1.
Comparative effects of vitamin and mineral supplements in the management of type 2 diabetes in primary care: A systematic review and network meta-analysis of randomized controlled trials.
Xia, J, Yu, J, Xu, H, Zhou, Y, Li, H, Yin, S, Xu, D, Wang, Y, Xia, H, Liao, W, et al
Pharmacological research. 2023;188:106647
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Type 2 diabetes mellitus (T2DM), characterised by sustained hyperglycaemia and insulin resistance, remains a severe driver of chronic metabolic diseases such as cardiovascular diseases. The aim of this study was to investigate and compare the efficacy of vitamin and mineral supplements in the management of glycaemic control and lipid metabolism for type 2 diabetic patients to inform clinical practice. This study is a systematic review and meta-analysis of one hundred and seventy articles with a total of 4223 adults with T2DM. Participants were randomised to either the placebo/no treatment group (n= 6345) or to the treatment group (n= 7878). Results show that: - chromium was the most effective micronutrient for decreasing fasting blood glucose and insulin resistance. - vitamin K was the top-ranked micronutrient in reducing haemoglobin A1C and fasting insulin levels. - vanadium was the top-ranked micronutrient in total cholesterol reductions. - niacin was ranked as the most effective in triglycerides reductions and increasing high-density lipoprotein cholesterol levels. - vitamin E was the top-ranked micronutrient in low-density lipoprotein cholesterol reductions. Authors conclude that micronutrient supplements especially chromium, vitamin E, vitamin K, vanadium, and niacin supplements, may be more effective in the management of T2DM compared with other micronutrients.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Clinicians could consider the adjunctive effect of micronutrients supplements, such as chromium, vitamin E, vitamin K, vanadium, and niacin supplements in a nutrition protocol to manage T2DM and slow or prevent its complications.
- The study authors state that the vitamin and mineral supplements under review had a statistically significant improvement, however they did not reach the study threshold for clinical significance. Therefore they advise caution in utilising micronutrient supplements in the management of glucose and lipid metabolism for T2DM.
Evidence Category:
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X
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:
Objectives
The aim of this systematic review was to evaluate the comparative effects of vitamin and mineral supplements on managing glycemic control and lipid metabolism for type 2 diabetes mellitus (T2DM).
Methodology
This systematic review is registered with PROSPERO and adhered to PRISMA-2020 guidelines for network meta-analysis
The Cochrane Collaboration’s risk-of-bias tool was used to assess eligible randomised trials
8 prespecified markers identified and assessed in this study : 1) HbA1c (%), 2) fasting blood glucose (mmol/L), 3) total cholesterol (mmol/L), 4) triglycerides (mmol/L), 5) fasting insulin (μIU/mL), 6) HOMA-IR, 7) LDL-c (mmol/L), and 8) HDL-c (mmol/L).
Results
- 170 RCT trials of 14223 participants with T2DM treated with vitamin supplements, mineral supplements, or placebo/no treatment were included
- Low to very low certainty evidence established chromium supplements as the most effective in reducing fasting blood glucose levels and homeostasis model assessment of insulin resistance (SUCRAs: 90.4% and 78.3%, respectively)
- Vitamin K supplements ranked best in reducing glycated haemoglobin A1c and fasting insulin levels (SUCRAs: 97.0% and 82.3%, respectively), with moderate to very low certainty evidence
- Vanadium supplements ranked best in lowering total cholesterol levels with very low evidence certainty (SUCRAs:100%)
- Niacin supplements ranked best in triglyceride reductions and increasing high-density lipo-protein cholesterol levels with low to very low evidence certainty (SUCRAs:93.7% and 94.6%, respectively)
- Vitamin E supplements ranked best in reducing low-density lipoprotein cholesterol levels with very low evidence certainty (SUCRAs:80.0%).
