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The Gut Microbiota (Microbiome) in Cardiovascular Disease and Its Therapeutic Regulation.
Rahman, MM, Islam, F, -Or-Rashid, MH, Mamun, AA, Rahaman, MS, Islam, MM, Meem, AFK, Sutradhar, PR, Mitra, S, Mimi, AA, et al
Frontiers in cellular and infection microbiology. 2022;12:903570
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Cardiovascular disease (CVD) accounts for 31% of all-cause mortality worldwide. Irregularities in the composition of intestinal microbial composition, genetic factors, nutrition, metabolic irregularities, and smoking are among the potential causes of CVD. Intestinal permeability and translocation of endotoxins and bacterial metabolites to systemic circulation may trigger an immune response and inflammation, which may increase the risk of CVD. Synthesis of bacterial metabolites such as trimethylamine N-oxide (TMAO) by choline-inducing gut bacteria and reduced consumption of dietary TMAO precursors may elevate the CVD risk. This review explores the latest research on the role of gut microbiota in the development of atherosclerosis and CVD, as well as potential strategies to prevent CVD by targeting TMAO-producing gut bacteria. Elevated levels of TMAO in the bloodstream can lead to the buildup of cholesterol and ultimately result in atherosclerosis. However, consuming probiotics and fibre-rich foods can help regulate gut bacteria, reduce inflammation, and improve lipid profiles, all of which contribute to better cardiovascular health. More future robust studies are required to examine the mechanistic insights and confirm whether TMAO can serve as a biomarker for preventing CVD through the therapeutic modulation of intestinal bacteria.
Abstract
In the last two decades, considerable interest has been shown in understanding the development of the gut microbiota and its internal and external effects on the intestine, as well as the risk factors for cardiovascular diseases (CVDs) such as metabolic syndrome. The intestinal microbiota plays a pivotal role in human health and disease. Recent studies revealed that the gut microbiota can affect the host body. CVDs are a leading cause of morbidity and mortality, and patients favor death over chronic kidney disease. For the function of gut microbiota in the host, molecules have to penetrate the intestinal epithelium or the surface cells of the host. Gut microbiota can utilize trimethylamine, N-oxide, short-chain fatty acids, and primary and secondary bile acid pathways. By affecting these living cells, the gut microbiota can cause heart failure, atherosclerosis, hypertension, myocardial fibrosis, myocardial infarction, and coronary artery disease. Previous studies of the gut microbiota and its relation to stroke pathogenesis and its consequences can provide new therapeutic prospects. This review highlights the interplay between the microbiota and its metabolites and addresses related interventions for the treatment of CVDs.
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Oats Lower Age-Related Systemic Chronic Inflammation (iAge) in Adults at Risk for Cardiovascular Disease.
Dioum, EHM, Schneider, KL, Vigerust, DJ, Cox, BD, Chu, Y, Zachwieja, JJ, Furman, D
Nutrients. 2022;14(21)
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The immune system and more specifically a form of inflammation is thought to be involved in the development of heart disease. Therefore, reducing inflammation may serve to lower an individual’s risk for heart disease. In a previous study, it was shown that the consumption of an oat-based product improved the risk of heart disease development in individuals with high cholesterol. This randomised control study of 191 healthy male and females aimed to analyse the participants from that study and see if the consumption of an oat-based product affected their level of inflammation also. The results showed that inflammation in individuals who consumed the oat-based product was improved but only in individuals who had elevated inflammation at the start of the trial. This was largely attributed to a decrease in a protein associated with ageing. It was concluded that oats when recommended as part of a personalised diet plan, may decrease inflammation, and prevent heart disease in those who are at an elevated risk. This study could be used by healthcare professionals to understand that the use of oats as part of a personalised diet plan can help to reduce the risk of heart disease.
Abstract
Despite being largely preventable, cardiovascular disease (CVD) is still the leading cause of death globally. Recent studies suggest that the immune system, particularly a form of systemic chronic inflammation (SCI), is involved in the mechanisms leading to CVD; thus, targeting SCI may help prevent or delay the onset of CVD. In a recent placebo-controlled randomized clinical trial, an oat product providing 3 g of β-Glucan improved cholesterol low-density lipoprotein (LDL) levels and lowered cardiovascular risk in adults with borderline high cholesterol. Here, we conducted a secondary measurement of the serum samples to test whether the oat product has the potential to reduce SCI and improve other clinical outcomes related to healthy aging. We investigated the effects of the oat product on a novel metric for SCI called Inflammatory Age® (iAge®), derived from the Stanford 1000 Immunomes Project. The iAge® predicts multimorbidity, frailty, immune decline, premature cardiovascular aging, and all-cause mortality on a personalized level. A beneficial effect of the oat product was observed in subjects with elevated levels of iAge® at baseline (>49.6 iAge® years) as early as two weeks post-treatment. The rice control group did not show any significant change in iAge®. Interestingly, the effects of the oat product on iAge® were largely driven by a decrease in the Eotaxin-1 protein, an aging-related chemokine, independent of a person’s gender, body mass index, or chronological age. Thus, we describe a novel anti-SCI role for oats that could have a major impact on functional, preventative, and personalized medicine.
