{"paper_id":"2bb1a5f1-79c5-404a-a4e1-f480ec9edaf3","body_text":"Effects of bread fortification with pomegranate peel powder on inflammation biomarkers, oxidative stress, and mood status in patients with type 2 diabetes: A randomized placebo-controlled trial | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Effects of bread fortification with pomegranate peel powder on inflammation biomarkers, oxidative stress, and mood status in patients with type 2 diabetes: A randomized placebo-controlled trial Maryam Zare, Mohammad Javad Tarrahi, Omid Sadeghi, Mozhgan Karimifar, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5254735/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background : To assess the effects of bread fortified with pomegranate peel powder (PPP) on inflammation, oxidative stress, and mood indices in patients with type 2 diabetes mellitus (T2DM). Methods : In total, 90 T2DM patients were randomized to receive either bread fortified with 3.5% pomegranate peel powder (PPP) (n=45) or PPP-free bread for 12 weeks. Dietary intake throughout the trial was assessed via food records. Laboratory parameters, including total antioxidant capacity (TAC), malondialdehyde (MDA), high-sensitivity C-reactive protein (hs-CRP), and psychological disorders, including depression, anxiety, and stress, were assessed at the beginning and end of the study. Results: 77 diabetic patients completed the trial (PPP group = 39 and control group = 38). Based on the compliance assessment, adherence to the interventions was high in the trial. We detected significant reductions in hs-CRP levels (intervention group: change = -0.56 ± 1.29, P=0.01; control group: change = -0.81± 1.16, p<0.001) and depression scores (intervention group: change= -1.33 ± 3.66, P=0.04; control group): -1.44 ± 2.83, p=0.01). There was no significant difference between the groups. After adjusting for confounding factors, the significant effect within the group disappeared. Other variables, including MDA, TAC, anxiety, and stress, did not significantly change in the PPP-fortified bread group. Conclusion : While intake of PPP-fortified bread for 12 weeks did not significantly affect oxidative stress, hs-CRP, or mental health in T2DM patients, some positive outcomes related to inflammatory and mood states should be explored. Trial registration Iranian Registry of Clinical Trials : The trial was registered in the Iranian Registry of Clinical Trials (available at www.irct.ir , with ID: IRCT20191209045672N1) on 21/09/2020. Pomegranate Bread Diabetes mellitus Inflammation Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction The prevalence of type 2 diabetes mellitus (T2DM) is increasing at an alarming rate [ 1 ]. T2DM is prevalent among 9.3% of adults[ 2 ]. In Iran, it is estimated that 9.2 million people are affected[ 2 ]. Patients with T2DM usually experience several complications, such as foot ulcers, dental disease, and reduced resistance to infections, which negatively affect patients’ quality of life[ 3 ]. Additionally, these patients are at increased risk of several chronic diseases, including cardiovascular disease (CVD), nephropathy, retinopathy, and liver diseases[ 4 ]. In addition, T2DM imposes a high economic burden on the healthcare system [ 5 ]. Therefore, finding an appropriate strategy for the management of this disease is urgently needed. Previous studies have proposed several pharmacological and nonpharmacological interventions for the management of T2DM [ 6 ]. Owing to several complications of pharmacological methods, nonpharmacological therapies such as dietary interventions, supplementation with some nutrients, and herbal medicine have received great attention [ 7 ]. Recently, intervention with polyphenol-rich supplements or food has been shown to have a beneficial effect on the clinical outcomes of diabetic patients (e.g., by modulating oxidative stress and anti-inflammatory responses) [ 8 ]. Among polyphenol-rich foods, pomegranate and its peel have received much attention. In a clinical trial, intervention with pomegranate peel extract significantly reduced hs-CRP in diabetic patients [ 9 ]. Despite the presented evidence, it is not clear whether the addition of pomegranate peel to foods can affect the outcomes of diabetic patients. Bread is a good candidate for fortification because it comprises the majority of individuals around the world [ 10 ], as does the Iranian diet, in which more than 60% of the energy is from carbohydrates, particularly from different types of bread [ 11 ]. Notably, most types of bread in Iranian food culture are prepared with refined grains. Therefore, changing the composition of bread may affect health outcomes, particularly for diabetic patients. Given the current evidence of the possible beneficial effect of pomegranate peel on the outcomes of diabetic patients, we decided to fortify bread with this functional food. Therefore, the present clinical trial aimed to assess the effects of bread fortified with pomegranate peel powder (PPP) on hs-CRP, oxidative stress, and mental health in patients with T2DM. Materials and methods Study population This investigation was a randomized, blinded, parallel clinical trial. Details on the participants, study design, and data collection were published previously[ 12 ]. Participants were diabetic patients referred to the outpatient clinic of the Endocrine and Metabolism Research Center (Isfahan University Medical Sciences, Isfahan, Iran) and health centers of Isfahan city from May 2021 to January 2023. Considering a type 1 error of 5%, a type 2 error of 20%, and a study power of 80%, the required sample size was calculated via the relevant formula. Accordingly, we included 45 patients with T2DM in each group. The study inclusion criteria were as follows: 1) patients who were diagnosed with T2DM within the last 5 years, 2) patients aged 40–60 years, 3) those who had HbA1c levels between 5.7% and 8.0% over the past 3 months, and 4) patients who had a body mass index (BMI) ≤ 30 kg/m 2 . Patients with chronic kidney or liver diseases (cirrhosis and hepatitis), patients who were pregnant or lactating, those taking hormone replacement therapy (insulin or others), those who adhered to a special diet and patients who received antioxidant supplements during the last 3 months were excluded. During the trial, patients who changed the dosages and types of medications, those who were unwilling to continue the trial, and those who reported complications due to possible side effects were excluded as well. This study was conducted in accordance with the Helsinki Declaration, and written informed consent was obtained from all participants. The protocol of the present trial was approved by the Ethical Committee at the Isfahan University of Medical Sciences (approval no. IR. MUI.RESEARCH.REC.1399.087) and registered at www.IRCT.ir (ID: IRCT20191209045672N1). Furthermore, our study was reported on the basis of the Consolidated Standards of Reporting Trials (CONSORT) statement guidelines [ 13 ]. Study design Among the 11,165 evaluated cases, only 520 diabetic patients met the inclusion criteria. One hundred and twelve patients agreed to participate in the study. During the run-in period, we excluded 22 patients because they were unwilling to follow the trial. Distance areas from their homes, COVID-19 strikes, and a lack of blood sugar control were the main reasons for their exclusion. At the first visit, we measured the fasting blood glucose of the participants with a glucometer, and those whose blood glucose was less than 150 mg/dL were included in the study. After the ruin period, 10 participants were excluded because their HbA1c (glycated hemoglobin) level was > 8%. Finally, the remaining 90 patients were randomly allocated into two equal groups via computer-generated random numbers. The patients were allocated to either PPP-fortified bread or PPP-free bread groups. Both types of bread were identical in terms of shape, size, and packaging. All the breads had the same appearance, so it was impossible to distinguish each one. During the run-in period, all patients received a control bread. During the run-in period, two sessions were held for all patients. In each session, adherence to bread intake and possible complications related to bread intake were assessed to select patients with high compliance. After the run-in period, all patients (n = 90) were followed for 12 weeks. The investigator and patients were in touch through text messaging and phone calls during the trial. Additionally, they were asked not to change their usual dietary intake or physical activity throughout the study. At baseline and at the end of the trial, a fasting blood sample and mental health data were collected from each participant. We used dietary records to evaluate adherence to the intervention. Additionally, compliance with bread intake was monitored through routine visits and phone interviews once a week. However, there were no biochemical indicators for the intake of bread. Physical activity was assessed via two 3-day physical activity records at baseline and at the end of the trial. In addition to physical activity, usual dietary intake was assessed via two 3-day food records before and after the intervention. A trained nutritionist described how to fill out the food and physical activity records. The records were checked by a nutritionist. To report the correct amount of food intake, a food album was provided to them. After the dietary records were collected, the serving sizes were converted to grams per day. The average intakes of energy and nutrients for each 3-day record were subsequently calculated via a customized version of Nutritionist IV software (First Data Bank; Hearst Corp, San Bruno, CA, USA). Interventions Pomegranate peel powder : Pomegranate fruits were purchased from Fars Province, Iran. The pomegranate peels were separated and then dried and ground into powder. The PPP mixture was stored at − 20°C until the bread was prepared. For the preparation of PPP-rich bread, 3.5 grams of PPP per 100 grams was added to the wheat flour. This dosage was safe and was selected on the basis of previous studies [ 14 ]. Other constituents that are used for bread preparation include sourdough, rye flour, salt, sugar, yeast, and water. The composition of each 100-gr bread was 63 gr plain flour, 14 gr rye flour, 14 gr whole wheat flour, 2 gr gluten, 1.4 gr yeast, 0.14 gr brown sugar, 0.1 gr improver, 0.8 gr salt, 1.4 gr sourdough. The only difference between the pomegranate bread and the control bread was the addition of PPP. Simin Bread Company, Isfahan, Iran produced both breads. MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) test The MTT colorimetric measure of pure PPP against fibroblast L929 cells was conducted according to the Badano JA method [ 15 ]. Briefly, 100 µL of cell suspension in RPMI-1640 medium (1 × 10 4 cells/well) was seeded into each well of a 96-well microplate and then incubated for 24 h (37°C and humidified 5% CO 2 air). After that, the old medium was removed, and 100 µL of different concentrations of PPP were added to each well and incubated for another 24, 48, or 72 h under similar conditions. Consequently, 10 µL of MTT solution (5 mg/mL PBS) was added to each well of the plates in the dark and incubated at 37°C for 2–3 h. To dissolve the formed formazan crystals, the old media containing MTT was removed, and DMSO (100 µL) was gently added to each well. The optical density of each well was measured with an ELISA plate reader (Startfix-2100, Awareness, USA) at 570 nm. DMSO (1%) and doxorubicin were used as negative and positive controls, respectively. The concentrations that inhibited half of the cell population (IC50) were obtained by modeling the percentage of cytotoxicity versus the concentration of PPP. The assay was performed in triplicate, and the results are reported as the means ± standard deviations (SDs). The cell viability (%) was determined according to Eq. ( 2 ). $$\\:\\text{%}\\text{C}\\text{e}\\text{l}\\text{l}\\:\\text{v}\\text{i}\\text{a}\\text{b}\\text{i}\\text{l}\\text{i}\\text{t}\\text{y}=\\:\\:\\frac{\\text{A}\\text{b}\\text{s}\\text{o}\\text{r}\\text{b}\\text{a}\\text{n}\\text{c}\\text{e}\\:\\text{o}\\text{f}\\:\\text{t}\\text{r}\\text{e}\\text{a}\\text{t}\\text{e}\\text{d}\\:\\text{c}\\text{e}\\text{l}\\text{l}\\text{s}-\\:\\text{b}\\text{a}\\text{c}\\text{k}\\text{g}\\text{r}\\text{o}\\text{u}\\text{n}\\text{d}\\:\\text{a}\\text{b}\\text{s}\\text{o}\\text{r}\\text{b}\\text{a}\\text{n}\\text{c}\\text{e}\\left(\\text{b}\\right)\\:}{\\text{A}\\text{b}\\text{s}\\text{o}\\text{r}\\text{b}\\text{a}\\text{n}\\text{c}\\text{e}\\:\\text{o}\\text{f}\\:\\text{u}\\text{n}\\text{t}\\text{r}\\text{e}\\text{a}\\text{t}\\text{e}\\text{d}\\:\\text{c}\\text{e}\\text{l}\\text{l}\\text{s}\\left(\\text{c}\\right)-\\:\\text{b}\\text{a}\\text{c}\\text{k}\\text{g}\\text{r}\\text{o}\\text{u}\\text{n}\\text{d}\\:\\text{a}\\text{b}\\text{s}\\text{o}\\text{r}\\text{b}\\text{a}\\text{n}\\text{c}\\text{e}\\left(\\text{b}\\right)\\:}\\:\\times\\:100$$ 2 where b = blank and c = control. Assessment of variables Data on age, sex, education, medication, supplement use, and history of diseases were collected via an interview-based questionnaire. Anthropometric measurements, including weight and height, were measured via standard techniques. All measurements