Fasting and Long COVID: What the Latest Science Says About Recovery
As the global impact of long COVID continues to unfold, researchers are now focusing on fasting as a possible therapeutic strategy. This renewed interest isn’t just about metabolism—it’s about cellular energy, mitochondrial resilience, and immune repair.
This isn’t new territory for me. Over a decade ago, I published the first peer-reviewed paper proposing mitoprotective dietary strategies—like fasting, caloric restriction, and ketogenic diets—for postviral conditions like ME/CFS.
I like to come back to this topic often to stay up-to-date with new research.
What Are Mitoprotective Diets—and Why They Matter in ME/CFS
Mitoprotective diets are dietary strategies designed to support and protect mitochondria—the parts of our cells responsible for producing energy. In ME/CFS, research increasingly points to mitochondrial dysfunction as a key contributor to symptoms like profound fatigue, post-exertional malaise, and brain fog. Diets such as intermittent fasting, caloric restriction, and ketogenic eating have been shown to enhance mitochondrial efficiency, reduce oxidative stress, and improve cellular energy balance. These effects are especially relevant in ME/CFS, where the energy system is under constant strain. By targeting the underlying metabolic abnormalities observed in ME/CFS, mitoprotective diets offer a non-pharmaceutical approach that aligns with the condition’s pathophysiology.
Why These Same Diets May Help in Long COVID
Long COVID shares many of the same biological features seen in ME/CFS, including reduced energy production, chronic inflammation, and impaired recovery after exertion. Early research suggests that long COVID may also involve mitochondrial stress, glucose metabolism issues in the brain, and ongoing immune activation. Because mitoprotective diets target these same systems, by supporting mitochondrial function and reducing oxidative damage, they may also hold promise for those recovering from long COVID.
How Fasting and Ketogenic Diets Boost NAD⁺ to Support Recovery
NAD⁺ (nicotinamide adenine dinucleotide) is a critical coenzyme that powers energy production, supports DNA repair, and regulates immune responses. In chronic illnesses like long COVID, NAD⁺ levels are often depleted due to viral stress, inflammation, and cellular damage, contributing to symptoms like fatigue, brain fog, and poor recovery.
Here’s how fasting and ketogenic diets can help restore NAD⁺ levels:
They increase NAD⁺ availability by shifting the body into a low-glucose, fat-burning state
This activates key energy-sensing enzymes like SIRT1 and SIRT3, which depend on NAD⁺ to function
These enzymes support mitochondrial repair, boost antioxidant defenses, and regulate inflammation
Higher NAD⁺ also promotes mitophagy, the body’s way of clearing out damaged mitochondria to improve energy efficiency
Fasting, especially when combined with a ketogenic dietary pattern, is one of the most effective non-pharmaceutical ways to naturally raise NAD⁺ levels. This makes it a compelling strategy in long COVID recovery protocols, particularly for those struggling with energy metabolism and immune regulation.
The NAD⁺ Piece in ME/CFS
While direct measurements of NAD⁺ levels in ME/CFS patients are limited, several studies provide indirect evidence suggesting that NAD⁺ depletion may play a role in the condition's pathophysiology.
Research has shown that ME/CFS patients exhibit impaired mitochondrial function and increased oxidative stress. These mitochondrial abnormalities can lead to reduced activity of NAD⁺-dependent enzymes, such as SIRT1 and SIRT3, which are crucial for maintaining cellular energy balance and protecting against oxidative damage. The diminished activity of these enzymes implies a potential deficiency in NAD⁺ availability.
For instance, a study by Fluge et al. demonstrated that ME/CFS patients have a distinct metabolic profile characterized by impaired pyruvate dehydrogenase function, leading to reduced ATP production and increased reliance on amino acid metabolism (1). This metabolic shift suggests a disruption in NAD⁺-dependent pathways.
Additionally, a review by Morris and Maes highlighted the role of oxidative and nitrosative stress in ME/CFS, which can deplete NAD⁺ levels and impair the function of sirtuins, further exacerbating mitochondrial dysfunction (2).
While these findings do not provide direct measurements of NAD⁺ levels, they collectively support the hypothesis that NAD⁺ depletion contributes to the mitochondrial and metabolic disturbances observed in ME/CFS.
NAD⁺ Depletion in Long COVID: Emerging Evidence and Therapeutic Implications
Recent studies have highlighted the potential role of NAD⁺ depletion in the pathophysiology of long COVID (10). It’s believed that deficiency may contribute to the persistent symptoms observed in long COVID patients.It’s
Key Findings:
SARS-CoV-2 infection has been shown to upregulate NAD⁺-consuming enzymes, leading to a reduction in NAD⁺ levels (10)
A pilot study involving 36 patients with persistent fatigue post-COVID-19 assessed NAD⁺ supplementation and found improvements in fatigue and quality of life (10)
NAD⁺ boosters like NR and NMN are being explored to improve mitochondrial function and reduce inflammation in long COVID (10)
Implications for Treatment:
These findings suggest NAD⁺ depletion may be a contributing factor to long COVID. Restoring NAD⁺ levels through dietary or supplemental means could improve energy production, immune balance, and resilience to stress.
Fasting and Brain Fog: Ketones May Help Where Glucose Fails
Research indicates that individuals with long COVID often experience brain glucose hypometabolism—a reduced ability of the brain to use glucose efficiently. This dysfunction may underlie symptoms like brain fog and cognitive fatigue (3).
