Nutritional advice

Dietary DHA, DPA and EPA are associated with higher lung function among current smokers

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Objectives:
Does dietary intake of n-3 PUFAs (such as DHA, EPA, DPA and ALA) or fish consumption improve lung function?

Study design:
This review article included 9 cohort studies from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (n = 37,077 black and white participants).

In each cohort and each ancestry, separately, associations of dietary n-3 PUFA/fish intake with lung function were estimated in linear regression models.
Fixed-effects meta-analysis was used to generate summarized effect estimates across the cohorts and ancestries.

The lung function was measured by the forced expiratory volume in 1 second (FEV1) and the forced vital capacity (FVC).

Results and conclusions:
The investigators found dietary DPA, DHA, EPA and fish intake significantly improved forced expiratory volume in one second (FEV1) and forced vital capacity (FVC).
However, dietary α-linolenic acid (ALA) had little to no association with these lung function parameters.

The investigators found associations were similar for black and white participants and consistent in direction and magnitude across most cohort studies.

The investigators found for all participants, 1 standard deviation (SD) higher dietary intake of DPA (∼30 mg/d), DHA (∼200 mg/d) and EPA (∼150 mg/d) were associated with 12-16 mL higher FEV1 and 10-15 mL higher FVC.
The effect estimates for fish consumption were in the same direction but smaller in magnitude.

The investigators found ∼200 mg/d DHA and ∼150 mg/d EPA were associated with 28-32 mL higher FEV1 and 24-25 mL higher FVC in current smokers.

The investigators found ∼200 mg/d DHA and ∼150 mg/d EPA were associated with 17-21 mL higher FEV1 and 7-12 mL higher FVC in former smokers.

The investigators found ∼200 mg/d DHA and ∼150 mg/d EPA had little to no association with FEV1 and FVC in never smokers.

The investigators concluded that dietary ∼200 mg/d DHA, ∼30 mg/d DPA and ∼150 mg/d EPA and fish intake are associated with higher lung function, especially among current and former smokers.

Original title:
Positive Associations of Dietary Marine Omega-3 Polyunsaturated Fatty Acids with Lung Function: A Meta-analysis (P18-087-19) by Patchen B, Xu J, […], Cassano P.

Link:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6579416/  

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DHA, DPA and EPA are found in fish.

 

Exercise intervention in kidney transplant recipients improves quality of life

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Objectives:
Whether exercise can improve cardiovascular health in kidney transplant recipients (KTRs) is unclear. Therefore, this review article (meta-analysis) has been conducted.

Does exercise improve cardiovascular health in kidney transplant recipients?

Study design:
This review article included 12 RCTs (trials) in the review and 11 RCTs for further qualitative analysis.
Most trials provided a 30-60 minutes exercise session for 2-4 times per week.
In terms of the total intervention period, most trials ranged from 10 weeks to 6 months.

Results and conclusions:
The investigators found in 5 trials with a total of 199 participants that exercise had no effects on either systolic [MD = 1.67, 95% CI = -2.17 to 5.51, p = 0.39] or diastolic blood pressure [MD = 0.65, 95% CI = -4.02 to 5.32, p = 0.78].

The investigators found in 3 trials with a total of 261 participants that exercise had no significant benefits in overall lipid profile [MD = 0.03, 95% CI = -0.09 to 0.15, p = 0.62].
In subgroup analysis, total cholesterol [p = 0.15], LDL cholesterol [p = 0.83] and triglyceride [p = 0.82] were not ameliorated by exercise.

The investigators found in 2 trials with 22 subjects in the exercise group and 28 controls that a 12 months of resistance training or regimens of aerobic or resistance training for 12 weeks was not associated with an improvement in kidney function [MD = 2.60, 95% CI = -12.88 to 13.09, p = 0.74].

The investigators found that aerobic training, resistance training or the combination during 12 weeks to 12 months was not associated with an improvement on body weight [MD = -2.02, 95% CI = -8.24 to 4.20, p = 0.52, n = 3] or BMI [MD = 0.12, 95% CI = -1.52 to 1.77, p = 0.88, n = 4].

The investigators found in 2 trials with a total of 64 participants that a 12-week exercise showed a consistent improvement in small arterial stiffness [MD = -1.14, 95% CI = -2.19 to -0.08, p = 0.03].

The investigators found in 5 trials with a total of 202 participants that aerobic training, resistance training or combined method over the course of 12 weeks to 12 months had a significant improvement in exercise capacity (VO2 peak) [MD = 2.25, 95% CI = 0.54 to 3.69, p = 0.01]. 

The investigators found exercise improved quality of life in different aspects, with significant enhancement in social functioning [MD = 16.76, 95% CI = 2.16 to 31.37, p = 0.02] and overall QOL scores [MD = 12.87, 95% CI = 6.80 to 18.94, p 0.01].

The investigators concluded exercise intervention in kidney transplant recipients improves arterial stiffness and it also improves exercise tolerance and quality of life. Additional long-term RCTs examining a greater number of patients are needed to understand the effects of exercise on cardiovascular health in kidney transplant recipients.

Original title:
Effects of exercise training on cardiovascular risk factors in kidney transplant recipients: a systematic review and meta-analysis by Chen G, Liu Gao L and Li X.

Link:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6534232/

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200g vegetables per day reduce gallstone disease

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Objectives:
The role of fruit and vegetables (FVs) consumption in decreasing gallstone disease risk remains contradictory.Therefore, this review article has been conducted.

Does fruit or vegetables consumption reduce risk of gallstone disease?

Study design:
This review article included 1 cross-sectional study, 1 case-control studie and 9 cohort studies, covering approximately 33,983 patients with gallstone disease and 1,53,3752 participants.

Results and conclusions:
The investigators found in a pooled analysis, vegetables consumption was significantly related to a decreased gallstone disease risk of 17% [RR  =  0.83, 95% CI = 0.74-0.94, I2  =  91.1%]. This reduced gallstone disease risk was solid in most subgroup analysis.

The investigators found in a pooled analysis, fruits consumption was significantly related to a decreased gallstone disease risk of 12% [RR  =  0.88, 95% CI = 0.83-0.92, I2  =  0.01%].  
This reduced gallstone disease risk was solid in most subgroup analysis.

The investigators found nonlinear dose-response analysis indicated that gallstone risk was reduced by 4% [RR  =  0.96, 95% CI = 0.93-0.98, p =0.001] for every 200 g per day increment in vegetables consumption.

