⚗️ Supplement Rationale

The Protocol

A 10-ingredient powder blend targeting the core mechanisms of Post-Acute COVID Vaccination Syndrome — mitochondrial dysfunction, vascular impairment, oxidative stress, and immune dysregulation.

10 Ingredients
2 Scoops / Day
90 Day Protocol

Protocol Overview

All ingredients are combined into a single pre-measured powder. Two scoops daily, taken with water, for 90 days. No separate pills or complex schedules.

Ingredient Doses per Daily Serving

L-Glutamine 14 g
L-Citrulline 5.75 g
Creatine Monohydrate 5 g
L-Serine 4 g
L-Arginine 3 g
NAC (N-Acetyl Cysteine) 2.5 g
Acetyl L-Carnitine 2 g
Taurine 1.5 g
Vitamin C 1 g
NMN (Nicotinamide Mononucleotide) 0.25 g

Mitochondrial Support

Creatine ALCAR NMN Taurine NAC
🔨

Vascular & NO Signalling

L-Citrulline L-Arginine Vitamin C Taurine
🛡

Oxidative Stress & Inflammation

NAC Vitamin C L-Glutamine Taurine
🧠

Neurological & Cognitive

L-Serine ALCAR Creatine NMN

Ingredient Rationale

For each ingredient: what it does at a cellular level, why it is relevant to PACVS, and what the clinical evidence shows.

1

L-Glutamine

Gut barrier integrity · Immune fuel · Glutathione precursor
14 g

Mechanism

Glutamine is the most abundant free amino acid in the body and the primary fuel source for rapidly dividing immune cells (lymphocytes, macrophages) and intestinal epithelial cells. It is conditionally essential during illness, when endogenous synthesis cannot meet demand.

In post-viral states, glutamine depletion impairs gut barrier integrity, allowing bacterial products to translocate into circulation and amplify systemic inflammation. Glutamine also feeds the TCA cycle via alpha-ketoglutarate and serves as a precursor to glutathione — the body's primary antioxidant.

  • Maintains tight junctions of the intestinal epithelium
  • Fuels lymphocyte proliferation and macrophage function
  • Rate-limiting substrate for glutathione synthesis
  • Feeds alpha-ketoglutarate into the TCA cycle

Clinical Evidence

Strong

Glutamine depletion is well-documented in critical illness, major surgery, and post-viral syndromes. Supplementation at 0.2–0.5 g/kg/day reduces infection rates, shortens ICU stays, and improves nitrogen balance in multiple RCTs.

In post-COVID and ME/CFS cohorts, gut microbiome disruption and intestinal permeability are consistent findings. Restoring glutamine availability directly addresses this upstream driver of systemic inflammation.

The 14 g dose reflects established therapeutic use (approximately 0.2 g/kg for an adult) rather than the lower supplemental doses used in healthy populations.

Literature & Clinical Trials
Key References
  • López-Hernández et al. 2023 — Glutamine depleted in PASC plasma 2 years post-infection; pathway enrichment confirms urea cycle dysregulation (Sci Rep)
  • Cengiz et al. 2020 — 10g glutamine 3×/day in acute COVID-19 reduced hospitalisation duration (Clin Nutr Exp)
  • Wischmeyer et al. 2001 — Glutamine reduces ICU length of stay and infection rates across 4 RCTs (Crit Care Med)
  • Coeffier et al. 2010 — Glutamine maintains tight junction integrity and reduces intestinal permeability (Clin Nutr)
⬡ PubChem CID 5961 — L-Glutamine
Clinical Trials
  • Completed NCT04426487 — L-Glutamine in COVID-19 patients (n=60, Brazil 2020)
  • Ongoing NCT05321810 — Glutamine supplementation in post-COVID fatigue (n=40)
  • OSMF VitalScan4PACVS OSMF-VS4P-001 — 14g/day as component of 10-ingredient metabolic protocol (ClinicalTrials.gov registration pending)
2

L-Citrulline

Nitric oxide production · Vascular function · Arginine recycling
5.75 g

Mechanism

Citrulline is converted to arginine in the kidney via the urea cycle, then used by nitric oxide synthase (NOS) to generate nitric oxide (NO). Unlike direct arginine supplementation, citrulline bypasses first-pass hepatic arginase catabolism, producing more sustained and meaningful elevations in plasma arginine and NO.

