bluuebunny/crossref_metadata_2025 huggingface dataset:
Nutritional Interventions in Primary Mitochondrial Disorders: Challenges and Barriers to the Use of Dietary Supplements
Authors: Avila Luisa Rios , Camp Kathryn , Krotoski Danuta , Kuszak Adam J. , Coates Paul M.
Published: November 2023

Dietary supplements have historically been used in the management of primary mitochondrial disorders (PMD) due to their potential benefits and perceived low risk, even though little evidence exists regarding their effectiveness. PMDs are rare and clinically, phenotypically, and genetically heterogeneous. Thus patient recruitment for randomized controlled trials (RCTs) has proven to be challenging. Only a few RCTs examining dietary supplements, singly or in combination with other vitamins and cofactors, are reported in the literature. Most of the evidence of efficacy comes from case reports or small open trials, which makes interpretation of the results difficult and often inconclusive. In December 2014 the Office of Dietary Supplements (ODS) at the National Institutes of Health (NIH) sponsored a workshop entitled “Nutritional Interventions in Primary Mitochondrial

Disorders

Developing an Evidence Base” (https://ods.od.nih.gov/News/Mito2014_ExecutiveSummary.aspx) with the goals of exploring the use of nutritional interventions in PMD and identify knowledge gaps regarding their safety and efficacy; identifying research opportunities; and forging collaborations among researchers, clinicians, patient advocacy groups, and federal partners. Co‐sponsors included NIH's National Center for Advancing Translational Sciences, Office of Rare Diseases Research, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the Wellcome Trust, and the United Mitochondrial Diseases Foundation. Attendees included researchers, health care professionals, representatives from advocacy organizations and industry, and government scientists and regulators. As a result of the workshop, working groups of experts were formed to address seven key areas identified as critical issues that need to move forward for the identification of safe and effective nutritional therapies for PMD. These areas were: 1) defining the disease, 2) clinical trial design, 3) biomarker selection, 4) mechanistic approaches, 5) challenges in using dietary supplements, 6) standards of clinical care, and 7) collaboration issues. As a short term action to address one of these areas, ODS is collaboratively developing fact sheets to provide patients and health professionals with critically evaluated information about the use of dietary supplements in PMD. These joint efforts demonstrate an effective model for fostering and enhancing collaborations among NIH and basic research, clinical, patient, pharmaceutical industry, and regulatory stakeholders in the mitochondrial disease community.
Substitution of glucose with whole eggs or egg whites during an oral glucose challenge mitigates impairments in postprandial vascular endothelial function by attenuating hyperglycemia‐mediated increases in lipid peroxidation
Authors: McDonald Joshua , Schill Kevin , Mah Eunice , Volek Jeff , Bruno Richard
Published: November 2023

Postprandial hyperglycemia (PPH) is a better predictor of CVD than fasting glucose, with evidence supporting that PPH transiently impairs vascular endothelial function (VEF) in an oxidative stress‐dependent manner. We hypothesized that co‐ingesting egg‐based meals with a glucose challenge would mitigate PPH‐mediated impairments in VEF by limiting lipid peroxidation. In a randomized, cross‐over study, prediabetic obese adults (n = 20; 31.9 ± 1.6 y; 105.0 ± 0.9 mg/dL; 31.1 ± 0.7 kg/m2) ingested isocaloric test meals (400 kcal) containing 100 g glucose (GLUCOSE), or 75 g glucose with 1.5 whole eggs (EGG), 7 egg whites (EGG‐W), or 2 egg yolks (EGG‐Y) prior to evaluating brachial artery flow‐mediated dilation (FMD, %) and plasma glucose and malondialdehyde (MDA) at 30 min intervals for 3 h. Change in FMD (ΔFMD%) during GLUCOSE was maximally lowered at 30 min, and improved at 60 min relative to 30 min, and was restored to levels no different from baseline at 90–180 min. This was accompanied by increases in plasma glucose that peaked at 30 min, and remained elevated through 120 min, until returning to concentrations not different from baseline at 150 min. MDA was higher at 30–120 min relative to baseline, and by 120 min it was significantly lower than peak (60 min) concentrations and not different from baseline concentrations. Regardless of egg‐based meal, ΔFMD% was lower at 30 min relative to baseline, but only ΔFMD% of EGG‐Y was reduced to the extent observed in GLUCOSE. At 60 min, ΔFMD% of EGG and EGG‐W were restored to levels not different from baseline, whereas GLUCOSE and EGG‐Y remained lower than baseline levels, and not different from ΔFMD% at 30 min. By 90 min, ΔFMD% of all treatments were not different from each other and were restored to levels not different from baseline with the exception that EGG‐Y remained lower through 180 min. Relative to GLUCOSE, ΔFMD% AUC0–3 h was increased to a similar extent in EGG and EGG‐W whereas EGG‐Y was not different from GLUCOSE and was lower than those of EGG and EGG‐W. Plasma glucose AUC0–3 h and ΔMDA AUC0–3 h were not different between GLUCOSE and EGG‐Y, but were similarly lower in EGG and EGG‐W compared with GLUCOSE and EGG‐Y. Collectively, replacing a portion of carbohydrate during a glucose challenge with whole eggs or egg whites, but not egg yolks, mitigates PPH‐mediated impairments in VEF by limiting glycemia and lipid peroxidation. Supported by the Egg Nutrition Center.

Support or Funding Information

Egg Nutrition Center
No Effect of Sugar Sweetened or Diet Beverages on Performance of a Battery of Cognitive Assessment Tests
Authors: Lowndes Joshua , Angelopoulos Theodore J , Rippe James M
Published: November 2023

Introduction

Dietary sugar has been alleged to contribute to the obesity epidemic. As a primary source of sugar in the American diet Sugar Sweetened Beverages (SSB) have been specifically targeted for caution. It has been argued that it is not just an issue of calories or metabolic products, but also sweetness of beverages as both SSB and diet beverages which may produce changes in cerebral activity and associated cognitive impairment under experimental conditions. However, few data exists on how typical consumption of these beverages may affect cognitive function.