The investigators found nonlinear dose-response analysis indicated that gallstone risk was reduced by 3% [RR  =  0.97, 95% CI = 0.96-0.98, p =0.001] for every 200 g per day increment in fruits consumption.

The investigators concluded that vegetables and fruits consumption, particularly 200g fruits or 200g vegetables per day is correlated with a reduced risk of gallstone disease.

Original title:
Fruits and vegetables consumption and the risk of gallstone diasease: A systematic review and meta-analysis by Zhang JW, Xiong JP, [...], Zhao HT.

Link:
https://www.ncbi.nlm.nih.gov/pubmed/31305451

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≥12 weeks of L-carnitine supplements reduce inflammation

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Objectives:
Has L-carnitine supplementation positive effects on inflammatory mediators including C-reactive protein (CRP), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)?

Study design:
This review article included 13 RCTs.

Results and conclusions:
The investigators found L-carnitine supplementation was significantly associated with lower levels of CRP in comparison to controls [WMD = -1.23 mg/L, 95% CI = -1.73 to -0.72 mg/dL, p  0.0001].
This reduced effect was greatest during an intervention of more than 12 weeks.

The investigators found L-carnitine supplementation was also significantly associated with lower levels of IL-6 in comparison to controls [WMD = -0.85 pg/dL, 95% CI = -1.38 to -0.32 pg/dL, p = 0.002].
This reduced effect was greatest during an intervention of more than 12 weeks.

The investigators found L-carnitine supplementation was also significantly associated with lower levels of TNF-α in comparison to controls [WMD = -0.37 pg/dL, 95% CI = -0.68 to -0.06 pg/dL, p = 0.018].
This reduced effect was greatest during an intervention of more than 12 weeks.

The investigators concluded that L-carnitine supplementation reduces levels of inflammatory mediators, especially in studies with a duration of more than 12 weeks. Further studies with different doses and intervention durations and separately in men and women are necessary.

Original title:
The effect of L-carnitine on inflammatory mediators: a systematic review and meta-analysis of randomized clinical trials by Haghighatdoost F, Jabbari M and Hariri M.

Link:
https://www.ncbi.nlm.nih.gov/pubmed/30915521 

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Plasma creatinine seems to be a promising prognostic biomarker for ALS

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Objectives:
Plasma creatinine has been described as a prognostic biomarker for Amyotrophic Lateral Sclerosis (ALS), but with conflicting results in the literature. Therefore, this review article (meta-analysis) has been conducted.

Does a high plasma creatinine concentration reduce risk of ALS?

Study design:
This review article included 14 distinct cohorts (19 studies).

The overall quality of the studies was low mainly due to potential attrition bias and several studies did not report analyzable results raising concern regarding a potential reporting bias.

Results and conclusions:
The investigators found for baseline plasma creatinine, mortality risk was 28% lower when creatinine was higher than 88.4 µmol/L [HR = 0.72, 95% CI = 0.58 to 0.88, p = 0.0003] and was 25% lower if creatinine was above versus below the median [HR = 0.75, 95% CI = 0.63 to 0.89, p = 0.0008].

The investigators found a significant positive correlation between plasma creatinine at baseline and functional score and between creatinine decline and functional score decline [p  0.0001 for both].

The investigators found, however, a negative correlation between plasma creatinine and functional score decline [p = 0.033].

The investigators concluded plasma creatinine seems to be a promising prognostic biomarker for ALS. However, new studies with sound methodology and standardized criteria for the evaluation of ALS progression should be conducted to validate plasma creatinine as a clinical biomarker for ALS prognosis.

Original title:
Plasma creatinine and amyotrophic lateral sclerosis prognosis: a systematic review and meta-analysis by Lanznaster D, Bejan-Angoulvant T, […], Blasco H.

Link:
https://www.ncbi.nlm.nih.gov/pubmed/30961401

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10-40 g/day dietary fiber intake reduce diverticular disease risk

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Objectives:
A high intake of dietary fibre has been associated with a reduced risk of diverticular disease in several studies. However, the dose-response relationship between fibre intake and diverticular disease risk has varied and the available studies have not been summarised in a meta-analysis yet. Therefore, this review article (meta-analysis) has been conducted.

Is there a dose-response relationship between fibre intake and reduced risk of diverticular disease?

Study design:
This review article included 5 prospective cohort studies with 19,282 cases (persons with a diverticular disease) and 865,829 participants.

There was no evidence of publication bias with Egger's test, p = 0.58.

Results and conclusions:
The investigators found every 10 g/day increase of dietary fibre intake significantly reduced risk of diverticular disease with 26% [summary RR = 0.74, 95% CI = 0.71-0.78, I2 = 0%]. This significantly reduced risk persisted in subgroup and sensitivity analyses.

The investigators found no evidence of a nonlinear association between dietary fibre intake and diverticular disease risk [p nonlinearity = 0.35].

The investigators found compared to 7.5 g/day, 20 g/day of dietary fibre intake significantly reduced risk of diverticular disease with 23%.

The investigators found compared to 7.5 g/day, 30 g/day of dietary fibre intake significantly reduced risk of diverticular disease with 41%.

The investigators found compared to 7.5 g/day, 40 g/day of dietary fibre intake significantly reduced risk of diverticular disease with 58%.

The investigators found every 10 g/day increase of dietary cereal fibre intake significantly reduced risk of diverticular disease with 26% [summary RR = 0.74, 95% CI = 0.67-0.81, I2 = 60%, n = 4].

The investigators found every 10 g/day increase of dietary fruit fibre intake significantly reduced risk of diverticular disease with 44% [summary RR = 0.56, 95% CI = 0.37-0.84, I2 = 73%, n = 2].

The investigators found every 10 g/day increase of dietary vegetable fibre intake non-significantly reduced risk of diverticular disease with 20% [summary RR = 0.80, 95% CI = 0.45-0.1.44, I2 = 87%, n = 2].

The investigators concluded that 10-40 g/day dietary fiber intake, particularly cereal and fruit fibre reduces risk of diverticular disease. However, further studies are needed on fibre types and risk of diverticular disease and diverticulitis.

Original title:
Dietary fibre intake and the risk of diverticular disease: a systematic review and meta-analysis of prospective studies by Aune D, Sen A, […], Riboli E.

