A Critical Review on Vasoactive Nutrients for the Management of Endothelial Dysfunction and Arterial Stiffness in Individuals under Cardiovascular Risk.

Pathophysiological conditions such as endothelial dysfunction and arterial stiffness, characterized by low nitric oxide bioavailability, deficient endothelium-dependent vasodilation and heart effort, predispose individuals to atherosclerotic lesions and cardiac events. Nitrate (NO3-), L-arginine, L-citrulline and potassium (K+) can mitigate arterial dysfunction and stiffness by intensifying NO bioavailability. Dietary compounds such as L-arginine, L-citrulline, NO3- and K+ exert vasoactive effects as demonstrated in clinical interventions by noninvasive flow-mediated vasodilation (FMD) and pulse-wave velocity (PWV) prognostic techniques. Daily L-arginine intakes ranging from 4.5 to 21 g lead to increased FMD and reduced PWV responses. Isolated L-citrulline intake of at least 5.6 g has a better effect compared to watermelon extract, which is only effective on endothelial function when supplemented for longer than 6 weeks and contains at least 6 g of L-citrulline. NO3- supplementation employing beetroot at doses greater than 370 mg promotes hemodynamic effects through the NO3--NO2-/NO pathway, a well-documented effect. A potassium intake of 1.5 g/day can restore endothelial function and arterial mobility, where decreased vascular tone takes place via ATPase pump/hyperpolarization and natriuresis, leading to muscle relaxation and NO release. These dietary interventions, alone or synergically, can ameliorate endothelial dysfunction and should be considered as adjuvant therapies in cardiovascular diseases.

Toxic Metals and Metalloids in Infant Formulas Marketed in Brazil, and Child Health Risks According to the Target Hazard Quotients and Target Cancer Risk.

Children are highly vulnerable to chemical exposure. Thus, metal and metalloid in infant formulas are a concern, although studies in this regard are still relatively scarce. Thus, the presence of aluminum, arsenic, cadmium, tin, mercury, lead, and uranium was investigated in infant formulas marketed in Brazil by inductively coupled plasma mass spectrometry, and the Target Hazard Quotients (THQ) and Target Cancer Risk (TCR) were calculated in to assess the potential risk of toxicity for children who consume these products continuously. Aluminum ranging from 0.432 ± 0.049 to 1.241 ± 0.113 mg·kg-1, arsenic from 0.012 ± 0.009 to 0.034 ± 0.006 mg·kg-1, and tin from 0.007 ± 0.003 to 0.095 ± 0.024 mg·kg-1 were the major elements, while cadmium and uranium were present at the lowest concentrations. According to the THQ, arsenic contents in infant formulas showed a THQ > 1, indicating potential health risk concerns for newborns or children. Minimal carcinogenic risks were observed for the elements considered carcinogenic. Metabolic and nutritional interactions are also discussed. This study indicates the need to improve infant formula surveillance concerning contamination by potentially toxic and carcinogenic elements.

Macrominerals and Trace Minerals in Commercial Infant Formulas Marketed in Brazil: Compliance With Established Minimum and Maximum Requirements, Label Statements, and Estimated Daily Intake.

Infant formulas are the main nutritional source for infants when breastfeeding is not possible or recommended. The daily need for specific nutrients, such as essential minerals, in early stages of a child's life is high because of rapid infant growth and development, which impose metabolic flux increases on these pathways to support growth, physical activity, and defense against infections. In this context, this research aimed to determine macromineral and trace mineral contents in starting (phase 1) and follow-up (phase 2) infant formulas marketed in Brazil (n = 30) by inductively coupled plasma-mass spectrometry, calculate estimated daily intakes, and compare them to reference values regarding adequate intake and tolerable upper intake levels. The highest concentrations of macrominerals were observed in Ca, K, P, and Na, and trace minerals in Fe, Zn, Mn, and Cu. Certain homogeneity only to trace mineral contents was observed when analyzing inter-batch values from same manufacturers. In general, all phase 1 and phase 2 infant formula brands and batches met or exceeded Fe, Zn, Cu, Mo, and Se contents when compared to maximum limits established by Codex Alimentarius. In addition, Zn contents in eight phase 1 and in four phase 2 infant formulas were above the contents established by the tolerable upper intake level for children aged 0-6 and/or 7-12 months, respectively. These findings highlight the need to expand regular infant formula inspection concerning nutritional quality, as some composition aspects of these foods must be improved to follow international guidelines, since ideal requirements for infant formula composition, quality, and safety interfere in child development and adult health.

