Managing folate deficiency implies filling the gap between laboratory and clinical assessment.

The characterization of folate status in subjects at risk of deficiency and with altered vitamin homeostasis is crucial to endorse preventive intervention health policies, especially in developed countries. Several physiological changes (i.e. pregnancy), clinical situations and diseases have been associated to increased requirement, impaired intake and absorption of folate. However clinical practice guidelines (CPG) endorse folic acid supplementation generally discarding the use of its determination in serum to assess the risk of deficiency and/or its concentration at baseline. Poor confidence on the diagnostic accuracy of serum folate assays still persists in the current CPGs although recent standardization efforts have greatly improved inter-method variability and precision. In this review we critically appraise the methodological issues concerning laboratory folate determination and the evidence on the potential adverse effects of folic acid exposure. The final aim is to build a sound background to promote serum folate-based cost-effective health care policies by optimizing folic acid supplementation in subjects at risk of deficiency and with altered folate homeostasis. Our first result was to adjust in relation to current serum folate assays the thresholds reported by CPGs as index of folate status, defined on the association with metabolic and hematologic indicators. We identify a statistically significant difference between the estimated thresholds and accordingly show that the assessment of folate status actually changes in relation to the assay employed. The use of the method-dependent thresholds here reported may pragmatically endorse the stewardship of folic acid supplementation in clinical practice and increase the cost-effectiveness of health care policies.

COVID-19: A Review on the Role of Trace Elements Present in Saudi Arabian Traditional Dietary Supplements.

The novel coronavirus infection is also called COVID-19 (coronavirus disease 2019). The infection has affected millions of people worldwide and caused morbidity as well mortality in patients with pre-existing chronic conditions such as metabolic, respiratory and cardiovascular disorders. The severity of the disease is mostly seen in people with low immunity and chronic sufferers of respiratory, cardiovascular and metabolic disorders. To date, there is no specific treatment available for COVID-19. Precaution and prevention are the most recommended options followed for controlling the spread of infection. Trace elements such as zinc, calcium, iron and magnesium play an important role in boosting the immunity of the host system. These components assist in the development and functioning of lymphocytes, cytokines, free radicals, inflammatory mediators and endothelial functioning. This review summarizes the common dietary supplements that are regularly consumed in Saudi Arabia and are known to contain these vital trace elements. Data available in Google Scholar, NCBI, PUBMED, EMBASE and Web of Science about COVID-19, micronutrients, trace elements and nutritional supplements of Saudi Arabia was collected. By highlighting the traditionally used dietary components containing the essential elements, this review could provide useful knowledge crucial for building immunity in the population.

The Botanical Safety Consortium: A public-private partnership to enhance the botanical safety toolkit.

Botanical dietary supplement use is widespread and growing, therefore, ensuring the safety of botanical products is a public health priority. This commentary describes the mission and objectives of the Botanical Safety Consortium (BSC) - a public-private partnership aimed at enhancing the toolkit for conducting the safety evaluation of botanicals. This partnership is the result of a Memorandum of Understanding between the US FDA, the National Institute of Environmental Health Sciences, and the Health and Environmental Sciences Institute. The BSC serves as a global forum for scientists from government, academia, consumer health groups, industry, and non-profit organizations to work collaboratively on adapting and integrating new approach methodologies (NAMs) into routine botanical safety assessments. The objectives of the BSC are to: 1) engage with a group of global stakeholders to leverage scientific safety approaches; 2) establish appropriate levels of chemical characterization for botanicals as complex mixtures; 3) identify pragmatic, fit-for-purpose NAMs to evaluate botanical safety; 4) evaluate the application of these tools via comparison to the currently available safety information on selected botanicals; 5) and integrate these tools into a framework that can facilitate the evaluation of botanicals. Initially, the BSC is focused on oral exposure from dietary supplements, but this scope could be expanded in future phases of work. This commentary provides an overview of the structure, goals, and strategies of this initiative and insights regarding our first objectives, namely the selection and prioritization of botanicals based on putative toxicological properties.

Potential mental and physical benefits of supplementation with a high-dose, B-complex multivitamin/mineral supplement: what is the evidence? / Posibles beneficios mentales y físicos de la suplementación con un preparado multivitamínico/mineral del complejo B en dosis altas: ¿qué evidencia hay?