Link:
https://www.ncbi.nlm.nih.gov/pubmed/31037341

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40 grams of fiber per day corresponds to a diet with 2 grams of fiber per 100 kcal. The easiest way to follow a diet with 2 grams of fiber per 100 kcal is to choose only products/meals with 2 grams of fiber per 100 kcal. Check here which products/meals provide 2 grams of fiber per 100 kcal.

Diverticular disease is the general name for a common condition that causes small bulges (diverticula) or sacs to form in the wall of the large intestine (colon). Although these sacs can form anywhere in the colon, they are most common in the sigmoid colon (part of the large intestine closest to the rectum). The recent literature does not identify diverticular disease as a long-term risk factor for colorectal cancer.
 

Higher hemoglobin levels decrease transfusion risk in predialysis patients with CKD

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Objectives:
Anemia is one of the major complications in predialysis patients with chronic kidney disease (CKD). A clearer cognition of the prognostic impact of hemoglobin (Hb) or hematocrit (Hct) target on the outcomes of predialysis patients with CKD is significant. Therefore, this review article (meta-analysis) has been conducted.

Does higher hemoglobin levels decrease transfusion risk in predialysis patients with CKD?

Study design:
This review article included 13 RCTs involving 7,606 patients.

Results and conclusions:
The investigators found compared to lower hemoglobin levels, predialysis patients with chronic kidney disease with higher hemoglobin levels had a significantly lower risk of 49% for transfusion [risk ratio = 0.59, 95% CI = 0.52 to 0.67, p 0.00001].

The investigators found, however, no significant difference in all-cause mortality [RR = 1.10, 95% CI = 0.98 to 1.23, p = 0.11], stroke [RR = 1.32, 95% CI = 0.82 to 2.10, p = 0.25] and treatment of renal replacement including hemodialysis, peritoneal dialysis and renal transplant [RR = 1.08, 95% CI = 0.95 to 1.22, p = 0.23] between the higher hemoglobin group and the lower one.

The investigators concluded higher hemoglobin levels when treating predialysis patients with chronic kidney disease decrease the risk of transfusion without increasing the risk of death, stroke and treatment of renal replacement.

Original title:
Therapeutic targets for the anemia of predialysis chronic kidney disease: a meta-analysis of randomized, controlled trials by Liu H, Ye Y, […], Liu X.

Link:
https://www.ncbi.nlm.nih.gov/pubmed/30755495

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Magnesium deficiency increases risk of ADHD

Objectives:
Current research suggests conflicting evidence surrounding the association between serum magnesium levels and the diagnosis of attention deficit hyperactivity disorder (ADHD). Therefore, this review article (meta-analysis) has been conducted.

Does serum magnesium deficiency increase risk of ADHD?

Study design:
This review article included 7 observational studies, which reported the mean and standard deviation (SD) of magnesium concentration in both ADHD and control groups.

Results and conclusions:
The investigators found random-effects meta-analysis showed that subjects with ADHD had 0.105 mmol/L [95% CI = -0.188 to -0.022, p 0.013, I2 = 96.2%, p = 0.0103] lower serum magnesium levels compared with to their healthy controls.

The investigators concluded this meta-analysis supports the theory that an inverse relationship between serum magnesium deficiency and ADHD exists. High heterogeneity amongst the included studies suggests that there is a residual need for observational and community-based studies to further investigate this issue.

Original title:
Magnesium status and attention deficit hyperactivity disorder (ADHD): A meta-analysis by Effatpanah M, Rezaei M, […], Hashemi R.

Link:
https://www.ncbi.nlm.nih.gov/pubmed/30807974

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3 mg creatine/kg/day for 14 days improve anaerobic performance in soccer players

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Objectives:
Studies have shown that creatine supplementation increases intramuscular creatine concentrations, favoring the energy system of phosphagens, which may help explain the observed improvements in high-intensity exercise performance. However, research on physical performance in soccer has shown controversial results, in part because the energy system used is not taken into account. Therefore, this review article (meta-analysis) has been conducted.

Does creatine supplementation improve physical performance in soccer players?

Study design:
This review article included 9 RCTs with a total sample of 168 soccer players (118 males, 50 females) with an average age of 20.3 ± 2.0 years (from 15 to 30 years, as an average for the experimental sample).

The meta-analysis was performed using the random effects model and pooled standardized mean differences (SMD) (Hedges's g).

Results and conclusions:
The investigators found that creatine supplementation did not present beneficial effects on aerobic performance tests [SMD = -0.05, 95% CI = -0.37 to 0.28, p = 0.78] and phosphagen metabolism performance tests (strength, single jump, single sprint and agility tests: SMD = 0.21, 95% CI = -0.03 to 0.45, p = 0.08].

The investigators found, however, creatine supplementation showed beneficial effects on anaerobic performance tests [SMD = 1.23, 95% CI = 0.55 to 1.91, p 0.001].
Concretely, creatine supplementation demonstrated a large and significant effect on Wingate test performance [SMD = 2.26, 95% CI = 1.40 to 3.11, p 0.001].

The investigators concluded creatine supplementation with a loading dose of 20-30 g/day, divided 3-4 times per day, ingested for 6 to 7 days and followed by 5 g/day for 9 weeks or with a low dose of 3 mg/kg/day for 14 days presents positive effects on improving physical performance tests related to anaerobic metabolism, especially anaerobic power, in soccer players.

Original title:
Effects of Creatine Supplementation on Athletic Performance in Soccer Players: A Systematic Review and Meta-Analysis by Mielgo-Ayuso J, Calleja-Gonzalez J, […], Fernández-Lázaro D.

Link:
https://www.mdpi.com/2072-6643/11/4/757/htm

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Physical activity reduces lung cancer among smokers

Objectives:
Epidemiological evidences regarding the association between physical activity and the risk of lung cancer are still controversial. Therefore, this review article has been conducted.

Does physical activity reduce risk of lung cancer?

Study design:
This review article included 20 cohort studies with a total of 2,965,811 participants and 31,807 lung cancer cases.

The study population were adults with age of >18 years.
Most studies were adjusted for major confounders including age, sex, smoking status and body mass index, etc.

The quality scores ranged from 5 to 9 with a median score of 8.
3 studies were evaluated with a score of 7 and others with a score of ≥7. Thus, the majority of the studies included in the meta-analysis were assessed as high-quality studies.