Nitric oxide is a vasodilator, anti-platelet, and anti-inflammatory signalling molecule produced by endothelial cells. Its depletion is a central feature of endothelial dysfunction — a hallmark of PACVS.

  • More effective than arginine at raising plasma NO levels
  • Reduces arterial stiffness and improves microvascular flow
  • Inhibits platelet aggregation and endothelial activation
  • Reduces blood pressure and exercise-induced fatigue

Clinical Evidence

Strong

Citrulline supplementation at 3–6 g/day consistently improves NO bioavailability, reduces arterial stiffness, and improves exercise performance and recovery in clinical trials. Meta-analyses confirm efficacy across cardiovascular and fatigue endpoints.

Endothelial dysfunction and reduced NO production are documented in Long COVID and PACVS. Salivary nitric oxide — one of the trial's primary biomarkers — provides a non-invasive window on systemic NO status that citrulline supplementation is expected to raise.

Literature & Clinical Trials
Key References
  • Böger et al. 2007 — Citrulline dose-dependently raises plasma arginine and L-arg/ADMA ratio more effectively than L-arginine (Br J Clin Pharmacol)
  • Castillo et al. 1993 — ~40% of oral L-arginine catabolised by intestinal arginase on first pass; citrulline bypasses this entirely (Am J Physiol)
  • López-Hernández et al. 2023 — Ornithine/citrulline ratio elevated in Class B PASC patients; urea cycle metabolism in top 5 dysregulated pathways (Sci Rep)
  • Suzuki et al. 2016 — 2.4g/day citrulline × 7 days: cycling time-trial −1.5% (p<0.05), reduced muscle fatigue (J Int Soc Sports Nutr)
  • Misu et al. 2018 — Citrulline 250mg/kg × 15 days ↑ PGC-1α mRNA and protein in skeletal muscle, improved exercise performance
⬡ PubChem CID 9750 — L-Citrulline
Clinical Trials
  • Completed NCT04570384 — IV citrulline in COVID-19 ARDS (Asklepion Pharmaceuticals)
  • Completed NCT04404426 — CACOLAC: citrulline in COVID-19 ARDS, Rennes University
  • Ongoing NCT05481177 — COVIVA: citrulline/NO pathway in long COVID POTS (Mount Sinai)
  • OSMF VitalScan4PACVS OSMF-VS4P-001 — 5.75g/day alongside L-arginine (combined NO axis; ClinicalTrials.gov pending)
3

L-Serine

Neuronal membrane synthesis · Myelin support · One-carbon metabolism
4 g

Mechanism

Serine is a conditionally essential amino acid serving as the precursor to phosphatidylserine (a key neuronal membrane phospholipid), glycine, sphingolipids, and cysteine. It is central to one-carbon metabolism via the folate cycle, which underpins methylation reactions required for gene regulation, neurotransmitter synthesis, and DNA repair.

In the nervous system, serine is specifically required for the synthesis of myelin sphingolipids and for normal glial function. Serine deficiency produces progressive peripheral neuropathy and cognitive impairment.

  • Precursor to phosphatidylserine (neuronal membrane integrity)
  • Required for sphingolipid and myelin synthesis
  • Feeds one-carbon/folate cycle for methylation
  • Precursor to glycine and cysteine

Clinical Evidence

Emerging

Small fibre neuropathy and cognitive impairment are prevalent in PACVS cohorts. Serine supplementation has been studied in hereditary spastic paraplegia and ALS — neurological conditions sharing mechanistic overlap with post-viral neuropathy — with doses up to 15 g/day used safely.

Plasma serine levels are reduced in ME/CFS patients in some cohort studies, suggesting impaired synthesis or excess catabolism. At 4 g/day, this protocol uses a conservative therapeutic dose with a well-established safety profile.

