OBJECTIVE:

To define what role vitamin C may or may not play in the treatment of asthma.

DATA SOURCES:

A comprehensive literature search of relevant English-language papers identified through a Medline search and from bibliographies of the identified papers.

STUDY SELECTION:

We identified papers and studies pertaining to vitamin C in asthma and allergy and analyzed these studies according to their design, inclusion and exclusion criteria, population studied, variables or factors tested, method of intervention or treatment with vitamin C, and results and conclusions. We reviewed our data and divided it based on significant or insignificant roles of vitamin C in asthma and allergy.

RESULTS:

From our review, we found a number of studies that support the use of vitamin C in asthma and allergy. Significant results include positive effects on pulmonary function tests, bronchoprovocation challenges with methacholine or histamine or allergens, improvement in white blood cell function and motility, and a decrease in respiratory infections. Our review also revealed several studies that did not support a beneficial role in vitamin C in asthma and allergy. These studies did not report improvements in pulmonary function tests or bronchoprovocation challenges. No benefit was noted in these studies when testing cutaneous reactivity or specific immunologic factors and levels.

CONCLUSIONS:

Clearly from our review, the role of vitamin C in asthma and allergy is not well defined. The majority of the studies were short term and assessed immediate effects of vitamin C supplementation. Long term supplementation with vitamin C or delayed effects need to be studied. Although, the current literature does not support a definite indication for the use of vitamin C in asthma and allergy, the promising and positive studies revive curiosity and interest. With a large portion of health care dollars being spent on alternative medicine and vitamin C in particular, further studies are needed to define its role.

OBJECTIVE:

To evaluate the literature on supplemental vitamin C and vitamin E therapy in the prevention and treatment of Alzheimer's disease (AD).

DATA SOURCES:

Literature retrieval was accessed through MEDLINE (1966-March 2005) using the key words antioxidants, vitamin C, vitamin E, Alzheimer's disease, and dementia. International Pharmaceutical Abstracts (1970-March 2005), Current Contents (1996-March 2005), Cochrane Database of Systematic Reviews (1994-March 2005), and Ebsco's Academic Search Elite (1975-March 2005) were searched with the same key words.

STUDY SELECTION AND DATA EXTRACTION:

Articles related to the objective that were identified through PubMed were included.

DATA SYNTHESIS:

Oral supplementation of vitamin C (ascorbic acid) and vitamin E (D-alfa-tocopherol acetate) alone and in combination have been shown to decrease oxidative DNA damage in animal studies in vivo, in vitro, and in situ. Recent results of a prospective observational study (n = 4740) suggest that the combined use of vitamin E 400 IU daily and vitamin C 500 mg daily for at least 3 years was associated with the reduction of AD prevalence (OR 0.22; 95% CI 0.05 to 0.60) and incidence (HR 0.36; 95% CI 0.09 to 0.99). Contradicting this is a previous prospective observational study (n = 980) evaluating the relationship between 4 years of vitamin C and E intake and the incidence of AD, which detected no difference in the incidence of AD during the 4-year follow-up. Recent meta-analysis results suggest that doses of vitamin E ≥400 IU daily for more than one year are associated with increased all-cause mortality. Mega-trial results suggest that vitamin E doses ≥400 IU daily for 6.9 years in patients with preexisting vascular disease or diabetes mellitus increase the incidence of heart failure, with no other outcome benefits noted.

CONCLUSIONS:

In the absence of prospective, randomized, controlled clinical trials documenting benefits that outweigh recently documented morbidity and mortality risks, vitamin E supplements should not be recommended for primary or secondary prevention of AD. Although the risks of taking high doses of vitamin C are lower than those with vitamin E, the lack of consistent efficacy data for vitamin C in preventing or treating AD should discourage its routine use for this purpose.

BACKGROUND:

Vitamin C supplementation may help reduce the risk of pregnancy complications such as pre-eclampsia, intrauterine growth restriction and maternal anaemia. There is a need to evaluate the efficacy and safety of vitamin C supplementation in pregnancy.

