Research Findings on Diet and Nutritional Therapy

[Research Update]

Recent Research Findings

on Diet and Nutritional Therapy

Compiled by Kevin W Chen, PhD  MPH


Effect of lower sodium intake on health: systematic review and meta-analysesBMJ. 2013 Apr 3; 346:f1326. By Aburto NJ, Ziolkovska A, Hooper L, et al. from Dept of Nutrition for Health and Development, World Health Organization, Switzerland.

OBJECTIVE:  To assess the effect of decreased sodium intake on blood pressure, related cardiovascular diseases, and potential adverse effects such as changes in blood lipids, catecholamine levels, and renal function.  DATA SOURCES:  Cochrane Central Register of Controlled Trials, Medline, Embase, WHO International Clinical Trials Registry Platform, the Latin American and Caribbean health science literature database, and the reference lists of previous reviews.   STUDY SELECTION: Randomised controlled trials (RCT) and prospective cohort studies in non-acutely ill adults and children assessing the relations between sodium intake and blood pressure, renal function, blood lipids, and catecholamine levels, and in non-acutely ill adults all cause mortality, cardiovascular disease, stroke, and coronary heart disease.  Potential studies were screened independently and in duplicate and study characteristics and outcomes extracted. When possible we conducted a meta-analysis to estimate the effect of lower sodium intake using the inverse variance method and a random effects model. We present results as mean differences or risk ratios, with 95% confidence intervals.   RESULTS:  We included 14 cohort studies and five RCTs reporting all cause mortality, cardiovascular disease, stroke, or coronary heart disease; and 37 RCTs measuring blood pressure, renal function, blood lipids, and catecholamine levels in adults. Nine controlled trials and one cohort study in children reporting on blood pressure were also included. In adults a reduction in sodium intake significantly reduced resting systolic blood pressure by 3.39 mm Hg (95% confidence interval 2.46 to 4.31) and resting diastolic blood pressure by 1.54 mm Hg (0.98 to 2.11). When sodium intake was <2 g/day versus ≥ 2 g/day, systolic blood pressure was reduced by 3.47 mm Hg (0.76 to 6.18) and diastolic blood pressure by 1.81 mm Hg (0.54 to 3.08). Decreased sodium intake had no significant adverse effect on blood lipids, catecholamine levels, or renal function in adults (P>0.05). There were insufficient RCTs to assess the effects of reduced sodium intake on mortality and morbidity. The associations in cohort studies between sodium intake and all cause mortality, incident fatal and non-fatal cardiovascular disease, and coronary heart disease were non-significant (P>0.05). Increased sodium intake was associated with an increased risk of stroke (risk ratio 1.24, 95% confidence interval 1.08 to 1.43), stroke mortality (1.63, 1.27 to 2.10), and coronary heart disease mortality (1.32, 1.13 to 1.53). In children, a reduction in sodium intake significantly reduced systolic blood pressure by 0.84 mm Hg (0.25 to 1.43) and diastolic blood pressure by 0.87 mm Hg (0.14 to 1.60). CONCLUSIONS:  High quality evidence in non-acutely ill adults shows that reduced sodium intake reduces blood pressure and has no adverse effect on blood lipids, catecholamine levels, or renal function, and moderate quality evidence in children shows that a reduction in sodium intake reduces blood pressure. Lower sodium intake is also associated with a reduced risk of stroke and fatal coronary heart disease in adults. The totality of evidence suggests that most people will likely benefit from reducing sodium intake.

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Dietary fiber intake and risk of first stroke: a systematic review and meta-analysisStroke. 2013 May;44(5):1360-8. By  Threapleton DE, Greenwood DC, Evans CE, et al. from School of Food Science & Nutrition, University of Leeds, Leeds, UK.