Methods

For six months all participants followed the ADA Exchange Diet, individually tailored according to each participant's caloric needs. Participants were required to incorporate 2 servings (12oz) per day of a Sugar Sweetened Beverage (SSB) or Diet Beverage (Diet), both caffeine free. A third group who drank only water were also included as a control. Before and after the intervention participants were assessed on a battery of tests that measure a wide variety of cognitive functions (CANTAB). The tests used were: Spatial Working Memory (SWM), Intra‐Extra Dimensional Set Shift (IED), Stop Signal Task (SST), Delayed Matching to Sample (DMS), Paired Associates Learning (PAL), and Rapid Visual Information Processing (RVP). In additional participants also performed the Iowa Gambling Test (IGT). Data presented are means ± SD.

Results

None of the groups gained a significant amount of weight in the combined study population (161. ± 24 vs 162 ± 23.9 lbs, p=0.075), nor were there any differences among groups (interaction p=0.899). There was a decrease in the strategy score for SWM in the pooled study population (32.5 ± 5.7 vs 30.8 ± 6.5, p<0.05), yet this coincided with a decrease in SWM errors (26.0 ±20.2 vs 21.3 ± 16.0, p<0.01). RVP A’ also increased (0.90 ± 0.06 vs 0.92 ± 0.5, p<0.05). Diet showed a greater improvement in memory in PAL relative to the water group (respectively 19.9 ±3.9 vs 21.8 ± 2.8 and 21.9 ± 3.2 vs 20.0 ± 4.6, p<0.05). No other measures changed from pre to post intervention and none other than PAL Memory were affected by group assignment (p>0.05).

Conclusion

These data do not support the theory that regular consumption of sweet beverages, either SSB or diet, cause cognitive changes that have previously been associated with the development of obesity.

Support or Funding Information

Supported by an unrestricted grant from The Coca Cola Company
Associations between Long Chain Polyunsaturated Fatty Acids and Cardiovascular Risk Factors in Youth with Type 1 Diabetes: SEARCH Nutrition Ancillary Study
Authors: Couch Sarah Collins , Crandell Jamie , King Irena , Peairs Abigail , Shah Amy , Dolan Lawrence , Tooze Janet , Crume Tessa , Mayer‐Davis Elizabeth
Published: November 2023

There is ongoing debate regarding the optimal quantity and relative proportion of n‐3 and n‐6 polyunsaturated fatty acids (PUFAs) for cardiovascular benefits. This debate is clinically relevant to youth with type 1 diabetes who are prone to cardiovascular disease (CVD) and its complications. In this longitudinal study we explored the relationships between plasma n‐3 and n‐6 PUFAs and Δ5 and Δ6 desaturase activities (D5D and D6D, respectively) and fasting lipids in youth with type 1 diabetes. Incident cases of type 1 diabetes seen for a baseline exam (N=914) and at 1‐year (N=416) were included. Plasma phospholipid n‐6 PUFAs included linoleic acid (LA), dihomo‐γ‐linolenic acid (DGLA) and arachidonic acid (AA); n‐3 PUFAs included α‐linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). Estimated D5D and D6D were calculated as FA product‐to‐precursor ratios, where D5D= AA/DGLA and D6D = DGLA/LA. Models for individual PUFAs, D5D and D6D were adjusted for age, parental education, race, sex, clinic site, diabetes duration, insulin regimen, insulin dose/kg, HbA1c, insulin sensitivity score, and body mass index z‐score and included random effects to account for the repeated measurements. Favorable lipid associations were found between LA and low‐density lipoprotein (LDL) cholesterol (β= −0.58, P<0.05); AA, plasma triglycerides (TG) (β= −0.04, P<0.05) and TG/high‐density lipoprotein (HDL)‐C (β= −0.04, P<0.05); and D5D, plasma TG (β= −0.2, P<0.05) and TG/HDL‐cholesterol (β= −0.23, P<0.05). Findings were mixed for the n‐3 PUFAs and DGLA: ALA was positively associated with plasma TG (β= 0.33, P<0.05) and HDL cholesterol (β= 9.86, P<0.05); EPA was positively associated with total cholesterol (β= 8.17, P<0.05), LDL cholesterol (β=5.74, P<0.01) and HDL cholesterol (β= 2.27, P<0.01); and DGLA was positively associated with TG/HDL‐cholesterol (β= 0.05, P<0.05) These findings suggest a beneficial effect of the n‐6 PUFAs LA and AA on CVD lipid risk profile; mixed results for the n‐3 PUFAs add to the considerable controversy regarding these FAs in the prevention of CVD risk. Further research is needed to determine the mechanism by which PUFAs alter plasma lipids and whether the associations observed are related to long‐term health outcomes in youth with type 1 diabetes.

Support or Funding Information

Grant Support: SEARCH for Diabetes in Youth is funded by the Centers for Disease Control and Prevention (PA numbers 00097, DP‐05‐069, and DP‐10‐001) and supported by the National Institute of Diabetes and Digestive and Kidney Diseases.
Meta‐Analysis of Saturated Fatty Acid Intake and Breast Cancer Risk
Authors: Xia Hui , Sun Guiju , Wang Shaokang
Published: November 2023

Objective

The associations between saturated fatty acid (SFA) consumption and risk of breast cancer (BC) remains inconclusive. Therefore, we conducted this meta‐analysis to determine the quantitative relations between dietary SFA intake and incidence of BC.

Methods

Literatures published up to April 2015 were systematically screened through Pubmed and Web of Science. Relevant publication quality was evaluated by conducting the NOS (Newcastle‐Ottawa scale). We used fixed effects models or random effect models to calculate the summary RRs (relative risks) and ORs (odds ratios), and conducted sensitivity analyses and evaluated the publication bias.

