Figure - uploaded by Harri Hemilä
Content may be subject to copyright.
![The association between vitamin C effect and baseline histamine PC20 level on the common-cold-day. Baseline PC20 level indicates the histamine PC20 level before vitamin C administration on the common-cold day in the Bucca et al. study
[25,26]. Adjusted vitamin C effect indicates that the vitamin C effect of the second day (after recovery at 6 wk) is subtracted from the vitamin C effect on the common-cold-day. For example, participant #9 had a 7.45-fold increase in PC20 level on the common-cold-day and a 1.88-fold increase in PC20 level on the second day. This gives an adjusted vitamin C effect of 3.96 (7.45/1.88). Adding the baseline histamine PC20 level to the null model increased the model fit by χ2(1 df) = 6.2, P = .013. The horizontal dash (−) line indicates the level of vitamin C effect after recovery. The numbers indicate the identification numbers used in Additional file 2. See the Additional file 3 for the calculations of the linear model.](profile/Harri-Hemilae-2/publication/258953438/figure/fig1/AS:216455204347908@1428618350352/The-association-between-vitamin-C-effect-and-baseline-histamine-PC20-level-on-the.png)
The association between vitamin C effect and baseline histamine PC20 level on the common-cold-day. Baseline PC20 level indicates the histamine PC20 level before vitamin C administration on the common-cold day in the Bucca et al. study [25,26]. Adjusted vitamin C effect indicates that the vitamin C effect of the second day (after recovery at 6 wk) is subtracted from the vitamin C effect on the common-cold-day. For example, participant #9 had a 7.45-fold increase in PC20 level on the common-cold-day and a 1.88-fold increase in PC20 level on the second day. This gives an adjusted vitamin C effect of 3.96 (7.45/1.88). Adding the baseline histamine PC20 level to the null model increased the model fit by χ2(1 df) = 6.2, P = .013. The horizontal dash (−) line indicates the level of vitamin C effect after recovery. The numbers indicate the identification numbers used in Additional file 2. See the Additional file 3 for the calculations of the linear model.
Source publication
Asthma exacerbations are often induced by the common cold, which, in turn, can be alleviated by vitamin C.
To investigate whether vitamin C administration influences common cold-induced asthma.
Systematic review and statistical analysis of the identified trials. Medline, Scopus and Cochrane Central were searched for studies that give information on...
Contexts in source publication
Context 1
... a linear model, the adjusted vitamin C effect was significantly explained by the baseline log(PC 20 ) level: χ 2 (1 df ) = 6.2, P = .013 ( Figure 1). See Additional file 3 for the calculations. ...Context 2
... indicates that the effect of vitamin C on bronchial hypersensitivity was different between the two test days separated by 6 weeks. Furthermore, a linear regression analysis revealed that the difference in the vitamin C effect between the two study days depended significantly on the baseline histamine PC 20 level determined on the common- cold-day (Figure 1). If there are factors causing bias in the self-controlled comparison and if the factors are constant on both study days, they would be removed from the calculation of the adjusted vitamin C effect, i.e., the difference in effect between the two study days. ...Context 3
... potential factors include the placebo effect and tachy- phylaxis. The linear regression model indicated there were no differences in the vitamin C effects between the two study days when the baseline histamine PC 20 level was 25 mg/ml on the common-cold-day (Figure 1). However, when the baseline PC 20 level was 2 mg/ml on the common-cold-day, the model predicted that vitamin C administration would increase the histamine PC 20 level 4.7-fold over the corresponding effect after recovery from the cold. ...Context 4
... if there is a constant placebo effect or tachyphylaxis that would cause bias, such effects would be eliminated from the calculation of the adjusted vitamin C effect, i.e., the difference in effects between the two study days. Therefore, the strong association between the adjusted vitamin C effect and the baseline histamine PC 20 level is a further argument against the placebo effect and the tachyphylaxis effect (Figure 1). In conclusion, the placebo effect is not an issue and tachyphylaxis does not explain the 3.2-fold increase in the histamine PC 20 level of common cold patients who were administered vitamin C. ...Context 5
... publication bias cannot explain findings that are not published in the original study reports. Therefore, publication bias cannot explain the association between the PC 20 level on the common-cold day and the adjusted vitamin C effect (Figure 1). This systematic review was done by one person and one person might have a higher error rate in the extraction of data than a group. ...Citations
... There is strong evidence that Vitamin C is also effective for many conditions other than scurvy. In controlled trials, Vitamin C has improved endothelial function [4,5,6], lowered blood pressure [7], increased left ventricular ejection fraction [8,9,10,11,12], decreased the incidence of atrial fibrillation [13,14,15] , protected against contrast-induced acute lung injury [16,17], decreased glucose levels in patients with type 2 Diabetes [18], decreased bronchoconstriction [19] , shortened the duration of colds [20,21,22,23,24,25,26], decreased the incidence of colds in physically stressed people [27,28,29] and it has prevented pain [30,31,32) . There is also evidence that Vitamin C has a beneficial effect on pneumonia [26,33]. ...