were performed by M Z in the morning while the participants wore underwear. The height was measured to the nearest 0.1 cm without footwear using a stadiometer (Seca, Hamburg, Germany). Weight was measured to the nearest 0.1 kg with light clothing using a Seca Beam Balance (Seca). BMI was calculated via the following formula: weight (kg)/height (m) 2 (kg/m 2 ). Data on outcome variables, including laboratory parameters and psychological factors, were collected at baseline and 3 months post-intervention. Laboratory measurements Blood samples (10 mL) were taken after 12 hours of overnight fasting at the beginning and end of the intervention period. Then, the serum samples were separated and stored at − 80°C until further analysis. HbA1c, total antioxidant capacity (TAC), malondialdehyde (MDA), and hs-CRP were measured as primary outcomes. A latex immunoturbidimetric assay was used to measure hs-CRP (aptec, Belgium). The cupric-reducing antioxidant capacity method was used to measure the serum TAC via a standard kit (Kiazist Life Sciences, Iran). The assessment of MDA was based on thiobarbituric acid reactive substances (TBARS) measured with a standard kit (Kiazist Life Sciences, Iran). The HbA1c levels were measured with a BT1500 device via turbidimetric immunoassay. All kits had an intra-assay CV˂10% and an interassay CV ˂ 8%. Mental health The Depression, Anxiety, and Stress Scale-21 (DASS-21) was used to measure mood status at baseline and 3 months after the intervention [ 16 ]. The DASS-21 is a self-report questionnaire with three subscales comprising seven questions related to each subscale. Mood status is evaluated as the endpoint. Each question uses a four-point (0–3) Likert scale to identify the severity of depression, anxiety, and stress. Samani et al. reported that the scale had appropriate validity and reliability among Iranian people [ 17 ]. Statistical analysis Statistical analyses were conducted via the per-protocol approach. The per-protocol analysis included data from those individuals who completed the intervention. The normality of continuous variables was assessed by skewness and the Kolmogorov–Smirnov test. All outcome variables in the current study were normally distributed. To assess the differences between the intervention and control groups in terms of continuous variables, an independent samples t test was used. The chi-square test was used to assess the distribution of categorical variables among the 2 groups. To perform a within-subject comparison in each group, we used a paired sample t test. Additionally, changes in outcome variables were compared between the two groups via the independent samples t test. To assess the effects of PPP-fortified bread on inflammation and mental health, we used analysis of covariance (ANCOVA and MANCOVA) with age, sex and weight as covariates. A P value less than 0.05 was considered significant. Statistical analysis was conducted via SPSS version 20 (SPSS Inc., Chicago, IL, USA). Results Cytotoxicity and IC50 The results of the cytotoxicity of the PPP against the fibroblast L929 cell line are presented in Figs. 1-3. As shown in Fig. 1, increasing the concentration of PPP from 125 to 1900 µg/ml increased the cytotoxicity against fibroblasts (Fig. 1). There was no significant difference in the IC50 of PPP after 24 h and 48 h, confirming that the toxicity of PPP was not time dependent until 48 h. However, after 72 h, the cytotoxicity increased, and there was a significant difference (P<0.05) in the cytotoxicity after 24 h and 72 h, which can be attributed to the release of antioxidant compounds from PPP to the medium (Fig. 2). Moreover, the cell viability at different concentrations decreased with increasing concentrations from 125 to 1900 (μg/mL) (Fig. 3). Baseline characteristics and dietary intake Among the 90 T2DM patients (35 men and 55 women) at baseline, seven in the control group and six in the intervention group were excluded because of side effects related to the intervention (n=4), very low compliance (n=4), COVID-19 infection (n=2), unwillingness to continue the study (n=1), or severe disease or surgery (n=2). Finally, 77 subjects (39 in the intervention group and 38 in the control group) completed the intervention period. The flow diagram of this study is shown in Fig. 4 . The baseline characteristics of the T2DM patients in the PPP-fortified bread and control groups are displayed in Table 1 . We found no significant differences between the two groups in terms of demographic variables, past medical history, drug and supplement use, or anthropometric measures. Additionally, there were no significant differences in physical activity between the groups throughout the trial. The results of the 3-day food records revealed no significant differences between the two groups in terms of energy, macronutrient, or micronutrient intake ( Table 2 ). The effects of PPP-fortified bread on the serum concentrations of hs-CRP, TAC, and MDA and mental health are presented in Table 3 . The hs-CRP levels were 2.75 ± 1.56 at baseline and 2.19 ± 2.03 at the end of the trial in the intervention group and 2.45 ± 1.38 at baseline and 1.64 ± 1.19 at the end of the trial in the control group. The hs-CRP levels decreased in the two groups; however, these changes were not significant between the groups. The depression scores were lower (6.66 ± 4.60 at baseline vs. 5.33 ± 4.36 at the end of the trial, P = 0.04) in the intervention group and (5.89 ± 4.32 at baseline vs. 4.44 ± 4.28 at the end of the trial) in the control group. These reductions were significant within the two groups, although these changes were not significant between the groups. The TAC, MDA, stress, and anxiety scores were not significantly different between the two groups. When we controlled for age, sex and weight via ANCOVA and MANCOVA, no differences were detected. Side effects During the study, the only reported adverse event was gastrointestinal complications, including constipation and stomach discomfort (3 patients in the intervention group and 1 patient in the control group). Discussion In the present study, we found that, compared with the control bread, PPP-fortified bread had no significant effect on hs-CRP, oxidative stress, or mental health. To the best of our knowledge, this study assessed the effects of PPP-fortified bread on the clinical outcomes of T2DM patients. Diabetes is one of the major challenging issues in public health [ 18 ]. The levels of inflammatory biomarkers are greater in diabetic patients than in nondiabetic patients. Moreover, as inflammatory biomarkers are connected with endothelial dysfunction, they can increase the risk of cardiovascular diseases (CVDs) among diabetic individuals [ 19 ]. In addition to CVD, patients with T2DM are at increased risk for psychological symptoms such as depression, anxiety, and stress, which may have additional negative effects on their quality of life [ 20 ]. Pharmacological treatments, along with lifestyle modifications (diet and exercise), are suggested to meet glycemic targets in these patients. However, it is not clear whether adding PPP to the formulation of main food items such as bread enhances the health properties of PPP. At the beginning of the study, there was no clinical study on pomegranate peel; however, a similar study with a smaller sample size was conducted after we registered our proposal at the IRCT[ 21 ]. Our study revealed that, after the consumption of PPP-fortified bread for 12 weeks, the hs-CRP marker was ameliorated in T2DM patients. However, compared with that of the control bread, the change was not significant. Previous studies have examined the effects of PPP supplements or extracts on inflammation, but no study has investigated PPP-fortified foods. In a clinical trial, Haghighian et al. reported that PPP extract for 8 weeks and Grabež M et al. for 6 weeks significantly decreased the levels of inflammatory biomarkers in obese women with dyslipidemia and in patients with type 2 diabetes mellitus, respectively [ 9 , 22 ]. Moreover, a significant decrease in hs-CRP concentrations (32%) was observed after 12 weeks of administration of 250 mL/day pomegranate juice in diabetic patients [ 23 ]. There are mechanisms indicating the beneficial effect of the PPP on inflammation. The PPP contains punicalagin and ellagic acid, which have a reducing effect on proinflammatory cytokines [ 24 ]. This effect is mediated by the inhibitory effects of punicalagin and ellagic acid on the mitogen-activated protein kinase (MAPK) pathway, which is involved in inflammatory conditions. Moreover, the PPP is a rich source of polyphenols that induce anti-inflammatory effects through the inhibition of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) and the attenuation of oxidative stress [ 25 ]. In this study, we also did not find any significant changes in the serum MDA or TAC levels. In contrast, Bagheri et al. reported that the consumption of 200 mg/kg pomegranate peel extract in rats decreased the MDA content compared with that in a control group [ 26 ]. Jafari et al. reported that daily consumption of pomegranate peel extract (450 mg/d) for 8 weeks ameliorated MDA levels in hemodialysis patients [ 27 ]. The beneficial effect of 1 g pomegranate peel hydroalcoholic extract on MDA levels in osteoarthritis patients was also reported in another clinical trial [ 28 ]. Haghighian et al. reported that treatment with PPP extracts for 8 weeks increased TAC levels. Another study by Özlem Özpak Akkuş et al. reported that the use of bread with pomegranate peel for 8 weeks did not change the TAC level[ 21 ]. In the present study, although the number of polyphenols in PPP-fortified bread was greater than that in the control bread, it did not affect the MDA or TAC levels. Further studies are needed to illustrate these findings in this regard. The lack of a significant effect of PPP-fortified bread on hs-CRP and oxidative stress might be explained by the interaction of available nutrients in bread with the polyphenols of PPP. Fiber and other nutrients in bread might decrease the absorption of polyphenols. Additionally, Iranians usually consume bread with other foods, such as cheese, legumes, nuts, dairy products, and other grains. These foods contain high amounts of fiber, vitamins, and minerals. Some of these compounds may interact with the effects of bread polyphenols as well as their absorption. Notably, the bread in this study could decrease within groups. Although this reduction was not significant between the groups, it was of clinical importance. Therefore, the effects of long-term or usual intake of PPP-fortified bread on inflammatory biomarkers and oxidative stress are not clear. However, further studies are needed to examine this effect. The results of our study revealed a decreasing trend in depression scores in both groups; however, this reduction was not significant in the between-group comparison. The reduction in both groups, with the exception of extra attention given, may be due to the whole-grain bread and sourdough used for PPP-fortified bread. Previous studies have shown a significant inverse association between whole grains and depression among Iranian adults[ 29 ]. Therefore, it seems that PPP-fortified bread has no significant effect on psychological status. In contrast with our findings, Barghchi et al. reported that, compared with weight loss alone, PPP supplementation along with a weight loss diet for 8 weeks decreased depression and stress scores [ 30 ]. Therefore, the administration of PPP supplements might be more effective than PPP fortification in terms of its effects on mental health. To the best of our knowledge, this investigation is a randomized clinical trial to assess the effects of bread fortified with PPP on the clinical outcomes of patients with T2DM. Moreover, the present trial was performed in a homogenous population through strict inclusion–exclusion criteria. Furthermore, dietary intake and physical activity were monitored throughout the study. We also included both genders; hence, the findings could apply to both genders. Some limitations in our study should be considered when our findings are interpreted. Because of funding limitations, we could not use an ELISA kit for oxidative stress measurement. We could not measure specific biomarkers for compliance assessment; however, adherence to the intervention was assessed via dietary records. In the current study, only patients with type 2 diabetes were included; therefore, the generalizability of our findings to T1DM patients should be done with caution. We provided a portion of the bread that a person consumed throughout the day (100 g/day). Therefore, the effect of nonfortified bread cannot be excluded. In conclusion, compared with the control bread, dietary intake of PPP-fortified bread for 12 weeks had no significant effect on hs-CRP, oxidative stress, or psychological indices among individuals with T2DM. However, the ability of PPP-fortified bread to reduce hs-CRP levels in the within-group comparison might be clinically important. Notably, the dosage of PPP administered in the current study had no side effects. Further investigations should be conducted to assess the effects of PPP fortification using other foods, such as dairy products. According to the results of the MTT assay, the administered dosage of PPP in bread (3.5 g/100 g bread) was safe and did not result in significant toxicity. Declarations The authors declare that they have no conflicts of interest. Funding The present study was supported by a grant from Isfahan University of Medical Sciences under project number 398978. Author Contribution CRediT authorship contribution statement: Maryam Zare: Project administration, Investigation, Methodology, writing the original draft. Mohammad Javad Tarrahi: developed the statistical design and analysis, reviewing and editing the draft.Omid Sadeghi:developed the statistical design and analysis, reviewing and editing the draft.Mozhgan Karimifar: clinical assistance, Investigation, and editing draft. Sayed Amir Hossein Goli: Food Science. Methodology, reviewing, and editing the draft.Reza Amani: Supervision of study, conceptualization, writing - reviewing & editing. All the authors have seen and approved the last version of the manuscript. Acknowledgments The present work is part of the Ph.D. thesis approved by Isfahan University of Medical Sciences (approval no: IRCT20191209045672N1). The authors wish to thank all patients who kindly participated in the current study. The cooperation of the laboratory staff at the Endocrine and Metabolic Research Center is much appreciated. The authors are especially grateful to Dr. Sahar Saraf-Bank, Dr. Sanaz Mehrabani, Mahsa Rezazadegan, and Azam Khani. Data availability The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request. References Khan MAB, Hashim MJ, King JK, Govender RD, Mustafa H, Al Kaabi J. Epidemiology of Type 2 Diabetes - Global Burden of Disease and Forecasted Trends. J Epidemiol global health. 