loren Marks is a chiropractic physician who has been practicing in New York City for over 35 years. He’s the founder of the Integrative Assessment Technique, or IAT which is an assessment methodology embracing nutritional-biochemistry, emotional health, and structural neurology. He’s also a postgraduate instructor, a noted speaker, and frequent lecturer. 

What is Methylation

Methylation is an important metabolic process. Methylation happens in every cell; in every organ of the body. And, it takes place more than a billion times a second.

To understand the process, you first have to know that there is a molecule called methyl which is composed of carbon and hydrogen (CH3). This molecule occurs in the cell and plays an important role in many processes in the body including eliminating heavy metals, detoxification, repairing damaged DNA, and creating new cells. 

Mental Health and Methylation 

Methylation plays a role in energy production, mood balancing, and neural transmission in the brain. The three main neurotransmitters that are controlled or expressed through methylation are serotonin, dopamine and norepinephrine – all of these correlate with depression, anxiety, and other issues with mental health. It’s important to note that the methylation pathways in the brain depend on good nutrition. 

What is the MTHFR Gene?

Many people become familiar with methylation in relation to the MTHFR gene which can be identified through commercial DNA tests like 23 and Me. MTHFR is short for methylenetetrahydrofolate reductase. When geneticists looked at the different genes that control the methylation process, MTHFR has the highest molecular weight, which means it’s the largest gene in a pool of over 20 genes. They assumed it had significant impact on methylation because of this dominance but further research has revealed that the smaller genes actually they can significantly impact the effectiveness of methylation.

The MTHFR gene is responsible for the metabolism of methyl folate. MTHFR has two different alleles that, if they are mutated (which is common), can render the gene incapable of metabolizing methylfolate. 

What Does it Mean to Have Mutated MTHFR Gene?

Many people become concerned that they have a mutation but Dr. Marks says that it doesn’t necessarily mean you’re in trouble. There are many other things to consider including how this is impacting your ability to process methyl. 

The MTHFR can be expressed due to a predilection based on the genes that you inherited from your parents, but your lifestyle choices (the food you eat, the water you drink, the air you breathe, the stress that you’re living with day to day) play a role. Research shows that lifestyle can trigger the expression of MTHFR gene.

Diagnosing Methylation

It’s important to work with a doctor to determine what’s happening with methylation. Having the MTHFR gene doesn’t mean there is a methylation problem – you could be balanced, be an over-methlator, or an under-methylator. 

There are two blood tests that can determine methylation efficiency. One is called a whole blood histamine. The normal range on this test is 40 to 70. If you’re in that range, even if you have MTHFR, then your global methylation status is actually balanced out by other genes.

The second test you can get is the SAMe ratio test. Testing the S-adenosyl-L-methionine (SAMe) ratio will reveal whether you are net over or under in methyl. 

How to Treat Methyl Related Depression and Anxiety

Rebalancing methyl levels may help with depression and anxiety. Depending on whether you are over or under methylator, there are supplements that can help. But, the wrong supplements can be problematic. For example, in some cases methyl folate can lower serotonin which is not what someone wants if they are dealing with depression or anxiety. 

Dr. William Walsh identified 5 biotypes of depression: undermethylation, folate deficiency, copper overload, pyrrole disorder, and toxic metals. Identifying which biotype is behind the depression will inform the correct supplement treatment. Additional tests can further inform treatment which could include: SAMe, methionine, antioxidants, zinc and B6 (if you have pyrrole disorder) and copper.In the majority of cases, applying the right nutrient therapy, reducing oxidative load, improving diet, and exercising.

For Over methylators, Dr. Marks suggests niacin or niacinamide for over methylators (because it binds to methyl), calcium fulminate, mineral manganese, B12, B6, zinc, vitamin C and a special form of vitamin E called tocotrienols. He also recommends taking antioxidants for the oxidative load.

Mystery Solved

DNA tests revealed that Allison had the MTHFR gene. Further testing revealed that she was an over methylator. She had reacted to the B vitamins she’d taken because they were methyl based and her over methylation had spiked her methyl levels. 

To balance this, Allison took 1 capsule of Niacin CRT per day to soak up the methyl. We also used a supplement called  B12 ND from premier research labs which is B12 in the adenosyl cobalamin form and folinic acid instead of methyl folate for source of natural folic acid. 

After 3 weeks on this protocol, Allison noticed a change. She described it as something lifting, almost like a veil. 

Allison also had an elevated level of copper which we saw that through a hair test. I gave her 90 mg of Zinc Supreme,  3000 mg of Vitamin C and 250 micrograms of Molybdenum to balance that. Please note that those zinc dosages are high due to her specific high level of copper. I don’t normally recommend that someone supplements with such high doses of zinc daily unless they have high copper and are under the care of a professional. 

We monitored Allison’s copper levels over the next few months and on the 3rd hair test we saw the levels back in the normal range at which point we stopped the extra zinc, vitamin C and Molybdenum.

With the copper down and her methylation more in check, we were able to stop the niacin as well. She now only uses niacin when needed if she feels any of her past symptoms that came with over methylating.


Allison rebalanced her methyl and was so excited to be feeling better. After years of medications and frustrations, she finally understood the role of methylation in her mental health. Now, she feels capable to track of her methyl levels and adjust as need be to keep herself balanced. 

Important Note

Methylation is a process and so can and often will shift as we go through life. It’s important to monitor and adjust as needed. When we take out methyl groups with niacin and don’t give any extra, it is possible that over methylators can still become low in methyls and therefore temporarily be under methylators. Like Allison, these levels should be closely monitored and treated appropriately. 

Eliminating Health Mysteries

For Allison, we were able to find that missing piece of the health puzzle and help her regain her mental health. Could methyl levels be the missing clue for you or someone in your life? Share this episode with them.


Thanks to my guest Dr. Loren Marks. You can connect with him through his website or on Facebook

Histamine determination whole blood can be done at Labcorp only (Test # 081315)

Suggested Products:

Niacin CRT 

B12 ND 

Zinc Supreme Vitamin C 


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