Main Research Findings

1) Stimulation therapy with vitamin C improves rehabilitation, immune system functioning, and nutritional status in patients who have had a stroke.

2) Supplementation with vitamin C during cardiac surgery decreases oxidative stress and improves erythrocyte deformability during cardiopulmonary bypass.

 

Selected Data

1) This study conducted by the research team of Wang et al aimed to evaluate the effectiveness of vitamin C stimulation in improving swallowing function, nutritional status, and immune function in stroke patients with dysphagia. The study involved 120 stroke patients diagnosed with dysphagia; these patients were randomly divided into two equal groups: a control group and a vitamin C stimulation group, with 60 patients in each. All participants completed the designated training regimen, and no statistically significant differences were found in the general baseline characteristics between the two groups, indicating successful randomization [1].

Patients were included in the study if they met the following criteria: they were diagnosed with stroke using imaging tools such as CT or MRI in accordance with the diagnostic criteria established by the national cerebrovascular disease academic conference; were confirmed to have swallowing dysfunction via the water swallow test or swallowing imaging studies; had experienced their first cerebral hemisphere stroke with disease duration under three months; had normal cognitive function and no history of mental illness; had stable vital signs and no severe organ dysfunction or pacemaker implantation; had water swallow test levels rated between 3 and 5; and had provided informed consent. Exclusion criteria included unstable vital signs, severe cognitive, visual, or auditory impairments, history of psychiatric illness, severe complications such as lung infection, myocardial infarction, gastrointestinal ulcers, or non-stroke-related dysphagia.

The control group received standard swallowing rehabilitation therapy. This therapy included a variety of approaches aimed at enhancing the strength and coordination of the oral and facial muscles responsible for swallowing. Training involved sensory and muscle strength stimulation targeting the lips, tongue, jaw, and soft palate. Indirect swallowing therapy involved using frozen wet cotton swabs to stimulate the soft palate and posterior pharyngeal wall, thus promoting the pharyngeal reflex. Additional techniques, such as glottal closure training through vocalization exercises, and ingestion practice using different swallowing postures including but not limited to empty swallowing, turning head swallowing, and nodding swallowing, were also employed. Patients were guided to chew and swallow carefully, ensuring the previous bite had been fully swallowed before the next. Foods of uniform density and appropriate viscosity were selected to minimize residue. This rehabilitation was performed once daily for 30 minutes over a two-week period by trained therapists who were blinded to group allocation [1].

The Vitamin C group received the same standard rehabilitation training, augmented with vitamin C stimulation. In this group, vitamin C delivered via 0.1 g tablet was applied to both sides of the tongue using a cotton swab twice daily. Patients were guided to perform a variety of swallowing actions including but not limited to empty, sideways, alternating, and nodding swallowing. Additional exercises included tongue massage and chewing muscle stimulation using the patients’ cleaned fingers dipped in vitamin C powder. These sessions were conducted five to six times per training period, lasting about 15 minutes each, over a two-week period. The added vitamin C was intended to stimulate the oral and orofacial muscles and enhance sensory feedback, thereby improving swallowing function [1].

To assess clinical efficacy, several evaluations were used. The water swallow test was conducted with patients consuming warm water at a temperature of 37–40°C under standardized conditions. Water swallow test results were categorized into five levels, from level I: normal swallowing without interruption or coughing; to level V: inability to drink due to frequent coughing. Treatment outcomes were rated as follows: “recovery” defined as reaching level I and resolving dysphagia, “effectual” defined as improving by at least two water swallow test levels but not reaching level I, “effective” defined as improvement by one water swallow test level, and “ineffective” defined as no change in water swallow test score.

Another major assessment tool used was the Video Fluoroscopic Swallowing Study Under X-ray fluoroscopy, patients were asked to consume foods of different consistencies and quantities including: 2 ml nectar-like, 5 ml honey-like, and 10 ml pudding-like. Their swallowing was observed from frontal and lateral views. Video Fluoroscopic Swallowing Study scores ranged up to 10 points and were calculated based on three components: the oral stage, the pharyngeal stage, and aspiration. The oral stage was scored from 0 to 3, depending on the patient’s ability to form and move a food bolus. The pharyngeal stage was scored from 0 to 3, evaluating reflexes and residue after swallowing. The aspiration score ranged from 0 to 4, with higher scores reflecting better control and absence of aspiration [1].