There might be little indication of publication bias in this meta-analysis.

Results and conclusions:
The investigators found compared with the low level of physical activity, the high level of physical activity significantly reduced risk of lung cancer with 17% [pooled RR = 0.83, 95% CI = 0.77 to 0.90, I2 = 62.6%, p heterogeneity 0.001].

The investigators found in subgroup analyses, compared with the low level of physical activity, the high level of physical activity significantly reduced risk of lung cancer among women with 10% [pooled RR = 0.90, 95% CI = 0.82 to 0.99].

The investigators found in subgroup analyses compared with the low level of physical activity, the high level of physical activity significantly reduced risk of lung cancer among men with 19% [pooled RR = 0.81, 95% CI = 0.73 to 0.90].

The investigators found smokers with a high level of physical activity were associated with a 10% lower risk for lung cancer [RR = 0.90, 95% CI = 0.84 to 0.97], while the association was not significant among non-smokers [RR = 0.95, 95% CI = 0.88 to 1.03].

Subgroups analysis stratified by whether the studies adjusted for smoking intensity and durations yielded the same magnitude of RR.

However, the RR for subgroups without adjustment for dietary factors was 0.74 [95% CI = 0.71 to 0.77], which was significantly lower than that with dietary factors adjusted [RR = 0.89, 95% CI = 0.84 to 0.95].

The investigators found in sensitivity analyses, the pooled RRs ranged from 0.82 [95% CI = 0.76 to 0.89] to 0.86 [95% CI = 0.81 to 0.92]. The trend was generally similar with the overall analysis.

The investigators concluded a high level of physical activity reduces risk of lung cancer among smokers. Large interventional studies are expected to further verify these findings. If the inverse association, as well as the effect modification by smoking status, reflects a causal relation, future precision prevention of lung cancer by increased physical activity may be more effective when targeting to smokers rather than non-smokers.

Original title:
Association Between Physical Activity and Lower Risk of Lung Cancer: A Meta-Analysis of Cohort Studies by Liu Y, Li Y, […], Fan XX.

Link:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6349707/

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3 cups/d coffee consumption reduce risk of all-cause mortality

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Objectives:
Previous meta-analysis showed an inverse association between coffee consumption and all-cause mortality. However, the relationship between caffeinated and decaffeinated coffee consumption and all-cause mortality is inconsistent. Therefore, this review article has been conducted.

Do both caffeinated and decaffeinated coffee consumption reduce all-cause mortality?

Study design:
This review article included 21 cohort studies with a total of 10,103,115 study participants and 240,303 deaths.

Results and conclusions:
The investigators found a nonlinear association between coffee consumption and all-cause mortality [p nonlinearity 0.001].

The investigators found compared with no or rare coffee consumption that 3 cups/d coffee consumption significantly reduced risk of all-cause mortality with 13% [RR = 0.87, 95% CI = 0.84 to 0.89].

The investigators concluded that 3 cups/d coffee consumption reduce risk of all-cause mortality. The reduced risks are similar for caffeinated coffee and decaffeinated coffee.

Original title:
Caffeinated and decaffeinated coffee consumption and risk of all-cause mortality: a dose-response meta-analysis of cohort studies by Li Q, Liu Y, […], Hu D.

Link:
https://www.ncbi.nlm.nih.gov/pubmed/30786114

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Dietary n-3 PUFAs reduce ulcerative colitis

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Objectives:
Fish consumption and dietary intake of n-3 polyunsaturated acids (PUFAs) may be associated with inflammatory bowel disease (IBD). Therefore, this review article has been conducted.

Is there an association between fish consumption or dietary intake of n-3 polyunsaturated acids (PUFAs) and inflammatory bowel disease risk?

Study design:
This review article included 5 prospective cohort studies and 7 case-control studies with a total sample size of 282,610 participants which 2,002 of them were cases of inflammatory bowel disease (1,061 Crohn's disease (CD) and 937 ulcerative colitis (UC)).

Results and conclusions:
The investigators found fish consumption significantly reduced risk of Crohn's disease with 46% [pooled effect size = 0.54, 95% CI = 0.31-0.96, p = 0.03].

The investigators found there was no relationship between total dietary n-3 PUFAs intake and inflammatory bowel disease risk [pooled effect size = 1.17, 95% CI = 0.80-1.72, p = 0.41].

The investigators found dietary long-chain n-3 PUFAs significantly reduced ulcerative colitis risk with 25% [pooled effect size = 0.75, 95% CI = 0.57-0.98, p = 0.03].

The investigators found no association between dietary α-linolenic acid (ALA) and inflammatory bowel disease risk [pooled effect size = 1.17, 95% CI = 0.63-2.17, p = 0.62].

The investigators concluded fish consumption reduces risk of Crohn's disease and dietary intake of long-chain n-3 PUFAs reduces risk of ulcerative colitis.

Original title:
Dietary intake of fish, n-3 polyunsaturated fatty acids, and risk of inflammatory bowel disease: a systematic review and meta-analysis of observational studies by Mozaffari H, Daneshzad E, […], Azadbakht L.

Link:
https://www.ncbi.nlm.nih.gov/pubmed/30680455

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15 minutes/week sunlight exposure decreases risk of Parkinson's disease

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Objectives:
Is there an association between vitamin D and Parkinson's disease risk?

Study design:
This review article included 8 studies.

Results and conclusions:
The investigators found when compared with normal controls, 25-hydroxyvitamin D insufficiency (30 ng/mL) significantly increased risk of Parkinson's disease with 77% [OR = 1.77, 95% CI = 1.29 to 2.43, p 0.001].

The investigators found when compared with normal controls, 25-hydroxyvitamin D deficiency (20 ng/mL) significantly increased risk of Parkinson's disease with 155% [OR = 2.55, 95% CI = 1.98 to 3.27, p 0.001].

The investigators found 15 minutes/week sunlight exposure significantly decreased risk of Parkinson's disease with 98% [OR = 0.02, 95% CI = 0.00 to 0.10, p 0.001].

The investigators found the use of vitamin D supplements was effective in increasing 25-hydroxyvitamin D levels [SMD = 1.79, 95% CI = 1.40 to 2.18, p 0.001], but had no significant effect on motor function [MD = -1.82, 95% CI = -5.10 to 1.45, p = 0.275] in patients with Parkinson's disease.

