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

research2693
Oct 22
6 min read

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.

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.

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.

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).

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.

💬 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.

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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