Nutrient-nutrient Interactions Research Articles

Nutrient-Nutrient Interactions Among Broccoli Glucosinolates and Their Implications for Breeding Cruciferous Crops to Enhance Human Health.

Broccoli (Brassica oleracea L. Italica group) is a widely consumed cruciferous vegetable valued for its gastrointestinal and immune health benefits. However, the individual contributions and interactions of broccoli glucosinolates, as they hydrolyze into bioactive isothiocyanates, remain poorly understood. This study investigated mixtures of four major aliphatic glucosinolates-glucoraphanin, gluconapin, progoitrin, and sinigrin-in individual and combinational models to assess their effects on human colorectal cell proliferation. Combination index analysis revealed moderate to strong antagonistic interactions among these glucosinolates, with the most significant antagonism observed during enzymatic hydrolysis by myrosinase. Mixture analysis identified an optimal glucosinolate ratio including glucoraphanin (81-84%), gluconapin (9-19%), and others (0-7%) to maximize their antiproliferative effects (adjusted R2 > 0.80). This optimal profile was achievable within the target broccoli mapping population. Testing the near-optimal VB067 isogenic broccoli line showed a 44% increase in antiproliferative activity compared to the initial breeding parent or an average sister line. This study highlights the potential of leveraging nutrient-nutrient interactions to guide molecular breeding and produce functional varieties of cruciferous vegetables with optimized health benefits.

Investigation of Potential Food Intake Biomarkers by LC-MS/MS: Suitability Under Conditions Close to Everyday Live.

Food intake biomarkers are proposed to be a more reliable tool for investigating the nutritional status compared to food diaries or food frequency questionnaires. Nevertheless, biomarkers have some disadvantages such as the influence of the individual lifestyle, different metabolism, nutrient-nutrient interaction or the specificity of the used biomarkers. To evaluate the suitability of several biomarkers, a study under conditions close to everyday life was conducted. Ten healthy volunteers were divided into three groups who followed different meal plans for 24h and collected their entire urine. Afterward, several potential biomarkers were quantified using an LC-MS/MS approach. To further investigate the suitability of those biomarkers, the results were investigated with the main goal of grouping the participants according to their provided diet, while the first author did not have any knowledge of the meal plans or other specific knowledge about the study design. The use of different biomarkers enables the evaluation of different eating habits without any prior wash out period or bigger than usual portion sizes. Especially long-term biomarkers seem to have a good suitability. Very high intakes and very low intakes are easier to distinguish than a moderate intake. Food intake biomarkers are proposed as a more reliable tool than food diaries or food frequency questionnaires. Nevertheless, data under realistic conditions are rarely available. In this study, ten volunteers were divided into three groups with different meal plans. An LC-MS/MS approach was performed and the data were further investigated with the main goal of grouping the participants according their provided diet, while the first author did not have any knowledge about the meal plans.

New aspects on nutraceutical formulations of whey protein concentrate sweetened with steviol glycosides for patients with non-communicable diseases

The current paper aimed to highlight new aspects of nutraceuticals with proven health benefits for patients with non-communicable diseases (NCDs). Four nutraceutical formulations were structured scientifically according to the Indian Standard (IS: 8220/1976) for “Specification for Protein-Rich Concentrated Nutrient Supplementary Foods”. High-quality milk derivatives with considerable protein content (10g protein/serving) rich in essential amino acids with valuable branched chain amino acids (BCAAs) reaching about 18% of total amino acids content and calcium content 325 mg/serving were included in whey protein concentrate (WPC) and skim milk powder (SMP). Zero-calorie artificial sweetener steviol glycosides (SGs) from a natural source (stevia leaf extract) were added with vitamins, minerals, and natural flavors. One of the new aspects is the valuable nutrient-nutrient interaction, as in the synergistic effect between WPC and SGs. Also, the presence of natural flavors (vanilla-cinnamon-coffee-raw cocoa) has great effects with their contents of bioactive components and antioxidants. Valuable applications of these nutraceuticals were discussed here to show their medicinal benefits with regular consumption by patients with NCDs and those with special food needs, such as in malnourished people, pregnant and lactating women, adolescents, and athletes to improve their physical activity, mentality, and overall performance summed up in the term of improving quality of life (QoL). Research design was carried out by applying evidence-based approaches. Well-structured scientific publications were examined thoroughly to collect updated information about using these nutraceuticals as adjuvant therapy in the treatment protocols for patients with NCDs.