Literature & Clinical Trials
Key References
  • Saito et al. 2024 — Serine depleted in PASC; level inversely correlated with neuropsychiatric symptom scores (Front Immunol)
  • Kantrowitz et al. 2015 — 2.1g D-serine raised serum D-serine and improved cognitive performance in healthy volunteers (Schizophr Res)
  • Ferreira et al. 2020 — L-serine supplementation safe to 15g/day; used in ALS and hereditary spastic paraplegia with neuroprotective rationale
  • Nance et al. 2017 — Serine required for mitochondrial structural integrity; deficiency leads to mitochondrial fragmentation (Cell Metab)
⬡ PubChem CID 5951 — L-Serine
Clinical Trials
  • Completed NCT01835782 — L-serine in hereditary spastic paraplegia (safety and tolerability; up to 15g/day)
  • Ongoing NCT04602026 — Serine and glycine supplementation in neurological conditions
  • OSMF VitalScan4PACVS OSMF-VS4P-001 — 4g/day targeting PACVS neuropsychiatric symptoms (ClinicalTrials.gov pending)
4

L-Arginine

Direct NO substrate · Creatine synthesis · Immune modulation
3 g

Mechanism

Arginine is the direct substrate for nitric oxide synthase and provides the guanidino group for creatine synthesis. It also participates in the urea cycle for nitrogen disposal and modulates T-cell and macrophage function. When combined with citrulline, the two amino acids create a sustained NO-generation cycle: citrulline raises systemic arginine availability, while arginine provides the immediate NOS substrate.

  • Direct NOS substrate — immediately available for NO production
  • Synergistic with citrulline for sustained plasma arginine elevation
  • Required for creatine biosynthesis
  • Modulates macrophage polarisation and T-cell activity

Clinical Evidence

Strong

A 2021 RCT (Tosato et al., European Review for Medical and Pharmacological Sciences) combined L-arginine (1.66 g × 3/day) with vitamin C in Long COVID patients — demonstrating significant reductions in fatigue, dyspnoea, and improved 6-minute walk distance versus placebo over 4 weeks.

This is direct RCT evidence for the arginine-vitamin C combination in a post-acute COVID phenotype, providing the strongest available clinical anchor for this protocol's NO-pathway approach.

Literature & Clinical Trials
Key References
  • Tosato et al. 2022 — L-arginine + Vit C RCT (n=56, 28 days): fatigue 8.7% vs 80.1% placebo (p<0.0001); 6MWT d=0.56; eNOS ratio d=0.72 (Nutrients)
  • Calvani et al. 2023 — Secondary analysis confirming arginine supplementation restores L-arginine/ADMA ratio in PASC (EJNMMI)
  • Romero et al. 2013 — The arginine paradox: arginase and eNOS compete for arginine; Vmax of arginase 1,000× greater than eNOS (Pharmacol Ther)
  • Castillo et al. 1993 — Quantified splanchnic first-pass catabolism of oral arginine (~40% intestinal, 15% hepatic) (Am J Physiol)
⬡ PubChem CID 6322 — L-Arginine
Clinical Trials
  • Completed NCT04869592 — L-arginine + Vit C in long COVID (Tosato et al. 2022 primary trial)
  • Ongoing NCT05367778 — L-arginine in post-COVID exercise intolerance (follow-on)
  • OSMF VitalScan4PACVS OSMF-VS4P-001 — 3g/day L-arginine alongside 5.75g citrulline (dual NO-axis; ClinicalTrials.gov pending)
5

Creatine Monohydrate

Rapid ATP buffering · Mitochondrial bypass · Cognitive support
5 g

Mechanism

Phosphocreatine is the body's fastest ATP regeneration system, replenishing ATP from ADP in under one second without requiring mitochondrial involvement. In cells with impaired mitochondrial function — a core feature of PACVS — the phosphocreatine system provides an alternative energy pathway for muscle contraction and neuronal activity.

Beyond acute energy buffering, creatine supports mitochondrial biogenesis, reduces lactate accumulation, and has well-documented neuroprotective effects by maintaining neuronal energy homeostasis.

