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Efficacy of Supplementary Vitamins C and E on Anxiety, Depression and Stress in Type 2 Diabetic Patients: A Randomized, Single-blind, Placebo-controlled Trial

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Abstract

Diabetes mellitus as one of the most prevalent endocrine disease is associated with high oxidative stress. Anxiety, stress and depression are common neuropsychiatric features in diabetic patients. Hyperglycemia leads to increased oxidative stress which in turn diminishes antioxidant defense system. On the other hand oxidative stress is the leading cause of depression and anxiety disorders. Thus, it seems that diabetes could accelerate the trend of psychiatric diseases. In this randomized single-blind study, evaluation of the effects of two antioxidants (vitamin C and vitamin E) was done on Stress, depression and anxiety levels in 45 diabetic patients for six weeks. The patients were randomly divided in three groups of vitamin E (400 IU day(-1)), vitamin C (1000 mg day(-1)) and placebo. DASS-21 (Depression Anxiety Stress Scales 21-item) questionnaire items were read to each patient and completed by the main investigator of this study before and after six weeks of supplementation. The scores of depression, anxiety and stress were evaluated separately based on the DASS questionnaire. The results showed a significant decrease in anxiety level (p = 0.005) in vitamin C group compared to other groups but there were no significant differences between groups in terms of changes in stress and depression scores. In conclusion, this study suggests that short-term supplementation of vitamin C is safe and beneficial for reducing anxiety levels in diabetic patients through alleviating oxidative damage.
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... Otra teoría incluye la falta de protección del tejido cerebral al estrés oxidativo, por medio del barrido de radicales libres, mecanismo que es llevado a cabo por diferentes vitaminas (por ejemplo, E, C y A). En relación con esto, Mazloom et al. (24) describieron una disminución de la ansiedad en pacientes que recibieron vitamina A durante seis semanas y, así, demostraron una asociación entre la alteración de concentraciones de vitamina A y el desarrollo de síntomas ansiosos. ...
... Asimismo, Mazloom et al. (24) informaron que los estados de estrés como la ansiedad tienen un efecto neurotóxico a través de radicales reactivos que afectan la plasticidad sináptica y la morfología de las dendritas. Igualmente, evidenciaron una relación entre el estrés oxidativo celular y regulación de la ansiedad. ...
... También se halló en la literatura que la minoría de pacientes recibe un adecuado tratamiento para la ND (16), a pesar de que diversos estudios han demostrado la disminución del dolor neuropático con el uso de antidepresivos, que también pueden llevar a la posterior reducción de los síntomas ansiosos (24). Al contrario, se ha encontrado como opción terapéutica la exenatida, análoga del GLP-1, que proporciona efectos ansiolíticos y antidepresivos, además de revertir la ND (28,29). ...
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Introducción: La neuropatía diabética es una complicación microvascular de la diabetes mellitus. Se caracteriza por una afectación en los nervios que produce un dolor tipo corrientazo, quemadura o punzada. Este dolor neuropático se ha asociado con alto riesgo de síntomas ansiosos en los pacientes que la padecen, lo que genera así una carga económica mayor en pacientes con neuropatía diabética. Objetivo: Describir la información actual en la literatura sobre la relación entre la neuropatía diabética sintomática y el riesgo de trastorno de ansiedad concomitante. Métodos: Búsqueda en paralelo por cuatro revisores en las bases de datos Ovid, Pubmed, SciELO y Cochrane. Resultados: De los 1140 artículos encontrados, 56 fueron evaluados en texto completo. Se encontró una prevalencia variada de síntomas ansiosos y depresivos en pacientes con neuropatía diabética, evaluados mediante diferentes cuestionarios y escalas. Algunos estudios encontraron asociación entre ansiedad, trastornos del sueño e inadecuado control glucémico. Se han reportado como factores de buen pronóstico la educación temprana y el manejo de dolor neuropático, siendo estos últimos los determinantes de la calidad de vida y la productividad en estos pacientes. Conclusión: La relación entre neuropatía diabética y los síntomas ansiosos puede ser bidireccional. Dados estos hallazgos y su posible impacto individual y en salud pública, se plantean oportunidades para llenar las brechas de prevención primaria, diagnóstico precoz y tratamiento en esta población, las cuales deberán definirse en futuras investigaciones.
