In Blog, Diet, Exercise, Health, Health Professionals, Lifestyle, multiple sclerosis, Research

Do you need activated B vitamins or MTHFR Complete?

Fatigue is one of top reasons people with multiple sclerosis (MS) leave employment. Cognitive decline is the next most common reason. I had years of relentlessly worsening fatigue. My neurologist gave me Provigil to treat the fatigue, which provided a slight improvement. I was still exhausted by 10 in the morning, but I definitely was more exhausted without it.

When I found myself in a tilt/recline wheelchair, I asked myself if I was doing everything I could to support my body and health. That was when I began reading the basic science to look for things that might help.

I would eventually decide that mitochondrial strain was the cause of disability in the setting of secondary and primary progressive MS. So I created a cocktail of supplements to support my mitochondria, which included lipoic acid, carnitine, coenzyme Q, and B vitamins. The cocktail did not recover my energy, strength, or stamina. After six months, I stopped them.

After 36 hours, I couldn’t get out of bed and go to work. Three days after I stopped taking my cocktail of supplements, Jackie suggested I start taking it again. The next morning I was back to my usual level of energy and was able to go back to work.

I was super excited. Two weeks later, I retested the experiment, stopping the supplements again. After 36 hours, I could not get out of bed. Again, I resumed my supplements 3 days after stopping them, and was able to go back to work the following morning. The success of this second experiment inspired me. I read more research papers and continued tinkering with my supplement cocktail to support my mitochondria.

That was 2008. In the intervening 14 years, I have learned a lot more about B vitamin pathways, genetic variants, and homocysteine metabolism.

In my clinical practice I ask my patients about their family history. Do they have relatives with macular degeneration, a leading cause of blindness? Do they have a family history of anxiety, depression, bipolar, or schizophrenia? Do they have a family history of memory problems, dementia, Parkinson’s, seizures, neuropathies, or restless legs? Do they have a family history of cardiovascular disease? Do they have a personal history of any of those same issues?

I have multiple aunts with macular degeneration and multiple uncles with early heart disease. I have family members with schizophrenia, bipolar, seizures, restless legs, and neuropathies. All this means I likely have multiple genetic variants that influence how my cells manage methylation pathways.

Methylation pathways are the B vitamin pathways for folate (vitamin B9), cobalamin (vitamin B12), pyridoxine (vitamin B6), riboflavin (B2), and thiamin (vitamin B1). I have checked my genetics and those of my family members and confirmed we have multiple genetic variants of the methylation pathways involving one or more of the following pathways: folate (vitamin B9), cobalamin (vitamin B12), pyridoxine (vitamin B6), and riboflavin (vitamin B2). These genetic variants are single nucleotide pathways where a single nucleotide is swapped with a different nucleotide (called SNPs) in the DNA. This change can produce good or bad outcomes. Sometimes SNPs make changes that are fatal. Sometimes SNPs improve the vitality of the organism and are beneficial. In other cases, SNPs create inefficiencies in our chemistry and increase the probability of chronic symptoms.

I’ve also checked my homocysteine, a marker for the efficiency of B vitamin utilization by our cells. Mine is elevated, which further indicates I do not have efficient methylation. My enzymes have a difficult time activating the B vitamins in the foods I eat into the active forms that methylate the B vitamins and cycle methionine to homocysteine. This explains why my homocysteine was moderately to severely elevated, placing me at risk of cognitive decline and early heart disease. To address these problems, I added activated B vitamins to my supplement cocktail.

The activated Bs were helpful, but I needed an even higher dose of the activated folate and cobalamin. I kept checking my homocysteine every 6 months until it was optimal, 5 to 7.5 mmol/L. (The conventional cutoff for elevated homocysteine is 15 mmol/L, though some labs place the upper level at 10 mmol/L.) I did not want to overcorrect, as that can be a problem too. Elevated homocysteine is toxic to brain cells3,4 and retinal cells5,6 and is a marker of insufficient B vitamin levels, which can contribute to the development of cardiovascular, neurological, and psychiatric disorders.4,7

In my clinical practice, I check my patients’ basic primary care labs (complete blood count, kidney function, liver function, and metabolic health). I also monitor folate, vitamin B12, homocysteine, and methylmalonic acid levels to understand their B vitamin status. I review the folate, B12, methylmalonic, and homocysteine levels and begin replacing the missing B vitamins.