OBJECTIVES:

To evaluate the effects of vitamin C supplementation, alone or in combination with other separate supplements on pregnancy outcomes, adverse events, side effects and use of health resources.

SEARCH METHODS:

We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 March 2015) and reference lists of retrieved studies.

SELECTION CRITERIA:

All randomised or quasi-randomised controlled trials evaluating vitamin C supplementation in pregnant women. Interventions using a multivitamin supplement containing vitamin C or where the primary supplement was iron were excluded.

DATA COLLECTION AND ANALYSIS:

Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy.

MAIN RESULTS:

Twenty-nine trials involving 24,300 women are included in this review. Overall, 11 trials were judged to be of low risk of bias, eight were high risk of bias and for 10 trials it was unclear. No clear differences were seen between women supplemented with vitamin C alone or in combination with other supplements compared with placebo or no control for the risk of stillbirth (risk ratio (RR) 1.15, 95% confidence intervals (CI) 0.89 to 1.49; 20,038 participants; 11 studies; I² = 0%; moderate quality evidence), neonatal death (RR 0.79, 95% CI 0.58 to 1.08; 19,575 participants; 11 studies; I² = 0%), perinatal death (average RR 1.07, 95% CI 0.77 to 1.49; 17,105 participants; seven studies; I² = 35%), birthweight (mean difference (MD) 26.88 g, 95% CI -18.81 to 72.58; 17,326 participants; 13 studies; I² = 69%), intrauterine growth restriction (RR 0.98, 95% CI 0.91 to 1.06; 20,361 participants; 12 studies; I² = 15%; high quality evidence), preterm birth (average RR 0.99, 95% CI 0.90 to 1.10; 22,250 participants; 16 studies; I² = 49%; high quality evidence), preterm PROM (prelabour rupture of membranes) (average RR 0.98, 95% CI 0.70 to 1.36; 16,825 participants; 10 studies; I² = 70%; low quality evidence), term PROM (average RR 1.26, 95% CI 0.62 to 2.56; 2674 participants; three studies; I² = 87%), and clinical pre-eclampsia (average RR 0.92, 95% CI 0.80 to 1.05; 21,956 participants; 16 studies; I² = 41%; high quality evidence).Women supplemented with vitamin C alone or in combination with other supplements compared with placebo or no control were at decreased risk of having a placental abruption (RR 0.64, 95% CI 0.44 to 0.92; 15,755 participants; eight studies; I² = 0%; high quality evidence) and had a small increase in gestational age at birth (MD 0.31, 95% CI 0.01 to 0.61; 14,062 participants; nine studies; I² = 65%), however they were also more likely to self-report abdominal pain (RR 1.66, 95% CI 1.16 to 2.37; 1877 participants; one study). In the subgroup analyses based on the type of supplement, vitamin C supplementation alone was associated with a reduced risk of preterm PROM (average RR 0.66, 95% CI 0.48 to 0.91; 1282 participants; five studies; I² = 0%) and term PROM (average RR 0.55, 95% CI 0.32 to 0.94; 170 participants; one study). Conversely, the risk of term PROM was increased when supplementation included vitamin C and vitamin E (average RR 1.73, 95% CI 1.34 to 2.23; 3060 participants; two studies; I² = 0%). There were no differences in the effects of vitamin C on other outcomes in the subgroup analyses examining the type of supplement. There were no differing patterns in other subgroups of women based on underlying risk of pregnancy complications, timing of commencement of supplementation or dietary intake of vitamin C prior to trial entry. The GRADE quality of the evidence was high for intrauterine growth restriction, preterm birth, and placental abruption, moderate for stillbirth and clinical pre-eclampsia, low for preterm PROM.

