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Hung Van Le* Biologics & Drug Targets, ProSci LLC, Rockaway, The United States ORCID https://orcid.org/0000-0002-6913-2373 (Hung Van Le) Abstract This narrative review summarizes key recent clinical findings on the daily use of multivitamin-mineral (MVM) supplements, with emphasis on evidence most relevant to aging and personal health decisions. Recent randomized trials suggest that daily MVM use in older adults may provide modest but clinically meaningful benefits in selected domains, especially global cognition and episodic memory, with less consistent evidence for executive function. Additional findings support a reduction in cataract incidence, a potential benefit for some cancer outcomes, and a possible slowing of biological aging as measured by epigenetic clocks. By contrast, current evidence does not support clear benefits for cardiovascular disease prevention, adjudicated mild cognitive impairment, dementia incidence, or age-related macular degeneration. These findings both complement and contrast with current recommendations from major health agencies, which remain cautious and do not endorse routine MVM use for all adults. The practical implication is not that everyone should take a daily MVM, but that the newer evidence provides a stronger basis for individualized decision-making. Readers may find this information useful when considering their own diet, age, chronic conditions, medications, and family history, and when deciding whether discussion of MVM supplementation with a clinician is warranted as part of a broader strategy to support healthy aging. Bottom line Current evidence suggests that multivitamin-mineral supplementation in older adults: May help
Has not been shown to help
Should not replace
Introduction Although the topic may seem trivial and often appears in the news or in everyday conversation, the concerns are legitimate. Vitamin and mineral deficiencies are a worldwide problem, especially in lower-income countries where inadequate nutrition remains widespread. One recent estimate suggests that up to 5 billion of the world’s 8.3 billion people have micronutrient deficiencies, with different effects in males and females [1]. Even in higher-income settings, adequate intake is not guaranteed because diet, lifestyle, health status, cultural factors, and aging all influence nutritional needs. Fortunately, people in higher-income countries have access to abundant, generally clear guidance on meeting micronutrient needs through diet and, when appropriate, supplementation. In the United States, for example, the Centers for Disease Control and Prevention (CDC) provides guidance about micronutrients, the U.S. Preventive Services Task Force (USPSTF) offers its own recommendations, and the National Institutes of Health (NIH) Office of Dietary Supplements provides fact sheets for consumers and health professionals. Despite the guidance provided by health agencies, many people still rely primarily on advice from trusted clinicians when deciding whether to take multivitamin-mineral supplements (MVMs). Others, more skeptical of the medical establishment, related industries, or public health agencies, may follow medical news closely to better understand their health and the implications of new findings. Recent reports that daily MVM use may slow epigenetic clocks [2] are likely to renew interest in a familiar question: whether to take MVMs, and if so, at what stage of life. Do daily multivitamins slow epigenetic clocks and reduce biological age? The original study by Li et al. (2026) [3] was a prespecified ancillary analysis of the Cocoa Supplement and Multivitamin Outcomes Study (COSMOS), a large randomized, placebo-controlled trial involving 958 older adults with a mean age of 70 years. Participants received a daily multivitamin-multimineral supplement (Centrum Silver), cocoa extract, both interventions, or placebo. Researchers measured five DNA methylation-based “epigenetic clocks” at baseline and again after two years. The main finding for the multivitamin arm was a statistically significant slowing of biological aging on two of the five clocks studied, especially PCPhenoAge [4] and PCGrimAge [5]. The estimated effect corresponded to roughly 2.5 to 5 fewer months of biological aging over two years. Participants whose biological age exceeded their chronological age at baseline appeared to benefit most. Additional analyses suggested that participants whose clock measures improved also showed lower inflammation and better preservation of cognitive function. Methodologically, this is among the strongest supplement studies conducted to date because it was randomized, placebo-controlled, prospectively planned, and based on a relatively large, well-characterized cohort. The findings are thought-provoking, but by themselves they are unlikely to change clinical practice for prescribing multivitamin-mineral supplements to older adults. That caution is understandable because the study also has important limitations. Most importantly, epigenetic clocks are surrogate end points. They do not show that participants lived longer, avoided disability, prevented fractures, or reduced cardiovascular events. Instead, they reflect changes in biomarkers