Objective: to perform a systematic literature review to examine the effects of high-dose, B-complex multivitamin/mineral supplementation on physical, mental, and energy outcomes in healthy and ‘at-risk' (suboptimal nutritional status/subclinical symptoms at baseline) adult populations. Methods: PubMed was searched for relevant randomized controlled trials until January 2020. Results: overall, 136 publications were identified. In the seven randomised, double-blind, placebo-controlled studies considered eligible for inclusion, supplementation in healthy populations predominantly showed improvements in perceived stress, physical stamina, concentration, and general mental health, and significant reductions in anxiety and improvements in self-reported vigour. However, not all of these outcomes were significant, and statistical correction for multiple outcomes was not commonly employed. Studies investigating brain mapping following supplementation indicated increased functional activity in brain regions related to processing of attention, executive control, and working memory during cognitive tasks. Conclusions: while there is certainly a need for further studies on the neurocognitive and physical benefits of micronutrient supplementation, this review provides generally supportive evidence for the benefits of a high-dose, B-complex multivitamin/mineral supplement in healthy and at-risk populations in terms of physical, mental, and energy outcomes. (AU)

Objetivo: realizar una revisión sistemática de la literatura para valorar los efectos de la administración de suplementos multivitamínicos/minerales del complejo B en dosis altas sobre los resultados físicos, mentales y energéticos en poblaciones adultas sanas y en situaciones especiales de riesgo (estado nutricional subóptimo/síntomas subclínicos al inicio del estudio). Métodos: se realizaron búsquedas en PubMed de ensayos controlados aleatorios relevantes hasta enero de 2020.Resultados: en total se identificaron 136 publicaciones. En los siete estudios aleatorizados, doble ciego y controlados con placebo considerados elegibles para la inclusión, la suplementación en poblaciones sanas mostró predominantemente mejoras en la percepción del estrés, la resistencia física, la concentración y la salud mental general, así como una reducción significativa de la ansiedad y mejoras en la vitalidad según la autoevaluación de los participantes. Sin embargo, no todos estos resultados fueron significativos y la corrección estadística para múltiples resultados no se empleó habitualmente. Los estudios sobre el mapeo cerebral después de la suplementación, indicaron un aumento de la actividad funcional en las regiones del cerebro relacionadas con el procesamiento de la atención, el control ejecutivo y la memoria de trabajo durante tareas cognitivas. Conclusiones: si bien ciertamente existe la necesidad de realizar más estudios sobre los beneficios neurocognitivos y físicos de la suplementación con micronutrientes, esta revisión proporciona evidencia en general sobre los beneficios de un suplemento multivitamínico/mineral del complejo B en dosis altas, en poblaciones sanas y en situaciones de riesgo, en términos de resultados físicos, mentales y energéticos. (AU)

Vitamin supplementation in healthy patients: What does the evidence support?

This review, with handy tables, summarizes which vitamins offer proven benefits-and which don't.

Screening for consistency and contamination within and between bottles of 29 herbal supplements.

In the United States the marketing of dietary supplements, of which the majority are herbal supplements, is currently a multibillion-dollar industry involving use from over half of the adult population. Due to their frequency of use and the lack of regulation of herbal supplements by the Food and Drug Administration (FDA) it is important for the health and safety of consumers to know about consistency of supplements and any possible contamination by harmful products, such as heavy metals or microorganisms. The purpose of the study was to determine consistency and contamination within and between bottles of common herbal supplements. Duplicate bottles of 29 herbal supplements were tested for consistency for antioxidant activity, phenolic concentration and flavonoid concentration under methanolic and water extraction. The supplements were also analyzed for the presence of metals and fungal contaminants. For all of the supplements tested there was high variability around the mean in antioxidant activity, phenolic concentrations and flavonoid concentrations, with coefficients of variation (CV) ranging from 0-120. Zinc was found in almost 90% of the supplements, nickel in about half of the supplements and lead in none of the supplements. Approximately 60% of the supplements contained fungal isolates. Although the majority of the fungi that were found in the supplements are generally not hazardous to human health, many of them could be problematic to sensitive groups, such as immunocompromised individuals. The data, which demonstrates contamination and a lack of consistency, in conjunction with previous studies on supplement contamination, strengthen the case that the FDA should regulate over-the-counter herbal supplements the same way that they regulate food and drugs. Until such time it is crucial that consumers are informed that many of the supplements that they take may lack the standardization that would reduce the chance of contamination and lead to consistency from one pill to the next.

Authentication of garlic (Allium sativum L.) supplements using a trnLUAA mini-barcode.

Garlic (Allium sativum), a widely distributed plant with great cultural and medicinal significance, is one of the most popular herbal dietary supplements in Europe and North America. Garlic supplements are consumed for a variety of reasons, including for their purported antihypertensive, antibacterial, and anticarcinogenic effects. The steady increase in the global herbal dietary supplement market paired with a global patchwork of regulatory frameworks makes the development of assays for authentication of these products increasingly important. A DNA mini-barcode assay was developed using the P6 loop of the plastid trnLUAA intron to positively identify A. sativum products. Analysis of 43 commercially available garlic herbal dietary supplements produced mini-barcode sequences for 33 supplements, all of which contained detectable amounts of A. sativum. The trnLUAA P6 mini-barcode can be highly useful for specimen identification, particularly for samples that may contain degraded DNA.