AUTHORS' CONCLUSIONS:

The data do not support routine vitamin C supplementation alone or in combination with other supplements for the prevention of fetal or neonatal death, poor fetal growth, preterm birth or pre-eclampsia. Further research is required to elucidate the possible role of vitamin C in the prevention of placental abruption and prelabour rupture of membranes. There was no convincing evidence that vitamin C supplementation alone or in combination with other supplements results in other important benefits or harms.

BACKGROUND:

As the primary source of dietary vitamin C is fruit and to some extent vegetables, the plasma level of vitamin C has been considered a good surrogate or predictor of vitamin C intake by fruit and vegetable consumption. The purpose of this systematic review was to investigate the relationship between dietary vitamin C intakes measured by different dietary methods and plasma levels of vitamin C.

METHOD:

We searched the literature up to May 2006 through the OVID interface: MEDLINE (from 1960) and EMBASE (from 1988). We also reviewed the reference lists in the articles, reviews, and textbooks retrieved. A total of 26 studies were selected and their results were combined using meta-analytic techniques with random-effect model approach.

RESULTS:

The overall result of this study showed a positive correlation coefficient between Food Frequency Questionnaire (FFQ) and biomarker (r = 0.35 for "both" genders, 0.39 for females, and 0.46 for males). Also the correlation between Dietary Recalls (DR)/diary and biomarker was 0.46 for "both" genders, 0.44 for females, and 0.36 for males. An overall correlation of 0.39 was found when using the weight record method. Adjusting for energy intake improved the observed correlation for FFQ from 0.31 to 0.41. In addition, we compared the correlation for smokers and non-smokers for both genders (

FFQ:

for non-smoker r = 0.45, adjusted for smoking r = 0.33).

CONCLUSION:

Our findings show that FFQ and DR/diary have a moderate relationship with plasma vitamin C. The correlation may be affected/influenced by the presence of external factors such as vitamin bioavailability, absorption condition, stress and food processing and storage time, or by error in reporting vitamin C intake.

Background: Tetanus is a severe disease that can be prevented by vaccination. In developing countries vaccination coverage is not always high. Cases still occur also in developed countries, particularly in elderly people owing to their reduced immuno protection. There are about 1 million tetanus cases per year globally. In animal studies, vitamin C has protected against various infections and bacterial toxins. In a study with rats, vitamin C protected against the purified tetanus toxin. Objectives: To assess the prophylactic and therapeutic effect of vitamin C on tetanus. Search methods: In May 2013 we searched the Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); and Ovid EMBASE for this third update. Selection criteria: Controlled trials of vitamin C as a prevention or treatment for tetanus, whether or not these were placebo controlled, in any language, published or unpublished. Two review authors independently made inclusion decisions. Data collection and analysis: Both review authors independently extracted data from trial reports and assessed methodological quality. Since one of the cells in a 2 × 2 table had no events, we calculated the odds ratio (OR) and its 95% confidence interval (CI) for case fatality rate by using the Peto-method. Another of the 2 × 2 tables had no empty cells and the inverse-variance method was used to calculate its risk ratio (RR) estimate and 95% CI. We also used the Fisher's exact test to calculate the exact 95% CI for the OR of the 2 × 2 table with the empty cell. Main results: One single trial was eligible for inclusion. This non-randomised, unblinded, controlled trial undertaken in Bangladesh involved 117 tetanus patients. Vitamin C at a dosage of 1 g/day was administered intravenously alongside conventional treatment. At recruitment, the participants were stratified into two age groups and the results were reported by age. There was a significant difference in the vitamin C effect between the two age groups (P = 0.01). In the tetanus patients aged 1 to 12 years (n = 62), vitamin C treatment was associated with a 100% reduction in case fatality rate (95% CI from -100% to -94%). In patients aged 13 to 30 years (n = 55), vitamin C treatment was associated with a 45% reduction in case fatality rate (95% CI from -69% to -5%). Authors' conclusions: A single, non-randomised, poorly reported trial of vitamin C as a treatment for tetanus suggests a considerable reduction in mortality. However, concerns about trial quality mean that this result must be interpreted with caution and vitamin C cannot be recommended as a treatment for tetanus on the basis of this evidence. New trials should be carried out to examine the effect of vitamin C on tetanus treatment.

