cause-effect relationship. As a result foods are considered as only sums of nutrients and calories; and one nutrient is generally associated with one deregulated metabolism then one chronic disease (e.g., relationship between saturated fats, dyslipidemia and atherosclerosis whereas it is a reducing association). Reductionism can be considered as the main deep cause at the roots of diet-related chronic diseases that are encountered in populations consuming the most fractionated/recombined and refined ultra-processed foods, the ultimate consequence of reductionism. Indeed, if foods are only sums of nutrients why not cracking them in a multitude of nutrients and to recombine them. Nutritional supplements, functional foods and ultra-processed foods are therefore the consequences of our modern reductionist science. They are also based on the assumption that food health potential is based on its composition only.

On the contrary, holism views whole foods as more than a sum of nutrients because of synergy of action of nutrients and food matrix effect. Holistic nutrition science defines food health potential as combination of both matrix and compositional effects. Food is more than the only sum of nutrients (2 > 1+1). Matrix effect is crucial because it impacts satiety potential and nutrient bioavailability, both playing a crucial role to maintain a good health. Therefore two foods of identical composition but with a different matrix have not the same health potential.

Therefore to fight against the increasing prevalence of diet-related chronic diseases we need today to base more nutrition science on the holistic paradigm. Whereas recombined/refined ultra-processed foods are the fruit of reductionism whole and complex foods participate more of the holistic paradigm which should encourage technologists to less process foods to preserve their matrix, and public authorities to lay emphasis on minimally-processed foods as a basis of a healthy diet.

In addition to food science and technology the holistic paradigm may find other important applications in the study of diets on human health. Randomized controlled studies are coming from reductionist and pharmacologist designs, very far from real life, and cannot yield long-term and effective applicable results. Nutrition science is not pharmacology and foods are not drugs: therefore application of holism should prompt nutritionists to carry out intervention studies in complex real life conditions (taking into account all aspects of dietary lifestyles), and not to control only one.

Finally reductionist and holistic paradigms are both necessary: however more importance to holism should be given. Reductionism only becomes meaningful when it is embedded and circumsumed in a thorough and holistic reflection. If not, reductionism turns around, and only produces partial scientific truths devoted to agro food industry benefits.

**Keywords:** Holism, Reductionism, Nutrition, Food matrix, Processing

## IS THE RCT THE BEST WE CAN DO?

Martínez-González, Miguel Ángel.

Universidad de Navarra. CIBEROBN. Spain. Harvard T.H. Chan School of Public Health. Boston, USA.

Large randomized controlled trials (RCTs) are apparently the only way to circumventing the methodological problems of observational research, such as misclassification, reverse causation and residual confounding.

But small, short-term RCTs with surrogate markers of disease as the outcome are clearly not the solution. To give a high value to changes in any single surrogate biomarker is a mistaken approach, given that there are multiple pathways leading from diet to disease. Moreover, the induction period can vary for the different pathways in which diverse biomarkers are involved, thus limiting the possibility of assessing multiple biomarker combinations at any time point. Furthermore, other lesser-known pathways could account for a substantial proportion of clinical events. Therefore, the gold standard should be long-term RCTs with hard clinical events. In them, participants should be willing for a long period (usually at least 5-6 years) to eat what the investigators decided that they should eat, not what they like to eat. This is very problematic.

A highly prevalent tenet in the current nutrition literature is that “prospective cohort studies provide evidence only of statistical associations (“mere correlations”) but not causation whatsoever, because only RCTs can answer causal questions”. Under that assertion, most of the current practices and policies in public health would lack sufficient scientific foundation. The truth is that sound and effective public health actions have been based in well-designed, conducted and analyzed observational epidemiologic studies. They do provide valid answers to causal questions in nutrition.

The criteria for causality established by Bradford Hill long time ago are the leading principles to obtain causal inferences from observational studies. They keep their validity nowadays. Cause and effect associations can be drawn when most of these criteria are met, especially when there is consistency among many well conducted observational studies.

Conversely, methodological challenges in designing RCTs in nutrition can frequently induce biases. They speak against any “fundamentalism” for the RCTs. They include the intensity of the “intervention” to be delivered to the control group, selection biases due to selective attritions, deficient adherence to the prescribed diet (suboptimal compliance is the rule and not the exception), contamination of the control group with the intervention protocol, erroneous assumptions about the induction period or potential effect modifiers, and, very especially a small and insufficient contrast in the diets of the intervention and control groups. These biases tend to operate towards the null and several RCTs in nutrition ended as non-informative, after astronomic expenses and many years of work. The PREDIMED trial, showing the benefits of the Mediterranean diet was an exception. But the results of PREDIMED were highly consistent with those of observational cohorts.

Therefore, very often, RCTs are not the best design to answer causal questions regarding long-term effects of dietary exposures. Because a well-conducted cohort study can simulate an RCT when the most important confounders have been controlled for, the
combination of RCTs with well-conducted and analyzed cohort studies should be the optimal approach to draw causal inferences in nutrition.

**Keywords:** Randomized clinical trials, Mediterranea diet, intervention, cardiovascular disease

## NUTRITION IN TRANSITION, THOUGHTS AND ACTIONS OF A MULTIDISCIPLINARY WORKING GROUP

(1)de Vries, Jan; (2)Feskens, Edith.

(1)De Vries Nutrition Solutions. The Netherlands.; (2)Division Human Nutrition, Wageningen University. The Netherlands.

In the past decades valuable knowledge has been produced about the interaction of nutrients, food and the human body. The mostly multidisciplinary approach in nutrition science has accomplished a lot, both scientifically and socially. Despite this, nutrition sciences appear to be in a crisis. Public reluctance to trust nutritional insights creates space for many authors with nutrition messages that are not aligned with general views of nutrition and health.

In the Netherlands, recently a multidisciplinary discussion group was formed to start a structured discussion about the capabilities and credibility of nutrition sciences. The group consists of scientists with a background in nutrition, epidemiology, physiology, medical sciences, behavioral sciences, philosophy, ethics and statistics. Since 2015 we organized several discussions about the limitations recognized in nutrition sciences, such as discussions about “health”, causation”, “evidence” etc. In 2016 we organized a dedicated workshop with scientists from a diversity of disciplines invited on a personal title.

We diagnosed that nutrition science is meeting its inherent boundaries, which hampers conceptual and methodological progress and the translation of novel insights into societal benefit and trust. The methods in nutrition sciences need to change to accommodate the questions that arise from the major upcoming societal challenges.

The benefits of nutrition interventions aiming at prevention of chronic diseases cannot be related to one single cause. Despite the multifactorial causation of chronic diseases the pharmacological model of double blind placebo controlled intervention studies, usually called clinical studies, is considered as the method to prove causation. We think that this approach to prove causation needs to be reconsidered.

Ingestion of complex molecular foods interact with complex body function aiming at life-long prevention. In general a reductionist approach cannot be translated into benefits. Medicinal interventions readdress an unhealthy to a healthy condition in the shortest time span possible. The different employments of nutrition and medicines make the paradigms of sciences almost oppositional.

