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Effects of Antioxidants on Pain Perception in Patients with Fibromyalgia-A Systematic Review.
Fernández-Araque, A, Verde, Z, Torres-Ortega, C, Sainz-Gil, M, Velasco-Gonzalez, V, González-Bernal, JJ, Mielgo-Ayuso, J
Journal of clinical medicine. 2022;11(9)
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Fibromyalgia (FM) is characterised by widespread chronic pain, fatigue, sleep disturbances, and cognitive impairment. As a result of oxidative stress, reactive oxygen species (ROS) are produced and improperly disposed of, resulting in peripheral and central sensitisations, and a reduction of the pain threshold in FM patients. It is well known that antioxidants are protective against oxidative stress and that reducing antioxidant levels can result in increased pain in patients with FM. An overview of 17 studies was conducted to evaluate the effect of antioxidant supplementation on pain perception and the appropriate duration of treatment for FM patients in this systematic review. This systematic review found that supplementation with Fibromyalgine® (Fib) (that contains vitamin C, acerola ginger root, and freeze-dried royal jelly), 300-400 gm/d of coenzyme Q10 alone in combination with Pregabalin, ferric carboxymaltose, vitamin C, E, and Nigella sativa, magnesium + amitriptyline, acetyl L-carnitine, and Sun Chlorella™ green algae are effective in reducing pain perception in FM patients. In patients with FM, alpha-lipoic acid supplementation significantly reduced pain scores. 80% of FM patients reported reduced pain after supplement treatment for at least six weeks. There is a need for further robust long-term studies to confirm the effectiveness and clinical applicability of antioxidants in the management of FM, as well as to identify the pathophysiology of FM. This research may, however, be used by healthcare professionals to gain a better understanding of the potential benefits of antioxidants in the treatment of pain associated with FM.
Abstract
In recent years, antioxidant supplements have become popular to counteract the effects of oxidative stress in fibromyalgia and one of its most distressing symptoms, pain. The aim of this systematic review was to summarize the effects of antioxidant supplementation on pain levels perceived by patients diagnosed with fibromyalgia. The words used respected the medical search terms related to our objective including antioxidants, fibromyalgia, pain, and supplementation. Seventeen relevant articles were identified within Medline (PubMed), Scopus, Web of Science (WOS), the Cochrane Database of Systematic Review, and the Cochrane Central Register of Controlled Trials. This review found that antioxidant supplementation is efficient in reducing pain in nine of the studies reviewed. Studies with a duration of supplementation of at least 6 weeks showed a benefit on pain perception in 80% of the patients included in these studies. The benefits shown by vitamins and coenzyme Q10 are remarkable. Further research is needed to identify the effects of other types of antioxidants, such as extra virgin olive oil and turmeric. More homogeneous interventions in terms of antioxidant doses administered and duration would allow the effects on pain to be addressed more comprehensively.
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Do B Vitamins Enhance the Effect of Omega-3 Polyunsaturated Fatty Acids on Cardiovascular Diseases? A Systematic Review of Clinical Trials.
Zhu, J, Xun, PC, Kolencik, M, Yang, KF, Fly, AD, Kahe, K
Nutrients. 2022;14(8)
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Dietary intake of B-vitamins or omega-3 polyunsaturated fatty acids (PUFAs) has been found to be inversely related to cardiovascular disease (CVD). The aim of this study was to examine whether the combined supplementation of B-vitamins and omega-3 PUFAs could provide additional beneficial effects on improving risk factors to prevent CVD beyond the effects of either of them alone. This study is a systematic review of fifteen studies. The sample sizes ranged from 12 to 2501 participants with study duration ranging from 4 weeks to 4.7 years. Results show that the combined supplementation with B-vitamins and omega-3 PUFAs may be promising and more effective at reducing plasma homocysteine, triglycerides and low-density lipoprotein cholesterol than each supplementation alone. Authors conclude that: - there is no solid evidence that the joint supplementation of B-vitamins and omega-3 PUFAs can offer a synergistic effect on preventing CVD and decreasing the relevant morbidity and/or mortality in susceptible populations. - dietetic strategies for preventing CVD need to focus more on the importance of considering effects at the whole food and dietary patterns level. - further well-designed high-quality trials that will use the combined supplementation of B vitamins and omega-3 PUFAs or dietary patterns rich in these two types of nutrients are required.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Combined vitamin B and n3 PUFA supplementation might have favourable health effects
- Combined vitamin B and n3 PUFA supplementation could help in the primary and secondary prevention of cardiovascular disease
- The suggested favourable dose ranges are vitamin B6: 2.5–80 mg/day, vitamin B12: 20–1000 μg/day, folic acid: 150–10000 μg/day, and n3 PUFA 0.2–2) g/day.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
- The paper reviews whether combined supplementation of vitamin B (B2, B6, B9, and B12) and omega-3 polyunsaturated fatty acids (n3 PUFA) outweighs the individual cardiovascular benefits of each supplement. Registered in PROSPERO under CRD42018085993
- A total of 15 clinical studies including 8,263 individuals published from December 2021, that investigated the combined effects of the supplements met inclusion criteria and were included in the review
- Although the results indicate the beneficial effects of combined supplementation in primary and secondary cardiovascular prevention, firm conclusions cannot be drawn from the existing data, and more studies are needed in this area.
