A Physicians Examination of Panoxol (Vasonoxol) in Relation to Stroke Prevention and Recovery

1. Executive Summary

Panoxol, a dietary supplement now marketed as Vasonoxol, has been promoted for its potential benefits in vascular health, including specific claims regarding stroke prevention and recovery.1 This report provides a comprehensive analysis of Panoxol/Vasonoxol, its constituent ingredients, the scientific evidence underpinning its purported effects, and associated safety considerations, with a particular focus on its relevance to cerebrovascular health.

The supplement's formulation includes L-arginine, L-citrulline, horse chestnut seed extract, Ginkgo biloba, cayenne pepper, and red yeast rice.1 The primary proposed mechanism centers on enhancing nitric oxide (NO) production and improving endothelial function.1 While individual components of the formula possess some scientific support for cardiovascular or neuroprotective actions, direct clinical evidence substantiating the efficacy of the specific Panoxol/Vasonoxol formulation in human stroke prevention or recovery is not apparent from the available documentation.

Panoxol/Vasonoxol is described as a patent-protected product (US Patent 8,691,295 B2) developed by Clinical & Herbal Innovations, Inc., a subsidiary of Solei Systems, Inc..2 However, significant safety concerns emerge, particularly regarding the inclusion of red yeast rice. This ingredient contains monacolin K, a substance chemically identical to lovastatin, and carries risks of adverse effects similar to statin medications, including musculoskeletal and liver issues.4 Furthermore, red yeast rice supplements are often susceptible to contamination with citrinin, a nephrotoxic mycotoxin.5 Regulatory bodies such as the European Food Safety Authority (EFSA) have expressed serious concerns about the safety of monacolins from red yeast rice, even at low daily intakes.4

A notable disparity exists between the direct stroke-related claims found in earlier promotional materials 1 and the more generalized vascular health claims presented in current marketing, which are accompanied by standard FDA disclaimers for dietary supplements.7 This report concludes that there is a substantial gap between the marketing assertions for Panoxol/Vasonoxol concerning stroke and the robust clinical validation required for such specific therapeutic claims. The safety profile, especially related to red yeast rice, necessitates careful consideration and greater transparency from the manufacturer.

2. Introduction to Panoxol (Vasonoxol): Product Profile and Claims

2.1. Background: From Panoxol to Vasonoxol

The dietary supplement in question was initially marketed under the name Panoxol and has subsequently been rebranded as Vasonoxol [User Query]. The trademark for VASONOXOL was filed in February 2015 and registered in November 2016.9 Despite the name change, SEC filings from 2018 still referred to the website www.panoxol.com as a sales portal for the product.2 This transition in branding is noteworthy for accurately tracking the product's history and market presence. The change may also serve to mitigate potential confusion with unrelated topical acne treatment products marketed under the name "PanOxyl".10 The continued reference to the original "panoxol.com" domain alongside the newer "Vasonoxol" branding 2 could suggest several possibilities: it might reflect a gradual transitional branding strategy, an effort to maintain any brand equity associated with the original name, or simply a delay in updating all corporate and regulatory documentation. Such dual branding or phased renaming has implications for consumer recognition and the company's marketing logistics.

2.2. Manufacturer: Clinical & Herbal Innovations, Inc.

Panoxol/Vasonoxol is a product of Clinical & Herbal Innovations, Inc. (CHII). This entity is a 100% wholly-owned subsidiary of Solei Systems, Inc., following an acquisition that occurred on October 20, 2017.2 Understanding this corporate structure provides context for the product's development, marketing, and overall accountability. The acquisition of CHII by Solei Systems, Inc., a publicly reporting entity, may have influenced the product's research and development trajectory, available marketing resources, and distribution strategies. For instance, SEC filings for Solei Systems mention plans to "Continue R&D and begin clinical trials to prove the supplement's proprietary and synergistic benefits" 2, indicating a potential for increased investment in substantiating product claims, driven by the strategic objectives of the parent company.

2.3. Patent and Proprietary Formulation

The product is consistently described as "patent-protected".2 This protection refers to US Patent 8,691,295 B2, titled "DIETARY SUPPLEMENT FOR VASCULAR HEALTH," which was granted on April 8, 2014, with a priority date from a provisional application filed on October 26, 2011.3 The patent abstract and claims detail a composition comprising L-Arginine, L-Citrulline, Ginkgo Biloba, Horse Chestnut, Red Yeast Rice, and Cayenne Pepper.3

An important aspect of the intellectual property is its ownership. The patent is not directly owned by Clinical & Herbal Innovations, Inc. or Solei Systems, Inc., but rather by Charles O. Scott, who is the majority shareholder, CEO, and Chairman of Solei Systems, Inc. Mr. Scott licenses the product to CHII.2 A Patent License Agreement was executed between Charles Scott and CHII on October 31, 2018. Furthermore, Solei Systems, Inc. had an agreement to purchase this patent from Mr. Scott on or before December 31, 2023, with the price to be determined by an independent third party.2 This licensing arrangement, rather than direct company ownership of the core intellectual property, could have implications for the company's asset valuation and long-term control over the product, particularly in scenarios involving leadership changes or corporate restructuring. The outcome of the planned patent purchase by the 2023 deadline is not detailed in the provided information but would be a significant factor in the company's IP strategy.