Conclusion
- Micronutrient supplements, such as chromium, vitamin E, vitamin K, vanadium, and niacin supplements, may be efficacious in managing T2DM
- It should be noted that the evidence certainty for all was low.
Clinical practice applications:
- Chromium plays an important role in carbohydrate and lipid metabolism and was the most effective micronutrient for decreasing fasting blood glucose, HbA1c, fasting insulin, and HOMA-IR reductions. More pronounced effects were seen for chromium than vitamin E, vitamin C, niacin, selenium, and magnesium supplements
- Vitamin K was the top-ranked micronutrient in reducing HbA1c and fasting insulin levels. The mechanism through which Vitamin K affects glucose metabolism is proposed as activation of the AMP-activated protein kinase/sirtuin 1, that in turn increases phosphocreatine 3-kinase and glucose transporter 2 to decrease insulin resistance and fasting glucose.
- Vanadium was the top-ranked micronutrient in total cholesterol (TC) reductions, where supplementation dosage should be carefully considered, as vanadium compounds can be moderately or highly toxic. Vanadium supplementation is only recommended in cases of vanadium deficiency or diabetes, hyperlipidemia, and hypertension, where the intake of vanadium from food should be enhanced in preference to supplementation
- Niacin was ranked as the most effective in triglyceride (TG) reductions and increasing HDL cholesterol levels. The dose of niacin could not be determined
- Vitamin E was the top-ranked micronutrient in low-density lipo- protein (LDL) cholesterol reductions.
Considerations for future research:
- Considering the clinical importance of these findings, new research is needed to get better insight into the efficacy of micronutrient supplements in managing T2DM
- Selenium homeostasis, selenoprotein, insulin signaling/secretion, and carbohydrate/lipid metabolism are linked in multiple and complex ways but the authors could not explain why chromium supplementation would lower blood glucose more effectively than selenium supplementation, and suggest more research is needed to clarify this
- While vitamin K status could be an emerging treatment target in T2DM prevention and management, it remains to be determined whether vitamin K supplementation has an advantage over other nutrients in terms of hypoglycemic effect, and further research is necessary
- The beneficial effect of vitamin E and niacin supplements regarding lipid metabolism warrant investigation through more rigorous comparative studies.
Abstract
Medical nutrition treatment can manage diabetes and slow or prevent its complications. The comparative effects of micronutrient supplements, however, have not yet been well established. We aimed at evaluating the comparative effects of vitamin and mineral supplements on managing glycemic control and lipid metabolism for type 2 diabetes mellitus (T2DM) to inform clinical practice. Electronic and hand searches for randomized controlled trials (RCTs) were performed until June 1, 2022. We selected RCTs enrolling patients with T2DM who were treated with vitamin supplements, mineral supplements, or placebo/no treatment. Data were pooled via frequentist random-effects network meta-analyses. A total of 170 eligible trials and 14223 participants were included. Low to very low certainty evidence established chromium supplements as the most effective in reducing fasting blood glucose levels and homeostasis model assessment of insulin resistance (SUCRAs: 90.4% and 78.3%, respectively). Vitamin K supplements ranked best in reducing glycated hemoglobin A1c and fasting insulin levels (SUCRAs: 97.0% and 82.3%, respectively), with moderate to very low certainty evidence. Vanadium supplements ranked best in lowering total cholesterol levels with very low evidence certainty (SUCRAs:100%). Niacin supplements ranked best in triglyceride reductions and increasing high-density lipoprotein cholesterol levels with low to very low evidence certainty (SUCRAs:93.7% and 94.6%, respectively). Vitamin E supplements ranked best in reducing low-density lipoprotein cholesterol levels with very low evidence certainty (SUCRAs:80.0%). Our analyses indicated that micronutrient supplements, especially chromium, vitamin E, vitamin K, vanadium, and niacin supplements, may be more efficacious in managing T2DM than other micronutrients. Considering the clinical importance of these findings, new research is needed to get better insight into this issue.
2.
