Defining the Triangle – Part 2: Chemical

In the absence of trauma, the body breaks down on the inside before symptoms arise on the outside. Too often our perception of health is predicated upon physical appearance; i.e. the 6-pack, instagram model who can eat whatever they want and sustain this ideal balance. Furthermore, we take inventory of our body status and conclude if we are not acutely sick, then we must also be in good health.
This is reactionary, old school thinking. With today’s technology we have so many resources to make accurate inferences on multiple aspects on our internal environment to address dysfunction before symptoms arise.
In this post we’ll be breaking down 4 key areas when it comes to optimizing the status of your chemical balance: Inflammation, Neurotransmitters, Hormones and Methylation.
disclaimer: methylation is one of my favorite topics so we’re diving deep ladies and gentlemen.


Inflammation is the mother of all disease, as a response to the environment we nourish ourselves with.

Inflammation is potentiated by several environmental and lifestyle factors:

  • Blood sugar imbalance
  • Hormones status
  • Nutritional quality
  • Poor detoxification
  • Oxygen deficiency
  • Psychological stress

Leaky Gut: the driver of inflammation

In my opinion, one of the primary sources of inflammation is leaky gut. Think about it this way: our gut has the most interaction with our environment, and therefore what we eat provides the most information about our environment to the body. This is the primary reason behind food is medicine.

As we consume damaging foods such as refined carbs, lectins, excess sugar and hydrogenated fats, the lining of our gut begins to breakdown and over time allow more and larger molecules to get through. On the other side of the gut lining, 65% of your immune system resides to patrol the molecules that are entering. As breakdown continues and more foreign invades enter, the immune system gets put on red alert and begins to surge so much that inherently friendly fire takes place and some of our own tissues get attacked. This is believed to be one of the sources of auto-immunity and food sensitivities.

The immune system requires a huge amount of energy to do its job, and therefore must have a steady source of energy to ‘supply the troops’. One of the reasons we store fat in the gut is because this is where the immune system is most active. Fat is there because of the inflammation, and the inflammation is there because you have a leak in your gut. There are studies suggesting a direct correlation to the amount of inflammation with the amount of fat surrounding blood vessels, the epicenter of cardiovascular disease.

If you take a look at the graph above, there are extensions of inflammation such as brain inflammation, stress chemistry and auto-immunity. Briefly speaking, the blood brain barrier (BBB) functions as a tight net to selectively allow certain things in. Ironically, the same tissue that makes up the lining of the gut makes up the blood brain barrier; therefore if you have leaky gut, you are very likely to have a compromised BBB.


A very simple test we like to perform to directionally hint at a compromised BBB (proposed by Dr. Datis Kharrazian) is a GABA challenge via oral supplementation. GABA is the brain’s primary inhibitory neurotransmitter, and dampens activity in the brain giving you the feeling of sleepiness. When taken orally, once this molecule enters the blood stream it is too big to pass through a healthy BBB, and therefore if you experience the sensation of sleepiness it is likely you have a permeable barrier.

To directly measure the barrier system, Cyrex Labs has fantastic panel to assess zonulin, occludin, actomyosin and LPS antibodies to better understand the severity of intestinal permeability. This can significantly point us in the right direction as it relates to treatment duration.


It is an under-appreciated fact that primary raw materials needed for making many neurotransmitters are nutrients: amino acids, vitamins, minerals and other natural biochemicals we obtain from food. The challenge is to identify specific nutrient imbalances present in an individual and provide treatments designed to normalize levels in the blood and brain. This precise nutrient therapy should optimize around 2 things:

  1. Normalizing the concentration of nutrients needed for making neurotransmitters
  2. Nutrient therapies to assist epigenetic regulation of neurotransmitter activity

Many times when it comes to neurotransmitter health, the typical approach is to measure your levels to determine pathological highs or lows with a snapshot of data, in which an intervention is introduced to normalize the value. Rarely do we investigate the root cause from a bird’s eye view to better discern through the true nature of the pathology.

Think about it like this: would you be able to determine the cause of a car accident by looking at a picture of the skid marks on the road? Likely not. However if you were given different angles of each car or even had seen a video of the accident, you would be able to come to a conclusion with much greater certainty.

To be able to understand the entire picture, we have to take fluctuation, or flux into consideration. Flux is knowing and understanding the status of each of these parts:

1. Molecule

2. Receptor

3. Action

4. Clearance

Through this lens, we are more equipped to observe areas of dysfunction from a 30,000 foot view.