Clinical practice applications:
In comparison with a single supplement alone, the combined administration of vitamin B and n3 PUFA might have:
- Hypolipidemic effects, by reducing triglycerides and LDL-cholesterol. Some of the studies indicate a lowering of LDL-c up to 13% and triglycerides up to 24%
- Anti-inflammatory effects, by reducing homocysteine. Based on some of the studies, the lowering effects might go up to 39%.
Dietary practice might benefit from the following:
- The authors highlighted food-based and healthy dietary pattern-based strategies should include food sources rich in these nutrients such as fish, vegetables, fruit, legumes, nuts, and eggs
- The authors conclude that intake of whole foods and whole diets rich in desirable foods (such as MedDiet) should be encouraged
- The supplementation dose ranges in the studies covered by the review were the following: vitamin B6: 2.5–80 mg/day, vitamin B12: 20–1000 μg/day, folic acid: 150–10000 μg/day and n3 PUFA 0.2–2) g/day
- Limitations of the systematic review include different supplementation regimens, variability of study designs in terms of duration of the intervention, existence of placebo group, dosages and the inability to monitor study subjects’ habitual diet.
Considerations for future research:
- Future studies should be designed regarding the need for a uniform methodological approach in testing the combined effects of vitamin B complex and n3 PUFA supplements
- The studies should investigate supplementation strategies and dietary patterns rich in both nutrients.
Abstract
Studies have suggested that B vitamins or omega-3 polyunsaturated fatty acids (PUFAs) may deter the development of cardiovascular disease (CVD). This systematic review aims to examine whether the combined supplementation of both B vitamins and omega-3 PUFAs could provide additional beneficial effects to prevent CVD beyond the effect of each supplement based on clinical trials published up to December 2021. The overall findings are inconsistent and inconclusive, yet the combined supplementation of these two nutrients may be more effective at reducing plasma homocysteine, triglyceride, and low-density lipoprotein-cholesterol than the individual components. The underlying mechanisms mainly include alleviating endothelial dysfunction, inhibiting atherosclerosis and lesion initiation, reducing oxidative stress, suppressing activation of pro-inflammatory cytokines, regulating endothelial nitric oxide synthase, and interfering with methylation of genes that promote atherogenesis. Although biologically plausible, the existing literature is insufficient to draw any firm conclusion regarding whether B vitamins can further enhance the potential beneficial effects of omega-3 PUFA intake on either primary or secondary prevention of CVD. The inconsistent findings may be largely explained by the methodological challenges. Therefore, well-designed high-quality trials that will use the combined supplementation of B vitamins and omega-3 PUFAs or dietary patterns rich in these two types of nutrients are warranted.
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Vitamin C-An Adjunctive Therapy for Respiratory Infection, Sepsis and COVID-19.