Results

We identified a total of 52 studies (24 cohort studies and 28 case‐control studies), with over 50000 females diagnosed with BC. The associations between dietary SFA intake and risk of BC were 1.18 for case‐control studies (high vs low intake, 95% confidence interval (CI) = 1.03–1.34) and 1.04 for cohort studies (95% CI = 0.97–1.11). When restricted analyses to population‐based studies, positive associations were observed for both cohort (RR (95% CI) = 1.11 (1.01–1.21) and case‐control studies (OR (95% CI) = 1.26 (1.03–1.53)). Additionally, for case‐control studies, significant positive associations between higher SFA intake and BC risk were observed for Asian (OR (95% CI) = 1.17 (1.02–1.34) and Caucasian (OR (95% CI) = 1.19 (1.00–1.41)), as well as for postmenopausal women (OR= 1.33, 95% CI: 1.02–1.73). In contrast, higher dietary SFA intake was not associated with risk of BC among premenopausal women, in cohort studies or hospital‐based studies.

Conclusion

A positive association between higher dietary SFA intake and postmenopausal BC risk was observed in case‐control but not in cohort studies. More studies are warranted to confirm these findings.

Support or Funding Information

the National Natural Science Foundation (No. 81001244 and No. 81573144)
Impact of Meal Composition on Postprandial Lipid Responses in Overweight/Obese Participants
Authors: Franklin Brian , Adams‐Huet Beverley , Jaffery Manall , Mitchell Joel , Oliver Jonathan , Phillips Melody , Bouza Brooke , Dart Lyn , Shah Meena
Published: November 2023

The effect of high protein (HP) versus high monounsaturated fat (HMF) meals on postprandial lipid responses is unclear. Twenty‐four overweight/obese participants (12 males and 12 females; age: 38.7 ± 15.3 (mean ± standard deviation) years; BMI: 31.6 ± 4.0 kg/m2) were recruited for the study. Each participant was fed a HP (31.9% energy from protein) and HMF (35.2% energy from total fat and 20.7% energy from monounsaturated fat) meal, on different days, in a random order. The meals had similar energy and carbohydrate contents. Blood samples were drawn in the fasting and postprandial (30, 60, 120, and 180 min) states and assessed for triglycerides (TG), total cholesterol (TC), high‐density lipoprotein cholesterol (HDLC), non‐HDLC, and TC:HDLC ratio. Mixed model repeated measures analysis showed a significant meal composition by time interaction for TG (p = 0.002). The TG response (median (25th and 75th percentiles)) was significantly lower on the HP versus HMF meal at 120 min (HP: 138.0 (111.4, 192.8) mg/dL; HMF: 191.8 (156.3, 291.8) mg/dL; p = 0.001) and 180 min (HP: 158.3 (119.8, 217.1) mg/dL; HMF: 231.3 (161.9, 345.6) mg/dL; p = 0.002). No meal composition or meal composition by time effect (p ≥ 0.05) was seen for any of the other lipids. In conclusion, a HP meal resulted in a lower postprandial TG response compared to a HMF meal. No other lipids were affected.

Support or Funding Information

This study was funded by a TCU Invests in Scholarship grant.
Effects Of Low Calorie High‐Protein, And High‐Carbohydrate Breakfasts On Metabolic And Glycemic Responses And Food Perceptions In Overweight Women
Authors: Rao Manisha , Avalos Marco , Wildman Robert , DiMarco Nancy
Published: November 2023

BACKGROUND

High protein consumption, especially at breakfast, has been promoted to improve postprandial appetite constructs, resting energy expenditure (REE), glycemic responses and reduce calorie consumption at a subsequent meal.

PURPOSE

This study examined the acute effects of (a) a low calorie protein bar, (b) an isocaloric carbohydrate breakfast and (c) no breakfast on postprandial hunger, satiety, resting metabolic rate (RMR), plasma glucose and calorie intake at subsequent meal.

METHODS

Eleven overweight, but healthy, sedentary women (age 23.4 ± 5.0 y, body mass index 27.4 ± 1.54 kg/m2) completed the randomized repeated measures study. The study consisted of three single‐breakfast treatments: (a) 180–190 kcal protein breakfast (PRO: 15g protein, 21g carbohydrate, and 5g fat), (b) isocaloric carbohydrate breakfast (CHO: <1g protein, 36g carbohydrate, and 6g fat) and (c) breakfast skipper (SKP). Plasma glucose concentrations, RMR and self‐perceived hunger and satiety assessments were performed at baseline and repeated over a period of three hours after breakfast (30 min, 60 min, 120 min and 180 min). This was followed by a free‐choice ad libitum lunch to determine calorie consumption.

RESULTS

Repeated measures analysis of variance (ANOVA) showed no significant differences between the effects of time, treatment, and time X treatment interaction on postprandial plasma glucose concentration, and RMR (p>0.05). Changes between pre‐breakfast and pre‐lunch hunger scores for each of the treatments were not significantly different (p>0.05). Total area under curve (AUC) for glucose responses were statistically similar for both PRO and CHO (AUCPRO= 533.78 kcal/180 min vs AUCCHO= 561.29 kcal/180 min; p>0.05). The three treatments resulted in statistically insignificant differences in average calories consumed at lunches (PRO=469.09 ± 78.32 kcal vs CHO=499.49 ± 144.36 kcal vs SKP=568.68 ± 207.77 kcal). Treatment and time yielded significant main effects on fullness/satiety responses. The PRO, elicited a significantly greater satiety score than CHO (p<0.05). Satiety declined significantly by the 120‐ and 180‐min post‐breakfast, irrespective of the treatment (p<0.05).