Effects of whey and soy protein supplementation on inflammatory cytokines in older adults: a systematic review and meta-analysis.
Prokopidis, K, Mazidi, M, Sankaranarayanan, R, Tajik, B, McArdle, A, Isanejad, M
The British journal of nutrition. 2023;129(5):759-770
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Reduced muscle mass and reduction in physical activity may lead to sarcopenia in older people. Age-related sarcopenia is associated with increased systemic low-grade inflammation and obesity. Protein supplementation is found to be beneficial in reducing circulating pro-inflammatory cytokines in old people. Previous research has shown that supplementation with isolated whey and soy protein reduces the levels of inflammatory cytokines in older adults. However, there is limited research on intact whey and soy protein supplementation in reducing age-related inflammation. This systematic review and meta-analysis investigated the effect of intact whey and soy protein on serum inflammatory markers such as C-reactive protein (CRP), Interleukin-6 (IL6) and TNF-α in older adults. The results of this meta-analysis show a significant reduction in circulating IL-6 and TNF-α levels after the supplementation with whey and soy protein. The addition of soy isoflavones resulted in a further decline in serum CRP levels. Subgroup analysis showed that the whey protein supplementation significantly improved sarcopenia and pre-frailty. Healthcare professionals can use the result of this systematic review and meta-analysis to understand the anti-inflammatory properties of intact whey and soy protein and soy isoflavones. However, further robust studies are required to assess the anti-inflammatory properties of whey and soy protein due to the high heterogeneity of included studies in this review.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Nutritional strategies such as whey and soy protein supplementation may be regarded as safe and effective to attenuate adverse changes in muscle mass with ageing, however need to be considered alongside individual dietary intake and health status.
- Consider optimising protein intake and quality of protein through diet as an alternative or first line strategy.
Evidence Category:
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X
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
- A decline in muscle mass and physical capacity, known as sarcopenia, may start in the fourth decade with accumulation of adiposity, resulting in elevated circulating proinflammatory cytokines.
- Systematic and local elevation of oxidative stress and reactive oxygen species accumulation may accelerate age-related muscle wasting, however may be mitigated with antioxidant nutrients.
- This SR and MA evaluated whey and soy proteins effects on interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α) and C-reactive protein (CRP) in older adults.
Methods
SR followed PRISMA guidelines, was registered on PROSPERO and included 31 RCT studies published in English between 2004-21. Intervention group received soy/whey supplements and comparator group received a placebo; circulating levels of CRP, IL-6 and/or TNF-α were assessed. MA used random-effects to calculate the pooled effects. Overall quality of evidence was rated as moderate.
Results
Males and females with a mean age 50 - 80 years were included.
Whey protein:
- IL-6 levels were reduced significantly (Number of studies (k) = 12, Mean Difference (MD): −0·79, 95 % Confidence Interval (CI): −1·15, −0·42, p< 0.01), however, high heterogeneity was observed (I2 = 96 %).
- Treatment duration ≤ 8 weeks showed a significant reduction in serum CRP (k = 4, MD: –0·30, 95 % CI: –0·39, –0·21, I2 = 0 %) compared with > 8 weeks (k = 6, MD: 0·13, 95 % CI: –0·13, 0·40, I2 = 9 %), whereas TNF-α and IL-6 remained unaltered.
- Individuals with sarcopenia and pre-frailty displayed a significant reduction of IL-6 (k = 3, MD: –0·98, 95 % CI: –1·56, –0·39, I2 = 0 %) but no benefits were observed for CRP or TNF.
Soy protein:
- There was a significant reduction in TNF-α (k = 6, MD: −0·16, 95 % CI: −0·26, p<0·05).
- The addition of isoflavones demonstrated a significant decrease in TNF-α (k = 5, MD: –0·20, 95 % CI: –0·31, –0·08, I2 = 34 %) but an increase in CRP (k = 7, MD: 0·53, 95 % CI: 0·12, 0·94), however high heterogeneity was observed in the latter (I2 = 91 %).