The efficacy of fish oil in preventing coronary heart disease: A systematic review and meta-analysis.

BACKGROUND: Coronary heart disease (CHD) is one of the most common causes of death and disease burden in the world. Current fish oil aiming to prevent and treat CHD have shown a large variety of effects with low levels of evidence. OBJECTIVE: To evaluate the efficacy of fish oil for protection against CHD, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating the use of fish oil for protection against CHD. METHODS: We retrieved relevant articles published from January 1966 to January 2020 by searching the PubMed, EMBASE, Cochrane CENTRAL, and Web of Science databases. RCTs of fish oil in preventing CHD were selected. The study quality was evaluated using the Cochrane Risk of Bias tool with RevMan 5.3 software. The first selection involved 360 citations. After screening and evaluation of suitability, 19 RCTs adjusted for clustering were included in the meta-analysis. All selected manuscripts considered that fish oil was effective in preventing CHD, secondary outcome measures included angina, sepsis and death. RESULTS: Compared with the control group, fish oil may confer significant protection against CHD (odds ratio = 0.84; 95% confidence interval: 0.72-0.98). There was no significant difference in the incidence of secondary outcomes between the observation group and the control group (P > .05). CONCLUSION: The above results show that fish oil plays an important role in reducing CHD and cardiovascular events. However, because of the suboptimal quality of the studies included into the meta-analysis, these results do not justify adding fish oils systematically to the heavy pharmaceutical assortment already recommended in CHD patients. REGISTRATION DETAILS: CRD42020183719.

Efectos de la ingesta de lácteos enriquecidos de forma natural con selenio y omega-3 en una muestra de mujeres posmenopáusicas con síndrome metabólico: un ensayo clínico aleatorizado, triple ciego y controlado con placebo / Effects of the intake of dairy products naturally enriched with selenium and omega-3 polyunsaturated fatty acids in a sample of postmenopausal women with metabolic syndrome: a randomized, triple-blind, placebo-controlled clinical trial

Introducción: el síndrome metabólico de las mujeres posmenopáusicas puede mejorar con una alimentación saludable. Objetivos: evaluar si una intervención alimentaria con productos lácteos enriquecidos en selenio y ácidos grasos poliinsaturados omega-3 aumenta los niveles de selenio y mejora los factores de riesgo cardiovascular en las mujeres posmenopáusicas con síndrome metabólico. Material y métodos: ensayo clínico aleatorizado, triple ciego y controlado, realizado en atención primaria. Captación: abril 2018, 46 mujeres posmenopáusicas con síndrome metabólico consumidoras habituales de lácteos. Aleatorización: 23 en el grupo de control y 23 en el grupo experimental. Intervención: consumo durante 3 meses de lácteos enriquecidos naturalmente con selenio y ácidos grasos poliinsaturados omega-3 (leche, yogur y queso fresco). Controles: consumo de lácteos convencionales. Variable principal: selenio en plasma; secundarias: criterios del síndrome metabólico. Número de registro 2018/256, Comité de Ética Galicia. Resultados: finalizaron 23 mujeres en el grupo de control y 21 en el grupo de intervención. Aumentó el selenio en el grupo de intervención (7,2 µg/L, IC del 95 %: 3,7/10,8) frente al grupo de control (-4,5 µg/L, IC del 95 %: -8/-1) (p < 0,001) y disminuyó el colesterol unido a lipoproteínas de muy baja densidad (-2,3 mg/dl, IC del 95 %: -5,6/1) respecto al grupo de control (1,9 mg/dl, IC del 95 %: -0,7/4,5) (p = 0,043). Las mujeres del grupo experimental mejoraron respecto a su medición basal en perímetro de cintura (p = 0,010), índice de masa corporal (p = 0,047) y colesterol unido a lipoproteínas de alta densidad (p < 0,001). Conclusiones: una intervención con lácteos enriquecidos naturalmente con selenio y omega-3 en mujeres posmenopáusicas con síndrome metabólico puede mejorar los niveles de selenio en plasma y de colesterol unido a lipoproteínas de muy baja densidad. (AU)