BACKGROUND:   Fiber intake is associated with reduced stroke risk in prospective studies, but no meta-analysis has been published to date.  METHODS: Multiple electronic databases were searched for healthy participant studies reporting fiber intake and incidence of first hemorrhagic or ischemic stroke, published between January 1990 and May 2012.  RESULTS: Eight cohort studies from the United States, northern Europe, Australia, and Japan met inclusion criteria. Total dietary fiber intake was inversely associated with risk of hemorrhagic plus ischemic stroke, with some evidence of heterogeneity between studies (I(2); relative risk per 7 g/day, 0.93; 95% confidence interval, 0.88-0.98; I(2)=59%). Soluble fiber intake, per 4 g/day, was not associated with stroke risk reduction with evidence of low heterogeneity between studies, relative risk 0.94 (95% confidence interval, 0.88-1.01; I(2)=21%). There were few studies reporting stroke risk in relation to insoluble fiber or fiber from cereals, fruit, or vegetables.  CONCLUSIONS:  Greater dietary fiber intake is significantly associated with lower risk of first stroke. Overall, findings support dietary recommendations to increase intake of total dietary fiber. However, a paucity of data on fiber from different foods precludes conclusions regarding the association between fiber type and stroke. There is a need for future studies to focus on fiber type and to examine risk for ischemic and hemorrhagic strokes separately.


Nutritional support and functional capacity in chronic obstructive pulmonary disease: a systematic review and meta-analysisRespirology. 2013 May;18(4):616-29. By Collins PF, Elia M, Stratton RJ. From  Institute of Human Nutrition, Southampton General Hospital, University of Southampton, Southampton, UK.

Currently, there is confusion about the value of using nutritional support to treat malnutrition and improve functional outcomes in chronic obstructive pulmonary disease (COPD). This systematic review and meta-analysis of randomized, controlled trials (RCT) aimed to clarify the effectiveness of nutritional support in improving functional outcomes in COPD. A systematic review identified 12 RCT (n = 448) in stable COPD patients investigating the effects of nutritional support (dietary advice (1 RCT), oral nutritional supplements (10 RCT), enteral tube feeding (1 RCT)) versus control on functional outcomes. Meta-analysis of the changes induced by intervention found that while respiratory function (forced expiratory volume in 1 s, lung capacity, blood gases) was unresponsive to nutritional support, both inspiratory and expiratory muscle strength (maximal inspiratory mouth pressure +3.86 standard error (SE) 1.89 cm H2 O, P = 0.041; maximal expiratory mouth pressure +11.85 SE 5.54 cm H2 O, P = 0.032) and handgrip strength (+1.35 SE 0.69 kg, P = 0.05) were significantly improved and associated with weight gains of ≥2 kg. Nutritional support produced significant improvements in quality of life in some trials, although meta-analysis was not possible. It also led to improved exercise performance and enhancement of exercise rehabilitation programmes. This systematic review and meta-analysis demonstrates that nutritional support in COPD results in significant improvements in a number of clinically relevant functional outcomes, complementing a previous review showing improvements innutritional intake and weight.

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Systematic review and meta-analysis of different dietary approaches to the management of type 2 diabetes.  Am J Clin Nutr. 2013 Mar;97(3):505-16.  By Ajala O, English P, Pinkney J. from Dept of Diabetes and Endocrinology, Peninsula College of Medicine and Dentistry, Plymouth, UK.

BACKGROUND: There is evidence that reducing blood glucose concentrations, inducing weight loss, and improving the lipid profile reduces cardiovascular risk in people with type 2 diabetes. OBJECTIVE: We assessed the effect of various diets on glycemic control, lipids, and weight loss.  DESIGN: We conducted searches of PubMed, Embase, and Google Scholar to August 2011. We included randomized controlled trials (RCTs) with interventions that lasted ≥6 mo that compared low-carbohydrate, vegetarian, vegan, low-glycemic index (GI), high-fiber, Mediterranean, and high-protein diets with control diets including low-fat, high-GI, American Diabetes Association, European Association for the Study of Diabetes, and low-protein diets.  RESULTS:  A total of 20 RCTs were included (n = 3073 included in final analyses across 3460 randomly assigned individuals). The low-carbohydrate, low-GI, Mediterranean, and high-protein diets all led to a greater improvement in glycemic control [glycated hemoglobin reductions of -0.12% (P = 0.04), -0.14% (P = 0.008), -0.47% (P < 0.00001), and -0.28% (P < 0.00001), respectively] compared with their respective control diets, with the largest effect size seen in the Mediterranean diet. Low-carbohydrate and Mediterranean diets led to greater weight loss [-0.69 kg (P = 0.21) and -1.84 kg (P < 0.00001), respectively], with an increase in HDL seen in all diets except the high-protein diet.   CONCLUSION:  Low-carbohydrate, low-GI, Mediterranean, and high-protein diets are effective in improving various markers of cardiovascular risk in people with diabetes and should be considered in the overall strategy of diabetes management.


