Folic Acid and Folate Cycle

 

So we said that there are 3 vitamins involved in the methylation process: Folic Acid (B9), B12 and B6.

Folic Acid/ Folate

Folic acid is the synthetic (man-made) version of folate, which is a type of vitamin B9. Your body uses folate (and folic acid) to make new cells, especially red blood cells, and to keep your DNA in good shape.

Think of it like a building material for your body. Folic acid helps with things like:

• Cell growth: It’s especially important when you’re pregnant because it helps your baby’s brain and spine develop properly.
  
• Preventing birth defects: Adequate folic acid before and during early pregnancy can prevent serious birth defects in the brain and spine.
  
• Supporting overall health: It also helps maintain heart health by keeping your blood vessels healthy and preventing high levels of homocysteine (an amino acid that can be linked to heart disease).
  

So, it’s essentially a key nutrient to keep things running smoothly in your body!

Here are the common symptoms of folic acid deficiency:

🩸 1. Fatigue and Weakness

• Feeling unusually tired
  
• Low energy levels
  
• May be due to megaloblastic anaemia (large, immature red blood cells)
  

😵‍💫 2. Difficulty Concentrating

• Brain fog
  
• Poor memory
  
• Trouble focusing
  

😟 3. Irritability or Mood Changes

• Feeling depressed or anxious
  
• Mood swings
  

😮‍💨 4. Shortness of Breath and Dizziness

• Especially during physical activity
  
• Due to reduced oxygen delivery in the blood
  

👅 5. Mouth and Tongue Issues

• Sore or swollen tongue (glossitis)
  
• Mouth ulcers
  
• Cracks at the corners of the mouth
  

🧴 6. Pale or Yellowish Skin

• Due to reduced healthy red blood cell production
  

👶 7. Birth Defects (in pregnancy)

• Neural tube defects like spina bifida
  
• Important to get enough folic acid before and during pregnancy
  

🧬 8. Elevated Homocysteine Levels

Not a symptom you feel, but high levels can increase the risk of heart disease

Folate vs Folic Acid vs Folinic Acid

🔹 1. Folate (Natural Form)

• ✅ What it is: The natural form of vitamin B9 found in foods
  
• ✅ Sources: Leafy greens, legumes, fruits, liver
  
• ✅ Body use: Easily converted by the body (with the help of enzymes like MTHFR) into the active form: 5-MTHF (5-methyltetrahydrofolate)
  
• ✅ Best for: Everyday nutrition, especially from whole foods
  

🔹 2. Folic Acid (Synthetic Form)

• 🧪 What it is: A synthetic version of vitamin B9, used in supplements and fortified foods
  
• ⚠️ Note: Must be converted into 5-MTHF by the body — a process that can be slow or inefficient, especially in people with MTHFR gene variants
  
• ✅ Sources: Fortified cereals, flours, vitamins
  
• ⚠️ Too much: Excess unmetabolized folic acid may circulate in the blood, which could have unknown long-term effects
  

🔹 3. Folinic Acid (Activated Form)

• ⚡ What it is: A form of folate that is already partially activated, bypassing some steps in metabolism
  
• ✅ Used in: Certain medical treatments (e.g. chemotherapy, MTHFR issues)
  
• 💊 Also called: Leucovorin
  
• ✅ Best for: People with difficulty converting folic acid or needing rapid absorption (e.g., MTHFR mutation, certain health conditions)
  

🧬 Summary Table:

Type	Natural/Synthetic	Requires MTHFR?	Found in	Best For
Folate	Natural	Yes	Leafy greens, beans	Everyday health, whole foods
Folic Acid	Synthetic	Yes	Supplements, cereals	General supplementation
Folinic Acid	Activated	No	Prescription meds	MTHFR issues, medical conditions

People who do not eat enough folate-rich foods can also develop Folic acid deficiency anaemia and low levels of red blood cells (amendment suggested by Dr Louise Lindenberg).

The Folate Cycle is MTHFR C667T and A1298C.

The genetic SNPs that are normally tested for folate metabolism are MTHFR 677T and 1298; however, there are many more. For Alex’s test, only MTHFR C667T and A1298C were tested for. (Amendment suggested by Dr Louise Lindenberg).

🔹 What Is Vitamin B2?

• Also called Riboflavin
  
• A water-soluble B-vitamin
  
• Essential for energy production, cell function, and metabolism of fats, proteins, and carbs
  

🔧 What Does It Do?