2020;10(1):107–11. Saeedi P, Petersohn I, Salpea P, Malanda B, Karuranga S, Unwin N et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas. Diabetes research and clinical practice. 2019;157:107843. Deshpande AD, Harris-Hayes M, Schootman M. 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Grabež M, Škrbić R, Stojiljković MP, Vučić VM, Grujić VR, Jakovljević V, et al. A prospective, randomized, double-blind, placebo-controlled trial of polyphenols on the outcomes of inflammatory factors and oxidative stress in patients with type 2 diabetes mellitus. Rev Cardiovasc Med. 2022;23(2):57. Sohrab G, Nasrollahzadeh J, Zand H, Amiri Z, Tohidi M, Kimiagar M. Effects of pomegranate juice consumption on inflammatory markers in patients with type 2 diabetes: A randomized, placebo-controlled trial. J Res Med sciences: official J Isfahan Univ Med Sci. 2014;19(3):215. Abbaspoor Z, Amani A, Afshari P, Jafarirad S. The effect of education through mobile phone short message service on promoting self-care in prediabetic pregnant women: A randomized controlled trial. J Telemed Telecare. 2020;26(4):200–6. Vitale M, Vaccaro O, Masulli M, Bonora E, Del Prato S, Giorda CB, et al. Polyphenol intake and cardiovascular risk factors in a population with type 2 diabetes: The TOSCA. IT study. Clin Nutr. 2017;36(6):1686–92. Bagheri S, Khorramabadi RM, Assadollahi V, Khosravi P, Cheraghi Venol A, Veiskerami S, et al. The effects of pomegranate peel extract on the gene expressions of antioxidant enzymes in a rat model of alloxan-induced diabetes. Arch Physiol Biochem. 2023;129(4):870–8. Jafari T, Fallah AA, Bahrami M, Lorigooini Z. Effects of pomegranate peel extract and vitamin E on oxidative stress and antioxidative capacity of hemodialysis patients: a randomized controlled clinical trial. J Funct Foods. 2020;72:104069. Mahdavi AM, Javadivala Z. Systematic review of the effects of pomegranate (Punica granatum) on osteoarthritis. Health Promotion Perspect. 2021;11(4):411. Sadeghi O, Sadeghian M, Rahmani S, Maleki V, Larijani B, Esmaillzadeh A. Whole-grain consumption does not affect obesity measures: an updated systematic review and meta-analysis of randomized clinical trials. Adv Nutr. 2020;11(2):280–92. Barghchi H, Milkarizi N, Dehnavi Z, Askari VR, Rajabzade F, Ostad AN et al. The Effects of pomegranate Peel Supplementation on Depression, Anxiety, and Stress Symptoms of Patients with Nonalcoholic Fatty Liver: A Randomized Clinical Trial. J Nutr Fasting Health. 2023;11(2). Tables Table 1: Baseline characteristics of the study participants a . Variable Bread with PPP Control P value b Sex 0.13 Female (%) 53.3 (24) 68.9 (31) Age 51.88 ± 5.10 55.02 ± 4.97 0.004 Body weight (kg) 72.51 ± 8.41 69.29 ± 9.67 0.09 HbA 1 C (%) 6.51 ± 0.96 6.49 ± 0.97 0.92 Physical activity (MET/hour/day) 32.33 ± 4.48 32.55 ± 4.91 0.84 Education level n (%) Diploma and university degree 77.8 (35) 80 (36) 0.79 Medication use Anti-diabetic (%) 88.9 (40) 77.8 (35) 0.16 Statins (%) 66.7 (30) 60 (27) 0.51 Anti-depressants (%) 13.3 (6) 4.4 (2) 0.26 a Values are presented as the means ± SDs and percentages for quantitative and qualitative variables, respectively. b Results from the chi-square test for qualitative variables and the independent t test for quantitative variables. Table 2: Dietary intake at baseline and after 12 weeks of intervention a . Nutrients Intervention (n=45) Control (n=45) P value b Energy (kcal/day) Week 0 1998.98 ± 468.98 1979.65 ± 444.51 Change -61.17.80 ± 383.92 -116.98 ± 318.76 0.57 Carbohydrate(g/day) Week 0 300.16 ± 79.44 306.15 ± 78.60 Change -10.59 ± 63.03 -21.15 ± 49.56 0.50 Protein(g/day) Week 0 69.39 ± 19.51 70.82 ± 14.97 Change -2.11 ± 21.70 -3.28 ± 16.73 0.82 Fat (g/day) Week 0 62.26 ± 20.67 55.83 ±19.48 Change -1.87 ± 21.50 -2.00 ± 21.67 0.98 Vitamin C (mg/d) Week 0 109.50 ±55.32 117.82 ± 65.58 Change 9.86 ±84.54 -1.08 ± 70.23 0.61 Vitamin E (mg/d) Week 0 20.97 ± 8.40 20.59 ± 11.66 Change -0.58 ± 11.53 -1.20 ± 13.78 0.85 Selenium (mcg/d) Week 0 0.08 ± 0.03 0.08 ± 0.03 Change 0.00 ± 0.05 -0.00 ± 0.04 0.60 Zinc (mg/d) Week 0 7.2 ± 2.3 6.98 ± 1.96 Change 0.24 ± 2.93 0.11 ± 2.79 0.87 Vit A(mcg/d) Week 0 983.58 ± 784.04 798.69 ± 454.00 Change -58.20 ±1169.33 -210.45 ± 920 0.60 Beta-carotene(mcg/d) Week 0 397.35 ± 716.74 275.25 ± 311.68 Change 82.19 ± 648.73 -61.23 ±362.13 0.33 a Values are reported as the mean ± SD b Obtained from independent t tests. Table 3: Effects of treatment with PPP on inflammation , oxidative stress markers and mood scores ͣa Variables Intervention P value b Control p value b p value c p value d Pre Post Pre Post Hs-CRP (mg/dL) 2.75 ± 1.56 2.19 ± 2.03 0.01 2.45 ± 1.38 1.64 ± 1.19 <0.001 Change -0.56 ± 1.29 -0.81 ± 1.16 0.37 0.30 MDA (nmol/mL) 232.51 ± 104.87 217.67 ± 70.47 0.447 236.09 ± 76.84 213.24 ± 53.03 0.07 Change -14.84 ± 117.36 -22.85 ± 75.33 0.72 0.87 TAC (nmol/mL) 1467.92 ± 309.77 1513.87 ± 395.99 0.34 1606.35 ± 303.60 1608.16 ±324.34 0.96 Change 45.94 ± 298.39 1.81 ± 274.49 0.50 0.49 Depression 6.66 ± 4.60 5.33 ± 4.36 0.04 5.89 ± 4.32 4.44 ± 4.28 0.01 Change -1.33 ± 3.66 -1.44 ± 2.83 0.89 0.65 Anxiety 5.30 ± 4.11 6.03 ±3.80 0.17 4.72 ± 3.89 5.62 ± 3.25 0.08 Change 0.72 ± 3.00 0.89 ± 2.73 0.81 0.92 Stress 9.27 ± 6.09 8.15 ± 5.48 0.24 7.13 ± 5.24 6.86 ± 5.73 0.66 Change -1.12 ± 5.42 -0.27 ± 3.42 0.47 0.45 a Variables are expressed as the mean ± SE b Calculated by paired-samples t test c Calculated via an independent t test d Obtained from multivariable analysis of covariance (MANCOVA), adjusted for age, sex, and baseline weight. MDA: malondialdehyde; TAC: total antioxidant capacity; hs-CRP: high-sensitivity C-reactive protein Additional Declarations No competing interests reported. Supplementary Files CONSORT2010Checklist.doc graghical.jpg Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {\"props\":{\"pageProps\":{\"initialData\":{\"identity\":\"rs-5254735\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":true,\"archivedVersions\":[],\"articleType\":\"Research Article\",\"associatedPublications\":[],\"authors\":[{\"id\":367291894,\"identity\":\"189736cd-3a7f-4ea3-9ffb-2bcc6efb0d80\",\"order_by\":0,\"name\":\"Maryam Zare\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Isfahan University of Medical Sciences\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Maryam\",\"middleName\":\"\",\"lastName\":\"Zare\",\"suffix\":\"\"},{\"id\":367291895,\"identity\":\"c3952e52-7031-49c2-9b17-5b3279b24c59\",\"order_by\":1,\"name\":\"Mohammad Javad 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2\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":21017,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eComparison of the IC50 values of pomegranate compounds at 24, 48, and 72 hours in fibroblast lines via Tukey's multiple comparisons test.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"2.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-5254735/v1/8230fa3357a7798ffd9f3426.png\"},{\"id\":67295590,\"identity\":\"8565e10d-6c5a-4755-8ffa-162be79629e5\",\"added_by\":\"auto\",\"created_at\":\"2024-10-23 10:58:46\",\"extension\":\"png\",\"order_by\":3,\"title\":\"Figure 3\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":59641,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eCell viability after treatment with different concentrations of 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10:50:46\",\"extension\":\"jpg\",\"order_by\":2,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"supplement\",\"size\":93375,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"graghical.jpg\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-5254735/v1/6f7b00ee9b8f5f2a3059d7e8.jpg\"}],\"financialInterests\":\"No competing interests reported.\",\"formattedTitle\":\"Effects of bread fortification with pomegranate peel powder on inflammation biomarkers, oxidative stress, and mood status in patients with type 2 diabetes: A randomized placebo-controlled trial\",\"fulltext\":[{\"header\":\"Introduction\",\"content\":\"\\u003cp\\u003eThe prevalence of type 2 diabetes mellitus (T2DM) is increasing at an alarming rate [\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e]. T2DM is prevalent among 9.3% of adults[\\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e]. In Iran, it is estimated that 9.2\\u0026nbsp;million people are affected[\\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e]. Patients with T2DM usually experience several complications, such as foot ulcers, dental disease, and reduced resistance to infections, which negatively affect patients\\u0026rsquo; quality of life[\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e]. Additionally, these patients are at increased risk of several chronic diseases, including cardiovascular disease (CVD), nephropathy, retinopathy, and liver diseases[\\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e]. In addition, T2DM imposes a high economic burden on the healthcare system [\\u003cspan citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e]. Therefore, finding an appropriate strategy for the management of this disease is urgently needed.\\u003c/p\\u003e \\u003cp\\u003ePrevious studies have proposed several pharmacological and nonpharmacological interventions for the management of T2DM [\\u003cspan citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e]. Owing to several complications of pharmacological methods, nonpharmacological therapies such as dietary interventions, supplementation with some nutrients, and herbal medicine have received great attention [\\u003cspan citationid=\\\"CR7\\\" class=\\\"CitationRef\\\"\\u003e7\\u003c/span\\u003e]. Recently, intervention with polyphenol-rich supplements or food has been shown to have a beneficial effect on the clinical outcomes of diabetic patients (e.g., by modulating oxidative stress and anti-inflammatory responses) [\\u003cspan citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e]. Among polyphenol-rich foods, pomegranate and its peel have received much attention. In a clinical trial, intervention with pomegranate peel extract significantly reduced hs-CRP in diabetic patients [\\u003cspan citationid=\\\"CR9\\\" class=\\\"CitationRef\\\"\\u003e9\\u003c/span\\u003e].\\u003c/p\\u003e \\u003cp\\u003eDespite the presented evidence, it is not clear whether the addition of pomegranate peel to foods can affect the outcomes of diabetic patients. Bread is a good candidate for fortification because it comprises the majority of individuals around the world [\\u003cspan citationid=\\\"CR10\\\" class=\\\"CitationRef\\\"\\u003e10\\u003c/span\\u003e], as does the Iranian diet, in which more than 60% of the energy is from carbohydrates, particularly from different types of bread [\\u003cspan citationid=\\\"CR11\\\" class=\\\"CitationRef\\\"\\u003e11\\u003c/span\\u003e]. Notably, most types of bread in Iranian food culture are prepared with refined grains. Therefore, changing the composition of bread may affect health outcomes, particularly for diabetic patients. Given the current evidence of the possible beneficial effect of pomegranate peel on the outcomes of diabetic patients, we decided to fortify bread with this functional food. Therefore, the present clinical trial aimed to assess the effects of bread fortified with pomegranate peel powder (PPP) on hs-CRP, oxidative stress, and mental health in patients with T2DM.