Holford, P, Carr, AC, Jovic, TH, Ali, SR, Whitaker, IS, Marik, PE, Smith, AD
Nutrients. 2020;12(12)
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High levels of vitamin C are likely required during viral infections due to its ability to decrease inflammation and control the immune system. This large review looked at 119 studies surrounding this. Evidence supporting vitamin C deficiency during several viral infections was reviewed, however studies in Covid-19 are lacking. At the time of writing, 45 trials of vitamin C and Covid-19 were in progress. It was stated that deficiency could be due to increased use during infection. The authors reviewed clinical research of vitamin C in colds, pneumonia, sepsis and Covid-19. The general trend was that severity of symptoms and duration of illness decreased with vitamin C. Vitamin C supplementation was generally considered safe, although those with history of kidney stones or kidney dysfunction should be cautious. It was concluded that the potential of vitamin C to reduce inflammation and influence the immune system alongside its safety profile and low cost, makes it a possible therapy for those with Covid-19. This paper could be used by healthcare professionals to help understand the overall role of vitamin C in viral infections with a view to recommendation to individuals with viral infections.
Abstract
There are limited proven therapies for COVID-19. Vitamin C's antioxidant, anti-inflammatory and immunomodulating effects make it a potential therapeutic candidate, both for the prevention and amelioration of COVID-19 infection, and as an adjunctive therapy in the critical care of COVID-19. This literature review focuses on vitamin C deficiency in respiratory infections, including COVID-19, and the mechanisms of action in infectious disease, including support of the stress response, its role in preventing and treating colds and pneumonia, and its role in treating sepsis and COVID-19. The evidence to date indicates that oral vitamin C (2-8 g/day) may reduce the incidence and duration of respiratory infections and intravenous vitamin C (6-24 g/day) has been shown to reduce mortality, intensive care unit (ICU) and hospital stays, and time on mechanical ventilation for severe respiratory infections. Further trials are urgently warranted. Given the favourable safety profile and low cost of vitamin C, and the frequency of vitamin C deficiency in respiratory infections, it may be worthwhile testing patients' vitamin C status and treating them accordingly with intravenous administration within ICUs and oral administration in hospitalised persons with COVID-19.
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Menopause-Associated Lipid Metabolic Disorders and Foods Beneficial for Postmenopausal Women.
Ko, SH, Kim, HS
Nutrients. 2020;12(1)
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Menopause is the absence of menstruation due to the loss of ovarian activity with ageing. During this transition period, changes in hormones, primarily the decline in the oestrogen estradiol, give rise to altered lipid metabolism. An unfavourable lipid profile presents a risk for metabolic disorders, such as cardiovascular diseases and type 2 diabetes. Post-menopausal changes also lead to shifts in body fat and fat distribution, resulting in an increased tendency for central fat accumulation and obesity. Obesity is associated with insulin resistance. This susceptibility for weight accumulation is possibly also driven by the age-associated decline in skeletal muscle, which reduces metabolic energy expenditure. This review summarizes the physiology of menopause and postmenopause and the consequential impact on lipid metabolism. In addition, there is a discussion of dietary recommendations, nutritional and plant-derived compounds that could support the management of menopause associated changes in lipid levels, metabolic risk factors and obesity. The recommendations discussed include traditional healthy diets and low-calorie diets, with attention drawn to adequate protein intake. Furthermore, the role of probiotics, nutritional and plant-sourced constituents are considered, including Vitamin D, Omega-3 fatty acids, antioxidants like Vitamin A, β-carotene, Vitamin C and E, genistein, resveratrol, flavonoids, indoles and capsaicin. The authors advocate sourcing these compounds from a varied whole-foods diet, which would minimize nutrient interactions and absorption issues that can occur with supplementation. This review may be of interest to those supporting the nutritional needs of menopausal and post-menopausal women, that are experiencing or are at risk of experiencing metabolic disorders.
Abstract
Menopause is clinically diagnosed as a condition when a woman has not menstruated for one year. During the menopausal transition period, there is an emergence of various lipid metabolic disorders due to hormonal changes, such as decreased levels of estrogens and increased levels of circulating androgens; these may lead to the development of metabolic syndromes including cardiovascular diseases and type 2 diabetes. Dysregulation of lipid metabolism affects the body fat mass, fat-free mass, fatty acid metabolism, and various aspects of energy metabolism, such as basal metabolic ratio, adiposity, and obesity. Moreover, menopause is also associated with alterations in the levels of various lipids circulating in the blood, such as lipoproteins, apolipoproteins, low-density lipoproteins (LDLs), high-density lipoproteins (HDL) and triacylglycerol (TG). Alterations in lipid metabolism and excessive adipose tissue play a key role in the synthesis of excess fatty acids, adipocytokines, proinflammatory cytokines, and reactive oxygen species, which cause lipid peroxidation and result in the development of insulin resistance, abdominal adiposity, and dyslipidemia. This review discusses dietary recommendations and beneficial compounds, such as vitamin D, omega-3 fatty acids, antioxidants, phytochemicals-and their food sources-to aid the management of abnormal lipid metabolism in postmenopausal women.