CONCLUSIONS

High‐protein, energy‐restricted diets have been associated with several health benefits. Although not significantly different from the other breakfasts, the data trended toward improvements in hunger, RMR, glucose response and subsequent calorie intake and a notable increase in satiety following the consumption of a low‐calorie protein breakfast. It may be concluded that 15g of protein may not be sufficient to positively affect variables for the study population.

Support or Funding Information

Dymatize Enterprise LLC, Texas Woman's University Institute for Women's Health, and Texas Woman's University Office of Research and Sponsored Programs
Metabolic effects of exogenous ketone supplementation – an alternative or adjuvant to the ketogenic diet as a cancer therapy?
Authors: Poff Angela , Kesl Shannon , Ward Nathan , D'Agostino Dominic
Published: November 2023

Cancers exhibit an abnormal metabolism characterized by increased glucose consumption. Studies suggest that unlike healthy tissues, cancer cells are unable to efficiently utilize ketones for energy, a vulnerability exploited by a potential new therapy, the high fat low carbohydrate ketogenic diet (KD). To improve clinical feasibility, we developed a line of ketone supplements (KS) which induce nutritional ketosis in a dose‐dependent fashion regardless of dietary carbohydrate intake. We previously showed that KS inhibits proliferation and viability in vitro and are as effective as the KD in slowing tumor growth and prolonging survival in the VM‐M3 model of metastatic cancer. Thus, we sought to further characterize the metabolic effects, safety, and practicality of KS. Healthy rats were administered KS by oral gavage or in their food for 1–4 months. KS rapidly elevated blood ketones to therapeutic levels (2–5mM), and simultaneously decreased blood glucose by 20%. KS altered a number of metabolic pathways which may contribute to its anti‐cancer effects. Markers of both oxidative stress (oxidized glutathione) and antioxidant capacity (carnosine and anserine) were elevated by KS. Carnosine, which was nearly 4‐fold higher in KS‐treated rats, inhibits anaerobic glycolysis, slows tumor growth and metastasis, and increases survival in cancer models. Several (14) lysophospholipids, which are elevated in the blood of cancer patients and shown to induce tumorigenesis and metastasis in vivo, were decreased by KS. Inflammatory profiling revealed decreases in many pro‐inflammatory cytokines, including IL‐1β, IL‐6, IFN‐γ, MCP‐1, and RANTES. KS appears safe as there were no signs of toxicity or adverse changes in total cholesterol, HDL, LDL, triglycerides, or markers of liver/kidney function over the chronic treatment protocol. KS may be a useful alternative or adjuvant to the KD as a novel, potential cancer therapy.
A Clinical Study for the Effect of Kimchi Intake on Colon Health of Korean Young Adults
Authors: Park Kun‐Young , Kim Hee‐Young , Park Eui‐Sung , Shin Ji‐Hun
Published: November 2023

We evaluated effects of kimchi intake on colon health of Korean young adults. For this study, 28 participants (age range 18–36) were assigned to two groups, consumed 210 g/day of standardized kimchi (group S, n=14), or anti‐cancer kimchi (group A, n=14) for 28 days, respectively. All volunteers could take usual meal, except for antibiotics and probiotics. Serum, urine, and stool were taken from volunteers on the first and last (28th) days. We evaluated nutrient intake, anthropometric measurement, the levels of serum markers (total cholesterol (TC), triglyceride (TG), HDL‐c, LDL‐c, AST, ALT, ALP, insulin, leptin, adiponectin, interleukin‐6 (IL‐6), TNF‐α and hs‐CRP), and the fecal markers (pH, β‐glucosidase and β‐glucuronidase). Kimchi consumption decreased in body fat mass and percentage. In serum markers, kimchi intake decreased the levels of LDL‐c (p<0.05), and increased in HDL‐c (p<0.01) and adiponectin (p<0.05). Especially, group A significantly decreased in the levels of TC, TG, and IL‐6 (p<0.05). In fecal analysis, kimchi intake decreased pH level and activities of β‐glucosidase and β‐glucuronidase (p<0.01). In conclusion, intake of kimchi can improve serum cholesterols, adiponectin, and effectively decrease fecal pH and harmful enzymes of β‐glucosidase and β‐glucuronidase. Especially, anti‐cancer kimchi showed better effect on TC, TG, and pro‐inflammatory biomarkers (IL‐6 and hs‐CRP) reduction. Thus, kimchi intake can improve human colon health.
Microbial Correlates of Changes In Colon Prostaglandin E2 In Humans: Role Of Mucinophilic Bacteria
Authors: Chan Rena , Ren Jianwei , Sidahmed ElKhansa , Turgeon D. Kim , Ruffin Mack T. , Sen Ananda , Martens Eric , Djuric Zora
Published: November 2023

Prostaglandin E2 is a pro‐inflammatory mediator in the colon that is tightly linked with risk of colon cancer. We conducted a dietary intervention trial aimed at reducing colon prostaglandin E2 in subjects who had an increased risk of colon cancer. Subjects were randomized to a Healthy Eating or a Mediterranean diet for six months. Biopsies of the colon were obtained before and after dietary intervention, without prior preparation of the bowels. Two colon biopsies from each subject were analyzed for concentrations of eicosanoids, and an additional, nearby, biopsy was subjected to 16s sequencing to identify the bacterial taxa adhering to the mucin layer. Data was available for 85 subjects at baseline, and 67 subjects had complete data at both time points. There were few changes in eicosanoids and microbial taxa after dietary intervention. Since the diets were self‐selected and different individuals met their macronutrient dietary goals using different foods, we conducted correlative studies of prostaglandin E2 with adherent taxa at baseline as well as studies of changes over time. We focused on mucinophilic bacteria that can degrade both fiber and mucin. It has been previously demonstrated in many studies that Akkermansia mucinophilia is associated with beneficial, anti‐inflammatory effects on the host as well as protection from intestinal tumors in mice. At baseline, the relative abundance of Akkermansia mucinophilia and the abundance of total Verrucomicrobia taxa (Akkermansia and three other taxa) was negatively correlated with expression cyclooxygenases‐1 and 2 which catalyze synthesis of prostaglandin E2. The relative abundance of Verrucomicrobia and Akkermansia was also negatively correlated with serum cytokines, indicating a relationship with systemic inflammatory status (p<0.03). Change in prostaglandin E2 concentration over 6 months in the colon was significantly and negatively correlated with change in abundance of Akkermansia mucinophilia and Verrucomicrobia (p<0.02 in each case). The dietary factor that appeared to be most influential on changes in Akkermansia mucinophilia and Verrucomicrobia was total saturated fat intake, which was correlated negatively. Fiber intake notably had a weaker influence on the abundance of Akkermansia mucinophilia or Verrucomicrobia in the colon biopsies. These results show the potential influence of the bacterial populations adhering to the mucus layer of the colon on the inter‐individual variation in colonic epithelial prostaglandin E2.