In addition to swallowing assessments, the study also evaluated the patients’ nutritional status using several markers such as body mass index, serum albumin, total serum protein, and hemoglobin. Body mass index was calculated by dividing weight by height squared, with a normal range defined as 18.5–23.9. Blood samples were collected under fasting conditions before and after the intervention to measure the biochemical indicators using standard laboratory procedures [1].

2) The study conducted by the research team of Tai et al recruited patients who underwent cardiac surgery requiring hypothermic cardiopulmonary bypass. Several exclusion criteria were applied to ensure patient safety and data consistency. Patients under 20 years old, those currently using digitalis, with a history of hyperuricemia, advanced chronic kidney disease defined by an estimated glomerular filtration rate of <30 mL/min, red blood cell disorders such as glucose-6-phosphate dehydrogenase deficiency or thalassemia, or those with a preoperative left ventricular ejection fraction less than 30% were excluded from the study [2].

Standard intraoperative monitoring was applied to all patients. This included five-lead continuous electrocardiogram, peripheral pulse oximetry, capnography, direct arterial blood pressure measurement, and pulmonary artery catheterization for cardiac output monitoring using a Swan-Ganz thermodilution catheter. Anesthesia induction was achieved with 1–2.5 μg/kg fentanyl and 1–2.5 mg/.kg propofol. 0.8–1.0 Rocuronium mg/kg was administered to facilitate tracheal intubation. Anesthesia was maintained with sevoflurane at 1–3 vol% in oxygen, adjusting the fraction of inspired oxygen between 0.5 and 1.0 to maintain adequate oxygenation [2].

Volume status was closely monitored using stroke volume variation derived from arterial pressure waveform analysis through the FloTrac/Vigileo system. When stroke volume variation exceeded 15%, fluid therapy with 150 mL of lactated Ringer’s or 0.9% sodium chloride solution was administered to optimize preload. Red blood cell transfusion was considered if hemoglobin levels dropped below 8.0 g/dL. To support cardiac function, intravenous epinephrine infusion of 2–10 μg/min was initiated if the cardiac index fell below 2.5 L·min/m2.

Key hemodynamic parameters including heart rate, systemic and pulmonary blood pressures, cardiac index, systemic vascular resistance, pulmonary vascular resistance, and central mixed venous oxygen saturation, were recorded at two critical time points: 15 minutes after anesthesia induction and 15 minutes after weaning from cardiopulmonary bypass. Additionally, peripheral microcirculation was assessed by measuring skin blood flow on the palmar surface using a laser Doppler flowmeter [2].

Cardiopulmonary bypass was performed using HL-30 roller pumps and Affinity NT oxygenators. The pump flow rate was adjusted to deliver 2.2 L/min/square meter of body surface area, with a reduction to 0.5 L/min during aortic clamping and unclamping phases. The core temperature was maintained between 32 and 34°C to induce hypothermia during bypass. Cardioplegia, using 15–29°C Custodiol HTK solution, was administered either antegrade or retrograde depending on the clinical case. Weaning from cardiopulmonary bypass was initiated only after the patient’s systemic temperature rose above 36°C.

The treatment protocol involved intravenous infusion of Vitamin C at 20 mg/kg administered within 10 minutes during the rewarming phase of cardiopulmonary bypass. The control group received an equivalent volume of 0.9% sodium chloride solution as a placebo. The primary outcome focused on erythrocyte deformability, which was assessed by measuring the tyrosine phosphorylation level of nonmuscle myosin IIA in the erythrocyte membrane. Nonmuscle myosin IIA phosphorylation is closely related to the flexibility and deformability of red blood cells, which is critical for their passage through the microcirculation [2].