Effectiveness of Mediterranean Diet on Diabetic Control and Cardiovascular Risk Modification Among Patients With Type 2 Diabetes Mellitus in Oman: A Study Protocol

Introduction: In the recent years, there is remarkable increased in the prevalence of Type 2 Diabetes Mellitus (T2DM) in Middle East countries including Oman. There is good evidence that Mediterranean Diet (MedDiet) is effective over diabetes control and several cardiovascular risk factors in different populations, with little compelling evidence among Omanis. This paper describes the protocol of a wait-list, open labelled, randomized control trial, with its main objective aimed to determine the effectiveness of Mediterranean Diet intervention on glycaemic control and cardiovascular risks among T2DM patients in Oman. Methods: A total of 140 eligible T2DM patients will be recruited. Participants in the intervention group will undergo a six-month MedDiet program comprising of different activities (individual dietary counseling, cooking classes, phone calls and social media messages) while the control group will continue with standard diabetes care. Data collection will be conducted at baseline, after three and six months. The 2 x 3 mixed-design ANOVA will be used to determine the mean changes in outcome variables over the full study period between the two groups. Discussion: Epidemiology studies on nutrition and health had focused on dietary pattern, which provides an opportunity to account for nutrient-nutrient interactions lately. Mediterranean Diet has produced consistent findings on its protective role in diabetes management, with little information on its effectiveness in population outside of Mediterranean basin, including Oman. The outcomes of current study will be used to inform community and health care professionals on the effectiveness and practically of MedDiet on diabetes management.

Nutrient Intake Patterns Predict Homeostatic Dysregulation in an Older Quebec Population

The geometric framework for nutrition has largely been applied to macronutrients in experimental settings. Here, we utilize the framework to examine both macro and micronutrient intake patterns in observational human data. We used nutritional intake patterns (3x 24h recall per visit) of 1754 older Quebecers from the NuAge cohort to predict multi-system homeostatic dysregulation scores calculated from 30 biomarkers. Intermediate intake of both macro- and micronutrients was generally associated with lower dysregulation scores (i.e., better health). Furthermore, there were often nutrient-nutrient interactions, such that the optimal level of one nutrient depends on the intake level of others. However, higher protein intake was generally associated with better health, and results varied substantially across different dysregulation systems. Accordingly, even though nutrition does have important effects on health trajectories during aging, it will be challenging to arrive at population-level recommendations to fine-tune nutrient intake patterns to optimize health beyond “everything in moderation.” Part of a symposium sponsored by the Nutrition Interest Group.

Recurrence quantification analysis to characterize cyclical components of environmental elemental exposures during fetal and postnatal development.

Environmental exposures to essential and toxic elements may alter health trajectories, depending on the timing, intensity, and mixture of exposures. In epidemiologic studies, these factors are typically analyzed as a function of elemental concentrations in biological matrices measured at one or more points in time. Such an approach, however, fails to account for the temporal cyclicity in the metabolism of environmental chemicals, which if perturbed may lead to adverse health outcomes. Here, we conceptualize and apply a non-linear method–recurrence quantification analysis (RQA)–to quantify cyclical components of prenatal and early postnatal exposure profiles for elements essential to normal development, including Zn, Mn, Mg, and Ca, and elements associated with deleterious health effects or narrow tolerance ranges, including Pb, As, and Cr. We found robust evidence of cyclical patterns in the metabolic profiles of nutrient elements, which we validated against randomized twin-surrogate time-series, and further found that nutrient dynamical properties differ from those of Cr, As, and Pb. Furthermore, we extended this approach to provide a novel method of quantifying dynamic interactions between two environmental exposures. To achieve this, we used cross-recurrence quantification analysis (CRQA), and found that elemental nutrient-nutrient interactions differed from those involving toxicants. These rhythmic regulatory interactions, which we characterize in two geographically distinct cohorts, have not previously been uncovered using traditional regression-based approaches, and may provide a critical unit of analysis for environmental and dietary exposures in epidemiological studies.

Plausible ergogenic effects of vitamin D on athletic performance and recovery.

