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Effects of multi-domain intervention on intrinsic capacity in older adults: A systematic review of randomized controlled trials (RCTs).
Liao, X, Shen, J, Li, M
Experimental gerontology. 2023;174:112112
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With the increase of age, the physiological reserve of the elderly decreases, which leads to the increase of physical vulnerability and the decrease of anti-stress ability, showing a series of frailty manifestations. Intrinsic capacity (refers to the comprehensive capacity of all physical and mental capacities of an individual) is central to maintaining function in older adults, and maintaining optimal intrinsic capacity is important to promote healthy aging. The aim of this study was to assess randomised controlled trials of multidomain interventions to further validate their effectiveness in the maintenance and enhancement of function in older adults, and to formulate strategies for preventive care and clinical practice. This study was a systematic review and meta-analysis of twenty-five publications. Results showed that multi-domain interventions can improve indicators of vital domains in older adults and integrate to optimise intrinsic capacity (refers to the comprehensive capacity of all physical and mental capacities of an individual) through potential interaction mechanisms. Authors concluded that because older adults may not be able to receive overly complex interventions due to limitations in their integrative abilities, the involvement of older adults and the sustainability of interventions should be considered before implementing them.
Abstract
Intrinsic capacity is central to the maintenance of function in older adults, and maintaining optimal intrinsic capacity is of great importance to promote healthy aging. The purpose of this systematic review and meta-analysis was to analyze the impact of multi-domain interventions on intrinsic capacity in older adults, intervention components, and potential interactions between components. A total of 6740 published articles were screened until August 2022, and the review included 25 randomized controlled trials that analyzed populations, interventions, control groups, and outcomes. The meta-analysis showed improvements in the primary outcome indicators in the intervention group compared to the control group. These included increased scores on the Mini-Mental State Examination as an indicator of cognitive function, decreased scores on the Geriatric Depression Scale (GDS-15) as an indicator of psychological ability and increased scores on the Short Physical Performance Battery (SPPB) as an indicator of physical performance, with only the SPPB indicator analyzed showing greater heterogeneity. Significant improvements were also seen in the secondary indicators Time-to-Walk Test (TUG), gait speed, Chair Stand Test (CST), grip strength values and BMI. There was insufficient data for the Mini Nutritional Assessment (MNA) as an indicator of vitality to conduct a meta-analysis. Studies were of moderate to high quality. The results of this review indicate that multi-domain interventions can maintain the level of intrinsic capacity in older adults and are equally effective in older adults with declining self-care abilities.
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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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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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Effect of Vitamin D Supplementation on Inflammatory Biomarkers in School-Aged Children with Attention Deficit Hyperactivity Disorder.
Samadi, M, Gholami, F, Seyedi, M, Jalali, M, Effatpanah, M, Yekaninejad, MS, Abdolahi, M, Chamari, M, Mohammadzadeh Honarvar, N
International journal of clinical practice. 2022;2022:1256408
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Attention deficit hyperactivity disorder (ADHD) is one of the most prevalent psychiatric and developmental disorders among children and adolescents. Besides clinical impairments, these children have challenges with school performance and independent socioeconomic factors. The aim of this study was to assess the possible effects of vitamin D on inflammatory cytokines (tumour necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6)) levels in children with ADHD. This study is a randomised, double-blind, placebo-controlled clinical trial which was conducted on 86 children aged 6–12. Patients were randomly assigned to two groups to receive vitamin D3 or a placebo. Results show children with ADHD taking vitamin D supplementation for 3 months demonstrated a significant increase in serum levels of Vitamin D3. However, serum levels of IL-6 and TNF-α were not significantly influenced by vitamin D administration. Authors conclude that their findings failed to find a favourable effect of 3 months of supplementation with vitamin D on inflammatory cytokines. Thus, they highly recommend conducting further studies with different doses of vitamin D and various designs in addition to differences in the characteristics of participants.
Abstract
METHOD This randomized double-blind, placebo-controlled trial was conducted on 75 school-aged children with a diagnosis of ADHD based on DSM-V criteria. Children were randomly allocated to receive either vitamin D3 (2000 IU/day) or a placebo for 3 months. Serum IL-6, TNF-α, and 25(OH) D were assessed before and after the intervention to determine the effects of vitamin D on the highlighted parameters. RESULTS Serum levels of 25(OH) D increased significantly in the vitamin D group (P=0.01). However, no significant differences in serum IL-6 and TNF-α were found between both groups at the baseline and at the end of the intervention. CONCLUSION The findings revealed that vitamin D supplementation for 3 months is not efficacious in reducing inflammatory cytokines in children with ADHD. Further studies are required to confirm these results.
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Nutrition to Prevent or Treat Cognitive Impairment in Older Adults: A GRADE Recommendation.