Nutrition sciences is strongly influenced by a reductionist focus. Due to political choices scientists need to search for private funding. That research focusses on products and nutrients instead

of food patterns, generating beliefs of quick wins. These myths need objective evaluation.

Such critical assessment is not the first. Concerns have been raised immediately after the landmark publication on Evidence Based Medicine in 1992. We have not been able to identify a structured discussion about the limitations of the capability and credibility of nutrition sciences.

The evidence we seek, the questions we ask, the funding and organisation threaten our credibility. A discussion is needed to agree on different ways of working and knowing. A new nutrition science agenda may provide plenty of potential for excitement and includes reaching out to multiple disciplines that are important to create answers needed on future questions. In parallel to and based on the outcomes of our discussions we aim at developing research projects creating new generation nutrition sciences that is incorporating as many as possible scientific disciplines. New partnerships, activities and agendas are the cornerstones for a more capable and credible nutrition science.

**Keywords:** Credibility, Magic bullets and myths, paradigms, Multidisciplinary science.

**Conflict of Interest disclosure:** Jan de Vries is working as consultant in the nutrition science area (www.devriesnutrition-solutions.nl). Edith Feskens is professor at the Division Human Nutrition, Wageningen University. No financial support from private origin has supported the project Nutrition in Transition in the Netherlands.

## LINKING AGRICULTURE AND NUTRITION EDUCATION TO IMPROVE ACCESS TO QUALITY FOODS FOR YOUNG CHILDREN

(1)Wijesinha Bettoni, Ramani; (2)Muehlhoff, Ellen; (3)Westaway, Elizabeth; (4)Jeremias, Theresa; (5)Nordin, Stacia; (6)Garz, Julia.

(1)PhD. Nutrition Officer. Food and Agriculture Organization of the United Nations. Rome, Italy.; (2)Formerly FAO Rome); (3)(PhD. Formerly FAO Rome); (4)CARE Germany-Luxembourg, Bonn, Germany; (5)University of Illinois at Urbana-Champaign, Champaign, USA and Feed the Future Malawi.Strengthening Agricultural and Nutrition Extension, Lilongwe, Malawi (formerly FAO Malawi); (6)Plan International, Hamburg, Germany.

Agriculture has a central role to play in nutrition by supplying nutritious, healthy and affordable foods in a sustainable manner. When integrated with nutrition education for behaviour change, agricultural interventions have the ability to improve young child and family diets. Process reviews were conducted in Cambodia and Malawi of food security projects carried out by the Food and Agriculture Organization of the United Nations (FAO) that provided agricultural support and community-based nutrition education on improved infant and young child feeding (IYCF). In both countries, household visits were carried out with mothers/caregivers, and interviews and Focus Group Discussions (FGD) were conducted with purposively selected project stakeholders (53 in Cambodia, 170 in Malawi). Results showed that adoption of improved IYCF practices
were facilitated by participation in nutrition education and practical cooking sessions, with supportive family and community structures playing an important role. Barriers faced by families and caregivers included women's workload and lack of access to high quality foods, such as fruits, vegetables, legumes, nuts and animal source foods. Implementation challenges included coordination issues in regard to cross-sectoral targeting strategies and ineffective capacities of extension services to deliver a community-based IYCF nutrition education programme. Lessons learned from the project can guide future integrated agriculture-IYCF nutrition education programmes to help ensure better young child nutrition outcomes.

**Keywords:** Infant and young child feeding, complementary food, nutrition education, agriculture, Cambodia, Malawi

**Further collaborators:**

Acknowledgements:

We are grateful to the German Federal Ministry of Food and Agriculture (BMEL) for funding the IMCF project, under which the process reviews in Cambodia and Malawi were carried out. We would like to thank the European Union and the Government of Flanders, Belgium for funding the FAO MALIS Cambodia and IFSN Malawi projects, respectively. We appreciate the support of colleagues of the FAO MALIS and IFSN projects, line ministries, NGOs and community volunteers, enumerators, drivers and translators, with implementation of the process reviews; they made this work possible. We are grateful to colleagues of the FAO MALIS and IFSN projects and the FAO Headquarters backstopping team, who made invaluable contributions in the collection, processing, transcription, translation and analysis of the process review data. Special mention is due to Iean Russell, former MALIS Project Manager, Wells Kumwenda, former IFSN Project Coordinator and the late Lawrence Chakholoma, IFSN Project Nutritionist for their dedication and support. Irmgard Jordan from Justus Liebig University in Giessen, Germany is also acknowledged for her insightful comments on the manuscript. Last but not least, special thanks are due to the project participants who provided information and shared perceptions on their daily lives.

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# TRENDS AND PRACTICE IN CLINICAL NUTRITION

## EFFECT OF PROBIOTICS ON HUMAN BLOOD UREA LEVELS IN PATIENTS WITH CHRONIC RENAL FAILURE

Chronic Kidney Disease (CKD) accelerates cardiovascular disease (CVD), predisposes to infectious diseases and numerous

other morbidities that increase mortality, that shortens the life span and impairs the patient's quality of life. Most of these abnormalities are mediated by systemic inflammation, that is common in CKD. Uremic toxins retained as a result of altered kidney function contribute significantly to this inflammatory state and the rearrangement in many body organs. Dysbiosis (a quantitative and qualitative alteration of intestinal microflora), is a consequence of changes in intestinal transit, decreased protein absorption, decrease in dietary fibre intake, treatment with oral iron and frequent use of antibiotics that are very common in CKD.

The human gastrointestinal microbiota represents the largest body microbial load. This bacterial load and its products have been shown to contribute to both the progression of CKD and activation of the inflammatory cascade in CKD. Thus, gut dysbiosis characterized by a disruption of the homeostatic balance in gastrointestinal tract in CKD is associated with the production of nephrotoxins (mainly urea, indoxyl sulfate, p-cresil sulfate, etc), which are introduced to the systemic circulation, contributing to systemic inflammation, and possibly to the progression of CKD.

Systemic inflammation and uraemic toxins play a central role in the pathophysiology of atherosclerosis, as well as in other complications associated with CKD, and it is suggested a role of bacterial metabolites (from probiotics) in the gut, as potential uremic toxins modulators, reducing the progression of CKD and associated uremia.

Probiotics are defined as "living micro-organisms" that, being administered in adequate amounts, provide a health benefit to the host. Recently, it has been demonstrated the potential benefits of probiotics in CKD. They have been shown to be associated with a change in small bowel pathobiology by modifying the metabolic actions of small bowel bacterial overgrowth, reducing the generation of toxins and carcinogens and promoting nutrition with no adverse side effects.

The efficacy of using different types of probiotics at different doses with the aim to reduce levels of uraemic toxins and to delay the progression of CKD has been investigated in in vitro models, animal models and in patients with CKD. However, to date, there are no large-scale intervention studies and studies on clinical events to support their widespread use. There are only small studies, most of which, observe a decrease in uraemic toxin levels like urea.