2.4. Stated Purpose: Focus on Vascular Health and Stroke 1

A 2015 document titled "Panoxol™ for Stroke Prevention and Recovery" explicitly states that the product, when used in conjunction with appropriate blood pressure control, diet, and exercise, "can be expected to assist in the prevention as well as recovery from stroke".1 The document further elaborates that Panoxol targets endothelial dysfunction and atherosclerotic disease, which are significant contributors to stroke pathology.1 The proposed mechanisms include improving nitric oxide availability, promoting relaxation of blood vessels, and reducing the endothelium's susceptibility to cholesterol plaquing and subsequent clot formation.1

These are highly specific and strong claims related to a serious medical condition. A critical evaluation of the evidence supporting these direct assertions regarding stroke is a central focus of this report. It is noteworthy that the directness of these 2015 stroke-related claims 1 appears to differ from the more generalized language used in more recent marketing materials for Vasonoxol and Panoxol Plus. For example, the Vasonoxol website emphasizes support for "healthy blood flow, blood pressure, and heart resilience" 8, and an Amazon listing for "Panoxol Plus" mentions it "may help with high blood pressure and may provide cardiovascular benefits".7 This apparent shift from specific disease treatment/prevention claims to more general structure/function claims is a common adaptation for dietary supplements navigating the regulatory landscape enforced by the Food and Drug Administration (FDA), which strictly limits disease claims for non-drug products.7 Such a shift could reflect a strategic decision to align marketing with regulatory expectations or an evolution in the product's target demographic and positioning.

3. Ingredient Composition and Purported Mechanisms of Action

3.1. Detailed Breakdown of Active Ingredients

The core formulation of Panoxol, as described in the 2015 PDF document 1 and the US Patent 8,691,295 B2 3, consists of six key ingredients: L-arginine, L-citrulline, Horse Chestnut Seed Extract, Ginkgo Biloba, Cayenne Pepper, and Red Yeast Rice. This composition is also largely reflected on the current Vasonoxol website.8 A variant, "Panoxol Plus," available on Amazon, includes these six ingredients and additionally incorporates Vitamin D and Fulvic Acid (from Shilajit Extract).7

The specific dosages of these ingredients vary between the patent documentation and the marketed "Panoxol Plus" product. The 2015 PDF focusing on stroke does not provide specific quantities.1 This report will primarily address the six core ingredients common to the formulations discussed in the context of stroke claims.

Table 1: Panoxol/Vasonoxol Ingredients, Dosages (from available sources), and Claimed Role in Vascular Health/Stroke

The discrepancy in ingredient dosages between the patent specifications 3 and the marketed "Panoxol Plus" product 7 is substantial for several components. For instance, the patent describes a preferred embodiment with 1000mg each of L-Arginine and L-Citrulline, 1000mg of Horse Chestnut, 1200mg of Red Yeast Rice, and 2000mg of Cayenne Pepper per two tablets. In contrast, "Panoxol Plus" contains 500mg each of L-Arginine and L-Citrulline, 250mg of Horse Chestnut, 300mg of Red Yeast Rice, and 580mg of Cayenne Pepper extract per three tablets.7 Such variations could arise from considerations of cost, safety (particularly for ingredients like Red Yeast Rice or high-dose Cayenne), regulatory restrictions, or formulation adjustments based on perceived efficacy at lower doses. This divergence raises critical questions about which formulation the original, strong "stroke prevention and recovery" claims 1 were intended to represent. The efficacy of many herbal and nutritional ingredients is dose-dependent, so the relevance of scientific studies conducted at specific dosages must be carefully weighed against the actual composition of the marketed product. The patent's notation of "<0.4% active ingredient" for Red Yeast Rice 3 is also a key detail, likely referring to the concentration of monacolin K. If a 1200mg dose of Red Yeast Rice contains less than 0.4% monacolin K, this translates to less than 4.8mg of monacolin K, a dosage level that falls within the range of concern for regulatory bodies like EFSA.

3.2. The Central Role of Nitric Oxide and Endothelial Function

A cornerstone of Panoxol/Vasonoxol's purported mechanism of action is the enhancement of nitric oxide (NO) synthesis and bioavailability, primarily attributed to its L-arginine and L-citrulline content.1 The product materials emphasize that endothelial dysfunction is a common factor in various cardiovascular diseases and a precursor to conditions like hypertension and atherosclerosis, which are major risk factors for stroke.1 NO is a crucial endogenous signaling molecule that plays a vital role in maintaining vascular homeostasis. It mediates vasodilation (relaxation of blood vessels), inhibits platelet aggregation, prevents leukocyte adhesion to the endothelium, and limits the proliferation of vascular smooth muscle cells. Consequently, strategies aimed at improving endothelial function and augmenting NO levels are recognized as valid therapeutic targets for promoting cardiovascular health.

While the biochemical rationale for enhancing NO to improve vascular health is sound, the direct extrapolation of this mechanism to achieve "stroke prevention and recovery" as a primary outcome for this specific multi-ingredient supplement requires more than general assertions or effects on intermediate markers like blood pressure.2 The pathophysiology of stroke is complex and multifactorial, involving ischemic cascades, excitotoxicity, inflammation, oxidative stress, and thrombotic events, which may not be solely or adequately addressed by NO enhancement alone. Therefore, the leap from "improves NO levels" to "prevents stroke and aids in recovery" is a significant one that necessitates robust clinical evidence specific to the Panoxol/Vasonoxol formulation and its effects on direct stroke outcomes in human populations.

3.3. Claimed Synergistic Effects for Stroke Prevention and Recovery

The promotional material for Panoxol asserts that "Each ingredient works at multiple points in the progression of endothelial dysfunction and atherosclerotic disease, and the combination is synergistic in effect".1 The concept of synergy, where the combined effect of multiple components is greater than the sum of their individual effects, is frequently invoked for multi-ingredient dietary supplements. Such claims are appealing as they suggest enhanced efficacy from the specific blend.

