Methylation is a biochemical process in the body where a molecule called a methyl group (one carbon atom bonded to three hydrogen atoms) is added to other molecules. This process plays a critical role in detoxification, as it helps the body neutralize and eliminate toxins, hormones, and heavy metals.
Methylation also supports optimal health by regulating DNA repair, producing energy, synthesizing neurotransmitters, and maintaining healthy immune and cardiovascular systems. Efficient methylation ensures that the body can effectively respond to environmental and internal stressors, keeping key systems in balance.

Methylation works as a "clean-up crew" by attaching methyl groups to toxins or hormones, making them stable and ready for elimination. Proper methylation is dependent on nutrients like B12, folate, and B6, which act as cofactors.

​When methylation is impaired (due to nutrient deficiencies, genetic mutations like MTHFR, or high toxin load), detoxification can be less efficient, contributing to toxin buildup and health issues.​

MTHFR Gene Mutations

Optimal health hinges on how well your body can detoxify toxins, balance nutrients, and regulate cellular processes. One of the key players in these processes is the MTHFR gene. When this gene is impaired by a mutation, it can disrupt the body's ability to detoxify, potentially leading to various health challenges.
MTHFR stands for methylenetetrahydrofolate reductase, an enzyme responsible for converting folate (vitamin B9) into its active form, methylfolate. Methylfolate is crucial for methylation, a biochemical process involved in:
  • Detoxifying toxins and heavy metals.
  • Regulating neurotransmitters.
  • Synthesizing DNA and repairing genetic material.
  • Processing hormones like estrogen.
Mutations in the MTHFR gene can impair this enzyme's efficiency, slowing down methylation and detoxification.

MTHFR gene mutations, also called polymorphisms, are inherited. The two most studied variants are C677T and A1298C.
  • Single Mutation: If you inherit one copy of the mutation (heterozygous), enzyme activity may be slightly reduced.
  • Double Mutation: If both gene copies carry the mutation (homozygous), enzyme activity can drop significantly, potentially by 40-70%.
While the mutations themselves are inherited, their effects may be amplified by environmental and lifestyle factors, including:
  • Toxin Exposure: Chemicals, pesticides, and heavy metals increase the detoxification burden.
  • Nutrient Deficiencies: Lack of B vitamins, particularly B12, folate, and B6, worsens methylation deficits.
  • Chronic Stress: Heightened stress depletes resources required for methylation.
  • Poor Gut Health: Dysbiosis and inflammation reduce nutrient absorption and increase toxin load.

A compromised MTHFR gene slows methylation, weakening the body’s ability to:
  • Neutralize Toxins:
    Methylation helps detoxify heavy metals like mercury and arsenic, as well as chemicals and drugs. Reduced methylation efficiency leaves toxins circulating longer, potentially causing inflammation and oxidative stress.
  • Process Estrogen and Hormones:
    Impaired methylation leads to the accumulation of harmful estrogen metabolites, increasing the risk of hormonal imbalances and conditions like estrogen dominance.
  • Support Antioxidant Defense:
    Methylation generates glutathione, the body’s master antioxidant. Reduced glutathione levels leave the body vulnerable to free radicals and cellular damage.
  • Balance Neurotransmitters:
    Methylation is essential for producing and breaking down neurotransmitters like serotonin, dopamine, and norepinephrine. Imbalances may contribute to mood disorders, anxiety, and fatigue.
​An MTHFR gene mutation does not define your health destiny. While it can pose challenges, an integrated approach emphasizes that through targeted nutrition, lifestyle changes, and toxin reduction, you can optimize methylation, support detoxification, and thrive. 
  1. Optimize Nutrient Intake: Consume methylated nutrients (e.g., methylfolate and methylcobalamin [B12]) to bypass the impaired enzyme. Include B6 (pyridoxine), magnesium, and riboflavin (B2), which are methylation cofactors. Eat folate-rich foods like leafy greens, avocados, and lentils.
  2. Reduce Toxin Exposure: Minimize contact with pesticides, plastics, heavy metals, and processed foods. Use natural cleaning products and personal care items.
  3. Support Detox Pathways: Include glutathione-boosting foods (e.g., cruciferous vegetables, garlic, and onions). Engage in practices like sweating (sauna or exercise) and ensuring regular bowel movements.
  4. Address Gut Health: Restore the microbiome with probiotics and prebiotics. Avoid inflammatory foods, such as gluten and refined sugar.
  5. Manage Stress: Practice mindfulness, yoga, or meditation to reduce stress and conserve methylation resources.
  6. Test for MTHFR and Related Markers: Functional testing for MTHFR gene variants, homocysteine levels, and nutrient deficiencies can provide insights into methylation status.