We recently demonstrated in a randomised trial in 30 patients KDIGO 3 and 4 stages of CKD, that there was a decrease in serum urea level greater than 10% after a conventional dietetic treatment plus a probiotic (lactobacillus casei shirota) in a dose of 6 x 10⁹ CFU.

Based on the results obtained to date, it can be concluded that further investigations on the effects and adequate doses are necessary to prevent and help minimize the production of uremic toxins in CKD patients.

**Keywords:** Urea, probiotics, doses, chronic kidney disease, inflammation

<footnote>(1) Espinosa Cuevas, María de los Angeles; (2) Atilano-Carsi, Ximena;</footnote>

<footnote>(2) Miranda Alatriste, Paola.</footnote>

<footnote>(1) PhD. Nutritionist. Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán. Departamento de Nefrología y Metabolismo Mineral; (2) PhD. Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán. Departamento de Nefrología y Metabolismo Mineral.</footnote>
## FODMAP, SIBO and gut microbiome

Knight, Karina.

MBA. MS. RD. Nutritionist. University of Miami. California
Nutrition Group. USA.

The gut ecosystem is complex and contingent upon multiple factors, diet is of relevance because it can induce rapid changes within 1-2 weeks in gut microbiota composition and function. Production of gut derived metabolites from diet is limited by the composition of the gut microbiota. Fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs), short-chain carbohydrates that are poorly absorbed by the small intestines. An increasing body of research shows that these food molecules trigger symptoms of IBS and some other digestive disorders such as small intestine bacterial overgrowth (SIBO). Because these food molecules are not properly absorbed, they transpire in the large intestine, where bacteria that live in the gut feed on them and then produce gas byproducts, namely hydrogen and methane. However, a diet low in FODMAPs appears to alleviate many of these problems. Plant based fiber, undigested protein, fat and carbohydrates influence the composition and metabolic activity of the microbiome. Agrarian diets high in fruit/legume fiber associated with increase in microbial diversity, whereas Western diet is associated with a decrease of beneficial Firmucutes and increase of Proteobacteria. Diet plays a role in microbiota but may be constrained by other factors: Gut microbiota likely differs in globally distinct populations. Low-FODMAP diet reduces beneficial probiotic microbiota and increases fecal pH, long-term impact is unknown.

**Keywords:** Gut microbiome, Small intestinal bacterial overgrowth, Irritable bowel syndrome, Low-FODMAP diet, probiotics.

Cachexia was divided also into stages ranging from the early weight loss to death. These stages are known as precachexia. Cachexia and refractory cachexia. It is necessary to know the definitions of each stage because it has been observed in recent studies that if nutritional support is provided until advanced stages of cachexia, there is no nutritional therapy. On the other hand, early nutritional interventions are the best choice of nutritional support in cancer patients. Because of this, early nutritional risk detection is required at the time of cancer diagnosis or from hospital admission to prevent the development of cachexia.

With this background, we have developed many research studies in Mexico City General Hospital, that are aimed to: determining nutritional and body composition in cancer patients at the diagnosis, before and after surgical treatments; to detect patients at nutritional risk; to know the effect of some specific nutrient therapies on inflammatory processes and oxidative stress in cancer patients; as well as the effects of standardized and specialized nutritional therapies and its effect on survival. All the strategies above are daily focused on the detection of nutritional risk and nutritional treatment of patients with cancer in the clinical nutrition service that we have also developed tertiary level in a public hospital in Mexico City.

More specifically, our studies showed that malnutrition is still highly prevalent in oncology patients. We found that cancer patients that started nutritional treatment on time had better outcomes and tolerance to oncology treatments. Supplementation with antioxidants in cervical cancer patients showed a significant effect on hemoglobin levels conservation, quality of life and it had not effect cancer recurrence. On the other hand, omega-3 fatty acids supplementation with EPA can regulate inflammation in head and neck cancer patients and leads to maintain their body composition and weight until the end of the antineoplastic treatment.

**Keywords:** Cancer, clinical trials, nutrition

## PRACTICAL ISSUES IN NUTRITION INTERVENTION IN CANCER PATIENTS

Fuchs-Tarlovsky, Vanessa.

PhD. Nutritionist. Hospital General de México. Servicio de Oncología.

Cancer is a public health problem that leads to malnutrition. There is enough evidence to show that 40% of hospitalized patients with cancer are malnourished or with high risk of becoming malnourished, because of the tumor itself and symptoms like nausea, vomiting, decreased appetite, and early satiety that leads to unintentional weight loss.

This specific type of malnutrition is known as cancer-cachexia. This is a concept that has evolved over the years, however it is not until 2011 that K Fearon et al. published an expert consensus that standardized the definition and classification of this condition. The consensus defined cachexia as a “multifactorial syndrome defined by an ongoing loss of skeletal muscle mass (with or without loss of fat mass) that cannot be reversed by conventional nutritional support and leads to progressive functional impairment”.

## ADVANCES IN DIABETES NUTRITION THERAPY

(1)Ruiz Cervantes, Gloria Marcela; (2)Melgarejo Hernández, Marco;

(3)Landa Anell, Victoria.

(1)MCN. Nutritionist. Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán. Centro de Atención Integral del Paciente con Diabetes; (2)Nutritionist. Nutritionist. Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán. Centro de Atención Integral del Paciente con Diabetes;

(3)Nutritionist. Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán. Centro de Atención Integral del Paciente con Diabetes.

Medical nutrition therapy (MNT) is essential for the optimal management of people living with diabetes (PWD). MNT is associated with the improvement of values of HbA1c 0.3-1% for patients with type 1 diabetes and 0.5-2% for type 2 diabetes, particularly in newly diagnosed patients or those who had HbA1c levels greater than 8%.

Different percentages of macronutrient distribution have been evaluated for diabetes prevention and treatment, however, there is
no consensus of an ideal percentage for PWD. Therefore macronu-
trient distribution should be individualized, based on preferences,
weight and metabolic goals. In a systematic review, non-significant
differences were found in HbA1c and other metabolic parameters
between a different amount of carbohydrate (from 39% to 57%),
protein (0.8-2.0 g/kg/d) and fat (from 27% to 40%) intake. PWD
taking MNT alone or those who do not follow an intensive insu-
lin therapy should be encouraged to comply to a consistent pat-
tern of carbohydate intake with respect to time and amount (basic
carbohydrate counting). On the other hand, patients on intensive
insulin therapy or with insulin pump therapy should be trained
on advanced carbohydrate counting, since this strategy has been
effective for lowering HbA1c levels on a long-term follow-up (12
months), besides increasing the quality of life despite more insulin
injections. Refined carbohydrates and added sugars should be re-
placed with whole grains, vegetables, legumes, fruits and non-fat
dairy. Non-nutritive sweeteners could be utilized instead of caloric
sweeteners to reduce overall calories, as long as the total daily in-
take is not affected. Regarding protein intake, there was a non-sig-
nificant difference in the glomerular filtration rate reduction with
an ingestion of 0.7 to 2 g/kg/day in PWD. In terms of fat intake, a
diet rich in monounsaturated fats may reduce cardiovascular risk
on a long term basis, replacing a low fat/high carbohydrate diet.
N-3 fatty acids showed nonsignificant benefits on metabolic levels,
particulary on glucose, however there was a significant reduction
in tryglycerides in patients with hypertryglyceridemia. The pro-
motion of adequate eating patterns, like Mediterranean, DASH
or plant-based diets, has a greater impact than the prescription of
particular food or nutrients.

