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Antioxidant vitamins supplementation reduce endometriosis related pelvic pain in humans: a systematic review and meta-analysis.
Zheng, SH, Chen, XX, Chen, Y, Wu, ZC, Chen, XQ, Li, XL
Reproductive biology and endocrinology : RB&E. 2023;21(1):79
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Endometriosis is a common gynaecological disorder in reproductive-age women which leads to infertility and pain symptoms. Current pain management approaches involve medications and surgical treatments, but their side effects and risk of recurrence have led to the exploration of alternative options. The aim of this study was to clarify the potential effects of antioxidant vitamins supplementation on endometriosis. This study was a systematic review and meta-analysis of eleven studies, comprising a total of 589 patients. Results showed that antioxidant vitamins supplementation can effectively alleviate endometriosis-related pain and reduce inflammatory markers. Authors conclude that antioxidant vitamins supplementation can be considered as an alternative treatment either on its own or in combination with other methods for managing endometriosis-related pain. However, further research would help to provide a clearer understanding of the role of antioxidant vitamins supplementation in women with endometriosis.
Abstract
OBJECTIVE This study aimed to clarify the effect of antioxidant vitamins supplementation on endometriosis-related pain. METHODS A systematic search of PubMed, Web of Science, Cochrane Library, Scopus, and China National Knowledge Infrastructure (CNK) databases was conducted to identify relevant studies published in English and Chinese up to 16 March 2023. The search terms used were "endometriosis" OR "endometrioma" OR "endometrium" AND "antioxidant" OR "Vitamin C" OR "Vitamin E" OR "Vitamin D" OR "25-OHD" OR "25(OH)D" OR "25-hydroxyvitamin D". Eligible studies were randomized controlled trials (RCTs) that assessed pain scores using the Visual Analogue Scale (VAS). Mean differences or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the effect of antioxidant vitamins supplementation on endometriosis. The quality of the included studies was assessed using the Cochrane Risk of Bias Tool. The study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. RESULTS A total of 13 RCTs involving 589 patients were included in this meta-analysis. We identified 11 studies that evaluated the effect of antioxidant vitamins supplementation on endometriosis-related pain. The results indicated that the supplementation of antioxidant vitamins can effectively alleviate endometriosis-related pain. Subgroup analysis showed that the supplementation of vitamin E (with or without vitamin C) had a positive effect on improving clinical pelvic pain in patients with chronic pelvic pain. Conversely, supplementation of vitamin D was associated with a reduction in pelvic pain in endometriosis patients, but the difference was not statistically significant compared to the placebo. Additionally, we observed changes in oxidative stress markers following vitamin supplementation. Plasma malondialdehyde (MDA) concentration decreased in patients with endometriosis after antioxidant vitamin supplementation, and the plasma MDA level was inversely correlated with the time and dose of vitamin E and C supplementation. Furthermore, the inflammatory markers in peritoneal fluid, including RANTES, interleukin-6, and monocyte chemoattractant protein-1, significantly decreased after antioxidant therapy. These findings suggest that antioxidant vitamins may alleviate pain in endometriosis patients by reducing inflammation. CONCLUSIONS The included studies support the potential role of antioxidant vitamins in the management of endometriosis. Supplementation with antioxidant vitamins effectively reduced the severity of dysmenorrhea, improved dyspareunia and pelvic pain, and enhanced quality of life in these patients. Therefore, antioxidant vitamin therapy could be considered as an alternative treatment method, either alone or in combination with other approaches, for endometriosis-related pain. TRIAL REGISTRATION PROSPERO registration number: CRD42023415198.
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Effect of vitamin D supplementation on cardiac-metabolic risk factors in elderly: a systematic review and meta-analysis of clinical trials.