Fat Intake After Diagnosis and Risk of Lethal Prostate Cancer and All-Cause MortalityJAMA Intern Med. 2013 Jun 10:1-8.  By Richman EL, Kenfield SA, Chavarro JE, et al.

Nearly 2.5 million men currently live with prostate cancer in the United States, yet little is known about the association between diet after diagnosis and prostate cancer progression and overall mortality.   OBJECTIVE To examine postdiagnostic fat intake in relation to lethal prostate cancer and all-cause mortality.  DESIGN AND PARTICIPANTS: Prospective study of 4577 men with nonmetastatic prostate cancer in the Health Professionals Follow-up Study (1986-2010).  EXPOSURES: Post-diagnostic intake of saturated, monounsaturated, polyunsaturated, trans, animal, and vegetable fat.  MAIN OUTCOMES:  Lethal prostate cancer (distant metastases or prostate cancer-specific death) and all-cause mortality.   RESULTS: We observed 315 events of lethal prostate cancer and 1064 deaths (median follow-up, 8.4 years). Crude rates per 1000 person-years for lethal prostate cancer were as follows (highest vs lowest quintile of fat intake): 7.6 vs 7.3 for saturated, 6.4 vs 7.2 for monounsaturated, 5.8 vs 8.2 for polyunsaturated, 8.7 vs 6.1 for trans, 8.3 vs 5.7 for animal, and 4.7 vs 8.7 for vegetable fat. For all-cause mortality, the rates were 28.4 vs 21.4 for saturated, 20.0 vs 23.7 for monounsaturated, 17.1 vs 29.4 for polyunsaturated, 32.4 vs 17.1 for trans, 32.0 vs 17.2 for animal, and 15.4 vs 32.7 for vegetable fat. Replacing 10% of energy intake from carbohydrate with vegetable fat was associated with a lower risk of lethal prostate cancer (hazard ratio [HR], 0.71; 95% CI, 0.51-0.98; P = .04) and all-cause mortality (HR, 0.74; 95% CI, 0.61-0.88; P = .001). No other fats were associated with lethal prostate cancer. Saturated and trans fats after diagnosis (replacing 5% and 1% of energy from carbohydrate, respectively) were associated with higher all-cause mortality (HR, 1.30 [95% CI, 1.05-1.60; P = .02] and 1.25 [95% CI, 1.05-1.49; P = .01], respectively).  CONCLUSIONSAmong men with nonmetastatic prostate cancer, replacing carbohydrates and animal fat with vegetable fat may reduce the risk of all-cause mortality. The potential benefit of vegetable fat for prostate cancer-specific outcomes merits further research.


Nutritional interventions for reducing morbidity and mortality in people with HIV.  Cochrane Database Syst Rev. 2013 Feb 28;2:CD004536. By Grobler L, Siegfried N, Visser ME, et al. from Centre for Evidence-based Health Care, Stellenbosch University, Cape Town, South Africa. .