Nutritional strategies, such as portion control, the plate meth-
od, sample menus, carbohydrate counting, exchange list, food
lists, simplify plan and goal establishment should be used based
on patient's needs, preferences, food access, health literacy and
numeracy, motivation and barriers to change. Identifying and re-
ducing this barriers is essential for the implementation of a more
accurate educational strategy. At the Center for Comprehensive
Care of the Patient with Diabetes (CAIPaDi) the identification of
barriers to MNT adherence at baseline, the use of a nutritional
simplified plan and baby steps strategies based on the identified
barriers have shown statistical significance in the reduction of cal-
orie consumption, weight and waist circunference after 3 months.

**Keywords:** Diabetes, medical nutrition therapy, CAIPaDi,
barriers

TRENDS AND PRACTICE IN CLINICAL NUTRITION

Nava-González, Edna Judith.

PhD. Certified Nutritionist. School of Public Health and Nutrition.
Autonomous University of Nuevo Leon. President of the Mexican
College of Nutrition.

Nutritional Sciences include nutrition processes as well as food
components, their actions, interaction and balance in conjunction

with health and disease. The applications of nutrition science re-
late to integrated human biology systems that gradually become
adjusted in the way a person changes qualitatively or quantitatively
over time.

The advance in the knowledge about the role of nutrients in different clinical pictures is continuous and not exempt from controversies (glutamine, arginine, fatty acids, antioxidants), which opens an enriching debate in search of a closer approximation to its functions, beyond the solely fact of offering a nutrition approach. This situation forces the professional in nutrition sciences to be prepared in depth in various fields such as modulation of inflammation and immunity, control of oxidative stress, and aging among others.

If we focus our knowledge on metabolic diseases related to
nutrition, it is necessary to take into account the environment to
provide a specific and individualized nutritional therapy. It has
been insufficient to only intervene on the main conventional en-
vironmental factors that contribute to the development of these
chronic diseases (obesity, type 2 diabetes, many cancers) which
include lack of physical activity, a sedentary lifestyle, unhealthy
eating habits, availability of very cheap foods, large portion sizes,
high levels of refined carbohydrates, calorically dense foods, and
consumption of saturated fats.

A broader view of environmental exposure is needed beyond conventional risk behaviors to discover the main causes of chronic diseases, not only the ones occurring in the external environment, but also those that impact internally, integrating a conceptual framework of a series of measurable biological events secondary to the environment, which directly cause inflammation, oxidative stress, lipid peroxidation, infections, alterations in the gut microbiota, causally associated with prominent classes of endocrine disruptors, immune response modulators, and agents that bind to cellular receptors.

Exposures to these agents can be monitored in the blood either
by direct measurement or by looking for their effects on physio-
logical processes such as metabolism. These processes influenced
by the external environment generate products that serve as mo-
lecular signatures and biomarkers in the blood. Therefore, an ex-
tension of the current generation of biomarkers could have a cru-
cial role to play in a specific diagnostic profile from the internal
environment that would be causally associated with the external
environment.

On the other hand, the functional components of foods may
have a great impact on the incidence and treatment of multiple
diseases. The nutritional message must be widely communicated:
we need extensive research on phytochemicals and chemoprotec-
tive functional food ingredients that can regulate inflammation,
oxidative stress and lipid peroxidation.

In conclusion, it is our responsibility to deepen the knowledge
of areas related to nutrition in order to offer in the near future a
more precise and individualized preventive care.

**Keywords:** Nutritional Sciences, Trends, Evidence-Based Practice, Clinical medicine
# VITAMIN C - ARE CURRENT RECOMMENDATIONS SUFFICIENT?

## WHAT IS THE OPTIMUM INTAKE OF VITAMIN C?

Carr, Anitra.

PhD. Senior Research Fellow. Department of Pathology.
University of Otago, Christchurch. New Zealand.

Historically, recommended dietary allowances (RDAs) for vitamin C were based on prevention of the deficiency disease scurvy. Now, more countries are basing their recommended intakes on antioxidant and other putative health effects of vitamin C as well as on biochemical markers of these. However, whether these recommendations provide optimal intakes of vitamin C is uncertain because of the difficulty in defining the 'optimal intake'. Vitamin C intakes which provide plasma saturation (i.e. ~200 mg/d) are considered optimal by some researchers. Although intakes of ~100 mg/d are sufficient to saturate white blood cells, we have found that muscle tissue vitamin C levels continue to rise with increasing intakes up to plasma saturation. Large population-based surveys in Europe and North America have provided insights into the normal dietary intakes and plasma levels of these cohorts, as well as the prevalence of hypovitaminosis C (i.e. <23 µmol/L) and deficiency (i.e. <11 µmol/L). Some countries have higher recommended dietary intakes for smokers and pregnant women due to their increased requirements for vitamin C. We, and others, have also shown that individuals with hypovitaminosis C have higher requirements for vitamin C, likely due to depleted tissue status. Clearly a 'one size fits all' intake recommendation is complicated by numerous confounding factors. This talk outlines various ways of determining the optimum intake of vitamin C.

**Keywords:** Vitamin C, hypovitaminosis C, dietary intakes, plasma status, RDAs

## BIOMARKERS FOR VITAMIN C REQUIREMENT

(1)Elste, Volker; (2)Troesch, Barbara; (3)Eggersdorfer, Manfred; (4)Weber, Peter.

(1)PhD. Dr. med vet. DSM Nutritional Products AG. Switzerland;

(2)Dr. sc. ETH. DSM Nutritional Products AG. Switzerland; (3)Prof. Dr. DSM Nutritional Products AG. Switzerland; (4)Prof. Dr. med. DSM Nutritional Products AG. Switzerland.

Intake recommendations for vitamin C are currently defined using markers for status, as no suitable functional biomarker has as yet been identified. There are different functional biomarkers for Vitamin C but up to now, no one was identified that could be used as a basis to define dietary intake recommendations for vitamin C. Emerging evidence support neutrophil motility as such a functional biomarker. A recent in vitro study showed that adequate levels of vitamin C were needed for this function to work

optimally when measured as chemotaxis and chemokinesis. Furthermore, in a human intervention study with healthy subjects, neutrophil motility was optimal at intakes at ~250 mg/d.

These findings are supported by established knowledge including a Cochrane review which showed a significant reduction in the duration of episodes of common cold in children as well as in adults with regular vitamin C intakes in a similar range. This is in line with human kinetic studies where plasma saturation was reached with 200 mg/ day and also the related vitamin C transporters reached their maximum at this dose. Additionally, in observational studies it was shown that at plasma level of 75 µmol/L, which can be reached with vitamin C intakes of ≥200 mg/d, incidences of cardiovascular disease were lowest. A relationship between vitamin C concentration, severity of atherosclerosis and inflammation in peripheral artery disease patients could be shown.