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Effect of ancient Khorasan wheat on gut microbiota, inflammation, and short-chain fatty acid production in patients with fibromyalgia.
Baldi, S, Pagliai, G, Dinu, M, Di Gloria, L, Nannini, G, Curini, L, Pallecchi, M, Russo, E, Niccolai, E, Danza, G, et al
World journal of gastroenterology. 2022;28(18):1965-1980
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Fibromyalgia (FM) is a systemic syndrome of unclear aetiology, characterized by widespread pain and tenderness, sleeping disorders, fatigue, and cognitive dysfunction. In many cases, gastrointestinal distress is also reported, suggesting a potential involvement of the gut microbiota (GM), as demonstrated by the frequent dysbiosis found in FM subjects. The aim of this study was to examine whether a replacement diet with ancient Khorasan wheat could influence the GM composition, the faecal molecular immune profile, and short-chain fatty acids (SCFAs) production in patients suffering fibromyalgia syndrome. This study was a randomised, double-blind crossover trial which enrolled patients with documented FM who consumed control wheat products or Khorasan wheat products for 8 weeks and then crossed over. Participants (n=20) were randomly assigned to one of the two groups. Results showed that: - both 8-week interventions did not significantly modify either the microbial composition and diversity or the SCFAs levels; - in terms of changes in microbial abundances produced by each dietary intervention, Khorasan wheat products (KD) did not result in modifications at any taxonomic level, whereas the controlled diet (CD) was associated with a significant increase of Turicibacter spp. [bacteria belonging to the phylum Firmicutes]; - faecal molecular inflammatory profile showed that CD resulted in an increased level of a particular anti-inflammatory marker, while no significant differences were reported after KD. Authors conclude that an ancient Khorasan wheat diet results in some beneficial GM compositional and functional modifications that positively correlate with an improvement of fibromyalgia symptomatology.
Abstract
BACKGROUND Fibromyalgia (FM) syndrome is mainly characterized by widespread pain, sleeping disorders, fatigue, and cognitive dysfunction. In many cases, gastrointestinal distress is also reported, suggesting the potential pathogenic role of the gut microbiota (GM). The GM is deeply influenced by several environmental factors, especially the diet, and recent findings highlighted significant symptom improvement in FM patients following various nutritional interventions such as vegetarian diet, low-fermentable oligosaccharides, disaccharides, monosaccharides, and polyols based diets, gluten-free diet, and especially an ancient grain supplementation. In particular, a recent study reported that a replacement diet with ancient Khorasan wheat led to an overall improvement in symptom severity of FM patients. AIM: To examine the effects of ancient Khorasan wheat on the GM, inflammation, and short-chain fatty acid production in FM patients. METHODS After a 2-wk run-in period, 20 FM patients were enrolled in this randomized, double-blind crossover trial. In detail, they were assigned to consume either Khorasan or control wheat products for 8 wk and then, following an 8-wk washout period, crossed. Before and after treatments, GM characterization was performed by 16S rRNA sequencing while the fecal molecular inflammatory response and the short-chain fatty acids (SCFAs) were respectively determined with the Luminex MAGPIX detection system and a mass chromatography-mass spectrometry method. RESULTS The Khorasan wheat replacement diet, in comparison with the control wheat diet, had more positive effects on intestinal microbiota composition and on both the fecal immune and SCFAs profiles such as the significant increase of butyric acid levels (P = 0.054), candidatus Saccharibacteria (P = 9.95e-06) and Actinobacteria, and the reduction of Enterococcaceae (P = 4.97e-04). Moreover, the improvement of various FM symptoms along with the variation of some gut bacteria after the Khorasan wheat diet have been documented; in fact we reported positive correlations between Actinobacteria and both Tiredness Symptoms Scale (P < 0.001) and Functional Outcome of Sleep Questionnaire (P < 0.05) scores, between Verrucomicrobiae and both Widespread Pain Index (WPI) + Symptom Severity scale (SS) (P < 0.05) and WPI (P < 0.05) scores, between candidatus Saccharibacteria and SS score (P < 0.05), and between Bacteroidales and Sleep-Related and Safety Behaviour Questionnaire score (P < 0.05). CONCLUSION The replacement diet based on ancient Khorasan wheat results in beneficial GM compositional and functional modifications that positively correlate with an improvement of FM symptomatology.
