Micronutrient interrelationships: Synergism and antagonism
Abstract
Appropriate physiological functioning requires optimal nutrition, which needs to be in balance to prevent potential detrimental interactions, especially when administered at pharmacological dosages. Many nutrients function in harmony to complement digestive function and assimilation. Some may hinder these processes and compete for uptake, while others may also be required in tandem to assist in metabolism which may ultimately affect a number biochemical cycles.Many similar synergistic and antagonistic functions exist within human physiology and should be considered, particularly in the health and research arenas, where positive outcomes may be more likely if nutrient preparations are formulated with assistant supplementary nutrients, while nutrient related confounders need also to be accounted for. A variety of these are discussed in detail, with emphasis on relationships in health and disease.
... This indicates that the smallest dose of Cu, including the more readily absorbed form, Cu-NPs, decreased Cu and Zn antagonism in gastrointestinal absorption, as noted in other experiments (Adegbenjo et al. 2014;Ognik et al., 2016). In the case of Fe, digestibility coefficients were higher at the lowest dietary addition of Cu, which corroborates the findings of other authors (Linder and Hazegh-Azam, 1996;Schoendorfer and Davies, 2012), indicating that Cu and Fe compete for transport and bioavailability. ...
... However, a different relationship has also been reported: Cu deficiency reduces Fe absorption, which is linked to intestinal Fe transport being Cu-dependent (Schoendorfer and Davies 2012). ...
It was hypothesized that dietary copper (Cu) nanoparticles, as a substitute for the commonly used copper sulfate, could contribute to lowering the dietary inclusion levels of Cu without compromising growth performance or reducing Cu digestibility and utilization in turkeys. An experiment was carried out on 648 one-day-old Hybrid Converter turkeys divided into 6 groups with 6 replicates per group in a two-factorial design with 3 dietary inclusion levels of Cu (20, 10 and 2 mg kg ⁻¹ ) and 2 dietary sources of Cu, copper sulfate and Cu nanoparticles (Cu-SUL and Cu-NPs, respectively). The apparent digestibility coefficients of minerals were determined after 6 weeks, and tissue samples were collected after 14 weeks of experimental feeding. A decrease in the dietary inclusion levels of Cu from 20 to 10 and 2 mg kg ⁻¹ did not reduce the body weights of turkeys at 42 and 98 days of age. In comparison with the remaining treatments, the lowest dietary inclusion level of Cu significantly decreased MDA concentrations in small intestinal tissue (P=0.002) and in the bursa of Fabricius (P=0.001). The replacement of Cu-SUL with Cu-NPs differentially modulated the redox status of selected tissues, i.e., enhanced SOD activity in small intestinal tissue (P=0.001) and decreased total glutathione levels in the bursa of Fabricius (P=0.005). In general, neither the different levels nor sources of additional dietary Cu (main factors) exerted negative effects on the histological structure of the duodenum and jejunum in turkeys. The intestinal digestibility of Cu increased with decreasing dietary Cu levels, and as a consequence, the highest apparent digestibility coefficient of Cu (and zinc) was noted in turkeys fed diets with the addition of 2 mg kg ⁻¹ Cu-NPs. Therefore, the environmental burden of excreted Cu was substantially reduced along with decreasing dietary Cu levels but it did not depend on the Cu source.
... This is thought to result from the reduced synthesis of vitamin Adependent zinc-binding protein in ileal mucosa. On the other hand, zinc plays a regulatory role in vitamin A transport via the synthesis of retinol-binding protein, a cofactor role in the oxidative conversion of retinol to retinaldehyde [184]. Therefore, taking vitamins A and D with zinc has been identified as a strategy to augment zinc absorption [185]. ...
Children with autism spectrum disorder may exhibit nutritional deficiencies due to reduced intake, genetic variants, autoantibodies interfering with vitamin transport, and the accumulation of toxic compounds that consume vitamins. Importantly, vitamins and metal ions are essential for several metabolic pathways and for neurotransmitter functioning. The therapeutic benefits of supplementing vitamins, minerals (Zinc, Magnesium, Molybdenum, and Selenium), and other cofactors (coenzyme Q10, alpha-lipoic acid, and tetrahydrobiopterin) are mediated through their cofactor as well as non-cofactor functions. Interestingly, some vitamins can be safely administered at levels far above the dose typically used to correct the deficiency and exert effects beyond their functional role as enzyme cofactors. Moreover, the interrelationships between these nutrients can be leveraged to obtain synergistic effects using combinations. The present review discusses the current evidence for using vitamins, minerals, and cofactors in autism spectrum disorder, the rationale behind their use, and the prospects for future use.