Vitamin C is focus of intense interest with respect to its role in treatment of critically ill pat Introduction- ients. It has vast beneficial effects including the attenuation of lipid peroxidation, reduced vascular permeability, preservation of endothelial function and microcirculatory flow. To assess the role of ascorbic acid as an adjunct b Aim- y comparing the three different doses of ascorbic acid in terms of Sequential Organ Failure Assessment (SOFA)Score, acute inflammatory markers- C-reactive protein (CRP), serum lactate levels, Red Cell Distribution width, dose and duration of norepinephrine administration. Total of 233 patients having sepsis admitted to ICU of Rajindra hosp Methods- ital were enrolled in study. Of these, 23 patients died before completing the study duration of 96 hours. Hence, data of 210 patients (70 in each of the three groups) was analyzed using SPSS software and Microsoft excel. Patients received intravenous ascorbic acid 50mg/kg/24hours, 100mg/kg/24 hours, 200 mg/kg/24 hours for 96 hours in group A, group B and group C respectively. there was significant reduction in SOFA scores, CRP levels, red cell distribution wid Results- th, serum lactate levels in all the three groups However, maximum reduction in SOFA scores, CRP levels and red cell distribution width was in group C There was significant reduction in mean dose of noradrenaline in all the three groups and statistically significant difference in mean duration of noradrenaline infusion in all the three groups. We Conclusionconclude that addition of ascorbic acid has improved mean arterial pressure and reduction in dose and duration of noradrenaline in all the three groups indicating early reversal of shock. It also has led to marked reduction in Sofa score, serum lactate levels, CRP and red cell distribution width.
... Four of the reviewed studies showed that vitamin-C supplements significantly contributed to the reduction in asthma severity, number of attacks and asthma admission rate. 7,8,10,13 One reviewed study showed that vitamin C supplementation reduced the dosage of corticosteroids required by steroid dependent asthma patients. 9 Three reviewed studies showed improved PFT with vitamin C supplementation (FEV1 and FEF 25-75) in asthmatics. ...
Objective: To investigate the effect of vitamin C supplementation in decreasing asthma severity, medications, and improving pulmonary function tests (PFTs). Methodology: Search of electronic databases was conducted to identify relevant studies published from January 2010 up to November 2023. A total of 105 records were initially identified. After filtering and screening, just 9 studies met the inclusion criteria; 3 were reviews, while the remaining 6 were original. Of the original studies, one was experimental, performed on 24 male Balb/c mice while the remaining 5 were performed on 969 asthmatic patients. Except for the experimental study, the selected studies were performed in different settings and on different ethnicities at the age of seven years and over. Results: The results showed antioxidant effects of vitamin C in asthmatic patients and experimental models. The studies showed that vitamin-C supplements significantly contributed to the reduction in asthma severity, number of attacks, admission rate, and asthma medications. Also, improvement of PFTs and suppression of asthma phenotype features in asthma mouse models. Only one review showed non-significant improvement in symptoms and PFTs, with significant improvement in malondialdehyde level and superoxide dismutase activity. Conclusion: Vitamin C supplementation to asthmatic patients showed improvements in asthma symptoms and PFTs, decreases the dose of asthma medications through potentiation of their efficacy, and less reactive response in asthma mouse model.