  • Fastest ATP regeneration — bypasses mitochondrial bottleneck
  • Reduces lactic acid accumulation during exertion
  • Neuroprotective — maintains neuronal ATP under metabolic stress
  • Supports mitochondrial membrane potential

Clinical Evidence

Strong

Creatine monohydrate has one of the most extensive safety and efficacy profiles in nutritional supplementation. Hundreds of trials confirm improved exercise performance, reduced fatigue, and cognitive benefit across healthy and clinical populations.

In post-exertional malaise — the central disabling feature of ME/CFS and PACVS — creatine supplementation is particularly rational because PEM is mechanistically linked to a crash in mitochondrial ATP output. 5 g/day is the standard maintenance dose across the literature.

Literature & Clinical Trials
Key References
  • Slankamenac et al. 2023 — 4g/day × 6 months double-blind RCT: mental fatigue d=1.02, ageusia d=1.23, concentration d=1.19–2.46 (caution: n=6/group) (Food Sci Nutr)
  • Slankamenac et al. 2024 — 8-week creatine ± glucose in long COVID: body aches d=1.33, concentration d=0.80 (J Nutr Sci Vitaminol)
  • Frontiers RCT 2026 — 6g/day creatine (n=67): fatigue −2.05 pts (95% CI −3.47 to −0.63; p=0.005) — best-powered trial to date (Front Nutr)
  • de Boer et al. 2022 — PASC CPET: ↓fat oxidation + ↑lactate — mechanistic context for creatine's lactate-buffering benefit (Am J Respir Crit Care Med)
⬡ PubChem CID 586 — Creatine
Clinical Trials
  • Completed NCT05589246 — Creatine in post-COVID fatigue (Novi Sad group, 2022–2023)
  • Ongoing NCT05848986 — Creatine monohydrate in ME/CFS and long COVID (n=80)
  • OSMF VitalScan4PACVS OSMF-VS4P-001 — 5g/day creatine as part of 10-ingredient metabolic protocol (ClinicalTrials.gov pending)
6

Acetyl L-Carnitine

Fatty acid oxidation · Mitochondrial metabolism · Neuronal repair
2 g

Mechanism

L-carnitine is the transporter that shuttles long-chain fatty acids across the inner mitochondrial membrane for beta-oxidation. Without adequate carnitine, fatty acids cannot enter the mitochondria and ATP production from lipids is impaired. The acetyl form (ALCAR) crosses the blood-brain barrier, acting additionally as an acetyl group donor for acetylcholine synthesis and neuronal metabolism.

ALCAR also reduces oxidative damage to mitochondrial membranes and supports the activity of complex I of the electron transport chain.

  • Essential for mitochondrial fatty acid import
  • Crosses blood-brain barrier — supports neuronal energy
  • Acetyl group donor for acetylcholine synthesis
  • Reduces mitochondrial oxidative damage

Clinical Evidence

Strong

Carnitine deficiency is documented in ME/CFS and correlates with fatigue severity. ALCAR supplementation at 2–3 g/day has been studied in ME/CFS, HIV-associated neuropathy, fibromyalgia, and hepatic encephalopathy — with improvements in fatigue, pain, and cognitive function across multiple trials.

Impaired fat oxidation — measurable by reduced respiratory exchange ratio during exercise — is a documented feature of post-acute COVID syndrome. ALCAR directly addresses this metabolic impairment.

Literature & Clinical Trials
Key References
  • Scaturro et al. 2022 Null result at 1g/day in PASC rehabilitation: no significant improvement in dyspnoea or functional scores. Protocol uses 2g based on dose-response reasoning (Appl Sci)
  • Guntur et al. 2022 — Long-chain acylcarnitines elevated in PASC plasma, confirming fatty acid transport bottleneck and mitochondrial import failure (Metabolites)
  • de Boer et al. 2022 — CPET in PASC: ↓fat oxidation rates at graded exercise. Establishes the mechanistic target for ALCAR intervention (AJRCCM)
  • Talebi et al. 2022 — L-carnitine supplementation significantly improves survival in mild-to-moderate COVID-19 (Pharmacol Rep)
⬡ PubChem CID 7045767 — Acetyl-L-Carnitine
Clinical Trials
  • Null 1g NCT04762953 — ALCAR in PASC rehabilitation (Scaturro 2022; null at 1g/day — dose may be insufficient)
  • Ongoing NCT05396820 — Carnitine in ME/CFS/long COVID fatigue (higher dose)
  • OSMF VitalScan4PACVS OSMF-VS4P-001 — 2g/day (double the null-result dose; targeting dose-response threshold; ClinicalTrials.gov pending)
7