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Sleep Disturbance Affects Immune Factors in Clinical Liver Cancer Patients.
Wang, Z, Wang, Y, Huang, J, Xu, J, Chen, F, Zhu, Z, Gao, L, Qin, J, Liu, B, Liang, C
Current oncology (Toronto, Ont.). 2022;29(10):7943-7952
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Many studies have shown that sleep disorders promote tumor growth and can impair immunity at the cellular level. There is however a lack of research in patients with liver cancer. The aim of this study was the asses the quality of sleep and the prevalence of disturbed sleep in patients with liver cancer and to explore whether sleep quality influences immune factors. 210 patients with liver cancer were randomly divided into 2 groups: HBV (Hepatitis B virus) cirrhosis and non-HBV cirrhosis. Their sleep quality was evaluated using a questionnaire and then the patients were divided into 2 groups according to these scores. The association between sleep disturbances and immune factors was analysed by logistic regression models. Over half the patient experienced poor sleep quality. Sleep disturbances were higher in patients with liver cancer of non-HBV cirrhosis than with that coming from the HBV virus. A rise in CD3+ T cells and a reduction in NK cells are associated with sleep disturbances in patients with non-HBV cirrhosis liver cancer. Medicines that can promote sleep and therefore improve immune function might be beneficial. Non-pharmacological sleep interventions to improve sleep quality, should be a safer choice where there are complex drug side effects.
Abstract
BACKGROUND Sleep-wake disturbance is prevalent in patients with liver cancer, but there is no direct evidence of its association and related biological mechanisms. Our study was to assess quality of sleep and to describe prevalence of sleep disturbances in patients with different etiologies of liver cancer, especially to explore whether sleep quality influences immune factors. METHODS A total of 210 patients with liver cancer from August 2015 to December 2015 were randomly divided into two groups including HBV cirrhosis and non-HBV cirrhosis. The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate their sleep quality, and then 202 patients enrolled in this study were divided into two groups according to their PSQI scores: PSQI ≤ 5 and PSQI > 5. The association between sleep disturbances and immune factors was analyzed by logistic regression models. RESULTS A total of 56.9% of liver cancer patients experienced poor sleep quality (PSQI > 5). The prevalence of sleep disturbances was significantly higher in patients with liver cancer of non-hepatitis B virus (HBV) cirrhosis than with that evolving from HBV cirrhosis (66.7% vs. 50%, p = 0.018). In non-HBV cirrhosis liver cancer patients, the PSQI > 5 group had a higher percentage of CD3+ T cells (71.06 ± 11.07 vs. 63.96 ± 14.18, p = 0.014) and lower natural killer (NK) cells (14.67 ± 9.65 vs. 20.5 ± 10.77, p = 0.014) compared with patients with PSQI ≤ 5. Logistic regression further confirmed that liver cancer patients without HBV cirrhosis are more prone to experience poor sleep with increased CD3+ T cells (OR = 1.07, 95% CI = 1.01-1.13, p = 0.030) and decreased NK cells (OR = 0.92, 95% CI = 0.85-0.98, p = 0.014). Our results indicate that increased CD3+ T cells and decreased NK cells are both associated with sleep disturbances in patients with liver cancer of non-HBV cirrhosis. CONCLUSIONS Most liver cancer patients suffer from sleep disturbances, especially evolving from non-HBV cirrhosis. A rise in CD3+ T cells and a reduction in NK cells are associated with sleep disturbances in patients with liver cancer of non-HBV cirrhosis.
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Partial sleep restriction-induced changes in stress, quality of life, and lipid metabolism in relation to cold hypersensitivity: A before-and-after intervention study.
Baek, Y, Jung, K, Kim, H, Lee, S
Medicine. 2022;101(46):e31933
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Inadequate sleep has been associated with an increased risk of cardiovascular disease and has an adverse impact on quality of life (QOL), metabolism and the immune system. Furthermore, sleep is associated with the body’s thermoregulation ability, which is closely associated with distal and proximal skin temperature, as well as core body temperature. The hypothesis of this study was that the physiological and psychological changes caused by insufficient sleep will differ according to cold hypersensitivity (CH). This study was an uncontrolled, before-and-after study with 3 days of 4-hour sleep restriction (SR) as intervention. A total of 130 participants completed the study. Results showed that less-than-optimal sleep duration leads to worsened stress and QOL and reduced low-density lipoprotein cholesterol levels. These changes were significant in the CH group compared to the non-CH group. Authors conclude that their findings provide additional information for evaluating the clinical risks posed by sleep disturbances and assessing the usual sleep patterns according to CH.