Support or Funding Information

Supported by NIH grant CA120381, Cancer Biology Training Grant 5T32CA009676, and Cancer Center Support Grant P30 CA046592
Primary Prevention of Colorectal Cancer Incidence among Omani Adults Population
Authors: Waly Mostafa I , Padmanabhan Smitha , Ali Amanat , Al‐Farsi Yahaya M , AL‐Moundhri Mansour S
Published: November 2023

Background

Various Western studies have revealed that colorectal cancer (CRC) carcinogenesis is modifiable in accordance to certain dietary factors with potential anticancer properties. Little is known about the change in risk conferred by family history of CRC as a person ages. In Oman, the rate of CRC is increasing dramatically and there are no published reports about the dietary pattern and lifestyle characteristics of CRC among Omani adults.

Objective

The current study was attempted to identify different dietary factors that might synergize with sedentary life style in the etiology of CRC in individuals with a family history of the disease.

Methods

A cross sectional study included 124 healthy Omani individuals with a Family history of CRC. A detailed family history of CRC was obtained at enrollment, and the retrospective dietary intake of the study subjects was estimated using a semi‐quantitative food frequency questionnaire, and fasting blood samples were drawn to assess their serum levels of B‐vitamins (folate, vitamins B6 and B12), vitamin C, homocysteine (HCY), and oxidative stress markers including glutathione (GSH), malondialdehyde (MDA), and nitrites and nitrates (NN).

Results

Taking Omani adults population with family history with CRC as a high risk group; it was observed that they had a lower dietary intake of vitamin C and B‐vitamins as compared to the corresponding recommended dietary allowances. Biochemical analyses revealed depletion of GSH, and an elevation in the serum levels of HCY, MDA, and NN.

Conclusion

These results suggest that low intake of B‐vitamins and dietary antioxidants are involved in the etiology of hyperhomocysteinemia and oxidative stress, the typical risk factors for CRC. Clinical practice for subjects with a family history of CRC should be modified to align biochemical analyses with CRC testing.

Support or Funding Information

Internal Grant Funding (IG/AGR/FOOD/14/02), College of Agricultural and Marine Sciences, Sultan Qaboos University
High serum folate concentration increases the mortality risk in patients with stage 1–3 colorectal cancer: a follow‐up study
Authors: Huang Shih‐Chien , Huang Yi‐Chia , Chiang Feng‐Fan , Wang Hwei‐Ming
Published: November 2023

Although the possible dual role of serum folate in the development and progression of colorectal cancer (CRC) has been investigated, the association of serum folate with the survival risk of CRC is not clear. The purpose of this study was to assess the association of serum folate concentration with the mortality of CRC in patients with stage 1–3 CRC after curative tumor resection. This was a follow‐up study. Serum folate and plasma homocysteine concentrations of 137 patients with stage 1–3 CRC after curative tumor resection were measured at baseline and during a median follow‐up time of 1215 days till death (overall mortality) occurred or to the end of the study. Baseline plasma homocysteine concentration had no effect on the mortality of CRC, while high baseline serum folate concentration significantly increased the mortality of CRC after no adjustment or adjustment of potential confounders (hazard ratio, 1.03, 95% CI, 1.01 – 1.06). High serum folate concentration seems to have an adverse effect on patients with stage 1–3 CRC after curative tumor resection.

Support or Funding Information

This study was supported by the Ministry of Science and Technology, Taiwan (NSC 101‐2320‐B‐040‐016‐MY3 and MOST 104‐2320‐B‐040‐009‐MY3 and 104‐2320‐B‐040‐009‐MY3).
Diverse bioenergetic profiles of M1/M2 macrophages exposed to anthocyanins and their phenolic metabolites
Authors: Komarnytsky Slavko , Overall John , Wilson Mickey , Esposito Debora
Published: November 2023

Differentiation of monocytes occurs at the site of inflammation into the pro‐inflammatory (M1, glycolytic) or anti‐inflammatory (M2, oxidative) phenotype. Chronic disorders associated with low‐grade inflammatory responses are characterized by presence of pro‐inflammatory mediators that induce the recruitment and activation of predominantly M1 macrophages in the metabolically active tissues. In this study, we show that anthocyanin‐treated macrophages developed a distinct metabolic profile with respect to glycolysis versus oxidative phosphorylation, in part by increasing spare respiratory capacity and therefore shifting to mitochondria as their main source of ATP. Decreased glycolysis in anthocyanin‐treated macrophages was accompanied by decrease in 2‐NBDG deoxyglucose uptake and expression changes of Glut‐1, Hk‐1, and Hk‐2 proteins involved in transmembrane glucose transport. Different effects exerted by individual anthocyanins suggested that the presence of the methylated hydroxyls on the B ring might be critical for their greater biological activity. Numerous anthocyanin metabolites significantly reduced various cytokine and chemokine biomarkers of inflammation, with syringic and ferulic acids producing the greatest effects. Similar effects were observed in the murine gastrointestinal and mesenteric adipose tissues exposed to portal circulation. These data clearly indicate that exposure of macrophages to anthocyanins and their metabolites changes cellular bioenergetics in these cells and may be partially responsible for changes in their biological function in response to chronic metabolic stress.