... As intervention duration varied, data closest to the three-month timepoint were extracted and used in meta-analysis. Six studies reported data between four to 12 weeks [29][30][31][32]35,36], and three reported data at six months [34,37,38]. Detailed characteristics of the included studies are presented in Table 3. ...
... Three of the studies [35,36,39] used only vitamin E as part of the intervention, while the remaining studies used other constituents in addition to vitamin E, such as omega-3 fatty acids, omega-6 fatty acids, and pravastatin [34,36]. Three of the studies [29,31,40] used omega-3 fatty acids among the other constituents. ...
... Three of the studies [35,36,39] used only vitamin E as part of the intervention, while the remaining studies used other constituents in addition to vitamin E, such as omega-3 fatty acids, omega-6 fatty acids, and pravastatin [34,36]. Three of the studies [29,31,40] used omega-3 fatty acids among the other constituents. ...
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Background: Recently, it has been discovered that anti-inflammatory and anti-oxidative pathways play a role in depression and anxiety. Lower serum levels of antioxidants, such as vitamin E, have been implicated in both depression and anxiety. Methods: This PROSPERO-registered systematic review (Reference: CRD42021260058) is reported according to PRISMA guidelines. PubMed, EMBASE, CENTRAL, PsycINFO, and CINAHL were searched from inception to June 2021. Results: Twelve studies were included in this systematic review, and nine in meta-analysis of vitamin E versus placebo. For depression, meta-analysis of 354 participants showed a standardised mean difference of -0.88 (95% CI: -1.54, -0.21; I2 = 87%) favouring vitamin E. For anxiety, meta-analysis of 306 participants showed a standardised mean difference of -0.86 (95% CI: -2.11, 0.40; I2 = 95%) favouring vitamin E. Three of the studies involved a pure comparison of vitamin E against placebo, while others included constituents such as omega-3 fatty acids. Nine of the studies were at low risk of bias, two had some concerns, and one was at high risk of bias. Conclusion: Vitamin E supplementation has shown inconclusive results in ameliorating both depression and anxiety. Containing a reassuring safety profile and low cost, future studies would be of promise, and they would benefit from both larger sample sizes and from excluding other constituents, such as omega-3 fatty acids, from experimental and comparator arms.
... Several randomized controlled trials (RCTs) have evaluated the effects of vitamin C supplementation on depression, however, the results have been inconsistent [24][25][26] [27,28]. ...
... The literature search identified 698 relevant articles, of which 73 were eligible for further assessment. A final total of 10 studies met the inclusion criteria, which included 836 total participants (419 assigned to the vitamin C group, 417 assigned to the control group) [24][25][26][27][28]32,[36][37][38][39]. The study screening and eligibility assessment process is displayed in Fig. 1. ...
... Three studies were conducted in Europe (Italy, Germany, Scotland) [25,27,32], four studies were conducted in Iran [24,26,28,37], and others were conducted in Argentina [39], China [38], and Australia [36]. Half of trials were conducted in a subclinical depressed population [24,27,28,32,37], whereas the other half of trials were performed in patients with clinical depression [25,26,36,38,39]. ...
Article
Objective We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to clarify the effect of vitamin C supplementation on mood in both depressed and non-depressed populations. Methods A systematic search of PubMed, EMBASE, ISI web of science and Scopus databases was conducted, from inception to 1 March 2020. Random-effects meta-analyses were used to estimate the effect size (as Hedge’s g) of vitamin C supplementation on depressive symptoms. Results Finding from 10 trials with 836 participants revealed no significant improvement in mood status in overall analysis (n = 10, Hedge’s g = 0.09; 95% confidence interval: −0.15 to 0.33; P = 0.465). However, subgroup analysis showed beneficial effects of vitamin C supplementation in patients who were not prescribed antidepressants (subclinical depressed) (n = 5, Hedge’s g: −0.18; 95% CI: −0.35, −0.01, P = 0.041; I2 = 0.00%,). Conclusions Although no significant effect on mood status was observed in overall population, this meta-analysis tentatively suggests that vitamin C may produce mood-elevating effects in patients with subclinical depression. Further research is recommended to reach a firm conclusion.