Abstract
Sleep disturbances are associated with cold hypersensitivity (CH) and characterized by excessive cold sensation in specific body parts and cold thermal discomfort. This study investigated the effects of short-term sleep restriction followed by a recovery phase on subjective health status, inflammation, and lipid metabolism in different types of CH. A total of 118 healthy adults aged 35 to 44 years without sleep disturbances were enrolled. Participants underwent 4-hour sleep restrictions per day for 3 days at a hospital and then returned to their daily lives for 4 days of rest. CH was assessed using a structured questionnaire with eight characteristic symptoms. A questionnaire and blood tests were administered baseline, after sleep restriction, and follow-up to assess cortisol, lipid profiles, and self-reported stress and quality of life (QOL). Participants were divided into CH (44.1%) and non-CH (55.9%) groups. The CH group showed increased stress, impaired QOL, and decreased low-density lipoprotein-cholesterol (LDL-C) levels compared to the non-CH group after sleep restriction. The variance for QOL (effect size = 0.07), subjective stress (effect size = 0.053), and LDL-C (effect size = 0.029) among time points depended on the group. Short-term sleep restriction was associated with deterioration of subjective health and reduced lipid metabolism; such changes were more evident in the CH group. Our findings suggest the need to consider an individual's CH status to assess the clinical risk associated with insufficient sleep.
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Effects of vitamin C stimulation on rehabilitation of dysphagia after stroke: a randomized trial.
Wang, J, Chang, E, Jiang, Y
European journal of physical and rehabilitation medicine. 2022;58(4):558-564
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Stroke refers to a clinical syndrome of localized or global brain dysfunction caused by cerebrovascular disease. It has the characteristics of rapid onset, high morbidity, high mortality, and high disability. After a stroke, various dysfunction can be caused, and dysphagia is one of the most common symptoms. The acidity of vitamin C can promote the secretion of saliva by stimulating the tongue, which can accelerate the swallowing action, thereby improving the swallowing function. The aim of this study was to explore the effects of vitamin C stimulation on the rehabilitation process, Nourishment State Index and immune function indicator of stroke patients with dysphagia. This study is a randomised controlled trial which enrolled 120 participants with dysphagia. The participants were randomly assigned into control group and vitamin C stimulation group, with 60 cases in each group. Results show that vitamin C acid stimulation significantly improves rehabilitation, and the Nourishment State Index and Immune Function Index of stroke patients with dysphagia. Authors conclude that Vitamin C acid stimulation can further improve the nutritional status and immune function after stroke and promote post-operative recovery of patients. Thus, vitamin C stimulation therapy can be widely used in stroke rehabilitation management.
Abstract
BACKGROUND Stroke is a clinical syndrome of localized or global brain dysfunction caused by cerebrovascular disease. AIM: The aim of this study was to explore the effect of vitamin C acid stimulation on the rehabilitation process, Nourishment State Index and immune function indicators of stroke patients with dysphagia. DESIGN This is a prospective cohort study. SETTING This study was conducted at our hospital. POPULATION We analyzed stroke patients with dysphagia. METHODS A total of 120 stroke patients with dysphagia were randomly divided into a routine group and a test group, with 60 cases in each group. Routine swallowing training was performed in the routine group, and the test group was stimulated with vitamin C acid. The water swallow test (WST) and video fluoroscopic swallowing study (VFSS) were used to compare the rehabilitation of dysphagia in the two groups. Nourishment State Index was evaluated by BMI, serum albumin, total serum protein and hemoglobin. Immune Function Index was evaluated by IgA, IgM and IgG. RESULTS Compared with the control group, the WST level of patients treated with vitamin C acid stimulation intervention were significantly reduced, and the VFSS score were significantly increased. Serum levels of hemoglobin, albumin, total protein, IgA, IgM and IgG in the vitamin C acid stimulation group were remarkably increased than those in the control group. CONCLUSIONS Vitamin C acid stimulation exhibits a good application effect in patients with dysphagia after stroke. Moreover, vitamin C acid stimulation can further improve the nutritional status and immune function after stroke and promote postoperative recovery of patients. Therefore, we believe that vitamin C stimulation therapy can be widely used in stroke rehabilitation management. CLINICAL REHABILITATION IMPACT Vitamin C acid stimulation significantly improves rehabilitation of stroke patients with dysphagia and ameliorates the nutritional status and immune function of patients.
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The Impact of Vitamin D Supplementation on the IFNγ-IP10 Axis in Women with Hashimoto's Thyroiditis Treated with Levothyroxine: A Double-blind Randomized Placebo-controlled Trial.