Introduction: metabolic syndrome in postmenopausal women can improve with a healthy diet. Objectives: to evaluate whether a dietary intervention with dairy products naturally enriched with selenium and omega-3 polyunsaturated fatty acids increases selenium plasma levels and improves cardiovascular risk factors in postmenopausal women with metabolic syndrome. Material and methods: a randomized, triple-blind, controlled clinical trial carried out in GP surgeries. Recruitment: April 2018, 46 postmenopausal women with metabolic syndrome who were frequent dairy consumers. Randomization: 23 in control group and 23 in experimental group. Intervention: consumption of dairy products naturally enriched with selenium and omega-3 polyunsaturated fatty acids (milk, yogurt, fresh cheese) for three months. Controls took conventional dairy. Primary endpoint: plasma selenium levels; secondary endpoints: metabolic syndrome criteria. Registration number 2018/256, Galicia Ethics Committee. Results: in all, 23 women in the control group and 21 in the intervention group completed the trial. Selenium increased in the intervention group (7.2 µg/L, 95 % CI, 3.7/10.8) compared to the control group (-4.5 µg/L, 95 % CI, -8/-1) (p < 0.001) and very low-density lipoprotein cholesterol decreased (-2.3 mg/dL, 95 % CI, -5.6/1) compared to the control group (1.9 mg/dL, 95 % CI, -0.7/4.5) (p = 0.043). Waist circumference (p = 0.010), body mass index (p = 0.047) and high-density lipoprotein cholesterol (p < 0.001) in the experimental group improved in comparison to baseline measurements. Conclusions: an intervention with dairy products naturally enriched with selenium and omega-3 in a sample of postmenopausal women with metabolic syndrome can improve plasma selenium levels and very low-density lipoprotein cholesterol. (AU)

Influencia de los carotenoides sobre los marcadores de riesgo cardiometabólico en mujeres peri y posmenopáusicas / Influence of dietary carotenoids on biomarkers of cardiometabolic risk in peri- and post-menopausal women

Introducción: durante la menopausia hay una mayor tendencia a la obesidad y el depósito de grasa visceral, aumentando el riesgo cardiometabólico. Objetivos: evaluar mediante un estudio de intervención el efecto del consumo de carotenoides sobre los biomarcadores relacionados con el riesgo cardiometabólico en mujeres peri y posmenopáusicas. Métodos: se seleccionaron 12 mujeres peri y posmenopáusicas, sin antecedentes de enfermedad cardiovascular pero con algún factor de riesgo cardiometabólico. Durante 4 semanas se suplementó su dieta con zumo de naranja-zanahoria, zumo de tomate y espinacas cocidas, proporcionando una ingesta de 415 mg de carotenoides totales a la semana (carotenos, criptoxantina, licopeno y luteína + zeaxantina). En el momento inicial (TI) y en el final (TF) se midieron los parámetros antropométricos y se analizaron los parámetros bioquímicos, los carotenoides plasmáticos y los biomarcadores de estrés oxidativo, de inflamación y de función endotelial. Resultados: en el TF se observaron cambios significativos, disminuyendo el colesterol unido a LDL y el índice aterogénico, y aumentando el colesterol-HDL. Los carotenoides plasmáticos se incrementaron significativamente (p < 0,05) de 0,56 µg/ml en el TI hasta 1,22 µg/ml en el TF. Paralelamente se observaron cambios significativos (p < 0,05) en los biomarcadores de estrés oxidativo e inflamación, disminuyendo la proteína C-reactiva y el malonaldehído, y aumentando la adiponectina. Por el contrario, los biomarcadores de daño endotelial (sVCAM y sICAM) y la capacidad antioxidante (ORAC) no mostraron cambios tras la intervención. Conclusiones: el consumo de carotenoides aumenta los niveles plasmáticos de carotenoides y disminuye la dislipemia aterogénica, y mejora los biomarcadores de inflamación y el estrés oxidativo, lo que está relacionado con una disminución del riesgo cardiometabólico. (AU)

Background: peri- and post-menopausal women exhibit a high tendency towards obesity and visceral fat deposition, which increases cardiometabolic risk. Objective: to evaluate through a prospective nutritional study the effect of carotenoid consumption on cardiometabolic risk biomarkers in peri- and post-menopausal women. Material and methods: twelve peri- and post-menopausal women without previous symptoms of cardiovascular disease, but with some cardiometabolic risk factor, were recruited. Their diet was supplemented during 4 weeks with orange-carrot juice, tomato juice, and boiled spinach, providing 415 mg of total carotenoids/week (carotenes, cryptoxanthin, lycopene, and lutein + zeaxanthin). At the beginning (TI) and at the end (TF) of the intervention period blood samples were drawn to measure biochemical parameters, oxidative stress, inflammation and endothelial function biomarkers, and plasma carotenoid levels. Results: at TF a significant decrease (p < 0.05) in LDL-cholesterol and atherogenic index, and an increase in HDL-cholesterol were observed. Plasma carotenoids increased significantly (p < 0.05) from 0.56 µg/mL at TI to 1.22 µg/mL at TF. Concurrently, a shift in oxidative stress and inflammation biomarkers was detected, with a decrease in plasma C-reactive protein and malonaldehyde levels, and an increase in adiponectin. However, endothelial dysfunction biomarkers (sVCAM and sICAM) and total antioxidant capacity remained unchanged. Conclusions: dietary supplementation with carotenoids leads to an increase in plasma carotenoids, a decrease in atherogenic dyslipidemia, and an improvement in oxidative stress and inflammation biomarkers, which indicates a reduction in cardiometabolic risk. (AU)