... However, other supplementations, such as vitamin E, C, and ferrous sulfate, did not offer a significant reduction in the depression score in this study due to many factors, such as the short trial duration, limited sample size in each group, low effective doses, and inadequate measurement at the start and end of the trial. 58 Furthermore, we observed that carnitine's effect in lowering depression parameter scores was linked to improved mitochondrial performance, antioxidant effects, increased cholinergic neurotransmission, enhanced protein, and gene expression, which affected brain metabolism, thereby aiding the improvement of neuropsychological function. 60 Coenzyme Q10, nanocurcumin, and curcumin also had neuroprotective properties, including antioxidant and antiinflammatory activities. ...
... 81 Alternatively, the study by Mazloom reported that although the effect of vitamins C and E did not have significant results on depression levels compared with the placebo in patients with diabetes type-2, vitamin C caused a substantial change in anxiety levels. 58 This change was proposed to be caused by the short duration of treatment and inadequate doses of vitamin C and E. However, Amr et al 82 reported that vitamin C supplementation of 500 mg twice a day with fluoxetine (SSRI antidepressant) of 10 mg per day, administered orally in pediatric patients with MDDs, led to a significant reduction in depressive symptoms compared to the group given fluoxetine alone. This finding shows that vitamin C can be an adjunctive therapy for antidepressant drugs. ...
Article
Depression is a mood disturbance condition that occurs for more than two weeks in a row, leading to suicide. Due to adverse effects of depression, antidepressants and adjunctive therapies, such as dietary supplementation, are used for treatment. Therefore, this review explored and summarized dietary supplements' types, dosages, and effectiveness in preventing and treating depression. A literature search of the PubMed database was conducted in August 2021 to identify studies assessing depression, after which scale measurements based on dietary supplements were identified. From the obtained 221 studies, we selected 63 papers. Results showed PUFA (EPA and DHA combination), vitamin D, and probiotics as the most common supplementation used in clinical studies to reduce depressive symptoms. We also observed that although the total daily PUFA dosage that exhibited beneficial effects was in the range of 0.7-2 g EPA and 0.4-0.8 g DHA daily, with an administration period of three weeks to four months, positive vitamin D-based supplementation effects were observed after administering doses of 2000 IU/day or 50,000 IU/week between 8 weeks and 24 months. Alternatively, microbes from the genus Lactobacillus and Bifidobacterium in the probiotic group with a minimum dose of 108 CFU in various dose forms effectively treated depression. Besides, a depression scale was helpful to assess the effect of an intervention on depression. Hence, PUFA, vitamin D, and probiotics were proposed as adjunctive therapies for depression treatment based on the results from this study.
... Thus, mental disorders and metabolic diseases may cause a vicious cycle and exacerbate each other [6]. In a study, it was reported that short-term supplementation of 1000 mg vitamin C for 6 weeks significantly reduced anxiety levels in diabetic patients through alleviating oxidative damage [35]. In addition, ALA supplementation for 3 months at a dosage 300 mg twice a day had beneficial effects on improving the oxidative, inflammatory, and mood conditions in patients suffering from episodic migraine [36]. ...
Article
Background This investigation was performed to assess the effects of alpha-lipoic acid (ALA) supplementation on psychological status and markers of inflammation and oxidative damage in patients with type 2 diabetes mellitus (T2DM) and coronary heart disease (CHD). Methods This randomized, double-blind, placebo-controlled trial was performed in 60 patients with T2DM and CHD, aged 45–85 years. Patients were randomized into two groups to receive either 600 mg/day ALA (n = 30) or placebo (n = 30) for 12 weeks. Results ALA supplementation significantly decreased Beck Depression Inventory index (BDI) (-5.1 ± 3.5 vs. -1.1 ± 4.8, P = 0.001) when compared with the placebo. ALA supplementation resulted also in a significant reduction of serum high sensitivity C-reactive protein (hs-CRP) (-0.8 ± 1.4 vs. +0.5 ± 0.6 mg/L, P < 0.001) and malondialdehyde (MDA) (-0.3 ± 0.2 vs. -0.1 ± 0.3 µmol/L, P = 0.003), and a significant increase in plasma total antioxidant capacity (TAC) levels (+ 26.8 ± 36.0 vs. -4.6 ± 43.4 mmol/L, P = 0.007) when compared with the placebo. ALA intake upregulated transforming growth factor beta (TGF-β) (P = 0.03) and downregulated gene expression of interleukin-1 (IL-1) (P = 0.001) in peripheral blood mononuclear cells of patients with T2DM and CHD as well. Conclusions ALA supplementation for 12 weeks in patients with T2DM and CHD had beneficial effects on BDI, hs-CRP, TAC, MDA values, and gene expression of IL-1 and TGF-β.