A mild elevation of homocysteine is 7.6 mmol/L to 15 mmol/L, moderate elevation is 16 to 30 mmol/L, severe elevation is 31 to 60 mmol/L, and very severe elevation is > 60 mmol/ L. People with mild homocysteine elevation are often able to correct their homocysteine with 1-2 daily capsules of Activated B vitamins. People with moderate elevations are sometimes able to correct their homocysteine with 2 capsules of Activated Bs each day. People with severe and very severe elevations of homocysteine are more likely to need higher doses of activated folate, activated cobalamin, and other activated B vitamins as well as closer follow up of their homocysteine. They are more likely to benefit from MTHFR Complete.

I test my patients’ homocysteine every 3 months and make adjustments to supplements based on the results, until the patient reaches an optimal homocysteine level between 5-7.5 mmol/L. I do not want people to go below 5. If it falls below 5, I lower the B vitamin dose. You can ask your medical team to monitor your B vitamins and homocysteine. If you are unable to obtain these labs through your medical team, you may be able to obtain them through Your Lab Work. I also follow the homocysteine every 3 months to ensure my patients’

The foods that we eat have a variety of vitamins and minerals that are critical to healthy cells and bodies. Most commercially available vitamin supplements are made with synthetic vitamins, which share many of the properties of naturally occurring vitamins but are not quite as effective. For example, folic acid is a synthetic B vitamin that is used to fortify white flours to reduce the risk of neural tube defects but has been associated with increased risk of cancer (likely because it can suppress some of the activity of natural form of folate).1,2

I recommend that my patients avoid synthetic vitamin preparations and instead take a B vitamin complex that utilizes the activated forms of the vitamins, which bypass problem SNPs. The activated form of vitamin B12 (methylcobalamin), B9 (methylfolate), and B6 (pyridoxal-5-phosphate) reduces homocysteine to more optimal levels. I also recommend activated vitamin B1 (benfotiamine), which supports brain,8 retinal9,10 and heart health11, and activated vitamin B2 (riboflavin 5 phosphate) for those with migraine and chronic headache.12,13 Other activated B vitamins that may be useful include niacin and niacinamide, which have been helpful in migraine and chronic headache14; choline, an important nutrient for cognition and mental health15,16; and biotin, which is involved the production of myelin.17

All B vitamins work together synergistically to support the physiology of our cells.18,19 Thus I urge my patients to take a B complex to reduce the risk of insufficiency of these key vitamins and the symptoms that may cause or worsen. Activated Bs contain the entire spectrum of B vitamins to support cardiovascular, neurological, and retinal health, including vitamins B2, B6, and B12; benfotiamine, a fat soluble, more physiologically active form of thiamine; and folate as Quatrefolic®, which is proven to have greater stability, solubility, and bioavailability than calcium salt forms of 5-MTHF.

Activated Bs are an excellent way to ensure that you do not have an insufficiency of these key vitamins, even if you have an SNP that increases your vulnerability to retinal, cardiovascular, neurological, or psychiatric issues because of mild to moderate elevation of homocysteine. If you have severe or very severe elevation of homocysteine, you will likely benefit from higher doses of methylfolate, methylcobalamin, pyridoxal-5-phosphate, riboflavin 5’-phosphate, and trimethylglycine (betaine), which are found in MTHFR Complete.

My fatigue was resolved years ago, and I have been successful with helping thousands of people resolve their fatigue using diet, lifestyle, and targeted supplements. I take a careful history, asking about family history, personal history, and request relevant labs. Then I provide specific recommendations to address problems with B vitamin metabolism that contribute to fatigue and increased risk of neurodegeneration, early heart disease, and macular degeneration.

Learn more about The Wahls Protocol® Supplement Collection:

Shop MTHFR Complete

MTHFR Complete is a comprehensive formula designed to support optimal methylation and help maintain healthy homocysteine levels already within normal range.

It features five key nutrients that are involved in homocysteine metabolism: folate as calcium folinate and Quatrefolic® for increased bioactivity trimethylglycine and vitamins B12, B6, and B2.

These five nutrients, provided in activated forms, support enhanced methylation and overall cardiovascular health.*

MTHFR Complete provides 5-methyltetrahydrofolate (active folate), pyridoxal 5’-phosphate (active B6), methylcobalamin (active B12), riboflavin 5’-phosphate (active vitamin B2), and anhydrous betaine (trimethylglycine).

These five nutrients promote the process of methylation. Methylation is the addition of a methyl group (a carbon atom with three hydrogen atoms attached) to proteins, enzymes, chemicals, DNA, or amino acids like homocysteine.