The purpose of this review is to examine vitamin D in the context of sport nutrition and its potential role in optimizing athletic performance. Vitamin D receptors (VDR) and vitamin D response elements (VDREs) are located in almost every tissue within the human body including skeletal muscle. The hormonally-active form of vitamin D, 1,25-dihydroxyvitamin D, has been shown to play critical roles in the human body and regulates over 900 gene variants. Based on the literature presented, it is plausible that vitamin D levels above the normal reference range (up to 100 nmol/L) might increase skeletal muscle function, decrease recovery time from training, increase both force and power production, and increase testosterone production, each of which could potentiate athletic performance. Therefore, maintaining higher levels of vitamin D could prove beneficial for athletic performance. Despite this situation, large portions of athletic populations are vitamin D deficient. Currently, the research is inconclusive with regards to the optimal intake of vitamin D, the specific forms of vitamin D one should ingest, and the distinct nutrient-nutrient interactions of vitamin D with vitamin K that affect arterial calcification and hypervitaminosis. Furthermore, it is possible that dosages exceeding the recommendations for vitamin D (i.e. dosages up to 4000-5000 IU/day), in combination with 50 to 1000 mcg/day of vitamin K1 and K2 could aid athletic performance. This review will investigate these topics, and specifically their relevance to athletic performance.

American society for parenteral and enteral nutrition (a.s.p.e.N.) standards of practice for nutrition support pharmacists.

American society for parenteral and enteral nutrition (a.s.p.e.N.) standards of practice for nutrition support pharmacists.

Exploring mechanisms of diet-colon cancer associations through candidate molecular interaction networks.

BackgroundEpidemiological studies in the recent years have investigated the relationship between dietary habits and disease risk demonstrating that diet has a direct effect on public health. Especially plant-based diets -fruits, vegetables and herbs- are known as a source of molecules with pharmacological properties for treatment of several malignancies. Unquestionably, for developing specific intervention strategies to reduce cancer risk there is a need for a more extensive and holistic examination of the dietary components for exploring the mechanisms of action and understanding the nutrient-nutrient interactions. Here, we used colon cancer as a proof-of-concept for understanding key regulatory sites of diet on the disease pathway.ResultsWe started from a unique vantage point by having a database of 158 plants positively associated to colon cancer reduction and their molecular composition (~3,500 unique compounds). We generated a comprehensive picture of the interaction profile of these edible and non-edible plants with a predefined candidate colon cancer target space consisting of ~1,900 proteins. This knowledge allowed us to study systematically the key components in colon cancer that are targeted synergistically by phytochemicals and identify statistically significant and highly correlated protein networks that could be perturbed by dietary habits.ConclusionWe propose here a framework for interrogating the critical targets in colon cancer processes and identifying plant-based dietary interventions as important modifiers using a systems chemical biology approach. Our methodology for better delineating prevention of colon cancer by nutritional interventions relies heavily on the availability of information about the small molecule constituents of our diet and it can be expanded to any other disease class that previous evidence has linked to lifestyle.

Nutrition in pelvic radiation disease and inflammatory bowel disease: similarities and differences.

Due to the intestinal inflammation, tissue damage, and painful abdominal symptoms restricting dietary intake associated with both diseases, patients with intestinal pelvic radiation disease (PRD) or inflammatory bowel disease (IBD) are at increased risk to develop protein calorie malnutrition and micronutrient deficiencies. In the current paper, we review the nutritional management of both diseases, listing the similar approaches of nutritional management and the nutritional implications of intestinal dysfunction of both diseases. Malnutrition is prevalent in patients with either disease and nutritional risk screening and assessment of nutritional status are required for designing the proper nutritional intervention plan. This plan may include dietary management, oral nutritional supplementation, and enteral and/or parenteral nutrition. In addition to managing malnutrition, nutrients exert immune modulating effects during periods of intestinal inflammation and can play a role in mitigating the risks associated with the disease activity. Consistently, exclusive enteral feeding is recommended for inducing remission in pediatric patients with active Crohn's disease, with less clear guidelines on use in patients with ulcerative colitis. The field of immune modulating nutrition is an evolving science that takes into consideration the specific mechanism of action of nutrients, nutrient-nutrient interaction, and preexisting nutritional status of the patients.

Home fortification with calcium reduces Hb response to iron among anaemic Bangladeshi infants consuming a new multi-micronutrient powder formulation.