However, additional studies are needed to investigate further the reliability and accuracy of neutrophil motility as a functional marker of vitamin C dependent immune function. Given the number of people affected by common cold, cardiovascular disease and others, defining recommendations with the highest risk reduction for these diseases is of paramount importance.

The evidence would suggest that daily intakes of 200 mg vitamin C might be advisable for the general adult population, which can be achieved by means of a diverse diet.

**Keywords:** Vitamin C; ascorbic acid; dietary reference value; immune function; neutrophil motility

**Conflict of Interest disclosure:** All authors are employed by DSM Nutritional Products Ltd., a bulk producer of vitamins.

## THE PHARMACOKINETICS OF VITAMIN C

Lykkesfeldt, Jens.

Professor at University of Copenhagen, Denmark.

Vitamin C is a low molecular weight water soluble antioxidant vital to human health. Vitamin C homeostasis is tightly controlled by the body and sophisticated ways of preserving and allocating the body's ascorbate resources to organs in need has evolved including ascorbate recycling and tissue specific accumulation and retainment. Vitamin C pharmacokinetics differs markedly from that of an average drug in that vitamin C e.g. follows complex saturation kinetics and is subjected to active reabsorption in the kidneys at physiological levels. The lack of acknowledgment of these and other factors have led to poorly designed and misinterpreted human intervention studies that expectedly have shown no effect of vitamin C supplementation. The present talk outlines the pharmacokinetics of vitamin C and how it impacts the proper design of intervention studies with vitamin C.

**Keywords:** Vitamin C; distribution; pharmacokinetics; trials
## VITAMIN C RECOMMENDATIONS: PHARMACOKINETICS AND FUNCTION

(1)Levine, Mark; (2)Wang, Yaohui; (3)Violet, Pierre-Christian;

(4)Tu, Hongbin; (5)Wang, Yu; (6)Ebenuwa, Ifechukwude; (7)Guelce, Dominique.

(1)M.D. Physician Scientist. National Institute of Diabetes and Digestive and Kidney Diseases. National Institutes of Health. Bethesda MD 20892 1372; (2)MD Biologist. National Institute of Diabetes and Digestive and Kidney Diseases. National Institutes of Health. Bethesda MD 20892 1372; (3)PhD. Postdoctoral Fellow. National Institute of Diabetes and Digestive and Kidney Diseases. National Institutes of Health. Bethesda MD 20892 1372; (4)PhD. Staff Scientist. National Institute of Diabetes and Digestive and Kidney Diseases. National Institutes of Health. Bethesda MD 20892 1372; (5)PhD. Research Fellow. National Institute of Diabetes and Digestive and Kidney Diseases. National Institutes of Health. Bethesda MD 20892 1372; (6)MD. Staff Clinician. National Institute of Diabetes and Digestive and Kidney Diseases. National Institutes of Health. Bethesda MD 20892 1372; (7)BA. PostBac Program. National Institute of Diabetes and Digestive and Kidney Diseases. National Institutes of Health. Bethesda MD 20892 1372.

Vitamin C (ascorbic acid) Recommended Dietary Allowances have two foundations: pharmacokinetics, and function in relation to in vivo concentration. Human pharmacokinetics data for ascorbic acid are more detailed than for nearly all other vitamins. Such pharmacokinetics data have substantial value. For ascorbic acid, pharmacokinetics data reveal that with oral dosing ascorbic acid plasma concentrations are tightly controlled. At least four mechanisms are responsible: intestinal absorption, or bioavailability; tissue transport: renal reabsorption/excretion; and utilization in vivo. At doses between 100-200 mg daily: intestinal absorption is near maximum; tissue transport is close to saturation; and renal excretion is close to estimated threshold. Utilization data, though often indirect, suggest that accelerated ascorbate utilization occurs in some diseases such as sepsis or in critically ill patients. Pharmacokinetics data also show that tight control is by-passed with intravenous administration of ascorbic acid as a drug. Intravenous ascorbic acid administration, as a function of dose given, produces pharmacologic concentrations. These concentrations have promising efficacy in cancer treatment, including studies in humans, with minimal side effects. Applicability of pharmacologic ascorbate in cancer therapy and in critically ill patients would not have been apparent without the foundation of pharmacokinetics. To date, there are few datasets linking ascorbate function in vivo to its concentration in vivo. For this reason, in vitro functional data with human neutrophils are used to characterize ascorbate function in relation to its concentration. These data have limitations. In vivo functional assessments, endpoints, or validated biomarkers are needed to improve accuracy of recommended dietary allowance recommendations for ascorbate, and for other vitamins.

**Keywords:** Vitamin C, ascorbic acid, recommendations, pharmacokinetics

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## MEANING OF LINEAR GROWTH: APPROPRIATE USE OF GROWTH AS A MEASURE IN DEVELOPMENT

### BIOLOGY OF LINEAR GROWTH: PROCESSES AND NUTRITIONAL, HORMONAL, AND INFLAMMATORY DETERMINANTS

Lampl, Michelle.

Nutrition Department. Emory University. USA

Longitudinal studies of humans document that suboptimal nutrition during early life has long-term consequences on skeletal size. This outcome is highly dependent on the developmental age when the insult is experienced. Nutrition acts at the individual's cellular level: individuals consume nutrients and these translate to growth through a system of cell-level processes. Understanding the specific cellular events responsible for skeletal growth and development is essential in order to identify the critical periods during which the organism is at-risk for growth perturbation and intervention. Skeletal growth regulation takes place within distinctive anatomical sites during individually-specific time frames. This involves molecular mechanisms acting at sequential life cycle stages of the cells responsible for bone elongation at the site of long bone growth, the endochondral growth plate. Extracellular cues regarding energetic status and constituent availability are translated by intracellular signaling pathways to influence regulatory networks at cellular control points governing bone elongation and maturation. Nutrients influence this cascade as the source of both the necessary substrates and extracellular cues which regulate the signal transduction pathways that control anabolic processes. Moreover, while the limiting resource for growth is generally viewed to be a direct reflection of energy availability, other mechanisms that reflect nutritional influences include the allocation of common precursor cells to the chondrocytic lineage, osteoblast-specific cellular bioenergetics, and downstream hormonal and cytokine effects. When these developmental phases are perturbed, skeletal growth deficits occur that may or may not be entirely recoverable.

**Keywords:** Bone growth, endochondral bone, critical period

### HISTORY OF USING OF GROWTH AS A MEASURE OF HEALTHY CHILD DEVELOPMENT

(1)Krasevec, Julia; (2)Krasevec, Julia.

(1)UNICEF; (2)Statistics and Monitoring Specialist. UNICEF. New York.