Conclusion
- The study found a significant reduction in IL-6 following whey protein with effects augmented in those with frailty and sarcopenia and a significant reduction in TNF-α following soy protein with effects augmented by additional soy isoflavones, possibly due to antioxidant effects.
Clinical practice applications:
- Consider whey and/or soy protein supplementation in older adults particularly those reported with pre-frailty and sarcopenia as an effective and safe strategy to attenuate low-grade inflammation and associated risks.
- Soy isoflavones may have additional antioxidant benefits for older adults although further research is needed to confirm this due to high heterogeneity found.
Considerations for future research:
Future research could:
- Evaluate other factors which influence the inflammatory profile such as nutrient density, vitamins and minerals supplementation and exercise.
- Include those with co-morbidities and healthy populations with placebo comparator groups.
- Evaluate dose and type of soy isoflavones on circulating inflammatory markers and the effect of combined whey and soy protein.
Abstract
BACKGROUND AND AIMS Low-grade inflammation is a mediator of muscle proteostasis. This study aimed to investigate the effects of isolated whey and soy proteins on inflammatory markers. METHODS We conducted a systematic literature search of randomised controlled trials (RCT) through MEDLINE, Web of Science, Scopus and Cochrane Library databases from inception until September 2021. To determine the effectiveness of isolated proteins on circulating levels of C-reactive protein (CRP), IL-6 and TNF-α, a meta-analysis using a random-effects model was used to calculate the pooled effects (CRD42021252603). RESULTS Thirty-one RCT met the inclusion criteria and were included in the systematic review and meta-analysis. A significant reduction of circulating IL-6 levels following whey protein [Mean Difference (MD): -0·79, 95 % CI: -1·15, -0·42, I2 = 96 %] and TNF-α levels following soy protein supplementation (MD: -0·16, 95 % CI: -0·26, -0·05, I2 = 68 %) was observed. The addition of soy isoflavones exerted a further decline in circulating TNF-α levels (MD: -0·20, 95 % CI: -0·31, -0·08, I2 = 34 %). According to subgroup analysis, whey protein led to a statistically significant decrease in circulating IL-6 levels in individuals with sarcopenia and pre-frailty (MD: -0·98, 95 % CI: -1·56, -0·39, I2 = 0 %). These findings may be dependent on participant characteristics and treatment duration. CONCLUSIONS These data support that whey and soy protein supplementation elicit anti-inflammatory effects by reducing circulating IL-6 and TNF-α levels, respectively. This effect may be enhanced by soy isoflavones and may be more prominent in individuals with sarcopenia.
3.
Diets for weight management in adults with type 2 diabetes: an umbrella review of published meta-analyses and systematic review of trials of diets for diabetes remission.
Churuangsuk, C, Hall, J, Reynolds, A, Griffin, SJ, Combet, E, Lean, MEJ
Diabetologia. 2022;65(1):14-36
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Type 2 diabetes (T2D) is a global epidemic. Although it is a complex disease, it is mainly driven by weight gain. The benefits of weight loss for T2D are well known, but patients and healthcare practitioners do not have clear guidance as to which dietary strategies may be effective to achieve and to maintain weight loss. The aim of this study is to review a number of studies of weight loss diets in T2D patients to see which ones are the most effective. Also, to see which dietary patterns support type 2 diabetes remission. Greatest weight loss was reported with very low energy diets including formula meal replacements. Low-carbohydrate diets were no better for weight loss than higher-carbohydrate/low-fat diets. High-protein, Mediterranean, high-monounsaturated-fatty-acid, vegetarian and low-glycaemic-index diets all achieved minimal or no difference from control diets. Diets for weight management in people with type 2 diabetes do not support any particular macronutrient profile or style over others. Very low energy diets and formula meal replacements appear to be the most effective. Programmes including a hypocaloric formula ‘total diet replacement’ induction phase were most effective for type 2 diabetes remission. Further research is needed to assess longer-term impacts on weight, glycaemic control, clinical outcomes and diabetes complications.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Authors highlight current evidence on diets for T2D remission is limited but believe remission can be achieved if sufficient weight loss is maintained. The main contributor to HbA1c reduction and remission appears to be weight loss, irrespective of diet type
- Nice Guidelines highlight the remission of diabetes occurs when a patient no longer satisfies the diagnostic criteria, without receiving glucose-lowering medication. By 2019 in one UK GP practice 27% of the practice population with T2D who followed a LCD for 23 months, lost weight and lowered their HbA1c to 48 mmol/mol (NICE target range) in conjunction with prescribed medication
- This review highlights an opportunity for Nutritional Therapy Practitioners to successfully work with LCD approaches to support weight loss and improved HbA1c.