However, establishing true pharmacological synergy is scientifically rigorous and requires dedicated studies that compare the effects of the combination product against its individual active components and a placebo. The available documentation for Panoxol/Vasonoxol, including the "clinical experience study" on blood pressure 2, evaluates the effects of the combined formulation but does not provide data that would differentiate synergistic actions from merely additive effects of ingredients known to influence vascular parameters. In the absence of such specific research on this formulation for stroke-related endpoints, the claim of synergy, while theoretically plausible for certain combinations of bioactive compounds, remains an unsubstantiated assertion for Panoxol/Vasonoxol in the context of stroke prevention and recovery.

4. Review of Scientific Evidence: Individual Ingredients and Stroke

The following sections review the scientific evidence for each key ingredient of Panoxol/Vasonoxol, focusing on its relevance to cerebrovascular health and stroke, based on the provided information.

4.1. L-Arginine and L-Citrulline: Nitric Oxide Synthesis and Cerebrovascular Impact

Claimed Mechanism: L-arginine serves as the direct precursor for nitric oxide (NO) synthesis via NO synthase enzymes. L-citrulline is purported to enhance NO production by inhibiting arginase (an enzyme that degrades L-arginine) and by being efficiently recycled to L-arginine, thereby increasing L-arginine availability for NO synthesis. The combination is claimed to reverse endothelial dysfunction and improve NO bioavailability.1

Evidence Review:

Clinical research on L-arginine supplementation for stroke-like episodes in patients with Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes (MELAS) has yielded some positive findings, with one study reporting symptomatic improvement following L-arginine administration.12 However, this observation is not without debate, as other communications have questioned the overall benefit and methodology, noting that some patients experienced episodes despite L-arginine prophylaxis.13 The unique pathophysiology of MELAS, often involving impaired vasodilation due to NO deficiency in cerebral arteries, may make these patients particularly responsive (or theoretically responsive) to L-arginine, but these findings may not be broadly generalizable to common forms of ischemic or hemorrhagic stroke. The controversy even within this specific patient group underscores the complexity of translating a biochemical mechanism (NO production) into consistent clinical benefits.

L-citrulline, often in combination with malate (citrulline malate), has been investigated for its ergogenic and vasodilatory effects, attributed to its role as an NO enhancer.14 While some studies suggest improved exercise performance and vasodilation, the research results are described as equivocal, with uncertainty regarding whether the effects are due to L-citrulline, malate, or a synergistic interaction.14 In critically ill patients in an ICU setting, L-citrulline supplementation was associated with improvements in some metabolic markers (fasting blood sugar, cholesterol, LDL-C, hs-CRP) and a reduction in the duration of invasive ventilation.15 While these patients were not specifically stroke patients, the findings related to vascular and inflammatory markers are of general interest.

Analysis: The evidence for L-arginine in the specific context of MELAS-associated stroke-like episodes is mixed and its applicability to more prevalent stroke types is uncertain. L-citrulline shows potential for enhancing NO bioavailability and positively influencing some vascular health indicators in other populations. However, direct evidence from robust clinical trials demonstrating that the doses of L-arginine and L-citrulline present in Panoxol/Vasonoxol lead to prevention of common stroke types or improved recovery in a general population is not provided in the available materials.

4.2. Horse Chestnut Seed Extract (Aescin): Endothelial Protection and Anti-inflammatory Actions

Claimed Mechanism: Horse chestnut seed extract (HCSE) is stated to protect the endothelium. Its active component, aescin (or escin), is claimed to prevent damaging inflammation, downregulate inflammatory genes, and upregulate healing genes, based on a mouse model of stroke.1

Evidence Review:

The primary body of clinical evidence for HCSE relates to its efficacy in treating chronic venous insufficiency (CVI). Systematic reviews have concluded that HCSE is superior to placebo and comparable to reference medications (e.g., rutosides, compression therapy) in reducing symptoms of CVI, such as lower leg volume, ankle and calf circumference, leg pain, and pruritus.16 Aescin is believed to exert these effects by promoting blood circulation through veins, reducing swelling and inflammation, potentially by "sealing" leaking capillaries, improving the elastic strength of veins, and inhibiting enzymes that damage blood vessel walls.17

The connection to stroke, as presented in the Panoxol promotional material 1, relies on the general concept of endothelial protection and anti-inflammatory mechanisms, supported by a reference to a study in a mouse model of global cerebral ischemia where aescin reportedly attenuated cognitive deficits and hippocampal injury.1

Analysis: While HCSE has well-established benefits for venous disorders, its direct relevance to arterial events like stroke is less clear. The pathophysiology of CVI (venous valve incompetence, venous hypertension) differs significantly from that of most strokes (arterial occlusion or hemorrhage). Although endothelial protection and anti-inflammatory effects are broadly beneficial for vascular health, extrapolating efficacy from CVI treatment or a single preclinical mouse study to human stroke prevention or recovery is speculative. Human clinical trial data supporting the use of HCSE for stroke is absent in the provided documentation.

4.3. Ginkgo Biloba: Neuroprotection and Cerebral Circulation

Claimed Mechanism: Ginkgo biloba is described as a neuroprotective supplement that improves blood flow to the brain and is helpful in both ischemic and hemorrhagic strokes. A specific claim highlights a randomized, double-blind, placebo-controlled study where Ginkgo biloba administration reportedly tripled the likelihood of 4-month improvement in ischemic stroke patients.1

Evidence Review:

The scientific literature on Ginkgo biloba for stroke presents a mixed and evolving picture. An older review (data up to 2009) of 10 trials involving 792 patients with acute ischemic stroke found limited evidence of benefit from Ginkgo biloba extract (oral tablets or intravenous injections) on neurological improvement or dependency, with many trials suffering from methodological limitations.18 Only one of these trials was described as a rigorous randomized, placebo-controlled, double-blind study, and its results did not conclusively support efficacy.18

