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Effects of Oral Vitamin C Supplementation on Anxiety in Students: A Double-Blind, Randomized, Placebo-Controlled Trial

Authors:
  • National Institute of Study and Research in Education

Abstract

Vitamin C ascorbic acid) is a well-known antioxidant that is involved in anxiety, stress, depression, fatigue and mood state in humans. Studies have suggested that oxidative stress may trigger neuropsychological disorders. Antioxidants may play an important therapeutic role in combating the damage caused by oxidative stress in individuals that suffer from anxiety. In this context, it was hypothesized that oral vitamin C supplementation would reduce anxiety. However, few up to date studies have evaluated the consequences of oral vitamin C supplementation on anxiety in humans. The present study examined the effects of oral vitamin C supplements in 42 high school students, in a randomized, double-blind, placebo-controlled trial. The students were given either vitamin C (500 mg day(-1)) or placebo. Plasma concentrations of vitamin C and blood pressure were measured before the intervention and then one day after the intervention. Anxiety levels were evaluated for each student before and after 14 days following supplementation with the Beck Anxiety Inventory. Results showed that vitamin C reduced anxiety levels and led to higher plasma vitamin C concentration compared to the placebo. The mean heart rates were also significantly different between vitamin C group and placebo control group. Present study results not only provide evidence that vitamin C plays an important therapeutic role for anxiety but also point a possible use for antioxidants in the prevention or reduction of anxiety. This suggests that a diet rich in vitamin C may be an effective adjunct to medical and psychological treatment of anxiety and improve academic performance.
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... It is co-factors in the synthesis of endogenous substances such as catecholamines and vasopressin. [13] Catecholamines such as dopamine and adrenaline levels are altered in anxiety. The studies on the antianxiety action of Vitamin C in terms of change in behavior post-Vitamin C supplementation are limited. ...
... The antianxiety action of Vitamin C compared to placebo was seen after 2 weeks of supplementation in medical students by a significant reduction in heart rate in the Vitamin C group than the group received placebo. [13] Depression Anxiety Stress Scale 21-item score was significantly reduced in the Vitamin C supplementation diabetic patient group compared to the Vitamin E supplementation diabetic patient group. [19] One of the study's benefits was its non-invasive methods, and the medicine under investigation was a widely used, relatively safe water-soluble vitamin. ...
Article
Background: Anxiety is one of the common mental disorders. Non-fatal health loss is one of the consequences of anxiety disorders. Oxidative stress may also play a role in anxiety disorders. As an antioxidant, Vitamin C can create stable ascorbate free radicals and lower reactive oxygen species. In addition, Vitamin C can prevent damage caused by free radicals. Oxidative stress can also lead to depression, schizophrenia, and bipolar disorder. Aim and Objectives: The aim and objectives of the study are to compare the antianxiety effects of Vitamin C, buspirone, and diazepam in albino rats using elevated plus maze and hole board apparatus. Materials and Methods: 36 albino rats of either sex were divided into 6 groups of 6 rats each and drugs were administered orally. Group 1 received distilled water 10 ml/kg, Group 2 received Vitamin C 200 mg/kg, Group 3 received buspirone 10 mg/kg, Group 4 received diazepam 1 mg/kg, Group 5 received buspirone 10 mg/kg + Vitamin C 200 mg/kg, and Group 6 received diazepam 1 mg/kg + Vitamin C 200 mg/kg. Antianxiety effects of these drugs were tested after 14 days of drug administration using hole board apparatus and elevated plus maze. The methods used for statistical analysis were mean, standard deviation, confidence interval, median, interquartile range (IQR), frequency and percentage, ANOVA, Kruskal–Wallis test, and Fisher’s exact test. Results: On average time spent in open arms by Group 5 was 98.00 sec (IQR: 19.75–138.00) which was higher than other groups, but it was not statistically significant (P = 0.845). The time spent in closed arms in seconds by Group 4 was 245 ± 28.863, which was higher than other groups, but it was not statistically significant (P = 0. 805). On average head dip by Group 5 was 9.83 ± 4.708, which was higher than other groups, but it was not statistically significant (P = 0.141). Conclusion: Group 5 rats that received buspirone and Vitamin C, followed by Group 6 rats that received diazepam and Vitamin C had spent more time and had more entries into the open arms. Furthermore, Groups 5 and 6 animals had a greater number of head dips in the hole board apparatus compared to the behavior of all animals in other groups. Buspirone and diazepam are known anxiolytics. When these drugs were given in combination with Vitamin C, the antianxiety behaviors in rats were more compared to the drugs given alone in the present study but it was not statistically significant.