thought to track biological aging. Whether modest improvements in these clocks translate into meaningful clinical benefits remains uncertain. A biomarker can reach statistical significance without producing clear patient benefit. In addition, the effect size was modest, not all clocks changed, and the study was not designed to identify which components of the multivitamin-multimineral supplement produced the observed effect. Without a stronger mechanistic basis, targeted recommendations would be difficult. The most encouraging aspect of the study is its consistency with earlier COSMOS and Physicians’ Health Studies (PHS) examining the effects of daily multivitamin use on major health outcomes. The new findings on biological age, as measured by epigenetic clocks, should therefore be interpreted in the context of the broader clinical evidence from those large trials. Effects of daily MVM treatment on cancer incidence The effects of daily MVM use on cancer incidence were examined in both the PHS and COSMOS trials. In a randomized, double-blind, placebo-controlled trial, Gaziano et al. [6] evaluated daily MVM use in 14,641 U.S. male physicians aged 50 years or older in PHS II, including 1,312 men with a history of cancer at randomization. Median follow-up was 11.2 years (range, 10.7–13.3). Among men with and without a prior cancer history, daily MVM use was associated with a modest reduction in overall cancer incidence. Subgroup analyses further suggested that survivors of epithelial cancers may have benefited the most. A later COSMOS trial, reported by Sesso et al. [7], examined a larger and more heterogeneous cohort of 21,442 U.S. adults (12,666 women aged 65 years or older and 8,776 men aged 60 years or older) who were free of major cardiovascular disease and recently diagnosed cancer at baseline. This randomized, double-blind, placebo-controlled trial had a much shorter median follow-up of 3.6 years. In contrast to PHS II, COSMOS found no statistically significant difference in overall cancer incidence or all-cause mortality between the multivitamin and placebo groups. However, subgroup analyses by cancer site suggested a significant reduction in lung cancer incidence. These results are not necessarily contradictory. PHS II showed a small reduction in total cancer incidence after more than a decade of supplementation in male physicians, whereas COSMOS found no statistically significant reduction during a much shorter follow-up in an older, more heterogeneous population. Given the substantial differences in follow-up duration, demographic composition, and baseline risk, the two trials are best viewed as complementary rather than as directly comparable tests of the same hypothesis. Effects of daily MVM treatment on cognition, memory, and executive function Three COSMOS studies reported since 2023 have provided the clearest evidence to date on the cognitive effects of daily MVM supplementation in older adults. In COSMOS-Mind, a randomized, double-blind, placebo-controlled substudy of 2,262 participants (mean age 73 years; 60% women; 89% non-Hispanic White), Baker et al. [8] evaluated the effect of daily MVM use on global cognition after a mean follow-up of three years. Compared with placebo, daily MVM supplementation produced a statistically significant benefit in global cognition, with the largest effect among participants with a history of cardiovascular disease. Benefits were also observed for episodic memory and executive function. In the same year, Yeung et al. [9] analyzed a different COSMOS subgroup, COSMOS-Web, consisting of 3,562 older adults (mean age 71 years; 67% women; 93% non-Hispanic White) followed for up to three years. The primary end point was episodic memory at one year, with three secondary outcomes assessed over three years: episodic memory, performance on novel object recognition tasks, and executive function. Compared with placebo, participants assigned to daily MVM supplementation showed significantly better episodic memory at one year and across the full three-year follow-up. No significant differences were detected for the other two secondary outcomes. The most recent analysis, reported by Vyas et al. [10], drew on all three cognitive COSMOS subgroups: COSMOS-Clinic (573 participants, two years of follow-up), COSMOS-Web (2,472 participants, three years), and COSMOS-Mind (2,158 participants, three years). COSMOS-Clinic was used to assess global cognition as the primary end point, with episodic memory and executive function as secondary outcomes after two years. The study found modest benefits in global cognition and significantly more favorable change in episodic memory, but no benefit for executive function or attention. The authors then performed a meta-analysis across all three COSMOS cognitive subgroups, focusing on global cognition and episodic memory as primary outcomes. Compared with placebo, daily MVM supplementation was associated with significantly more favorable change over time in both domains. Taken together, these three studies suggest that daily MVM supplementation improves global cognition and episodic memory in older adults, whereas evidence for executive function is less consistent. Memory improvement appears to be the most robust and reproducible