Buckinx, F, Aubertin-Leheudre, M
The journal of prevention of Alzheimer's disease. 2021;8(1):110-116
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Cognitive impairment is a public health problem due to its increasing prevalence in the aging population. Despite pharmacological advances, there are not yet effective treatments to delay or reverse cognitive impairment. Moreover, there is limited knowledge of Alzheimer disease modifiable risk factors namely nutrition. The aim of this review was to grade, classify and provide recommendations for the preferred diet to prevent or to treat cognitive impairment. This review shows that: - some nutritional factors appear to either increase the risk of cognitive decline or protect against it. - risk could be conferred by diets high in milk and dairy products whereas some protection can be offered by adhering to a Mediterranean diet to decrease the risk of cognitive decline. - it is important to follow a diet rich in mono- and poly- unsaturated fatty acids, fruit and vegetable, vitamin D and low in saturated fatty acids. Authors conclude that diet is an important modifiable factor to prevent or protect against cognitive decline.
Abstract
Aging is associated with cognitive declines leading to mild cognitive impairments or Alzheimer disease. Nutrition appear to protect from aging. Some dietary factors could either increase or protect against cognitive declines. This article aimed to provide GRADE recommendations related to nutrition aspects able to prevent or to treat cognitive impairments. A comprehensive literature review was performed using Medline database. The GRADE approach was used to classify quality of the existing evidence (systematic review or meta-analysis).The GRADE process led us to formulate seven key nutritional recommendations to manage cognitive declines, but did not allow us to do it for protein, vitamin B or antioxidants. Thus, 1) adherence to a Mediterranean diet (GRADE 1B); 2) high-level of consumption of mono- or poly- unsaturated fatty acids combined to a low consumption of saturated fatty acids (GRADE 1B); 3) high consumption of fruits and vegetables (GRADE 1B); 4) higher vitamin D intake (GRADE 1C) than the recommended daily allowance. In addition, a ketogenic diet, a low consumption of whole-fat dairy products or a caloric restriction are promising nutritional habits although the evidence does not yet support widespread uptake (GRADE 2C). In conclusion, nutrition is an important modifiable factor to prevent or protect against cognitive decline. Nevertheless, more studies are required to determine specific guidelines such as duration and amounts of nutrients to help older adult to maintain a healthy cognitive life.
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The effects of vitamin D supplementation on interictal serum levels of calcitonin gene-related peptide (CGRP) in episodic migraine patients: post hoc analysis of a randomized double-blind placebo-controlled trial.
Ghorbani, Z, Rafiee, P, Fotouhi, A, Haghighi, S, Rasekh Magham, R, Ahmadi, ZS, Djalali, M, Zareei, M, Razeghi Jahromi, S, Shahemi, S, et al
The journal of headache and pain. 2020;21(1):22
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The exact causes of migraine are still unknown, but it has been shown that chemical messengers in the brain are released during migraines, which causes the blood vessels to increase in size resulting in inflammation. Vitamin D has been shown in previous trials to be of benefit to individuals with migraines, yet it is not fully understood how it does this. Therefore, this 16-week randomised control trial aimed to determine the effect of vitamin D supplementation on one of the chemical messengers thought to cause inflammation in the brain and on disability associated with migraine episodes. The results showed that vitamin D supplementation improved disability associated with migraine and that this may have been due to an improvement in one of the chemical messengers in the brain that is associated with inflammation. It was concluded that vitamin D supplementation may improve migraines, but further studies are warranted. This study could be used by healthcare professionals to understand how vitamin D may be of benefit to those who suffer from migraines.
Abstract
BACKGROUND Emerging evidence showed promising effects of vitamin D on headaches characteristics. Thus, it seems there is still a need for more researches to clarify the mechanisms by which this vitamin exerts anti-migraine effects. METHODS The present study was conducted as a 16-week randomized double-blind placebo-controlled trial on 80 episodic migraine patients allocated in 2 parallel groups each consisted of 40 patients who received vitamin D 2000 IU/d or placebo. At baseline and after the intervention completion, headache diaries and migraine disability assessment questionnaire (MIDAS) were used to assess migraine related variables in patients. Also, interictal serum concentration of calcitonin gene-related peptide (CGRP) (as the dominant mediator of migraine pain pathogenesis) was evaluated using ELISA method. RESULTS The mean (SD) of age in the vitamin D and placebo groups was 37 (8) and 38 (12) years, respectively. ANCOVA test adjusted for baseline values, and confounders showed vitamin D supplementation resulted in a significant improvement in MIDAS score after 12 weeks in the intervention group (21.49 (16.22-26.77)) compared to placebo (31.16 (25.51-36.82) P value: 0.016). Moreover, after controlling for baseline levels, and other variables using ANCOVA, CGRP level was appeared to be significantly lower following vitamin D supplementation (153.26 (133.03-173.49) ng/L) than the patients in the placebo arm (188.35 (167.15-209.54) ng/L) (P value = 0.022). CONCLUSION According to the current findings, vitamin D supplementation in episodic migraineurs, particularly in those with migraine with aura, may potentially improve migraine headache characteristics and disability probably through attenuating CGRP levels. Therefore, these results could provide a new insight into anti-nociceptive effects of vitamin D; however, more studies are required to confirm our findings. TRIAL REGISTRATION The trial is registered in the Iranian registry of clinical trials (IRCT) at 11 July 2018, with IRCT code: IRCT20151128025267N6.