Shop Activated B’s

Activated B’s contains the entire spectrum of B vitamins to support adrenal, neurological, and stress-related functions.

It features activated forms of vitamins B2, B6, and B12 benfotiamine, a fat-soluble, more physiologically active form of thiamin and folate as Quatrefolic®, which is proven to have greater stability, solubility, and bioavailability over calcium salt forms of 5-MTHF.

  • Supports Carbohydrate Metabolism*
  • Supports Healthy Nervous System/Adrenal/Immune Function*
  • Supports Cardiovascular Health*
  • Supports Healthy Mental Function and Mood



  1. Wien TN, Pike E, Wisloff T, Staff A, Smeland S, Klemp M. Cancer risk with folic acid supplements: a systematic review and meta-analysis. BMJ Open. 2012;2(1):e000653.
  2. Baggott JE, Oster RA, Tamura T. Meta-analysis of cancer risk in folic acid supplementation trials. Cancer Epidemiol. 2012;36(1):78-81.
  3. Ansari R, Mahta A, Mallack E, Luo JJ. Hyperhomocysteinemia and neurologic disorders: a review. J Clin Neurol. 2014;10(4):281-288.
  4. Obeid R, McCaddon A, Herrmann W. The role of hyperhomocysteinemia and B-vitamin deficiency in neurological and psychiatric diseases. Clin Chem Lab Med. 2007;45(12):1590-1606.
  5. Ola MS, Nawaz MI, Khan HA, Alhomida AS. Neurodegeneration and neuroprotection in diabetic retinopathy. Int J Mol Sci. 2013;14(2):2559-2572.
  6. Elsherbiny NM, Sharma I, Kira D, et al. Homocysteine Induces Inflammation in Retina and Brain. Biomolecules. 2020;10(3).
  7. Dardiotis E, Arseniou S, Sokratous M, et al. Vitamin B12, folate, and homocysteine levels and multiple sclerosis: A meta-analysis. Mult Scler Relat Disord. 2017;17:190-197.
  8. Dhir S, Tarasenko M, Napoli E, Giulivi C. Neurological, Psychiatric, and Biochemical Aspects of Thiamine Deficiency in Children and Adults. Front Psychiatry. 2019;10:207.
  9. Chakrabarti R, Chen M, Liu W, Chen S. Preventive effects of benfotiamine in chronic diabetic complications. J Diabetes Investig. 2011;2(2):123-131.
  10. Cinici E, Mammadov R, Findik H, et al. The Protective Effect of Thiamine Pryophosphate Against Sugar-Induced Retinal Neovascularisation in Rats. Int J Vitam Nutr Res. 2018;88(3-4):137-143.
  11. Wong EKC, Lee JY, Chow J, et al. High-Dose Thiamine Supplementation in Older Patients With Heart Failure: A Pilot Randomized Controlled Crossover Trial (THIAMINE-HF). CJC Open. 2022;4(6):532-539.
  12. Grech O, Mollan SP, Wakerley BR, Fulton D, Lavery GG, Sinclair AJ. The Role of Metabolism in Migraine Pathophysiology and Susceptibility. Life (Basel). 2021;11(5).
  13. Lisicki M, Schoenen J. Metabolic treatments of migraine. Expert Rev Neurother. 2020;20(3):295-302.
  14. Fila M, Chojnacki C, Chojnacki J, Blasiak J. Nutrients to Improve Mitochondrial Function to Reduce Brain Energy Deficit and Oxidative Stress in Migraine. Nutrients. 2021;13(12).
  15. Freedman R, Hunter SK, Law AJ, Clark AM, Roberts A, Hoffman MC. Choline, folic acid, Vitamin D, and fetal brain development in the psychosis spectrum. Schizophr Res. 2021.
  16. Gonzalez HF, Visentin S. Micronutrients and neurodevelopment: An update. Arch Argent Pediatr. 2016;114(6):570-575.
  17. Sedel F, Papeix C, Bellanger A, et al. High doses of biotin in chronic progressive multiple sclerosis: a pilot study. Mult Scler Relat Disord. 2015;4(2):159-169.
  18. Borges-Vieira JG, Cardoso CKS. Efficacy of B-vitamins and vitamin D therapy in improving depressive and anxiety disorders: a systematic review of randomized controlled trials. Nutr Neurosci. 2022:1-21.
  19. Kennedy DO. B Vitamins and the Brain: Mechanisms, Dose and Efficacy–A Review. Nutrients. 2016;8(2):68.
Recent Posts

Start typing and press Enter to search