Qorbani, M, Zarei, M, Moradi, Y, Appannah, G, Djalainia, S, Pourrostami, K, Ejtahed, HS, Mahdavi-Gorabi, A, Naderali, EK, Khazdouz, M
Diabetology & metabolic syndrome. 2022;14(1):88
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Modifiable risk factors such as dyslipidemia, hyperglycemia, obesity, and hypertension are characteristics of cardio-metabolic disorder which may lead to diabetes or cardiovascular disease. Previous research has shown an association between vitamin D deficiency and cardio-metabolic disorders. Studies have also shown that vitamin D deficiency is prevalent in older people. Therefore, this systematic review and meta-analysis evaluated the beneficial effects of Vitamin D supplementation (VDS) on the cardio-metabolic profile in elderly people. Twelve studies are included in this systematic review and meta-analysis. VDS dosage ranged from 400 IU/day to 4000 IU/day generally in most of the included studies, and the duration of intervention ranged from two months to one year. This systematic review and meta-analysis showed an improvement in total cholesterol and triglycerides followed by VDS in elderly participants. The subgroup analysis revealed improved glycaemic indices in elderly people with glycaemic irregularities. Longer-term VDS intervention improved glycaemic control. Further robust studies are required as there is high heterogeneity in the form of the vitamin D, dosage, duration, route of administration and study design of the included studies in this research. However, healthcare professionals can use the results of this study to understand the therapeutic value of VDS in improving the cardio-metabolic health of elderly people.
Abstract
BACKGROUND There has been a longstanding interest in the potential effect of vitamin D in preventing cardiac-metabolic diseases. However, there are divergent results regarding the impact of vitamin D supplementation (VDS) on managing cardiac-metabolic outcomes in the elderly population. MATERIAL AND METHOD We systematically searched electronic databases; Web of Science, PubMed, Scopus, EMBASE, Cochrane, and ProQuest. We included all trials that evaluated the effect of VDS on cardiac-metabolic risk factors in the elderly population, which were published until 30 September 2021. The effects of VDS on cardiac-metabolic outcomes were assessed using standardized mean difference (SMD). A random-effect model was used to pool the SMD and 95% confidence interval (CI). RESULT The literature search identified 4409 studies, of which 12 trials met inclusion criteria. Results of random effect meta-analysis indicated a significant reduction in total cholesterol (TC) (SMD: - 0.14 mg/dl; 95% CI: - 0.25, - 0.02) and triglyceride (TG) (SMD: - 0.45 mg/dl; 95% CI: - 0.86, - 0.04) with VDS compared to the placebo. The subgroup analyses revealed that the reduction of TG in patients with diabetes and vitamin D deficiency was significant. Furthermore, short-term intervention (≤ 6 months) induced a significantly lower level of TG and insulin in comparison to longer duration (> 6 months). CONCLUSION The study suggests that VDS could improve insulin concentration and dyslipidemia in the elderly population. The systematic review was registered in Alborz university of medical sciences with 2060-01-03-1397 number and the Ethics council IR.ABZUMS.REC.1397.207 number.
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Circulating levels of maternal vitamin D and risk of ADHD in offspring: results from the Vitamin D Antenatal Asthma Reduction Trial.
Chu, SH, Huang, M, Kelly, RS, Kachroo, P, Litonjua, AA, Weiss, ST, Lasky-Su, J
International journal of epidemiology. 2022;51(3):910-918
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Acting as both a nutrient and a hormone, vitamin D has been found to play a critical role in neurodevelopment across sensitive periods in utero, infancy and early childhood. Among neurodevelopmental and behavioural disorders in early life, attention-deficit/hyperactivity disorder (ADHD) is the most common among children worldwide. Low levels of circulating 25-hydroxy-vitamin D [25(OH)D] have been shown to associate with prevalent ADHD. The aims of this study were to (i) determine the association between maternal vitamin D levels in the first and third trimesters of pregnancy and the risk of offspring ADHD by age 6 years or later; and (ii) to identify potential sensitive periods in utero during which vitamin D levels might be most important for reducing risk of ADHD. This is an ancillary study of the Vitamin D Antenatal Asthma Reduction Trial (VDAART). The VDAART was a randomised, double-blinded, multicentre, clinical trial in which 876 participating mothers were recruited between 10–18 weeks of gestation and assigned to receive either 4400 or 400 IU/day of vitamin D throughout pregnancy. Results show protective associations between maternal 25(OH)D sufficiency in the third trimester and child ADHD, but not at baseline. Furthermore, both at baseline and in the third trimester, there were higher odds of ADHD in male offspring as compared with female offspring with 25(OH)D insufficient mothers (analyses limited by small sample sizes) Authors conclude that higher levels of maternal vitamin D during pregnancy may play a protective role against risk of ADHD in offspring, but further studies are needed to confirm this association and any therapeutic potential therein.