Increasing the Power of Polyphenols through Nanoencapsulation for Adjuvant Therapy against Cardiovascular Diseases.

Polyphenols play a therapeutic role in vascular diseases, acting in inherent illness-associate conditions such as inflammation, diabetes, dyslipidemia, hypertension, and oxidative stress, as demonstrated by clinical trials and epidemiological surveys. The main polyphenol cardioprotective mechanisms rely on increased nitric oxide, decreased asymmetric dimethylarginine levels, upregulation of genes encoding antioxidant enzymes via the Nrf2-ARE pathway and anti-inflammatory action through the redox-sensitive transcription factor NF-κB and PPAR-γ receptor. However, poor polyphenol bioavailability and extensive metabolization restrict their applicability. Polyphenols carried by nanoparticles circumvent these limitations providing controlled release and better solubility, chemical protection, and target achievement. Nano-encapsulate polyphenols loaded in food grade polymers and lipids appear to be safe, gaining resistance in the enteric route for intestinal absorption, in which the mucoadhesiveness ensures their increased uptake, achieving high systemic levels in non-metabolized forms. Nano-capsules confer a gradual release to these compounds, as well as longer half-lives and cell and whole organism permanence, reinforcing their effectiveness, as demonstrated in pre-clinical trials, enabling their application as an adjuvant therapy against cardiovascular diseases. Polyphenol entrapment in nanoparticles should be encouraged in nutraceutical manufacturing for the fortification of foods and beverages. This study discusses pre-clinical trials evaluating how nano-encapsulate polyphenols following oral administration can aid in cardiovascular performance.

Taro Lectin Can Act as a Cytokine-Mimetic Compound, Stimulating Myeloid and T Lymphocyte Lineages and Protecting Progenitors in Murine Bone Marrow.

Taro (Colocasia esculenta) corm is traditionally consumed as a medicinal plant to stimulate immune responses and restore a health status. Tarin, a taro lectin, is considered responsible for the immunomodulatory effects of taro. In the present study, in order to investigate the effects of tarin on bone marrow hematopoietic population, murine cells were stimulated with tarin combined with a highly enriched conditioned medium containing either IL-3 or GM-CSF. Cells challenged with tarin proliferated in a dose-dependent manner, evidenced by the increase in cell density and number of clusters and colonies. Tarin exhibited a cytokine-mimetic effect similar to IL-3 and GM-CSF, increasing granulocytic cell lineage percentages, demonstrated by an increase in the relative percentage of Gr-1+ cells. Tarin does not increase lymphocytic lineages, but phenotyping revealed that the relative percentage of CD3+ cells was increased with a concomitant decrease in CD19+ and IL-7Rα+ cells. Most bone marrow cells were stained with tarin-FITC, indicating non-selective tarin binding, a phenomenon that must still be elucidated. In conclusion, taro corms contain an immunomodulatory lectin able to boost the immune system by promoting myeloid and lymphoid hematopoietic progenitor cell proliferation and differentiation.

Polyphenols from Root, Tubercles and Grains Cropped in Brazil: Chemical and Nutritional Characterization and Their Effects on Human Health and Diseases.

Throughout evolution, plants have developed the ability to produce secondary phenolic metabolites, which are important for their interactions with the environment, reproductive strategies and defense mechanisms. These (poly)phenolic compounds are a heterogeneous group of natural antioxidants found in vegetables, cereals and leguminous that exert beneficial and protective actions on human health, playing roles such as enzymatic reaction inhibitors and cofactors, toxic chemicals scavengers and biochemical reaction substrates, increasing the absorption of essential nutrients and selectively inhibiting deleterious intestinal bacteria. Polyphenols present in some commodity grains, such as soy and cocoa beans, as well as in other vegetables considered security foods for developing countries, including cassava, taro and beetroot, all of them cropped in Brazil, have been identified and quantified in order to point out their bioavailability and the adequate dietary intake to promote health. The effects of the flavonoid and non-flavonoid compounds present in these vegetables, their metabolism and their effects on preventing chronic and degenerative disorders like cancers, diabetes, osteoporosis, cardiovascular and neurological diseases are herein discussed based on recent epidemiological studies.