... The relationship between ascorbic acid and depression was initially based on the observation of clinical manifestations of ascorbic acid deficiency [30], and some clinical studies had also explored vitamin C as an adjuvant therapy for depression [31,32]. Some studies explored the relationship between vitamin C and the emotional state in acutely hospitalized patients [31] and type 2 diabetic patients [33]; the study found that vitamin C supplementation improved their emotional levels. Some controlled experiments found that supplementing foods with high vitamin C can improve the mood of adult men [34], and the intake of vitamin C in the diet of depressed students decreased significantly [35]. ...
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Vitamin C is a water-soluble antioxidant. Reducing the level of oxidative stress can alleviate depression. Therefore, we investigated the correlation between dietary vitamin C intake and the risk of depressive symptoms in the general population. Data from the 2007–2018 National Health and Nutrition Examination Survey were used in our study. The dietary intake of vitamin C was assessed by two 24-hour dietary recalls. Depressive symptoms were assessed with the Patient Health Questionnaire-9. Logistic regression and restricted cubic spline models were applied to assess the relationship between dietary vitamin C intake and the risk of depressive symptoms. The multivariate adjusted odds ratio (95% confidence interval) of depressive symptoms for the highest vs. lowest category of dietary vitamin C intake and vitamin C intake derived from vegetables were 0.73 (0.58–0.91) and 0.73 (0.56–0.95). In subgroup analyses, dietary vitamin C intake was negatively correlated with the risk of depressive symptoms in females 18–39 years old and 40–59 year-old groups. A dose-response analysis showed that there was a nonlinear relationship between dietary vitamin C intake and the risk of depressive symptoms. Dietary vitamin C intake and vitamin C intake derived from vegetables were inversely associated with the risk of depressive symptoms among the general population. We recommend increasing the intake of vegetables in daily diet.
... In a randomized controlled study with type 2 diabetics, adjunctive administration of 2 x 500 mg vitamin C per day for a period of four months led to a significant decrease in insulin resistance, HbA1C values and plasma levels of total cholesterol, LDL cholesterol and triglyceride, compared with placebo (Paolisso et al., 1995). Further, supplementary administration of vitamin C appears to enhance the metabolic regulatory activity of the antidiabetic medication metformin (Dakhale et al., 2011) and to have a positive effect on complications like depression (Mazloom et al., 2013) and periodontitis (Gokhale et al., 2013) in diabetics. ...
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Diabetes mellitus is a heterogeneous metabolic syndrome characterized by chronic hyperglycemia with partial or total lack of insulin secretion and insulin resistance. The most common symptoms are polydipsia, polyuria, blurred vision, slow healing sore, nerve damage. Diabetes, being a metabolic, endocrine disorder is directly connected to carbohydrates, lipid, and protein metabolism. As a result, nutrition therapy forms an integral part of diabetes management. Daily caloric intake of 50% - 55% carbohydrates is recommended. Carbohydrate with low glycaemic index is preferred to those with high glycaemic index. Nonnutritive sweeteners are also encouraged for people with diabetes to add increased variety to their food choices. The protein requirement for persons with diabetes is not different from the general population, 15-20 % of total caloric intake. Both soluble and insoluble fibers are encouraged in amounts similar to the recommendations for the general population (20–35 g). Fibers are useful as they prolong gastric emptying, prevent constipation, lower serum cholesterol level, and reduce nutrients diffusion rates, thus reducing blood glucose response. A low-fat diet is advisable for diabetics in order to reach and maintain good weight and health. As part of a healthy diet, 30% of daily calories should come from fats, and of these less than 10% should be saturated fat, less than 10% polyunsaturated fat and 10- 15% monounsaturated fat. As the general population, people with diabetes have no need for vitamin and mineral supplementation when the dietary intake is adequate. Despite much research on nutritional factors in the etiology and management of diabetes, the risk associated with several individual nutrients is not entirely clear. In order to achieve maximum benefit from nutritional interventions in the management of diabetes changes in government policies and legislation will be needed in addition to individual and community-based programs.