Expert Review
Conflicts of interest:
None
Take Home Message:
Ensure that women in pregnancy, and possibly also those seeking to conceive, have adequate vitamin D status in order to reduce the risk of ADHD in offspring.
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:
Background
This paper describes a secondary data analysis from an RCT that looked at the effect of prenatal vitamin D supplementation on risk of childhood asthma in offspring. Enrolled women aged 18–39 years with a history of asthma, eczema or allergic rhinitis, or whose partner (biological father of child) had a history of the aforementioned condition, received either 400 IU or 4400 IU vitamin D daily for the duration of their pregnancy. Offspring follow-up is still ongoing.
Aims
The current study aims were twofold: (i) to determine the association between maternal vitamin D levels in trimesters 1 and 3 and the risk of attention deficit/hyperactivity disorder (ADHD) in offspring diagnosed by age 6 years or later; and (ii) to identify potentially sensitive periods during gestation in which vitamin D levels may be especially important for reducing risk of ADHD.
Methods
The analytical sample included 679 mother-child pairs, from the original sample of 876 participating mothers. No sample size calculation was reported, though the sample was considered representative of the overall RCT study population.
Maternal vitamin D (serum 25(OH)D) was classified as follows
- Highly deficient <12 ng/mL
- Deficient 12 ng/mL to 19.9 ng/mL
- Insufficient 20 ng/mL to 29.9 ng/mL
- Sufficient ≥30 ng/mL
ADHD status was assessed through parental reporting between ages 6 and 9 years.
Results
No baseline associations between a vitamin D sufficient status and offspring ADHD in maternal samples collected during trimester 1 were observed (OR 1.06, 95% CI 0.51–2.19; P.0.871), though this association became statistically significant at trimester 3 (OR 0.47, 95% CI 0.26–0.84; P.0.011). This translated to a 53% less chance of having a child with ADHD at age 6 or later among mothers with vitamin D sufficiency compared with children of mothers with vitamin D deficiency. There was also a linear trend in the protective association of vitamin D sufficiency (≥30 ng/mL) on reduced risk of offspring ADHD at age 6 years or later in data from trimester 3. Stratified analyses revealed a protective association for sufficient maternal vitamin D status and offspring ADHD among males (OR 0.47, 95% CI 0.23–0.94).
Conclusions
The authors concluded that vitamin D sufficiency (≥30 ng/mL) in the 3rd trimester of gestation may decrease the risk of ADHD development in offspring.
Notes: The authors reported no relevant conflicts of interest.
Clinical practice applications:
Ensuring a sufficient vitamin D status by the 3rd trimester of pregnancy may help to lessen the risk of ADHD in offspring. Nutritional therapists and other clinicians working with pregnant women or women looking to conceive should consider checking vitamin D status and providing corrective supplementation and lifestyle advice to augment vitamin D levels where indicated.
Considerations for future research:
The authors of this study postulated that the statistically significant protective association between vitamin D at trimester 3 and ADHD in offspring was not significant in trimester 1 due to a low observed variability in vitamin D status (>75% of women were vitamin D insufficient), and thus the statistical test being underpowered to see difference between groups with sufficient or insufficient status.
Further research could expand upon this hypothesis to test whether vitamin D status in trimester 1, or preconceptually, may offer a protective association for ADHD and other related neurological conditions that may manifest in early life.
Abstract
BACKGROUND Low levels of circulating 25-hydroxy-vitamin D [25(OH)D] have been shown to associate with prevalent attention-deficit/hyperactivity disorder (ADHD), but few studies have examined the association between 25(OH)D during fetal development and risk of childhood ADHD. METHODS Maternal plasma 25(OH)D was measured at 10-18 and 32-38 weeks of gestation, with sufficiency defined as 25(OH)D ≥ 30 ng/ml. Offspring ADHD status between ages 6-9 years was measured by parent report of clinical ADHD diagnosis among 680 mother-child pairs from the Vitamin D Antenatal Asthma Reduction Trial. Association between maternal 25(OH)D and child ADHD was assessed using logistic regression, adjusting for maternal age, race and ethnicity. Effect modification by offspring sex was also assessed. RESULTS No associations between maternal 25(OH)D at 10-18 weeks of gestation and offspring ADHD were observed. In the third trimester, we observed associations between maternal vitamin D sufficiency and offspring ADHD [odds ratio (OR) 0.47, 95% confidence interval (CI) 0.26-0.84], in addition to maternal 25(OH)D sufficiency category, comparing the deficient (OR 0.34, 95% CI 0.12-0.94), insufficient (OR 0.41, 95% CI 0.15-1.10) and sufficient (OR 0.20, 95% CI 0.08-0.54) categories against highly deficient 25(OH)D, respectively. Stratified analyses revealed a protective association for sufficient maternal 25(OH)D and child ADHD among males (OR 0.47, 95% CI 0.23-0.94); the synergy index for additive effect modification of risk was 1.78 (95% CI 0.62-5.08). CONCLUSIONS Higher levels of maternal vitamin D in the third trimester are associated with lower risk of ADHD in offspring, with modest evidence for a stronger effect among male offspring. However, larger studies will be necessary to confirm these findings.