More recently, a 2025 meta-analysis of 27 randomized controlled trials (RCTs) involving 3,336 patients with ischemic stroke investigated the efficacy and safety of specific ginkgo terpene lactone preparations (diterpene ginkgolides meglumine injection - DGMI, and ginkgolide injection) when combined with antiplatelet drugs.19 This meta-analysis found that the combination treatment significantly improved the overall clinical response rate, reduced neurological deficit scores (NIHSS), and improved activities of daily living (Barthel Index) compared to antiplatelet therapy alone. The safety profile was favorable, with no significant increase in adverse events. However, the meta-analysis did not find significant differences in long-term prognosis (modified Rankin Scale scores) or platelet function, and noted the presence of publication bias and methodological limitations in some included studies (e.g., lack of blinding, allocation concealment).19

Analysis: The recent meta-analysis 19 offers more encouraging results for specific injectable preparations of ginkgo terpene lactones used as an adjunct to standard antiplatelet therapy in ischemic stroke. This aligns directionally with the positive claims made for Panoxol. However, it is crucial to consider the differences in preparation and administration route. Panoxol/Vasonoxol is an oral supplement containing a Ginkgo biloba extract. The bioavailability and achieved systemic concentrations from an oral extract may differ considerably from those of injectable ginkgo terpene lactones. Therefore, while the field of Ginkgo research in stroke is advancing, the direct applicability of findings from studies using injectable forms to an oral supplement like Panoxol/Vasonoxol requires careful consideration. The specific RCT cited in the Panoxol PDF (Savadi Oskouei et al. 1) would need to be scrutinized for its methodology, the type of Ginkgo preparation used, and its overall quality to ascertain its relevance.

4.4. Cayenne Pepper (Capsaicin): Antioxidant and Vascular Benefits

Claimed Mechanism: Cayenne pepper is described as a potent antioxidant that improves stroke risk and contributory risk factors such as hypertension, atherosclerosis, diabetes, and obesity.1

Evidence Review:

Capsaicin, the active pungent component in cayenne pepper, has been the subject of considerable experimental research regarding its neuroprotective and vasoprotective properties. Reviews of this research suggest that capsaicin may protect against ischemic or excitotoxic cerebral neuronal injury and could potentially lower the risk of cerebral stroke.20 The proposed mechanisms are multifaceted and include:

• Activation of the Transient Receptor Potential Vanilloid 1 (TRPV1) channel, leading to downstream effects.

• Induction of a mild hypothermic response, which can be neuroprotective.

• Antioxidant and anti-inflammatory actions, reducing oxidative stress and the release of pro-inflammatory mediators.

• Vasodilator effects, mediated by the release of neuropeptides like CGRP, potentially improving cerebral blood flow.

• Anti-thrombotic actions, by inhibiting platelet aggregation and blood coagulation factors (demonstrated in vitro).

• Favorable effects on lipid profiles, such as lowering LDL cholesterol and preventing lipoprotein oxidation.

• Inhibition of excitotoxicity and modulation of microglial activation.20

The vast majority of this evidence stems from in vitro studies (cell cultures) and in vivo animal models of stroke or related pathologies.21 Human clinical trial data directly linking dietary cayenne pepper or capsaicin supplementation to stroke prevention or improved recovery outcomes is limited in the provided documentation.

Analysis: The preclinical evidence for capsaicin's neuroprotective and vasoprotective mechanisms is scientifically compelling. However, a significant translational gap exists between these experimental findings (often involving specific, sometimes high, doses or direct applications of capsaicin) and the effects of dietary supplementation with cayenne pepper extract in humans. The dosage of cayenne pepper extract in Panoxol/Vasonoxol (e.g., 580mg in Panoxol Plus 7, or a much higher 2000mg of Capsicum in the patent 3) would need to deliver a sufficient amount of capsaicinoids to achieve the biologically active concentrations demonstrated in experimental settings. Furthermore, the gastrointestinal tolerability of high oral doses of capsaicin can be a concern for some individuals. While the potential is intriguing, the current evidence for the specific Panoxol/Vasonoxol formulation relies on indirect inference from these preclinical mechanisms.

4.5. Red Yeast Rice (Monacolin K): Cholesterol Management and Cardiovascular/Stroke Risk

Claimed Mechanism: Red Yeast Rice (RYR) is claimed to improve cholesterol profiles, diminish oxidative stress, and limit the expression of cell adhesion molecules, thereby making the endothelium less 'sticky' and less prone to cholesterol plaque formation, which contributes to stroke prevention.1

Evidence Review:

RYR contains monacolins, notably monacolin K, which is chemically identical to the prescription drug lovastatin and acts by inhibiting HMG-CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis.5 Numerous studies and meta-analyses have demonstrated that RYR effectively lowers LDL cholesterol (by 15-25%) and total cholesterol.22

Of particular relevance to stroke, one review cites a large Chinese clinical trial involving 1,445 elderly patients (65-75 years) with a history of myocardial infarction who received RYR supplementation ( Xuezhikang, a specific RYR extract) or placebo for approximately 4.5 years.22 This study reported that RYR supplementation significantly reduced the risk of nonfatal myocardial infarction, coronary death, all-cause mortality, and notably, a 44.1% reduction in the risk of stroke.22

However, the efficacy of RYR is counterbalanced by significant safety concerns. The European Food Safety Authority (EFSA) has issued strong warnings about monacolins from RYR, stating that exposure to monacolin K, even at intake levels as low as 3 mg/day, could lead to severe adverse effects on the musculoskeletal system (including rhabdomyolysis) and the liver.4 EFSA concluded it was unable to identify a daily intake of monacolins from RYR that does not raise safety concerns.4 The National Center for Complementary and Integrative Health (NCCIH) in the U.S. also highlights that RYR products containing significant amounts of monacolin K can have side effects similar to statin drugs (muscle, kidney, liver damage) and that RYR products with enhanced or added lovastatin are considered unapproved new drugs by the FDA.5