Controversia actual sobre el papel crítico de los ácidos grasos poliinsaturados de cadena larga, araquidónico (ARA) y docosahexaenoico (DHA), en el lactante / Controversy about the critical role of long-chain polyunsaturated fatty acids, arachidonic acid (ARA) and docosahexaenoic acid (DHA), during infancy

Los ácidos grasos poliinsaturados de cadena larga (AGPI-CL) son críticos para el crecimiento y desarrollo infantil, en particular los ácidos araquidónico (ARA, C20:4n-6) y docosahexaenoico (DHA, C22:6n-3). El ARA y el DHA son componentes de los fosfolípidos de las membranas celulares y desempeñan importantes funciones en la división, diferenciación y señalización celular, siendo el DHA el ácido graso de la serie n-3 predominante en el cerebro y la retina en desarrollo. Durante el tercer trimestre de la gestación, los AGPI-CL aumentan de forma sustancial en la circulación fetal, observándose un proceso de “biomagnificación” en el cerebro fetal. Además, los AGPI-CL son precursores de los eicosanoides y metabolitos implicados en la modulación de la intensidad y duración de la respuesta inmunitaria. La síntesis de AGPI-CL implica un complejo proceso de desaturación y elongación desde los precursores principales, el ácido linoleico (18:3 n-6) (LA) (serie n-6) y el ácido α-linolénico (20:3 n-3) (LNA) (serie n-3), por los cuales compiten las enzimas desaturasas (FADS) y elongasas (ELOVL). Es importante indicar que en los primeros meses de vida, como consecuencia de la baja actividad enzimática, la síntesis de AGPI-CL a partir de LA y LNA es reducida, especialmente en los niños con variaciones en los genes que codifican las FADS y ELOVL involucradas en la síntesis de AGPI-CL y que, por tanto, son incapaces de cubrir por sí mismos sus necesidades de ARA y DHA. Los homocigotos para el haplotipo A de las FADS (97 % de la población latinoamericana) muestran niveles de ARA y DHA de tan solo un 43 % y un 24 %, respectivamente, inferiores a los de los individuos con haplotipo D (más frecuente en Europa, África y Asia). (AU)

Long-chain polyunsaturated fatty acids (LC-PUFAs) are critical for infant growth and development, particularly arachidonic acid (ARA, C20:4n-6) and docosahexaenoic acid (DHA, C22:6n-3). ARA and DHA are components of cell membrane phospholipids and play an important role in cell division, differentiation, and signaling; and DHA is the n-3 fatty acid predominant in the developing brain and retina. During the third trimester of pregnancy, LC-PUFAs increase substantially in fetal circulation, and a “biomagnification” process in the fetal brain is observed. Moreover, LC-PUFAs are precursors of eicosanoids and metabolites, which modulate the intensity and duration of the immune response.LC-PUFA synthesis implies complex desaturation and elongation processes on their principal precursors, linoleic acid (LA) (18:3 n-6) (series n-6) and α-linolenic acid (LNA) (20:3 n-3) (series n-3), where fatty acid desaturases (FADS) and elongases (ELOVL) are competing. It is important to notice that during the first months of life, as a consequence of low enzymatic activity, LC-PUFA synthesis from LA and LNA is reduced, especially in those infants carrying variations in the FADS and ELOVL genes, which are involved in LC-PUFA synthesis, and so they are unable to supply their own DHA and ARA needs. Homozygote infants for FADS haplotype A (97 % of the Latinoamerican population) show low levels of ARA (only 43 %) and DHA (only 24 %) when compared to those carrying haplotype D (more prevalent in Europe, Africa and Asia). (AU)

Functional Cupcake for Preventing Vitamin A Deficiency and Correlated Anemia and Oxidative Stress.

