“As your body processes folate, it makes folinic acid along with serine and glycine—nutrients that help with energy, mood, and cell repair.”

 

Production of Folinic Acid, Serine and Glycine:

 

 

 

 

 

 

 

🧠 Folate and the Folate Cycle

1. Folate receptors are like little doors on your cells that let folate (a type of vitamin B9) from food into your cells.

2. Once inside, folate goes through a few steps to be turned into forms your body can use:

   • First, it becomes DHF (dihydrofolate).

   • Then it turns into THF (tetrahydrofolate) using an enzyme called DHFR (dihydrofolate reductase).

3. From THF, it’s converted into 5,10-methylene-THF (also known as folinic acid). During this step, the body also produces important amino acids like serine and glycine, which help with energy, mood, and detox.

4. Finally, 5,10-methylene-THF turns into 5-methyl-THF, which is the active form of folate that your body uses for:

   • DNA repair

   • Detox

   • Mood and brain function

   • Methylation (turning genes on and off)

⚠️ Folic Acid vs. Natural Folate – Why It Matters

• Folic acid is a synthetic form of folate used in many supplements and fortified foods.

• Your body has to convert folic acid through the folate cycle to use it.

• If someone has a methylation issue (like an MTHFR gene mutation), their body struggles to convert folic acid efficiently.

• This means unprocessed folic acid can build up in the body and cause problems, blocking the active folate your cells actually need.

✅ Better Choices for Folate:

• Use methylfolate (5-MTHF) or folinic acid instead of folic acid — these are already in active or nearly active forms.

• Eat more dark green leafy vegetables like spinach, kale, and broccoli — these are rich in natural folate.

🧬 In simple terms:

Folic acid is like raw ingredients your body has to cook. If your “kitchen” (methylation) isn’t working well, it’s better to eat food that’s already prepared — like folate or folinic acid — to keep your body and brain healthy.

Remember this picture?

 

 

 

 

The conversion of folic acid into folinic acid takes place in the ‘Organic Farming’ cycle shown in the diagram. Within this cycle, the enzyme Thymidylate Synthase plays a crucial role by converting dUMP into dTMP, which is essential for making DNA. For this entire folate cycle to function, the enzyme DHFR (Dihydrofolate Reductase) must be active at the beginning to convert folic acid into usable forms. Thymidylate Synthase also helps regulate dUMP and dTMP levels, preventing imbalances that could lead to DNA damage.

Then to get to the COMT results, you have to move on the BH4 Cycle…

BH4: Better Health 4 Life cycle

The BH4 cycle is like the spark plug for your brain and blood flow, helping you make happy chemicals and keeping your heart healthy. But stress, toxins, or methylation problems can drain BH4 and cause fatigue, mood problems, and inflammation.

This cycle is responsible for creating the 5 neurotransmitters which scientists say is not missing, but very low in production in Autistic people: Serotonin, Dopamine, Epinephrine, Nor-epinephrine and Melatonin.

🧠 The BH4 Cycle (Tetrahydrobiopterin Cycle) is a tiny but powerful process in your body that helps with:

• Making neurotransmitters like serotonin (mood), dopamine (motivation), and norepinephrine (focus)

• Supporting nitric oxide production, which controls blood flow and heart health

• Reducing inflammation and oxidative stress

🔬 What Is BH4?

• BH4 (Tetrahydrobiopterin) is like a helper molecule (cofactor) that enzymes need to do important jobs in your body.

🚀 What the BH4 Cycle Does:

⚠️ When BH4 Is Low:

• Trouble making neurotransmitters → anxiety, depression, ADHD, mood swings

• Poor nitric oxide → high blood pressure, poor circulation, fatigue

• Increased oxidative stress → inflammation, immune problems

• BH4 gets easily used up by toxins, stress, infections, or heavy metals

🧬 How BH4 Connects to Methylation:

• BH4 works closely with the methylation cycle and folate cycle

• Methylation and BH4 share resources, like SAMe and folate, to stay balanced

• If methylation isn’t working well (like with MTHFR issues), BH4 can also struggle

🍎 How to Support the BH4 Cycle:

✅ Increase:

• Folate (5-MTHF) and B12 — support the upstream cycles

• Vitamin C — protects BH4 from oxidation

• Selenium, zinc, magnesium — needed for enzyme function

• L-arginine supports nitric oxide

• Toxin reduction — lower heavy metals, mould, infections

BH4 is MTHFR A1298C. 

Let’s look at Alex’s COMT results:

Though there was no impact on his MTHFR A1298C, …

MTHFR	677 C>T	TT	Severely impacted
	1298 A>C	AA	normal

… his COMT was moderately impacted

COMT

472 G>A

AG

moderately impacted

COMT 472 G>A – AG (Heterzygous, Val/Met)

🧠 What does COMT do?

COMT is a special enzyme in your body that helps clear out extra brain chemicals and hormones, like:

• Dopamine (helps with mood and focus)
  
  
• Adrenaline & noradrenaline (stress and alertness hormones)
  
  
• Estrogen by-products (from hormone breakdown)
  

It does this by adding a “methyl group” (a little chemical tag) to these substances, which helps the body safely remove them. The methyl group comes from a helper nutrient called SAMe (S-adenosyl methionine).

🧬 What does the A allele mean?

If someone has the A version of the COMT gene:

• Their enzyme works 3–4 times slower than normal.
  
  
• This means hormones like dopamine and estrogen may build up.
  
  
• This can raise the risk for issues like estrogen-related cancers (e.g., breast cancer), and affect mood or stress response.
  

✅ What can help?