... Given the evidence indicating that vitamin C has a greater effect on the more severe forms of the common cold, it is possible that the vitamin may also have an effect on some of the complications of the common cold. Systematic reviews have indicated that vitamin C may be beneficial for common cold-induced asthma [54] and pneumonia [55,56]. ...
Background
Randomized trials have shown that vitamin C shortens the duration of common colds. Some trials reported greater effects on severe cold symptoms compared with mild symptoms. This review systematically compares the effects of vitamin C on severe and mild common cold symptoms.
Methods
We included all placebo-controlled trials of orally administered vitamin C in doses of at least 1 g/day for the common cold for people in good health at baseline. The analysis was restricted to trials which reported both the total duration of the common cold, and the severity of the common cold measured using severity scales, the duration of more severe stages of the cold, or proxies for severe colds such as days indoors. Findings were pooled using the inverse variance, fixed effect options of the metacont function of the R package meta to calculate the ratio of means estimate.
Results
Fifteen comparisons from 10 trials which reported both mild and severe symptoms were identified. All trials were randomized and double-blind. Compared to placebo, vitamin C significantly decreased the severity of the common cold by 15% (95% CI 9–21%). The direct comparison of the effect of vitamin C on mild and severe symptoms was limited to five comparisons which found that vitamin C had a significant benefit on the duration of severe symptoms. In this subset, there was a significant difference in the size of the effect of vitamin C on the overall duration of colds versus the duration of severe colds (P = 0.002), and vitamin C had no significant effect on the duration of mild symptoms.
Conclusions
The common cold is the leading cause of acute morbidity and a major cause of absenteeism from work and school. However, absenteeism is dependent on the severity of symptoms. The finding that vitamin C may have a greater effect on more severe measures of the common cold is therefore important. Further research on the therapeutic effects of vitamin C on the common cold should measure outcomes of differing levels of severity.
... Cold weather can pose health risks to the pediatric population globally, such as asthma exacerbations, allergic rhinitis, and atopic dermatitis [28]. Moreover, cold weather and reduced sunlight exposure can hinder the cutaneous synthesis of vitamin D in children, potentially leading to vitamin D deficiency [29]. ...
Background
Established associated factors for DDH include female sex, breech presentation, family history, congenital malformations, oligohydramnios, and maternal hyperthyroidism. However, evidence for environmental factors that may contribute to DDH is limited and inconsistent.
Methods
A systematic review of medical literature was conducted to collect data on environmental factors, including latitude, longitude, average yearly precipitation, average yearly temperature, minimum monthly temperature, and maximum monthly temperature, from all institutions that published articles on DDH. Univariate linear regression analysis was used to examine the correlation between environmental factors and DDH incidence, while multiple regression analysis was conducted to identify significant associated factors for DDH incidence.
Results
Data from a total of 93 unique manuscripts were analyzed, revealing a significant negative correlation between DDH incidence and temperature, including average yearly temperature (r = -0.27, p = 0.008), minimum monthly temperature (r = -0.28, p = 0.006), and maximum monthly temperature (r = -0.23, p = 0.029). Additionally, there was a significant positive correlation between DDH incidence and latitude (r = 0.27, p = 0.009), and a significant negative correlation between DDH incidence and average yearly precipitation (r = -0.29, p = 0.004). In the final multiple regression analysis, temperature, including average yearly temperature, minimum monthly temperature, and maximum monthly temperature, were identified as significant associated factors for DDH incidence.
Conclusion
The findings of this study suggest an association between cold weather and DDH incidence. Further research should explore the link between cold weather and DDH incidence, offering insights into potential interventions for cold climates.
... Mast cells play a crucial role in the development and progression of AD and various allergic conditions [17]. Several studies have shown that vitamin C administration can attenuate mast-cell-mediated bronchial hypersensitivity or allergies [22]. Furthermore, in cases of AD caused by house mites, the application of a topical ointment containing a combination of vitamin C and zinc oxide has been observed to decrease the presence of mast cells in the skin of mice that have been exposed to mites [23]. ...