Evidence Category:
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X
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:
- 19 meta-analyses (MA) on weight-loss diets, involving 23 primary trials were assessed using A Measurement Tool to Assess Systematic Reviews (AMSTAR) 2. Findings were synthesised by diet type and study quality (Cochrane Risk of Bias tool 2.0 and Risk Of Bias In Non-randomised Studies – of Interventions [ROBINS-I]) with GRADE applied
- Weight loss diets in the review included: Formula meal replacements (high quality, GRADE moderate) achieved 2.4 kg (95% CI −3.3, −1.4) greater weight loss over 12–52 weeks. Low-carbohydrate diets were no better for weight loss than higher-carbohydrate/low-fat diets (high quality, GRADE high). High-protein, Mediterranean, high-monounsaturated-fatty-acid, vegetarian and low-glycaemic-index diets all achieved minimal (0.3– 2 kg) or no difference from control diets (low to critically low quality, GRADE very low/moderate)
- Greatest weight loss was reported with very low energy diets (VLED), (400–500 kcal). However, this study found that low-carbohydrate diets (LCD) (21–70g of carbohydrate daily from1000–1500 kcal) were no better for weight loss than higher-carbohydrate/low-fat diets
- Time period of diets / length of observation / intervention: (1) Formula meal replacements (>12–52 wk), (2) LCDs ranged between (>8 wk to 4 years), (3) Very low energy diets (>8–12 wk), (4) High- protein (>4->8 wks), Mediterranean (>4->8 wk), high-monounsaturated-fatty-acid (>2wk), vegetarian (≥3wk) and low-glycaemic-index diets (≥6mo)
- Authors highlight weight reduction is fundamental for T2D management and remission
- This MA found that VLED and formula meal replacement appear the most effective approaches for weight management with T2D by providing less energy than self-administered food-based diets
- Potential pathophysiological mechanisms highlighted by authors are HbA1c reduction and remission which appear to be from weight loss, with only small differences between diet types assessed over 3–12 months, irrespective of diet type
- Study limitations: Many meta-analyses were of ‘low’ and ‘critically low’ AMSTAR 2 quality, predominantly through ‘no protocol reported’ (despite clear and sound methods) and no assessment of publication bias
- Most studies included European participants, such that findings may not be equally applicable to other ethnic and/or deprived communities. Durations of interventions varied, where weight regain is frequent over a longer period. Authors highlight evidence from clinical practice is needed to identify safe and effective approaches to achieve and maintain weight loss
- Authors highlight primary studies should use an RCT design, with data analyses conducted ‘blind’. They should define the intervention clearly (e.g., diets, physical activity, and behavioural and psychological support), and address separately the induction (usually 3–6 months) and maintenance (≥12 months)
- This research received no funding
- The authors declared no conflicts of interest.
Clinical practice applications:
- While this study found a variety of dietary compositions can be used effectively for weight management with T2D, VLED was successfully used to achieve remission for T2D
- Programmes with a ’total diet replacement’ induction phase were the most effective dietary approach for T2D remission (up to 61% of participants at 1 year).