finding, and improvement in global cognition is reasonably well supported. A benefit for executive function remains plausible but is not yet firmly established. This may reflect greater biological heterogeneity in executive function or the use of measures that are noisier and less statistically powerful. Effects of daily MVM treatment on cognitive impairment and dementia Progressive decline in global cognition, memory, and executive function can lead to mild cognitive impairment (MCI) and, eventually, dementia—outcomes that can be formally adjudicated by expert panels. Sachs et al. [11] examined whether daily MVM supplementation, compared with placebo, affected the incidence of adjudicated MCI and all-cause dementia in the COSMOS-Mind cohort of 2,662 participants with a mean age of 73 years. After three years of follow-up, the incidence of neither outcome differed significantly between the MVM and placebo groups. However, among participants adjudicated as having MCI, those assigned to daily MVM performed better on tests of global cognition and executive function when scores at the time of adjudication were compared with scores obtained one year earlier. In the smaller subgroup adjudicated as having dementia, no clear differences were observed in global cognition, executive function, or memory. These latter results should be interpreted cautiously because the dementia subgroup was small and therefore statistically underpowered. Overall, COSMOS-Mind did not show that daily MVM supplementation reduces the incidence of cognitive impairment or dementia over three years, but the favorable cognitive findings within the MCI subgroup are consistent with the broader cognitive benefits reported elsewhere in COSMOS, including by Baker et al. (2023) [8]. Effects of daily MVM treatment on cataract and age-related macular degeneration (AMD) Cataracts are common in older adults, whereas AMD is less common but remains a major cause of vision loss. Christen et al. [12] evaluated whether long-term daily multivitamin supplementation affected the incidence of cataract and age-related macular degeneration in 14,641 male physicians aged 50 years or older in the Physicians’ Health Study. In this randomized, double-blind, placebo-controlled trial, participants were followed for a mean of 11.2 years. Daily multivitamin use was associated with a modest but statistically significant reduction in cataract risk, but it had no significant effect on visually significant AMD. The cataract finding is consistent with results from two smaller independent trials: Maraini et al. [13], which followed 1,020 participants aged 55 to 75 years for about nine years, and Sperduto et al. [14], which studied 2,141 participants aged 45 to 74 years in a rural Chinese community over five to six years. Effects of daily MVM treatment on cardiovascular disease Two large randomized trials—PHS II (Sesso, H. D. et al. [15]) and COSMOS (Sesso, H. D. et al. [7])—found that daily MVM supplementation did not reduce major cardiovascular events, myocardial infarction, stroke, or cardiovascular mortality. Mean treatment and follow-up durations were 11.2 years in PHS II and 3.6 years in COSMOS. The PHS II cohort included 14,641 U.S. male physicians aged 50 years or older, whereas COSMOS enrolled 21,442 U.S. adults, including 12,666 women aged 65 years or older and 8,776 men aged 60 years or older.  Discussion Taken together, the evidence reviewed here suggests that daily multivitamin-mineral (MVM) supplementation has produced several clinically relevant benefits in large randomized trials, although the strength of evidence varies by outcome. The most reproducible benefits have been observed in cognition among older adults, especially for global cognition and episodic memory in the COSMOS substudies, with less consistent evidence for executive function. Table 1 also indicates a modest reduction in overall cancer incidence in PHS II, a possible reduction in epithelial cancer incidence in that trial, a signal for lower lung cancer incidence in COSMOS, and a statistically significant reduction in cataract incidence in long-term follow-up studies. The newer COSMOS-Blood findings add a biologically interesting signal that daily MVM supplementation may modestly slow epigenetic aging, but this result should still be regarded as supportive rather than definitive because biological age is a surrogate marker rather than a hard clinical outcome. By contrast, the evidence does not currently support a reduction in cardiovascular events, mild cognitive impairment incidence, dementia incidence, or age-related macular degeneration. For personal health, these findings are potentially meaningful because they point to benefits in areas that strongly affect independence and quality of life with aging. Even modest preservation of memory or global cognition may matter to older adults who want to maintain functional autonomy, medication management, financial judgment, and social engagement. A small reduction in cancer incidence or cataract risk can also be clinically meaningful when applied over many years, especially because cataracts and cancer are common age-related conditions. At the same time, the significance of these benefits should not be overstated. The demonstrated effects