Atopic dermatitis (AD) is a chronic inflammatory disease characterized by dry and itchy skin. Recently, it has been reported that oxidative stress is involved in skin diseases, possibly including AD. Vitamin C, also referred to as ascorbic acid, is a vital water-soluble compound that functions as an essential nutrient. It plays a significant role as both an antioxidant and an additive in various pharmaceutical and food products. Despite the fact that vitamin C is easily oxidized, we have developed NXP081, a single-stranded DNA aptamer that selectively binds to vitamin C, thereby inhibiting its oxidation. The objective of the current research was to examine the impact of NXP081, an animal model of AD induced by 2,4-dinitrofluorobenzene (DNFB). The experimental drug NXP081, when taken orally, showed promising results in reducing inflammation and improving the skin conditions caused by DNFB. The administration of NXP081 resulted in a significant reduction in ear swelling and a noticeable improvement in the appearance of skin lesions. In addition, the administration of NXP081 resulted in a significant decrease in the migration of mast cells in the skin lesions induced by DNFB. Moreover, NXP081 inhibited the production of interferon-gamma (IFN-γ) in CD4+ T cells that were activated and derived from the lymph nodes. Our findings provide useful information about the anti-inflammatory effect of NXP081 on AD.
... As asthmatics have both lower vitamin C levels and intake, the supplementation of this vitamin may ameliorate the course of asthma by lowering the number of asthma attacks (exacerbations), the asthma symptom score, the ICS need [280], and decreasing respiratory symptoms such as sore throat or cough in exercise-and cold-induced asthma after stimulation [37,39]. Nonetheless, such supplementation has to be prolonged, since a short administration of the vitamin has no influence on the above mentioned outcomes [281]. ...
Vitamins play a crucial role in the proper functioning of organisms. Disturbances of their levels, seen as deficiency or excess, enhance the development of various diseases, including those of the cardiovascular, immune, or respiratory systems. The present paper aims to summarize the role of vitamins in one of the most common diseases of the respiratory system, asthma. This narrative review describes the influence of vitamins on asthma and its main symptoms such as bronchial hyperreactivity, airway inflammation, oxidative stress, and airway remodeling, as well as the correlation between vitamin intake and levels and the risk of asthma in both pre- and postnatal life.
... The goal of this paper is to demonstrate the bias against vitamin C by using examples primarily from the trials on vitamin C for infections. Some reviews and studies on vitamin C and respiratory infections [10][11][12][13][14][15] have been flawed [16][17][18][19][20][21][22][23], but this paper does not systematically review the effect of vitamin C on infections, since this is covered in other publications [4][5][6][7][8][9][24][25][26][27][28][29][30][31][32]. ...
... This lack of interest in the effects of vitamin C on the common cold and other infections is very unfortunate when we consider the statistically highly significant effects observed in the controlled trials on vitamin C (see Section 1 and Table 1). Although the regular supplementation trials serve as proof of the concept that vitamin C can shorten the duration of colds and alleviate severity [4,[24][25][26][27]31], there are many relevant questions that remain unanswered. ...
... One would expect that this could only be because large-scale controlled trials showed that vitamin C was ineffective. However, many rather large trials have demonstrated that vitamin C is effective [1][2][3][4][5][6][7][8][9][24][25][26][27][28][29][30][31][32] (Table 1). We postulate that there are several reasons why the interest in vitamin C and infections declined. ...
