Vitamin B12 and MND/ALS: Hope, science, and the impact of our genes.

When the first symptoms of motor neurone disease (MND) appear — a weak hand, a twitching muscle, a stumble that feels “off” — life can suddenly divide into before and after.

MND can feel merciless, but science continues to search for signs of hope. One such sign comes from a nutrient most people associate with energy and tiredness: Vitamin B12.

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An old vitamin with a new story

Vitamin B12 is not just another supplement. It acts like the body’s electrician, wiring and protecting the nervous system. Without it, the insulation around nerves (called myelin) begins to break down. Electrical signals then misfire, disrupting communication between the brain and body (Surendran et al., 2018).

Japanese researchers have explored an intriguing question: could large doses of Vitamin B12 protect motor neurones in MND? Their clinical trial tested ultra-high-dose methylcobalamin (50 mg injected twice weekly) in people newly diagnosed with amyotrophic lateral sclerosis (ALS), the most common form of MND. Participants who began treatment within one year of symptom onset experienced a 43% slower rate of functional decline compared with placebo (Oki et al., 2022).

In 2024, Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) approved methylcobalamin for “slowing the progression of functional impairment in patients with ALS” (PMDA, 2024).

Although the official indication did not specify early-stage ALS, improvement was seen in participants treated within one year of symptom onset. This highlights that earlier intervention appears to provide the greatest benefit.

It represents a remarkable shift: a vitamin once used primarily for anaemia now showing pharmacological promise in a neurodegenerative condition.

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How could vitamin B12 protect motor neurones?

Think of each motor neurone as a long electrical cable running from your spine to your muscles. It requires insulation, continuous maintenance, and a reliable energy source to function effectively.

Vitamin B12 supports all three of these processes. It helps to produce and repair myelin, fuels mitochondrial energy, and recycles homocysteine — a by-product that can damage cells if it accumulates (Surendran et al., 2018).

Laboratory studies show that high-dose B12 can slow neuronal damage and improve survival (Kaji et al., 2019). The JETALS human trial confirmed that when used pharmacologically, rather than simply as a nutrient, B12 can influence the pace of disease (Oki et al., 2022).

However, “slower decline” does not mean reversal. High-dose B12 may help protect remaining neurones rather than restore those already lost.

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The genetic puzzle behind B12

Not everyone processes vitamin B12 in the same way. The body’s ability to absorb and activate it depends partly on genetic SNPs — the tiny differences in our DNA that make each of us unique.

One example is the FUT2 gene, which influences how sugars coat the gut lining and support beneficial bacteria. Certain variants, known as non-secretors, are linked to lower blood B12 levels (Hazra et al., 2008), as though some of the “docking stations” for absorption are missing.

Another gene, TCN2, produces the protein that transports B12 through the bloodstream. A common variation changes its shape slightly, meaning less B12 reaches cells even when blood levels appear normal (Miller et al., 2009).

Other genes, including MTR and MTRR, act like recyclers, keeping B12 active in the methylation cycle and preventing homocysteine from rising (Surendran et al., 2018).

When these genes function less efficiently, the body’s demand for B12 increases. Although research has not yet confirmed whether these variants predict who will respond best to high-dose B12, they help explain why the same nutrient can behave differently in different people.

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When chemistry gets complicated: The mercury question

Some people worry that methylcobalamin — one form of vitamin B12 — might interact with mercury in the body and increase its toxicity. The concern makes sense: in nature, certain bacteria can convert mercury into methylmercury, a more harmful form that builds up in some fish (Cossa et al., 2022).

However, this process only occurs in bacteria, not humans. Those bacteria possess two genes, hgcA and hgcB, which allow them to add a methyl group to mercury (Parks et al., 2013). Human cells do not have these genes, so this transformation cannot occur in our bodies (Podar et al., 2015; Ruggiero et al., 2021).

In people, mercury is detoxified through a completely different process. The body binds it to glutathione — a natural antioxidant — and excretes it through the liver and kidneys (Clarkson & Magos, 2006; Cossa et al., 2022).

Even though methylcobalamin carries a methyl group, it cannot transfer it to mercury. Think of it as a key designed for a different lock — mercury simply is not that lock.