Support or Funding Information

This work was supported in part by NCSU Research and Innovation grant 2012–2246 (SK); University Global Partnership Network (UGPN) grant 2015 (SK); Plants for Human Health Institute grant 429350–42567 (SK); and Cell Culture and Phenotyping Core of the Plants for Human Health Institute, NC State University.
Allelic Variations in the Gene for Glutathione Peroxidase‐1 Differentially Affect Cell Migration as well as the Levels of pAkT and E‐Cadherin
Authors: Ekoue Dede N , Bera Soumen , Ansong Emmanuel , Hart Peter , Verduzco Fernando Magdaleno , Bonini Marcelo , Diamond Alan M
Published: November 2023

Glutathione peroxidase‐1 (GPx‐1) has been implicated in the risk of several diseases, including cancer, by genetic data indicating associations between allelic variations in the GPx‐1 gene and risk of disease. Two common variations are the codon 198 polymorphism that results in either a leucine (L) or proline (P) and the number of alanine repeat codons in the 5′‐end of the coding sequence. The combination of these variations affects the distribution of GPx‐1 between the mitochondria and cytoplasm and we have previously shown that both sequence and cellular location have a profound impact on its GPx‐1 function. To elucidate whether these variations in the GPx‐1 gene affect levels of signaling proteins implicated in cancer, GPx‐1A5P and GPx‐1A7L allelic variants were ectopically expressed in GPx‐1 null MCF‐7 human breast cancer cells and the levels of the anti‐oxidant stress response regulator Nrf2, the cell adhesion protein E‐Cadherin, the cell signaling protein pAkt, the anti‐apoptotic protein Bcl‐2 and the mitochondrial deacetylase Sirt3 were examined. Expression of GPx‐1A5P resulted in a 3‐fold decrease in E‐Cadherin while, in contrast, a 2‐fold increase in pAkt was observed with GPx‐1A7L expression. The expression of either GPx‐1 allele resulted in decreased Bcl‐2 levels compared to that seen in MCF‐7 control cells. While the levels of Nrf2 and Sirt3 were unchanged, ectopically expressing Sirt3 in HEPG2 human hepatocellular carcinoma cells resulted in a 2‐fold increase in GPx activity, indicating that GPx‐1 compartmentalization is likely to affect its cellular activity by impacting its availability for Sirt3 deacetylation. To determine whether GPx‐1A5P and GPx‐1A7L genotypes differentially affect cell migration, a transwell migration assay was performed and GPx‐1A5P transfectants were more migratory when compared to GPx‐1A7L and MCF‐7 control cells. These data expand upon the previously reported differences in the consequences of the expression of distinct GPx‐1 alleles in this model system.

Support or Funding Information

This research was supported by the National Cancer Institute of the National Institutes of Health under Award Number R21CA182103 awarded to AMD and DNE.
Folate Intake and Plasma Folate Concentration in Korean Adults
Authors: Cho Youn‐Ok , Kim Young‐Nam , Hwang Ji Hyeon
Published: November 2023

The purposes of this study were to determine folate intakes and plasma folate concentration and to evaluate folate status of Korean adults. Two hundred fifty‐four healthy adults (68 men and 186 women), aged 20–64 years, were recruited in the Seoul and metropolitan area, Gumi, and Kwangju, South Korea, from 2009 to 2011. Three consecutive 24‐hour recalls, information on folate supplementation, and fasting blood samples were collected from the subjects. The dietary and total (dietary plus supplemental) folate intake was 522.79 μg DEF/day and 582.37 μg DEF/day respectively. Folate intake of men was significantly higher than the intake of women (p<0.01). Approximately 16% of the subjects consumed total folate less than the Estimated Average Requirement. Plasma folate concentration was 26.97 nmol/L. Plasma folate of women was significantly higher than that of men. Total folate intake was significantly positively correlated to plasma folate concentration (r=0.32866, p<0.0001). Only 6 % of the Korean adults had plasma folate less than 6.8 nmol/L indicating a folate deficiency. In conclusion, folate intakes of Korean adults were generally adequate with Korean Dietary Reference Intakes for folate. Folate status was also adequate based on plasma folate concentration.

Support or Funding Information

Supported by 2015 research fund of National Research Foundation of Korea (NRF‐2011‐0021273).
Acceptability of a Fortified Atole Among Guatemalan Children who Attend Six Casa Del Niño Day Care Centers, and the Effects on Linear Growth and Hemoglobin Status
Authors: Villanueva Lisa M. , Norton Sharon A , Palacios Ana M , Reinhart Gregory A
Published: November 2023

A corn and soy atole fortified with 21 vitamins and minerals, including higher levels of iron and zinc than other locally available options, has been provided to children from 6–84 months of age attending 6 Sociedad Protectora del Niño day care centers in Guatemala since August of 2013. Trained staff prepared and fed the children one serving consisting of 18.75g (~one tablespoon) of dry product mixed with 8 oz of water, brought to a boil and served as a warm beverage 5 days per week throughout the year. The objectives of this study were to assess the changes in mean height for age Z‐scores (HAZ) and hemoglobin (Hb) after 21 months of intervention, and to quantify the amount of atole consumed by the children on two different non‐consecutive days. Children were followed‐up for anthropometry and Hb every 6 months. To evaluate the amount of atole that children consumed, a waste study was performed in 3 randomly selected nurseries, on two non‐consecutive days, using graduated cylinders and food scales to measure the amount of atole prepared and not consumed. Multivariate mixed model analyses were performed to evaluate changes over time in Z‐scores and Hb. Mean Hb improved on average of 0.5g/dL throughout the intervention (t=11.43, df=1761.15, p<0.001). Mean HAZ improved significantly in those children with HAZ<‐2 SD at baseline, showing an average monthly increase of ~0.03 SD, (t=6.15, df=1324, p<0.001) over the course of the intervention. The waste study indicated that children consumed 98.5% of the served beverage/day. This micronutrient intervention is effective in improving Hb concentrations and a significant effect in the improvement in HAZ among stunted children was also noted. The product is highly acceptable to children, making this fortified atole a good alternative to address chronic undernutrition in similar institutions in Guatemala and other Central American countries where atole consumption is a common habit and practice.