The investigators concluded that insufficiency and deficiency of 25-hydroxyvitamin D (vitamin D in blood) and reduced exposure to sunlight increase risk of Parkinson's disease. However, vitamin D supplements show no significant benefits in improving motor function for patients with Parkinson's disease.

Original title:
The Association Between Vitamin D Status, Vitamin D Supplementation, Sunlight Exposure, and Parkinson's Disease: A Systematic Review and Meta-Analysis by Zhou Z, Zhou R, [...], Li K.

Link:
https://www.ncbi.nlm.nih.gov/pubmed/30672512

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1-6g/d taurine supplementation improves human endurance performance

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Objectives:
Taurine is central to many physiological processes, some of which are augmented by exogenous supply and have the potential to facilitate endurance performance; however, its independent effects on performance have not been systematically analyzed. Therefore, this review article has been conducted.

Does supplementation of taurine improve human endurance performance?

Study design:
This review article included 10 peer-reviewed articles. A sub-analysis of time-to-exhaustion (TTE) trials (n = 7) was also performed.

The doses of taurine ranged from 1 to 6 g/day and were provided in single doses and for up to 2 weeks among a range of subjects.

Results and conclusions:
The investigators found that taurine supplementation significantly improved overall endurance performance [Hedges' g = 0.40, 95% CI = 0.12-0.67, p = 0.004], which was similar in TTE trials [Hedges' g = 0.43, 95% CI = 0.12-0.75, p = 0.007].

The investigators found no differences between acute or chronic supplementation for the full sample [p = 0.897] or the TTE group [p = 0.896].

The investigators found that the dose of taurine did not moderate its effect on endurance performance [p > 0.05].

The investigators concluded that human endurance performance can be improved by orally ingesting a single dose of taurine in varying amounts (1-6 g).

Original title:
The Effects of an Oral Taurine Dose and Supplementation Period on Endurance Exercise Performance in Humans: A Meta-Analysis by Waldron M, Patterson SD, […], Jeffries O.

Link:
https://www.ncbi.nlm.nih.gov/pubmed/29546641

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Dairy products, high purine vegetables, soy foods and coffee decrease gout

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Objectives:
Is there an association between dietary factors and the risk of gout and hyperuricemia?
 
Study design:
This review article included 10 prospective cohort studies (the follow-up duration ranged from 6 years to 26 year) and 9 cross-sectional studies.

Based on the Newcastle-Ottawa Scale (NOS), the quality assessment of included studies yielded a mean NOS score of 7.1, suggesting the presence of high methodologic quality.

Results and conclusions:
The investigators found in meta-analysis that the risk of getting gout significantly increased with:
29% [OR = 1.29, 95% CI = 1.16-1.44] for dietary red meat intake;
31% [OR = 1.31, 95% CI = 1.01-1.68] for dietary seafoods intake;
158% [OR = 2.58, 95% CI = 1.81-3.66] for dietary alcohol intake;
114% [OR = 2.14, 95% CI = 1.65-2.78] for dietary fructose intake.

The investigators found in meta-analysis that the risk of getting gout significantly decreased with:
44% [OR = 0.56, 95% CI = 0.44-0.70] for dietary dairy products intake;
15% [OR = 0.85, 95% CI = 0.76-0.96] for dietary soy foods intake;
14% [OR = 0.86, 95% CI = 0.75-0.98] for dietary high-purine vegetables intake;
53% [OR = 0.47, 95% CI = 0.37-0.59] for dietary coffee intake.

The investigators found in meta-analysis that the risk of getting hyperuricemia (an excess of uric acid in the blood) significantly increased with:
24% [OR = 1.24, 95% CI = 1.04-1.48] for dietary red meat intake;
47% [OR = 1.47, 95% CI = 1.16-1.86] for dietary seafoods intake;
106% [OR = 2.06, 95% CI = 1.60-2.67] for dietary alcohol intake;
85% [OR = 1.85, 95% CI = 1.66-2.07] for dietary fructose intake.

The investigators found in meta-analysis that the risk of getting hyperuricemia (an excess of uric acid in the blood) significantly decreased with:
50% [OR = 0.50, 95% CI = 0.37-0.66] for dietary dairy products intake;
30% [OR = 0.70, 95% CI = 0.56-0.88] for dietary soy foods intake.

The investigators found in meta-analysis that the risk of getting hyperuricemia (an excess of uric acid in the blood) non-significantly increase with:
10% [OR = 1.10, 95% CI = 0.88-1.39] for dietary high-purine vegetables intake.

The investigators found in meta-analysis that the risk of getting hyperuricemia (an excess of uric acid in the blood) non-significantly decreased with 24% [OR = 0.76, 95% CI = 0.55-1.06] for dietary coffee intake in men.
Non-significantly because OR of 1 was found in the 95% CI of 0.55 to 1.06. OR of 1 means no risk/association.

The investigators found in meta-analysis that the risk of getting hyperuricemia (an excess of uric acid in the blood) significantly increased with 58% [OR = 1.58, 95% CI = 1.16-2.16] for dietary coffee intake in women.
Significant because OR of 1 was not found in the 95% CI of 1.16 to 2.16. OR of 1 means no risk/association.

The investigators concluded that the risk of hyperuricemia and gout is positively correlated with the dietary intake of red meat, seafoods, alcohol or fructose and negatively with dairy products or soy foods. High-purine vegetables show no association with hyperuricemia, but negative association with gout. Coffee intake is negatively associated with gout risk, whereas it is positively associated with hyperuricemia risk in women.

Original title:
Dietary factors and risk of gout and hyperuricemia: a meta-analysis and systematic review by Li R, Yu K and Li C.

Link:
https://www.ncbi.nlm.nih.gov/pubmed/30485934

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Postherpetic neuralgia patients benefit from vitamin B12 supplementation

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Objectives:
Postherpetic neuralgia (PHN) is the most distressful complication of herpes zoster. Postherpetic neuralgia results in an impaired quality of life and higher healthcare utilization. Vitamin B12 has been proven to be effective in pain relief for various conditions. Therefore, this review article has been conducted.

Do postherpetic neuralgia patients benefit from vitamin B12 supplementation?

Study design:
This review article included 4 RCTs (published between 2013 and 2016) including 383 participants.

Results and conclusions:
The investigators found compared with the placebo group, the vitamin B12 group exhibited a significant decrease in the Numeric Rating Scale score, with a mean difference of -4.01 [95% CI = -4.70 to -3.33].