For people with higher mercury exposure, such as those who eat large predatory fish or have older dental fillings, some clinicians may prefer to use hydroxocobalamin, a non-methylated form of B12 that the body activates as needed (Podar et al., 2015). This is a precautionary choice rather than a sign that methyl-B12 is unsafe.

The evidence shows that methylcobalamin does not make mercury more toxic. Understanding the real chemistry helps replace fear with confidence.

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Keeping perspective

It can be tempting to see vitamin B12 as the missing piece, but science teaches humility.

The strongest evidence currently applies to early-stage ALS, where high-dose injections appear most effective (Oki et al., 2022). Beyond that, research continues to evolve. Genetic studies (Hazra et al., 2008; Miller et al., 2009) and findings on detoxification pathways add depth, though not certainty.

Progress in medicine does not always come from new drugs; sometimes it comes from seeing an old molecule in a new light. Vitamin B12 is not a miracle cure, but it reminds us that the body holds extraordinary capacity for repair when given the right support.

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Where You Nutrition Clinic fits

At You Nutrition Clinic, our practitioner Kerry combines nutrigenomics data, functional health markers, and the latest nutritional science to build a personalised understanding of each client’s unique biology - including B12 metabolism.

For someone living with MND/ALS, this may include exploring how genes influence B12 pathways, how diet affects inflammation and detoxification, and how subtle imbalances can be supported through nutrition and lifestyle.

If you would like to explore your own B12 pathways and other genetic profile, contact Kerry at You Nutrition Clinic for a personalised nutrigenomic consultation.

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💬  Stay Connected

If you’d like to learn more about the clinic or connect with our practitioners, visit You Nutrition Clinic — where education, science, and personalised nutrition come together.

Your biology tells a story. We help you understand it.

🧩  Connect with us

For research highlights, scientific insights, and the latest updates in nutritional neuroscience, follow us on Instagram:

👉 @nutritionandthebrain

Stay curious. Stay hopeful. Support your brain. 🧠

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References

Clarkson, T. W., & Magos, L. (2006). The toxicology of mercury and its chemical compounds. Critical Reviews in Toxicology, 36(8), 609–662. https://doi.org/10.1080/10408440600845619

Cossa, D., Heimbürger-Boavida, L. E., Liss, P. S., Mason, R. P., & Sonke, J. E. (2022). Mercury biogeochemical cycling in the ocean and policy implications. Nature Reviews Earth & Environment, 3(1), 42–58. https://doi.org/10.1038/s43017-021-00228-5

Hazra, A., Kraft, P., Selhub, J., Giovannucci, E. L., Thomas, G., Hoover, R. N., Chanock, S. J., & Hunter, D. J. (2008). Common variants of FUT2 are associated with plasma vitamin B12 levels. Nature Genetics, 40(10), 1160–1162. https://doi.org/10.1038/ng.210

Japan Pharmaceuticals and Medical Devices Agency (PMDA). (2024). Review report: Methylcobalamin injection for amyotrophic lateral sclerosis (ALS). Tokyo, Japan.

Kaji, R., Imai, T., Iwasaki, Y., et al. (2019). Ultra-high-dose methylcobalamin in amyotrophic lateral sclerosis: A long-term outcome study. Journal of Neurology, Neurosurgery & Psychiatry, 90(4), 451–457. https://doi.org/10.1136/jnnp-2018-318402

Miller, J. W., Ramos, M. I., Garrod, M. G., Flynn, M. A., Green, R., & Allen, L. H. (2009). Transcobalamin C776G genotype modifies the association between vitamin B12 and homocysteine in older adults. The Journal of Nutrition, 139(10), 1937–1942. https://doi.org/10.3945/jn.109.111922

Oki, R., Izumi, Y., Fujita, K., et al. (2022). Efficacy and safety of ultra-high-dose methylcobalamin in early-stage amyotrophic lateral sclerosis: A randomized clinical trial. JAMA Neurology, 79(6), 562–571. https://doi.org/10.1001/jamaneurol.2022.0901

Parks, J. M., Johs, A., Podar, M., Bridou, R., Hurt, R. A., Smith, S. D., Tomanicek, S. J., Qian, Y., Brown, S. D., Brandt, C. C., & Liang, L. (2013). The genetic basis for bacterial mercury methylation. Science, 339(6125), 1332–1335. https://doi.org/10.1126/science.1230667