\\u003c/p\\u003e\"},{\"header\":\"Materials and methods\",\"content\":\"\\u003cdiv id=\\\"Sec3\\\" class=\\\"Section2\\\"\\u003e\\n \\u003ch2\\u003eStudy population\\u003c/h2\\u003e\\n \\u003cp\\u003eThis investigation was a randomized, blinded, parallel clinical trial. Details on the participants, study design, and data collection were published previously[\\u003cspan class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e]. Participants were diabetic patients referred to the outpatient clinic of the Endocrine and Metabolism Research Center (Isfahan University Medical Sciences, Isfahan, Iran) and health centers of Isfahan city from May 2021 to January 2023. Considering a type 1 error of 5%, a type 2 error of 20%, and a study power of 80%, the required sample size was calculated via the relevant formula. Accordingly, we included 45 patients with T2DM in each group. The study inclusion criteria were as follows: 1) patients who were diagnosed with T2DM within the last 5 years, 2) patients aged 40\\u0026ndash;60 years, 3) those who had HbA1c levels between 5.7% and 8.0% over the past 3 months, and 4) patients who had a body mass index (BMI)\\u0026thinsp;\\u0026le;\\u0026thinsp;30 kg/m\\u003csup\\u003e2\\u003c/sup\\u003e. Patients with chronic kidney or liver diseases (cirrhosis and hepatitis), patients who were pregnant or lactating, those taking hormone replacement therapy (insulin or others), those who adhered to a special diet and patients who received antioxidant supplements during the last 3 months were excluded. During the trial, patients who changed the dosages and types of medications, those who were unwilling to continue the trial, and those who reported complications due to possible side effects were excluded as well. This study was conducted in accordance with the Helsinki Declaration, and written informed consent was obtained from all participants. The protocol of the present trial was approved by the Ethical Committee at the Isfahan University of Medical Sciences (approval no. IR. MUI.RESEARCH.REC.1399.087) and registered at \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003ewww.IRCT.ir\\u003c/span\\u003e\\u003c/span\\u003e (ID: IRCT20191209045672N1). Furthermore, our study was reported on the basis of the Consolidated Standards of Reporting Trials (CONSORT) statement guidelines [\\u003cspan class=\\\"CitationRef\\\"\\u003e13\\u003c/span\\u003e].\\u003c/p\\u003e\\n\\u003c/div\\u003e\\n\\u003ch3\\u003eStudy design\\u003c/h3\\u003e\\n\\u003cp\\u003eAmong the 11,165 evaluated cases, only 520 diabetic patients met the inclusion criteria. One hundred and twelve patients agreed to participate in the study. During the run-in period, we excluded 22 patients because they were unwilling to follow the trial. Distance areas from their homes, COVID-19 strikes, and a lack of blood sugar control were the main reasons for their exclusion. At the first visit, we measured the fasting blood glucose of the participants with a glucometer, and those whose blood glucose was less than 150 mg/dL were included in the study. After the ruin period, 10 participants were excluded because their HbA1c (glycated hemoglobin) level was \\u0026gt;\\u0026thinsp;8%. Finally, the remaining 90 patients were randomly allocated into two equal groups via computer-generated random numbers. The patients were allocated to either PPP-fortified bread or PPP-free bread groups. Both types of bread were identical in terms of shape, size, and packaging. All the breads had the same appearance, so it was impossible to distinguish each one. During the run-in period, all patients received a control bread. During the run-in period, two sessions were held for all patients. In each session, adherence to bread intake and possible complications related to bread intake were assessed to select patients with high compliance. After the run-in period, all patients (n\\u0026thinsp;=\\u0026thinsp;90) were followed for 12 weeks. The investigator and patients were in touch through text messaging and phone calls during the trial. Additionally, they were asked not to change their usual dietary intake or physical activity throughout the study. At baseline and at the end of the trial, a fasting blood sample and mental health data were collected from each participant. We used dietary records to evaluate adherence to the intervention. Additionally, compliance with bread intake was monitored through routine visits and phone interviews once a week. However, there were no biochemical indicators for the intake of bread.\\u003c/p\\u003e\\n\\u003cp\\u003ePhysical activity was assessed via two 3-day physical activity records at baseline and at the end of the trial. In addition to physical activity, usual dietary intake was assessed via two 3-day food records before and after the intervention. A trained nutritionist described how to fill out the food and physical activity records. The records were checked by a nutritionist. To report the correct amount of food intake, a food album was provided to them. After the dietary records were collected, the serving sizes were converted to grams per day. The average intakes of energy and nutrients for each 3-day record were subsequently calculated via a customized version of Nutritionist IV software (First Data Bank; Hearst Corp, San Bruno, CA, USA).\\u003c/p\\u003e\\n\\u003ch3\\u003eInterventions\\u003c/h3\\u003e\\n\\u003cdiv id=\\\"Sec6\\\" class=\\\"Section2\\\"\\u003e\\n \\u003ch2\\u003e\\u003cstrong\\u003ePomegranate peel powder\\u003c/strong\\u003e:\\u003c/h2\\u003e\\n \\u003cp\\u003ePomegranate fruits were purchased from Fars Province, Iran. The pomegranate peels were separated and then dried and ground into powder. The PPP mixture was stored at \\u0026minus;\\u0026thinsp;20\\u0026deg;C until the bread was prepared. For the preparation of PPP-rich bread, 3.5 grams of PPP per 100 grams was added to the wheat flour. This dosage was safe and was selected on the basis of previous studies [\\u003cspan class=\\\"CitationRef\\\"\\u003e14\\u003c/span\\u003e]. Other constituents that are used for bread preparation include sourdough, rye flour, salt, sugar, yeast, and water. The composition of each 100-gr bread was 63 gr plain flour, 14 gr rye flour, 14 gr whole wheat flour, 2 gr gluten, 1.4 gr yeast, 0.14 gr brown sugar, 0.1 gr improver, 0.8 gr salt, 1.4 gr sourdough. The only difference between the pomegranate bread and the control bread was the addition of PPP. Simin Bread Company, Isfahan, Iran produced both breads.\\u003c/p\\u003e\\n\\u003c/div\\u003e\\n\\u003ch3\\u003eMTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) test\\u003c/h3\\u003e\\n\\u003cp\\u003eThe MTT colorimetric measure of pure PPP against fibroblast L929 cells was conducted according to the Badano JA method [\\u003cspan class=\\\"CitationRef\\\"\\u003e15\\u003c/span\\u003e]. Briefly, 100 \\u0026micro;L of cell suspension in RPMI-1640 medium (1 \\u0026times; 10\\u003csup\\u003e4\\u003c/sup\\u003e cells/well) was seeded into each well of a 96-well microplate and then incubated for 24 h (37\\u0026deg;C and humidified 5% CO\\u003csub\\u003e2\\u003c/sub\\u003e air). After that, the old medium was removed, and 100 \\u0026micro;L of different concentrations of PPP were added to each well and incubated for another 24, 48, or 72 h under similar conditions. Consequently, 10 \\u0026micro;L of MTT solution (5 mg/mL PBS) was added to each well of the plates in the dark and incubated at 37\\u0026deg;C for 2\\u0026ndash;3 h. To dissolve the formed formazan crystals, the old media containing MTT was removed, and DMSO (100 \\u0026micro;L) was gently added to each well. The optical density of each well was measured with an ELISA plate reader (Startfix-2100, Awareness, USA) at 570 nm. DMSO (1%) and doxorubicin were used as negative and positive controls, respectively. The concentrations that inhibited half of the cell population (IC50) were obtained by modeling the percentage of cytotoxicity versus the concentration of PPP. The assay was performed in triplicate, and the results are reported as the means\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;standard deviations (SDs). The cell viability (%) was determined according to Eq.\\u0026nbsp;(\\u003cspan class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e).\\u003c/p\\u003e\\n\\u003cdiv id=\\\"Equ1\\\" class=\\\"Equation\\\"\\u003e\\n \\u003cdiv class=\\\"mathdisplay\\\" id=\\\"FileID_Equ1\\\" name=\\\"EquationSource\\\"\\u003e$$\\\\:\\\\text{%}\\\\text{C}\\\\text{e}\\\\text{l}\\\\text{l}\\\\:\\\\text{v}\\\\text{i}\\\\text{a}\\\\text{b}\\\\text{i}\\\\text{l}\\\\text{i}\\\\text{t}\\\\text{y}=\\\\:\\\\:\\\\frac{\\\\text{A}\\\\text{b}\\\\text{s}\\\\text{o}\\\\text{r}\\\\text{b}\\\\text{a}\\\\text{n}\\\\text{c}\\\\text{e}\\\\:\\\\text{o}\\\\text{f}\\\\:\\\\text{t}\\\\text{r}\\\\text{e}\\\\text{a}\\\\text{t}\\\\text{e}\\\\text{d}\\\\:\\\\text{c}\\\\text{e}\\\\text{l}\\\\text{l}\\\\text{s}-\\\\:\\\\text{b}\\\\text{a}\\\\text{c}\\\\text{k}\\\\text{g}\\\\text{r}\\\\text{o}\\\\text{u}\\\\text{n}\\\\text{d}\\\\:\\\\text{a}\\\\text{b}\\\\text{s}\\\\text{o}\\\\text{r}\\\\text{b}\\\\text{a}\\\\text{n}\\\\text{c}\\\\text{e}\\\\left(\\\\text{b}\\\\right)\\\\:}{\\\\text{A}\\\\text{b}\\\\text{s}\\\\text{o}\\\\text{r}\\\\text{b}\\\\text{a}\\\\text{n}\\\\text{c}\\\\text{e}\\\\:\\\\text{o}\\\\text{f}\\\\:\\\\text{u}\\\\text{n}\\\\text{t}\\\\text{r}\\\\text{e}\\\\text{a}\\\\text{t}\\\\text{e}\\\\text{d}\\\\:\\\\text{c}\\\\text{e}\\\\text{l}\\\\text{l}\\\\text{s}\\\\left(\\\\text{c}\\\\right)-\\\\:\\\\text{b}\\\\text{a}\\\\text{c}\\\\text{k}\\\\text{g}\\\\text{r}\\\\text{o}\\\\text{u}\\\\text{n}\\\\text{d}\\\\:\\\\text{a}\\\\text{b}\\\\text{s}\\\\text{o}\\\\text{r}\\\\text{b}\\\\text{a}\\\\text{n}\\\\text{c}\\\\text{e}\\\\left(\\\\text{b}\\\\right)\\\\:}\\\\:\\\\times\\\\:100$$\\u003c/div\\u003e\\u003cdiv class=\\\"EquationNumber\\\"\\u003e2\\u003c/div\\u003e\\u003c/div\\u003e\\u003cp\\u003ewhere b\\u0026thinsp;=\\u0026thinsp;blank and c\\u0026thinsp;=\\u0026thinsp;control.\\u003c/p\\u003e\\u003cdiv id=\\\"Sec8\\\" class=\\\"Section2\\\"\\u003e\\u003ch2\\u003eAssessment of variables\\u003c/h2\\u003e\\u003cp\\u003eData on age, sex, education, medication, supplement use, and history of diseases were collected via an interview-based questionnaire. Anthropometric measurements, including weight and height, were measured via standard techniques. All measurements were performed by M Z in the morning while the participants wore underwear. The height was measured to the nearest 0.1 cm without footwear using a stadiometer (Seca, Hamburg, Germany). Weight was measured to the nearest 0.1 kg with light clothing using a Seca Beam Balance (Seca). BMI was calculated via the following formula: weight (kg)/height (m) \\u003csup\\u003e2\\u003c/sup\\u003e (kg/m\\u003csup\\u003e2\\u003c/sup\\u003e). Data on outcome variables, including laboratory parameters and psychological factors, were collected at baseline and 3 months post-intervention.\\u003c/p\\u003e\\u003c/div\\u003e\\u003ch3\\u003eLaboratory measurements\\u003c/h3\\u003e\\u003cp\\u003eBlood samples (10 mL) were taken after 12 hours of overnight fasting at the beginning and end of the intervention period. Then, the serum samples were separated and stored at \\u0026minus;\\u0026thinsp;80\\u0026deg;C until further analysis. HbA1c, total antioxidant capacity (TAC), malondialdehyde (MDA), and hs-CRP were measured as primary outcomes. A latex immunoturbidimetric assay was used to measure hs-CRP (aptec, Belgium). The cupric-reducing antioxidant capacity method was used to measure the serum TAC via a standard kit (Kiazist Life Sciences, Iran). The assessment of MDA was based on thiobarbituric acid reactive substances (TBARS) measured with a standard kit (Kiazist Life Sciences, Iran). The HbA1c levels were measured with a BT1500 device via turbidimetric immunoassay. All kits had an intra-assay CV˂10% and an interassay CV ˂ 8%.\\u003c/p\\u003e\\u003ch3\\u003eMental health\\u003c/h3\\u003e\\u003cp\\u003e\\u003cem\\u003eThe\\u003c/em\\u003e Depression, Anxiety, and Stress Scale-21 (DASS-21) was used to measure mood status at baseline and 3 months after the intervention [\\u003cspan class=\\\"CitationRef\\\"\\u003e16\\u003c/span\\u003e]. The DASS-21 is a self-report questionnaire with three subscales comprising seven questions related to each subscale. Mood status is evaluated as the endpoint. Each question uses a four-point (0\\u0026ndash;3) Likert scale to identify the severity of depression, anxiety, and stress. Samani et al. reported that the scale had appropriate validity and reliability among Iranian people [\\u003cspan class=\\\"CitationRef\\\"\\u003e17\\u003c/span\\u003e].\\u003c/p\\u003e\\u003cdiv id=\\\"Sec11\\\" class=\\\"Section2\\\"\\u003e\\u003ch2\\u003eStatistical analysis\\u003c/h2\\u003e\\u003cp\\u003eStatistical analyses were conducted via the per-protocol approach. The per-protocol analysis included data from those individuals who completed the intervention. The normality of continuous variables was assessed by skewness and the Kolmogorov\\u0026ndash;Smirnov test. All outcome variables in the current study were normally distributed. To assess the differences between the intervention and control groups in terms of continuous variables, an independent samples t test was used. The chi-square test was used to assess the distribution of categorical variables among the 2 groups. To perform a within-subject comparison in each group, we used a paired sample t test. Additionally, changes in outcome variables were compared between the two groups via the independent samples t test. To assess the effects of PPP-fortified bread on inflammation and mental health, we used analysis of covariance (ANCOVA and MANCOVA) with age, sex and weight as covariates. A P value less than 0.05 was considered significant. Statistical analysis was conducted via SPSS version 20 (SPSS Inc., Chicago, IL, USA).