... We found "Ascorbate Recycling" to be uniquely significantly enriched in innate anxiety. Lower levels of these vitamins have been found in people suffering from anxiety disorders (Gautam et al., 2012;Mikkelsen et al., 2018;Chang et al., 2019;Silva et al., 2021), and vitamin C supplementation reduces anxiety symptoms (de Oliveira et al., 2015). The biological processes linking vitamin C with anxiety regulation is still poorly understood but could be mediated through its antioxidant properties or modulatory effects on the immune function (de Oliveira et al., 2015). ...
... Lower levels of these vitamins have been found in people suffering from anxiety disorders (Gautam et al., 2012;Mikkelsen et al., 2018;Chang et al., 2019;Silva et al., 2021), and vitamin C supplementation reduces anxiety symptoms (de Oliveira et al., 2015). The biological processes linking vitamin C with anxiety regulation is still poorly understood but could be mediated through its antioxidant properties or modulatory effects on the immune function (de Oliveira et al., 2015). In stress-induced anxiety, non-inflammatory biological pathways were associated with "Hepatic Fibrosis/Hepatic Stellate Cell activation" (containing genes associated with the extracellular matrix), and "Oxidative Phosphorylation", which have previously been linked to anxiety (Freitag et al., 2003;Hollis et al., 2015;Misiewicz et al., 2019;Blanco and Conant, 2021). ...
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Anxiety is an evolutionarily conserved response that is essential for survival. Pathological anxiety, however, is a maladaptive response to nonthreatening situations and greatly affects quality of life. The recent COVID-19 pandemic has increased the prevalence of anxiety symptoms and highlighted the urge to identify the molecular events that initiate pathological anxiety. To this aim, we investigated the extent of similarity of brain region-specific gene expression patterns associated with innate and stress-induced anxiety-like behavior. We compared the cortico-frontal (FCx) and hippocampal (Hpc) gene expression patterns of five inbred mouse strains with high or low levels of innate anxiety-like behavior with gene expression patterns of mice subjected to chronic social defeat stress. We found significantly large overlap of the Hpc but small overlap of the FCx gene expression patterns in innate and stress-induced anxiety, that however, converged onto common inflammation and immune system canonical pathways. Comparing the gene expression data with drug-gene interaction datasets revealed drug candidates, including medrysone, simvastatin, captopril, and sulpiride, that produced gene expression changes opposite to those observed in innate or stress-induced anxiety-like behavior. Together, our data provide a comprehensive overview of FCx and Hpc gene expression differences between innate and stress-induced anxiety and support the role of inflammation and immune system in anxiety-like behavior.
... At the functional level, a unique microbial metabolic pathway profile was present in TLEA's gut, such as ascorbic acid synthesis. Vitamin C(ascorbic acid) is a well-known antioxidant that is said to be involved in treating anxiety in humans (Oliveira et al., 2015;Pratiwi et al., 2019). Vitamin C supplementation at 3,000 mg daily lowered subjective stress against acute psychological stressors (Brody et al., 2002), and a relief effect on anxious mood was observed after vitamin C administration in healthy individuals (Oliveira et al., 2015;Moritz et al., 2017). ...
... Vitamin C(ascorbic acid) is a well-known antioxidant that is said to be involved in treating anxiety in humans (Oliveira et al., 2015;Pratiwi et al., 2019). Vitamin C supplementation at 3,000 mg daily lowered subjective stress against acute psychological stressors (Brody et al., 2002), and a relief effect on anxious mood was observed after vitamin C administration in healthy individuals (Oliveira et al., 2015;Moritz et al., 2017). Further studies will be needed to monitor changes in neurotransmitters, neurohormones, and neurotrophins in TLEA patients to understand the underlying mechanisms by which vitamin C affects TLEA brain function. ...