BACKGROUND:  Adequate nutrition is important for optimal immune and metabolic function.  Dietary support may, therefore, improve clinical outcomes in HIV-infected individuals by reducing the incidence of HIV-associated complications and attenuating progression of HIV disease, improving quality of life and ultimately reducing disease-related mortality.  OBJECTIVES: To evaluate the effectiveness of various macronutrient interventions, given orally, in reducing morbidity and mortality in adults and children living with HIV infection.  METHODS: We searched CENTRAL (up to August 2011), MEDLINE (1966 to August 2011), EMBASE (1988 to August 2011), LILACS (up to February 2012), and Gateway (March 2006-February 2010). We also scanned reference lists of articles and contacted authors of relevant studies and other researchers.  SELECTION CRITERIA:  Randomised controlled trials evaluating the effectiveness of macronutrient interventions compared with no nutritionalsupplements or placebo in the management of adults and children infected with HIV. DATA COLLECTION & ANALYSIS: Three reviewers independently applied study selection criteria, assessed study quality, and extracted data. Effects were assessed using mean difference and 95% confidence intervals. Homogenous studies were combined wherever it was clinically meaningful to do so and a meta-analysis using the random effects model was conducted. MAIN RESULTS:  Fourteen trials (including 1725 HIV positive adults and 271 HIV positive children), were included in this review. Neither supplementary food nor daily supplement of Spirulina significantly altered the risk of death compared with no supplement or placebo in malnourished, ART naive adult participants in the two studies which reported on this outcome. A nutritional supplement enhanced with protein did not significantly alter the risk of death compared to standard nutritional care in children with prolonged diarrhoea. Supplementation with macronutrient formulas given to provide protein and/or energy and fortified with micronutrients, in conjunction with nutrition counselling, significantly improved energy intake (3 trials; n=131; MD 393.57 kcal/day; 95% CI: 224.66 to 562.47;p<0.00001) and protein intake (2 trials; n=81; MD 23.5 g/day; 95% CI: 12.68, 34.01; p<0.00001) compared with no nutritional supplementation or nutrition counselling alone in adult participants with weight loss. In general supplementation with specific macronutrients such as amino acids, whey protein concentration or Spirulina did not significantly alter clinical, anthropometric or immunological outcomes compared with placebo in HIV-infected adults and children.  CONCLUSIONS:  Given the current evidence base, which is limited to fourteen relatively small trials all evaluating different macronutrient supplements in different populations at different stages of HIV infection and with varying treatment status, no firm conclusions can be drawn about the effects of macronutrient supplementation on morbidity and mortality in people living with HIV. It is, however, promising to see more studies being conducted in low-income countries, and particularly in children, where macronutrient supplementation both pre-antiretroviral treatment and in conjunction with antiretroviral treatment might prove to be beneficial.


Threshold for Improvement in Insulin Sensitivity with Adolescent Weight LossJournal  Pediatr.  2013 May 22. pii: S0022-3476(13)00420-4. By Abrams P, Levitt Katz LE, Moore RH, et al. from Division of Endocrinology and Diabetes, Department of Pediatrics, The Children’s Hospital of Philadelphia, Philadelphia, PA. Email:

OBJECTIVES:  To assess the association of weight loss and insulin sensitivity, glucose tolerance, and metabolic syndrome (MS) in obese adolescents following weight loss treatment, and to determine the threshold amount of weight loss required to observe improvements in these measures.  STUDY DESIGN:  A randomized, controlled behavioral weight loss trial was conducted with 113 obese adolescents. Changes in fasting insulin, homeostasis model assessment of insulin resistance, whole body insulin sensitivity index (WBISI), body mass index (BMI), and MS criteria were assessed at baseline and at month 4.  RESULTS: There was significant improvement in all measures of insulin sensitivity at month 4. Mean fasting insulin dropped from 22.3 to 16.6 μU/mL (P < .0001). Homeostasis model assessment of insulin resistance decreased significantly from 4.9 to 3.7 (P = .001) and WBISI increased significantly from 2.87 to 3.98 (P < .0001). An 8% reduction in BMI led to a significant improvement in WBISI (P = .03) and was the optimal threshold. Fewer individuals met criteria for MS after weight loss (P = .0038), although there were no significant changes in the individual features of the syndrome.  CONCLUSIONS:  In this trial, weight loss at month 4 was associated with improved insulin sensitivity in obese adolescents. An approximate decrease in BMI of 8% was the threshold level at which insulin sensitivity improved. As more weight loss programs are designed for obese adolescents, it will be important to have reasonable weight loss goals that will yield improvements in metabolic and cardiovascular disease risk factors.