Secondary outcomes included the measurement of plasma reactive oxygen species levels before and after cardiopulmonary bypass to assess oxidative stress. To further explore the molecular mechanisms underpinning changes in erythrocyte deformability following Vitamin C administration, the study also evaluated phosphorylation levels of key signaling proteins in erythrocyte membranes: vasodilator-stimulated phosphoprotein, focal adhesion kinase, and endothelial nitric oxide synthase [2].

Data on patient demographics, comorbidities, preoperative medications, left ventricular ejection fraction, and estimated glomerular filtration rate were retrieved from the hospital’s electronic medical records. The European System for Cardiac Operative Risk Evaluation II was used to assess surgical risk. Surgical and anesthetic variables such as type of surgery, anesthesia duration, bypass duration, aortic clamp time, intraoperative fluid management, use of vasoactive agents, blood loss, and blood transfusions were also collected to control for potential confounders.

Peripheral blood samples were taken 15 minutes after anesthesia induction and 15 minutes after cardiopulmonary bypass discontinuation to measure plasma reactive oxygen species levels using a commercial DCF ROS/RNS Assay Kit. After centrifugation, the plasma supernatant was incubated with reagents to produce a fluorescent signal proportional to reactive oxygen species concentration. Fluorescence was quantified with a microplate reader at an excitation wavelength of 480 nm and emission at 530 nm [2].

Erythrocyte membranes were isolated and subjected to immunoprecipitation and Western blot analyses to quantify phosphorylation levels of nonmuscle myosin IIA and other proteins of interest. Antibodies specific to nonmuscle myosin IIA, phosphorylated tyrosine residues, phosphorylated and total vasodilator-stimulated phosphoprotein, focal adhesion kinase, and endothelial nitric oxide synthase were used [2].

 

Discussion

1) The research team of Wang et al conducted a study investigating the effects of vitamin C stimulation on stroke patients suffering from dysphagia. The study involved 120 participants, evenly split into a control group and a vitamin C stimulation group, and compared several key health parameters before and after a two-week intervention period.

At the beginning of the experiment, the researchers evaluated the baseline characteristics of participants, including gender, age, educational level, smoking status, presence of diabetes, and initial Water Swallow Test grade. These characteristics were comparable between the two groups, ensuring the validity of subsequent comparisons. The primary goal was to assess whether vitamin C stimulation, when added to conventional swallowing rehabilitation training, would yield additional benefits in the recovery of swallowing function, nutritional status, and immune health [1].

Swallowing function was assessed using two key measures: the water swallow test and the Video Fluoroscopic Swallowing Study. Both assessment tools demonstrated significant improvements in swallowing ability in both groups following the two-week intervention. However, improvements were more pronounced in the vitamin C group. In terms of water swallow test levels, both groups showed reductions, indicating better swallowing performance, but the decrease in water swall test level was greater in the vitamin C group. This suggests that vitamin C stimulation led to more significant restoration of swallowing function [1].

Similarly, the Video Fluoroscopic Swallowing Study scores, which reflect the physiological effectiveness and safety of swallowing as observed through X-ray imaging, also improved in both groups. The baseline Video Fluoroscopic Swallowing Study scores were similar for both groups. After the intervention, the control group’s average Video Fluoroscopic Swallowing Study score rose to 7.17 ± 1.59, while the vitamin C group improved more significantly, reaching an average of 8.08 ± 1.52. These data indicate that vitamin C stimulation enhanced the motor coordination and muscle function involved in swallowing to a greater extent than routine therapy alone.

Further analysis categorized the clinical efficacy of treatments into four outcomes based on water swallow test improvements: recovery defined as complete resolution of dysphagia, effectual defined as improvement by two water swallow test levels, effective defined as by improvement by one level, and ineffective defined as by no improvement. Results showed that the vitamin C group had a higher percentage of patients classified as recovered or effectual, while the proportions of effective and ineffective outcomes were lower compared to the control group [1].