Addressing these issues holistically can transform an MTHFR mutation from a potential obstacle into an opportunity for enhanced well-being.

Homocysteine

Homocysteine is a naturally occurring amino acid produced in the body during the metabolism of methionine, an essential amino acid found in dietary protein. While homocysteine is a normal byproduct of biological processes, elevated levels can harm the body, contributing to chronic disease and poor detoxification. Understanding homocysteine's role is key to improving overall health and preventing disease.
Homocysteine is an intermediary molecule in the methionine cycle, which is critical for methylation—a process that supports DNA repair, neurotransmitter production, and detoxification. The methionine cycle consists of:
  • ​​Remethylation: converts homocysteine back into methionine, which requires folate, vitamin B12, and betaine.
  • Transsulfuration: converts homocysteine into cysteine, which is used to produce glutathione, an important antioxidant. This process requires vitamin B6.

In a healthy system, homocysteine is recycled or excreted efficiently. It is either:
  1. Reconverted to Methionine: With the help of methyl donors like folate (B9) and B12 (cobalamin).
  2. Converted to Cysteine: Via the transsulfuration pathway, requiring B6 (pyridoxine), and used to produce glutathione, the body’s master antioxidant.
When these processes are disrupted, homocysteine levels can rise, leading to negative health effects.
Elevated homocysteine not only disrupts detoxification but also contributes to chronic diseases. High homocysteine levels, a condition called hyperhomocysteinemia, are harmful because they contribute to:
  • Oxidative Stress:
    Excess homocysteine generates free radicals, causing damage to cells, proteins, and DNA. Increased oxidative stress and inflammation from high homocysteine are major risk factors. High homocysteine levels impairs nitric oxide production, reducing blood vessel flexibility, and can damage the endothelial lining of blood vessels, and increase the risk of atherosclerosis, heart attacks, and strokes.
  • Chronic Inflammation:
    Homocysteine irritates blood vessels, triggering inflammation and promoting a wide variety of conditions, including but not limited to fibromyalgia, irritable bowel disease, and autoimmune conditions, such as diabetes.
  • Impaired Detoxification:
    High homocysteine levels hinder the production of glutathione, weakening the body’s ability to neutralize and eliminate toxins, heavy metals, and free radicals.
  • Neurotoxicity:
    Elevated homocysteine is linked to neurodegenerative and neurodevelopmental diseases, including Alzheimer’s, Parkinson’s, schizophrenia, ADHD, bipolar disorder, depression, autism, down syndrome, by causing damage to neurons and increasing oxidative stress in the brain.
  • Hormonal Imbalances: Poor methylation affects estrogen metabolism, potentially contributing to conditions like thyroid disorders, PCOS and estrogen dominance.
  • Cancer: DNA damage from unchecked oxidative stress and poor methylation can increase cancer risk, including colon cancer, and leukemia.
  • Bone Health: High homocysteine levels can impair collagen cross-linking, leading to weaker bones and a higher risk of fractures.
  • Pregnancy Complications: Elevated levels can increase the risk of preeclampsia, miscarriage, infertility, and neural tube defects.​

Homocysteine sits at the crossroads of detoxification and chronic disease. By optimizing its metabolism through targeted nutrition and lifestyle changes, functional medicine empowers individuals to restore balance, enhance detoxification, and reduce the risk of chronic illness.

There are several factors that disrupt the pathways regulating homocysteine, leading to its buildup:
1. Nutrient Deficiencies: Inadequate levels of B vitamins, particularly B12, B6, and folate, impair homocysteine metabolism. Low magnesium and zinc levels also affect enzyme activity in these pathways.
2. MTHFR Gene Mutations:
Genetic variations in the MTHFR gene reduce the conversion of folate into its active form (methylfolate), slowing homocysteine clearance.
3. Dietary Imbalances: Excessive methionine intake from high-protein diets without adequate B vitamins can increase homocysteine production. Diets lacking leafy greens, whole grains, and organ meats fail to provide essential cofactors for homocysteine metabolism.
4. Chronic Stress:
Stress depletes nutrients like B vitamins and magnesium, exacerbating homocysteine accumulation.
5. Toxins and Inflammation:
Toxins, heavy metals, and inflammation place additional stress on the methylation and detoxification pathways, reducing the body's ability to clear homocysteine.
6. Gut Dysbiosis:
Poor gut health can impair nutrient absorption, particularly B12 and folate, leading to higher homocysteine levels.

