Common Study Designs of Nutrition Clinical Trials: Review of the Basic Elements and the Pros and Cons

Introduction: Nutrition Clinical Trials (NCTs) are pivotal in establishing causal links between nutritional interventions and chronic diseases. This review comprehensively examines prevalent clinical trial designs, emphasizing their strengths and limitations. The goal is to provide insights into the selection and optimization of these designs for dietary intervention studies. Methods: Various study designs in NCTs are explored, including quasi-experimental designs, double-blind randomized placebo-controlled trials for nutrient/functional foods supplementation, community-based lifestyle interventions, pragmatic nutrition interventions, and field trial projects. The characteristics, advantages, and challenges of each design are discussed. Real examples are presented to illustrate how these designs can be tailored and optimized for dietary intervention studies. Results: Parallel randomized clinical trials are acknowledged as the gold standard, despite requiring substantial sample sizes and having inherent limitations. Cross-over NCTs emerge as valuable for assessing temporary treatment effects while mitigating potential confounders and interpatient variability. However, they may not be suitable for acute diseases and progressive disorders, and attrition rates can be higher. Multi-arm randomized designs offer increased study power with a lower sample size but necessitate more intricate design, analysis, and result reporting. Conclusion: In conclusion, each study design in NCTs comes with its set of strengths and limitations. The selection of an appropriate design should consider determinants and common considerations to provide robust evidence for establishing cause-and-effect associations or assessing the safety and efficacy of food products in nutrition research. This comprehensive understanding aids researchers in making informed choices when planning and conducting nutrition clinical trials

Inorganic nitrate, a natural anti-obesity agent

Evidence for potential effects of inorganic nitrate (NO3) on body weight is limited to inconsistent findings of animal experiments. In this systematic review and meta-analysis, we aimed to quantify the overall effect of inorganic NO3, administered via drinking water, on body weight gain in rats. We searched PubMed, Scopus, and Embase databases, and the reference lists of published papers. Experiments on male rats, reported data on body weight in NO3-treated animals and controls, were included for quality assessment, meta-analyses, subgroup analyses, and meta-regressions. Of 173 initially obtained studies, 11 were eligible to be included in the analyses, which covered the years 2004 to 2019 and included a total of 43 intervention (n=395) and 43 control (n=395) arms. Overall, the final body weights were significantly lower in the NO3-supplemented groups compared to controls (WMD= –16.8 g, 95 % CI= –27.38, –6.24; P=0.002). Doses of NO3 higher than the median (> 72.94 mg L-1 d-1) and longer NO3 exposure (> 8 weeks) resulted in greater mean differences (WMD= –31.92 g, 95 % CI= –52.90, –10.94 and WMD= –23.16 g, 95 % CI= –35.64, –10.68 g). After exclusion of experiments using high doses of NO3 (> 400 mg L-1 d-1), the overall mean differences in body weights between the groups decreased by approximately 37 % but remained statistically significant (WMD= –10.11 g, 95 % CI= –19.04, –1.19, P=0.026). Mean changes in body weight were affected by age, baseline values in body weight, and the duration of the studies. These preliminary experimental findings strongly support the hypothesis that NO3 can be considered as a natural anti-obesity agent

Comparison of food intake in multiple sclerosis patients and healthy individuals – A hospital-based case-controlled study

ObjectivesNutritional factors affect the incidence, severity of symptoms and progression of multiple sclerosis (MS). However, the role of specific nutritional factors remains largely unknown in MS. We conducted this hospital-based case-controlled study to investigate the association between dietary intake and risk of MS.Methods: This study was conducted on 93 MS patients and 94 age-matched controls. MS was diagnosed based on 2010 McDonald criteria and Brain Magnetic Resonance Imaging. Dietary intake was assessed by using a validated semi-quantitative food frequency questionnaire. Odds ratio and 95% confidence interval of MS was calculated in different food item groups using multiple logistic regression models adjusted for potentially confounding variables and compared between the two groups. Results: There was no significant difference between age (34.62 ±9.68vs. 33.96±8.75) and BMI (23.96 ±4.07 vs. 24.47 ±4.07) of MS and control group respectively. Higher intake of processed meat (OR (95% CI)) = (2.07(1.18-3.63) and non-processed meat (1.38(1.13-1.68)) was found in the MS group compared with the control. Conclusion: Higher intake of processed meat and non-processed meat is associated with increased risk of MS. Further studies on the probable role of these nutritional factors in the pathogenesis of MS are suggested.