To support healthy COMT function:

• Eat more insoluble fibre (e.g., whole grains, carrots, cabbage)
  
• Choose good fats (like olive oil, nuts) and reduce bad ones (trans fats)
  
• Maintain a healthy weight
  
• Exercise regularly
  
• Get enough magnesium (leafy greens, pumpkin seeds, avocado)
  
• Eat plenty of antioxidants (berries, colourful veg)
  

❗ Avoid too much quercetin and green/black tea, as they slow COMT down even more.

🚦 How the Val/Met (G/A) variant affects function:

🔸 Val (G allele) = High COMT activity

• Breaks down dopamine & stress hormones faster.

• Typically calmer under stress, but may have lower dopamine in the prefrontal cortex, leading to:

  • Focus challenges

  • Lower working memory

  • Less reward sensitivity

🔸 Met (A allele) = Low COMT activity

• Breaks down dopamine & stress hormones slower.

• Higher dopamine levels, which boosts:

  • Focus

  • Creativity

  • Memory under normal conditions

• BUT… prone to:

  • Stress sensitivity

  • Anxiety

  • Overwhelm in high-pressure situations (dopamine overload)

🔸 Val/Met (G/A) – Alex’s Result

• Intermediate enzyme activity

• A balance:
  ✅ Can focus reasonably well
  ✅ Can handle stress moderately well

• You may experience:

  • Good cognitive flexibility

  • Occasional stress sensitivity or performance anxiety

  • Sometimes benefit from dopamine-supportive nutrients (tyrosine, B vitamins), and sometimes from calming supports (magnesium, mindfulness), depending on life demands.

🧠 Mood, Stress, and Cognition Impact:

🩺 Health & Methylation Impact:

• COMT uses methyl groups (via SAMe) — so slow COMT (Met carriers) puts a greater burden on your methylation system.

• This can:

  • Increase demand for methylation nutrients: B12, folate, SAMe, magnesium.

  • Impact detox of estrogen (estrogen metabolites are cleared via COMT), potentially affecting hormone balance.

• Fast COMT (Val) burns methyl groups less, but can lead to low dopamine-related issues.

🔥 Pain Sensitivity:

• Met carriers (A allele) = Higher pain sensitivity, since dopamine and norepinephrine modulate pain perception.

• Val carriers (G allele) = Higher pain threshold.

You as a Val/Met tend to be somewhere in the middle — not extremely pain-sensitive but not pain-resistant either.

🌱 What Can You Do About It?

✅ Support dopamine balance:

• Protein-rich foods (tyrosine)

• Adaptogens: Rhodiola, Ashwagandha

• Magnesium for calming

• Mindfulness to buffer stress

✅ Support methylation:

• B vitamins (especially methylated B12, folate)

• Magnesium

• Trimethylglycine (TMG) or SAMe if needed (watch for overstimulation)

✅ Estrogen detox (if needed):

• Cruciferous veggies (broccoli, cauliflower, cabbage)

• DIM or calcium-D-glucarate if estrogen dominance is an issue

🌈 In summary (Val/Met):

You have a flexible but sensitive system.
You can usually handle cognitive tasks well and manage stress reasonably, but under chronic stress, you may feel mentally overloaded or anxious. Supporting both dopamine and stress resilience, plus methylation, is key for optimal balance.

This whole cycle needs Vit B6 to function. Currently, Alex is taking P5P for his low B6.

 

🧠 COMT and Autism 

The COMT gene (Catechol-O-Methyltransferase) controls an enzyme that helps break down certain neurotransmitters, including:

• Dopamine (motivation, focus)

• Norepinephrine (alertness, stress response)

• Epinephrine (adrenaline) (fight or flight)

It also helps clear estrogen, detoxify toxins, and remove oxidative stress products.

🧬 COMT in People with Autism

Many individuals with Autism Spectrum Disorder (ASD) have variants (SNPs) in the COMT gene that make this enzyme work more slowly or less efficiently.

⚙️ When COMT Is Slow:

• Dopamine builds up → can cause rigid thinking, sensory overwhelm, mood swings, anxiety, irritability

• Trouble clearing stress chemicals (norepinephrine, epinephrine) → leads to high stress responses, poor sleep, hyperactivity

• Estrogen buildup (influences mood and immune response)

• Higher oxidative stress and inflammation, since COMT also helps process toxic byproducts

🔥 Signs of COMT Slow Activity in Autism:

• Sensory overload

• Emotional rigidity or meltdowns

• Anxiety, irritability, mood swings

• Sleep struggles

• Focus and attention challenges

• Reactivity to stress (fight-or-flight easily triggered)

🌿 Supporting COMT in Autism:

⚖️ COMT and Methylation Balance:

• COMT uses methyl groups (SAMe) to process neurotransmitters.

• If someone has MTHFR mutations (reduced methylation), COMT can get backed up.

• But over-supplementing methyl donors in COMT-slow individuals can cause anxiety, insomnia, and agitation — balance is key.

🧠 In Simple Terms:

COMT is the brain’s chemical cleanup crew. If it’s slow (common in autism), stress chemicals and dopamine pile up, causing mood, focus, and sensory problems. Supporting methylation, stress regulation, and detox helps keep COMT running smoothly.

COMT Gene: Symptoms, Diet, and Supplement Tips – levelheadedmind.com

PLEASE NOTE: ANY VIEWS REGARDING THE RESULTS ARE MY UNDERSTANDING AND DO NOT SERVE AS PROFESSIONAL ADVICE. THE TREATMENT RECOMMENDATION IS STRICTLY RELATED TO ALEX’S RESULTS AND NOT MEANT FOR SELF-TREATMENT. ALWAYS SPEAK TO YOUR HEALTHCARE PROVIDER BEFORE STARTING ANY TREATMENTS.