Another major safety issue is the potential contamination of RYR products with citrinin, a nephrotoxic mycotoxin.5 Studies have found that many commercial RYR supplements contain variable and sometimes inaccurately labeled amounts of monacolin K, and many are contaminated with citrinin, sometimes exceeding permissible limits, even in products labeled "citrinin free".6 A 2024 systematic review of clinical trials on monacolin K (2-10 mg/day) confirmed its beneficial effects on cholesterol but also noted that some studies reported adverse effects, leading to the suggestion that patients treated with monacolin K should be routinely monitored.23

Analysis: RYR has proven cholesterol-lowering effects, and evidence from at least one large clinical trial suggests it can reduce stroke risk in a high-risk secondary prevention population. This aligns with the proposed mechanism for stroke prevention via improved vascular health. However, these potential benefits are heavily overshadowed by serious safety concerns regarding monacolin K's statin-like adverse effects and the risk of citrinin contamination. The dose of monacolin K in Panoxol/Vasonoxol is not explicitly stated in most product materials, though the patent mentions "<0.4% active ingredient" for a 1200mg RYR dose, which could yield <4.8mg of monacolin K 3 – a level within EFSA's range of concern. The 300mg of RYR powder in Panoxol Plus 7 would also require quantification of its monacolin K content and assurance of citrinin safety. Without transparent data from the manufacturer on these critical quality and safety parameters, the inclusion of RYR in Panoxol/Vasonoxol raises significant safety questions.

4.6. Vitamin D (Primarily in "Panoxol Plus")

Claimed Mechanism: In the "Panoxol Plus" formulation, Vitamin D is included for "immunity support" and "cardiovascular well-being".7

Evidence Review:

Recent research has explored the role of Vitamin D in neurological health and post-stroke outcomes. A 2025 randomized controlled trial reported that daily supplementation with 2000 IU of Vitamin D3 in patients undergoing rehabilitation after an ischemic stroke significantly increased serum 25(OH)D levels and was associated with improved functional outcomes as measured by the Barthel Index.26 A narrative review also suggests that Vitamin D3 possesses neuroprotective, anti-inflammatory, and regenerative properties, and may play a role in ameliorating post-stroke depression and anxiety, although it notes that overall clinical trial results have been mixed.27

Analysis: There is emerging evidence suggesting a potential beneficial role for Vitamin D supplementation in post-stroke recovery and general neuroprotection. The dose of Vitamin D in "Panoxol Plus" (125 mcg, equivalent to 5000 IU) 7 is substantial and aligns with doses used in some research settings for achieving repletion or therapeutic effects. The inclusion of Vitamin D in this variant of Panoxol may be a strategic decision to capitalize on the growing awareness of Vitamin D's broad health benefits. However, it's important to recognize that this creates a distinct formulation from the original Panoxol described in the 2015 PDF.1 Consequently, claims and evidence related to the original formulation may not be directly applicable to the "Plus" version, and vice-versa, due to the presence of this additional high-dose active ingredient.

4.7. Fulvic Acid (Primarily in "Panoxol Plus")

Claimed Mechanism: The specific mechanism or benefit of Fulvic Acid in "Panoxol Plus" is not detailed in the product listing beyond its inclusion as 1mg (from Shilajit Extract 40%).7

Evidence Review:

Research on Fulvic Acid in the context of neurological health is limited and appears preliminary. One in vitro study found that fulvic acid can inhibit the aggregation and promote the disassembly of tau protein fibrils, which are associated with Alzheimer's disease.28 A general review on neuroprotective drugs for stroke did not specifically mention fulvic acid.29

Analysis: The current scientific evidence for Fulvic Acid, particularly concerning direct benefits for stroke prevention or recovery, is very sparse. The existing research primarily focuses on mechanisms related to Alzheimer's disease pathology (tauopathy), which differs from the primary pathophysiology of most strokes. The dosage of Fulvic Acid in "Panoxol Plus" (1mg) is also relatively small. Its inclusion may be more speculative, potentially aiming to add a novel ingredient with general antioxidant or neuroprotective connotations often associated with Shilajit, rather than being based on robust evidence for efficacy in cerebrovascular conditions. Its contribution to the overall claimed effects of Panoxol Plus for stroke-related concerns is highly uncertain based on the available information.

Table 2: Summary of Scientific Evidence for Individual Ingredients in Relation to Stroke

5. Clinical Evidence for Panoxol/Vasonoxol as a Formulation

5.1. Analysis of Studies on the Combined Panoxol/Vasonoxol Product

The primary piece of clinical data presented for the specific Panoxol/Vasonoxol formulation is a "90-day clinical experience study" conducted in July 2016. This study involved 150 patients, aged 65 to 85 years, and reportedly demonstrated a significant reduction in both systolic blood pressure (from an average of 131 mmHg to 124 mmHg, a 5% reduction) and diastolic blood pressure (from an average of 66 mmHg to 55 mmHg, a 20% reduction).2 Lowering blood pressure is clinically relevant because hypertension is a well-established and modifiable risk factor for stroke.1

However, the description "clinical experience study" 2 suggests that this investigation may have been observational or lacked the rigorous controls of a randomized clinical trial (RCT), such as a placebo group or blinding. An open-label study design, as mentioned in the context of a different nitric oxide supplement ("Vascanox HP" 30), is susceptible to various biases, including the placebo effect and regression to the mean, which can influence the perceived outcomes. The full methodology, peer-review status, and publication details of this 2016 study on Vasonoxol are not provided in the available documentation, making a thorough assessment of its validity and reliability challenging. While the reported blood pressure reductions are noted, particularly the substantial 20% decrease in diastolic pressure, the strength of this evidence as direct proof of Vasonoxol's efficacy for complex outcomes like stroke prevention or recovery is limited due to the potential methodological shortcomings and lack of detailed reporting.