To investigate whether the recommended dietary intake of Ca in anaemic infants compromises the expected Hb response, via home fortification with a new Ca- and Fe-containing Sprinkles™ micronutrient powder (MNP). A double-blind, randomized controlled, 2-month trial was conducted in Bangladesh. Infants were randomized to one of two MNP intervention groups containing Fe and other micronutrients, with or without Ca. Hb, anthropometrics and dietary intake were measured pre- and post-intervention while family demographics were collected at baseline. Twenty-six rural villages in the Kaliganj sub-district of Gazipur, Bangladesh. One hundred infants aged 6-11 months. A significant increase in Hb (MNP, 13·3 (sd 12·6) g/l v. Ca-MNP, 7·6 (sd 11·6) g/l; P < 0·0001) was noted in infants from both groups. However, infants receiving MNP without Ca had a significantly higher end-point Hb concentration (P = 0·024) and rate of anaemia recovery (P = 0·008). Infants receiving MNP with Ca were more likely to remain anaemic (OR 3·2; 95 % CI 1·4, 7·5). Groups did not differ in dietary intake or demographic and anthropometric indicators. Although both groups showed significant improvement in Hb status, the nutrient-nutrient interaction between Fe and Ca may have diminished the Hb response in infants receiving the Ca-containing MNP.

Vitamin C-related nutrient–nutrient and nutrient–gene interactions that modify folate status

Folate-related nutrient-nutrient and nutrient-gene interactions modify disease risk; we therefore examined synergistic relationships between dietary folic acid, vitamin C and variant folate genes with respect to red cell folate status. Two hundred and twelve subjects were examined using chemiluminescent immunoassay, PCR and food frequency questionnaire to determine red cell and serum folate, 14 folate gene polymorphisms, dietary folate (natural and synthetic) and vitamin C. When examined independently, synthetic PteGlu correlates best with red cell folate at higher levels of intake (p = 0.0102), while natural 5CH(3)-H(4)-PteGlu(n) correlates best with red cell folate at lower levels of intake (p = 0.0035). However, dietary vitamin C and 5CH(3)-H(4)-PteGlu(n) interact synergistically to correlate with red cell folate at higher levels of intake (p = 0.0005). No interaction between dietary vitamin C and PteGlu was observed. This 'natural' nutrient-nutrient interaction may provide an alternative to synthetic PteGlu supplementation that is now linked to adverse phenomena/health outcomes. On its own, vitamin C also correlates with red cell folate (p = 0.0150) and is strongly influenced by genetic variation in TS, MTHFR and MSR, genes critical for DNA and methionine biosynthesis that underpin erythropoiesis. Similarly, dietary vitamin C and 5CH(3)-H(4)-PteGlu(n) act synergistically to modify red cell folate status according to variation in folate genes: of note, heterozygosity for 2R3R-TS (p = 0.0181), SHMT (p = 0.0046) and all three MTHFR SNPs (p = 0.0023, 0.0015 and 0.0239 for G1793A, C677T and A1298C variants, respectively) promote a significant association with red cell folate. Again, all these genes are critical for nucleic acid biosynthesis. Folate variants with the strongest independent effect on folate status were C677T-MTHFR (p = 0.0004) and G1793A-MTHFR (p = 0.0173). 5CH(3)-H(4)-PteGlu(n) assimilation and variant folate gene expression products may be critically dependent on dietary vitamin C.

A single dose of c9,t11 or t10,c12 conjugated linoleic acid isomers perturbs vitamin A metabolism in mice

Conjugated linoleic acid (CLA) is a polyunsaturated fatty acid that has numerous biologic activities. Previous studies in rodents demonstrated that chronic intake of CLA t10,c12 or CLA c9,t11 isomers perturbs the metabolism of retinoids (vitamin A and its derivatives). Specifically, although both isomers increased liver retinoid levels, only CLA t10,c12 also stimulated hepatic retinol secretion into the bloodstream. Given that retinoid homeostasis in mammalian serum and tissues is crucial to maintain health, it is important to gain more insights into the mode of action of this nutrient-nutrient interaction. Here we hypothesized that an acute administration of either CLA isomer may also influence vitamin A metabolism. By gavaging wild-type and retinol-binding protein knockout mice with an oral bolus of radiolabeled retinol containing 1 of these 2 isomers, we showed that both CLA t10,c12 and CLA c9,t11 rapidly enhance hepatic uptake of dietary vitamin A and its resecretion from the liver in the form of retinol bound to retinol-binding protein. Indeed, in mice lacking this protein, the sole specific carrier for retinol in the circulation, this latter effect was blunted. In addition, by using a pharmacologic inhibitor of the clearance of chylomicrons, which distribute recently ingested vitamin A and lipids throughout the body, we provided evidence that CLA intake might rapidly enhance intestinal absorption of dietary vitamin A. These data demonstrate the existence of multiple levels of interaction between dietary CLA and retinoid metabolism and warrant further studies to understand the molecular mechanisms underlying these effects and their implications for human health.