\\u003c/p\\u003e\\u003c/div\\u003e\"},{\"header\":\"Results\",\"content\":\"\\u003cp\\u003e\\u003cstrong\\u003eCytotoxicity and IC50\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe results of the cytotoxicity of\\u0026nbsp;the\\u0026nbsp;PPP against the fibroblast L929 cell line are presented in\\u0026nbsp;Figs.\\u0026nbsp;1-3. As\\u0026nbsp;shown\\u0026nbsp;in Fig.\\u0026nbsp;1,\\u0026nbsp;increasing the concentration of PPP from 125 to 1900 \\u0026micro;g/ml\\u0026nbsp;increased\\u0026nbsp;the cytotoxicity against fibroblasts (Fig.\\u0026nbsp;1). There was\\u0026nbsp;no\\u0026nbsp;significant difference\\u0026nbsp;in\\u0026nbsp;the IC50 of PPP after 24 h and\\u0026nbsp;48 h, confirming\\u0026nbsp;that the toxicity of PPP was not time dependent until 48 h. However,\\u0026nbsp;after 72 h,\\u0026nbsp;the cytotoxicity increased,\\u0026nbsp;and there was a\\u0026nbsp;significant difference\\u0026nbsp;(P\\u0026lt;0.05)\\u0026nbsp;in\\u0026nbsp;the cytotoxicity after\\u0026nbsp;24\\u0026nbsp;h\\u0026nbsp;and\\u0026nbsp;72 h, which\\u0026nbsp;can be attributed to the release of antioxidant compounds from PPP to the medium (Fig. 2). Moreover, the cell viability\\u0026nbsp;at\\u0026nbsp;different concentrations decreased\\u0026nbsp;with\\u0026nbsp;increasing\\u0026nbsp;concentrations\\u0026nbsp;from 125 to 1900 (\\u0026mu;g/mL) (Fig.\\u0026nbsp;3).\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eBaseline characteristics and dietary intake\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eAmong\\u0026nbsp;the 90\\u0026nbsp;T2DM patients (35 men and 55 women)\\u0026nbsp;at baseline, seven in the control group and six in the intervention group were excluded\\u0026nbsp;because of\\u0026nbsp;side effects related to the intervention (n=4), very low compliance (n=4),\\u0026nbsp;COVID-19 infection (n=2), unwillingness to continue the study (n=1),\\u0026nbsp;or\\u0026nbsp;severe disease or surgery (n=2).\\u0026nbsp;Finally, 77 subjects (39 in the intervention\\u0026nbsp;group\\u0026nbsp;and 38 in the control group) completed the intervention period. The flow diagram of this study is shown in \\u003cstrong\\u003eFig. 4\\u003c/strong\\u003e.\\u003c/p\\u003e\\n\\u003cp\\u003eThe baseline characteristics of\\u0026nbsp;the\\u0026nbsp;T2DM patients in the PPP-fortified bread and control groups are displayed in \\u003cstrong\\u003eTable\\u0026nbsp;\\u003c/strong\\u003e\\u003cstrong\\u003e1\\u003c/strong\\u003e.\\u0026nbsp;We found no significant differences between the two groups in terms of demographic variables, past medical history, drug and supplement use,\\u0026nbsp;or\\u0026nbsp;anthropometric measures.\\u0026nbsp;Additionally,\\u0026nbsp;there were no significant differences\\u0026nbsp;in\\u0026nbsp;physical activity between the groups throughout the trial.\\u0026nbsp;The results of\\u0026nbsp;the\\u0026nbsp;3-day food records\\u0026nbsp;revealed\\u0026nbsp;no significant\\u0026nbsp;differences\\u0026nbsp;between the two groups in terms of energy, macronutrient,\\u0026nbsp;or\\u0026nbsp;micronutrient\\u0026nbsp;intake\\u0026nbsp;(\\u003cstrong\\u003eTable 2\\u003c/strong\\u003e).\\u003c/p\\u003e\\n\\u003cp\\u003eThe effects of PPP-fortified bread on\\u0026nbsp;the\\u0026nbsp;serum concentrations of hs-CRP, TAC,\\u0026nbsp;and\\u0026nbsp;MDA and mental health are presented in\\u0026nbsp;\\u003cstrong\\u003eTable 3\\u003c/strong\\u003e. The hs-CRP levels\\u0026nbsp;were\\u0026nbsp;2.75 \\u0026plusmn; 1.56 at baseline\\u0026nbsp;and\\u0026nbsp;2.19 \\u0026plusmn; 2.03 at the end of\\u0026nbsp;the\\u0026nbsp;trial in\\u0026nbsp;the\\u0026nbsp;intervention group and 2.45 \\u0026plusmn; 1.38 at baseline\\u0026nbsp;and\\u0026nbsp;1.64 \\u0026plusmn; 1.19 at the end of\\u0026nbsp;the\\u0026nbsp;trial in\\u0026nbsp;the\\u0026nbsp;control group. The hs-CRP levels decreased in\\u0026nbsp;the\\u0026nbsp;two groups; however, these changes were not significant between the groups.\\u003c/p\\u003e\\n\\u003cp\\u003eThe depression\\u0026nbsp;scores\\u0026nbsp;were lower\\u0026nbsp;(6.66 \\u0026plusmn; 4.60 at baseline vs. 5.33 \\u0026plusmn; 4.36 at the end of\\u0026nbsp;the\\u0026nbsp;trial, P\\u0026nbsp;=\\u0026nbsp;0.04) in\\u0026nbsp;the\\u0026nbsp;intervention group and (5.89 \\u0026plusmn; 4.32 at baseline vs. 4.44 \\u0026plusmn; 4.28 at the end of\\u0026nbsp;the\\u0026nbsp;trial) in\\u0026nbsp;the\\u0026nbsp;control group. These reductions were significant within\\u0026nbsp;the\\u0026nbsp;two groups, although these changes were not significant between the groups.\\u003c/p\\u003e\\n\\u003cp\\u003eThe TAC, MDA, stress, and anxiety scores\\u0026nbsp;were not significantly different\\u0026nbsp;between the\\u0026nbsp;two groups. When we controlled for age,\\u0026nbsp;sex\\u0026nbsp;and weight\\u0026nbsp;via\\u0026nbsp;ANCOVA and MANCOVA, no differences were\\u0026nbsp;detected.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eSide effects\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eDuring the study, the only reported adverse event was gastrointestinal complications, including constipation and stomach discomfort (3 patients in the intervention group and 1 patient in the control group).\\u003c/p\\u003e\"},{\"header\":\"Discussion\",\"content\":\"\\u003cp\\u003eIn the present study, we found that, compared with the control bread, PPP-fortified bread had no significant effect on hs-CRP, oxidative stress, or mental health. To the best of our knowledge, this study assessed the effects of PPP-fortified bread on the clinical outcomes of T2DM patients.\\u003c/p\\u003e \\u003cp\\u003eDiabetes is one of the major challenging issues in public health [\\u003cspan citationid=\\\"CR18\\\" class=\\\"CitationRef\\\"\\u003e18\\u003c/span\\u003e]. The levels of inflammatory biomarkers are greater in diabetic patients than in nondiabetic patients. Moreover, as inflammatory biomarkers are connected with endothelial dysfunction, they can increase the risk of cardiovascular diseases (CVDs) among diabetic individuals [\\u003cspan citationid=\\\"CR19\\\" class=\\\"CitationRef\\\"\\u003e19\\u003c/span\\u003e]. In addition to CVD, patients with T2DM are at increased risk for psychological symptoms such as depression, anxiety, and stress, which may have additional negative effects on their quality of life [\\u003cspan citationid=\\\"CR20\\\" class=\\\"CitationRef\\\"\\u003e20\\u003c/span\\u003e]. Pharmacological treatments, along with lifestyle modifications (diet and exercise), are suggested to meet glycemic targets in these patients. However, it is not clear whether adding PPP to the formulation of main food items such as bread enhances the health properties of PPP. At the beginning of the study, there was no clinical study on pomegranate peel; however, a similar study with a smaller sample size was conducted after we registered our proposal at the IRCT[\\u003cspan citationid=\\\"CR21\\\" class=\\\"CitationRef\\\"\\u003e21\\u003c/span\\u003e].\\u003c/p\\u003e \\u003cp\\u003eOur study revealed that, after the consumption of PPP-fortified bread for 12 weeks, the hs-CRP marker was ameliorated in T2DM patients. However, compared with that of the control bread, the change was not significant. Previous studies have examined the effects of PPP supplements or extracts on inflammation, but no study has investigated PPP-fortified foods. In a clinical trial, Haghighian et al. reported that PPP extract for 8 weeks and Grabež M et al. for 6 weeks significantly decreased the levels of inflammatory biomarkers in obese women with dyslipidemia and in patients with type 2 diabetes mellitus, respectively [\\u003cspan citationid=\\\"CR9\\\" class=\\\"CitationRef\\\"\\u003e9\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR22\\\" class=\\\"CitationRef\\\"\\u003e22\\u003c/span\\u003e]. Moreover, a significant decrease in hs-CRP concentrations (32%) was observed after 12 weeks of administration of 250 mL/day pomegranate juice in diabetic patients [\\u003cspan citationid=\\\"CR23\\\" class=\\\"CitationRef\\\"\\u003e23\\u003c/span\\u003e]. There are mechanisms indicating the beneficial effect of the PPP on inflammation. The PPP contains punicalagin and ellagic acid, which have a reducing effect on proinflammatory cytokines [\\u003cspan citationid=\\\"CR24\\\" class=\\\"CitationRef\\\"\\u003e24\\u003c/span\\u003e]. This effect is mediated by the inhibitory effects of punicalagin and ellagic acid on the mitogen-activated protein kinase (MAPK) pathway, which is involved in inflammatory conditions. Moreover, the PPP is a rich source of polyphenols that induce anti-inflammatory effects through the inhibition of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) and the attenuation of oxidative stress [\\u003cspan citationid=\\\"CR25\\\" class=\\\"CitationRef\\\"\\u003e25\\u003c/span\\u003e].\\u003c/p\\u003e \\u003cp\\u003eIn this study, we also did not find any significant changes in the serum MDA or TAC levels. In contrast, Bagheri et al. reported that the consumption of 200 mg/kg pomegranate peel extract in rats decreased the MDA content compared with that in a control group [\\u003cspan citationid=\\\"CR26\\\" class=\\\"CitationRef\\\"\\u003e26\\u003c/span\\u003e]. Jafari et al. reported that daily consumption of pomegranate peel extract (450 mg/d) for 8 weeks ameliorated MDA levels in hemodialysis patients [\\u003cspan citationid=\\\"CR27\\\" class=\\\"CitationRef\\\"\\u003e27\\u003c/span\\u003e]. The beneficial effect of 1 g pomegranate peel hydroalcoholic extract on MDA levels in osteoarthritis patients was also reported in another clinical trial [\\u003cspan citationid=\\\"CR28\\\" class=\\\"CitationRef\\\"\\u003e28\\u003c/span\\u003e]. Haghighian et al. reported that treatment with PPP extracts for 8 weeks increased TAC levels. Another study by \\u0026Ouml;zlem \\u0026Ouml;zpak Akkuş et al. reported that the use of bread with pomegranate peel for 8 weeks did not change the TAC level[\\u003cspan citationid=\\\"CR21\\\" class=\\\"CitationRef\\\"\\u003e21\\u003c/span\\u003e]. In the present study, although the number of polyphenols in PPP-fortified bread was greater than that in the control bread, it did not affect the MDA or TAC levels. Further studies are needed to illustrate these findings in this regard.\\u003c/p\\u003e \\u003cp\\u003eThe lack of a significant effect of PPP-fortified bread on hs-CRP and oxidative stress might be explained by the interaction of available nutrients in bread with the polyphenols of PPP. Fiber and other nutrients in bread might decrease the absorption of polyphenols. Additionally, Iranians usually consume bread with other foods, such as cheese, legumes, nuts, dairy products, and other grains. These foods contain high amounts of fiber, vitamins, and minerals. Some of these compounds may interact with the effects of bread polyphenols as well as their absorption. Notably, the bread in this study could decrease within groups. Although this reduction was not significant between the groups, it was of clinical importance. Therefore, the effects of long-term or usual intake of PPP-fortified bread on inflammatory biomarkers and oxidative stress are not clear. However, further studies are needed to examine this effect.\\u003c/p\\u003e \\u003cp\\u003eThe results of our study revealed a decreasing trend in depression scores in both groups; however, this reduction was not significant in the between-group comparison. The reduction in both groups, with the exception of extra attention given, may be due to the whole-grain bread and sourdough used for PPP-fortified bread. Previous studies have shown a significant inverse association between whole grains and depression among Iranian adults[\\u003cspan citationid=\\\"CR29\\\" class=\\\"CitationRef\\\"\\u003e29\\u003c/span\\u003e]. Therefore, it seems that PPP-fortified bread has no significant effect on psychological status. In contrast with our findings, Barghchi et al. reported that, compared with weight loss alone, PPP supplementation along with a weight loss diet for 8 weeks decreased depression and stress scores [\\u003cspan citationid=\\\"CR30\\\" class=\\\"CitationRef\\\"\\u003e30\\u003c/span\\u003e]. Therefore, the administration of PPP supplements might be more effective than PPP fortification in terms of its effects on mental health.\\u003c/p\\u003e \\u003cp\\u003eTo the best of our knowledge, this investigation is a randomized clinical trial to assess the effects of bread fortified with PPP on the clinical outcomes of patients with T2DM. Moreover, the present trial was performed in a homogenous population through strict inclusion\\u0026ndash;exclusion criteria. Furthermore, dietary intake and physical activity were monitored throughout the study. We also included both genders; hence, the findings could apply to both genders. Some limitations in our study should be considered when our findings are interpreted. Because of funding limitations, we could not use an ELISA kit for oxidative stress measurement. We could not measure specific biomarkers for compliance assessment; however, adherence to the intervention was assessed via dietary records. In the current study, only patients with type 2 diabetes were included; therefore, the generalizability of our findings to T1DM patients should be done with caution. We provided a portion of the bread that a person consumed throughout the day (100 g/day). Therefore, the effect of nonfortified bread cannot be excluded.