Podar, M., Gilmour, C. C., Brandt, C. C., Smit, E., Johs, A., Hurt, R. A., Brown, S. D., & Parks, J. M. (2015). Global prevalence and distribution of genes and microorganisms involved in mercury methylation. Science Advances, 1(9), e1500675. https://doi.org/10.1126/sciadv.1500675

Ruggiero, L., Goni, F., & Arnaldi, P. (2021). Methylmercury exposure and detoxification in humans: Mechanisms, genetics, and clinical implications. Toxicology Letters, 348, 35–48. https://doi.org/10.1016/j.toxlet.2021.05.008

Surendran, S., Adaikalakoteswari, A., Saravanan, P., & Shenoy, A. (2018). An update on vitamin B12-related gene polymorphisms and B12 status. Genes & Nutrition, 13(2). https://doi.org/10.1186/s12263-018-0591-9

Inclusion body myositis (IBM) vs ALS: Why subtle differences matter

When two shadows overlap

IBM and ALS can appear similar in their earliest stages, and this confusion is not rare. In one biopsy-confirmed clinical series, around 13 percent of patients later proven to have IBM were initially misdiagnosed as ALS or another motor neuron disorder (Dabby et al., 2001). Their electromyography (EMG) results showed nerve-like irritation — fibrillations, fasciculations, and motor-unit remodelling — yet, none went on to develop the hallmark upper-motor-neuron signs of ALS, such as spasticity or a positive Babinski reflex (Dabby et al., 2001).

In other words, IBM can look like ALS in the lab long before it tells its true story in the body. The muscles weaken, but without the dramatic acceleration or rigid reflexes that characterise ALS. For many patients, time, along with careful observation and sometimes a muscle biopsy, becomes the ultimate diagnostic test (Je et al., 2025). For those affected, that slower rhythm brings both relief and uncertainty: IBM is rarely fatal, but it’s stubborn, chronic, and life-altering.

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The immune system’s misfire

Under a microscope, IBM looks like a battle fought in slow motion. Immune cells called CD8⁺ T lymphocytes infiltrate muscle fibres that look perfectly normal, as if mistaking friend for foe (Allameen et al., 2025). These cells often express KLRG1, a marker of senescence (immune ageing), meaning they’ve lost their ability to switch off. Like overzealous soldiers, they keep firing long after the danger has passed, releasing toxic molecules that erode healthy muscle over time (Allameen et al., 2025). This creates a smouldering inflammation - not a blaze, but a steady, low-grade burn that damages tissue little by little.

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Inside the muscle: stress, repair, and decline

In 2024, researchers used single-nucleus RNA sequencing and spatial transcriptomics to map IBM muscle at unprecedented depth (Wischnewski et al., 2024). They found that fast-twitch fibres (the ones that help us grip, climb, and move with speed) are under the most strain. These fibres show stress-response genes (GADD45A) and signs of protein accumulation via the p62 pathway, sitting directly beside clusters of immune cells (Wischnewski et al., 2024).

It’s a bit like a neighbourhood where alarms never stop ringing, the constant immune “noise” keeps muscles from resting or repairing. Other molecular findings include increased ACHE gene activity, vital for nerve-muscle communication. When disrupted, it can mimic “functional denervation”, muscles behave as though disconnected from nerves, even when nerves are still present (Wischnewski et al., 2024).

Inside each fibre, mitochondria struggle, misfolded proteins pile up, and the cell’s recycling systems (autophagy and proteasomes) are overwhelmed. As damage builds, the immune system ramps up again, a loop of injury and repair that never quite resolves.

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Lifestyle & nutritional strategies: What the evidence says

Even though no medication has yet proven curative, research suggests that lifestyle interventions — particularly nutrition, exercise, and rehabilitation — can influence function and quality of life.