TAS2R38 bitter taste genetics, dietary vitamin C, and both natural and synthetic dietary folic acid predict folate status, a key micronutrient in the pathoaetiology of adenomatous polyps

Taste perception may influence dietary preferences and nutrient intakes contributing to diet-related disease susceptibility. This study examined bitter taste genetics and whether variation in the TAS2R38 gene at three polymorphic loci (A49P, V262A and I296V) could alter dietary and systemic folate levels and dietary vitamin C intake, and whether a nutrigenetic circuit existed that might link bitter taste, folate/antioxidant status and risk for a colonic adenomatous polyp. TAS2R38 diplotype predicted bitter taste (PROP) phenotype (p value <0.00001) and red cell folate status (p=0.0179) consistent with the diplotype that has the broadest range of bitter perception (AVI/PAV) also possessing the highest average red cell folate value. However, TAS2R38 diplotype did not predict dietary intake of methylfolic acid, pteroylmonoglutamic acid or total folic acid. Neither did it predict dietary intake of vitamin C. Despite this, intake of dietary folate predicts red cell folate with analysis pointing to a key nutrient-nutrient interaction between vitamin C intake and systemic folate status. Analysis of 38 patients with an adenomatous polyp and 164 controls showed that individually, dietary nutrient intake, nutrient status and taste diplotype did not influence polyp risk. However, red cell folate status (in individuals below the population median value) did interact with bitter taste diplotype (AVI/PAV) to predict polyp risk (p=0.0145). Furthermore, synthetic folic acid (below median intake) was statistically associated with adenoma occurrence (p=0.0215); individuals with adenomatous polyps had a 1.77× higher intake than controls. Additionally, stepwise regression taking account of all dietary nutrients showed a tight relationship between methylfolic acid (but not pteroylmonoglutamic acid) intake and red cell folate level in those with a low folate status and occurrence of an adenomatous polyp (p=0.0039). These findings point to a role for folate in the pathoaetiology of adenomatous polyps, with the natural and synthetic vitamers not necessarily having the same biological effect.

California Hass Avocado: Profiling of Carotenoids, Tocopherol, Fatty Acid, and Fat Content during Maturation and from Different Growing Areas

The California Hass avocado ( Persea americana ) is an example of a domesticated berry fruit that matures on the tree during its growing season but ripens only after being harvested. Avocados are typically harvested multiple times during the growing season in California. Previous research has demonstrated potential health benefits of avocados and extracts of avocado against inflammation and cancer cell growth, but seasonal variations in the phytochemical profile of the fruits being studied may affect the results obtained in future research. Therefore, in the present study, avocados were harvested in January, April, July, and September, 2008, from four different growing locations in California (San Luis Obispo, Ventura, Riverside, and San Diego) and analyzed for total fat content, fatty acid profile, carotenoids, and vitamin E. A significant increase in total carotenoid and fat content of avocados from all regions was noted as the season progressed from January to September. Four carotenoids not previously described in the avocado were quantified. The total content of carotenoids was highly correlated with the total fat content (r = 0.99, p < 0.001) demonstrating a remarkable degree of constancy of carotenoid intake per gram of fat content in the California Hass avocado. Future clinical research on the health benefits of the avocado should specify the time of harvest, degree of ripening, growing area, and the total phytochemical profile of the fruit or extract being studied. These steps will enable researchers to account for potential nutrient-nutrient interactions that might affect the research outcomes.