5.2. Assessment of Evidence Supporting Synergistic Effects for Stroke

As previously discussed (Section 3.3), the Panoxol promotional material claims that its ingredients act synergistically.1 However, no specific studies are provided in the available information that directly test or substantiate this claim for the Panoxol/Vasonoxol combination, particularly in the context of stroke prevention or recovery. Proving pharmacological synergy requires specific experimental designs that compare the effect of the combination against the effects of its individual components and placebo. In the absence of such dedicated research for this formulation, the assertion of synergy remains theoretical and unconfirmed for stroke-related endpoints. This lack of dedicated synergy studies is not uncommon in the dietary supplement industry, as such research can be complex and costly. Often, synergy is inferred from the multiple plausible mechanisms of individual ingredients rather than demonstrated through direct comparative testing of the final formulation.

5.3. Other Clinical Trials or Research

A review of the provided information did not identify any other clinical trials specifically evaluating the Panoxol or Vasonoxol formulation for stroke prevention or recovery. While several snippets discuss clinical trials related to stroke or vascular health (e.g., studies on an herbal prescription "HH333" 31, Prourokinase 33, or a different supplement named "Vascanox HP" 30), these are not studies of Panoxol/Vasonoxol. It is important to distinguish research on unrelated products or general stroke therapies from evidence pertaining directly to the supplement in question.

Notably, a 2018 SEC filing for Solei Systems, Inc. (the parent company of Clinical & Herbal Innovations, Inc.) mentioned future plans to "Continue R&D and begin clinical trials to prove the supplement's proprietary and synergistic benefits".2 This forward-looking statement implicitly acknowledges that, as of 2018, robust clinical trial data proving such benefits for Panoxol/Vasonoxol were not yet available or completed. The current documentation does not provide updates on the outcomes of any such subsequently initiated trials for this specific formulation in the context of stroke.

6. Safety, Tolerability, and Regulatory Status

6.1. Reported Safety Information and FDA Disclaimers for Panoxol/Vasonoxol

Marketing materials for Panoxol/Vasonoxol include standard disclaimers typical for dietary supplements sold in the United States. For instance, an Amazon product page for "Panoxol Plus" clearly states: "Statements regarding dietary supplements have not been evaluated by the FDA and are not intended to diagnose, treat, cure, or prevent any disease or health condition".7 The same page advises consumers to consult a physician before use if they are taking any prescription or over-the-counter medication or if they have any pre-existing medical condition. It also states the product is not intended for pregnant or lactating women.7 Similarly, the FAQ section on the Vasonoxol website advises consultation with a physician before starting the supplement, especially if on medication.8

These disclaimers are mandated by the FDA and underscore the regulatory status of dietary supplements, which are not subjected to the same pre-market approval process for safety and efficacy as pharmaceutical drugs. The presence of these disclaimers, particularly the clause about not being intended to "diagnose, treat, cure, or prevent any disease," stands in contrast to the strong therapeutic claims made in the 2015 Panoxol PDF, which asserted the product could "assist in the prevention as well as recovery from stroke".1 This highlights the careful navigation required by supplement manufacturers to comply with FDA regulations that prohibit making explicit or implicit disease treatment or prevention claims for products not approved as drugs.

6.2. Specific Safety Considerations for Key Ingredients

Beyond general disclaimers, the safety profile of Panoxol/Vasonoxol must also be considered in light of the known risks associated with its individual ingredients.

• Red Yeast Rice (Monacolin K): This ingredient presents the most significant safety concerns.

• Monacolin K Effects: As monacolin K is chemically identical to lovastatin, RYR can cause statin-like adverse effects, primarily affecting the musculoskeletal system (e.g., myalgia, myopathy, rhabdomyolysis) and the liver (e.g., elevated liver enzymes, hepatitis).4 The European Food Safety Authority (EFSA) has expressed serious concerns, stating that adverse effects have been reported even at monacolin K intakes as low as 3 mg/day, and EFSA has been unable to identify a safe daily intake level.4

• Citrinin Contamination: RYR is prone to contamination with citrinin, a mycotoxin that is nephrotoxic (damaging to the kidneys).5 Studies have shown that many commercial RYR supplements contain citrinin, sometimes at levels exceeding regulatory limits, even in products falsely labeled as "citrinin free".6 The European Union has progressively tightened limits for citrinin in RYR supplements.6

• Variability: The monacolin K content in RYR products can be highly variable and often inaccurately labeled.5 This makes it difficult for consumers and healthcare providers to assess the potential for efficacy and risk.

• Regulatory Status: In the U.S., the FDA considers RYR products that have been enhanced with or contain added lovastatin to be unapproved new drugs and thus illegal to market as dietary supplements.5

• The Panoxol/Vasonoxol patent mentions RYR with "<0.4% active ingredient" 3, and the Panoxol Plus product lists 300mg of RYR powder.7 However, specific monacolin K dosage per serving and comprehensive citrinin testing data for the RYR used in Vasonoxol are not provided in the available product information 8, which is a critical omission given the well-documented risks.

• Ginkgo Biloba: Ginkgo biloba extracts may increase the risk of bleeding, particularly when used concurrently with anticoagulant or antiplatelet medications (e.g., warfarin, aspirin), which are commonly prescribed to stroke patients or those at high risk of stroke.18 Adverse events reported in some trials include bleeding.18

• Horse Chestnut Seed Extract: While standardized extracts are generally considered safe for short-term use, unprocessed horse chestnut seeds are poisonous.17 Theoretical concerns with extracts include an increased risk of bleeding and potential effects on blood sugar levels. Commonly reported side effects are usually mild and infrequent, such as gastrointestinal complaints, dizziness, headache, and itching.17

• Cayenne Pepper (Capsaicin): In culinary amounts, cayenne is generally recognized as safe. However, concentrated extracts or high doses in supplement form can cause gastrointestinal irritation, burning sensations, or discomfort in susceptible individuals.