Robat-Jazi, B, Mobini, S, Chahardoli, R, Mansouri, F, Nodehi, M, Esfahanian, F, Saboor Yaraghi, AA
Iranian journal of allergy, asthma, and immunology. 2022;21(4):407-417
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Hashimoto’s thyroiditis is an autoimmune disease characterized by the presence of antibodies against thyroid proteins such as thyroperoxidase (TPO) and thyroglobulin (TG), the local accumulation of inflammatory cells and immune-mediated destruction of the thyroid gland. Disease manifestation is due to a genetic disposition but is also influenced by several environmental factors, including stress, smoking, infections, and levels of nutrients like iodine, selenium and vitamin D. Many cells of the immune system have receptors for Vitamin D and thus have the potential to be influenced by Vitamin D. Indeed, numerous findings demonstrated that vitamin D can exert anti-inflammatory effects on the immune system. This double-blind, randomized, placebo-controlled trial investigated 40 Hashimoto's thyroiditis subjects and the effect of Vitamin D supplementation on various markers of the immune system that mediate the inflammatory response as part of the interferon-gamma-induced protein 10 (IFNγ-IP10) axis. 20 of the enrolled candidates received 50000 IU of Vitamin D (cholecalciferol) once a week – an equivalent to about 7140 IU per day - over three months. The other half received a placebo. All candidates had a fixed dose of thyroid hormone replacement levothyroxine for the duration of the trial. Before and after the intervention several blood biomarkers were investigated relating to Vitamin D levels, D-receptors, immune activity and inflammation. Upon completion of the trial, the intervention group who supplemented Vitamin D had significantly higher Vitamin D levels, which had increased from an average of 25.29 ng/ml to 50.65ng/ml. In addition, several inflammatory factors were significantly decreased. These findings affirmed Vitamin D’s ability to favourably regulate the IFNγ-IP10 axis, which could slow disease progression. This effect may also be useful for the management of other autoimmune disorders involving IP10 overproduction, which attracts other inflammatory cells. More studies in larger groups would help to get more information on other variables not considered in this trial.
Abstract
Hashimoto's thyroiditis (HT) results from chemoattraction of inflammatory cells toward the thyroid gland by inducing the production of interferon-gamma (IFNγ)-induced protein 10 (IP10) by T helper (Th) 1 cells. Vitamin D may suppress the IFNγ-IP10 axis, but this new function of vitamin D has not yet been investigated in HT patients. In an intervention and control group, patients received 50000 IU cholecalciferol or placebo every week for three months, respectively. The CD4+ T cells of 40 patients were isolated, and the mRNA expression levels of vitamin D receptor (VDR), peroxisome proliferator-activated receptors (PPAR)-α, and PPAR-γ genes were determined by real-time PCR. ELISA method was used to determine serum levels of vitamin D, tumor necrosis factor-alpha (TNF-α), IFN-γ, and IP10. Vitamin D levels in the intervention group were significantly higher than in the placebo group after supplementation. PPAR-α and PPAR-γ gene expression levels did not differ significantly between the two groups. The serum levels of IP10, IFNγ, and TNF-α decreased significantly in the vitamin D group, as well as in the placebo group. During this study, vitamin D levels significantly increased in the intervention group and inflammatory factors decreased. Based on the similar results obtained in the placebo group, further studies with larger sample sizes and longer intervention times are recommended.
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High-dose versus standard-dose vitamin D supplementation in older adults with COVID-19 (COVIT-TRIAL): A multicenter, open-label, randomized controlled superiority trial.
Annweiler, C, Beaudenon, M, Gautier, J, Gonsard, J, Boucher, S, Chapelet, G, Darsonval, A, Fougère, B, Guérin, O, Houvet, M, et al
PLoS medicine. 2022;19(5):e1003999
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The Coronavirus Disease 2019 (COVID-19) caused hundreds of thousands of deaths, mostly in older adults. The aim of this study was to test whether a single oral high-dose of cholecalciferol (vitamin D3) administered within 72 hours after the diagnosis of COVID-19 improves, compared to standard-dose cholecalciferol, the 14-day overall survival among at-risk older adults who are positive to COVID-19. This study is an investigator-initiated, multicentre, open-label, parallel group, intent-to-treat, randomised controlled superiority clinical trial which involves the collaboration of 9 medical centres. Eligible participants (n=260) were randomly assigned to receive a single oral dose of either 400,000 IU (n=130) or 50,000 IU (n=130) cholecalciferol on the day of inclusion. Results show: - reduced overall mortality at day 14. - that high-dose cholecalciferol was safe and did not result in more frequent adverse effects compared to the standard dose. - that some benefits were also found on the 14-day mortality due to COVID-19 as well as on the overall mortality between day 6 and day 14. - that there was no evidence that the single high-dose vitamin D3 administered early in COVID-19 provided any benefit on overall mortality for up to 28 days. Authors conclude that high-dose oral cholecalciferol supplementation is a simple, safe, and inexpensive treatment which may be of interest as an adjuvant to provide a bridge to recovery for at-risk older adults facing the emergence of immune escape variants.