The investigators found compared with the placebo group, vitamin B12 administration improved the quality of life of postherpetic neuralgia patients with moderate quality evidence and significantly decreased the number of patients using analgesics.

The investigators concluded that vitamin B12 appears to be an attractive complementary therapy for postherpetic neuralgia patients. However, further investigation is needed before conclusive recommendations can be made.

Original title:
Vitamin B12 for herpetic neuralgia: A meta-analysis of randomised controlled trials by Wang JY, Wu YH, [...], Lu PH.

Link:
https://www.ncbi.nlm.nih.gov/pubmed/30477853

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Postherpetic neuralgia (PHN) is a nerve pain (neuralgia) that persists after a shingles rash has cleared. Postherpetic neuralgia is caused by the chickenpox (varicella-zoster) virus.
 

320 to 1500 mg/day magnesium supplementation decreases CRP levels

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Objectives:
Does magnesium supplementation reduce C-reactive protein concentrations in humans?

Study design:
This review article included 8 RCTs (2004-2014) with 349 participants.

The mean age of participants ranged from 18 to 85 years.
The range of duration of the supplementation intervention across studies was from 8 h to 6.5 months.
The consumed range of magnesium dose in these studies was from 320 to 1500 mg/day. The baseline level (at the start of the study) of the CRP varied between the studies from 0.42 mg/dL as minimum to 9.4 mg/dL as maximum.

Results and conclusions:
The investigators found magnesium supplementation significantly reduced serum CRP levels [WMD = -1.33 mg/dL, 95% CI = -2.63 to -0.02, p 0.001, I2 = 29.1%, p 0.123] across all studies.
In leave-one-out sensitivity analyses, the pooled effect estimates remained similar across all studies for CRP levels [WMD = -1.33 mg/dL, 95% CI = -2.63 to -0.02].

The investigators found after adjustment of the effect size for potential publication bias using the “trim and fill” correction, no potentially missing studies were imputed in the funnel plot [WMD = -1.33 mg/dL, 95% CI = -2.63 to -0.02]. The “fail-safe N” test showed that 146 studies would be needed to bring the WMD down to a non-significant [p > 0.05] value.

The investigators found in random-effects meta-regression changes in serum CRP levels were independent of the dosage of magnesium [slope = -0.004, 95% CI = -0.03 to 0.02, p = 0.720, and duration [slope = -0.06, 95% CI = -0.37 to 0.24, p = 0.681] of supplementation.

The investigators found in 4 RCTs that subjects with a baseline CRP of ≥ 2 mg/dL had more significant reduction in the serum CRP level [WMD = -2.95 mg/dL, 95% CI = -3.35 to -2.25, p 0.001, I2 = 1.1%, p = 0.952] compared with subjects with a baseline CRP of 2 mg/dL [WMD = -0.23 mg/dL, 95% CI = -0.195 to -0.326, p 0.001, I2 = 1.3% p = 0.923].

The investigators found magnesium supplementation non-significantly reduced IL-6 levels [WMD = -0.16 pg/dL, 95% CI = -3.52 to 3.26, p = 0.236, I2 = 2.3%, p = 0.802] across all studies.

The investigators found magnesium supplementation significantly increased TNF-α levels [WMD = 1.97 pg/dL, 95% CI = 1.12 to 2.82, p = 0.043, I2 = 2.1%, p = 0.869] across all studies.

The investigators found magnesium supplementation non-significantly decreased fasting blood glucose (FBG) levels [WMD = -0.61 mg/dL, 95% CI = -2.72 to 1.48, p = 0.182, I2 = 6.1%, p = 0.742] across all studies.

The investigators found magnesium supplementation non-significantly decreased systolic blood pressure levels [WMD = -0.93 mmHg, 95% CI = -3.03 to 1.20, p = 0.293, I2 = 3.6%, p = 0.526] across all studies.

The investigators found magnesium supplementation non-significantly decreased diastolic blood pressure levels [WMD = -0.30 mmHg, 95% CI = -2.80 to 2.19, p = 0.639, I2 = 3.8%, p = 0.489] across all studies.

The investigators found magnesium supplementation non-significantly increased BMI levels [WMD = 0.27 kg/m2, 95% CI = -0.59 to 1.15, p = 0.542, I2 = 2.0%, p = 0.906] across all studies.  

The investigators concluded that 320 to 1500 mg/day magnesium supplementation decreases serum CRP levels, especially with the baseline values ≥ 2 mg/dL. To provide more conclusive results and clarify the mechanistic pathways, RCTs with a larger sample size and a long-term follow-up period are warranted.

Original title:
Effect of magnesium supplements on serum C-reactive protein: a systematic review and meta-analysis by Mazidi M, Rezaie P and Banach M.

Link:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6040119/

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1 g/day salt reduction reduces blood pressure in end-stage renal disease

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Objectives:
Dietary salt reduction in the general population lowers blood pressure and cardiovascular risk. Despite being widely recommended, there is limited evidence as to whether this is applicable to individuals with end-stage renal disease (ESRD) receiving dialysis. Therefore, this review article has been conducted.

Study design:
This review article included 4 RCTs (91 participants), of which 3 were crossover trials and 1 was a parallel study.
Participants were 18 years and over; a reduction in salt intake of at least 1 g/day over 1 week and no concomitant interventions during the study.
The primary outcome was change in systolic and diastolic blood pressure.

Results and conclusions:
The investigators found dietary salt reduction was associated with an 8.4 mmHg [95% CI = 4.8-12.0, Ι2 = 0%] reduction in systolic blood pressure and a 4.4 mmHg [95% CI = 2.2-6.6, Ι2 = 0%] reduction in diastolic blood pressure.

The investigators concluded that a reduction in salt intake of at least 1 g/day over 1 week reduces blood pressure among individuals with end-stage renal disease (ESRD) receiving dialysis.

Original title:
The effect of dietary salt on blood pressure in individuals receiving chronic dialysis: a systematic review and meta-analysis of randomised controlled trials by Cole NI, Swift PA, […], Suckling RJ.

Link:
https://www.ncbi.nlm.nih.gov/pubmed/30413764

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Coffee consumption is associated with a higher circulating level of adiponectin in women

Objectives:
The association between coffee consumption and the circulating level of adiponectin and leptin has been evaluated in several epidemiological studies with conflicting results. Therefore, this review article has been conducted.