... Its deficiency is associated with depression (Pullar et al., 2018). Short-term supplementation of vitamin C significantly decreased anxiety levels in diabetic patients through alleviating oxidative damage (Mazloom et al., 2013), and reverses depressive symptoms (Nguyen et al., 2017;Pullar et al., 2018). ...
Article
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Depression is a serious mental and mood disorder with global health and economic burden. This burden may be overwhelming in low income countries, although there are insufficient data. Most antidepressant formulations are predicated on the monoamine, neuroendocrine and neuro-inflammation hypotheses, with little or no cognizance to other neurochemicals altered in depression. A nutritional strategy with or without conventional antidepressants is recommended, as nutrition plays vital roles in the onset, severity and duration of depression, with poor nutrition contributing to its pathogenesis. This review discusses nutritional potentials of utilizing omega-3 fatty acids, proteins, vitamins, minerals and herbs or their phytochemicals in the management of depression with the aim of reducing depression burden. Literature search of empirical data in books and journals in data bases including but not limited to PubMed, Scopus, Science Direct, Web of Science and Google Scholar that might contain discussions of sampling were sought, their full text obtained, and searched for relevant content to determine eligibility. Omega-3 fatty and amino acids had significant positive anti-depression outcomes, while vitamins and minerals although essential, enhanced omega-3 fatty and amino acids activities. Some herbs either as whole extracts or their phytochemicals/metabolites had significant positive anti-depression efficacy. Nutrition through the application of necessary food classes or herbs as well as their phytochemicals, may go a long way to effectively manage depression. This therefore will provide inexpensive, natural, and non-invasive therapeutic means with reduced adverse effects that can also be applied alongside clinical management. This nutritional strategy should be given more attention in research, assessment and treatment for those with depression and other mental illness in low income countries, especially in Africa.
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Ascorbic acid, a water-soluble vitamin, is highly concentrated in the brain and participates in neuronal modulation and regulation of central nervous system (CNS) homeostasis. Ascorbic acid has emerged as a neuroprotective compound against neurotoxicants and neurodegenerative diseases, including Alzheimer’s disease, multiple sclerosis and amyotrophic lateral sclerosis. Moreover, it improves behavioral and biochemical alterations in psychiatric disorders, including schizophrenia, anxiety, major depressive disorder, and bipolar disorder. Some recent studies have advanced the knowledge on the mechanisms associated with the preventive and therapeutic effects of ascorbic acid by showing that they are linked to improved neurogenesis and synaptic plasticity. This review shows that ascorbic acid has the potential to regulate positively stem cell generation and proliferation. Moreover, it improves neuronal differentiation of precursors cells, promotes adult hippocampal neurogenesis, and has synaptogenic effects that are possibly linked to its protective or therapeutic effects in the brain.
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Increasing evidence in both experimental and clinical studies suggests that oxidative stress plays a major role in the pathogenesis of both types of diabetes mellitus. Free radicals are formed disproportionately in diabetes by glucose oxidation, nonenzymatic glycation of proteins, and the subsequent oxidative degradation of glycated proteins. Abnormally high levels of free radicals and the simultaneous decline of antioxidant defense mechanisms can lead to damage of cellular organelles and enzymes, increased lipid peroxidation, and development of insulin resistance. These consequences of oxidative stress can promote the development of complications of diabetes mellitus. Changes in oxidative stress biomarkers, including superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase, glutathione levels, vitamins, lipid peroxidation, nitrite concentration, nonenzymatic glycosylated proteins, and hyperglycemia in diabetes, and their consequences, are discussed in this review. In vivo studies of the effects of various conventional and alternative drugs on these biomarkers are surveyed. There is a need to continue to explore the relationship between free radicals, diabetes, and its complications, and to elucidate the mechanisms by which increased oxidative stress accelerates the development of diabetic complications, in an effort to expand treatment options.