are generally modest, they do not establish that MVMs are a substitute for a healthy diet, and they do not show broad protection across all major chronic diseases. The most reasonable interpretation is that daily MVM supplementation may serve as a low-risk supportive strategy for selected adults, particularly when micronutrient intake may be less reliable because of age, appetite changes, chronic illness, restricted diets, or medication use. These newer findings also create an important tension with current health agency recommendations. The U.S. Preventive Services Task Force (USPSTF) states that evidence remains insufficient to recommend for or against multivitamins for the prevention of cancer or cardiovascular disease in community-dwelling, nonpregnant adults, while specifically recommending against beta carotene and vitamin E for those purposes. That position is understandable because the USPSTF framework focuses on prevention of major clinical end points in generally healthy populations and gives substantial weight to consistency, magnitude of effect, and certainty across trials. Similarly, the NIH Office of Dietary Supplements emphasizes that MVMs do not replace healthy dietary patterns, that formulations vary substantially, and that supplements can help fill nutrient gaps but can also increase the risk of excessive intake of some nutrients. The CDC likewise frames micronutrient sufficiency as important for health but does not treat routine MVM use as a universal preventive intervention for all adults. In other words, the newer trial results do not necessarily overturn existing agency guidance; rather, they suggest that the evidence base for selected benefits of daily MVM supplementation in older adults is becoming stronger than many recommendations currently reflect. A practical way to leverage this information is to think about MVM supplementation through the lens of personal risk rather than as a universal rule. A person with a family history of cognitive decline, memory problems, cataracts, or certain cancers might view the current data as a reason to discuss a standard, age-appropriate MVM with a clinician, especially if dietary intake is inconsistent or if there are risk factors for micronutrient insufficiency such as gastrointestinal disease, vegetarian or highly restrictive eating patterns, low appetite, frailty, polypharmacy, or alcohol overuse. Someone with established cardiovascular disease should recognize that current evidence does not support MVM use as a strategy to prevent heart attack, stroke, or cardiovascular death, even though cognitive benefits may still be relevant in some subgroups. Likewise, a person with a strong family history of dementia should understand that the current evidence is more supportive for slowing cognitive decline than for preventing adjudicated dementia over the short term. This distinction matters because expectations should be realistic: MVMs may help preserve function in some domains, but they should not be presented as a proven way to prevent all age-related diseases. As for timing, the best time to think seriously about MVM supplementation is probably before nutritional vulnerability becomes obvious, but not necessarily in early adulthood for everyone. The clearest trial evidence in this review comes from adults in later life, generally from the early 60s onward, when risks of cognitive decline, cataract, cancer, and subclinical nutritional insufficiency become more relevant. For many people, midlife is therefore a reasonable time to begin considering whether their diet, health conditions, medications, and family history justify supplementation, while older adulthood is the period in which potential benefits may be most actionable. This does not mean that every healthy younger adult should take a daily MVM, nor does it imply that starting later guarantees benefit. Rather, it suggests that MVM use is best approached as part of anticipatory aging care: a decision revisited when diet quality declines, chronic disease accumulates, or family history raises concern about cognitive or age-related outcomes. In that sense, the new evidence is most useful not as a blanket recommendation, but as a prompt for individualized, age-aware decision-making grounded in both personal health context and the limits of the current evidence. Conclusion Our review summarizes the latest clinical findings on the daily use of multivitamin-mineral (MVM) supplements and shows that the evidence now supports selected benefits more clearly than many people may realize, particularly for global cognition, episodic memory, cataract risk, and possibly biological aging, with a potential benefit for some cancer outcomes, while benefits for cardiovascular disease, dementia, and some other outcomes remain unproven. In that sense, this review both supplements and contrasts current information and recommendations from health agencies, which appropriately remain cautious and do not endorse routine MVM use for all adults. The most useful implication is not a blanket recommendation, but a stronger basis for individualized reflection and action. At different stages of life, especially in midlife and older adulthood, individuals can use this information to consider their diet, health conditions, medications, and family history, discuss the possible role of MVM supplementation with their doctors, and decide whether a standard, age-appropriate product fits their overall preventive health strategy. Used thoughtfully, MVM supplementation may be one small but meaningful part of a broader plan to support healthy aging. References