Is there an association between coffee consumption and the circulating level of adiponectin and leptin in humans?

Study design:
This review article included 12 cross-sectional studies.

Results and conclusions:
The investigators found when compared the highest versus the lowest coffee intake category, coffee consumption was associated with a higher circulating adiponectin level [SMD = 0.11, 95% CI = 0.06 to 0.17, p 0.001].

The investigators found in subgroup analysis when compared the highest versus the lowest coffee intake category, coffee consumption was associated with a higher circulating adiponectin level in women [SMD = 0.11, 95% CI = 0.02 to 0.20, p = 0.01], but not in men [SMD = 0.03, 95% CI = -0.08 to 0.14, p = 0.59].

The investigators found when compared the highest versus the lowest coffee intake category, coffee consumption was associated with a lower circulating leptin level [SMD = -0.19, 95% CI = -0.28 to -0.10, p 0.001].

The investigators concluded that coffee consumption is associated with a higher circulating level of adiponectin in women and a lower circulating level of leptin. However, more well-designed prospective cohort studies and randomised controlled trials are needed to further elaborate the concerned issues.

Original title:
Associations of coffee consumption with circulating level of adiponectin and leptin. A meta-analysis of observational studies by Zhang Y and Zhang DZ.

Link:
https://www.ncbi.nlm.nih.gov/pubmed/29513118

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Adiponectin is a unique adipokine, which is specifically and abundantly expressed in adipose tissues and improves insulin resistance. Having insulin resistance may increase the risk of type 2 diabetes and metabolic syndrome.

Higher intakes of fruit and vegetables improve immune function

Afbeelding

Objectives:
Inflammation is associated with an increased risk of a range of chronic diseases. A diet high in fruit and vegetables may help to reduce inflammation, as fruit and vegetables are rich sources of antioxidants and other biologically active substances, which may improve immune function. Therefore, this meta-analysis (systematic review) has been conducted.

Does fruit or vegetables intake reduce inflammation and improve immune function?

Study design:
This review article included 71 clinical trials and 12 were observational studies (n = 10 cross-sectional studies and n = 2 cohort studies).

Results and conclusions:
The investigators found among observational studies (n = 10 studies) an inverse association between intakes of fruit or vegetables and inflammatory biomarkers.

The investigators found the majority of the intervention studies (n = 48 studies) reported beneficial effects of fruit or vegetable intake on ≥1 biomarker of systemic or airway inflammation.

The investigators found a meta-analysis of included studies showed that fruit or vegetable intake significantly decreased circulating levels of C-reactive protein and tumor necrosis factor-α [p 0.05] and significantly increased the γδ-T cell population [p 0.05].

The investigators concluded that higher intakes of fruit and vegetables lead to both a reduction in proinflammatory mediators and an enhanced immune cell profile.

Original title:
Effects of fruit and vegetable consumption on inflammatory biomarkers and immune cell populations: a systematic literature review and meta-analysis by Hosseini B, Berthon BS, […], Wood LG.

Link:
https://www.ncbi.nlm.nih.gov/pubmed/29931038

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The level of C-reactive protein (CRP), which can be measured in your blood, increases when there's inflammation in your body.

Tumour necrosis factor-alpha (TNF-alpha) is recognized as an important mediator in many cytokine-dependent inflammatory events.

 

Oral supplementation with chondroitin sulfate reduces pain in knee osteoarthritis

Afbeelding

Objectives:
Although glucosamine and chondroitin sulfate have showed beneficial effects on joint tissues in osteoarthritis (OA), their therapeutic use in the clinical setting is still debatable. Therefore, this meta-analysis (systematic review) has been conducted.

Do glucosamine and chondroitin sulfate supplements relieve pain of knee osteoarthritis?

Study design:
This review article included RCTs.

The pain of knee osteoarthritis was measured using the Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) and/or the Visual Analog Scale (VAS).

Results and conclusions:
The investigators found that glucosamine supplements significantly reduced pain of knee osteoarthritis (expressed as Visual Analog Scale (VAS) [WMD = - 7.41 mm, 95% CI = - 14.31 to - 0.51, p = 0.04].
Significant means that there is an association with a 95% confidence.

The investigators found that chondroitin supplements significantly reduced pain of knee osteoarthritis (expressed as Visual Analog Scale (VAS) [WMD = - 8.35 mm, 95% CI = - 11.84 to - 4.85, p  0.00001].
Significant because the found p-value of 0.00001 is less than 0.05.

The investigators found that the combination of glucosamine and chondroitin supplements non-significantly reduced pain of knee osteoarthritis (expressed as Visual Analog Scale (VAS) [WMD = - 0.28 mm, 95% CI = - 8.87 to 8.32, p = 0.95].
Non-significantly because the found p-value of 0.95 is greater than 0.05.

The investigators found that none of the glucosamine, chondroitin supplements or their combination had a significant positive effect on the total WOMAC index and its subscores.

The investigators concluded that oral supplementation with glucosamine or chondroitin sulfate reduces pain in knee osteoarthritis. However, there is no additional effect using both therapeutic agents in combination for the management of symptomatic knee osteoarthritis.

Original title:
Effect of glucosamine and chondroitin sulfate in symptomatic knee osteoarthritis: a systematic review and meta-analysis of randomized placebo-controlled trials by Simental-Mendía M, Sánchez-García A, […], Simental-Mendía LE.

Link:
https://www.ncbi.nlm.nih.gov/pubmed/29947998

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Milk increases acne

Afbeelding

Objectives:
In the past, some observational studies have been carried out on the relationship between milk and dairy intake and risk of acne occurrence. However, their results were conflicting. Therefore, this meta-analysis (systematic review) has been conducted.

Does milk and dairy intake increase risk of acne?

Study design:
This review article included observational studies.

Results and conclusions:
The investigators found for highest compared with lowest category of dairy intake a significantly increased risk of 161% for acne [OR = 2.61, 95% CI = 1.20 to 5.67].

Significant means that there is an association with a 95% confidence.

The investigators found for highest compared with lowest category of total milk intake a significantly increased risk of 48% for acne [OR = 1.48, 95% CI = 1.31 to 1.66].
Significantly means it can be said with a 95% confidence that a high total milk intake really increased the risk of getting acne with 48%. 