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Inflammaging and Oxidative Stress in Human Diseases: From Molecular Mechanisms to Novel Treatments.
Zuo, L, Prather, ER, Stetskiv, M, Garrison, DE, Meade, JR, Peace, TI, Zhou, T
International journal of molecular sciences. 2019;20(18)
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Reactive oxygen species (ROS) are produced during normal metabolic processes or can be induced by environmental factors. High levels of ROS in the cell can lead to oxidation causing cellular damage and a subsequent increase in inflammation, which is a significant contributor to disease. Age-associated increases in such chronic, low-grade inflammation is also referred to as inflammaging. This review summarizes how inflammaging plays a role in various age-related health conditions. Described are the mechanisms of how ROS and the age-related decline in cellular turn-over and immune activation contribute to the pathology of cardiovascular disease, cancer, neurodegeneration concerning Alzheimer’s and Parkinson’s disease, diabetes and rheumatoid arthritis. Furthermore, the authors discuss potential treatments that could assist in the management of such inflammaging-related diseases. These include vaccines to stimulate immune activity, stem cell intervention, drugs like metformin, nutritional and nutraceutical supplements like zinc, vitamin E, vitamins C, D, carotenoids, polyphenols and flavonoids like resveratrol, red algae extract and melatonin. Addressed are also general dietary concepts like calorie restriction, the benefits of the Mediterranean diet or a whole foods diet, and the potential of specific plant derived compounds like baicalin and sulforaphanes. The authors also briefly highlight the importance of the gut microbiome, as a poor gut microbiota has been associated with unfavourable age-related immune alterations and overall inflammaging. This review provides a comprehensive resource, detailing the effects and mechanisms of oxidative damage and its contribution to age-related diseases, including a list of interventions to consider when navigating the impact and risks associated with inflammaging.
Abstract
It has been proposed that a chronic state of inflammation correlated with aging known as inflammaging, is implicated in multiple disease states commonly observed in the elderly population. Inflammaging is associated with over-abundance of reactive oxygen species in the cell, which can lead to oxidation and damage of cellular components, increased inflammation, and activation of cell death pathways. This review focuses on inflammaging and its contribution to various age-related diseases such as cardiovascular disease, cancer, neurodegenerative diseases, chronic obstructive pulmonary disease, diabetes, and rheumatoid arthritis. Recently published mechanistic details of the roles of reactive oxygen species in inflammaging and various diseases will also be discussed. Advancements in potential treatments to ameliorate inflammaging, oxidative stress, and consequently, reduce the morbidity of multiple disease states will be explored.
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Vitamin C and Immune Function.
Carr, AC, Maggini, S
Nutrients. 2017;9(11)
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Vitamin C is essential to immune function and performs several crucial roles supporting cellular function in both the innate and adaptive immune system. Low storage capacity means a regular intake of a minimum 100-200mg of Vit C daily is necessary for adequate plasma levels. A potent antioxidant, Vit C can readily donate electrons as part of its immuno-protective role protecting against oxidative damage. VitC is a cofactor for the transportation of fatty acids into the cell mitochondria as well as numerous gene regulatory enzymes, including those involved in the cardiovascular response to infection. Structurally, Vit C supports barrier integrity and wound healing and concentrations of the vitamin accumulate in the epidermis. White leukocyte cells actively accumulate intracellular stores of Vit C indicating an important role in immune signalling. Neutrophils use Vit C to help migration to infection sites in the body and it enhances the differentiation and proliferation of B- and T-cells. Vit C has been shown to moderate inflammatory cytokines and reduce infection severity and longevity. Specifically, supplementation with high dose Vit C appears to be able to both prevent and ameliorate respiratory and systemic infections such as pneumonia. In summary, optimal levels of Vit C are necessary for proper immune function and resistance to infections.