... In this respect, several nutrients work together to enhance digestive function and absorption by complementing one another. In contrast, some may obstruct these processes and compete for absorption, while others may be needed to work in tandem to facilitate metabolism, potentially affecting a variety of biochemical processes [34]. The human body has a lot of synergistic and antagonistic functionalities that need to be taken into account, especially in the health and research fields, and where nutrient-related confounding factors also need to be taken into consideration [35]. ...
Food components have long been recognized to play a fundamental role in the growth and development of the human body, conferring protective functionalities against foreign matter that can be severe public health problems. Micronutrients such as vitamins and minerals are essential to the human body, and individuals must meet their daily requirements through dietary sources. Micronutrients act as immunomodulators and protect the host immune response, thus preventing immune evasion by pathogenic organisms. Several experimental investigations have been undertaken to appraise the immunomodulatory functions of vitamins and minerals. Based on these experimental findings, this review describes the immune-boosting functionalities of micronutrients and the mechanisms of action through which these functions are mediated. Deficiencies of vitamins and minerals in plasma concentrations can lead to a reduction in the performance of the immune system functioning, representing a key contributor to unfavorable immunological states. This review provides a descriptive overview of the characteristics of the immune system and the utilization of micronutrients (vitamins and minerals) in preventative strategies designed to reduce morbidity and mortality among patients suffering from immune invasions or autoimmune disorders.
... This finding by Maggini et al. 8,62 highlights that plausible interactions occurring between certain micronutrients when used in tandem may potentially have synergistic, or even antagonistic, effects on cold management. 63 Thus, significantly different effects on guarding against and treating cold may be observed when a combination of micronutrients are provided, compared with when they were provided alone. In addition, our review does not account for the effects of micronutrients provided via non-oral means, such as through topical creams, nasal gels, or intravenously, some of which presented positive effects on the outcomes of interest in this review. ...
The common cold had resulted in significant economic and social burden worldwide. The effect of vitamin C on preventing common cold in healthy adults has been investigated extensively, but not that of other micronutrients. Thus, we aim to assess the effects of providing micronutrients singly through oral means, on cold incidence, and/or management (in terms of cold duration and symptom severity) in healthy adults from systematically searched randomized controlled trials. From four electronic databases, 660 identified studies were screened and data were extracted from 20 studies (zinc, 10; vitamin D, 8; and vitamins A and E, 2). The quality of selected studies was assessed using the Cochrane risk of bias tool and certainty in the outcomes was assessed with the Grading of Recommendations Assessment, Development and Evaluation approach. The review found that micronutrients supplementation, except vitamin C, may not prevent cold incidence or reduce symptom severity among healthy adults. However, zinc supplementation was observed to potentially reduce cold duration by 2.25 days (when zinc is provided singly, 95% CI: -3.39, -1.12). This suggests that zinc supplementation may reduce the overall burden due to common cold among healthy adults.
... The results with a significance level of P < 0.05 were considered statistically significant. The presence of synergies (an element favors the presence of another element in a tissue) or antagonisms (higher concentrations of an element associated with lower levels of another) between elements was explored using Pearson's correlations (Schoendorfer and Davies 2012;Mikolic et al. 2016). ...