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The Role of Vitamin D in Sleep Disorders of Children and Adolescents: A Systematic Review.
Prono, F, Bernardi, K, Ferri, R, Bruni, O
International journal of molecular sciences. 2022;23(3)
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Vitamin D deficiency or insufficiency is a global epidemic, estimated to affect over one billion people worldwide, including children. The main function of vitamin D is the regulation of bone homeostasis but it is also involved in many other conditions such as cardiovascular disease, cancer, diabetes mellitus and autoimmune disorders. Recent studies show that sufficient levels of vitamin D seem to be necessary to maintain sleep and low vitamin D levels have been associated with shorter sleep duration. This systematic review is the first to assess the association between Vitamin D and sleep disorders in children, 14 articles were included. Vitamin D deficiency in children is associated with decreased sleep duration and poorer sleep efficiency, as well as with delayed bedtimes. Children with reduced vitamin D serum levels have a higher risk of excessive daytime sleepiness (EDS). Since vitamin D levels influence sleep duration, sleep duration can also influence vitamin D serum concentration suggesting a bidirectional relationship. Evidence is scarce and so further high-quality prospective cohort studies and well-designed randomized controlled trials (RCTs) are needed to determine the effect of vitamin D supplementation in children with sleep disorders.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Vitamin D plays an important role in the sleep quality of children. Healthcare practitioners may wish to establish vitamin D status in children presenting with sleep disturbances.
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:
Introduction
Vitamin D levels have been associated with improved sleep in adults, but few studies have concentrated on the paediatric population. In order to identify if vitamin D plays a role regulating sleep in children and adolescents the paper reviewed studies, which looked at vitamin D in relation to sleep duration and quality of sleep. This included the following sleep disorders: obstructive sleep apnoea (OSA), restless leg syndrome (RLS) and insomnia.
Methods
- A broad systematic review following the PRISMA guidelines and using PubMed and Cochrane databases
- Search identified 748 papers. After exclusions for non-relevance, incorrect age group, or lack of data on sleep, 14 papers were included
- Due to the shortage of papers on this topic none of these papers were excluded, regardless of quality
- The participants in each study varied from 39 to 5289.
Results
The results highlighted:
- Plasma levels of vitamin D affect sleep duration and quality of sleep in children. Data taken from 5 studies
- Vitamin D cord blood levels were correlated to sleep in preschool children. Partly this was due to the mother’s vitamin D level during pregnancy affecting the level of vitamin D available to the foetus. Venous blood vitamin D level was linked to the sleep wake cycle of children. Data taken from 2 studies
- OSA was more likely to develop in children who had low vitamin D levels with a risk of 14.16% compared to a control group of 5.83% (1 study)
- Vitamin D supplementation was found to reduce neuron damage caused by hypoxia (1 study)
- An association exists between parental vitamin D insufficiency and their child’s vitamin D status (1 study). Data taken from 5 studies
- Vitamin D levels in specific diseases, such as coeliac disease (CD) showed a negative correlation with RLS
- For familial Mediterranean fever (FMF) vitamin D deficiency reduced sleep quality (36.5%). Data taken from 2 studies.
Conclusion
Notwithstanding the small number of studies, the review shows vitamin D deficiency, defined as <20 ng/mL, is associated with an increased risk for sleep disorders in children.