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Hung Van Le* Biologics & Drug Targets, ProSci LLC, Rockaway, The United States ORCID https://orcid.org/0000-0002-6913-2373 (Hung Van Le) Abstract
Post-polio syndrome (PPS) is a progressive neuromuscular disorder that affects a substantial proportion of long-term survivors of poliomyelitis. Traditionally viewed as a consequence of motor unit exhaustion, PPS is increasingly recognized as a multifactorial condition involving neurodegeneration, chronic low-grade inflammation, and, more recently, persistent low-level poliovirus infection. These emerging insights point to a more complex disease model that integrates viral persistence, impaired humoral immunity, and metabolic stress in compensatory motor units. Vitamin D, a pleiotropic secosteroid hormone, has been implicated in several biological processes relevant to PPS, including immune regulation, mitochondrial function, and muscle physiology. Recent findings indicate that vitamin D deficiency is common in PPS patients and may contribute to impaired immune competence and disease progression. While vitamin D does not directly target the primary neurodegenerative process, it may enhance neuromuscular resilience through immunomodulatory and metabolic effects. This review examines the mechanistic intersections between vitamin D signaling and PPS pathophysiology, with particular emphasis on immune function, mitochondrial energetics, and neuromuscular junction stability. It further discusses the clinical role of vitamin D as a supportive intervention and evaluates the potential need for antiviral strategies considering evidence for persistent poliovirus infection. A multimodal therapeutic approach combining antiviral therapy, immune optimization, and metabolic support is proposed as a rational framework for future PPS management. Clinical Bottom Line
Introduction Post-polio syndrome (PPS) is a late-onset neurological disorder that affects individuals decades after recovery from acute poliomyelitis caused by Poliovirus. Clinically, PPS is characterized by new or progressive muscle weakness, fatigue, pain, and functional decline following a prolonged period of neurological stability. The syndrome typically emerges 15 to 40 years after the initial infection and represents one of the most significant long-term complications of the global poliomyelitis epidemics of the 20th century. Although the incidence of acute poliomyelitis has declined dramatically due to widespread vaccination programs, the population of polio survivors remains substantial. Current estimates suggest that 15–20 million individuals worldwide are living with the sequelae of prior poliovirus infection [1], of whom approximately 20–85% may develop PPS depending on diagnostic criteria [2]. As this population ages, PPS represents an increasing clinical and public health challenge, particularly in regions with historically high poliomyelitis burden. Currently, there is no disease-modifying therapy for PPS. Management remains largely supportive and includes physical rehabilitation, with carefully tailored exercise programs to optimize motor unit function while avoiding overuse, symptomatic treatment for pain, fatigue, and sleep disturbances, and orthotic support and assistive devices to improve mobility. Among pharmacological approaches, intravenous immunoglobulin (IVIG) has shown modest benefits in selected patients, particularly in reducing pain and inflammatory markers, although its effects on muscle strength and long-term progression remain limited. In this context of limited therapeutic options, there is increasing interest in interventions that can enhance systemic resilience rather than directly reverse neuronal loss. Vitamin D has attracted attention due to its broad biological activity, including immunomodulatory, metabolic, and neuromuscular effects. Notably, recent studies have identified a high prevalence of vitamin D deficiency in PPS patients, raising the possibility that it may contribute to disease pathophysiology rather than merely reflect lifestyle factors. This review aims to integrate current knowledge on PPS with emerging insights into vitamin D biology and antiviral strategies. By examining the intersections between viral persistence, immune function, and neuromuscular degeneration, it seeks to propose a more comprehensive framework for understanding and managing PPS. Pathophysiology of Post-Polio Syndrome: from motor unit failure to persistent viral signaling Post-polio syndrome (PPS) is classically explained by progressive failure of enlarged motor units that compensated for the initial loss of anterior horn cells after acute poliomyelitis. Over decades, these metabolically stressed neurons undergo distal degeneration, leading to neuromuscular junction (NMJ) instability and denervation [3]. However, this “purely degenerative” view has been challenged by accumulating immunological