Solutions for elevated homocysteine

Addressing elevated homocysteine involves personalized strategies to optimize methylation, support detoxification, and improve nutrient status.

  • B Vitamins: Supplement with active forms of B12 (methylcobalamin), folate (methylfolate), and B6 (pyridoxal-5-phosphate). These vitamins act as cofactors in the pathways that metabolize homocysteine. 
    Foods rich in folate: Leafy greens, broccoli, asparagus, lentils, and avocados 
    Foods rich in vitamin B6: Poultry, fish, potatoes, and bananas. 
    ​Foods rich in vitamin B12: Grass-fed meats, eggs, wild-caught fish, dairy products​
  • Betaine (Trimethylglycine): Found in foods like spinach, beets, and whole grains, betaine helps convert homocysteine back into methionine.
  • Magnesium: Supports enzymatic activity in the methionine cycle.​
  • Zinc: Aids enzyme function in homocysteine metabolism.
  • Choline and Betaine: Found in eggs and beets, these nutrients provide additional methyl donors to lower homocysteine.
  • Limit excess methionine: Balance high-protein diets with ample B vitamins to offset homocysteine production.
  • Omega-3 Fatty Acids: Found in cod liver oil - can help reduce inflammation and improve cardiovascular health.
Lifestyle and Detoxification Support
  • Reduce Toxin Exposure: Minimize contact with heavy metals, processed foods, and chemicals.
  • Support Gut Health: Use probiotics and avoid inflammatory foods like refined sugar and gluten.
  • Manage Stress: Conditions like hypothyroidism, insulin resistance, and chronic stress deplete riboflavin stores. Practice mindfulness, meditation, or yoga to conserve methylation resources.
  • Exercise: Regular physical activity helps lower homocysteine by improving vascular health and detox pathways.
  • Avoid Smoking and Excessive Alcohol: Both can elevate homocysteine levels and increase oxidative stress.​

Homocysteine is not inherently harmful, but its elevation signals deeper imbalances in methylation and detoxification pathways. Addressing these through personalized, root-cause strategies can significantly enhance health and well-being.

Methylation vs. Telomerase: Unraveling the Secrets to Longevity

Aging is no longer seen as an unchangeable process but as a series of biological events influenced by our environment, lifestyle, and genetics. Two critical factors driving aging and longevity—are methylation and telomerase activity. Together, these powerful biological mechanisms control the stability of our genetic material and the way our bodies adapt to environmental stressors.  While they operate in different ways, they both are crucially interconnected and mutually influential in aging, disease prevention, cellular health, and longevity. A deeper understanding of these processes offers insights into how we might slow aging and extend healthspan.
​As mentioned, methylation is a biochemical process where a methyl group (CH3) is added to molecules, and in this case, DNA. This small modification has profound effects on gene expression, turning certain genes "on" or "off." As we age, DNA methylation patterns change, contributing to the deterioration of cellular function. Hypomethylation (too little methylation) can lead to genomic instability, while hypermethylation (too much methylation) may silence important protective genes. Both extremes accelerate aging and increase susceptibility to chronic diseases like cancer, cardiovascular disease, and neurodegeneration.

The epigenetic clock is a biological marker of aging that uses DNA methylation patterns to predict biological age. It differs from chronological age, reflecting the cumulative impact of lifestyle, environment, and genetics on aging processes.

Telomerase is an enzyme that maintains telomeres, the protective caps at the ends of chromosomes. Each time a cell divides, telomeres shorten, eventually leading to cellular aging or death when they become critically short. Telomerase counteracts this process by replenishing lost telomere segments.
Methylation and telomerase activity are two sides of the same coin when it comes to aging. While methylation governs the quality of cellular function and gene regulation, telomerase preserves the quantity of healthy cell divisions. Together, these mechanisms provide a roadmap to healthier aging.
​
By optimizing these processes through diet, lifestyle, and emerging therapies, we can not only slow the ticking of the epigenetic clock but also preserve the telomeric buffer that protects our genetic material. The future of longevity lies in harnessing the synergy between methylation and telomerase to unlock the full potential of cellular health.
  • Epigenetic Regulation: Determines which genes are expressed, influencing cellular function.
  • DNA Stability and Repair: Protects DNA from mutations and aids in repair.
  • Detoxification: Facilitates the removal of toxins and metabolic waste.
  • Inflammation Control: Regulates immune responses, reducing chronic inflammation.
How does Methylation Drive the Epigenetic Clock?
Certain regions of DNA undergo predictable methylation changes with age, known as "age-related methylation drift." The balance between proper and improper methylation determines the speed of the epigenetic clock.
what are the Implications of a Faster Epigenetic Clock?
  • Accelerated aging at the cellular level, resulting in increased risk of age-related diseases like Alzheimer's, diabetes, and osteoporosis.
How can you Slow the Epigenetic Clock with Methylation Optimization?
  • ​Diet: Nutrients like folate, B vitamins, and choline support methylation.
  • Lifestyle: Stress management, regular exercise, and sleep reduce oxidative stress that disrupts methylation.
  • Targeted Therapies: Emerging interventions like methyl donors or epigenetic reprogramming are being studied for their anti-aging potential.