Early parenteral nutrition and growth outcomes in preterm infants: a systematic review and meta-analysis.  Am J Clin Nutr. 2013 Apr;97(4):816-26. By Moyses HE, Johnson MJ, Leaf AA, Cornelius VR. From National Institute for Health Research Foundation Trust, Southampton, UK.

BACKGROUND:  The achievement of adequate nutritional intakes in preterm infants is challenging and may explain the poor growth often seen in this group. The use of early parenteral nutrition (PN) is one potential strategy to address this problem, although the benefits and harms are unknown.  OBJECTIVE: We determined whether earlier administration of PN benefits growth outcomes in preterm infants.  DESIGN:  We conducted a systematic review of randomized controlled trials (RCTs) and observational studies. RESULTS:  Eight RCTs and 13 observational studies met the inclusion criteria (n = 553 and 1796 infants). The meta-analysis was limited by disparate growth-outcome measures. An assessment of bias was difficult because of inadequate reporting. Results are given as mean differences (95% CIs). Early PN reduced the time to regain birth weight by 2.2 d (1.1, 3.2 d) for RCTs and 3.2 d (2.0, 4.4 d) in observational studies. The maximum percentage weight loss with early PN was lower by 3.1 percentage points (1.7, 4.5 percentage points) for RCTs and by 3.5 percentage points (2.6, 4.3 percentage points) for observational studies. Early PN improved weight at discharge or 36 wk postmenstrual age by 14.9 g (5.3, 24.5 g) (observational studies only), but no benefit was shown for length or head circumference. There was no evidence that early PN significantly affects risk of mortality, necrotizing enterocolitis, sepsis, chronic lung disease, intraventricular hemorrhage, or cholestasis.  CONCLUSIONS:  The results of this review, although subject to some limitations, show that early PN provides a benefit for some short-term growth outcomes. No evidence that early PN increases morbidity or mortality was found. Neonatal research would benefit from the development of a set of core growth outcome measures.


Nonpharmacological interventions for ADHD: systematic review and meta-analyses of randomized controlled trials of dietary and psychological treatmentsAm J Psychiatry. 2013 Mar 1;170(3):275-89.  By Sonuga-Barke EJ, Brandeis D, Cortese S, et al and European ADHD Guidelines Group. From Dept of Psychology, University of Southampton, UK.

OBJECTIVE:  Nonpharmacological treatments are available for attention deficit hyperactivity disorder (ADHD), although their efficacy remains uncertain. The authors undertook meta-analyses of the efficacy of dietary (restricted elimination diets, artificial food color exclusions, and free fatty acid supplementation) and psychological (cognitive training, neurofeedback, and behavioral interventions) ADHD treatments.  METHOD: Using a common systematic search and a rigorous coding and data extraction strategy across domains, the authors searched electronic databases to identify published randomized controlled trials that involved individuals who were diagnosed with ADHD (or who met a validated cutoff on a recognized rating scale) and that included an ADHD outcome.  RESULTS: Fifty-four of the 2,904 nonduplicate screened records were included in the analyses. Two different analyses were performed. When the outcome measure was based on ADHD assessments by raters closest to the therapeutic setting, all dietary (standardized mean differences=0.21-0.48) and psychological (standardized mean differences=0.40-0.64) treatments produced statistically significant effects. However, when the best probably blinded assessment was employed, effects remained significant for free fatty acid supplementation (standardized mean difference=0.16) and artificial food color exclusion (standardized mean difference=0.42) but were substantially attenuated to nonsignificant levels for other treatments.  CONCLUSIONS:  Free fatty acid supplementation produced small but significant reductions in ADHD symptoms even with probably blinded assessments, although the clinical significance of these effects remains to be determined. Artificial food color exclusion produced larger effects but often in individuals selected for food sensitivities. Better evidence for efficacy from blinded assessments is required for behavioral interventions, neurofeedback, cognitive training, and restricted elimination diets before they can be supported as treatments for core ADHD symptoms.


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