Clinical practice applications:
- Due to the role vitamin D plays in sleep in children, establishing vitamin D status may be useful for children presenting with sleep disturbances
- Adequate vitamin D levels during pregnancy are important to establish a vitamin D pool in the foetus
- Vitamin D supplementation is something to rule out in the case of OSA and associated hypoxia, metabolic dysfunction and systemic inflammation in children
- Due to the negative impact poor sleep has on the body, improving sleep quality at a young age could form an important part of preventative health care.
Considerations for future research:
- Additional studies are required to support the conclusion in this study
- Due to the low number of studies, any additional research should be of a high standard and include prospective cohort studies and randomised control trials.
Abstract
This review investigates the association between vitamin D and sleep disorders. Vitamin D is an essential nutrient known to play an important role in the growth and bone health of the human body, but it also appears to play a role in sleep. The goal of our review is to examine the association between vitamin D and sleep disorders in children and adolescents. We summarize the evidence about the role and the mechanism of action of vitamin D in children and adolescents with sleep disorders such as insomnia, obstructive sleep apnea (OSA), restless legs syndrome (RLS), and other sleep disorders. Systematic electronic database searches were conducted using Pubmed and Cochrane Library. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed. The studies that met the established inclusion criteria were analyzed and compared. Results suggest a strict relationship between vitamin D deficiency in children and sleep disorders. There is evidence that vitamin D is implicated in the different neurochemical mechanisms involved in sleep regulation and mainly in the serotonergic and dopaminergic pathways. This might be responsible for the association of vitamin D deficiency and restless sleep, sleep hyperhidrosis, OSA, and RLS.
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Nutritional intervention for diabetes mellitus with Alzheimer's disease.
Li, Z, Li, S, Xiao, Y, Zhong, T, Yu, X, Wang, L
Frontiers in nutrition. 2022;9:1046726
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Diabetes Mellitus (DM) affects more than 463 million people worldwide. Similarly, the number of deaths related to Alzheimer’s disease (AD) has increased by 145%. There are several common risk factors for Type 2 Diabetes and AD, including obesity, insulin resistance, and ageing, as well as common pathological mechanisms, including altered insulin signalling, oxidative stress, neuroinflammation, mitochondrial dysfunction, formation of glycated proteins and metabolic syndrome. This review aims to summarize the therapeutic effects of different nutritional therapy strategies on the reduction of DM and AD risk. Controlling blood sugar levels and reducing calorie intake is crucial to preventing diabetes and Alzheimer's disease. The low-carbohydrate, ketogenic, and Mediterranean diets have been found to improve glucose control in people with Type 2 diabetes (T2D). In addition, MIND (Mediterranean-DASH Diet Intervention for Neurodegenerative Delay) and a ketogenic diet may improve cognition in AD patients. Lactobacillus, Bifidobacterium probiotics, and prebiotics, such as inulin, may inhibit the progression of T2D and AD diseases by suppressing inflammation and modulating gut microbes. In addition, vitamins A, C, D, E, B6, B12, folate, long-chain polyunsaturated fatty acids, zinc, magnesium, and polyphenols may improve cognitive decline, homocysteine levels, and insulin resistance in AD and T2D patients. Healthcare professionals can use the results of this review to understand the beneficial effects of dietary strategies and multi-nutrient supplementation on DM and AD. However, further robust studies are required to investigate the risk factors and underlying mechanisms behind DM-combined AD progression.
Abstract
The combined disease burden of diabetes mellitus (DM) and Alzheimer's disease (AD) is increasing, and the two diseases share some common pathological changes. However, the pharmacotherapeutic approach to this clinical complexity is limited to symptomatic rather than disease-arresting, with the possible exception of metformin. Whether nutritional intervention might extend or synergize with these effects of metformin is of interest. In particular, dietary patterns with an emphasis on dietary diversity shown to affect cognitive function are of growing interest in a range of food cultural settings. This paper presents the association between diabetes and AD. In addition, the cross-cultural nutritional intervention programs with the potential to mitigate both insulin resistance (IR) and hyperglycemia, together with cognitive impairment are also reviewed. Both dietary patterns and nutritional supplementation showed the effects of improving glycemic control and reducing cognitive decline in diabetes associated with AD, but the intervention specificity remained controversial. Multi-nutrient supplements combined with diverse diets may have preventive and therapeutic potential for DM combined with AD, at least as related to the B vitamin group and folate-dependent homocysteine (Hcy). The nutritional intervention has promise in the prevention and management of DM and AD comorbidities, and more clinical studies would be of nutritional scientific merit.