Early neuroimaging and metabolic studies in ME/CFS also point to possible disruptions in brain energy metabolism, suggesting a similar mechanism may be involved (4).
How Fasting and Ketogenic Strategies May Help:
Ketone bodies, such as β-hydroxybutyrate, provide an alternative fuel to the brain (5)
Ketones have anti-inflammatory and antioxidant effects (5)
Ketogenic diets and fasting improve mitochondrial performance and support brain cell recovery (5)
Targeted nutrition strategies that increase ketone availability may improve cognitive clarity and fatigue in postviral conditions.
Rapamycin: A Pharmacological Mimic of Fasting for ME/CFS and Long COVID
Rapamycin, an mTOR inhibitor used in transplant medicine, is now being studied for its ability to mimic the effects of fasting and ketogenic diets at the cellular level. By inhibiting mTOR, rapamycin promotes autophagy, reduces inflammation, and supports mitochondrial repair, mechanisms disrupted in ME/CFS and long COVID.
Simmaron Research Foundation is leading a biomarker-driven pilot trial testing low-dose rapamycin in ME/CFS patients with impaired autophagy markers (ATG13) (6). The trial aims to measure symptom improvement and changes in biomarkers.
In parallel, PolyBio Research Foundation has launched a randomized controlled trial of low-dose rapamycin in long COVID patients to assess improvements in symptoms, metabolism, and inflammation over 24 weeks (6).
These studies position rapamycin as a promising pharmacological tool that mirrors the benefits of mitoprotective diets in a targeted way. You can bet I will write another blog when the outcomes of these studies are published!
New Study: Long-Term Fasting Improves Symptoms in Long COVID
A case series of 14 patients with long COVID who completed 6–16 days of medically supervised fasting (Buchinger Wilhelmi protocol) reported:
Symptom improvement in 13 out of 14 participants (9)
Reductions in fatigue, joint pain, breathlessness, and brain fog (9)
Improvements in metabolic markers: glucose, cholesterol, blood pressure (9)
No serious adverse events (9)
These findings support the potential of fasting to provide both subjective symptom relief and measurable biological improvements in long COVID. Please don’t try this at home! Such long fasts can be very dangerous and should be supervised by a clinician.
What’s Next? The FastCoV Trial
Researchers at the University of Luxembourg are now investigating intermittent fasting in long COVID through a randomized trial called FastCoV. The study will evaluate symptoms, metabolism, and immune markers to better understand fasting’s role in recovery. Stay tuned for that too!
Key Takeaways: Is Fasting Right for Long COVID?
Fasting and ketogenic strategies are emerging low-cost, low-risk options to support:
Mitochondrial repair
NAD⁺ restoration
Brain energy metabolism
Inflammatory balance
It has been amazing to watch this topic spread over the last decade since I first started talking and writing about it. These interventions are not appropriate for everyone, especially those underweight or with a history of disordered eating. But for many, they may represent a meaningful path forward. If you want help exploring whether fasting is right for your recovery plan, I offer 1:1 support based on the latest science and your individual needs.
References
Fluge Ø, Mella O, Bruland O, et al. Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy/chronic fatigue syndrome. JCI Insight. 2016;1(21):e89376. doi:10.1172/jci.insight.89376
Morris G, Maes M. Mitochondrial dysfunctions in myalgic encephalomyelitis/chronic fatigue syndrome explained by activated immuno-inflammatory, oxidative and nitrosative stress pathways. Metab Brain Dis. 2014;29(1):19-36. doi:10.1007/s11011-013-9435-x
Dhamne SC, Li Y, Nair V, et al. Brain hypometabolism and cognitive impairment in post-acute sequelae of SARS-CoV-2 infection (PASC): a neuroimaging study. Front Neurosci. 2024;18:1229028. doi:10.3389/fnins.2024.1229028
Eaton-Fitch N, Du Preez S, Cabanas H, Staines D, Marshall-Gradisnik S. A systematic review of neurological impairments in myalgic encephalomyelitis/chronic fatigue syndrome using neuroimaging techniques. Sci Rep. 2024;14(1):2439. doi:10.1038/s41598-025-91324-1
Norwitz NG, Hu MT, Clarke K. The mechanisms by which ketones reduce neuroinflammation and impact cognition in neurological diseases. Nutrients. 2020;12(10):3136. doi:10.3390/nu12103136
Simmaron Research Foundation. Rapamycin pilot treatment trial for ME/CFS. Simmaron Research. https://www.simmaronresearch.com/rapamycin-trial. Accessed May 10, 2025.
Wirth K, Scheibenbogen C. A unifying hypothesis of the pathophysiology of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): recognition and understanding of a neuroimmunometabolic disease. Front Neurol. 2021;12:701740. doi:10.3389/fneur.2021.701740
He W, Pan Y, Liu M, et al. Serum ATG13 from patients with myalgic encephalomyelitis/chronic fatigue syndrome activates microglia via the RAGE receptor and induces oxidative stress. Front Immunol. 2024;15:1267447. doi:10.3389/fimmu.2024.1267447
Jansen L, Mogler M, Krobot K, et al. Long-term fasting improves symptoms and cardiometabolic health in patients with post-acute sequelae of SARS-CoV-2 infection: a case series. J Transl Med. 2024;22(1):200. doi:10.1186/s12967-024-04793-w
Zhang X, Han K, Song L, et al. NAD⁺ metabolism and its roles in SARS-CoV-2 infection and long COVID. J Mol Cell Biol. 2024;16(1):1–10. doi:10.1093/jmcb/mjad058