The Effects of Inorganic Nitrate on Carbohydrate and Lipid Metabolism in Type 2 Diabetes: The Protocol of a Randomized Placebo-Controlled Clinical Trial

Background and Aim: Decreased bioavailability of nitric oxide (NO) in type 2 diabetes contributes to disrupted pathways of glucose/insulin homeostasis and progression of long-term complications. Due to its ability to convert to NO, inorganic nitrate (NO3) has been recently highlighted as a potential therapeutic agent in type 2 diabetes. Materials and Methods: This research entails a double-blind, randomized, placebo-controlled, phase II clinical trial that will be conducted on 62 type 2 diabetic patients. The patients will be randomized to receive a 6-month daily dose of NO3-rich beetroot powder (5 g/d, contains ~250 mg NO3) or placebo (5 g/d, contains <25 mg NO3). The primary outcome is glycosylated hemoglobin A1c (HbA1c). The study is powered to detect a 0.75% reduction in HbA1c levels between the groups. Fasting serum glucose, serum insulin, lipid parameters, liver enzymes, thyroid function tests and complete blood count will be measured as secondary outcomes. The measurements will be done at baseline, and will be repeated in the fourth, twelfth and twenty-fourth weeks. Protocol of the study was approved by the ethical committee of the Research Institute for Endocrine Sciences of Shahid Beheshti University of Medical Sciences (IR.SBMU.ENDOCRINE.REC.1395.322). The trial was registered in the Iranian Registry of Clinical Trials with the following identification: IRCT20180409039246N1

Comparing the impact of educational behavioral interventions on maternal sleep between face-to-face and electronic training groups, during the postpartum period

INTRODUCTION: The postpartum period is a transition to a critical stage. Moreover, the rapid changes experienced after delivery, expose the mother to unpleasant experiences such as changes in sleep patterns. Trying to an appropriate training method is necessary. This study aims to conduct a comparative study between the impact of face-to-face training and e-training on maternal sleep during the postpartum period. MATERIALS AND METHODS: The present study was empirically conducted on 110 postpartum mothers who visited the selected healthcare centers of Isfahan in 2015. Mothers randomly divided into three groups (face to face, electronic and control). Data collection tools included demographic and fertility questionnaire and Pittsburgh Sleep Quality Index. Intervention groups were received training such as mothers with necessary instructions regarding the health approaches, relaxation techniques, sleeping place, and energy-saving techniques. Mothers' quality of sleep was measured and compared before training (until the 10th day after childbirth) then in the second and third cares (from the 10th to 30th day after childbirth) in all three groups. Data were analyzed using descriptive statistics and ANOVA and analyze variance with repeated measures in SPSS (SPSS Inc., Chicago, IL, USA,) version 17. RESULTS: The results showed there was a significant difference among the sleep quality scores in the three times in the e-training (P < 0.001) and face-to-face groups (P < 0.001) and in the control group (P = 0.01), but the improvement in the sleep quality score has been higher in the two groups; e-training and face-to-face, than in the control group. In addition, the mothers' mean sleep quality score was different between the control group and face-to-face group as well as between the control group and e-training group. While, no statistically significant difference was found between the e-training group and face-to-face group. CONCLUSION: Training through both methods; face-to-face and electronic, had the same impact on maternal sleep quality during the postpartum period. Therefore, despite the belief that in-person trainings are more effective, the findings of this research showed the effectiveness of electronic methods too, and determined that this method, has the same effectiveness as the face-to-face method has

Comparing the impact of educational behavioral interventions on maternal sleep between face-to-face and electronic training groups, during the postpartum period

INTRODUCTION: The postpartum period is a transition to a critical stage. Moreover, the rapid changes experienced after delivery, expose the mother to unpleasant experiences such as changes in sleep patterns. Trying to an appropriate training method is necessary. This study aims to conduct a comparative study between the impact of face-to-face training and e-training on maternal sleep during the postpartum period. MATERIALS AND METHODS: The present study was empirically conducted on 110 postpartum mothers who visited the selected healthcare centers of Isfahan in 2015. Mothers randomly divided into three groups (face to face, electronic and control). Data collection tools included demographic and fertility questionnaire and Pittsburgh Sleep Quality Index. Intervention groups were received training such as mothers with necessary instructions regarding the health approaches, relaxation techniques, sleeping place, and energy-saving techniques. Mothers' quality of sleep was measured and compared before training (until the 10th day after childbirth) then in the second and third cares (from the 10th to 30th day after childbirth) in all three groups. Data were analyzed using descriptive statistics and ANOVA and analyze variance with repeated measures in SPSS (SPSS Inc., Chicago, IL, USA,) version 17. RESULTS: The results showed there was a significant difference among the sleep quality scores in the three times in the e-training (P < 0.001) and face-to-face groups (P < 0.001) and in the control group (P = 0.01), but the improvement in the sleep quality score has been higher in the two groups; e-training and face-to-face, than in the control group. In addition, the mothers' mean sleep quality score was different between the control group and face-to-face group as well as between the control group and e-training group. While, no statistically significant difference was found between the e-training group and face-to-face group. CONCLUSION: Training through both methods; face-to-face and electronic, had the same impact on maternal sleep quality during the postpartum period. Therefore, despite the belief that in-person trainings are more effective, the findings of this research showed the effectiveness of electronic methods too, and determined that this method, has the same effectiveness as the face-to-face method has

The Effect of Consumption of Unhealthy Snacks on Diet and the Risk of Metabolic Syndrome in Adults: Tehran Lipid and Glucose Study, Iran