The Ketogenic Diet: A Case That Sparked Interest

One of the most striking reports came from a 2020 case study of a 52-year-old woman with IBM who adopted a modified ketogenic diet (~60 % fat, 30 % protein, 5 % carbohydrate) for 12 months (Phillips et al., 2020). Before the diet, she experienced frequent falls, difficulty swallowing, pain, and depression. After a year, she could walk unaided, her swallowing and mood improved, and she reported no further falls. Blood markers of muscle damage dropped by 42 %, and MRI scans showed reduced inflammation and slower muscle loss (Phillips et al., 2020). Researchers propose that the ketogenic state may enhance mitochondrial efficiency, reduce inflammation, and stimulate autophagy, essentially giving the cell’s repair crews more time and fuel to work (Phillips et al., 2020). Still, this was one case, not a clinical trial, so the findings are hypothesis-generating, not conclusive. Such a diet should only be explored under expert-supervision.

Exercise and rehabilitation

Exercise remains the most consistently supported non-drug therapy. A 12-week aerobic and resistance program improved strength and aerobic capacity without worsening inflammation (Johnson et al., 2009). Low-load blood-flow-restriction training boosted strength and slowed decline (Jørgensen et al., 2018; Jørgensen et al., 2022), and inpatient rehabilitation for more than an hour daily led to better mobility outcomes (Tani et al., 2023).

High-intensity resistance programs in broader inflammatory myopathy groups, including IBM participants, improved muscle function and mood (Jensen et al., 2024). The message is clear: safe, structured movement helps muscles do more with what they have.

Swallowing & nutritional support

Up to 80 % of people with IBM experience swallowing difficulties (Mohannak et al., 2019). Early referral to speech-language therapy, texture-modified diets, and nutritional monitoring can prevent weight loss and aspiration (Esteban et al., 2021; Ambrocio et al., 2024).

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How You Nutrition Clinic walks beside you

At You Nutrition Clinic, we combine compassion with scientific clarity. Rather than focusing on what we don't know, we focus on what we do know. There is a heightened immune overreaction at play (often considered to be autoimmune), that can be calmed using various nutrients via diet and supplementation. There is muscle degradation that can be supported. And we can also optimise mitochondrial health, reduce oxidative stress and support autophagy.

IBM isn’t a storm that destroys overnight; it’s a tide that shifts slowly. And while we can’t yet stop it, we can learn to navigate it guided by science, compassion, and the quiet determination that defines every person living with it.

• Functional biomarker testing: We assess mitochondrial health, oxidative stress, and immune activation to map your internal landscape.

• Personalised nutrition: Diets are tailored to your biochemistry, supporting energy metabolism, immune balance, and cellular resilience.

• Collaborative care: We work collaboratively with your specialist team of neurologists, physiotherapists, and speech specialists.

• Adaptive strategy: Progress is tracked, reviewed, and refined as your needs evolve.

• Transparency: We share what’s proven, what’s promising, and what’s still being studied. Because honesty builds trust.

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💬  Stay connected

If you’d like to explore metabolic, immune, or nutritional strategies anchored in science, you can contact You Nutrition Clinic to speak with one of our practitioners about long-term brain and nervous system health.

To learn more, reach out to You Nutrition Clinic  for evidence-informed support.

🧩 Connect with us

For research updates, practical tips, and ongoing inspiration, follow us on Instagram:

👉 @nutritionandthebrain

Stay curious. Stay hopeful. Support your brain. 🧠

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References

Allameen, N. A., Salam, S., Reddy, V., & Machado, P. M. (2025). Inclusion body myositis and immunosenescence: Current evidence and future perspectives. Rheumatology (Oxford), 64(3), 952–961. https://doi.org/10.1093/rheumatology/keae614

Ambrocio, K. R., Aggarwal, R., Lacomis, D., & Zhang, X. (2024). Features of swallowing function in sporadic inclusion body myositis: Preliminary evidence using well-tested assessment frameworks. American Journal of Speech-Language Pathology, 33(6), 2793–2804. https://doi.org/10.1044/2024_AJSLP-24-00061

Dabby, R., Lange, D. J., Trojaborg, W., Hays, A. P., Lovelace, R. E., Brannagan, T. H., & Rowland, L. P. (2001). Inclusion body myositis mimicking motor neuron disease. Archives of Neurology, 58(8), 1253–1256. https://doi.org/10.1001/archneur.58.8.1253