data. Studies have demonstrated elevated cytokines in cerebrospinal fluid and blood, suggesting chronic low-grade inflammation [4-8]. This inflammatory component is substantially strengthened by recent work from Toniolo et al. [9] who reported evidence consistent with persistent low-level Poliovirus infection in long-term polio survivors with PPS. The evidence came from co-culturing PPS-derived samples, including peripheral blood leukocytes, cerebrospinal fluid, duodenal biopsy specimens, and skeletal muscle fragments, with poliovirus-susceptible cell lines. Poliovirus was then detected by RT-PCR in cell culture supernatants and by immunofluorescence in the cultured cell monolayers. This work was built on earlier studies by Leparc-Goffart et al. [10] and Julien et al. [11], which had identified poliovirus in the CSF of a smaller group of PPS patients using RT-PCR. The observed persistent infection supports a model in which ongoing viral persistence may drive chronic immune activation, rather than inflammation being purely secondary. The authors further described humoral immune deficiencies in PPS patients, altered neutralizing antibody profiles, and a high prevalence of vitamin D deficiency [12]. Together, these findings suggest that PPS may involve a triad of residual viral persistence, inadequate humoral immune control, and chronic low-grade inflammation. The available evidence reframes PPS as a hybrid condition, combining neurodegeneration, immune dysregulation, and possible viral persistence. Relevance of Vitamin D in PPS The prevalence of vitamin D deficiency raises questions about its ultimate role in the etiology of PPS. It could simply be a by-product of patients’ lifestyle (poor diet, inadequate mobility and physical activities, and limited sun exposure), or alternatively it could be a bona fide risk factor. A combination of both could be plausible as well. As an established pleiotropic modulator of multiple pathways [13] vitamin D could be uniquely positioned to affect the development of PPS. How vitamin D signaling intersects with PPS pathways is explored below. Immunomodulation and antiviral defense. Vitamin D signaling suppresses pro-inflammatory T helper 1 responses and reduces IFN-γ production [14]. Beyond dampening inflammation, vitamin D also enhances innate immune responses, supports antimicrobial peptide production, and modulates B cell function. In the context of the finding by Toniolo et al. [9,12], this is particularly relevant since vitamin D deficiency may exacerbate impaired humoral immunity, potentially allowing persistent poliovirus activity. Thus, vitamin D may not only reduce inflammation but also improve immune competence against residual viral antigenic stimulation. Muscle and mitochondrial energetics. Vitamin D influences skeletal muscle through improved mitochondrial oxidative function [15] and regulation of mitochondrial dynamics and respiration [16]. Given that PPS involves fatigable muscle and metabolically stressed motor units, vitamin D may enhance bioenergetic resilience, even if it does not halt neuronal loss. Neuromuscular junction stability and mitochondrial energetics. The progressive functional decline observed in Post-Polio Syndrome is closely linked to instability of the neuromuscular junction (NMJ), which represents the final common pathway of motor neuron degeneration. In PPS, surviving motor neurons form enlarged motor units that are metabolically overextended. Over time, this leads to distal axonal degeneration, impaired synaptic maintenance, and failure of reinnervation, with NMJ dysfunction preceding overt muscle fiber loss. A critical but often underemphasized aspect of NMJ stability is local energy supply. Maintenance of synaptic transmission, vesicle recycling, and ion homeostasis requires tightly regulated ATP production. This demand is met by mitochondria localized at both pre- and postsynaptic compartments, whose function is essential for sustaining neuromuscular signaling. In aging and neurodegenerative conditions, impairment of mitochondrial function—rather than sheer mitochondrial number—has been implicated as a limiting factor in synaptic resilience. Vitamin D has been shown to influence mitochondrial biology at multiple levels, including enhancement of oxidative phosphorylation, modulation of mitochondrial dynamics, and regulation of transcriptional programs involving PGC-1α [15,16]. Although there is no direct evidence that vitamin D regulates axonal mitochondrial transport or synapse-specific mitochondrial targeting, its effects on mitochondrial efficiency and cellular energetics provide a plausible mechanism for improving NMJ stability under conditions of metabolic stress. In this context, vitamin D may contribute to functional preservation of neuromuscular transmission by improving ATP availability in muscle and possibly nerve terminals, reducing oxidative stress that destabilizes synaptic structures, and supporting the metabolic demands of enlarged motor units. This interpretation aligns with the broader view of PPS as a disorder of metabolic exhaustion of compensatory motor units, where interventions that enhance bioenergetic capacity may delay functional decline. Collectively, these observations indicate that vitamin D