Abstract: Background & Aims: Unhealthy snacks contain high amounts of calories, simple sugars, fat, cholesterol, salt, additives, and conservatives. Increased consumption of these unhealthy snacks is one of the underlying factors for the prevalence of overweight, obesity, and metabolic disorders. In this study, we investigated the effects of unhealthy snacks on diet and the risk of metabolic syndrome after 3-years of follow-up in Tehranian adults. Methods: This longitudinal study was conducted within the framework of the Tehran Lipid and Glucose Study, between 2006-2008 and 2009-2011, on men and women in Tehran, Iran. Dietary intakes of participants were measured using a validated semi-quantitative food frequency questionnaire at baseline. Biochemical and anthropometric measurements were assessed at baseline and 3 years later. Multiple logistic regression models with adjustment for confounding factors were used to estimate the occurrence of metabolic syndrome (MetS) in each quartile of unhealthy snacks. Results: The mean age of participants was 37.8 ± 12.3 years, and the mean of body mass index was 26.0 ± 4.5 kg/m2. Moreover, 39% of the participants were male. Daily energy intake, dietary energy density, and total fat and sodium intake were higher in the fourth quartile of unhealthy snacks consumption. There was a significant decreasing trend in dietary intake of carbohydrate, calcium, zinc, selenium, and fiber parallel to increase in consumption of energy-dense snacks. Participants who were in the highest quartile of energy intake from unhealthy snacks consumed less whole grains, vegetables, and dairy products. After adjustment for potential confounders, the risk of metabolic syndrome had a significant positive association with salty snacks consumption, and a non-significant positive association with consumption of candies, chocolate, and soft drinks. Conclusion: Increased daily energy intake from unhealthy snacks could be a risk factor for the occurrence of metabolic syndrome. Keywords: Metabolic syndrome, Unhealthy snacks, Abdominal obesity, Insulin resistance, Dyslipidemia, Hypertensio

Lipid Accumulation Product Is Associated with Insulin Resistance, Lipid Peroxidation, and Systemic Inflammation in Type 2 Diabetic Patients

BackgroundLipid accumulation product (LAP) is a novel biomarker of central lipid accumulation related to risk of diabetes and cardiovascular disease. In this study, we assessed the association of LAP with glucose homeostasis, lipid and lipid peroxidation, and subclinical systemic inflammation in diabetic patients.MethodsThirty-nine male and 47 female type 2 diabetic patients were assessed for anthropometrics and biochemical measurements. LAP was calculated as [waist circumference (cm)-65]×[triglycerides (mmol/L)] in men, and [waist circumference (cm)-58]×[triglycerides (mmol/L)] in women. Associations of LAP with fasting glucose, insulin, insulin resistance index, lipid and lipoprotein levels, malondialdehyde, and high-sensitive C-reactive protein (hs-CRP) were assessed.ResultsMean age and LAP index were 53.6±9.6 and 51.9±31.2 years, respectively. After adjustments for age, sex and body mass index status, a significant positive correlation was observed between LAP index and fasting glucose (r=0.39, P<0.001), and homeostasis model assessment of insulin resistance (r=0.31, P<0.05). After additional adjustment for fasting glucose levels, antidiabetic and antilipidemic drugs, the LAP index was also correlated to total cholesterol (r=0.45, P<0.001), high density lipoprotein cholesterol (HDL-C) levels (r=-0.29, P<0.05), triglycerides to HDL-C ratio (r=0.89, P<0.001), malondialdehyde (r=0.65, P<0.001), and hs-CRP levels (r=0.27, P<0.05).ConclusionHigher central lipid accumulation in diabetic patients was related to higher insulin resistance, oxidative stress and systemic inflammation

Usual intake of dairy products and the chance of pre-diabetes regression to normal glycemia or progression to type 2 diabetes: a 9-year follow-up

Abstract Background We assessed the possible effect of usual dairy consumption on pre-diabetes (Pre-DM) remission or progression to type 2 diabetes (T2D). Methods Pre-DM adults (n = 334, mean age of 49.4 years, and 51.5% men) were assessed for dairy intakes (2006–2008) and followed up to 9 years for incidence of T2D or normal glycemia (NG). All biochemical measurements were done at baseline and all subsequent examinations with 3-y follow-up intervals. Multinomial regression models with adjustment of confounding variables were used to estimate odds ratios (OR) and 95% confidence intervals (CIs) of incident T2D and NG for each serving/d dairy consumption. Results The odds of NG was significantly elevated by 69% (OR = 1.69, 95% CI = 1.00–2.86, P = 0.05) per 200 g/d increased high-fat dairy intake, while the amount of total dairy or low-fat dairy was not related to the outcomes. Higher intakes of yogurt were more likely to be associated with an increased odds of NG (OR = 1.82, 95% CI = 1.20–2.74, P = 0.01). Usual intakes of milk, cheese, or cream-butter were not associated to Pre-DM remission or progression to T2D. Conclusion Regular dairy consumption may increase the chance of Pre-DM regression to NG