Support or Funding Information

This program was sponsored by The Mathile Institute for the Advancement of Human Nutrition
CALCIUM NUTRITIONAL STATUS OF SCHOOL CHILDREN IN NORTHWEST MEXICO: DIET AND URINARY EXCRETION
Authors: GRIJALVA‐HARO MARIA ISABEL , Zazueta‐Valenzuela Maryan Kazandra , Vargas‐Tequida Bianca , Nieblas‐Almada Amparo , Gonzàlez‐Siqueiros Luis Enrique , Ponce Josè Antonio
Published: November 2023

Introduction

Calcium intake by schoolchildren is important for growth and bone mineralization, making it necessary to meet the recommended daily intake. Sonora diet includes low dietary calcium intake and components that could affect the calcium metabolism, as fiber and phytate, who prevents its absorption, and high consumption of sodium, phosphorus, caffeine, and protein, which increase calcium urinary losses.

Objective

The aim of this study was to evaluate the nutritional status of calcium in Hermosillo school children, based on calcium intake and urinary calcium excretion, and dietary factors associated with their metabolism.

Methods

Weight and height were measured. A calcium intake adapted food frequency questionnaire (CFCA‐Ca) was applied in 226 schoolchildren from 6 to 8 years old. Random urine samples were collected (one sample per child). Calcium and creatinine were determined by atomic absorption and Randox commercial kit respectively.

Results

It was found out that the average daily calcium intake is 836 mg, which covers the 800 mg recommended intake at this age. However, poor calcium intake in 52% of children was found, with an average of 656 mg Ca/d, as a high consumption of dietary components that interfere with calcium metabolism. Calcium excretion ranged from 0.12 to 11 mg/dL, and from 5.75 to 446 mg/dL for creatinine, obtaining an average ratio of Ca/Cr of 0.04, which is considered low. Two hypercalciuria cases were detected (Ca/Cr>0.21). Negative associations of urinary calcium excretion with fiber, phytates and sodium intake, as well as positive associations with animal and total protein intake was found. Inadequate calcium intake and high consumption of dietary factors that inhibit absorption, contribute to the deficiency of this nutrient in Hermosillo children, that to be consistent, this population would be prone to growth deficit, suffer rickets or osteoporosis future.
Comparison of Methods to Assess Consumption of Micronutrient Powders (MNP) Among Young Children in Nepal
Authors: Ngeno Bernadette , Perrine Cria , Subedi Giri , Mebrahtu Saba , Dahal Pradiumna , Jefferds Maria Elena
Published: November 2023

Background

Assessing micronutrient powder (MNP) consumption is a key component of monitoring program performance; there is no gold standard for assessing MNP consumption in publichealth program settings.

Objective

To compare estimates of MNP consumption among young children assessed by maternal reportversus observation of unopened MNP sachets in the household.

Methods

Cross‐sectional household cluster surveys representative of children 6–23 months were conductedto assess an integrated infant and young child feeding and MNP pilot project inNepal. Mothers were given sixty sachets of MNP and instructed to give the childone sachet daily. Consumption of MNP was assessed by asking the mother toreport number of MNP sachets consumed and by observation of unused MNP sachetsin the household. Mothers who reported the child consumed 60 sachets were stillasked to show any remaining sachets. If none were shown, 0 sachets wererecorded. Among mothers who received 60 MNP sachets ≥2 months beforethe assessment, 205 mothers reported that the child did not consume all MNPsachets received, but did not show the remaining MNP sachets. The remaining 605children had maternal report of MNP consumption and valid data for observationof unopened MNP sachets including zero. Directly observed difference (DOD) ofMNP consumption was calculated by subtracting the number of observed unopened sachets from 60 sachets. We assessed the median difference, Spearman correlation coefficient, end digit preference, and categories of consumption ofDOD and maternal report of use.

Results

Median MNP consumption was 51.0 sachets by DOD and 57.0 sachets by maternal report. Median difference between DOD and maternal report of MNP consumed was 6.0 sachets; the correlation coefficient was 0.91. Among mothers, 68% and 6% reported the number of consumed MNP sachets ending with 0 and 5, respectively, whereas by DOD, 70% and 4% ended with 0 and 5, respectively. When we excluded children whose consumption of MNP was 60 sachets by either method, 16.9% and 8% reported the number of consumed MNP sachets ending with 0 and 5, respectively, whereas by DOD, 14.2% and 6.1% ended with 0 and 5, respectively. With MNP consumption grouped into 0–14 sachets, 15–29 sachets, 30–44 sachets, and 45–60 sachets, the percent categorized into the same groupings by the DOD and maternal reported consumption was 100%, 80.6%, 80.7% and 91.2% respectively.