<b>Background and Objective:</b> Vitamin A Deficiency (VAD) is a critical public health problem that affects the health of kids worldwide and may induce anemia and oxidative stress. The current study aimed to pre-clinically assess the effect of a cupcake, prepared to be served for primary school children, on vitamin A deficiency and related anemia and oxidative stress in rats. <b>Materials and Methods:</b> Flour of flash orange sweet potatoes, as a rich source of pro-vitamin A, was used to prepare the cupcake. The chemical composition, amino acids and sensory evaluation of the cupcake were done. The biological evaluation was carried out using 18 weaning rats in three groups (control group, vitamin A-deficient group and vitamin A-deficient group fed on a diet fortified with 20% of the prepared cupcake for two months). <b>Results:</b> The results indicated the high value of vitamin A in the prepared cupcake. Excellent sensory characteristics were noticed. Feeding on the VDA diet fortified with the prepared cupcake suppressed the reduction in Retinol-Binding Protein (RBP), hemoglobin and iron. Total Iron Binding Capacity (TIBC) increased in the VAD group. Also, feeding on the prepared cupcake suppressed the reduction in Superoxide Dismutase (SOD) and Glutathione Peroxidase (GPx) and the elevation of Malondialdehyde (MDA). <b>Conclusion:</b> It can be suggested that the prepared cupcake is promising in preventing of vitamin A deficiency and related anemia and oxidative stress. Thus, the prepared cupcake may be efficient for children to prevent vitamin A deficiency.

[Controversy about the critical role of long-chain polyunsaturated fatty acids, arachidonic acid (ARA) and docosahexaenoic acid (DHA), during infancy]. / Controversia actual sobre el papel crítico de los ácidos grasos poliinsaturados de cadena larga, araquidónico (ARA) y docosahexaenoico (DHA), en el lactante.

INTRODUCTION: Long-chain polyunsaturated fatty acids (LC-PUFAs) are critical for infant growth and development, particularly arachidonic acid (ARA, C20:4n-6) and docosahexaenoic acid (DHA, C22:6n-3). ARA and DHA are components of cell membrane phospholipids and play an important role in cell division, differentiation, and signaling; and DHA is the n-3 fatty acid predominant in the developing brain and retina. During the third trimester of pregnancy, LC-PUFAs increase substantially in fetal circulation, and a "biomagnification" process in the fetal brain is observed. Moreover, LC-PUFAs are precursors of eicosanoids and metabolites, which modulate the intensity and duration of the immune response. LC-PUFA synthesis implies complex desaturation and elongation processes on their principal precursors, linoleic acid (LA) (18:3 n-6) (series n-6) and α-linolenic acid (LNA) (20:3 n-3) (series n-3), where fatty acid desaturases (FADS) and elongases (ELOVL) are competing. It is important to notice that during the first months of life, as a consequence of low enzymatic activity, LC-PUFA synthesis from LA and LNA is reduced, especially in those infants carrying variations in the FADS and ELOVL genes, which are involved in LC-PUFA synthesis, and so they are unable to supply their own DHA and ARA needs. Homozygote infants for FADS haplotype A (97 % of the Latinoamerican population) show low levels of ARA (only 43 %) and DHA (only 24 %) when compared to those carrying haplotype D (more prevalent in Europe, Africa and Asia). Human milk is the only source of LA, LNA, ARA, and DHA for the neonate and infant till complementary feeding (CF) is introduced. Infants fed with infant formulas must receive enough amounts of LA, LNA, ARA, and DHA to cover their nutritional requirements. The new guidelines by the European Food Safety Authority (EFSA) (2016) recommend that infant formulas and follow-on formulas must contain 20-50 mg of DHA/100 kcal (0.5-1 % of total fatty acids, which is higher than in human milk and the majority of infant formulas in the market), and it is not necessary to add ARA. This new regulation, which is already applicable since February 2020, has resulted in profound controversy because there is no scientific evidence about its appropriateness and safety for healthy children. Then, different international expert groups have revised the research already published about the effects of ARA and DHA addition to infant formulas, and discussed different emerging questions from this European directive. The expert group led from the University of Granada (Spain) recommends the addition of ARA in similar or higher concentrations than those of DHA, at least equal to those present in human milk (0.3 % of total fatty acids), although preferably 0.5 % and up to around 0.64 % of total fatty acids, since new studies confirm the optimal intake of ARA and DHA during the different developmental stages. This recommendation could be of particular importance for infants carrying the haplotype A of FADS.