The growth curve is a fundamental tool that allows length and height measures to be used to ascertain whether healthy child growth and thus development is occurring at an individual or population level. The growth curve displays the size of a child over time while also visualizing how the growth velocity varies at different stages based on the steepness of the curve along different parts of
the trajectory. The first child height curve was published in the 18th century in George Buffon's Histoire Naturelle, using a chart developed by Count Philibert de Montbeillard who plotted his son's height every six months from birth to age 18 years. Since then, growth charts have expanded in scope to cover growth patterns of groups of children, becoming an important tool in child health screening. The United States developed growth reference charts using data from their National Health and Nutrition Examination Surveys that could be used to establish whether the growth of other individuals or groups of individuals were typical of the reference group. This growth reference was adopted by WHO in 1977 and used to monitor child growth and health globally for the next 30 years at regional, sub-regional, and national levels. As the US-based growth reference had a number of technical and biological limitations, including a large percentage of non-breastfed and formula-fed infants, WHO embarked on development of growth standards of children 0-5 years of age which represents how children should grow if exposed to optimal conditions while in utero and after birth. Data were collected from 6 countries (Brazil, Ghana, India, Norway, Oman, and the United States), for the development of the sex-specific growth standards and were published in 2006.

Since their publication, over 150 countries have adopted the WHO Growth Standards and use them as the basis for clinical screening of an individual child's growth and also to summarize the proportion of children in a population suffering from suboptimal growth. The use of one set of standards helps compare prevalence of malnutrition across countries, highlight populations at greatest need of intervention, and assess progress towards global goals such as the Sustainable Development Goals. The availability of standards for growth velocity has provided an additional way of assessing how well children are growing.

The standard tool for measuring child length and height has been a stadiometer, and while it serves the purpose of a calibrated piece of equipment, measurement error has been found in both clinical- and population-based applications, largely related to the proper positioning of small children who can be reluctant subjects. Looking forward, as various groups are working on the development of alternative tools to assess length and height, many of which are tablet-based and do not require any specific positioning of the child, there is potential for minimizing error and also for improved usability of the data.

**Keywords:** Height, length, measurement, growth standards

**Further collaborators:** Edward Frongillo Jr.

## THE MEANING OF LINEAR GROWTH: DIFFERENTIATING GROWTH AS A CAUSE VS. A MARKER OF OTHER OUTCOMES

Leroy, Jef.

Senior Research Fellow. Poverty, Health and Nutrition Division.
International Food Policy Research Institute. Washington, DC.
USA.

The prevention of undernutrition is receiving unprecedented global attention. Undernutrition during early life has severe con-

sequences, not only in infancy and childhood, but also during adulthood. Malnourished infants and young children are at increased risk of illness and death, and are also more likely to experience physical, cognitive, educational, and productivity deficits as adults. Much of the focus of this global effort is on reducing the prevalence of stunted linear growth (target 2.2 of the Sustainable Development Goals). Linear growth retardation is associated with a number of undesirable short-term (such as delays in cognitive development), medium-term (lower school achievement), and long-term outcomes (lower earnings and a higher probability of non-communicable chronic diseases at adulthood).

Our presentation will explain how these associations in combination with the focus on linear growth as a development target has created the impression that short stature is causally linked to these physical, cognitive, educational, and productivity outcomes and how it has created the false expectation that any intervention aimed at improving linear growth retardation (or reducing stunting) will subsequently lead to improvements in these outcomes. We will show how this misunderstanding appears to have contributed to two recent developments: the focus on aflatoxin exposure as a determinant of linear growth retardation and the renewed interest in catch-up growth. We will conclude with a framework that clearly differentiates between two key uses of linear growth: as an indicator or marker (reflective of the past or predicting future outcomes) and as an outcome in its own right.

**Keywords:** Child growth; stunting; marker; catch-up; aflatoxin

## APPROPRIATE USE OF LINEAR GROWTH AS A MEASURE IN DEVELOPMENT

Frongillo, Edward.

Department of Health Promotion, Education, and Behavior,
University of South Carolina, United States.

Early undernutrition results in risk of illness and death as well as physical, cognitive, educational, and productivity deficits later in life. Much of the current attention on undernutrition focuses on reducing stunting. This focus on linear growth in development reinforces the view that short stature is causally linked to both short- and long-term physical, cognitive, educational, and productivity outcomes, leading in turn to expectations that interventions aimed at reducing stunting through prevention of linear growth deficits will lead to improvements in negative consequences of undernutrition.

The nutrition development community has been confronting two related challenges. First, many studies report small or no intervention effects on reducing stunting, while sometimes reporting noticeable secular changes in linear growth over time. Second, the emphasis on nutrition-sensitive as well as nutrition-specific interventions leads to questioning whether linear growth is an appropriate primary outcome to measure.

About forty years ago it was established that well-nourished children throughout the world grew similarly on average. This equivalence provided a basis for using the assessment of children's
growth status for global and national monitoring of population
well-being. The 1987 First Report of the World Nutrition Situa-
tion by the United Nations Subcommittee on Nutrition used child
underweight prevalence, and ten years later sufficient data were
available for the Third Report to use stunting prevalence. Use of
stunting prevalence is appropriate for the purpose of monitoring
changes in child growth status at the population level, but not nec-
essarily for other purposes such as assessing whether interventions
have made a difference. Nutrition interventions may reach and
impact children, but may not impact length growth deficits in a
short period.

Child linear growth depends on both the prenatal and post-na-
tal environment, with the post-natal environment influencing
growth through nutritional intake and exposure to infection,
which in turn result from food security, care of children, and
health services and environment. Child growth status is thus
associated with child nutritional status, but it is not the same as
nutritional status. That is, length growth is a marker of nutrition
useful for some purposes, but is not nutrition. Furthermore, chil-
dren grow through complex biological mechanisms that unfold
daily and are only partially understood. Partial restoration of lost
growth is sometimes possible when constraints are removed, but
it is not clear if this is important. Some claims made that catch-up
growth of children can occur are based on misunderstanding of
both the concept of catch-up growth and analytic inference.

Interventions intended to have impact on one domain may
have positive or negative impact on others, so impact evaluations
should use a broad set of health, nutrition, and development meas-
ures and indicators. Furthermore, measures for immediate and
underlying determinants should be included, e.g., breastfeeding,
complementary feeding, and food processing; caregiving; and
hygiene and home health. There is need to develop, refine, and
validate measures and indicators for evaluation purposes, e.g.,
validation of child-development measures in low- and middle-in-
come countries and development of innovative markers of child
development.

**Keywords:** Growth, children, nutrition, interventions, evaluation

pathology can result. Indeed, chronic inflammation is the central
component of many human diseases including rheumatoid arthri-
tis, inflammatory bowel disease and asthma. Chronic low grade
inflammation is now recognised to be a component of lifestyle dis-
eases like obesity, type 2 diabetes and atherosclerosis. Both high
and low grade inflammation may result from failure of resolution
mechanisms. Fatty acids can regulate inflammatory processes, in-
cluding resolution. Some saturated fatty acids have been shown
to trigger inflammation by stimulating known pro-inflammatory
receptors like toll-like receptor 4. Cells involved in inflammation
typically contain a relatively high amount of the omega-6 fatty acid
arachidonic acid, which is a precursor of pro-inflammatory eicos-
anoids like prostaglandin E2 and leukotriene B4. The omega-3
fatty acids EPA and DHA are readily incorporated into inflam-
matory cells in a dose dependent manner. They can modify the
function of inflammatory cells through multiple mechanisms that
ultimately involve altered patterns of gene expression and altered
patterns of production of lipid and peptide mediators. These in-
clude decreased production of pro-inflammatory eicosanoids and
cytokines and increased production of pro-resolving mediators
like resolvins and protectins. Through these effects, EPA and DHA
can affect inflammatory cell responses and inflammatory process-
es and they act to counter the effects of saturated fatty acids, ome-
ga-6 fatty acids, and classic inflammatory stimuli (e.g. LPS). The
anti-inflammatory and inflammation resolving effects of EPA and
DHA are clinically relevant.