  • Methylation-Supporting Nutrients: Folate, B2, B6, B12, choline, and methionine.
  • Antioxidants: Combat oxidative stress that accelerates telomere shortening and disrupts methylation. Include foods like berries, green tea, and dark leafy greens.
  • Exercise: Moderate physical activity has been shown to lengthen telomeres and improve methylation patterns.
  • Stress Management: Practices like meditation and yoga lower cortisol levels, reducing damage to both methylation processes and telomeres.
  • Sleep Optimization: Restorative sleep is crucial for DNA repair, methylation efficiency, and telomere maintenance.
  • Epigenetic Reprogramming: Researchers are exploring how to reset the epigenetic clock through methylation interventions.
  • Telomerase Activation: Experimental therapies aim to boost telomerase activity safely, without triggering cancer risks.

What are the implications of a slower epigenetic clock?
  • Extends Cellular Lifespan: Prevents premature cellular senescence (aging).
  • Supports Tissue Regeneration: Maintains the function of stem cells, essential for repairing and replacing damaged tissues.
  • Prevents Chromosomal Damage: Protects DNA from instability and mutations.
how does Methylation Regulate Telomerase Activity?
  • Methylation patterns influence the expression of the TERT gene, which encodes telomerase.
  • Hypomethylation in specific regions can lead to either excessive telomerase activity (linked to cancer) or inadequate activity (linked to premature aging).
How does telomerase Protect Methylation Integrity?
  • Shortened telomeres lead to cellular stress and senescence, which disrupts proper methylation patterns.
  • By maintaining telomere length, telomerase helps preserve optimal DNA methylation and prevent "epigenetic drift."
What is the Synergistic Impact of telomeres and methylation on Aging?
  • Methylation ensures the epigenetic environment remains stable, reducing oxidative damage to telomeres.
  • Telomerase, in turn, safeguards cells from reaching a state where methylation patterns deteriorate.

Riboflavin: ​ The Game-Changer for MTHFR Mutations and Methylation Issues

When it comes to understanding the MTHFR gene and its role in health, the focus has long been on folate metabolism and methylation. But new research has revealed an unexpected hero: riboflavin (vitamin B2). For those with MTHFR mutations, riboflavin could be the key to overcoming inflammation, detoxification challenges, and chronic health issues.

Here’s where riboflavin comes in. It turns out that riboflavin is essential for MTHFR enzyme function. It helps the enzyme bind effectively to folic acid, enabling the production of methylfolate even in people with common MTHFR mutations like C677T.

Recent studies have turned conventional wisdom on its head:
  • Researchers discovered that MTHFR mutations impair the enzyme’s ability to bind riboflavin, reducing its activity.
  • By increasing riboflavin concentrations, they were able to restore full enzyme function, even in the presence of genetic mutations.
  • In human trials, a daily dose of just 1.6 mg of riboflavin reduced homocysteine levels by 40%, highlighting its impact on methylation and detoxification.

At first glance, riboflavin deficiency seems rare because most people meet the Recommended Daily Allowance (RDA). However, the RDA is designed to prevent severe deficiency symptoms, not optimize the many chemical processes riboflavin supports. In fact, studies suggest that 75% of boys, 87% of girls, and 41% of adults have inadequate riboflavin levels.

Proper methylation, supported by riboflavin, is critical for detoxification. Without enough riboflavin:
  • Homocysteine builds up, causing inflammation and oxidative stress.
  • Detoxification slows down, leaving toxins and heavy metals to accumulate.
  • The body struggles to regulate hormones, neurotransmitters, and DNA repair, increasing the risk of chronic conditions like heart disease, neurodegeneration, and hormonal imbalances.
By ensuring optimal riboflavin levels, you can support methylation, reduce homocysteine, and promote effective detoxification.