Abstract
Vitamin C is an essential micronutrient for humans, with pleiotropic functions related to its ability to donate electrons. It is a potent antioxidant and a cofactor for a family of biosynthetic and gene regulatory enzymes. Vitamin C contributes to immune defense by supporting various cellular functions of both the innate and adaptive immune system. Vitamin C supports epithelial barrier function against pathogens and promotes the oxidant scavenging activity of the skin, thereby potentially protecting against environmental oxidative stress. Vitamin C accumulates in phagocytic cells, such as neutrophils, and can enhance chemotaxis, phagocytosis, generation of reactive oxygen species, and ultimately microbial killing. It is also needed for apoptosis and clearance of the spent neutrophils from sites of infection by macrophages, thereby decreasing necrosis/NETosis and potential tissue damage. The role of vitamin C in lymphocytes is less clear, but it has been shown to enhance differentiation and proliferation of B- and T-cells, likely due to its gene regulating effects. Vitamin C deficiency results in impaired immunity and higher susceptibility to infections. In turn, infections significantly impact on vitamin C levels due to enhanced inflammation and metabolic requirements. Furthermore, supplementation with vitamin C appears to be able to both prevent and treat respiratory and systemic infections. Prophylactic prevention of infection requires dietary vitamin C intakes that provide at least adequate, if not saturating plasma levels (i.e., 100-200 mg/day), which optimize cell and tissue levels. In contrast, treatment of established infections requires significantly higher (gram) doses of the vitamin to compensate for the increased inflammatory response and metabolic demand.
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Vitamin C and Infections.
Hemilä, H
Nutrients. 2017;9(4)
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This article reviews the available literature on the effect of vitamin C on infections. In the early 20th century scurvy was found to be due to vitamin C deficiency and it was also observed that lack of vitamin C predisposed to infections, in particular pneumonia, which sparked interest in the connection between vitamin C and infections. Infections increase oxidative stress which may lead to a decrease in plasma levels of vitamin C, which has antioxidant properties, and much higher intakes of vitamin C may be necessary to maintain sufficiently high plasma levels during an infection. In animal studies vitamin C has been found to be beneficial against various infectious agents including bacteria, viruses, Candida albicans, and protozoa. The common cold is the most widely studied infection with regards to vitamin C. Vitamin C supplementation has been shown to only decrease the incidence of the common cold in specific subgroups but not the population as a whole. However, supplementing no less than 1g vitamin C per day significantly shortened the duration and alleviated severity of colds. Interpretation of studies is complicated by a number of factors, including dose of vitamin C, with up to a 240-fold difference between the lowest and highest vitamin C supplementary dose used in the common cold trials. This review also discusses why interest in the vitamin C/common cold research plummeted in the mid-1970s. Studies on vitamin C and pneumonia showed benefits, but as all these trials were done in specific population groups, the results cannot necessarily be generalised. There is insufficient clinical research into the use of vitamin C for other infections. The author concludes that in view of vitamin C being safe and cheap even modest clinical effects are worth exploring.
Abstract
In the early literature, vitamin C deficiency was associated with pneumonia. After its identification, a number of studies investigated the effects of vitamin C on diverse infections. A total of 148 animal studies indicated that vitamin C may alleviate or prevent infections caused by bacteria, viruses, and protozoa. The most extensively studied human infection is the common cold. Vitamin C administration does not decrease the average incidence of colds in the general population, yet it halved the number of colds in physically active people. Regularly administered vitamin C has shortened the duration of colds, indicating a biological effect. However, the role of vitamin C in common cold treatment is unclear. Two controlled trials found a statistically significant dose-response, for the duration of common cold symptoms, with up to 6-8 g/day of vitamin C. Thus, the negative findings of some therapeutic common cold studies might be explained by the low doses of 3-4 g/day of vitamin C. Three controlled trials found that vitamin C prevented pneumonia. Two controlled trials found a treatment benefit of vitamin C for pneumonia patients. One controlled trial reported treatment benefits for tetanus patients. The effects of vitamin C against infections should be investigated further.