Specifically, the recovery rate in the vitamin C group increased from 8.3% to 16.7%, and the rate of effectual improvement increased from 10% to 28.3%. Conversely, the rates for effective and ineffective outcomes decreased from 48.4% to 33.3% and from 33.3% to 21.7%, respectively. These findings confirm that while both interventions were beneficial, vitamin C stimulation led to a more substantial improvement in swallowing function. Importantly, the study found there was no significant difference in treatment efficacy between patients with ischemic and hemorrhagic strokes, suggesting that vitamin C stimulation could be effective across different types of stroke pathology [1].

Beyond swallowing function, the researchers examined the Nourishment State Index, which included several nutritional markers such as body mass index, serum hemoglobin, serum albumin, and serum total protein. Improvements in all these parameters were observed in both groups after treatment, reflecting general improvements in patients’ nutritional health. However, the vitamin C group demonstrated greater gains in each measure. For instance, body mass index increased more substantially in the vitamin C group, indicating better weight and nutritional restoration. Hemoglobin levels, which reflect oxygen-carrying capacity and overall nutritional status, also rose more significantly in this group. Similarly, improvements in serum albumin and total protein levels suggest enhanced protein synthesis and metabolic recovery, which are essential for tissue repair and immune function.

The researchers then turned their attention to immune function indices, including serum immunoglobulin levels, IgA, IgM, and IgG. These immunoglobulins are key components of the body’s immune defense system. Following the intervention, both groups showed elevated levels of all three immunoglobulins, indicating improved immune responses. Yet again, the improvements were more significant in the vitamin C group, implying that vitamin C stimulation not only facilitated physical rehabilitation but also enhanced systemic immunity. These results are consistent with the known antioxidant and immunomodulatory effects of vitamin C, which can support immune cell activity and reduce oxidative stress after a stroke [1].

2) The research team of Tai et al presents the results of a clinical study comparing the effects of Vitamin C supplementation versus placebo during cardiac surgery involving hypothermic cardiopulmonary bypass. The study analyzed baseline patient characteristics, intraoperative parameters, hemodynamic and biochemical data, oxidative stress levels, and phosphorylation states of key proteins in erythrocytes to understand how Vitamin C influences postoperative outcomes at both systemic and molecular levels.

The study included two groups: patients receiving Vitamin C supplementation and a control group receiving placebo. The original report showed that both groups were well-matched in terms of baseline characteristics. There were no significant differences in demographics or types of cardiac surgery performed between the groups, ensuring comparability for outcome analysis [2].

Similarly, several intraoperative parameters were comparable across groups. These included anesthesia duration, cardiopulmonary bypass duration, and the duration of aortic clamp cross time, indicating that the surgical and anesthetic conditions were similar. The use of blood transfusions and vasoactive agents was also not significantly different between groups. However, there was a notable trend toward reduced intraoperative blood loss in the Vitamin C group, with a median blood loss of 300 mL compared to 470 mL in the control group. This difference approached but did not reach statistical significance, suggesting a possible beneficial effect of Vitamin C on reducing bleeding during surgery.

Both groups showed similar patterns in systemic and peripheral hemodynamics following cardiopulmonary bypass. After weaning from cardiopulmonary bypass, patients in both groups experienced decreases in systemic blood pressure, systemic vascular resistance, pulmonary vascular resistance, serum hemoglobin levels, and peripheral skin blood flow relative to baseline values measured after anesthesia induction. These changes likely reflect the physiological impact of cardiopulmonary bypass and surgery, including vasodilation, hemodilution, and potential microcirculatory alterations [2].

In contrast, serum glucose and lactate levels increased after cardiopulmonary bypass in both groups, consistent with metabolic stress and potential tissue hypoxia or anaerobic metabolism during and after surgery. A key difference emerged in systemic vascular resistance between groups after cardiopulmonary bypass. The Vitamin C group exhibited a significantly higher systemic vascular resistance compared to the control group, indicating improved systemic vascular tone with Vitamin C supplementation. No differences were found in other parameters such as pulmonary vascular resistance, skin blood flow, serum lactate, or central mixed venous oxygen saturation after cardiopulmonary bypass between the groups [2].