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Introduction Patients with epilepsy are particularly vulnerable to the negative effects of anxiety disorders. In particular, temporal lobe epilepsy with anxiety disorders (TLEA) has attracted more attention in epilepsy research. The link between intestinal dysbiosis and TLEA has not been established yet. To gain deeper insight into the link between gut microbiota dysbiosis and factors affecting TLEA, the composition of the gut microbiome, including bacteria and fungi, has been examined. Methods The gut microbiota from 51 temporal lobe epilepsy patients has been subjected to sequencing targeting 16S rDNA (Illumina MiSeq) and from 45 temporal lobe epilepsy patients targeting the ITS-1 region (through pyrosequencing). A differential analysis has been conducted on the gut microbiota from the phylum to the genus level. Results TLEA patients' gut bacteria and fungal microbiota exhibited distinct characteristics and diversity as evidenced by high-throughput sequencing (HTS). TLEA patients showed higher abundances of Escherichia-Shigella (genus), Enterobacterales (order), Enterobacteriaceae (family), Proteobacteria (phylum), Gammaproteobacteria (class), and lower abundances of Clostridia (class), Firmicutes, Lachnospiraceae (family), Lachnospirales (order), and Ruminococcus (genus). Among fungi, Saccharomycetales fam. incertae sedis (family), Saccharomycetales (order), Saccharomycetes (class), and Ascomycota (phylum) were significantly more abundant in TLEA patients than in patients with temporal lobe epilepsy but without anxiety. Adoption and perception of seizure control significantly affected TLEA bacterial community structure, while yearly hospitalization frequency affected fungal community structures in TLEA patients. Conclusion Here, our study validated the gut microbiota dysbiosis of TLEA. Moreover, the pioneering study of bacterial and fungal microbiota profiles will help in understanding the course of TLEA and drive us toward preventing TLEA gut microbiota dysbiosis.
... Similarly, Mazidi et al. [35] showed that supplementing with 50 mg of saffron twice daily significantly reduced the anxiety scores compared to a placebo over a 12-week period (p < 0.001). Another randomized, double-blind trial conducted by de Oliveira et al. [36] revealed that participants receiving 500 mg of vitamin C supplementation for 14 days had a significantly lower mean anxiety score than the control group (16.86 ± 10.19 vs. 24.95 ± 13.11; p = 0.01). ...
Article
Antioxidant intake may contribute to the prevention of numerous diseases, particularly those related to stress-induced psychiatric and stress disorders. The current study aimed to assess the relationship between daily antioxidant intake (DAI) and Generalized Anxiety Disorder (GAD) in adults. It also sought to investigate the correlation between the type of diet in conjunction with DAI and the scores on GAD 7-Item Scale in adults. A cross-sectional design was used to examine if DAI was lower in individuals with GAD; followed by an interventional study of 40 adults with severe GAD, who were exposed to higher DAI for a period of 6 weeks. The results indicated that participants with severe GAD had significantly lower levels of DAI compared to healthy controls (p < 0.001). After 6 weeks of antioxidant supplementation, a significant decrease in GAD-7 scores of participants was observed (p < 0.001). The study found a significant negative relationship between DAI and GAD. KEYWORDS
... Experimental studies show that vitamin C has several antidepressant effects, such as anxiolytic effects [31,32], activation of the opioid system [33], inhibition of glutamate receptors [34] and modulation of GABA receptors [35], activation/modulation of monoaminergic and glutamatergic neurotransmitter systems and inhibition of N-methyl-D-aspartate receptors and nitric oxide synthesis [36,37], reversal of chronic corticosterone-induced hippocampal synaptic deficits [38], and reduction of oxidative damage [39,40]. ...
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Depression is on the rise and medication does not always provide satisfactory relief. This raises the question of a treatment gap that has not yet been (sufficiently) addressed. Inflammation and oxidative stress play an important pathophysiological role, which also leads to a deficiency of antioxidants such as vitamin C. This perspective mini-review reflects the results of a PubMed search combining the search terms depression with inflammation, oxidative stress and vitamin C. Vitamin C is an important antioxidant and co-factor for many neuronal metabolic and epigenetic pathways, and a deficiency is associated with depression and cognitive disorders. Inadequate vitamin C blood levels that do not yet result in somatic symptoms may induce neuropsychiatric scurvy, which is associated with increased neuroinflammation and characterized by depression and cognitive impairment. Experimental studies show that vitamin C has multifactorial effects on metabolic pathways relevant to depression. Treatment of vitamin C deficiency, which is more common than appreciated, should be considered in the management of depressed patients. Further studies should investigate whether the pharmacological administration of vitamin C has additional effects beyond the correction of deficiency.
... Um estudo realizado por Oliveira et al. (2015) mostrou que a suplementação de vitamina C em estudantes por 14 dias foi significativamente eficaz para reduzir os níveis de ansiedade. Esses achados demonstram a importância de uma alimentação saudável e variada, rica em alguns nutrientes específicos, pode auxiliar na prevenção e tratamento de transtornos psiquiátricos. ...
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