BACKGROUND:

Though vitamin C supplementation has shown no observed effects on stroke prevention in several clinical trials, uncertainty remains as to whether long-term, low-dose intake influences the development of stroke among general populations. Furthermore, the association between circulating vitamin C and the risk of stroke is also unclear. For further clarification of these issues, we conducted a meta-analysis of prospective studies.

METHODS AND RESULTS:

PubMed and EMBASE databases were searched, and the bibliographies of the retrieved articles were also reviewed to identify eligible studies. Summary relative risk (RRs) with corresponding 95% confidence intervals (CIs) were computed with a random-effects model. The summary RR for the high-versus-low categories was 0.81 (95% CI.: 0.74 to 0.90) for dietary vitamin C intake (11 studies), and 0.62 (95% CI.: 0.49 to 0.79) for circulating vitamin C (6 studies). The summary RR for each 100 mg/day increment in dietary vitamin C was 0.83 (95% CI.: 0.75 to 0.93) (10 studies), and for each 20 μmol/L increment in circulating vitamin C was 0.81 (95% CI.: 0.75 to 0.88) (5 studies). Few studies reported results for vitamin C supplements (RR for high-versus-low intake=0.83, 95% CI.: 0.62 to 1.10, 3 studies).

CONCLUSIONS:

This meta-analysis suggests significant inverse relationships between dietary vitamin C intake, circulating vitamin C, and risk of stroke.

BACKGROUND:

Pneumonia is one of the most common serious infections, causing two million deaths annually among young children in low-income countries. In high-income countries pneumonia is most significantly a problem of the elderly.

OBJECTIVES:

To assess the prophylactic and therapeutic effects of vitamin C on pneumonia.

SEARCH METHODS:

We searched CENTRAL 2013, Issue 3, MEDLINE (1950 to March week 4, 2013), EMBASE (1974 to April 2013) and Web of Science (1955 to April 2013).

SELECTION CRITERIA:

To assess the therapeutic effects of vitamin C, we selected placebo-controlled trials. To assess prophylactic effects, we selected controlled trials with or without a placebo.

DATA COLLECTION AND ANALYSIS:

Two review authors independently read the trial reports and extracted data.

MAIN RESULTS:

We identified three prophylactic trials which recorded 37 cases of community-acquired pneumonia in 2335 people. Only one was satisfactorily randomised, double-blind and placebo-controlled. Two trials examined military recruits and the third studied boys from "lower wage-earning classes" attending a boarding school in the UK during World War II. Each of these three trials found a statistically significant (80% or greater) reduction in pneumonia incidence in the vitamin C group. We identified two therapeutic trials involving 197 community-acquired pneumonia patients. Only one was satisfactorily randomised, double-blind and placebo-controlled. That trial studied elderly patients in the UK and found lower mortality and reduced severity in the vitamin C group; however, the benefit was restricted to the most ill patients. The other therapeutic trial studied adults with a wide age range in the former Soviet Union and found a dose-dependent reduction in the duration of pneumonia with two vitamin C doses. We identified one prophylactic trial recording 13 cases of hospital-acquired pneumonia in 37 severely burned patients; one-day administration of vitamin C had no effect on pneumonia incidence. The identified studies are clinically heterogeneous which limits their comparability. The included studies did not find adverse effects of vitamin C.

AUTHORS' CONCLUSIONS:

The prophylactic use of vitamin C to prevent pneumonia should be further investigated in populations who have a high incidence of pneumonia, especially if dietary vitamin C intake is low. Similarly, the therapeutic effects of vitamin C should be studied, especially in patients with low plasma vitamin C levels. The current evidence is too weak to advocate prophylactic use of vitamin C to prevent pneumonia in the general population. Nevertheless, therapeutic vitamin C supplementation may be reasonable for pneumonia patients who have low vitamin C plasma levels because its cost and risks are low.