may enhance the metabolic stability of existing synapses, thereby slowing functional deterioration. Clinical positioning: supplementation vs therapeutic dosing This leads to an important clinical consideration: in what context should vitamin D be used in PPS? As a nutritional supplement, maintaining adequate serum 25-hydroxyvitamin D levels (50-125 nmoles/L) is clearly warranted. PPS patients are at increased risk of deficiency due to reduced mobility and sun exposure, and correction of deficiency supports bone health, muscle function, and overall metabolic stability. The use of high-dose vitamin D as a therapeutic intervention remains uncertain. While high-dose regimens (100,000 IU cholecalciferol, every two weeks for 24 months) have shown benefits in Multiple in Sclerosis [17] and potentially in upper respiratory viral infections [18-20], there is currently no direct clinical evidence supporting such an approach in PPS. Moreover, vitamin D exhibits dose-dependent effects, and excessive supplementation may not yield proportional benefit. A more coherent approach is to incorporate vitamin D into a multimodal management strategy, alongside targeted physical therapy to optimize motor unit function, adequate protein and caloric intake, and interventions aimed at preserving mitochondrial and neuromuscular health. The goal here is to remove an exacerbating factor while hoping for disease modifications resulting from a beneficial effect on immune competence, muscle function, and bone health. The role of vitamin D supplementation in PPS is only supportive and there is clearly a need to look beyond seeking curative treatment. Therapeutic implications: beyond vitamin D Rationale for antiviral therapy. Evidence of persistent poliovirus infection and defective replication [10,11,9] supports consideration of antiviral therapy in PPS. Combined with physical rehabilitation and the immune and metabolic support potentially provided by vitamin D, an antiviral component could help form a more mechanistically comprehensive treatment strategy. However, no antiviral drugs are currently approved specifically for poliovirus, and historical drug-development efforts were limited in part by the success of global polio vaccination programs. Current development landscape. Momentum in the field has been sustained by the Polio Antivirals Initiative (PAI), which aims to develop therapies that reduce vaccine-derived poliovirus shedding in immunodeficient recipients of oral polio vaccines and mitigate the risk of prolonged excretion in a post-eradication setting. Current discovery efforts focus on four broad approaches: inhibitors of the viral capsid, viral protease, and RNA replication, as well as agents targeting host factors required for replication [21, 22]. Capsid inhibitors. Pleconaril and pocapavir are the most advanced candidates, having reached human studies in vaccine-derived poliovirus infection and oral poliovirus vaccine challenge models [23-27]. Pocapavir is also available for compassionate use through its developer, ViroDefense, or via the PAI. RNA-replication inhibitors. Ribavirin, a broad-spectrum inhibitor of viral RNA replication, has been used compassionately in a patient with vaccine-derived poliovirus infection but did not clear the virus [25]. In contrast, remdesivir was associated with viral clearance in that same patient [28]. Remdesivir (Veklury), a nucleoside analog widely used during the COVID-19 pandemic as an inhibitor of the SARS-CoV-2 RNA-dependent RNA polymerase, therefore represents an intriguing candidate for further study in persistent poliovirus infection. That signal should be interpreted cautiously: the remdesivir evidence is currently limited to a single case report and has not yet been independently replicated. Even so, its availability and established clinical safety profile make it a reasonable high-priority option for off-label compassionate use in carefully selected patients with documented persistent poliovirus infection and shedding. Other inhibitors and future directions. All known poliovirus protease inhibitors and agents targeting host factors remain at the preclinical stage [21,22]. Nevertheless, recent findings on persistent infection, together with renewed progress in antiviral development, provide a strong rationale for reinvigorating this field. From a compassionate-care perspective, such efforts are justified by the potentially large global burden. Conclusion Vitamin D is best understood as a pleiotropic adjunct in PPS, which may improve immune balance, mitochondrial function, and possibly NMJ resilience. Its deficiency, common in PPS, should be corrected as part of standard care. However, evidence for high-dose therapeutic use remains lacking and its effects are supportive rather than disease-modifying. In light of emerging evidence for persistent poliovirus infection and immune dysregulation, future therapeutic strategies should expand beyond supplementation alone. A combination approach including antiviral therapy, immune optimization, and metabolic support may offer the most rational path forward in PPS management. References
Acknowledgment: Dr. NhuCo Lethi provided the initial inspiration for this article on PPS. |
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