1. Focus on Food First
The best sources of riboflavin come from nutrient-dense organ meats:
  • Grass-fed beef liver: Just 4 ounces twice a week provides a rich supply of riboflavin.
  • Beef heart and kidney: Excellent alternatives for variety and taste preferences.
  • Other Foods: Wild-caught salmon, seaweed, and eggs also contain riboflavin, though in lower amounts.
2. Supplement Strategically
If organ meats aren’t appealing, consider high-quality supplements like Perfect Supplements Multi-Organs, which includes freeze-dried liver, heart, pancreas, spleen, thymus and kidney. This provides the benefits of these foods without the taste or hassle.

3. Address Depleting Factors
  • Support thyroid health to prevent riboflavin loss.
  • Optimize magnesium levels, as it’s a cofactor in riboflavin-dependent reactions.
  • Manage stress through mindfulness, regular exercise, and restorative sleep.

While supplementing with methylfolate can bypass MTHFR dysfunction, it’s often addressing the symptom, not the root cause. Riboflavin works upstream, ensuring the MTHFR enzyme functions as it should, allowing your body to naturally produce the methylfolate it needs.

Riboflavin is the overlooked nutrient that could transform how we approach MTHFR mutations, methylation, and detoxification. By optimizing your riboflavin status through diet and supplementation, you can support your body’s ability to detoxify, regulate inflammation, and protect against chronic disease.
​
For those with MTHFR mutations—or anyone looking to improve methylation—riboflavin isn’t just a supporting player. It’s a star nutrient that deserves a place at the forefront of your health strategy.

Testing Methylation

To assess methylation pathways effectively, there are several specialized lab tests that provide insight into the body’s ability to methylate, as well as potential dysfunctions in the methylation cycle. The following are the most relevant tests for detecting issues in methylation pathways:

1. Methylation Profile by Doctors Data
  • This test directly evaluates methylation activity by measuring key metabolites in the methylation cycle. It provides a detailed overview of:
  • S-Adenosylmethionine (SAM): The primary methyl donor in the body.
  • S-Adenosylhomocysteine (SAH): A metabolite of SAM, and the ratio of SAM/SAH is crucial for assessing methylation efficiency.
  • Methionine: An essential amino acid involved in the methylation cycle.
  • Homocysteine: Elevated homocysteine levels may indicate impaired methylation and are a key marker for cardiovascular health.
  • Cystathionine: A byproduct of homocysteine breakdown, which can indicate how well the transsulfuration pathway is working.

These markers help evaluate the efficiency of the methylation cycle and detect whether a patient is undermethylating or overmethylating.

2. MTHFR Gene Mutation Test
  • This is a genetic test that identifies common mutations in the MTHFR gene (such as C677T and A1298C), which can impair the conversion of folate to its active form, 5-methyltetrahydrofolate (5-MTHF). A deficiency in active folate can significantly impact methylation pathways and homocysteine levels.
  • It’s important to look at MTHFR in combination with other genes involved in methylation to assess the overall efficiency of the pathway.

3. Organic Acids Test (OAT)
  • Organic acids testing can provide indirect clues about methylation efficiency through specific metabolites. Key markers related to methylation include:
  • Methylmalonic Acid (MMA): Elevated MMA can indicate a functional B12 deficiency, which is critical for the methylation of homocysteine to methionine.
  • Folate Metabolites: The OAT can show deficiencies in the folate cycle, which is essential for methylation.
  • Homovanillic Acid (HVA) and Vanilmandelic Acid (VMA): These neurotransmitter metabolites can be influenced by methylation activity.
4. Complete Blood Count (CBC) and Homocysteine
  • Homocysteine levels, which can be ordered as a standard lab test, are a well-recognized marker of methylation efficiency. Elevated homocysteine levels are often associated with impaired methylation and can reflect deficiencies in methyl donors like folate, B12, or B6.
  • The CBC may reveal certain findings, such as macrocytic anemia, which can indicate deficiencies in B12 or folate, both crucial for proper methylation.

5. NutrEval by Genova Diagnostics
  • The NutrEval FMV (First Morning Void) is a comprehensive test that provides a deep look into nutrient status, including markers for methylation. Key measurements include:
  • Methylation Pathway Markers: Assess levels of SAM, SAH, and homocysteine.
  • B-Vitamins: B6, B12, and folate status are directly tied to methylation efficiency.
  • Methylated Folate (5-MTHF): Measures active folate, the form necessary for proper methylation.
  • Tetrahydrobiopterin (BH4): A critical cofactor in the methylation cycle that helps convert phenylalanine into neurotransmitters like dopamine and serotonin.