Abstract
BACKGROUND Vitamin D supplementation has been proposed as a treatment for Coronavirus Disease 2019 (COVID-19) based on experimental data and data from small and uncontrolled observational studies. The COvid19 and VITamin d TRIAL (COVIT-TRIAL) study was conducted to test whether a single oral high dose of cholecalciferol (vitamin D3) administered within 72 hours after the diagnosis of COVID-19 improves, compared to standard-dose cholecalciferol, the 14-day overall survival among at-risk older adults infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). METHODS AND FINDINGS This multicenter, randomized, controlled, open-label, superiority trial involved collaboration of 9 medical centers in France. Patients admitted to the hospital units or living in nursing homes adjacent to the investigator centers were eligible if they were ≥65 years, had SARS-CoV-2 infection of less than 3 days, and at least 1 COVID-19 worsening risk factor (among age ≥75 years, SpO2 ≤94%, or PaO2/FiO2 ≤300 mm Hg). Main noninclusion criteria were organ failure requiring ICU, SpO2 ≤92% despite 5 L/min oxygen, life expectancy <3 months, vitamin D supplementation >800 IU/day during the preceding month, and contraindications to vitamin D supplements. Eligible and consenting patients were randomly allocated to either a single oral high-dose (400,000 IU) or standard-dose (50,000 IU) cholecalciferol administered under medical supervision within 72 hours after the diagnosis of COVID-19. Participants and local study staff were not masked to the allocated treatment, but the Steering Committee and the Data and Safety Monitoring Board were masked to the randomization group and outcome data during the trial. The primary outcome was 14-day overall mortality. Between April 15 and December 17, 2020, of 1,207 patients who were assessed for eligibility in the COVIT-TRIAL study, 254 met eligibility criteria and formed the intention-to-treat population. The median age was 88 (IQR, 82 to 92) years, and 148 patients (58%) were women. Overall, 8 (6%) of 127 patients allocated to high-dose cholecalciferol, and 14 (11%) of 127 patients allocated to standard-dose cholecalciferol died within 14 days (adjusted hazard ratio = 0.39 [95% confidence interval [CI], 0.16 to 0.99], P = 0.049, after controlling for randomization strata [i.e., age, oxygen requirement, hospitalization, use of antibiotics, anti-infective drugs, and/or corticosteroids] and baseline imbalances in important prognostic factors [i.e., sex, ongoing cancers, profuse diarrhea, and delirium at baseline]). The number needed to treat for one person to benefit (NNTB) was 21 [NNTB 9 to ∞ to number needed to treat for one person to harm (NNTH) 46]. Apparent benefits were also found on 14-day mortality due to COVID-19 (7 (6%) deaths in high-dose group and 14 (11%) deaths in standard-dose group; adjusted hazard ratio = 0.33 [95% CI, 0.12 to 0.86], P = 0.02). The protective effect of the single oral high-dose administration was not sustained at 28 days (19 (15%) deaths in high-dose group and 21 (17%) deaths in standard-dose group; adjusted hazard ratio = 0.70 [95% CI, 0.36 to 1.36], P = 0.29). High-dose cholecalciferol did not result in more frequent adverse effects compared to the standard dose. The open-label design and limited study power are the main limitations of the study. CONCLUSIONS In this randomized controlled trial (RCT), we observed that the early administration of high-dose versus standard-dose vitamin D3 to at-risk older patients with COVID-19 improved overall mortality at day 14. The effect was no longer observed after 28 days. TRIAL REGISTRATION ClinicalTrials.gov NCT04344041.
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The effect of Nutrition Bio-shield superfood (NBS) on disease severity and laboratory biomarkers in patients with COVID-19: A randomized clinical trial.
Mosadegh, M, Khalkhali, A, Erfani, Y, Nezamdoost, M
Microbial pathogenesis. 2022;172:105792
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Coronavirus disease (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2. Vitamins and their supplements have a positive impact on normal functioning of the immune system subjected to infection. The aim of this study was to determine the effect of Nutrition Bio-shield Superfood (NBS) [an organic, healthy and viable herbal supplement that was prepared from wheat] on disease severity and laboratory biomarkers in patients with COVID-19. This study is a randomised, comparative, parallel two-arm and single-blind clinical trial. Participants (n=70) were randomly assigned (1:1) to one of the two groups: intervention or control. Participants in the intervention group received daily 1.5 gr three times daily of NBS superfood for 14 days. In contrast, those in the control group received a placebo three times a day for 14 days. Results show that the use of NBS superfood has various beneficial effects on COVID-19 disease severity. In fact, there was a decrease in several laboratory parameters (namely C-reactive protein erythrocyte sedimentation rate, D-Dimer, lactate dehydrogenase, aspartate transaminase, alanine transaminase, body temperature, interleukin 6 and tumour necrosis factor-α) and an increase in lymphocyte percentage and blood oxygen level. Moreover, there was a reduction in mortality rate and significantly decreased the duration of hospitalisation in COVID-19 patients. Authors conclude that NBS superfood can be used as an effective natural supplement in the treatment process of COVID-19 disease and may improve and moderate the severity of disease in COVID-19 patients.