NAC (N-Acetyl Cysteine)

Glutathione replenishment · Antioxidant · Anti-inflammatory
2.5 g

Mechanism

NAC is an acetylated cysteine derivative that serves as the primary precursor for glutathione synthesis. Cysteine is the rate-limiting substrate for glutathione, and NAC replenishes intracellular cysteine efficiently. Glutathione — the body's master antioxidant — neutralises reactive oxygen species, regenerates vitamin C and E, and detoxifies electrophilic compounds.

Beyond antioxidant function, NAC directly scavenges ROS, inhibits NF-κB inflammatory signalling, reduces platelet activation, and has mucolytic properties. It has a long record of clinical use and an excellent safety profile.

  • Replenishes glutathione — the primary cellular antioxidant
  • Inhibits NF-κB mediated inflammatory gene expression
  • Reduces platelet aggregation and hyperactivation
  • Direct free radical scavenging activity

Clinical Evidence

Strong

NAC has decades of clinical use — most prominently in acetaminophen overdose, COPD, and idiopathic pulmonary fibrosis. In the COVID context, NAC was proposed early as a therapeutic agent due to its ability to counter the cytokine storm and reduce oxidative stress.

Glutathione depletion and elevated oxidative stress are consistent findings in ME/CFS and Long COVID. Studies in these populations using 600 mg–2.4 g/day have reported improvements in fatigue and inflammatory markers. At 2.5 g/day, this protocol targets therapeutic rather than supplemental glutathione repletion.

Literature & Clinical Trials
Key References
  • Bellone, Siegel & Santin 2025 — Yale case series (n=9): vWF normalised in 3/3 NAC users vs 0/6 controls (p=0.0119); dyspnoea, brain fog, and fatigue improved (Gynecol Oncol Rep)
  • Guntur et al. 2022 — Impaired fatty acid beta-oxidation and elevated lipid peroxidation in PASC — primary mechanistic target for NAC's glutathione-protective role (Metabolites)
  • AXA1125 RCT 2023 — Restoring beta-oxidation significantly improves physical and cognitive fatigue in long COVID — validates NAC's upstream mechanism (eClinMed)
  • CoViNAC meta-analysis 2025 — 12 RCTs (n=1,125): NAC reduced COVID-19 mortality RR=0.59; NAC docks at SARS-CoV-2 Mpro catalytic site (computational)
  • Selem, Raszek, Varon & Halma 2026 — Systematic review: spike/mRNA persistence in 20 studies across multiple tissues post-vaccination (Future J Pharm Sci) [Disclosure: OSMF co-author]
⬡ PubChem CID 12035 — N-Acetyl-L-Cysteine
Clinical Trials
  • Preprint Li et al. 2025 — Double-blind RCT: NAC significantly improved SGRQ at 1, 3, 6 months post-discharge (acute COVID; not long COVID)
  • Ongoing NCT05356091 — NAC in post-COVID fatigue and oxidative stress (n=60)
  • OSMF VitalScan4PACVS OSMF-VS4P-001 — 2.5g/day; primary rationale is lipid metabolism restoration via glutathione, not spike protein (ClinicalTrials.gov pending)
8

Taurine

Mitochondrial membrane stability · Cardioprotection · Cytoprotection
1.5 g

Mechanism

Taurine is a sulfur-containing amino acid that is not incorporated into proteins but acts as a critical intracellular osmolyte and cytoprotective agent. It stabilises mitochondrial membranes, reduces electron transport chain ROS production, and modulates calcium ion handling in cardiac and skeletal muscle — relevant to the dysautonomia and cardiac symptoms in PACVS.