\\u003c/p\\u003e \\u003cp\\u003eIn conclusion, compared with the control bread, dietary intake of PPP-fortified bread for 12 weeks had no significant effect on hs-CRP, oxidative stress, or psychological indices among individuals with T2DM. However, the ability of PPP-fortified bread to reduce hs-CRP levels in the within-group comparison might be clinically important. Notably, the dosage of PPP administered in the current study had no side effects. Further investigations should be conducted to assess the effects of PPP fortification using other foods, such as dairy products. According to the results of the MTT assay, the administered dosage of PPP in bread (3.5 g/100 g bread) was safe and did not result in significant toxicity.\\u003c/p\\u003e\"},{\"header\":\"Declarations\",\"content\":\" \\u003cp\\u003eThe authors declare that they have no conflicts of interest.\\u003c/p\\u003e\\u003ch2\\u003eFunding\\u003c/h2\\u003e \\u003cp\\u003eThe present study was supported by a grant from Isfahan University of Medical Sciences under project number 398978.\\u003c/p\\u003e\\u003ch2\\u003eAuthor Contribution\\u003c/h2\\u003e\\u003cp\\u003eCRediT authorship contribution statement: Maryam Zare: Project administration, Investigation, Methodology, writing the original draft. Mohammad Javad Tarrahi: developed the statistical design and analysis, reviewing and editing the draft.Omid Sadeghi:developed the statistical design and analysis, reviewing and editing the draft.Mozhgan Karimifar: clinical assistance, Investigation, and editing draft. Sayed Amir Hossein Goli: Food Science. Methodology, reviewing, and editing the draft.Reza Amani: Supervision of study, conceptualization, writing - reviewing \\u0026amp; editing. All the authors have seen and approved the last version of the manuscript.\\u003c/p\\u003e\\u003ch2\\u003eAcknowledgments\\u003c/h2\\u003e \\u003cp\\u003e The present work is part of the Ph.D. thesis approved by Isfahan University of Medical Sciences (approval no: IRCT20191209045672N1). The authors wish to thank all patients who kindly participated in the current study. The cooperation of the laboratory staff at the Endocrine and Metabolic Research Center is much appreciated. The authors are especially grateful to Dr. Sahar Saraf-Bank, Dr. Sanaz Mehrabani, Mahsa Rezazadegan, and Azam Khani.\\u003c/p\\u003e\\u003ch2\\u003eData availability\\u003c/h2\\u003e \\u003cp\\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.\\u003c/p\\u003e\"},{\"header\":\"References\",\"content\":\"\\u003col\\u003e\\u003cli\\u003e\\u003cspan\\u003eKhan MAB, Hashim MJ, King JK, Govender RD, Mustafa H, Al Kaabi J. Epidemiology of Type 2 Diabetes - Global Burden of Disease and Forecasted Trends. J Epidemiol global health. 2020;10(1):107\\u0026ndash;11.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eSaeedi P, Petersohn I, Salpea P, Malanda B, Karuranga S, Unwin N et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas. Diabetes research and clinical practice. 2019;157:107843.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eDeshpande AD, Harris-Hayes M, Schootman M. Epidemiology of diabetes and diabetes-related complications. Phys Ther. 2008;88(11):1254\\u0026ndash;64.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eMart\\u0026iacute;n-Tim\\u0026oacute;n I, Sevillano-Collantes C, Segura-Galindo A, del Ca\\u0026ntilde;izo-G\\u0026oacute;mez FJ. Type 2 diabetes and cardiovascular disease: have all risk factors the same strength? World J diabetes. 2014;5(4):444.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eJavanbakht M, Baradaran HR, Mashayekhi A, Haghdoost AA, Khamseh ME, Kharazmi E, et al. Cost-of-illness analysis of type 2 diabetes mellitus in Iran. PLoS ONE. 2011;6(10):e26864.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eLeite RGOF, Banzato LR, Galendi JSC, Mendes AL, Bolfi F, Veroniki AA, et al. Effectiveness of nonpharmacological strategies in the management of type 2 diabetes in primary care: a protocol for a systematic review and network meta-analysis. BMJ open. 2020;10(1):e034481.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eEvans JL, Bahng M-K. NON-PHARMACEUTICAL INTERVENTION OPTIONS FOR TYPE 2 DIABETES.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eRaimundo AF, F\\u0026eacute;lix F, Andrade R, Garcia-Conesa M-T, Gonzalez-Sarrias A, Gilsa-Lopes J, et al. Combined effect of interventions with pure or enriched mixtures of (poly) phenols and anti-diabetic medication in type 2 diabetes management: a meta-analysis of randomized controlled human trials. Eur J Nutr. 2020;59:1329\\u0026ndash;43.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eHaghighian MK, Rafraf M, Moghaddam A, Hemmati S, Jafarabadi MA, Gargari BP. Pomegranate (Punica granatum L.) peel hydro alcoholic extract ameliorates cardiovascular risk factors in obese women with dyslipidemia: A double blind, randomized, placebo controlled pilot study. Eur J Integr Med. 2016;8(5):676\\u0026ndash;82.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eNikooyeh B, Neyestani TR, Zahedirad M, Mohammadi M, Hosseini SH, Abdollahi Z, et al. Vitamin D-fortified bread is as effective as supplement in improving vitamin D status: a randomized clinical trial. J Clin Endocrinol Metabolism. 2016;101(6):2511\\u0026ndash;9.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eHeidari Z, Feizi A, Azadbakht L, Mohammadifard N, Maghroun M, Sarrafzadegan N. Usual energy and macronutrient intakes in a large sample of Iranian middle-aged and elderly populations. Nutr Dietetics. 2019;76(2):174\\u0026ndash;83.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eZare M, Goli AH, Karimifar M, Tarrahi MJ, Rezaei A, Amani R. Effect of bread fortification with pomegranate peel powder on glycemic indicators, antioxidant status, inflammation and mood in patients with type 2 diabetes: Study protocol for a randomized, triple-blind, and placebo-controlled trial. J Diabetes Metabolic Disorders. 2023;22(1):921\\u0026ndash;9.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eBennett JA. The consolidated standards of reporting trials (CONSORT): Guidelines for reporting randomized trials. Nurs Res. 2005;54(2):128\\u0026ndash;32.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eSayed-Ahmed E. Evaluation of pomegranate peel fortified pan bread on body weight loss. Int J Nutr food Sci. 2014;3(5):411\\u0026ndash;20.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eBadano JA, Braber NV, Rossi Y, Vergara LD, Bohl L, Porporatto C, et al. Physicochemical, in vitro antioxidant and cytotoxic properties of water-soluble chitosan-lactose derivatives. Carbohydr Polym. 2019;224:115158.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eHenry JD, Crawford JR. The short-form version of the Depression Anxiety Stress Scales (DASS‐21): Construct validity and normative data in a large non‐clinical sample. Br J Clin Psychol. 2005;44(2):227\\u0026ndash;39.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eSahebi A, Asghari MJ, Salari RS. Validation of depression anxiety and stress scale (DASS-21) for an Iranian population. 2005.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eAmiri M. Diabetes mellitus type 2; an international challenge. Ann Res Dial. 2016;1(1):e04.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eGarcia C, Feve B, Ferre P, Halimi S, Baizri H, Bordier L, et al. Diabetes and inflammation: fundamental aspects and clinical implications. Diabetes Metab. 2010;36(5):327\\u0026ndash;38.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eEren I, Erdi \\u0026Ouml;, Şahin M. The effect of depression on quality of life of patients with type II diabetes mellitus. Depress Anxiety. 2008;25(2):98\\u0026ndash;106.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eAkkuş \\u0026Ouml;\\u0026Ouml;, Metin U, \\u0026Ccedil;amlık Z. The effects of pomegranate peel added bread on anthropometric measurements, metabolic and oxidative parameters in individuals with type 2 diabetes: a double-blind, randomized, placebo-controlled study. Nutr Res Pract. 2023;17(4):698\\u0026ndash;716.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eGrabež M, Škrbić R, Stojiljković MP, Vučić VM, Grujić VR, Jakovljević V, et al. A prospective, randomized, double-blind, placebo-controlled trial of polyphenols on the outcomes of inflammatory factors and oxidative stress in patients with type 2 diabetes mellitus. Rev Cardiovasc Med. 2022;23(2):57.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eSohrab G, Nasrollahzadeh J, Zand H, Amiri Z, Tohidi M, Kimiagar M. Effects of pomegranate juice consumption on inflammatory markers in patients with type 2 diabetes: A randomized, placebo-controlled trial. J Res Med sciences: official J Isfahan Univ Med Sci. 2014;19(3):215.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eAbbaspoor Z, Amani A, Afshari P, Jafarirad S. The effect of education through mobile phone short message service on promoting self-care in prediabetic pregnant women: A randomized controlled trial. J Telemed Telecare. 2020;26(4):200\\u0026ndash;6.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eVitale M, Vaccaro O, Masulli M, Bonora E, Del Prato S, Giorda CB, et al. Polyphenol intake and cardiovascular risk factors in a population with type 2 diabetes: The TOSCA. IT study. Clin Nutr. 2017;36(6):1686\\u0026ndash;92.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eBagheri S, Khorramabadi RM, Assadollahi V, Khosravi P, Cheraghi Venol A, Veiskerami S, et al. The effects of pomegranate peel extract on the gene expressions of antioxidant enzymes in a rat model of alloxan-induced diabetes. Arch Physiol Biochem. 2023;129(4):870\\u0026ndash;8.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eJafari T, Fallah AA, Bahrami M, Lorigooini Z. Effects of pomegranate peel extract and vitamin E on oxidative stress and antioxidative capacity of hemodialysis patients: a randomized controlled clinical trial. J Funct Foods. 2020;72:104069.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eMahdavi AM, Javadivala Z. Systematic review of the effects of pomegranate (Punica granatum) on osteoarthritis. Health Promotion Perspect. 2021;11(4):411.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eSadeghi O, Sadeghian M, Rahmani S, Maleki V, Larijani B, Esmaillzadeh A. Whole-grain consumption does not affect obesity measures: an updated systematic review and meta-analysis of randomized clinical trials. Adv Nutr. 2020;11(2):280\\u0026ndash;92.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eBarghchi H, Milkarizi N, Dehnavi Z, Askari VR, Rajabzade F, Ostad AN et al. The Effects of pomegranate Peel Supplementation on Depression, Anxiety, and Stress Symptoms of Patients with Nonalcoholic Fatty Liver: A Randomized Clinical Trial. J Nutr Fasting Health. 2023;11(2).\\u003c/span\\u003e\\u003c/li\\u003e\\u003c/ol\\u003e\"},{\"header\":\"Tables\",\"content\":\"\\u003cp\\u003e\\u003cstrong\\u003eTable 1: Baseline characteristics of the study participants\\u003csup\\u003ea\\u003c/sup\\u003e.\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003ctable border=\\\"0\\\" cellspacing=\\\"0\\\" cellpadding=\\\"0\\\"\\u003e\\n \\u003ctbody\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 44.2308%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eVariable\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 22.1154%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eBread with PPP\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20.1923%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eControl\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 13.4615%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eP value\\u003csup\\u003eb\\u003c/sup\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 44.2308%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eSex\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 22.1154%;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20.1923%;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 13.4615%;\\\"\\u003e\\n \\u003cp\\u003e0.13\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 44.2308%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eFemale (%)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 22.1154%;\\\"\\u003e\\n \\u003cp\\u003e53.3 (24)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20.1923%;\\\"\\u003e\\n \\u003cp\\u003e68.9 (31)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 13.4615%;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 44.2308%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eAge\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 22.1154%;\\\"\\u003e\\n \\u003cp\\u003e51.88 \\u0026plusmn; 5.10\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20.1923%;\\\"\\u003e\\n \\u003cp\\u003e55.02 \\u0026plusmn; 4.97\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 13.4615%;\\\"\\u003e\\n \\u003cp\\u003e0.004\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 44.2308%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eBody weight (kg)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 22.1154%;\\\"\\u003e\\n \\u003cp\\u003e72.51 \\u0026plusmn; 8.41\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20.1923%;\\\"\\u003e\\n \\u003cp\\u003e69.29 \\u0026plusmn; 9.67\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 