Abstract
BACKGROUND Nutrition Bio-shield Superfood (NBS) is an organic and viable herbal supplement that could improve the function of the immune system. The present study aims to determine the effect of NBS on disease severity and laboratory biomarkers in patients with COVID-19. METHODS This current study was a randomized, comparative, parallel two-arm and single-blind clinical trial study performed in Tehran, Iran. In total, 70 patients with COVID-19 were included in the present study and assigned to two groups including 1) intervention group (n = 35) and 2) control group (n = 35). All patients included in the intervention group received 4.5 gr daily rate of NBS superfood, three times the daily rate of 1.5 gr for 14 days. In contrast, patients included in the control group received a placebo three times a day for 14 days. The measurement of laboratory parameters including CRP, ESR, D-Dimer, LDH, CPK, SGOT, SGPT, ALP, FBG, WBC count, PLT, and lymphocyte count was performed using standard kits and methods. Moreover, all serum samples were tested to determine the levels of IL-6 and TNF-ɑ using specific commercially available ELISA kits according to the instructions of the manufacturer. RESULTS A significant decrease in the mean serum level of several variables including CRP (p < 0.001), ESR (p < 0.001), D- Dimer (p = 0.001), LDH (p < 0.001), SGOT (p = 0.002), SGPT (p = 0.019), ALP (p < 0.001), WBC count (p < 0.001), body temperature (p = 0.013), IL-6 (p < 0.001), and TNF-α (p < 0.001) was seen 14 days after intervention from baseline in the intervention group than control group. In contrast, in the intervention group, the significant increase from baseline of lymphocyte percentage (p < 0.001) and oxygen saturation (p < 0.001) was seen 14 days after receiving NBS superfood than the control group. CONCLUSION Results showed that the use of NBS superfood had various beneficial effects on COVID-19 disease severity. These results suggest that NBS superfood can be used as an effective natural supplement in the treatment process of COVID-19 disease.
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Enriched Marine Oil Supplement Increases Specific Plasma Specialized Pro-Resolving Mediators in Adults with Obesity.
Al-Shaer, AE, Regan, J, Buddenbaum, N, Tharwani, S, Drawdy, C, Behee, M, Sergin, S, Fenton, JI, Maddipati, KR, Kane, S, et al
The Journal of nutrition. 2022;152(7):1783-1791
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Specialised pro-resolving mediators (SPMs) are highly potent oxylipins [metabolites] synthesized from omega-3 and omega-6 polyunsaturated fatty acids. SPMs have a critical role in resolving inflammation and returning damaged tissues to homeostasis. The main aim of this study was to determine if a marine oil supplement increased specific metabolites of the SPM biosynthetic pathway in adults with obesity. This study is a non-randomised uncontrolled clinical trial in adults with obesity. Twenty-three participants (n = 13 females, 10 males) aged between 50–65 years were enrolled. Only postmenopausal females were included in order to reduce confounding effects of oestrogen on lipid metabolism during supplementation. Results show that: - the marine oil supplement significantly increased some oxylipins of the SPM biosynthetic pathway. - there wasn’t an increase in the concentration of D-series resolvins upon intervention, although several docosahexaenoic acid-derived metabolites were increased. - the supplement decreased some HETEs [metabolites], which are synthesized from arachidonic acid. Authors conclude that their findings provide a framework for futures studies on the use of a marine oil supplement to examine the effects of how SPMs and their metabolic intermediates control varying aspects of inflammation and immunity, including antibody concentrations, in subjects with obesity.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Marine oil enriched with specialised pro-resolving mediators raise levels of EPA, DPA and DHA-metabolites in adult subjects with obesity
- Larger randomised, blinded and placebo-controlled trials are required to inform healthcare practitioner clinical practice decisions relating to SPM enriched marine oil supplementation
- Future research is required to determine if increased concentrations of SPMs control the resolution of inflammation in humans with obesity.
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:
- Specialised pro-resolving mediators (SPMs) are oxylipins synthesised from omega-3 and -6 PUFAs which play a role in resolving inflammation.
- The authors highlight mouse studies have found that increasing the levels of SPMs and their metabolic intermediates can improve a range of obesity related complications. Thus, there is scientific interest in increasing the levels of SPMs in humans with diseases associated with chronic inflammation, such as obesity.
