Folate, also known as vitamin B9, is often associated solely with pregnancy and fetal development. However, its significance extends far beyond this critical period. Let's delve into the various roles that folate plays in the body and explore ways to ensure optimal intake for overall health.

Understanding Folate's Role: Methylation

Folate is crucial for a biochemical reaction known as methylation. In simple terms, methylation involves attaching a methyl group (a carbon atom surrounded by three hydrogen atoms) to a molecule, leading to important changes. These changes include:

  • Epigenetic Regulation: Methylation influences gene expression by modifying DNA tags, essentially altering our body's operating manual for different bodily functions.  Our DNA – the physical strands – are static or unchangeable unless damaged.  But along the strands are markers or tags which can turn certain sections of DNA on or off.  This influences how our genetics are expressed.  Think it as making changes to our body’s operating manual in how the different body systems function.  Epigenetic changes refers to the changes in our operating manual caused by turning on or off the tags on our DNA.  These changes are brought about by changes in our body environment (think diet and lifestyle) through the process of methylation. This is very good news for anyone who may have inherited some less-than-optimal genetics – you can change the outcomes.  Clinical practice has demonstrated that positive changes can be seen in as little as 3 months.

The M's are the methyl groups that act as on-and-off switches.

  • DNA Synthesis: Proper methylation is essential for accurate DNA replication (the copying that goes on with cell growth) which is a vital processes for cellular function and growth.
  • Energy Production: Methylation supports mitochondrial function, the powerhouse of cells responsible for producing energy.
  • Detoxification: Methylation aids in transforming fat-soluble toxins into water-soluble forms in the liver, facilitating their excretion from the body. This process is crucial for eliminating hormones, heavy metals, drugs, and other compounds that can accumulate and cause harm. 
  • Fertility: Folate is essential for DNA replication, cell differentiation, and embryonic development, highlighting its importance in reproductive health.

From that list, you can see that methylation is critically important to most body functions and either hyper or hypomethylation has been associated with various health disorders.  The methylation pathway (which is a name for the complex biochemical interactions occurring) requires certain substrates and cofactors to work.  Folate is the substrate that’s needed to provide the methyl group that methylation process is based on.  Essential cofactors are other B vitamins such as B12, B6, and B2 as well as zinc, and vit C.

Impact of Hashimoto's on Methylation

If you have Hashimoto's, you can may also experience problems with methylation due to the consequences of a slower metabolism as a result of Hashimoto's.  A sluggish thyroid includes a sluggish secretion of digestive enzymes, including stomach acid.  Adequate levels of stomach acid are required to absorb B vitamins, including folate and the methylation cofactors listed above.  Low folate results in poor methylation and health issues.

Genetic Variations and Methylation

Another group of people who may experience problems with methylation are those with inherited genetic variations. These single nucleotide polymorphisms (SNPs), can affect the methylation process in our bodies. Essentially, SNPs are changes in individual building blocks of our DNA that can influence how certain genes function. When SNPs occur in genes responsible for methylation, they can alter the activity of enzymes involved in this process. For instance, if a SNP happens in a gene that codes for an enzyme like methylenetetrahydrofolate reductase (MTHFR), which is crucial for methylation, it may affect how efficiently methylation occurs. These genetic variations can impact how genes are expressed and how our cells function, potentially influencing our health in the various ways outlined above.   

Supplemental folate can have varying impacts on SNPs affecting methylation, depending on the specific SNP and individual factors. In some cases, supplementation with folate may help compensate for reduced methylation capacity caused by certain SNPs. For example, individuals with the MTHFR SNP, may benefit from supplemental folate to support methylation processes.  However, the effectiveness of folate supplementation can be influenced by factors such as the type of folate used, dose, and overall nutrient status. Some individuals may require higher doses or different forms of folate to overcome the effects of specific SNPs. Additionally, other genetic and environmental factors can interact with SNPs to modulate the response to folate supplementation.

Assessing Folate Status:

Determining folate levels can be done through simple blood tests. 