• L-Arginine and L-Citrulline: These amino acids are generally well-tolerated. Potential side effects, particularly at higher doses, can include gastrointestinal issues such as nausea, abdominal pain, bloating, and diarrhea.

The significant safety concerns surrounding Red Yeast Rice, particularly the potential for statin-like adverse effects from monacolin K and the risk of citrinin contamination, place a substantial onus on the manufacturer, Clinical & Herbal Innovations, Inc., to provide transparent and verifiable data demonstrating the safety and quality of the RYR ingredient used in Vasonoxol. General claims of an "all-natural" 36 or "Safe, US-Patented Formula" 8 are insufficient when an ingredient has known potential toxins and drug-like pharmacological activity. The absence of explicit information on the Vasonoxol website 8 or other product materials regarding precise monacolin K levels per dose and rigorous citrinin testing results is a critical deficiency in light of these widely publicized risks.

6.3. Regulatory Landscape

Dietary supplements in the United States are regulated by the FDA under the Dietary Supplement Health and Education Act of 1994 (DSHEA). Unlike pharmaceutical drugs, supplements do not require FDA approval for safety and efficacy before they are marketed. The manufacturer is responsible for ensuring that their product is safe and that any claims made are truthful, not misleading, and substantiated. The FDA's role is primarily post-market surveillance, taking action against adulterated or misbranded products after they reach the market. As noted, the FDA considers RYR products with enhanced or added lovastatin to be unapproved new drugs.5

The regulatory approach to certain ingredients, like RYR, can differ significantly between jurisdictions. For example, while RYR supplements are widely available in the U.S. (subject to the caveat about added lovastatin), the European Union, through EFSA, has issued much stronger warnings regarding the safety of monacolins from RYR and has established stricter limits on contaminants like citrinin.4 This divergence can create confusion for consumers and underscores that the legality of sale in one region does not necessarily equate to a universal consensus on safety or risk-benefit assessment.

Table 3: Potential Safety Concerns and Contraindications for Panoxol/Vasonoxol and its Key Ingredients

7. Critical Analysis: Evaluating the Claims for Stroke Prevention and Recovery

7.1. Strength of Evidence for Product-Specific Claims vs. Individual Ingredient Data

The central claim derived from the 2015 Panoxol PDF is that the supplement "can be expected to assist in the prevention as well as recovery from stroke".1 This is a direct and significant therapeutic assertion. When evaluating this claim, it is crucial to distinguish between evidence supporting the effects of individual ingredients and evidence supporting the specific Panoxol/Vasonoxol formulation itself.

The primary evidence for the formulation consists of the 90-day "clinical experience study" which reported reductions in blood pressure.2 While managing hypertension is a key strategy in stroke prevention, this study did not directly assess stroke incidence, recurrence, or functional recovery as outcomes. Furthermore, the methodological details and peer-review status of this study are unclear, limiting its weight.

The evidence for the individual ingredients is varied:

• Ginkgo biloba (specifically injectable terpene lactones as an adjunct) has shown promise in improving clinical efficacy in ischemic stroke patients in a recent meta-analysis.19

• Red Yeast Rice has demonstrated cholesterol-lowering efficacy, and one large Chinese study indicated a reduction in stroke risk in a specific high-risk population.22 However, these benefits are significantly tempered by major safety concerns.4

• Capsaicin (from Cayenne) has extensive preclinical (experimental) data suggesting various neuroprotective and vasoprotective mechanisms 20, but human clinical trial evidence for stroke outcomes is lacking in the provided materials.

• L-arginine and L-citrulline have a biochemical rationale for improving NO production, with some clinical data in specific conditions (MELAS for L-arginine 12, ICU patients for L-citrulline 15), but direct evidence for common stroke prevention/recovery is limited.

• Horse Chestnut Seed Extract has strong evidence for chronic venous insufficiency 16, but its link to stroke relies on general mechanisms and a single mouse model cited in the PDF.1

• Vitamin D (in Panoxol Plus) has emerging evidence for supporting post-stroke functional recovery.26

• Fulvic Acid (in Panoxol Plus) has very preliminary in vitro data related to Alzheimer's pathology.28

A critical consideration is the dosage of ingredients in the marketed Panoxol/Vasonoxol product compared to dosages used in the cited scientific studies. As highlighted, the "Panoxol Plus" formulation 7 contains different, often lower, amounts of several key ingredients compared to the "preferred embodiment" described in the patent.3 The efficacy of many nutraceuticals is dose-dependent.

Overall, a significant gap exists. The transition from (1) individual ingredients having some plausible mechanisms or effects (often preclinical, in different populations, or at different doses) to (2) the specific Panoxol/Vasonoxol oral formulation directly preventing stroke or aiding recovery in humans, is not adequately supported by the provided evidence. The claim of synergy 1 also remains unproven for stroke outcomes. The argument that a combination of ingredients, each with some beneficial vascular property, will necessarily translate into a clinically meaningful impact on a complex outcome like stroke requires direct empirical validation for the specific formulation.

7.2. Addressing Gaps in Research

The most prominent research gap is the absence of high-quality, peer-reviewed, randomized controlled trials (RCTs) specifically designed to evaluate the Panoxol/Vasonoxol formulation (in its marketed form and dosage) for its effects on primary stroke outcomes. Such outcomes would include stroke incidence (prevention), stroke recurrence, and measures of functional recovery or neurological improvement after a stroke event in relevant human populations.