Function	Explanation
💥 Energy Production	Helps convert food into energy by supporting enzymes (especially in mitochondria)
🧬 Antioxidant Support	Needed to regenerate glutathione, your body’s key antioxidant
🧠 Supports Other B-Vitamins	Helps activate vitamin B6 and convert folate to its usable form
💓 Homocysteine Regulation	Works with folate, B6, and B12 to keep homocysteine levels in check
👀 Eye Health	Important for vision; helps prevent cataracts
🩺 Iron Metabolism	Helps the body absorb and use iron properly

🥦 Food Sources of Vitamin B2

Category	Examples
🥩 Animal Sources	Liver, eggs, dairy, beef, salmon
🌱 Plant Sources	Almonds, mushrooms, spinach, whole grains, fortified cereals
🥛 Fortified Foods	Plant-based milks and breads often contain added B2

⚠️ Signs of Deficiency

Symptom	Description
Cracks at the mouth corners	Cheilitis or angular stomatitis
Sore or red tongue	Glossitis
Fatigue	Due to poor energy metabolism
Light sensitivity	Eye strain or blurry vision
Skin issues	Dryness or inflammation, especially around the face

Deficiency is more common in people with:

• Poor diet
  
  
• Alcohol dependence
  
  
• Absorption issues (e.g. celiac, IBD)
  
  
• High physical stress or energy demands
  
  

💊 RDA (Recommended Daily Allowance)

Group	Amount
Adult men	1.3 mg/day
Adult women	1.1 mg/day
Pregnant	1.4 mg/day
Breastfeeding	1.6 mg/day

🧠 The Folate Pathway (Quick Recap)

Folate (vitamin B9) needs to be converted into its active form 5-MTHF (5-methyltetrahydrofolate) to help:

• Make DNA and new cells
  
• Control homocysteine (a harmful amino acid)
  
• Support methylation (a key process for brain, detox, mood, and more)
  

The MTHFR enzyme is what converts folate into this active form.

💡 Where Vitamin B2 Comes In

Vitamin B2 (Riboflavin) is essential for the MTHFR enzyme to work properly.
It acts like a co-pilot for the MTHFR enzyme.

🔧 Without enough B2:

• The MTHFR enzyme slows down
  
• Folate can’t be fully activated
  
• Homocysteine may build up
  
• Methylation gets disrupted
  

🧬 Especially Important If You Have the MTHFR C677T Variant

If you have the MTHFR C677T gene mutation:

• Your enzyme is already less efficient (especially if you’re TT genotype)
  
• Getting enough B2 can improve how well your enzyme works, even with the mutation
  
• Studies show that B2 supplements may lower homocysteine levels in people with this SNP
  

✅ Summary:

Role	What Happens
Vitamin B2	Helps MTHFR enzyme work
MTHFR enzyme	Converts folate into active form (5-MTHF)
5-MTHF	Supports methylation and lowers homocysteine

 

 

 

 

 

“The Folate Cycle is the ‘Organic Farming Region, ‘ where everything is homegrown. This Region grows ‘organic’ work tags (methyl groups) and is instrumental in the front-line production of new RNA and DNA. Still, this plantation is a bit old-fashioned, employing a chain gang (homocysteine) to help them get the work done. Though rarely considered in everyday life, RNA & DNA are essential to making you unique, as well as directing health and longevity. Despite this, there must be a balance between available work tags and crafting new genetic code. “

🌱 What Happens in the Folic Acid Pathway?

When you eat foods or take supplements with folic acid, here’s what your body does step-by-step:

1. Absorption
   Folic acid from food or supplements is absorbed in your small intestine.
   
2. Conversion to Active Form
   Your body can’t use folic acid directly. It first has to convert it into its active form called 5-MTHF (5-methyltetrahydrofolate).
   This step requires an enzyme called MTHFR.
   
   
3. Helping with Methylation
   Once folate becomes 5-MTHF, it joins a process called methylation.
   This is a vital chemical reaction that helps:
   
   • Build DNA and RNA
     
   • Detoxify harmful substances
     
   • Support mood and brain function
     
   • Turn certain genes on or off
     
4. Making Red Blood Cells
   Folate is also important in making healthy red blood cells. A lack of folate can lead to anaemia (low red blood cell count).
   
5. Working with Vitamin B12 and B6
   Folate works closely with vitamin B12 and vitamin B6 to keep homocysteine levels in check. Too much homocysteine can increase the risk of heart disease.
   

🔁 In Summary:

Folic acid → converted to 5-MTHF → helps with DNA, red blood cells, and methylation.)

So we start with Folic acid. Folic Acid is the synthetic form of Folate (B9). It is an important building block for DNA and RNA. Folic acid can be found in most multi-vitamins and is very often prescribed to pregnant women.

Folate or B9 can be found naturally in dark leafy greens; however, other food also contains folate.

So let’s look at Alex’s results for MTHFR C667T and A1298C:

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

Result: MTHFR 677 C>T

🧬 What is the T allele?

• It’s a version of a gene called MTHFR that some people inherit.
  