Direct measures include:

  • RBC (red blood cell) folate, which reflects folate status of previous 120 days.  Optimal range is between 1133 – 3408 nmol/L or 500 – 1504 ng/ml
  • Serum folate can act as an early marker of folate depletion.  Note that fasting level must be known to interpret the result. Optimal range is between 34 – 61 nmol/L or 15 – 27 ng/ml

Indirect or functional measures include:

  • Full (or whole or complete) blood count. Elevated levels of mean corpuscular volume (MCV) in red blood cells may indicate insufficient folate and/or vitamin B12 levels. Other indications include decreased hemoglobin or low levels of neutrophils (type of white blood cell).
  • Homocysteine. This is a molecule formed along the methylation pathway.  It increases with deficiencies in folate, B12, and B6.  Homocysteine can cause damage to endothelial lining of the arteries so is related to increases in the risks or cardiovascular disease and stroke, cancer, depression, and inflammatory bowel disease.  Optimal range is between 5 – 7.2 umol/L
Sources of Folate:

While supplementation is an option for many, obtaining folate from dietary sources is preferable. Adults typically require around 400 micrograms (μg) per day, with pregnant or lactating women needing more (500–600 μg/day). Here are some folate-rich foods and their approximate folate content per serving:

  • 1 cup of spinach: 260 μg
  • 1 cup of lentils: 358 μg
  • 1 cup of avocado: 90 μg
  • ¼ cup of sunflower seeds: 82 μg
  • ¼ cup of peanuts: 88 μg

These values do not imply the amount absorbed.  The bioavailability of food folates depend on both dietary and non-dietary factors.  These can include:

  • cooking method: folate is sensitive to heat, 
  • storage: exposure to light, air, and high temperatures during storage and processing can accelerate folate degradation. Choosing fresh, minimally processed foods and properly storing them can help maintain folate content.
  • gut health: intestinal health plays a crucial role in folate absorption. Conditions that affect the gastrointestinal tract, such as inflammatory bowel disease, celiac disease, and certain medications, can impair folate absorption. 
  • enzyme inhibition: some compounds present in foods can inhibit the activity of enzymes involved in folate absorption. For example, polyphenols found in tea, coffee, and certain fruits and vegetables can interfere with folate absorption.
Considering Folate Supplementation:

For those unable to meet their folate needs through diet alone, supplementation may be necessary. There are different forms of folate supplementation.

  • Folic acid, a common form of folate, is often added to fortified foods like bread. And it’s a common supplement for pregnant women to help ensure healthy neurological development for the fetus.  It has been hugely successful in this regard.  However, it is not an active or bioavailable form of folate and must be converted and there are those who have difficulty in this conversion. 
  • Folinic acid and 5-methylTHF are active forms of folate

Folate does not act on its own and various co-factors are needed for the methylation pathway.  These include: B12, B6, B2, and zinc.  It’s important that one has adequate levels of these nutrients before supplementing with folate.   In many cases a multivitamin or B complex can be more effective than folate alone or a single nutrient alone, especially in those with common nutrient deficiencies such as vegetarians, smokers, and those with digestive disorders. 

It's also important to consider a holistic approach.  While supplementation may provide a quick relief to symptoms, addressing root causes is necessary for long-term healing.  Diet and lifestyle must also be addressed.

In conclusion, folate is indispensable for numerous bodily functions, beyond its association with pregnancy. Understanding its roles and ensuring adequate intake through diet or supplementation is crucial for maintaining optimal health and well-being.

Summary:

Balanced methylation is essential for optimal health and is influenced by nutrient intake and inherited genetics variations (SNPs).

Methylation can be improved with optimal nutrient intake.

Must have adequate levels of B12, B6, B2, and zinc prior to folate supplementation.

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About the Author Sharon Walt


Dr Sharon is a certified Functional Medicine Health Coach who helps men and women with autoimmune disorders, such as Hashimoto's Thyroiditis, regain their health and start living life to the utmost again. 

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