13.4615%;\\\"\\u003e\\n \\u003cp\\u003e0.09\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 44.2308%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eHbA\\u003csub\\u003e1\\u003c/sub\\u003eC (%)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 22.1154%;\\\"\\u003e\\n \\u003cp\\u003e6.51 \\u0026plusmn; 0.96\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20.1923%;\\\"\\u003e\\n \\u003cp\\u003e6.49 \\u0026plusmn; 0.97\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 13.4615%;\\\"\\u003e\\n \\u003cp\\u003e0.92\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 44.2308%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003ePhysical activity (MET/hour/day)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 22.1154%;\\\"\\u003e\\n \\u003cp\\u003e32.33 \\u0026plusmn; 4.48\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20.1923%;\\\"\\u003e\\n \\u003cp\\u003e32.55 \\u0026plusmn; 4.91\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 13.4615%;\\\"\\u003e\\n \\u003cp\\u003e0.84\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 44.2308%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eEducation level n (%)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 22.1154%;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20.1923%;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 13.4615%;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 44.2308%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eDiploma and university degree\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 22.1154%;\\\"\\u003e\\n \\u003cp\\u003e77.8 (35)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20.1923%;\\\"\\u003e\\n \\u003cp\\u003e80 (36)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 13.4615%;\\\"\\u003e\\n \\u003cp\\u003e0.79\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 44.2308%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eMedication use\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 22.1154%;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20.1923%;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 13.4615%;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 44.2308%;\\\"\\u003e\\n \\u003cp\\u003eAnti-diabetic (%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 22.1154%;\\\"\\u003e\\n \\u003cp\\u003e88.9 (40)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20.1923%;\\\"\\u003e\\n \\u003cp\\u003e77.8 (35)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 13.4615%;\\\"\\u003e\\n \\u003cp\\u003e0.16\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 44.2308%;\\\"\\u003e\\n \\u003cp\\u003eStatins (%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 22.1154%;\\\"\\u003e\\n \\u003cp\\u003e66.7 (30)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20.1923%;\\\"\\u003e\\n \\u003cp\\u003e60 (27)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 13.4615%;\\\"\\u003e\\n \\u003cp\\u003e0.51\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 44.2308%;\\\"\\u003e\\n \\u003cp\\u003eAnti-depressants (%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 22.1154%;\\\"\\u003e\\n \\u003cp\\u003e13.3 (6)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20.1923%;\\\"\\u003e\\n \\u003cp\\u003e4.4 (2)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 13.4615%;\\\"\\u003e\\n \\u003cp\\u003e0.26\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/tbody\\u003e\\n\\u003c/table\\u003e\\n\\u003cp\\u003e\\u003csup\\u003ea\\u003c/sup\\u003eValues are presented as\\u0026nbsp;the means \\u0026plusmn; SDs and percentages\\u0026nbsp;for quantitative and qualitative variables, respectively.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003csup\\u003eb\\u0026nbsp;\\u003c/sup\\u003eResults from the chi-square test for qualitative variables and the independent t test for quantitative variables.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eTable 2: Dietary\\u0026nbsp;\\u003c/strong\\u003e\\u003cstrong\\u003eintake\\u003c/strong\\u003e\\u003cstrong\\u003e\\u0026nbsp;at baseline and\\u0026nbsp;\\u003c/strong\\u003e\\u003cstrong\\u003eafter\\u0026nbsp;\\u003c/strong\\u003e\\u003cstrong\\u003e12 weeks of intervention\\u003csup\\u003ea\\u003c/sup\\u003e.\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003ctable border=\\\"0\\\" cellspacing=\\\"0\\\" cellpadding=\\\"0\\\" width=\\\"643\\\"\\u003e\\n \\u003ctbody\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 39.1913%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eNutrients\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eIntervention (n=45)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eControl (n=45)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 12.2862%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eP value\\u003csup\\u003eb\\u003c/sup\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 39.1913%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eEnergy (kcal/day)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 12.2862%;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 39.1913%;\\\"\\u003e\\n \\u003cp\\u003eWeek 0\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e1998.98 \\u0026plusmn; 468.98\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e1979.65 \\u0026plusmn; 444.51\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 12.2862%;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 39.1913%;\\\"\\u003e\\n \\u003cp\\u003eChange\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e-61.17.80 \\u0026plusmn; 383.92\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e-116.98 \\u0026plusmn; 318.76\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 12.2862%;\\\"\\u003e\\n \\u003cp\\u003e0.57\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 39.1913%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eCarbohydrate(g/day)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 12.2862%;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 39.1913%;\\\"\\u003e\\n \\u003cp\\u003eWeek 0\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e300.16 \\u0026plusmn; 79.44\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e306.15 \\u0026plusmn; 78.60\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 12.2862%;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 39.1913%;\\\"\\u003e\\n \\u003cp\\u003eChange\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e-10.59 \\u0026plusmn; 63.03\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e-21.15 \\u0026plusmn; 49.56\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 12.2862%;\\\"\\u003e\\n \\u003cp\\u003e0.50\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 39.1913%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eProtein(g/day)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 12.2862%;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 39.1913%;\\\"\\u003e\\n \\u003cp\\u003eWeek 0\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e69.39 \\u0026plusmn; 19.51\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e70.82 \\u0026plusmn; 14.97\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 12.2862%;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 39.1913%;\\\"\\u003e\\n \\u003cp\\u003eChange\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e-2.11 \\u0026plusmn; 21.70\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e-3.28 \\u0026plusmn; 16.73\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 12.2862%;\\\"\\u003e\\n \\u003cp\\u003e0.82\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 39.1913%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eFat (g/day)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 12.2862%;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 39.1913%;\\\"\\u003e\\n \\u003cp\\u003eWeek 0\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e62.26 \\u0026plusmn; 20.67\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e55.83 \\u0026plusmn;19.48\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 12.2862%;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 39.1913%;\\\"\\u003e\\n \\u003cp\\u003eChange\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e-1.87 \\u0026plusmn; 21.50\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e-2.00 \\u0026plusmn; 21.67\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 12.2862%;\\\"\\u003e\\n \\u003cp\\u003e0.98\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 39.1913%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eVitamin C (mg/d)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 12.2862%;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 39.1913%;\\\"\\u003e\\n \\u003cp\\u003eWeek 0\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e109.50 \\u0026plusmn;55.32\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e117.82 \\u0026plusmn; 65.58\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 12.2862%;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 39.1913%;\\\"\\u003e\\n \\u003cp\\u003eChange\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e9.86 \\u0026plusmn;84.54\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e-1.08 \\u0026plusmn; 70.23\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 12.2862%;\\\"\\u003e\\n \\u003cp\\u003e0.61\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 39.1913%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eVitamin E (mg/d)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 12.2862%;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 39.1913%;\\\"\\u003e\\n \\u003cp\\u003eWeek 0\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e20.97 \\u0026plusmn; 8.40\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e20.59 \\u0026plusmn; 11.66\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 12.2862%;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 39.1913%;\\\"\\u003e\\n \\u003cp\\u003eChange\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e-0.58 \\u0026plusmn; 11.53\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e-1.20 \\u0026plusmn; 13.78\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 12.2862%;\\\"\\u003e\\n \\u003cp\\u003e0.85\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 39.1913%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eSelenium (mcg/d)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 12.2862%;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 39.1913%;\\\"\\u003e\\n \\u003cp\\u003eWeek 0\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e0.08 \\u0026plusmn; 0.03\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e0.08 \\u0026plusmn; 0.03\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 12.2862%;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 39.1913%;\\\"\\u003e\\n \\u003cp\\u003eChange\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e0.00 \\u0026plusmn; 0.05\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e-0.00 \\u0026plusmn; 0.04\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 12.2862%;\\\"\\u003e\\n \\u003cp\\u003e0.60\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 39.1913%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eZinc (mg/d)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 12.2862%;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 39.1913%;\\\"\\u003e\\n \\u003cp\\u003eWeek 0\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e7.2 \\u0026plusmn; 2.3\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e6.98 \\u0026plusmn; 1.96\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 12.2862%;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 39.1913%;\\\"\\u003e\\n \\u003cp\\u003eChange\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e0.24 \\u0026plusmn; 2.93\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e0.11 \\u0026plusmn; 2.79\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 12.2862%;\\\"\\u003e\\n \\u003cp\\u003e0.87\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 39.1913%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eVit A(mcg/d)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 12.2862%;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 39.1913%;\\\"\\u003e\\n \\u003cp\\u003eWeek 0\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e983.58 \\u0026plusmn; 784.04\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e798.69 \\u0026plusmn; 454.00\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 12.2862%;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 39.1913%;\\\"\\u003e\\n \\u003cp\\u003eChange\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e-58.20 \\u0026plusmn;1169.33\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e-210.45 \\u0026plusmn; 920\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 12.2862%;\\\"\\u003e\\n \\u003cp\\u003e0.60\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 39.1913%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eBeta-carotene(mcg/d)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 12.2862%;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 39.1913%;\\\"\\u003e\\n \\u003cp\\u003eWeek 0\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e397.35 \\u0026plusmn; 716.74\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e275.25 \\u0026plusmn; 311.68\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 12.2862%;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 39.1913%;\\\"\\u003e\\n \\u003cp\\u003eChange\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e82.19 \\u0026plusmn; 648.73\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 