Beetroot juice increase nitric oxide metabolites in both men and women regardless of body mass.

The nitrate (NO3(-)) present in beetroot juice (BJ) has been studied for its effect on the cardiovascular system by converting to nitric oxide (NO). In the present study, we evaluated the effect of BJ on the excretion of NO metabolites and its relationship with body mass in both men and women. NO metabolites - urinary NO3(-), nitrite (NO2(-)) and NOx were analyzed by using a high-performance liquid chromatography system. There were significant increases in urinary NO3(-), NO2(-) and NOx in BJ as compared to PLA (BJ without NO3(-)). No significant difference between men and women was observed in NO metabolites after BJ at any time point. There were no significant relationships between urinary NO3(-), NO2(-) and NOx and body mass in BJ intervention for both men and women. In conclusion, urinary NO metabolites after BJ consumption increases in similar manner between sexes regardless of body mass.

Hormonal response to L-arginine supplementation in physically active individuals.

BACKGROUND: Nutritional supplements based on the amino acid L-arginine have been hypothesized to improve exercise performance by increasing levels of insulin and growth hormone (GH). Changes of these parameters in response to L-arginine supplementation may clarify the mechanisms underlying its putative physiological effects on physical performance. OBJECTIVE: The aim of the study was to evaluate the effect of L-arginine supplementation on serum insulin, GH, Growth Factor Insulin-like (IGF-1), and cortisol in response to exercise. Exercise performance was also evaluated. DESIGN: Fifteen trained runners were divided into groups supplemented with 6 g of L-arginine (ARG) or placebo (PLA). Blood samples were collected before supplementation (T0), immediately after the first exercise session (T1), after the second exercise session (T2), and after 20 min of rest (T3). The exercise consisted of two bouts of 5 km time-trial running test. RESULTS: There was a significant increase in serum GH (T0: 3.28±0.95 vs. 3.21±0.5 ng/mL; T1: 4.35±0.23 vs. 4.17±0.13 ng/mL; T2: 4.22±0.25 vs. 4.17±0.09 ng/mL; T3: 4.14±0.29 vs. 4.13±0.18 ng/mL) and cortisol (T0: 198.71±53.77 vs. 207.57±69.51 nmol/L; T1: 458.16±116.12 vs. 433.26±101.77 nmol/L; T2: 454.61±125.21 vs. 431.88±74.82 nmol/L; T3: 311.14±102.91 vs. 362.26±110.42 nmol/L) after T1, T2, and T3, with no significant difference between the ARG and PLA groups, respectively. There was also no significant difference observed in the variables of IGF-1, insulin, and total running time between the ARG and PLA groups. CONCLUSIONS: The supplementation of L-arginine did not appear to stimulate the production of insulin, GH, and IGF-1 and, thus, provided no benefit in hormonal response or exercise performance in trained runners.

L-arginine does not improve biochemical and hormonal response in trained runners after 4 weeks of supplementation.

It has been hypothesized that L-arginine improves exercise performance by increasing nitric oxide synthesis and levels of insulin and growth hormone (GH). Metabolic and hormonal responses to chronic L-arginine supplementation may clarify the mechanisms underlying its putative physiologic effects on physical performance. Therefore, the aim of this study was to investigate the effects that 4 weeks of supplementation with L-arginine would have on metabolic and hormonal parameters at rest and in response to exercise. Fifteen healthy runners were divided into treatment (ARG; 6 g L-arginine) and placebo (PLA; 6 g cornstarch) groups. On the first visit, blood samples were collected for baseline, and the supplement or placebo was provided. After 4 weeks of supplementation (second visit), blood samples were collected at the following intervals: at rest, immediately after the first 5-km time-trial running test (5km-TT), immediately after the second 5km-TT, and after 20 minutes of recovery (+20). In addition to exercise performance (total running time), plasma nitrate, nitrite, nitrate plus nitrite, cyclic guanosine monophosphate, lactate, ammonia and serum insulin, GH, insulin-like growth factor 1, and cortisol concentrations were evaluated. There were significant increases in plasma nitrite, cyclic guanosine monophosphate, lactate, ammonia and serum GH, and cortisol at the first 5km-TT, immediately after the second 5km-TT, and +20 in both ARG and PLA. Nitrate plus nitrite and nitrate increased only at +20. No significant change was observed in serum insulin and insulin-like growth factor 1 in any sample period. Total running time did not differ significantly between the 2 tests, in either ARG or PLA. Thus, according to our results, 4 weeks of L-arginine supplementation did not cause beneficial changes in metabolic and hormonal parameters, beyond those achieved with exercise alone.