The study evaluated oxidative stress by measuring plasma reactive oxygen species levels before and after cardiopulmonary bypass. Both groups exhibited increases in plasma reactive oxygen species after cardiopulmonary bypass, reflecting the known oxidative stress associated with cardiopulmonary bypass and cardiac surgery. However, the increase in reactive oxygen species was significantly attenuated in the Vitamin C group, which had a mean fold increase of 1.661 ± 0.801, compared to a higher increase of 2.743 ± 1.802 in the control group. Despite this, the absolute reactive oxygen species levels measured after cardiopulmonary bypass were not statistically different between groups, indicating that while Vitamin C mitigated the rise in oxidative stress, it did not fully prevent it.

To understand the functional impact of altered oxidative stress, the researchers measured phosphorylation levels of NMIIA in erythrocyte membranes. NMIIA phosphorylation regulates erythrocyte deformability, which is crucial for efficient microcirculation and oxygen delivery. Results demonstrated a significant increase in tyrosine phosphorylation of NMIIA after cardiopulmonary bypass in both groups. In the Vitamin C group, phosphorylation increased 2.159 ± 0.887 fold, while the control group had a smaller but still significant increase of 1.384 ± 0.445 fold. Notably, post-cardiopulmonary bypass NMIIA phosphorylation was significantly higher in the Vitamin C group than in controls, suggesting that Vitamin C enhanced erythrocyte deformability through upregulation of NMIIA phosphorylation [2].

Since NMIIA activity is regulated by intracellular signaling pathways involving structural and regulatory proteins, the study investigated the phosphorylation of vasodilator-stimulated phosphoprotein and focal adhesion kinase, which are key molecules involved in cytoskeletal dynamics and cell adhesion.

Vasodilator-stimulated phosphoprotein phosphorylation at Ser239 did not change significantly after cardiopulmonary bypass in the Vitamin C group, indicating stable activation. However, in the control group, vasodilator-stimulated phosphoprotein phosphorylation decreased significantly to 0.737 ± 0.166 fold after cardiopulmonary bypass, suggesting impaired signaling. Correspondingly, vasodilator-stimulated phosphoprotein phosphorylation after cardiopulmonary bypass was significantly higher in the Vitamin C group compared to controls [2].

Focal adhesion kinase phosphorylation at Tyr397 increased significantly in the Vitamin C group following cardiopulmonary bypass but not in the control group. Post-cardiopulmonary bypass focal adhesion kinase phosphorylation was also significantly higher in the Vitamin C group relative to controls. These results imply that Vitamin C supplementation preserves or enhanced signaling pathways that regulate erythrocyte membrane structure and function.

The study also measured phosphorylation of endothelial nitric oxide synthase, a key enzyme in nitric oxide production, which is vital for vascular tone regulation and microcirculatory function. After cardiopulmonary bypass, endothelial nitric oxide synthase phosphorylation significantly increased in the Vitamin C group but not in the control group. Furthermore, post-cardiopulmonary bypass endothelial nitric oxide synthase phosphorylation levels were significantly higher in the Vitamin C group compared to controls. This suggests that Vitamin C may improve nitric oxide signaling within erythrocytes, potentially contributing to better vascular function after cardiopulmonary bypass [2].

 

Disclaimer

**LAB USE ONLY**
*This information is for educational purposes only and does not constitute medical advice. THE PRODUCTS DESCRIBED HEREIN ARE FOR RESEARCH USE ONLY. All clinical research must be conducted with oversight from the appropriate Institutional Review Board (IRB). All preclinical research must be conducted with oversight from the appropriate Institutional Animal Care and Use Committee (IACUC) following the guidelines of the Animal Welfare Act (AWA).

Citations

[1] Wang J, Chang E, Jiang Y. Effects of vitamin C stimulation on rehabilitation of dysphagia after stroke: a randomized trial. Eur J Phys Rehabil Med. 2022;58(4):558-564. doi:10.23736/S1973-9087.22.07337-3

[2] Tai YH, Wu HL, Chu YH, et al. Vitamin C supplementation attenuates oxidative stress and improves erythrocyte deformability in cardiac surgery with cardiopulmonary bypass. Chin J Physiol. 2022;65(5):241-249. doi:10.4103/0304-4920.358234

 

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