CRD COMMENTARY:

The review is not methodologically rigorous. No study inclusion criteria, or criteria to check the validity or relevance of included studies, are given. The outcomes used are not clearly defined. Studies that are described in the results section are not included in the Tables of studies. The majority of studies reported are very small. The studies are not ordered by methodological strength and so it is difficult to untangle the level of evidence for the various findings.

ANTECEDENTES:

La vitamina C (ácido ascórbico) en la prevención y el tratamiento del resfrío común ha sido objeto de controversia desde hace 70 años.

OBJETIVOS:

Conocer si la vitamina C reduce la incidencia, la duración o la gravedad del resfrío común cuando se usa como suplemento continuo regular diario o como terapia al inicio de los síntomas del resfrío.

ESTRATEGIA DE BÚSQUEDA:

Se realizaron búsquedas en CENTRAL 2012 número 11, MEDLINE (1966 hasta noviembre, semana 3, 2012), EMBASE (1990 a noviembre de 2012), CINAHL (desde enero 2010 hasta noviembre 2012), LILACS (enero 2010 hasta noviembre 2012) y Web of Science (enero 2010 hasta noviembre 2012). También se buscó en el registro de estudios de los Institutos Nacionales de Salud de EE.UU. y la ICTRP de la OMS el 29 de noviembre de 2012.

CRITERIOS DE SELECCIÓN:

Se excluyeron los estudios que utilizaron menos de 0,2 g por día de vitamina C y los estudios sin una comparación con placebo. Hemos restringido nuestro análisis a estudios controlados con placebo.

RECOPILACIÓN Y ANÁLISIS DE DATOS:

Dos revisores de forma independiente extrajeron los datos. Se evaluó tanto la "incidencia" de los resfriados durante la suplementación regular, como la proporción de participantes que presentaron uno o más resfriados durante el período de estudio. La "duración" fue el número medio de días de enfermedad de los episodios de resfrío.

RESULTADOS PRINCIPALES:

Veintinueve comparaciones de estudios, que incluyeron 11.306 participantes, contribuyeron al meta-análisis sobre el riesgo relativo (RR) de desarrollar un resfrío mientras se consumió regularmente vitamina C durante el período de estudio. En los estudios comunitarios generales que involucraron 10.708 participantes, el RR combinado fue 0,97 (intervalo de confianza (IC) del 95%: 0,94 a 1,00). Cinco ensayos con un total de 598 corredores de maratón, esquiadores y soldados realizando ejercicios subárticos arrojó un RR agrupado de 0,48 (IC del 95%: 0,35 a 0,64).
Treinta y un comparaciones examinaron el efecto de la vitamina C regular sobre la duración del resfrío común (9745 episodios). En adultos, la duración de los resfriados se redujo en un 8% (3% a 12%) y en los niños en un 14% (7% a 21%). En los niños, 1 a 2 g / día de vitamina C acortó los resfriados en un 18%. La severidad de los resfriados también se redujo con la administración regular de vitamina C.
Siete comparaciones examinaron el efecto terapéutico de la vitamina C (3249 episodios). No se observó un efecto consistente de la vitamina C en la duración o gravedad de los resfriados en los estudios terapéuticos.
La mayoría de los estudios incluidos fueron randomizados y doble ciego. La exclusión de los estudios que no eran randomizados o doble ciego no tuvo efecto sobre las conclusiones.

CONCLUSIONES DE LOS REVISORES:

El fracaso de la suplementación de vitamina C para reducir la incidencia de resfriados en la población general indica que la suplementación de rutina de vitamina C no es justificada, sin embargo, la vitamina C puede ser útil para las personas expuestas a períodos breves de ejercicio físico intenso. Los estudios sobre suplementación regular han mostrado que la vitamina C reduce la duración de los resfriados, pero esto no se replicó en los pocos estudios terapéuticos que han sido llevados a cabo. Sin embargo, dado el efecto consistente de la vitamina C sobre la duración y severidad de los resfriados en los estudios de suplementación regular, y el bajo costo y seguridad, puede ser útil en pacientes con resfrío común para poner a prueba de forma individual si la terapia con vitamina C es beneficiosa para ellos. Se justifican otros Ensayos Ransomizados Controlados terapéuticos.