INTRODUCCIÓN: Los ácidos grasos poliinsaturados de cadena larga (AGPI-CL) son críticos para el crecimiento y desarrollo infantil, en particular los ácidos araquidónico (ARA, C20:4n-6) y docosahexaenoico (DHA, C22:6n-3). El ARA y el DHA son componentes de los fosfolípidos de las membranas celulares y desempeñan importantes funciones en la división, diferenciación y señalización celular, siendo el DHA el ácido graso de la serie n-3 predominante en el cerebro y la retina en desarrollo. Durante el tercer trimestre de la gestación, los AGPI-CL aumentan de forma sustancial en la circulación fetal, observándose un proceso de "biomagnificación" en el cerebro fetal. Además, los AGPI-CL son precursores de los eicosanoides y metabolitos implicados en la modulación de la intensidad y duración de la respuesta inmunitaria. La síntesis de AGPI-CL implica un complejo proceso de desaturación y elongación desde los precursores principales, el ácido linoleico (18:3 n-6) (LA) (serie n-6) y el ácido α-linolénico (20:3 n-3) (LNA) (serie n-3), por los cuales compiten las enzimas desaturasas (FADS) y elongasas (ELOVL). Es importante indicar que en los primeros meses de vida, como consecuencia de la baja actividad enzimática, la síntesis de AGPI-CL a partir de LA y LNA es reducida, especialmente en los niños con variaciones en los genes que codifican las FADS y ELOVL involucradas en la síntesis de AGPI-CL y que, por tanto, son incapaces de cubrir por sí mismos sus necesidades de ARA y DHA. Los homocigotos para el haplotipo A de las FADS (97 % de la población latinoamericana) muestran niveles de ARA y DHA de tan solo un 43 % y un 24 %, respectivamente, inferiores a los de los individuos con haplotipo D (más frecuente en Europa, África y Asia). La leche humana constituye la única fuente de LA, LNA, ARA y DHA para el recién nacido y el lactante hasta la introducción de la alimentación complementaria (AC). Los niños alimentados con fórmulas infantiles deben recibir las cantidades de LA, LNA, ARA y DHA suficientes para cubrir los requerimientos nutricionales. La nueva normativa de la Autoridad Europea de Seguridad Alimentaria (EFSA) (2016) indica que las fórmulas infantiles de inicio y continuación deben contener entre 20 y 50 mg de DHA/100 kcal (0,5-1 % del total de ácidos grasos: más elevado que en la leche humana y en la mayoría de fórmulas infantiles comercializadas) sin la necesidad de incluir también ARA. Esta nueva regulación, que está vigente desde febrero de 2020, ha despertado una gran controversia, al no existir evidencia científica acerca de su pertinencia y seguridad para los niños sanos. Por ello, diferentes grupos de expertos internacionales han revisado la investigación publicada acerca del ARA y el DHA, y discutido diferentes cuestiones emergentes a partir de esta nueva directiva Europea. El grupo de expertos, liderado desde la Universidad de Granada (España), recomienda la adición de ARA en concentraciones iguales o mayores que las de DHA, alcanzando al menos el contenido presente en la leche humana (0,3 % del total de ácidos grasos), aunque preferiblemente un 0,5 % y hasta alrededor del 0,64 % del total de AG, hasta que nuevos estudios confirmen la ingesta óptima de ARA y DHA durante las distintas etapas del desarrollo. Esta recomendación podría ser de especial importancia para los niños portadores del haplotipo A de las FADS.

Potential mental and physical benefits of supplementation with a high-dose, B-complex multivitamin/mineral supplement: What is the evidence?

INTRODUCTION: Objective: to perform a systematic literature review to examine the effects of high-dose, B-complex multivitamin/mineral supplementation on physical, mental, and energy outcomes in healthy and 'at-risk' (suboptimal nutritional status/subclinical symptoms at baseline) adult populations. Methods: PubMed was searched for relevant randomized controlled trials until January 2020. Results: overall, 136 publications were identified. In the seven randomised, double-blind, placebo-controlled studies considered eligible for inclusion, supplementation in healthy populations predominantly showed improvements in perceived stress, physical stamina, concentration, and general mental health, and significant reductions in anxiety and improvements in self-reported vigour. However, not all of these outcomes were significant, and statistical correction for multiple outcomes was not commonly employed. Studies investigating brain mapping following supplementation indicated increased functional activity in brain regions related to processing of attention, executive control, and working memory during cognitive tasks. Conclusions: while there is certainly a need for further studies on the neurocognitive and physical benefits of micronutrient supplementation, this review provides generally supportive evidence for the benefits of a high-dose, B-complex multivitamin/mineral supplement in healthy and at-risk populations in terms of physical, mental, and energy outcomes.