Je, Y., Park, Y.-E., & Shin, Y. B. (2025). Differentiating inclusion body myositis from amyotrophic lateral sclerosis based on the features of dysphagia: Insights from a patient with rapidly progressive dysphagia. Journal of Clinical Neurology, 21(1), 83–85. https://doi.org/10.3988/jcn.2024.0134

Johnson, L. G., Collier, K. E., Edwards, D. J., Philippe, D. L., Eastwood, P. R., Walters, S. E., Thickbroom, G. W., & Mastaglia, F. L. (2009). Improvement in aerobic capacity after an exercise program in sporadic inclusion body myositis. Journal of Clinical Neuromuscular

Jørgensen, A. N., Aagaard, P., Frandsen, U., Boyle, E., & Diederichsen, L. P. (2018). Blood-flow restricted resistance training in patients with sporadic inclusion body myositis: A randomized controlled trial. Scandinavian Journal of Rheumatology, 47(5), 400–409. https://doi.org/10.1080/03009742.2017.1423109

Jørgensen, A. N., Jensen, K. Y., Nielsen, J. L., Frandsen, U., Hvid, L. G., Bjørnshauge, M., Diederichsen, L. P., & Aagaard, P. (2021). Effects of blood-flow restricted resistance training on mechanical muscle function and thigh lean mass in sIBM patients. Scandinavian Journal of Medicine & Science in Sports, 32(9), 1548–1558. https://doi.org/10.1111/sms.14079

Machado, P. M., McDermott, M. P., Blaettler, T., Sundgreen, C., Amato, A. A., Ciafaloni, E., … Dimachkie, M. M. (2023). Efficacy and safety of pharmacological treatments in inclusion body myositis: A systematic review. RMD Open, 11(1), e005176. https://doi.org/10.1136/rmdopen-2024-005176

Phillips, M. C. L., Murtagh, D. K. J., Ziad, F., Johnston, S. E., & Moon, B. G. (2020). Impact of a ketogenic diet on sporadic inclusion body myositis: A case study. Frontiers in Neurology, 11, 582402. https://doi.org/10.3389/fneur.2020.582402

Tani, T., Hoshino, T., Mori, T., & Sakai, Y. (2023). Increasing daily duration of rehabilitation for inpatients with severe conditions: Effect on activities of daily living. Journal of Rehabilitation Medicine, 55, jrm00326. https://doi.org/10.2340/jrm.v55.5289

Wischnewski, S., Thäwel, T., Ikenaga, C., Kocharyan, A., Lerma-Martin, C., Zulji, A., … Stenzel, W. (2024). Cell-type mapping of inflammatory muscle diseases by single-nucleus RNA sequencing and spatial transcriptomics: Identification of type II fiber stress signatures in IBM. Nature Aging, 4(6), 558–573. https://doi.org/10.1038/s43587-024-00645-9

p53: The guardian protein that may hold clues to ALS

In every cell of the body lives a small but powerful guardian called p53, a protein that constantly checks our DNA for damage.

When it finds a problem, p53 has a choice to make:

• Try to repair the damage, or

• If the damage is too severe, tell the cell to self-destruct before it causes harm.

In healthy tissue, this process keeps us safe. But in certain diseases, that same protective system can become overactive, and that may be what happens in Amyotrophic Lateral Sclerosis (ALS).

Recent research has begun to uncover how p53, once considered purely protective, may actually contribute to the loss of motor neurons that defines ALS.

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The Basics: What Is p53 and Why Does It Matter?

p53 acts as a cellular quality-control system. Often called “the guardian of the genome,” it helps cells survive short-term stress and prevents them from turning cancerous.

When damage or stress occurs, p53 coordinates a rapid response, pausing cell growth, boosting repair enzymes, or, in more serious cases, initiating apoptosis, the cell’s built-in self-destruct program.

In the brain and spinal cord, neurons rely on p53 to respond to stress signals. Normally, once the danger passes, p53 quietens down again. But in ALS, evidence suggests this balance breaks down.

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What the research shows

Elevated p53 in ALS

Early post-mortem studies found unusually high levels of p53 in the spinal cords of people with ALS. It wasn’t just sitting idle, it was active, switching on genes that trigger cell death (Martin et al., 2000).