Considerations for future research:
- Authors state future research should provide implementation with optimal support in real-life settings for weight loss, prevention of weight regain and remissions, rather than seek subtle differences from macronutrient compositions
- Future studies should report sufficient detail about macronutrient or micronutrient contents, or prescribed and reported energy intakes, including energy intake of nutrient-restricted diets.
Abstract
AIMS/HYPOTHESIS Weight reduction is fundamental for type 2 diabetes management and remission, but uncertainty exists over which diet type is best to achieve and maintain weight loss. We evaluated dietary approaches for weight loss, and remission, in people with type 2 diabetes to inform practice and clinical guidelines. METHODS First, we conducted a systematic review of published meta-analyses of RCTs of weight-loss diets. We searched MEDLINE (Ovid), PubMed, Web of Science and Cochrane Database of Systematic Reviews, up to 7 May 2021. We synthesised weight loss findings stratified by diet types and assessed meta-analyses quality with A Measurement Tool to Assess Systematic Reviews (AMSTAR) 2. We assessed certainty of pooled results of each meta-analysis using Grading of Recommendations, Assessment, Development and Evaluations (GRADE) (PROSPERO CRD42020169258). Second, we conducted a systematic review of any intervention studies reporting type 2 diabetes remission with weight-loss diets, in MEDLINE (via PubMed), Embase and Cochrane Central Register of Controlled Trials, up to 10 May 2021. Findings were synthesised by diet type and study quality (Cochrane Risk of Bias tool 2.0 and Risk Of Bias In Non-randomised Studies - of Interventions [ROBINS-I]), with GRADE applied (PROSPERO CRD42020208878). RESULTS We identified 19 meta-analyses of weight-loss diets, involving 2-23 primary trials (n = 100-1587), published 2013-2021. Twelve were 'critically low' or 'low' AMSTAR 2 quality, with seven 'high' quality. Greatest weight loss was reported with very low energy diets, 1.7-2.1 MJ/day (400-500 kcal) for 8-12 weeks (high-quality meta-analysis, GRADE low), achieving 6.6 kg (95% CI -9.5, -3.7) greater weight loss than low-energy diets (4.2-6.3 MJ/day [1000-1500 kcal]). Formula meal replacements (high quality, GRADE moderate) achieved 2.4 kg (95% CI -3.3, -1.4) greater weight loss over 12-52 weeks. Low-carbohydrate diets were no better for weight loss than higher-carbohydrate/low-fat diets (high quality, GRADE high). High-protein, Mediterranean, high-monounsaturated-fatty-acid, vegetarian and low-glycaemic-index diets all achieved minimal (0.3-2 kg) or no difference from control diets (low to critically low quality, GRADE very low/moderate). For type 2 diabetes remission, of 373 records, 16 met inclusion criteria. Remissions at 1 year were reported for a median 54% of participants in RCTs including initial low-energy total diet replacement (low-risk-of-bias study, GRADE high), and 11% and 15% for meal replacements and Mediterranean diets, respectively (some concerns for risk of bias in studies, GRADE moderate/low). For ketogenic/very low-carbohydrate and very low-energy food-based diets, the evidence for remission (20% and 22%, respectively) has serious and critical risk of bias, and GRADE certainty is very low. CONCLUSIONS/INTERPRETATION Published meta-analyses of hypocaloric diets for weight management in people with type 2 diabetes do not support any particular macronutrient profile or style over others. Very low energy diets and formula meal replacement appear the most effective approaches, generally providing less energy than self-administered food-based diets. Programmes including a hypocaloric formula 'total diet replacement' induction phase were most effective for type 2 diabetes remission. Most of the evidence is restricted to 1 year or less. Well-conducted research is needed to assess longer-term impacts on weight, glycaemic control, clinical outcomes and diabetes complications.
4.
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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X
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.