INTRODUCCIÓN: Objetivo: realizar una revisión sistemática de la literatura para valorar los efectos de la administración de suplementos multivitamínicos/minerales del complejo B en dosis altas sobre los resultados físicos, mentales y energéticos en poblaciones adultas sanas y en situaciones especiales de riesgo (estado nutricional subóptimo/síntomas subclínicos al inicio del estudio). Métodos: se realizaron búsquedas en PubMed de ensayos controlados aleatorios relevantes hasta enero 2020. Resultados: en total se identificaron 136 publicaciones. En los siete estudios aleatorizados, doble ciego y controlados con placebo considerados elegibles para la inclusión, la suplementación en poblaciones sanas mostró predominantemente mejoras en la percepción del estrés, la resistencia física, la concentración y la salud mental general, así como una reducción significativa de la ansiedad y mejoras en la vitalidad según la autoevaluación de los participantes. Sin embargo, no todos estos resultados fueron significativos y la corrección estadística para múltiples resultados no se empleó habitualmente. Los estudios sobre el mapeo cerebral después de la suplementación, indicaron un aumento de la actividad funcional en las regiones del cerebro relacionadas con el procesamiento de la atención, el control ejecutivo y la memoria de trabajo durante tareas cognitivas. Conclusiones: si bien ciertamente existe la necesidad de realizar más estudios sobre los beneficios neurocognitivos y físicos de la suplementación con micronutrientes, esta revisión proporciona evidencia en general sobre los beneficios de un suplemento multivitamínico/mineral del complejo B en dosis altas, en poblaciones sanas y en situaciones de riesgo, en términos de resultados físicos, mentales y energéticos.

Impact of vitamin C supplementation on placental DNA methylation changes related to maternal smoking: association with gene expression and respiratory outcomes.

BACKGROUND: Maternal smoking during pregnancy (MSDP) affects development of multiple organ systems including the placenta, lung, brain, and vasculature. In particular, children exposed to MSDP show lifelong deficits in pulmonary function and increased risk of asthma and wheeze. Our laboratory has previously shown that vitamin C supplementation during pregnancy prevents some of the adverse effects of MSDP on offspring respiratory outcomes. Epigenetic modifications, including DNA methylation (DNAm), are a likely link between in utero exposures and adverse health outcomes, and MSDP has previously been associated with DNAm changes in blood, placenta, and buccal epithelium. Analysis of placental DNAm may reveal critical targets of MSDP and vitamin C relevant to respiratory health outcomes. RESULTS: DNAm was measured in placentas obtained from 72 smokers enrolled in the VCSIP RCT: NCT03203603 (37 supplemented with vitamin C, 35 with placebo) and 24 never-smokers for reference. Methylation at one CpG, cg20790161, reached Bonferroni significance and was hypomethylated in vitamin C supplemented smokers versus placebo. Analysis of spatially related CpGs identified 93 candidate differentially methylated regions (DMRs) between treatment groups, including loci known to be associated with lung function, oxidative stress, fetal development and growth, and angiogenesis. Overlap of nominally significant differentially methylated CpGs (DMCs) in never-smokers versus placebo with nominally significant DMCs in vitamin C versus placebo identified 9059 candidate "restored CpGs" for association with placental transcript expression and respiratory outcomes. Methylation at 274 restored candidate CpG sites was associated with expression of 259 genes (FDR < 0.05). We further identified candidate CpGs associated with infant lung function (34 CpGs) and composite wheeze (1 CpG) at 12 months of age (FDR < 0.05). Increased methylation in the DIP2C, APOH/PRKCA, and additional candidate gene regions was associated with improved lung function and decreased wheeze in offspring of vitamin C-treated smokers. CONCLUSIONS: Vitamin C supplementation to pregnant smokers ameliorates changes associated with maternal smoking in placental DNA methylation and gene expression in pathways potentially linked to improved placental function and offspring respiratory health. Further work is necessary to validate candidate loci and elucidate the causal pathway between placental methylation changes and outcomes of offspring exposed to MSDP. Clinical trial registration ClinicalTrials.gov, NCT01723696. Registered November 6, 2012. https://clinicaltrials.gov/ct2/show/record/NCT01723696 .

A Graded Approach for Evaluating Health Claims about Plant-Based Food Supplements: Application of a Case Study Methodology.

The implementation of REGULATION (EC) No 1924/2006 has led to the formation of a list of health claims that can be used in food supplements (EU 432/2012). However, such supplements are often composed of plant preparations with claims omitted from this list. The peculiarity of plants is related to their long history of use, that could allow claims based on traditionally recognized health effects. In addition, the scientific literature has been enriched over the years through clinical studies that have assessed the bioavailability and efficacy of bioactive components, and investigated their mechanisms of action. Based on existing recognized models which aim to classify research according to the level of scientific evidence, Synadiet developed a three-grade model (A, B or C) for assessing plants health claims. In this paper, the applicability of the model is illustrated through an example for which a Grade B health claim attesting the possible contribution of red clover isoflavones to the improvement of blood lipid levels in postmenopausal women has been attributed. The model appears able to be easily extrapolated to claims pertaining to other plants. If adopted by consensus at European level, this model could initiate the implementation of a positive list of health claims on plant preparations.

How to proceed when it comes to vitamin D.

USPSTF findings would support screening selective populations at risk for deficiency. But the value of supplements for prevention is nil or still unknown.