Genetic and cellular evidence

Recent large-scale genetic studies show that p53 signalling is one of the most upregulated pathways in ALS motor neurons — particularly in people with C9orf72 gene mutations, but also in other ALS subtypes (Ziff et al., 2023).

The connection with TDP-43

Almost all people with ALS have clumps of a protein called TDP-43 inside their neurons. Laboratory studies show that when TDP-43 builds up abnormally, it can activate p53, leading to neuronal death (Vogt et al., 2018).

What happens when p53 is turned down?

In experimental models, reducing p53 activity protected neurons from degeneration. When researchers silenced or deleted the p53 gene, motor neurons survived longer and symptoms progressed more slowly (Maor-Nof et al., 2021).

Together, these findings suggest that while p53 begins as a guardian, chronic stress in ALS may push it to become an executioner.

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How Might This Happen?

Scientists don’t yet have the full answer, but several mechanisms are being explored:

• DNA damage that never gets repaired: Neurons in ALS show signs of DNA injury. If the damage persists, p53 remains switched on, continually pushing cells toward self-destruction.

• Oxidative stress: Motor neurons in ALS experience high levels of reactive oxygen species that damage DNA and mitochondria, keeping p53 active.

• Inflammation and immune activation: Overactive immune cells in the spinal cord release inflammatory signals that amplify p53’s effects.

• Toxic protein interactions: Proteins such as TDP-43 or SOD1 may directly interact with p53 or its regulators, tipping the balance toward a death signal.

These mechanisms remain areas of scientific investigation — promising, but not yet fully understood in humans.

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Why This Matters

Understanding p53 in ALS gives researchers a potential new therapeutic target. If future studies can find ways to restore balance, keeping p53 protective without letting it become destructive, it could help preserve motor neurons for longer.

But this must be done carefully. p53 also prevents cancer, so the goal is not to suppress it entirely, but to help the body maintain a healthy equilibrium between protection and repair.

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A Nutritional and Functional Perspective

From a nutritional and functional medicine perspective, this research highlights a broader truth about the brain and body: cellular stress and repair are two sides of the same coin.

Many of the same biological pressures that influence p53, oxidative damage, inflammation, mitochondrial stress, and poor energy metabolism, are also shaped by how we live, eat, and recover.

At You Nutrition Clinic, we work with individuals to help optimise the body’s internal environment, supporting the cellular systems that underpin neurological health and resilience.

Through personalised nutrition and lifestyle strategies, our practitioners help clients strengthen the foundations that influence how the nervous system responds to stress, energy demand, and repair.

Our work focuses on creating the best possible conditions for the body to maintain function, adapt, and protect itself over time, empowering clients to support their brain and nervous system health with confidence and understanding.

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💬 Stay Connected

If you’d like to learn more, you can contact You Nutrition Clinic to speak with one of our practitioners about supporting long-term brain and nervous system health.

🧩 Connect With Us

For more insights, research updates, and practical tips on brain health and nutrition, follow us on Instagram:

👉 @nutritionandthebrain

Stay inspired. Stay informed. Support your brain. 🧠

References

Martin, L. J., et al. (2000). p53 is abnormally elevated and active in the CNS in human amyotrophic lateral sclerosis. Experimental Neurology, 163(1), 123–131. https://doi.org/10.1006/exnr.2000.7352

Ziff, O. J., et al. (2023). Integrated transcriptome landscape of ALS identifies robust upregulation of p53 signalling. Nature Communications, 14, 2035. https://doi.org/10.1038/s41467-023-37630-6

Vogt, M. A., et al. (2018). TDP-43 induces p53-mediated cell death in neural progenitor cells. Scientific Reports, 8, 6656. https://doi.org/10.1038/s41598-018-26397-2

Maor-Nof, M., et al. (2021). p53 is a central regulator driving neurodegeneration caused by C9orf72 expansion. Nature Neuroscience, 24(6), 859–868. https://doi.org/10.1038/s41593-021-00861-7

Browne, S. E., & Beal, M. F. (2022). Mitochondrial dysfunction in ALS and MS. Free Radical Biology and Medicine, 188, 44–59. https://doi.org/10.1016/j.freeradbiomed.2022.01.017