6. SpectraCell Micronutrient Test
  • This test evaluates intracellular levels of micronutrients, including those crucial for methylation, like B12, B6, folate, choline, and methionine. Deficiencies in any of these nutrients can impair methylation processes.
​
7. Plasma Amino Acids Profile
  • An amino acids profile can help assess levels of key amino acids involved in the methylation cycle, such as:
  • Methionine: Essential for initiating the methylation cycle.
  • Cysteine: A byproduct of homocysteine breakdown that indicates how well homocysteine is being metabolized.
  • Glutathione: A critical antioxidant produced in the methylation cycle.

​Taking Action: The Integral Wellness Program​

For those seeking tangible solutions to enhance methylation and improve their overall well-being, the Integral Wellness Program offers a comprehensive approach to optimizing health and vitality. This flagship service provides personalized guidance and support in key areas of movement, nutrition, and lifestyle to directly enhance quality of life.
Online/In-Person Guidance
One of the standout features of the Integral Wellness Program is its flexibility, offering both online and in-person consultations tailored to individual preferences and needs. Whether you prefer the convenience of virtual sessions or the hands-on approach of in-person coaching, our team of experienced wellness professionals is dedicated to supporting you every step of the way.
Movement, Nutrition, and Lifestyle
The Integral Wellness Program takes a holistic approach to health, addressing modifiable factors and behaviors in three core areas:
  1. Movement: Through customized movement plans and exercise routines, participants are empowered to enhance physical fitness, flexibility, and overall mobility. Whether you're a seasoned athlete or new to fitness, our expert coaches will guide you towards achieving your movement goals safely and effectively.
  2. Nutrition: Central to the Integral Wellness Program is the emphasis on nutrient-dense foods and supplements to fuel and energize your body optimally. Our nutrition experts will work with you to develop personalized meal plans and dietary strategies tailored to your unique needs and preferences. By eliminating obesogen exposure and prioritizing wholesome, nourishing foods, you can support metabolic health and achieve sustainable weight management.
  3. Lifestyle: Beyond movement and nutrition, the Integral Wellness Program addresses lifestyle factors that contribute to overall well-being. From stress management techniques to sleep hygiene practices, our holistic approach encompasses all aspects of lifestyle optimization to promote balance, resilience, and vitality.

​Augmenting the Health Process
By participating in the Integral Wellness Program, you'll not only gain valuable knowledge and skills to navigate the challenges of modern living but also receive ongoing support and accountability to stay on track towards your health goals. Through targeted interventions aimed at eliminating obesogen exposure and promoting healthy behaviors, you can unlock your body's full potential and thrive in all aspects of life.
The Integral Wellness Program offers a transformative journey towards optimal health and vitality. By prioritizing movement, nutrition, and lifestyle modifications, participants can take proactive steps to combat the effects of obesogens and reclaim control over their well-being. With the guidance and support of our dedicated wellness professionals, you'll embark on a path of self-discovery, empowerment, and lasting transformation.

references

Hustad, Steinar, et al. “Riboflavin and Methylenetetrahydrofolate Reductase.” ​Nih.​Gov, Landes Bioscience, 2023, ​www.​ncbi.nlm.​nih.​gov/books/NBK6145/. 

García-Minguillán, Carlos J., et al. “Riboflavin Status Modifies the Effects of Methylenetetrahydrofolate Reductase (MTHFR) and Methionine Synthase Reductase (MTRR) Polymorphisms on Homocysteine.” Genes & Nutrition, vol. 9, no. 6, 17 Oct. 2014, https://doi.org/10.1007/s12263-014-0435-1. 

​Martinez-Morata, Irene, et al. “Influence of Folic Acid and Vitamin B12 Supplementation on Arsenic Methylation: A Double-Blinded, Placebo-Controlled Trial in Bangladeshi Children.” Environment International, vol. 187, 1 May 2024, p. 108715, pubmed.ncbi.nlm.nih.gov/38728816/, https://doi.org/10.1016/j.envint.2024.108715. 

​Qureshi, G., et al. “Is the Deficiency of Vitamin B12 Related to Oxidative Stress and Neurotoxicity in Parkinsons Patients?” CNS & Neurological Disorders - Drug Targets, vol. 7, no. 1, 1 Feb. 2008, pp. 20–27, https://doi.org/10.2174/187152708783885101.