Conclusions

Had the observation of the unused sachets been used aloneto assess MNP consumption, it would not have been possible to assess intake ofMNP for approximately 20% of children who had received MNP. Estimates ofMNP consumption by DOD and maternal report were similar.
Calcium effect on gene expression of proteins involved on iron absorption by Caco 2 cells
Authors: Mejía Julián Herrera , Builes Wildeman Zapata , Charry Diego Alejandro Gaitán
Published: November 2023

Calcium is the only dietary factor that affects both non‐heme and heme iron absorption in humans. Mechanisms behind this effect are not elucidated. An hypothesis is that calcium may modify gene expression of proteins involved in iron absorption. An interesting experimental model for evaluating this effect is the human cell line Caco‐2, which is easy to use and produces results that strongly correlate with the absorption of iron in humans

Objective

To evaluate the effect of calcium on expression of proteins involved on both heme, and non‐hemeiron absorption by Caco‐2 cells.

Methodology

Caco‐2 cells were seeded by 1h in a 2 μM de iron solution (ferrous sulfate) and calcium (chloride); calcium: iron molar ratios 0:1 to 1000:1. Iron absorption was determined by ferritin method, and gene expression by qRT‐PCR. Changes in ferritin and gene expression were reported as increment respect to a control (calcium: iron molar ratio=0:1). Differences between experimental conditions were evaluated by a one‐way ANOVA test; p<0.05 was considered significant.

Results

Calcium does not affect iron absorption. Calcium increases genes involved in non‐heme iron uptake: DcytB (p=0.003), and DMT1 (p=0.016). Otherwise, calcium decreases genes involved in heme iron uptake: HCP1 (p=0.002), and HMOX‐1 (p=0.012). Expression of FPN gene (efflux protein for both heme, and non‐heme iron) decreased by calcium exposition (p<0.0001).

Conclusion

The calcium effect of calcium on expression of gene involved on heme, and non‐heme iron uptake is opposite. Nevertheless, it decreases FPN expression which is the only protein involved on two iron types efflux from the enterocytes. This effect may explained the negative effect of calcium on iron absorption previously described in humans.

Support or Funding Information

CODI, Universidad de Antioquia.

Corporación Vidarium, Centro de Investigación en Nutrición Salud y Bienestar.
Iron‐dependent Regulation of Cytoglobin in Neuro 2A Cells
Authors: Fiddler Joanna , Soh Traces , Davis McKale , Chowanadisai Winyoo , Clarke Stephen
Published: November 2023

Iron deficiency (ID) is estimated to affect one‐third of the world's population. As an essential micronutrient, iron is required for DNA synthesis, cellular proliferation, and oxygen transport. Iron is potentially toxic through its ability to promote the generation of ROS, thus cellular iron is tightly controlled. A family of iron‐regulated cytosolic RNA binding proteins known as iron regulatory proteins (IRP) play a central role in maintaining cellular iron homeostasis by repressing translation of ferritin and stabilizing transferrin receptor (Tfrc) mRNA under iron deficient conditions. Independent of iron status, reactive oxygen species (ROS) can also increase IRP1 RNA binding activity indicating the convergence of iron and O2 sensing through IRP. Hypoxia is associated with increased generation of ROS and oxidative stress. Like other members of the globin family of proteins, cytoglobin (Cygb) contains a heme prosthetic group that coordinates O2 binding. Cygb gene expression is rapidly induced with hypoxia and is postulated to play a role in O2 storage under these conditions. Cygb is ubiquitously expressed but appears to be enriched in neurons. The aim of the current study was to examine the iron‐ and O2‐dependent regulation of Cygb mRNA expression in Neuro 2A cells. Cells were treated with 100 μM desferrioxamine (DFO) or 1% hypoxia for 18 hours. Following treatments, total RNA was extracted and reverse‐transcribed. Quantitative real‐time PCR was used to examine mRNA expression of Cygb, Hif1α, and Tfrc. To confirm cytosolic iron depletion, IRP RNA binding activity was also determined. Following treatment, IRP1 binding increased ~2‐fold in response to DFO though with 1% hypoxia IRP1 binding decreased. DFO treatment increased Cygb and Tfrc expression by >2‐fold with no change in Hif1a expression. In contrast to iron chelation, hypoxia reduced Cygb expression by ~50% whereas the expression of Tfrc and Hif1a mRNA unchanged. These results demonstrate that iron and O2 status may regulate Cygb independently and suggests different mechanisms for the control of Cygb expression. Current studies are focused on examining the potential mechanisms of regulation of Cygb under iron‐depleted and/or hypoxic conditions and will provide additional insight into the coordination of iron and O2 signaling in cells.
Development of experimental colitis is associated with dysregulation of mineral homeostasis and fecal conditions in rats
Authors: Tsuneki Ikuya , Iwaya Hitoshi , Shimizu Hidehisa , Hara Hiroshi , Ishizuka Satoshi
Published: November 2023

Ulcerative colitis (UC) is chronic inflammation in large intestine and the development of colitis is considered to be related with dietary factors and microbial environment. UC patients often suffer from symptoms such as diarrhea, bloody stool, frequent defecation and body weight loss. Dextran sulfate sodium (DSS) is used to induce the UC‐like symtoms in experimental animals. To prevent colitis with dietary intervention, we investigated appropriate end point and/or markers in DSS‐treated conditions, espesially in an early phase of the diseaase development. Fischer 344/Jcl male rats (four weeks old) were fed an AIN‐93G‐based diet with or without 1% DSS treatment for 10 days. Mineral levels in aorta plasma were measured by inductively coupled plasma‐mass spectrometry. Changes in the number of feces and appearence were scored every day. Conditions of the colitis were evaluated by disease activity index (DAI) and inflammation‐related gene expressions. Development of DSS colitis was confirmed in DSS‐tretaed rats according to the DAI and upregulation of tnfa, il6, and mcp1 expression in the colonic mucosa. There was a strong correlation among DAI, plasma Ca concentration, and the number of feces. Multivariate analysis revealed that not only plasma Ca but also Fe and Zn are also predictors for DAI. The number of feces as well as plasma mineral concentrations might be useful marker to identify appropriate end point to evaluate the effect of dietary intervention in DSS colitis.