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Add-On Effect of Selenium and Vitamin D Combined Supplementation in Early Control of Graves' Disease Hyperthyroidism During Methimazole Treatment.
Gallo, D, Mortara, L, Veronesi, G, Cattaneo, SA, Genoni, A, Gallazzi, M, Peruzzo, C, Lasalvia, P, Moretto, P, Bruno, A, et al
Frontiers in endocrinology. 2022;13:886451
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Graves’ disease (GD) is the most frequent cause of hyperthyroidism in iodine-replete geographical areas. Thionamide anti-thyroid drug therapy is the first-line treatment worldwide under most circumstances, but its major limitation is the high rate of relapses after drug discontinuation. Decreased serum concentrations of selenium (Se) and vitamin D (VitD) have been reported in newly diagnosed GD patients in observational studies. The aim of this study was to determine if concurrent supplementation with Se and VitD in Graves’ patients with suboptimal or low Se and VitD levels may improve early control of hyperthyroidism during methimazole (MMI) [thionamide] treatment. This study is a randomised, single-blinded, controlled, intervention trial. Forty-two patients were randomly assigned to treatment with MMI monotherapy (Group 1, MMI alone group) or MMI combined with Se and VitD (Group 2, intervention group). Results show that supplementation favours a significantly better control of hyperthyroidism, both at short-term (45 days) and long-term (180 and 270 days) assessments. In fact, during MMI treatment, Se and VitD supplementation facilitate restoration of euthyroidism and boost the improvement of quality of life. Authors conclude that Se and VitD status should be assessed at diagnosis of GD, and that Se and VitD supplementation should be offered at adequate and safe dosages even if a slight deficiency of these micronutrients is found.
Abstract
Prompt and stable control of hyperthyroidism is fundamental to avoid the detrimental effects of thyroid hormone excess, and antithyroid drugs, mainly methimazole (MMI), represent the first-line treatment for Graves' disease (GD) hyperthyroidism. Decreased serum concentrations of selenium (Se) and calcifediol (25(OH)D, VitD) have been reported in newly diagnosed GD patients in observational studies. Low Se levels might exacerbate oxidative stress by compromising the antioxidant machinery's response to reactive oxygen species, and low VitD levels might hamper the anti-inflammatory immune response. We performed a randomized controlled clinical trial (EudraCT 2017-00505011) to investigate whether Se and cholecalciferol (VitD) addition to MMI is associated with a prompter control of hyperthyroidism. Forty-two consecutive patients with newly-onset GD and marginal/insufficient Se and VitD levels were randomly assigned to treatment with either MMI monotherapy or MMI combined with Se and VitD. Se treatment was withdrawn after 180 days, while the other treatments were continued. Combination therapy resulted in a significantly greater reduction in serum FT4 concentration at 45 days (-37.9 pg/ml, CI 95%, -43.7 to -32.2 pg/ml) and 180 days (-36.5 pg/ml, CI 95%, -42 to -30.9 pg/ml) compared to MMI monotherapy (respectively: -25.7 pg/ml, CI 95%, -31.6 to -19.7 pg/ml and -22.9 pg/ml, CI 95%, -28 to -17.3 pg/ml, p 0.002). Data at 270 days confirmed this trend (-37.8 pg/ml, CI 95%, -43.6 to -32.1 pg/ml vs -24.4 pg/ml, CI 95%, -30.3 to -18.4 pg/ml). The quality of life (QoL) score was investigated by the validated "Thyroid-related Patient-Reported Outcome" questionnaire (ThyPRO). ThyPRO composite score showed a greater improvement in the intervention group at 45 days (-14.6, CI 95%, -18.8 to -10.4), 180 (-9, CI 95%, -13.9 to -4.2) and 270 days (-14.3, CI 95%, -19.5 to -9.1) compared to MMI group (respectively, -5.2, CI 95%, -9.5 to -1; -5.4, CI 95%, -10.6 to -0.2 and -3.5, CI 95%, -9 to -2.1, p 0-6 months and 6-9 months <0.05). Our results suggest that reaching optimal Se and VitD levels increases the early efficacy of MMI treatment when Se and VitD levels are suboptimal.