24.2613%;\\\"\\u003e\\n \\u003cp\\u003e-61.23 \\u0026plusmn;362.13\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 12.2862%;\\\"\\u003e\\n \\u003cp\\u003e0.33\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/tbody\\u003e\\n\\u003c/table\\u003e\\n\\u003cp\\u003e\\u003csup\\u003ea\\u003c/sup\\u003eValues are reported as\\u0026nbsp;the\\u0026nbsp;mean \\u0026plusmn; SD\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003csup\\u003eb\\u003c/sup\\u003eObtained from independent t tests. \\u003cstrong\\u003e\\u003cbr\\u003e\\u0026nbsp;\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eTable 3:\\u0026nbsp;\\u003c/strong\\u003e\\u003cstrong\\u003eEffects\\u003c/strong\\u003e\\u003cstrong\\u003e\\u0026nbsp;of treatment with PPP on inflammation\\u003c/strong\\u003e\\u003cstrong\\u003e,\\u003c/strong\\u003e\\u003cstrong\\u003e\\u0026nbsp;oxidative stress markers and mood scores\\u003csup\\u003eͣa\\u003c/sup\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cdiv align=\\\"\\\"\\u003e\\n \\u003ctable border=\\\"0\\\" cellspacing=\\\"0\\\" cellpadding=\\\"0\\\" width=\\\"879\\\"\\u003e\\n \\u003ctbody\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 153px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eVariables\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd colspan=\\\"2\\\" valign=\\\"top\\\" style=\\\"width: 254px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eIntervention\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eP value\\u003csup\\u003eb\\u003c/sup\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd colspan=\\\"2\\\" valign=\\\"top\\\" style=\\\"width: 246px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eControl\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003ep value\\u003csup\\u003eb\\u003c/sup\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003ep value\\u003csup\\u003ec\\u003c/sup\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003ep value\\u003csup\\u003ed\\u003c/sup\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 153px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 123px;\\\"\\u003e\\n \\u003cp\\u003ePre\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 130px;\\\"\\u003e\\n \\u003cp\\u003ePost\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\n \\u003cp\\u003e\\u003csup\\u003e\\u0026nbsp;\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 132px;\\\"\\u003e\\n \\u003cp\\u003ePre\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 113px;\\\"\\u003e\\n \\u003cp\\u003ePost\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 153px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eHs-CRP (mg/dL)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 123px;\\\"\\u003e\\n \\u003cp\\u003e2.75 \\u0026plusmn; 1.56\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 130px;\\\"\\u003e\\n \\u003cp\\u003e2.19 \\u0026plusmn; 2.03\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\n \\u003cp\\u003e0.01\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 132px;\\\"\\u003e\\n \\u003cp\\u003e2.45 \\u0026plusmn; 1.38\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 113px;\\\"\\u003e\\n \\u003cp\\u003e1.64 \\u0026plusmn; 1.19\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026lt;0.001\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 153px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eChange\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd colspan=\\\"2\\\" valign=\\\"top\\\" style=\\\"width: 254px;\\\"\\u003e\\n \\u003cp\\u003e-0.56 \\u0026plusmn; 1.29\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd colspan=\\\"2\\\" valign=\\\"top\\\" style=\\\"width: 246px;\\\"\\u003e\\n \\u003cp\\u003e-0.81 \\u0026plusmn; 1.16\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\n \\u003cp\\u003e0.37\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\n \\u003cp\\u003e0.30\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 153px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eMDA (nmol/mL)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 123px;\\\"\\u003e\\n \\u003cp\\u003e232.51 \\u0026plusmn; 104.87\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 130px;\\\"\\u003e\\n \\u003cp\\u003e217.67 \\u0026plusmn; 70.47\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\n \\u003cp\\u003e0.447\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 132px;\\\"\\u003e\\n \\u003cp\\u003e236.09 \\u0026plusmn; 76.84\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 113px;\\\"\\u003e\\n \\u003cp\\u003e213.24 \\u0026plusmn; 53.03\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\n \\u003cp\\u003e0.07\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 153px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eChange\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd colspan=\\\"2\\\" valign=\\\"top\\\" style=\\\"width: 254px;\\\"\\u003e\\n \\u003cp\\u003e-14.84 \\u0026plusmn; 117.36\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd colspan=\\\"2\\\" valign=\\\"top\\\" style=\\\"width: 246px;\\\"\\u003e\\n \\u003cp\\u003e-22.85 \\u0026plusmn; 75.33\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\n \\u003cp\\u003e0.72\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\n \\u003cp\\u003e0.87\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 153px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eTAC (nmol/mL)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 123px;\\\"\\u003e\\n \\u003cp\\u003e1467.92 \\u0026plusmn; 309.77\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 130px;\\\"\\u003e\\n \\u003cp\\u003e1513.87 \\u0026plusmn; 395.99\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\n \\u003cp\\u003e0.34\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 132px;\\\"\\u003e\\n \\u003cp\\u003e1606.35 \\u0026plusmn; 303.60\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 113px;\\\"\\u003e\\n \\u003cp\\u003e1608.16 \\u0026plusmn;324.34\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\n \\u003cp\\u003e0.96\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 153px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eChange\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd colspan=\\\"2\\\" valign=\\\"top\\\" style=\\\"width: 254px;\\\"\\u003e\\n \\u003cp\\u003e45.94 \\u0026plusmn; 298.39\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd colspan=\\\"2\\\" valign=\\\"top\\\" style=\\\"width: 246px;\\\"\\u003e\\n \\u003cp\\u003e1.81 \\u0026plusmn; 274.49\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\n \\u003cp\\u003e0.50\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\n \\u003cp\\u003e0.49\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 153px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eDepression\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 123px;\\\"\\u003e\\n \\u003cp\\u003e6.66 \\u0026plusmn; 4.60\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 130px;\\\"\\u003e\\n \\u003cp\\u003e5.33 \\u0026plusmn; 4.36\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\n \\u003cp\\u003e0.04\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 132px;\\\"\\u003e\\n \\u003cp\\u003e5.89 \\u0026plusmn; 4.32\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 113px;\\\"\\u003e\\n \\u003cp\\u003e4.44 \\u0026plusmn; 4.28\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\n \\u003cp\\u003e0.01\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 153px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eChange\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd colspan=\\\"2\\\" valign=\\\"top\\\" style=\\\"width: 254px;\\\"\\u003e\\n \\u003cp\\u003e-1.33 \\u0026plusmn; 3.66\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd colspan=\\\"2\\\" valign=\\\"top\\\" style=\\\"width: 246px;\\\"\\u003e\\n \\u003cp\\u003e-1.44 \\u0026plusmn; 2.83\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\n \\u003cp\\u003e0.89\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\n \\u003cp\\u003e0.65\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 153px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eAnxiety\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 123px;\\\"\\u003e\\n \\u003cp\\u003e5.30 \\u0026plusmn; 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5.42\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd colspan=\\\"2\\\" valign=\\\"top\\\" style=\\\"width: 246px;\\\"\\u003e\\n \\u003cp\\u003e-0.27 \\u0026plusmn; 3.42\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\n \\u003cp\\u003e0.47\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\n \\u003cp\\u003e0.45\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/tbody\\u003e\\n \\u003c/table\\u003e\\n\\u003c/div\\u003e\\n\\u003cp\\u003e\\u003csup\\u003ea\\u003c/sup\\u003eVariables are expressed as\\u0026nbsp;the\\u0026nbsp;mean \\u0026plusmn; SE\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003csup\\u003eb\\u003c/sup\\u003eCalculated by\\u0026nbsp;paired-samples t\\u0026nbsp;test\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003csup\\u003ec\\u003c/sup\\u003eCalculated\\u0026nbsp;via an\\u0026nbsp;independent t\\u0026nbsp;test\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003csup\\u003ed\\u003c/sup\\u003eObtained from multivariable analysis of covariance (MANCOVA), adjusted for age, sex, and baseline weight.\\u003c/p\\u003e\\n\\u003cp\\u003eMDA: malondialdehyde; TAC: total antioxidant capacity; hs-CRP: high-sensitivity C-reactive protein\\u0026nbsp;\\u003c/p\\u003e\"}],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":true,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":false,\"hideJournal\":true,\"highlight\":\"\",\"institution\":\"\",\"isAcceptedByJournal\":false,\"isAuthorSuppliedPdf\":false,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":false,\"isPdf\":false,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true},\"keywords\":\"Pomegranate, Bread, Diabetes mellitus, Inflammation\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-5254735/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-5254735/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003cp\\u003e\\u003cstrong\\u003eBackground\\u003c/strong\\u003e: To assess the effects of bread fortified with pomegranate peel powder (PPP) on inflammation, oxidative stress, and mood indices in patients with type 2 diabetes mellitus (T2DM).\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eMethods\\u003c/strong\\u003e: In total, 90 T2DM patients were randomized to receive either bread fortified with 3.5% pomegranate peel powder (PPP) (n=45) or PPP-free bread for 12 weeks. Dietary intake throughout the trial was assessed via food records. Laboratory parameters, including total antioxidant capacity (TAC), malondialdehyde (MDA), high-sensitivity C-reactive protein (hs-CRP), and psychological disorders, including depression, anxiety, and stress, were assessed at the beginning and end of the study.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eResults:\\u003c/strong\\u003e 77 diabetic patients completed the trial (PPP group = 39 and control group = 38). Based on the compliance assessment, adherence to the interventions was high in the trial. We detected significant reductions in hs-CRP levels (intervention group: change = -0.56 ± 1.29, P=0.01; control group: change = -0.81± 1.16, p\\u0026lt;0.001) and depression scores (intervention group: change= -1.33 ± 3.66, P=0.04; control group): -1.44 ± 2.83, p=0.01). There was no significant difference between the groups. After adjusting for confounding factors, the significant effect within the group disappeared. Other variables, including MDA, TAC, anxiety, and stress, did not significantly change in the PPP-fortified bread group.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConclusion\\u003c/strong\\u003e: While intake of PPP-fortified bread for 12 weeks did not significantly affect oxidative stress, hs-CRP, or mental health in T2DM patients, some positive outcomes related to inflammatory and mood states should be explored.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eTrial registration Iranian Registry of Clinical Trials\\u003c/strong\\u003e: The trial was\\u003cstrong\\u003e \\u003c/strong\\u003eregistered in the Iranian Registry of Clinical Trials (available at \\u003ca href=\\\"http://www.irct.ir/\\\"\\u003ewww.irct.ir\\u003c/a\\u003e, with ID: IRCT20191209045672N1) on 21/09/2020.\\u003c/p\\u003e\",\"manuscriptTitle\":\"Effects of bread fortification with pomegranate peel powder on inflammation biomarkers, oxidative stress, and mood status in patients with type 2 diabetes: A randomized placebo-controlled trial\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2024-10-23 10:42:41\",\"doi\":\"10.21203/rs.3.rs-5254735/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true}}],\"origin\":\"\",\"ownerIdentity\":\"f906b96f-e7a4-4581-bfe8-849d6f45b737\",\"owner\":[],\"postedDate\":\"October 23rd, 2024\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"posted\",\"subjectAreas\":[],\"tags\":[],\"updatedAt\":\"2024-10-31T10:53:48+00:00\",\"versionOfRecord\":[],\"versionCreatedAt\":\"2024-10-23 10:42:41\",\"video\":\"\",\"vorDoi\":\"\",\"vorDoiUrl\":\"\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-5254735\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-5254735\",\"identity\":\"rs-5254735\",\"version\":[\"v1\"]},\"buildId\":\"qtupq5eGEP_6zYnWcrvyt\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}