**Keywords:** Omega-3, Inflammation, Lipid mediator, Cytokine

INMUNOMODULATION BY PROBIOTICS AND
FERMENTED MILKS IN HEALTHY AND SICK SUB-
JECTS

Perdigón, Gabriela; Maldonado Galdeano, Carolina.

Researcher CONICET -CERELA; Tucumán University.

The immune stimulation by probiotics and fermented milk
containing probiotic bacteria(PFM) administered to healthy host,
induce a network of signals: a) stimulation of the intestinal epi-
thelial cells(IEC) and the immune cells associated to the lamina
propria, these facts are, induced by bacteria adhesion or by their
cell wall fragments stimulating the epithelial and the immune cells
to activate mainly the innate response b) The IEC induce the pro-
duction of different cytokines and chemokines able to send signals
to the immune cells of the lamina propria inducing an increase in
different markers of activation with the release of cytokines, which
will contribute to the Mucosal Immune System(MIS) activation c)
induce also activation of the adaptative response at local and sys-
temic levels, with an increase in the specific secretory IgA (S-IgA)
and specific IgG antibody respectively.

In sick host we demonstrated their effectiveness in the anti-in-
flammatory process such as enteric infections, and in allergy. In
malnutrition models (under nutrition and obesity) we observed
an improvement in the histology of intestine and thymus with an
improvements in the Immune System functionality. We demon-

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IMMUNONUTRITION IN HEALTH AND DISEASE:
ROLE OF BIOACTIVE COMPOUNDS

FATTY ACIDS: MASTER CONTROLLERS OF IN-
FLAMMATION

Calder, Philip C.

Faculty of Medicine, University of Southampton, Southampton,
UK.

Inflammation is a normal response being part of host defence
and initiating tissue repair. However, where inflammation is ex-
ccessive or uncontrolled, tissue damage, metabolic changes and
strated the anti-inflammatory effect of yogurt in IBD model, where we observed a decrease mainly in the inflammatory cytokine IL17. We also analyze the effect of yogurt in another model of chronic inflammation as obesity. In this study, we compared the effect of conventional yogurt and one containing probiotic bifidobacteria. We demonstrate the anti-inflammatory effect of both yogurts by decreasing of proinflammatory cytokines

What would be the biological significance of these observa-
tions: 1) that the innate response that is key in host defense is able
to be influenced by probiotics and fermented milk 2) that probiot-
ic strains, LFP or yogurt have an important role in the mechanisms
of the immune surveillance

We conclude that probiotic strains, PFM and yogurt have an
important role in the functionality of the MIS and in the immune
surveillance, through the mechanisms of immunoregulation

Keywords: Immunomodulation, Probiotic, Fermented Milk

DO DIETARY PATTERNS INFLUENCE PRO-INFLAMMATORY-DERIVED CYTOKINES LEVELS IN HEALTHY ADOLESCENTS? FINDINGS FROM A POPULATION-BASED STUDY OF ADOLESCENTS IN MALAYSIA

Foo, Leng Huat.

Universiti Sains Malaysia.

Background and objectives: The aims of the present study was to investigate the influence of dietary patterns on blood pro-Inflammatory-derived cytokines of tumor necrosis factor-alpha levels (TNF-a) and also to examine whether such influence was mediated by adiposity levels, assessed by anthropometry and dual-energy X-ray absorptiometry (DXA) device assessments, among 413 apparently healthy adolescent boys and girls aged 12 to 19 y. Methods: A validated food frequency questionnaire was used to assess dietary food patterns, in which three dietary food patterns were identified based on the principal component analysis method. Blood pro-inflammatory-derived cytokines of TNF-a was assessed by the ELISA assay method. Results: Three dietary patterns were identified namely, healthy-based food pattern, western-based and local-based food pattern. Higher scores of healthy-based dietary pattern, characterised by high intakes of vegetables, fruit, dairy products, nut and cereal-based foods, was significantly associated with lower concentrations of serum TNF-a after adjustment for age, race, gender, pubertal growth status, and moderate-to-vigorous physical activity levels. Even further adjustment for DXA-derived adiposity indices in the analysis models, adolescents with higher intakes of healthy-based food pattern had significantly lower serum blood pro-Inflammatory of TNF-a levels. On the contrary, neither western-based food pattern nor local-based food pattern was significantly associated with serum TNF-a levels. Conclusion: Intakes of healthy-based food pattern that is characterised by higher levels of vegetables, fruit, dairy products, nut and cereal-based foods was independently associated with lowering pro-inflammatory marker of TNF-a levels in the blood. This find-

ing suggests that lower intakes of healthy-based food pattern may
contribute directly to the development of low-grade inflammation
in these adolescents during these critical years of growth.

**Keywords:** Dietary patterns, pro-Inflammatory-derived cytokines, inflammation, Adolescents

HOW TO TACKLE PROTEIN AND ENERGY MAL-
NUTRITION IN THE ELDERLY

Kido, Yasuhiro.

PhD, Dietitian, Faculty of Human Health Science, Kanazawa
Gakuin University, Japan.

Now in Japan, we have seen an increase in the life expectancy, and the number of aged citizens is still increasing. In order to promote a society where the citizens can maintain an independent lifestyle even at an advanced age and expect a healthy life expectancy, without the need for nursing care due to physical dysfunction, attention has been focused recently on the importance of the relationship between physical dysfunction in the future and the prevention of frailty and sarcopenia. The target of these preventive measures is the skeletal muscle, and the goal is the maintenance of the skeletal muscle and structure. Due to the strong relationship between the skeletal muscle mass, muscular strength and physical functions with protein intake, attention has been drawn to the importance of protein. Compared with normal adults, in the elderly the protein synthesis in the skeletal muscle induced after a meal (after protein intake), shows a relatively reduced reactivity and some reports have indicated the presence of synthesis-resistant properties. Furthermore, some reports have indicated that, even if the essential amino acids required by the skeletal muscle in the elderly existed in the blood stream, the mammalian/mechanistic target of the rapamycin complex (mTORC) and the downstream signal activation were suppressed. In addition, some recent reports have indicated that the actual situation in the elderly is that the intake of protein is insufficient to maintain health.