Background: The association between dietary antioxidants and asthma or exercise-induced bronchoconstriction (EIB) is not fully understood. Vitamin C and vitamin E are natural antioxidants that are predominantly present in fruits and vegetables; inadequate vitamin E intake is associated with airway inflammation. It has been postulated that the combination may be more beneficial than either single antioxidant for people with asthma and exercise-induced bronchoconstriction. Objectives: To assess the effects of supplementation of vitamins C and E versus placebo (or no vitamin C and E supplementation) on exacerbations and health-related quality of life (HRQL) in adults and children with chronic asthma. To also examine the potential effects of vitamins C and E on exercise-induced bronchoconstriction in people with asthma and in people without a diagnosis of asthma who experience symptoms only on exercise. Search methods: Trials were identified from the Cochrane Airways Review Group Specialised Register and from trial registry websites. Searches were conducted in September 2013. Selection criteria: We included randomised controlled trials of adults and children with a diagnosis of asthma. We separately considered trials in which participants had received a diagnosis of exercise-induced bronchoconstriction (or exercise-induced asthma). Trials comparing vitamin C and E supplementation versus placebo were included. We included trials in which asthma management for treatment and control groups included similar background therapy. Short-term use of vitamins C and E at the time of exacerbation or for cold symptoms in people with asthma is outside the scope of this review. Data collection and analysis: Two review authors independently screened the titles and abstracts of potential studies and subsequently screened full-text study reports for inclusion. We used standard methods as expected by The Cochrane Collaboration. Main results: It was not possible to aggregate the five included studies (214 participants). Four studies (206 participants) addressed the question of whether differences in outcomes were seen when vitamin C and E supplementation versus placebo was provided for participants with asthma, and only one of those studies (160 children) included a paediatric population; the remaining three studies included a combined total of just 46 adults. An additional study considered the question of whether differences in outcomes were noted when vitamin C and E supplementation was compared with placebo for exercise-induced asthma; this trial included only eight participants. The randomisation process of the trials were unclear leading us to downgrade the quality of the evidence. Four of the studies were double blind while the other study was single blind. None of these studies provided data on our two prespecified primary outcome measures: exacerbations and HRQL. Lung function data obtained from the studies were inconclusive. The only studies that provided any suggestion of an effect, and only with some outcomes, were the paediatric study, especially for children with moderate to severe asthma, and the small study on exercise-induced asthma. Even so, this evidence was judged to be at moderate/low quality. Only one study contributed data on asthma symptoms and adverse events, reporting no evidence of an effect of the intervention for symptoms and that one participant in the treatment group dropped out due to cystitis. Authors' conclusions: It is not possible to draw firm conclusions from this review with respect to the comparison of vitamin C and E supplementation versus placebo in the management of asthma or exercise-induced bronchoconstriction. We found only one study relevant to exercise-induced bronchoconstriction; most included participants came from studies designed to assess the effect of vitamin supplementation on the impact of atmospheric pollutants (such as ozone). Evidence is lacking on the comparison of vitamin C and E supplementation versus placebo for asthma with respect to outcomes such as HRQL and exacerbations, which were not addressed by any of the included studies. When compared with lung function tests alone, HRQL scores and exacerbation frequency are better indicators of the severity of asthma, its impact on daily activities and its response to treatment in a patient population. These end points are well recognised in good quality studies of asthma management. However, clinical studies of vitamins C and E in the management of asthma using these important end points of exacerbations and effects on quality of life are not available, and evidence is insufficient to support robust conclusions on the role of vitamin C and E supplementation in asthma and exercise-induced breathlessness.