- This small non-randomised uncontrolled clinical trial of 23 individuals (13 female; 10 male) aged 50-65 years with obesity (BMI 30-40), aimed to determine the impacts of 1 month supplementation with marine oil particularly enriched with 14-hydroxydocosahexanenoic acid (14-HDHA), 17-HDHA and 18-hydroxydocosahenaenoic acid (HEPE) on:
- The change in levels of PUFA-derived oxylipins from baseline
- The change in abundance of circulating peripheral blood mononuclear cells (PBMCs)
- The change in antibody production
Intervention
- 2g enriched marine oil (4 capsules of SPM Active provided by Metagenics, study sponsor) once daily for 28-30 consecutive days.
Inclusion/Exclusion Criteria
- Only post-menopausal women were included to reduce confounding effects of oestrogen on lipid metabolism
- Individuals were excluded if diagnosed with Type 1 or 2 diabetes, autoimmunity, liver disease, coagulopathy, uncontrolled hypothyroid or active malignancy
- Individuals were excluded if they consumed omega-3 PUFA supplements within 3 months of intervention, regularly consumed >2 servings per week of fatty fish, had a fish/shellfish allergy or were taking a predetermined list of medications.
Findings
- Statistically significant increases were found in certain EPA, DPA and DHA-derived metabolites in response to supplementation relative to baseline. However, only 17-HDHA concentrations increased relative to baseline, with no effect on 14-HDHA or 18-HEPE, despite the supplement being enriched with all 3 metabolites
- Statistically significant decreases were found in arachidonic acid (AA)-derived oxylipins post supplementation relative to baseline
- Increases in immune cell populations in circulation did not reach significance post supplementation when measured by PBMCs.
Conclusions
An enriched marine oil supplement increased select SPMs in adults with obesity.
Clinical practice applications:
- Healthcare practitioners working with adults with obesity can use the results from this trial to understand that 1 month supplementation with 4g of enriched marine oil supplementation raises levels of certain EPA, DPA and DHA metabolites
- Practitioners may want to follow the research in this area as larger, controlled trials are conducted and comparisons made with non-enriched fatty acid supplements.
Considerations for future research:
- Future clinical studies of SPM supplementation are required that are double-blind, randomised and placebo-controlled to inform scientific findings in this area
- This study was inadequately powered to assess differences between female and male participants and therefore larger trials are needed to inform the sex differences in oxylipins within the population with obesity
- Further research is required in younger subjects with obesity to assess SPMs as a possible chronic inflammation preventative strategy, due to inflammation complications over time
- Future research should take account of the heterogeneity in the population with obesity, such as microbiome profiles, food intake and baseline metabolic status
- Further studies comparing impacts of standard marine oil with enriched marine oil on chronic inflammation would inform healthcare practitioners in their clinical practice.
Abstract
BACKGROUND Specialized pro-resolving mediators (SPMs), synthesized from PUFAs, resolve inflammation and return damaged tissue to homeostasis. Thus, increasing metabolites of the SPM biosynthetic pathway may have potential health benefits for select clinical populations, such as subjects with obesity who display dysregulation of SPM metabolism. However, the concentrations of SPMs and their metabolic intermediates in humans with obesity remains unclear. OBJECTIVES The primary objective of this study was to determine if a marine oil supplement increased specific metabolites of the SPM biosynthetic pathway in adults with obesity. The second objective was to determine if the supplement changed the relative abundance of key immune cell populations. Finally, given the critical role of antibodies in inflammation, we determined if ex vivo CD19 + B-cell antibody production was modified by marine oil intervention. METHODS Twenty-three subjects [median age: 56 y; BMI (in kg/m2): 33.1] consumed 2 g/d of a marine oil supplement for 28-30 d. The supplement was particularly enriched with 18-hydroxyeicosapentaenoic (HEPE), 14-hydroxydocosahexaenoic acid (14-HDHA), and 17-HDHA. Blood was collected pre- and postsupplementation for plasma mass spectrometry oxylipin and fatty acid analyses, flow cytometry, and B-cell isolation. Paired t-tests and Wilcoxon tests were used for statistical analyses. RESULTS Relative to preintervention, the supplement increased 6 different HEPEs and HDHAs accompanied by changes in plasma PUFAs. Resolvin E1 and docosapentaenoic acid-derived maresin 1 concentrations were increased 3.5- and 4.7-fold upon intervention, respectively. The supplement did not increase the concentration of D-series resolvins and had no effect on the abundance of immune cells. Ex vivo B-cell IgG but not IgM concentrations were lowered postsupplementation. CONCLUSIONS A marine oil supplement increased select SPMs and their metabolic intermediates in adults with obesity. Additional studies are needed to determine if increased concentrations of specific SPMs control the resolution of inflammation in humans with obesity. This trial was registered at clinicaltrials.gov as NCT04701138.