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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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Effects of vitamin D treatment on thyroid function and autoimmunity markers in patients with Hashimoto's thyroiditis-A meta-analysis of randomized controlled trials.
Jiang, H, Chen, X, Qian, X, Shao, S
Journal of clinical pharmacy and therapeutics. 2022;47(6):767-775
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Hashimoto's thyroiditis (HT), also called chronic lymphocytic thyroiditis, is the most prevalent organ-specific autoimmune disorder as well as the most common cause of thyroid hypofunction. The main purpose of HT treatment is the control of hypothyroidism, including oral administration of a synthetic hormone to achieve normal circulating thyrotropin levels. The aim of this study was to review the association between vitamin D treatment in patients with HT by assessing patients’ serum circulating 25-hydroxyvitamin D - 25(OH)D - level to evaluate whether a change occurs in the course of disease. This study is a systematic review and meta-analysis of seven cohorts of patients from six studies (3 prospective cohort studies and 3 randomised controlled trials). Results show that vitamin D might significantly increase the serum 25(OH)D levels and produce changes in thyroid peroxidase antibodies titres. However, there wasn't a significant association between serum vitamin D supplementation and the levels of thyroid-stimulating hormone, thyroglobulin antibodies, free triiodothyronine and free thyroxine. Authors conclude that their findings suggest that vitamin D is not associated with the function of the thyroid in patients with HT. Thus, further well-designed randomised controlled trials with sufficient sample sizes investigating the effect of vitamin D on thyroid function are still warranted.
Abstract
INTRODUCTION Recent evidence suggested that vitamin D deficiency was associated with Hashimoto's thyroiditis (HT) pathogenesis and thyroid hypofunction. This study aimed to investigate whether vitamin D supplementation would be effective in the prevention and progression of hypothyroidism in patients with HT. METHODS PubMed, Embase and the Cochrane library were searched for randomized controlled trials (RCTs) and prospective cohort studies published from inception to August 2021. RESULTS A total of 7 cohorts of patients from six clinical trials with 258 patients with HT were included. Significant difference was found (WMD = 19.00, 95% CI: 12.43, 25.58, p < 0.001; I2 = 90.0%, pheterogeneity < 0.001) between the vitamin D group and control group in serum 25-hydroxyvitamin D level. And the combined results indicated vitamin D supplementation significantly reduced the level of thyroid peroxidase antibodies (TPO-Ab) compared to the control group (WMD = -158.18, 95% CI: -301.92, -14.45, p = 0.031; I2 = 68.8%, pheterogeneity = 0.007). Whereas no significant differences were found on the levels of thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4) compared to the control group (p > 0.05). WHAT IS NEW AND CONCLUSION Our study demonstrated that vitamin D treatment might significantly increase the serum 25(OH)D levels and produce changes in TPO-Ab titres. No significant association was found between serum vitamin D treatment and the levels of TG-Ab, TSH, FT3 and FT4, suggesting that vitamin D is not associated with the function of the thyroid in patients with HT.
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Dietary factors that affect the risk of pre-eclampsia.
Perry, A, Stephanou, A, Rayman, MP
BMJ nutrition, prevention & health. 2022;5(1):118-133
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Pre-eclampsia is hypertension that becomes present after 20 weeks of gestation combined with proteinuria or another maternal organ dysfunction. It causes problems in 3%–5% of all pregnancies and is estimated to cause at least 42 000 maternal deaths annually. Other than early delivery of the fetus, there is no cure for pre-eclampsia. There is little published information on diet and pre-eclampsia, so the aim of this review is to look at a number of dietary factors and to develop a set of nutritional guidelines to reduce the risk of pre-eclampsia in pregnancy. This dietary review looks at: obesity and gestational weight gain and the discussion of weight management interventions. Fibre, probiotics and prebiotics. Specific dietary patterns such as: diets high in fruit and vegetables, western dietary patterns, New Nordic diet, dietary approaches to stop hypertension (DASH diet) and the Mediterranean style diet. Evidence for vitamin D, calcium, selenium, folic acid, B12 and multivitamins/minerals is looked at. The authors have summarised their conclusions in a table. However, it is emphasised that dietary recommendations should be considered in combination with other preventive actions such as a screening policy or pharmacological agents that may be appropriate for high-risk groups.