Taurine also conjugates bile acids, reduces inflammation via inhibition of neutrophil ROS production, and has direct anti-arrhythmic effects on cardiac conduction.

  • Stabilises inner mitochondrial membrane against oxidative damage
  • Modulates Ca²⁺ handling — relevant to cardiac arrhythmias and POTS
  • Anti-inflammatory via neutrophil ROS inhibition
  • Osmoprotective — protects cells under metabolic stress

Clinical Evidence

Strong

A 2023 study in Science (Singh et al.) demonstrated that taurine deficiency is a driver of the aging process across multiple species, and that taurine supplementation reversed markers of physiological aging including mitochondrial dysfunction and inflammation.

Clinical use of 3–6 g/day taurine is established in heart failure, where it improves cardiac output and reduces hospitalisation. At 1.5 g/day this protocol uses a conservative dose appropriate for a 90-day continuous protocol, targeting mitochondrial and cardiovascular support in PACVS.

Literature & Clinical Trials
Key References
  • Khoramjoo et al. 2024 — Plasma taurine inversely correlated with PASC severity: 148 μM (severe) vs 225 μM (recovered). One of the strongest depletion-to-severity correlations in PASC metabolomics (PLOS ONE)
  • Singh et al. 2023 — Taurine deficiency drives ageing across species; supplementation reversed mitochondrial dysfunction and inflammation markers (Science)
  • Militante & Lombardini 2002 — Taurine modifies mitochondrial tRNAs for respiratory chain efficiency; essential for OXPHOS fidelity (Amino Acids)
  • Sun et al. 2016 — 1.6g/day taurine × 12 weeks raised plasma taurine 34 μM in prehypertensive patients — therapeutic relevance to PASC severity gap (Hypertension)
⬡ PubChem CID 1123 — Taurine
Clinical Trials
  • Ongoing NCT05615142 — Taurine in long COVID fatigue and autonomic dysfunction (n=50)
  • Completed NCT02027636 — Taurine in chronic heart failure: improved cardiac output, reduced hospitalisation
  • OSMF VitalScan4PACVS OSMF-VS4P-001 — 1.5g/day; plasma taurine as candidate biomarker in study design (ClinicalTrials.gov pending)
9

Vitamin C

Antioxidant · Carnitine synthesis co-factor · Endothelial repair
1 g

Mechanism

Ascorbate is the primary water-soluble antioxidant in human plasma, scavenging ROS and regenerating vitamin E. It is an essential co-factor for two hydroxylation reactions required for L-carnitine biosynthesis — meaning that adequate vitamin C is a prerequisite for endogenous carnitine production and thus for efficient fat oxidation.

Vitamin C also drives collagen synthesis (via prolyl and lysyl hydroxylases), supports endothelial repair, and — at gram-level doses — augments the NO-producing effects of L-arginine by reducing oxidative inactivation of NO.

  • Required co-factor for L-carnitine synthesis (two enzymatic steps)
  • Reduces oxidative breakdown of NO — synergistic with arginine
  • Regenerates vitamin E in lipid membranes
  • Supports collagen synthesis for endothelial repair

Clinical Evidence

Strong

The Tosato et al. (2021) RCT combining L-arginine with vitamin C in Long COVID directly underpins this combination. Vitamin C deficiency was documented in hospitalised COVID patients and correlates with disease severity.

At 1 g/day, vitamin C exceeds the dose required for carnitine co-factor function and reaches the threshold at which plasma vitamin C becomes pharmacologically active as a vascular antioxidant — without the gastrointestinal tolerability concerns of higher doses.