Clinically, we don’t specifically measure neurotransmitter levels, rather the metabolite breakdown of them to observe potential areas of dysfunction within receptor, action and clearance. GPL has a fantastic Organic Acids Test (or OAT) to assess this.


Hormonal health is often not prioritized when it comes to promoting longevity and delaying the onset of chronic disease. However hormones play a vital role in communication throughout your body. Hormone balance is predicated upon:

  1. Blood sugar regulation
  2. Essential fatty acids
  3. Gut microbiota
  4. Liver detoxification pathways

Sleep = happy hormones.

The most important aspect of hormone health is sleep, as hormones are made during deep restorative sleep.


Clinically, to throughly understand hormone status I recommend DUTCH tests to my patients. DUTCH stands for Dried Urine Test for Comprehensive Hormones.


To truly appreciate optimizing cellular health, it’s imperative that we prioritize methylation. This process occurs billions of times per second, impacting the way we age and the incidence of disease. It is said by many that methylation will be a primary emphasis of medical research over the next 20 years, as it holds implications in biological aging, cognition, personality, mental and physical characteristics.

Why should we optimize methylation?

“If you want to know how important a single process is to a system, just look at how often that process is used within the system.” – Michael Chapman, ND

Our bodies are incredible at removing, trading and recycling methyl groups from one molecule to the next through the process of methylation. What this means essentially is the body has a specific way of “tagging” molecules to change what they do; inactivating a hormone or degrading a neurotransmitter are 2 critical examples. It’s fascinating to appreciate for a moment how many processes depend on methylation. Specifically, the methylation cycle is responsible for regulating:

  • Maintenance of DNA and RNA (determining which genes are turned on/off)
  • Methionine (needed for protein synthesis)
  • Neurotransmitters (dopamine, estrogen, adrenaline and serotonin degradation)
  • Glutathione (the most important anti-oxidant)
  • Cysteine (needed for detoxification and antioxidant production)
  • Sulfate (needed for detoxification, growth and repair)
  • Metallothionein (heavy metal detoxifier of lead and mercury)
  • Taurine (produces bile, increases GABA, manages seizures)
  • SAMe (primary methyl donor)
  • Homocysteine (waste product associated with cardiovascular disease and neurodegeneration)

You can see by this list that it’s imperative the methylation cycle is optimized for the body to operate at its highest capacity. Most biochemical pathways are affected by methylation and anything that slows this cycle down is putting your health at risk. During times of stress, environmental toxins, or poor digestion/absorption of nutrients, the methylation cycle becomes depleted of key vitamins and methyl donors and the individual tends to get sick at a faster rate.

90% of methylation goes towards making 2 things: creatine and phosphatidylcholine. You might pause for a second and say, “Wait, this important process is necessary for producing creatine? I thought body builders and athletes take creatine for muscles and increased energy? While that may be true, creatine is primarily used as the brain’s primary energy metabolism and provides the energy required for the stomach to produce stomach acid. If you know anything about the stomach, it requires an ENORMOUS amount of energy to function properly at a pH of 1.5 (really acidic). On the flip side, phosphatidylcholine makes up the membrane of every single cell in your body. The health of that membrane influences how receptors express themselves and furthermore how our cells communicate with the rest of the body. As you know by now, communication is key.

In respect to aging, methylation is also critical to epigenetics. Our cells are constantly altering the expression of genes in response to the environment, and methylation is one of the key processes cells use to silence genes.

What can I do about methylation right now?

Chris Masterjohn Ph.D recommends the following for supporting methylation:

  • Folate
  • – 100g

    – 2-3 servings of liver, sprouty legumes or leafy greens

    • Vitamin B12
    • – We can only absorb a days worth at a time

      – 1/3 of your meals should contain B12 (12 oz of meat, poultry, fish)

      • Choline or betaine
      • – 2-3 egg yolks per day

        – Supplement options: 1tsp of licithin OR 600mg alpha-GPC, 500mg TMG

        • Glycine
        • – 1-2 g of collagen (for every 10g of protein)

          – Bone broth if you know the amount of protein


          Clinically, I like to test the gold standard measure [1] of methylation: serum SAMe:SAH through Genova Labs


          Andrew Rostenburg

          David Sinclair

          Chris Masterjohn