Abstract
Pre-eclampsia affects 3%-5% of pregnant women worldwide and is associated with a range of adverse maternal and fetal outcomes, including maternal and/or fetal death. It particularly affects those with chronic hypertension, pregestational diabetes mellitus or a family history of pre-eclampsia. Other than early delivery of the fetus, there is no cure for pre-eclampsia. Since diet or dietary supplements may affect the risk, we have carried out an up-to-date, narrative literature review to assess the relationship between nutrition and pre-eclampsia. Several nutrients and dietary factors previously believed to be implicated in the risk of pre-eclampsia have now been shown to have no effect on risk; these include vitamins C and E, magnesium, salt, ω-3 long-chain polyunsaturated fatty acids (fish oils) and zinc. Body mass index is proportionally correlated with pre-eclampsia risk, therefore women should aim for a healthy pre-pregnancy body weight and avoid excessive gestational and interpregnancy weight gain. The association between the risk and progression of the pathophysiology of pre-eclampsia may explain the apparent benefit of dietary modifications resulting from increased consumption of fruits and vegetables (≥400 g/day), plant-based foods and vegetable oils and a limited intake of foods high in fat, sugar and salt. Consuming a high-fibre diet (25-30 g/day) may attenuate dyslipidaemia and reduce blood pressure and inflammation. Other key nutrients that may mitigate the risk include increased calcium intake, a daily multivitamin/mineral supplement and an adequate vitamin D status. For those with a low selenium intake (such as those living in Europe), fish/seafood intake could be increased to improve selenium intake or selenium could be supplemented in the recommended multivitamin/mineral supplement. Milk-based probiotics have also been found to be beneficial in pregnant women at risk. Our recommendations are summarised in a table of guidance for women at particular risk of developing pre-eclampsia.
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Associations between Dynamic Vitamin D Level and Thyroid Function during Pregnancy.
Wang, H, Wang, HJ, Jiao, M, Han, N, Xu, J, Bao, H, Liu, Z, Ji, Y
Nutrients. 2022;14(18)
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Thyroid hormones play a vital role in regulating metabolism. Adequate thyroid hormone levels are also critical during pregnancy for optimal fetal growth and development. The foetus is dependent on maternal thyroid hormones until its own thyroid gland matured in the second half of pregnancy. Furthermore, pregnancy impacts thyroid function leading to an increased demand for thyroid hormones. Thyroid disease has been associated with Vitamin D deficiency. During pregnancy, both thyroid disorders and Vitamin D deficiency can have adverse effects on pregnancy and pregnancy outcomes, hence a potential link between Vitamin D status and thyroid function has been postulated. To fill the gaps in previous research, this retrospective cohort study aimed to explore the associations between Vitamin D status and thyroid function throughout the pregnancy, in each trimester. The analysis of hospital data collected in Beijing demonstrated an association between Vitamin D levels and thyroid function throughout pregnancy. Such interlink appeared to be dynamic and changed depending on the stage of pregnancy. The author's findings affirmed that maintenance of adequate Vitamin D levels supports normal thyroid function which is an important nutritional strategy for a healthy pregnancy.
Abstract
Optimal Vitamin D (VitD) status and thyroid function are essential for pregnant women. This study aimed to explore associations between dynamic VitD status and thyroid function parameters in each trimester and throughout the pregnancy period. Information on all 8828 eligible participants was extracted from the Peking University Retrospective Birth Cohort in Tongzhou. Dynamic VitD status was represented as a combination of deficiency/sufficiency in the first and second trimesters. Thyroid function was assessed in three trimesters. The associations between VitD and thyroid function were assessed by multiple linear regression and generalized estimating equation models in each trimester and throughout the pregnancy period, respectively. The results indicated that both free thyroxine (fT4; β = 0.004; 95%CI: 0.003, 0.006; p < 0.001) and free triiodothyronine (fT3; β = 0.009; 95%CI: 0.004, 0.015; p = 0.001) had positive associations with VitD status in the first trimester. A VitD status that was sufficient in the first trimester and deficient in the second trimester had a lower TSH (β = -0.370; 95%CI: -0.710, -0.031; p = 0.033) compared with the group with sufficient VitD for both first and second trimesters. In conclusion, the associations between VitD and thyroid parameters existed throughout the pregnancy. Maintaining an adequate concentration of VitD is critical to support optimal thyroid function during pregnancy.