Evidence has shown unambiguously that, in certain contexts, vitamin C is effective against the common cold. However, in mainstream medicine, the views on vitamin C and infections have been determined by eminence-based medicine rather than evidence-based medicine. The rejection of the demonstrated benefits of vitamin C is largely explained by three papers published in 1975—two published in JAMA and one in the American Journal of Medicine—all of which have been standard citations in textbooks of medicine and nutrition and in nutritional recommendations. Two of the papers were authored by Thomas Chalmers, an influential expert in clinical trials, and the third was authored by Paul Meier, a famous medical statistician. In this paper, we summarize several flaws in the three papers. In addition, we describe problems with two recent randomized trial reports published in JAMA which were presented in a way that misled readers. We also discuss shortcomings in three recent JAMA editorials on vitamin C. While most of our examples are from JAMA, it is not the only journal with apparent bias against vitamin C, but it illustrates the general views in mainstream medicine. We also consider potential explanations for the widespread bias against vitamin C.
... Previous studies have shown that vitamin C administration attenuates a robust immune response [72]. In fact, mast cell-mediated bronchial hypersensitivity caused by the common cold was inhibited by the administration of vitamin C [73]. These patients exhibited decreased bronchial hypersensitivity to histamine and bronchoconstriction after vitamin C administration [40]. ...
There is an ongoing need for new therapeutic modalities against SARS-CoV-2 infection. Mast cell histamine has been implicated in the pathophysiology of COVID-19 as a regulator of proinflammatory, fibrotic, and thrombogenic processes. Consequently, mast cell histamine and its receptors represent promising pharmacological targets. At the same time, nutritional modulation of immune system function has been proposed and is being investigated for the prevention of COVID-19 or as an adjunctive strategy combined with conventional therapy. Several studies indicate that several immunonutrients can regulate mast cell activity to reduce the de novo synthesis and/or release of histamine and other mediators that are considered to mediate, at least in part, the complex pathophysiology present in COVID-19. This review summarizes the effects on mast cell histamine of common immunonutrients that have been investigated for use in COVID-19.
... A systematic review with Cochrane collaboration failed to demonstrate that vitamin C supplementation with doses over 200 mg reduced the incidence of colds in the general population, but the disease duration was reduced by 8% in adults and 14% in children. 60 Another study did not find a conclusive effect on prevention of COVID-19 with high doses of vitamin C. 55 Despite the inconclusive results with vitamin C prophylaxis for COVID-19, some authors recommend its use with the premise of the low risk of given intravenous vitamin C or through the oral route, added to the theoretical benefit in case of a serious infectious disease. 58,61-64 ...
Introduction
In light of the current COVID-19 pandemic, during which the world is confronted with a new, highly contagious virus that suppresses innate immunity as one of its initial virulence mechanisms, thus escaping from first-line human defense mechanisms, enhancing innate immunity seems a good preventive strategy.
Methods
Without the intention to write an official systematic review, but more to give an overview of possible strategies, in this review article we discuss several interventions that might stimulate innate immunity and thus our defense against (viral) respiratory tract infections. Some of these interventions can also stimulate the adaptive T- and B-cell responses, but our main focus is on the innate part of immunity. We divide the reviewed interventions into: 1) lifestyle related (exercise, >7 h sleep, forest walking, meditation/mindfulness, vitamin supplementation); 2) Non-specific immune stimulants (letting fever advance, bacterial vaccines, probiotics, dialyzable leukocyte extract, pidotimod), and 3) specific vaccines with heterologous effect (BCG vaccine, mumps-measles-rubeola vaccine, etc).
Results
For each of these interventions we briefly comment on their definition, possible mechanisms and evidence of clinical efficacy or lack of it, especially focusing on respiratory tract infections, viral infections, and eventually a reduced mortality in severe respiratory infections in the intensive care unit. At the end, a summary table demonstrates the best trials supporting (or not) clinical evidence.
Conclusion
Several interventions have some degree of evidence for enhancing the innate immune response and thus conveying possible benefit, but specific trials in COVID-19 should be conducted to support solid recommendations.
... Based on the published data some metanalysis were published over the years. Some of them included only studies performed in specific phenotypes of asthma (exercise-induced asthma, cold-induced asthma (Hemilä, 2013c(Hemilä, , 2013a(Hemilä, , 2013b, while others included RCT (Forte et al., 2018;Ram et al., 2004). Overall, it seems that vitamin C supplementation may have a positive effect in improving clinical symptoms in cold-induced asthma, but not in all cases. ...