Literature & Clinical Trials
Key References
  • Tosato et al. 2022 — Primary RCT combining L-arginine + vitamin C in long COVID (n=56): fatigue 8.7% vs 80.1% placebo (p<0.0001). Vitamin C component cannot be isolated but synergy is mechanistically established (Nutrients)
  • Berger et al. 2020 — Vitamin C deficiency documented in ICU COVID-19 patients; inversely correlated with illness severity (Crit Care)
  • Rebouche 2004 — Two hydroxylation steps in endogenous carnitine biosynthesis (via 6-N-trimethyllysine and γ-butyrobetaine) require vitamin C as co-factor (J Nutr)
  • Carr & Maggini 2017 — Vitamin C and immune function: comprehensive review of neutrophil, lymphocyte, and endothelial effects (Nutrients)
⬡ PubChem CID 54670067 — Ascorbic acid (Vitamin C)
Clinical Trials
  • Completed NCT04869592 — L-arginine + Vitamin C in long COVID (Tosato et al. 2022 primary trial, Italy)
  • Completed NCT04363749 — High-dose IV Vitamin C in COVID-19 ARDS (Wuhan, CITRIS-ALI follow-on)
  • OSMF VitalScan4PACVS OSMF-VS4P-001 — 1g/day; key rationale is carnitine co-factor + NO preservation synergy with arginine (ClinicalTrials.gov pending)
10

NMN (Nicotinamide Mononucleotide)

NAD⁺ repletion · Mitochondrial biogenesis · Sirtuin activation
0.25 g

Mechanism

NMN is a direct precursor to NAD⁺ (nicotinamide adenine dinucleotide), a molecule central to cellular energy metabolism, DNA repair, and gene regulation. NAD⁺ is required as an electron carrier in complex I and III of the mitochondrial electron transport chain and as a substrate for sirtuins — a family of deacylases that regulate inflammation, mitochondrial biogenesis, and stress response pathways.

NAD⁺ levels decline with age, illness, and oxidative stress. In post-viral illness, chronic immune activation and persistent oxidative stress deplete NAD⁺ rapidly through PARP activation (DNA repair) and CD38-mediated consumption.

  • Directly raises intracellular NAD⁺ levels
  • Activates SIRT1/SIRT3 — regulates mitochondrial biogenesis
  • Required for complex I and complex III electron transfer
  • Supports PARP-mediated DNA repair without depleting NAD⁺

Clinical Evidence

Emerging

Human trials by Yoshino et al. (2021, Science) confirmed that oral NMN raises NAD⁺ levels in blood, skeletal muscle, and peripheral blood mononuclear cells within weeks, with improvements in insulin sensitivity and muscle function in older women.

NAD⁺ depletion has been proposed as a key driver of Long COVID pathophysiology. At 250 mg/day, this protocol uses a dose consistent with the clinical trial literature — sufficient to raise NAD⁺ measurably while remaining within the dose range with established human safety data.

Literature & Clinical Trials
Key References
  • Isman et al. 2024 — NAD+ (iontophoresis) + low-dose naltrexone pilot: Chalder fatigue 25.9→17.4 (p<0.0001); 52% responders — cannot isolate NAD+ component (Brain Behav Immun Health)
  • Nicotinamide riboside RCT 2025 Null: NR significantly raised NAD⁺ but did NOT improve fatigue, cognition, sleep, or mood vs placebo. Exploratory within-group benefits at 10 weeks. Trial may have been underpowered (eClinMed)
  • Yoshino et al. 2021 — Oral NMN 250mg/day × 10 weeks: raised blood, muscle, and PBMC NAD⁺; improved insulin sensitivity and muscle function in postmenopausal women (Science)
  • Navas et al. 2021 — NAD⁺ depletion in COVID-19: PARP9, PARP10, PARP14, CD38 upregulated during immune activation; persistent depletion in long COVID proposed mechanism
⬡ PubChem CID 14180 — Nicotinamide mononucleotide (NMN)
Clinical Trials
  • Mixed NCT05127382 — NR (nicotinamide riboside) in long COVID: NAD⁺ ↑ but no significant symptom effect vs placebo (eClinMed 2025)
  • Ongoing NCT05795803 — NMN 500mg/day in long COVID fatigue and cognitive function (n=60, 2024)
  • Ongoing NCT06113302 — NAD⁺ pathway restoration in PASC: NMN vs niacin vs control
  • OSMF VitalScan4PACVS OSMF-VS4P-001 — 250mg/day NMN as mitochondrial co-factor component (ClinicalTrials.gov pending)

Register Your Interest

Be the first to hear when the VitalScan4PACVS self-funded pilot opens for participants and as results are published.

Register Your Interest →