Other notable gaps in the research include:

• Bioavailability Data: Lack of published studies on the bioavailability of the active compounds from the specific Panoxol/Vasonoxol matrix when taken orally. The absorption and metabolism of ingredients can be affected by the overall formulation.

• Red Yeast Rice Standardization and Safety: Critical uncertainty persists regarding the precise, standardized amount of monacolin K delivered per dose of Vasonoxol and, crucially, verified data confirming that the Red Yeast Rice used is consistently tested and free from unsafe levels of citrinin.

• Long-Term Safety Data: Limited information on the long-term safety and tolerability of the combined Panoxol/Vasonoxol formulation, especially considering the chronic use implied by prevention claims.

• Synergy Validation: No specific studies are presented that scientifically validate the claim of "synergistic effect" for stroke-related outcomes.

• Comparative Efficacy: No studies comparing Panoxol/Vasonoxol to standard medical therapies for stroke prevention or recovery.

The SEC filing from Solei Systems, Inc. in 2018, which mentioned plans to "begin clinical trials to prove the supplement's proprietary and synergistic benefits" 2, implicitly acknowledged the existence of these evidence gaps at that time. Whether such trials have since been conducted and published with positive results for stroke-related endpoints is not evident from the provided information.

8. Conclusion and Expert Recommendations

8.1. Summary of Findings on Panoxol/Vasonoxol in the Context of Stroke

Panoxol, now Vasonoxol, is a multi-ingredient dietary supplement marketed with a focus on vascular health, underpinned by the premise of enhancing nitric oxide production and improving endothelial function. Earlier promotional materials made direct claims regarding its utility in stroke prevention and recovery.1

An analysis of its components reveals that while individual ingredients like Ginkgo biloba (specific injectable forms), Red Yeast Rice (for cholesterol, with one study showing stroke risk reduction), capsaicin (preclinically), L-arginine/L-citrulline, and Vitamin D (in the "Plus" version) have some scientific rationale or supporting evidence for cardiovascular or neuroprotective effects, the Panoxol/Vasonoxol formulation as a whole lacks direct, robust clinical trial evidence demonstrating efficacy in preventing stroke or improving recovery from stroke in human populations. The one clinical study cited for the formulation focused on blood pressure reduction, which is a risk factor for stroke but not a direct measure of stroke outcome.2

Significant safety concerns, primarily associated with the Red Yeast Rice component, must be highlighted. These include the potential for statin-like adverse effects due to monacolin K and the risk of contamination with the nephrotoxin citrinin.4 The manufacturer's transparency regarding the precise monacolin K content per dose and rigorous citrinin testing for the RYR used in Vasonoxol is insufficient based on available public information.

There is also a noticeable discrepancy between the strong, specific stroke-related claims in historical documents 1 and the more general vascular health claims and standard FDA disclaimers found in current marketing materials.7 This likely reflects adaptation to regulatory requirements for dietary supplements.

8.2. Recommendations for Individuals Considering the Supplement for Stroke-Related Concerns

1. Prioritize Medical Consultation: Individuals concerned about stroke prevention, or those recovering from a stroke, should consult qualified healthcare professionals (e.g., neurologists, cardiologists, primary care physicians) for evidence-based medical advice, diagnosis, and treatment. Stroke is a serious medical condition that requires interventions with proven efficacy and safety.

2. Not a Substitute for Proven Therapies: Panoxol/Vasonoxol should not be considered a replacement for prescribed medications (e.g., antihypertensives, statins, antiplatelet agents) or established stroke prevention and management strategies. These strategies include managing risk factors like hypertension, diabetes, and hyperlipidemia with proven therapies, alongside lifestyle modifications such as a healthy diet, regular exercise, and smoking cessation.

3. Informed and Cautious Decision-Making: If an individual is considering using Panoxol/Vasonoxol, this decision should be made in close consultation with their physician. This discussion should include an awareness of the lack of direct clinical evidence for the product's efficacy in stroke, the potential safety issues (particularly concerning Red Yeast Rice), and possible interactions with other medications (e.g., Ginkgo biloba with anticoagulants).

4. Seek Manufacturer Transparency: Consumers and healthcare providers should actively seek detailed information from the manufacturer regarding the Vasonoxol formulation. Specifically, this includes verifiable data on the standardized monacolin K content per dose in the Red Yeast Rice component and independent third-party certification of rigorous testing for citrinin to ensure levels are below established safety thresholds. Information on any completed or ongoing clinical research supporting their specific health claims would also be pertinent.

8.3. Directions for Future Research

• For the Manufacturer (Clinical & Herbal Innovations, Inc. / Solei Systems, Inc.):

• To substantiate the claims related to stroke prevention and recovery, the manufacturer should invest in conducting and publishing high-quality, double-blind, placebo-controlled randomized clinical trials (RCTs) on the final, marketed Vasonoxol formulation. These trials should assess clinically relevant stroke outcomes (e.g., incidence, recurrence, validated neurological and functional recovery scales) in well-defined patient populations.

• Publicly provide detailed quality control specifications and certificates of analysis for their Red Yeast Rice ingredient, specifically detailing the standardized monacolin K content and comprehensive testing results for citrinin from accredited laboratories.

• If the claim of synergistic effects is to be maintained, conduct and publish studies specifically designed to investigate and validate such synergy for relevant physiological or clinical endpoints.

• For the Broader Scientific Community:

• Continued independent research is needed to better understand the precise roles, optimal dosages, and long-term safety of the individual botanical and nutritional components of such multi-ingredient supplements, particularly in the context of cerebrovascular health and disease.

• Further investigation into the potential interactions between these components and commonly prescribed medications for cardiovascular and neurological conditions is warranted.

• Development of standardized methodologies for assessing the efficacy and safety of complex herbal mixtures in clinical trials remains an important area.

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