Some rodents of the family Heteromyidae can survive without drinking water, as they obtain it from food. All these species have in common that they eat seeds and fruits. The content of trace metals in food varies depending on the local geology and anthropogenic activities. Baja California Sur has mineral deposits that have been exploited; thus, the metals released may be incorporated into seeds and fruits that are consumed by Heteromyidae. Therefore, metal content in the liver is expected to reflect the presence of mining in soil where these rodents thrive. Individuals from different species of Heteromyidae were collected at sites with mineral deposits; these were divided into two groups: rodents captured in sites with a history of mining operations (Santa Rosalia, San Juan de la Costa, and El Triunfo), and rodents captured in areas with no mining activities (El Vizcaíno, Punta Abreojos, Magdalena Island, and Santiago). The liver of these rodents was excised and its manganese, copper, cadmium, lead, zinc, nickel, and iron contents were determined using atomic absorption spectrophotometry. Manganese was the element that showed the highest significant differences between species, followed by zinc and copper. Iron and cadmium showed the lowest differences. Nickel and lead showed no differences. Chaetodipus arenarius showed significant differences between sites in copper and lead content; C. spinatus did not show significant differences for manganese, copper, nickel, and iron, but it did for cadmium and lead content. Differential accumulation of metals occurs across species. These results indicate that the same species could be used for comparative purposes in pollution monitoring. The comparison of different heteromid species, despite their sharing similar feeding habits and belonging to the same family, can lead to misinterpretation due to the variability of the results. This is probably due to the requirements and tolerances regarding essential elements, such as manganese and zinc, to or tolerance to non-essential elements such as cadmium and lead, which may vary across species.
Background:
Neural tube defects (NTDs) still occur among some women who consume 400 μg of folic acid for prevention. It has been hypothesized that intakes of methyl donors and other micronutrients involved in one-carbon metabolism may further protect against NTDs.
Objectives:
To investigate whether intakes of vitamin B6, vitamin B12, choline, betaine, methionine, thiamine, riboflavin, and zinc, individually or in combination, were associated with NTD risk reduction in offspring of women meeting the folic acid recommendations.
Methods:
Data were from the National Birth Defects Prevention Study (United States population-based, case-control). We restricted deliveries between 1999 and 2011 with daily periconceptional folic acid supplementation or estimated dietary folate equivalents ≥400 μg. NTD cases were live births, stillbirths, or terminations affected by spina bifida, anencephaly, or encephalocele (n = 1227). Controls were live births without a major birth defect (n = 7095). We categorized intake of each micronutrient as higher or lower based on a combination of diet (estimated from a food frequency questionnaire) and periconceptional vitamin supplementation. We estimated NTD associations for higher compared with lower intake of each micronutrient, individually and in combination, expressed as odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for age, race/ethnicity, education, and study center.
Results:
NTD associations with each micronutrient were weak to modest. Greater NTD reductions were observed with concurrent higher-amount intakes of multiple micronutrients. For instance, NTD odds were ∼50% lower among participants with ≥4 micronutrients with higher-amount intakes than among participants with ≤1 micronutrient with higher-amount intake (adjusted OR: 0.53; 95% CI: 0.33, 0.86). The strongest reduction occurred with concurrent higher-amount intakes of vitamin B6, vitamin B12, choline, betaine, and methionine (adjusted OR: 0.26; 95% CI: 0.09, 0.77) compared with ≤1 micronutrient with higher-amount intake.
Conclusions:
Our findings support that NTD prevention, in the context of folic acid fortification, could be augmented with intakes of methyl donors and other micronutrients involved in folate metabolism.
Riboflavin is unique among the water-soluble vitamins in that milk and dairy products make the greatest contribution to its intake in Western diets. Meat and fish are also good sources of riboflavin, and certain fruit and vegetables, especially dark-green vegetables, contain reasonably high concentrations. Biochemical signs of depletion arise within only a few days of dietary deprivation. Poor riboflavin status in Western countries seems to be of most concern for the elderly and adolescents, despite the diversity of riboflavin-rich foods available. However, discrepancies between dietary intake data and biochemical data suggest either that requirements are higher than hitherto thought or that biochemical thresholds for deficiency are inappropriate. This article reviews current evidence that diets low in riboflavin present specific health risks. There is reasonably good evidence that poor riboflavin status interferes with iron handling and contributes to the etiology of anemia when iron intakes are low. Various mechanisms for this have been proposed, including effects on the gastrointestinal tract that might compromise the handling of other nutrients. Riboflavin deficiency has been implicated as a risk factor for cancer, although this has not been satisfactorily established in humans. Current interest is focused on the role that riboflavin plays in determining circulating concentrations of homocysteine, a risk factor for cardiovascular disease. Other mechanisms have been proposed for a protective role of riboflavin in ischemia reperfusion injury; this requires further study. Riboflavin deficiency may exert some of its effects by reducing the metabolism of other B vitamins, notably folate and vitamin B-6.
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