Acute L-Arginine supplementation does not increase nitric oxide production in healthy subjects.

Dietary supplements containing L-arginine have been marketed with the purpose of increasing vasodilatation, and thus, blood and oxygen supply to the exercising muscle. The present study evaluated the acute effect of L-arginine supplementation on indicators of NO production, nitrite (NO2-) + nitrate (NO3-) (NOx), in healthy subjects. Plasma concentrations of asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) have also been addressed. Seventeen healthy males participated in a randomized, double-blind, placebo-controlled study. Blood samples were drawn from a left antecubital vein at baseline (T0). Afterwards, subjects were randomly submittedto 6 g of oral L-arginine supplementation (as L-arginine hydrochloride) or placebo (as corn starch); afterwards, the subjects remained at rest in supine position and blood samples were drawn again at 30 (T1), 60 (T2), 90 (T3) and 120 minutes (T4) after supplementation. To analyze NO production, NO3- was converted to NO2- by nitrate reductase, followed by the derivatization of NO2- with 2,3-diaminonaphthalene. NOx, ADMA and SDMA were analyzed using a high-performance liquid chromatography system and monitored with a fluorescence detector. Two-way ANOVA with repeated measures showed no significant changes in NOx concentrations on the L-arginine group as compared to placebo group at any of the fivetime points (T0: 17.6 ± 3.9 vs 14.6 ± 2.3 µmol/L; T1: 15.8 ± 2.4 vs 14.3 ± 1.7 µmol/L; T2: 16.8 ± 4.9 vs 13.7 ± 2.7 µmol/L; T3: 16.7 ± 3.9 vs 14.6 ± 2.1 µmol/L; T4: 15.1 ± 2.8 vs 13.5 ± 3.5 µmol/L). Furthermore, plasma levels of ADMA and SDMA were not statistically significant between the L-arginine and placebo groups at T0 (0.43 ± 0.19 vs 0.39 ± 0.15 µmol/L and 1.83 ± 1.13 vs 1.70 ± 0.62 µmol/L), respectively. In conclusion, acute L-arginine supplementation does not increase plasma concentration of NOx in healthy individuals with normal plasma concentrations of ADMA.

Acute l-arginine supplementation increases muscle blood volume but not strength performance.

l-Arginine (L-arg) is an amino acid precursor to nitric oxide (NO). Dietary supplements containing L-arg have been marketed with the purpose of increasing vasodilation, thereby elevating blood flow to the exercising muscle and enhancing the metabolic response to exercise. Our goal was to identify the acute effect of L-arg supplementation on biceps strength performance, indicators of NO production (nitrite and nitrate - NOx), and muscle blood volume (Mbv) and oxygenation (Mox) during recovery from 3 sets of resistance exercise. Fifteen males participated in a randomized, double-blind, placebo-controlled study. After withdrawing resting blood samples, the subjects were supplemented with 6 g of L-arg (ARG) or placebo (PLA). Monitoring of Mbv and Mox with near-infrared spectroscopy began 30 min after supplementation and lasted for 60 min. The exercise protocol (3 sets of 10 maximal voluntary contractions of isokinetic concentric elbow extension at 60°·s(-1), 2-min rest between sets) was initiated 80 min after supplementation. Blood samples were drawn at 30, 60, 90, and 120 min after supplementation. Repeated measures ANOVA showed that Mbv significantly (p ≤ 0.05) increased in ARG compared with the PLA during the recovery period of each set of resistance exercise. NOx, Mox, peak torque, total work, and set total work were not significantly different between groups. We found that acute L-arg supplementation increases Mbv during recovery from sets of resistance exercise with no increase in strength performance. It is still premature to recommend nutritional supplements containing L-arg as an ergogenic aid to increase muscle strength during resistance training in healthy subjects.