• This gene makes an enzyme that helps your body use folate (vitamin B9) properly.
  

🧪 What does the T allele do?

• It reduces the MTHFR enzyme’s activity:
  
  • If you have two copies of the T allele (called TT), your enzyme works at only 40% efficiency.
    

🔁 What happens in your body because of this?

Effect	What It Means
🚫 Less enzyme activity	Folate isn’t activated properly
⬆️ Homocysteine levels rise	A waste product (homocysteine) builds up in your blood
⬇️ DNA methylation drops	Your body can’t properly “tag” DNA to keep it healthy
⬆️ DNA adducts	Damage can occur to your DNA, which may increase disease risk

🥗 What do people with this gene need?

Nutrient	Why It’s Needed
Folate (especially in active form: 5-MTHF)	To bypass the slow MTHFR enzyme
Vitamin B2 (riboflavin)	Helps the MTHFR enzyme work better
Vitamin B6 & B12	Help reduce homocysteine levels

💊 How Much Folate?

• People with the TT type may need up to 800 mcg of folate daily
  
• It should ideally be in the form of 5-MTHF, not regular folic acid
  

✅ Bottom Line (in plain terms):

If you have the T version of the MTHFR gene, your body has a harder time using folate. That can lead to problems with your blood, DNA, and brain. You may need more folate, B2, B6, and B12, often with supplements to stay healthy.

To keep this whole process going, B2 must be present in high enough amounts in the body to allow other B vitamins including B6 and folic acid to properly do their jobs.

🧬 Vitamin B3 (Niacin) and Methylation

Vitamin B3, also known as niacin, plays an important supportive role in methylation by helping regulate the use of methyl groups in the body.

🔹 Key Functions of Vitamin B3 in Methylation:

Function	Explanation
🔋 Forms NAD⁺ / NADH / NADP⁺ / NADPH	These are coenzymes required in energy metabolism and redox reactions—critical for many methylation-related processes.
🔁 Helps recycle SAMe	Through its role in cellular energy metabolism, niacin indirectly supports the regeneration of SAMe (S-adenosylmethionine), the main methyl donor.
🧯 Reduces methyl drain	When there’s a B3 deficiency, the body uses methyl groups to make more niacin from tryptophan—this can deplete methyl donors.
🧠 Supports neurotransmitter balance	Needed for the conversion of tryptophan to serotonin and melatonin, which ties into the BH4 and methylation cycles.

🧪 Methylation & Niacin Balance:

• Too little B3 = body uses more methyl groups to synthesise it → strains the methylation cycle.
  
• Too much B3 (as niacin or niacinamide supplements) can deplete methyl donors like SAMe and folate.
  

✅ Best Food Sources:

• Chicken, turkey, tuna, beef liver
  
• Peanuts, mushrooms, brown rice, whole wheat
  
• Fortified cereals

Vitamin D and VDR receptors

☀️ What is Vitamin D?

• Vitamin D is a vitamin and hormone your body needs to stay healthy.
  
  
• It helps your body:
  
  • Absorb calcium for strong bones and teeth 🦴
    
  • Support your immune system 🛡️
    
  • Keep your mood and brain healthy 🧠
    
  • Regulate gene activity (like a dimmer switch)
    

Your body makes it when sunlight hits your skin 🌞.

🔑 What is the VDR? (Vitamin D Receptor)

• VDR stands for Vitamin D Receptor.
  
• It’s like a lock, and Vitamin D is the key.
  
• When Vitamin D attaches to the VDR:
  
  • It turns certain genes on or off
    
  • It helps control things like inflammation, immunity, and calcium use
    

🧬 VDR in the Methylation Cycle:

• VDR affects methylation-related genes like:
  
  • TAQ and Fok1 (types of VDR gene variations)
    
  • These affect how well your body uses vitamin D
    
• A weak or slow VDR response may mean:
  
  • You need more vitamin D
    
  • Your methylation and detox processes might be slower
    

🌿 In short:

Vitamin D is like sunshine fuel. The VDR is the control panel that helps your body use that fuel to keep your cells, bones, and immune system running smoothly.

 

 

 

 

Once vitamin D has been ingested in the diet or produced in the skin, the liver and kidneys convert it to its active form, called 1,25-dihydroxyvitamin D, or vitamin D3.

According to mainstream medical standards, there are three levels of vitamin D status: sufficient, insufficient, and deficient.

• People who are considered vitamin D “sufficient” have blood levels of at least 30 ng/mL. However, optimal vitamin D status is achieved with a minimum of 50 ng/mL.
• Those considered “insufficient” (meaning their bodies aren’t at optimal vitamin D capacity) have levels between 21 and 29 ng/mL.
• And those who are “deficient” are defined as having levels at or below 20 ng/mL.

 

 

 

 

 

 

 

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.