Multiple micronutrient supplements will not reduce incidence of low birthweight

Multiple micronutrient supplements will not reduce incidence of low birthweight

Vitamin D and cancer: current dilemmas and future research needs

A diversity of scientific literature supports a role for vitamin D in decreasing colorectal cancer incidence, but the available evidence provides only limited support for an inverse association between vitamin D status and the risk of other types of cancer. We need additional studies analyzing the dose-response relation between vitamin D status and cancer risk, the optimal level of 25-hydroxyvitamin D, the length of time required to observe an effect, and the time period of life when exposure is most relevant. Studies of vitamin D receptor polymorphisms have found that not all polymorphisms have the same association with cancer, and the cancer site could further dictate which polymorphisms might be most important; this indicates a need for more research on gene-environment interactions. Several dietary components and the balance between energy intake and expenditure influence vitamin D metabolism. These studies show that scientists need to identify confounders and modifiers of the biological response to vitamin D, including dietary factors, lifestyle factors such as exercise, and race or ethnicity. Transgenic and knockout animals are powerful tools for identifying the molecular targets of bioactive food components. Scientists should therefore make increased use of these models to identify molecular targets for vitamin D. Many research gaps relate to the need to develop predictive, validated, and sensitive biomarkers, including biomarkers that researchers can use to reliably evaluate intake or exposure to vitamin D, assess one or more specific biological effects that are linked to cancer, and effectively predict individual susceptibility as a function of nutrient-nutrient interactions and genetics.

Standards of Practice for Nutrition Support Pharmacists

of their professional time to nutrition support activities. These activities may include direct patient care, research relevant to nutrition support therapy, teaching, and administrative responsibilities. These standards are not intended for the pharmacist who occasionally provides nutrition support to patients, but rather to those who by virtue of education, training, experience, and personal interest wish to be identified as an NSP and provide expertise in collaboration with other healthcare professionals.

Retinoic Acid Modulates Hepatic Iron Homeostasis in Rats by Attenuating the RNA-Binding Activity of Iron Regulatory Proteins ,

Vitamin A deficiency has been widely associated with perturbations of iron homeostasis, a consequence that can be reversed by retinoid supplementation. Despite the numerous studies that demonstrate an interaction between these 2 nutrients, the mechanistic basis for this relation has not been well characterized. Because iron regulatory proteins (IRP) have been established as central regulators of iron homeostasis, we investigated the potential role of IRP in the regulation of iron homeostasis under conditions of vitamin A deficiency and supplementation with all-trans-retinoic acid (atRA). Rats were fed a control diet or a diet deficient in either vitamin A or iron or both micronutrients. Four parallel groups of rats were supplemented with atRA daily (30 μmol/kg body weight) during the final week of this study. As expected, iron-deficient (−Fe) rats exhibited a decrease in hepatic nonheme iron levels and a subsequent increase in IRP RNA-binding activity, resulting in diminished ferritin abundance. Interestingly, atRA supplementation inhibited the increase in IRP RNA-binding activity in −Fe rats to a level that was not significantly (P = 0.139) different from control values, and it partially restored ferritin abundance. This inhibition of IRP RNA-binding activity by atRA supplementation was also associated with a 40% reduction in transferrin receptor abundance. Taken together, these results indicate that IRP represent a mechanistic link between vitamin A and the regulation of iron homeostasis, a key finding toward further understanding this important nutrient-nutrient interaction.

Biomarkers for diet and cancer prevention research: potentials and challenges

As cancer incidence is projected to increase for decades there is a need for effective preventive strategies. Fortunately, evidence continues to mount that altering dietary habits is an effective and cost-efficient approach for reducing cancer risk and for modifying the biological behavior of tumors. Predictive, validated and sensitive biomarkers, including those that reliably evaluate "intake" or exposure to a specific food or bioactive component, that assess one or more specific biological "effects" that are linked to cancer, and that effectively predict individual "susceptibility" as a function of nutrient-nutrient interactions and genetics, are fundamental to evaluating who will benefit most from dietary interventions. These biomarkers must be readily accessible, easily and reliably assayed, and predictive of a key process(es) involved in cancer. The response to a food is determined not only by the effective concentration of the bioactive food component(s) reaching the target tissue, but also by the amount of the target requiring modification. Thus, this threshold response to foods and their components will vary from individual to individual. The key to understanding a personalized response is a greater knowledge of nutrigenomics, proteomics and metabolomics.