The investigators found for highest compared with lowest category of low-fat milk intake a significantly increased risk of 25% for acne [OR = 1.25, 95% CI = 1.10 to 1.43].
Significant because OR of 1 was not found in the 95% CI of 1.10 to 1.43. RR of 1 means no risk/association.

The investigators found for highest compared with lowest category of skim milk intake a significantly increased risk of 82% for acne [OR = 1.82, 95% CI = 1.34 to 2.47].

The investigators found results of dose-response analysis revealed a significant linear relationship between dairy, whole milk and skim milk and risk of acne and a nonlinear association between dairy, milk, low-fat milk and skim milk intake and acne.

The investigators concluded there is a positive relationship between dairy, total milk, whole milk, low-fat and skim milk consumption and acne occurrence. In contrary, there is no significant association between yogurt/cheese and acne development.

Original title:
Dairy intake and acne development: A meta-analysis of observational studies by Aghasi M, Golzarand M, […], Taheri F.

Link:
https://www.ncbi.nlm.nih.gov/pubmed/29778512

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1 time/week fish consumption from 6-9 months reduces asthma and wheeze in children up to 4.5 years old

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Objectives:
The evidence is mixed on the use of long chain omega 3 fatty acids in the prevention and management of childhood asthma. Therefore, this meta-analysis (systematic review) has been conducted.

Does fish consumption reduce risk of childhood asthma?

Study design:
This review article included 23 observational studies on fish intake in association with childhood asthma.

Results and conclusions:
The investigators found in 15/23 studies early introduction of fish (6-9 months) and regular consumption (at least once a week) improved asthma symptoms and reduced risk in children 0-14 years as compared to no fish consumption; 6/23 showed no effect and 2/23 studies suggested adverse effects.

The investigators found a significantly reduced risk of 25% [OR = 0.75, 95% CI = 0.60-0.95] for all fish intake on current asthma in children up to 4.5 years old. 

The investigators found a significantly reduced risk of 38% [OR = 0.62, 95% CI = 0.48-0.80] for all fish intake on current wheeze in children up to 4.5 years old.

The investigators found as compared to no fish intake, a significantly reduced risk of 65% [OR = 0.35, 95% CI = 0.18-0.67] for fatty fish intake on asthma in children 8-14 years old. 

The investigators concluded that introduction of fish early in life (6-9 months) and regular consumption of all fish (at least once a week) reduces asthma and wheeze in children up to 4.5 years old, while fatty fish intake has beneficial effects in older children (8-14 years). Future well-designed clinical trials are recommended to confirm the promising findings documented in this literature analysis.

Original title:
The role of fish intake on asthma in children: A meta-analysis of observational studies by Papamichael MM, Shrestha SK, [...], Erbas B.

Link:
https://www.ncbi.nlm.nih.gov/pubmed/29524247

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Milk protein supplements + resistance training increase fat-free mass in older adults

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Objectives:
Older adults experience age-related physiological changes that affect body weight and body composition. In general, nutrition and exercise have been identified as potent stimulators of protein synthesis in skeletal muscle. Milk proteins are excellent sources of all the essential amino acids and may represent an ideal protein source to promote muscle anabolism in older adults undergoing resistance training. However, several randomized control trials (RCTs) have yielded mixed results on the effects of milk proteins supplementation in combination with resistance training on body weight and composition. Therefore, this review article has been conducted.

Does supplementation of milk protein alone or in combination with resistance training, increase fat-free mass in older adults (age ≥ 60 years)?

Study design:
This review article included 10 RCTs involving 574 participants (mean age range from 60 to 80.8 years).

There was no statistical evidence of publication bias among the studies.

Results and conclusions:
The investigators found overall, the combination of milk proteins supplementation and resistance training had no significant effect on fat mass [0.30, 95% CI = -0.25 to 0.86 kg] or body weight [1.02, 95% CI = -0.01 to 2.04 kg].

The investigators found, however, a positive effect of milk proteins supplementation paired with resistance training on fat-free mass [0.74, 95% CI = 0.30 to 1.17 kg].

The investigators found greater fat-free mass gains were observed in studies that included more than 55 participants [0.73, 95% CI = 0.30 to 1.16 kg] and in studies that enrolled participants with aging-related medical conditions [1.60, 95% CI = 0.92 to 2.28 kg].

The investigators concluded supplementation of milk protein, in combination with resistance training, is effective to elicit fat-free mass gain in older adults (age ≥ 60 years).

Original title:
Effects of Milk Proteins Supplementation in Older Adults Undergoing Resistance Training: A Meta-Analysis of Randomized Control Trials by Hidayat K, Chen GC, […], Qin LQ.

Link:
https://www.ncbi.nlm.nih.gov/pubmed/29380851

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Aerobic exercise benefits global cognition in mild cognitive impairment patients

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Objectives:
Individuals with mild cognitive impairment (MCI) are at high risk for developing dementia. Physical exercise is a promising intervention for cognitive decline. Systematic reviews regarding the effects of physical exercise on cognitive and psychological outcomes among MCI patients are limited and a systematic review exploring the effects of exercise modalities on the results has not been conducted. Therefore, this review article has been conducted.

Do individuals with mild cognitive impairment benefit from physical exercise?

Study design:
This review article included 11 studies. The exercise interventions can be classified into 3 types: (a) aerobic exercise, (b) resistance exercise and (c) multi-modal exercise.

Results and conclusions:
The investigators found that physical exercise had beneficial effects for global cognition [SMD = 0.30, 95% CI = 0.10-0.49, p = 0.002].

The investigators found subgroup analysis demonstrated that aerobic exercise programmes were consistently associated with medium effect size [SMD = 0.54-0.58].

The investigators found, however, the effects of physical exercise on domain-specific cognitive function and psychological outcomes in mild cognitive impairment patients remained inconclusive.

The investigators found sensitivity analysis showed that types of control exerted influence on the outcomes.

The investigators concluded that physical exercise, aerobic exercise in particular, benefits global cognition in mild cognitive impairment patients. The evidence of physical exercise on domain-specific cognitive function and psychological outcomes remains unclear, more trials with rigorous study design are necessary to provide the evidence.

Original title:
The effectiveness of physical exercise on cognitive and psychological outcomes in individuals with mild cognitive impairment: A systematic review and meta-analysis by Song D, Yu DSF, […], Lei Y.

Link:
https://www.ncbi.nlm.nih.gov/pubmed/29334638

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