Up to the present, estimates of the protein requirement have been obtained using the nitrogen balance method, which derives the final estimate of the protein requirement through a step by step method where the intake of protein in changed in each step. However, the estimates of the protein requirement calculated using the nitrogen balance method showed a tendency for underestimated values. In 2007, a new method for estimates of the protein requirement was reported, called the indicator amino acid oxidation method. According to this new estimation method, the estimated protein requirement was 1.3 - 1.5 times that obtained by the previous method. Especially, for the elderly, the new estimates were almost the same as the estimates for the protein requirement for schoolchildren. Thus, for the elderly, we consider that it is im-
portant to promote "more protein intake and the intake of good protein."

**Keywords:** Protein requirement, nitrogen balance method, indicator amino acid oxidation method, frailty, elderly

**Further collaborators:**

Prof. Toshinori Nishimura, Faculty of Nutrition, Kagawa Nutrition University, Japan

Prof. Kraisid Tontisirin, Institute of Nutrition, Mahidol University, Thailand

Prof. Guoyao Wu, Department of Animal Science, Texas A&M University, USA

# DELICIOUSNESS, A STRATEGY FOR COMPLIANCE OF HIGH PROTEIN DIETS

Nishimura, Toshihide.

Ph. D., Professor, Kagawa Nutrition University. Professor emeritus, Hiroshima University. Japan.

It is well known that there are more than 10, 000 kinds of proteins in our body which are parts of tissues such as muscle, liver, heart, bone, hair, skin and brain, and lots of enzymes and hormones and so on. These body proteins are periodically renewed as protein metabolism to keep our health. Food proteins are resources for the newly synthesized protein in metabolism. Therefore, the taking food protein in daily meal plays an important role in keeping our health. In Japan, 60 grams and 50 grams of proteins are recommended to take from foods every day for male and female in adults (over 18 years old), respectively. Recently, old people over 65 years old are also recommended to take the same amount of proteins as young adults to prevent from sarcopenia caused by deficiency of muscle proteins. Especially, the essential amino acids are required for protein syntheses in body. Since these amino acids are not able to be synthesized in our body, they are supplied from food proteins.

It is well known that meats, fishes, milk products, eggs and soy bean in foods contains high amount of proteins. For example, roast beef loin, roast pork loin, roast chicken breast meat, and boiled soy bean 20.4, 26.7, 34.7 and 14.8 grams of protein in 100 grams of foods, respectively. Furthermore, these foods also have the well-balanced essential amino acids. Therefore, these stuffs should be supplied in daily meal.

Among these foods, meats are very popular as a delicious food. Although there are many factors to decide deliciousness of foods, taste, aroma and texture play a very important role in deliciousness of meats. In general, more-flavored and tender meats are recommended to be delicious ones. These qualities of meats are generated during post-mortem aging after slaughter. The meats immediately after slaughter are tough because of rigor mortis, and have less meat flavor. However, during storage, meats become tender, because structure of meats has loose by the action of proteases such as calpain and cathepsins. The more flavor in stored meats is generated by Maillard reaction between free amino acids and sugars, leading that in general, the conditioned meats are

more delicious. Recently, it has been found that umami substances such as glutamic acid and inosinate that increase during storage of meats play an important role in improvement of deliciousness in meats. They can enhance the intensity of retronasal aroma sensation of meats after putting meats into mouth. This effect leads to the deliciousness of the conditioned meats. The fat of meat has also been found to play an important role in deliciousness, because fats can hold aroma compounds of meats and give us continuity of aroma sensation. This is one of the reasons why the meat of Japanese black cattle is so delicious.

In this presentation, I would like to explain the importance of taking meats in daily meal to keep health and the deliciousness of meats.

**Keywords:** Meat, protein, health, deliciousness

# LIFE STAGE MANAGEMENT OF AMINO ACID NUTRITION

Tontisirin, Kraisid.

Professor and Senior Advisor, Institute of Nutrition, Mahidol University, Thailand.

Amino acids (AA) are structural and functional units of proteins. Based on nitrogen balance and growth, AAs have been classified into 9 indispensable (IAA) and 11 dispensable AAs which can be synthesized from IAA via various metabolic pathways. The latest FAO/WHO/UNU Expert's report in 2007 on protein and AA in human nutrition has estimated AAs requirement for infants during the first six months of life based on breast milk contents of protein and AAs. For older infants up to adolescents the AA requirements are based on the combination of AAs required for maintenance and for growth. For adults, the main criteria used is the AA oxidation resulting in higher requirement recommendations for all indispensable AAs with noticeable 2-3 times higher in lysine, threonine, isoleucine, leucine and valine requirements compared to the previous recommendation in 1985 which was based on N-balance criteria. It is recommended that the AA requirement pattern and also protein need of 0.8 g protein kg/day for elderly people are the same as that for adults.

Protein intake to fulfil requirement and de novo formation of AAs will provide adequate "Amino acid pool" for metabolic and other functions of AAs for good nutrition and wellbeing. Those functions include: protein synthesis and maintenance of protein synthesis machinery, DNA and RNA synthesis, taste and appetite, hormonal functions, neurological and immune functions, regulations of various metabolic functions, and source of energy such as branch chain AAs and alanine. With better understanding of AA requirements, roles of AAs in metabolism and body functions in both normal and illness conditions and the ability to produce industrially of various AAs, the AAs have been used for enteral and parenteral products for treatment of several inherited metabolic diseases and seriously ill patients who need nutritional support. Specific AA has been used for food fortification such as lysine and threonine to improve protein quality in food and feed, glutamate
for taste enhancement, BCAA for athlete and sport. Nutritionally it is quite remarkable to witness the progress in AA science, metabolism, production and utilization to fulfil AA requirements and functions in human life course.

**Keywords:** Amino acid nutrition

# THE ROLE OF LEUCINE IN OBESITY-INDUCED METABOLIC DISORDERS

(1)Wu, Guoyao; (2)Bazer, Fuller W.; (3)Meininger, Cynthia J.

(1)Texas A&M University, College Station, Texas, USA.; (2)Texas A&M University, College Station, Texas. USA.; (3)Texas A&M University, College Station, Texas, USA.

The prevalence of obesity (body mass index ≥30 kg/m2) has increased in many regions of the world over the past decade because of multiple factors, including individual genotypes, excessive energy intake, sedentary lifestyles, and reduced energy expenditure. Obesity, especially the central or visceral type, is a predisposing factor for the development of type 2 diabetes mellitus. This disease manifests as insulin resistance and multiple metabolic disorders, including hyperinsulinemia, impaired glucose tolerance, and dyslipidemia as risk factors for the development of cardiovascular diseases. In both humans and animals, a common characteristic of obesity is a marked elevation in the concentrations of leucine, one of the branched-chain amino acids (BCAAs), in plasma. Of interest, a 22% increase in the concentration of leucine in plasma is associated with insulin resistance and cardiovascular dysfunction in obese subjects. Reduced rates of leucine degradation via multiple organs including skeletal muscle, heart, adipose tissue and kidneys, may contribute to hyperleucinemia in obesity. Leucine is an activator of glutamine:fructose-6-phosphate aminotransferase (GFAT), which is the first and a rate-controlling enzyme in catalyzing the synthesis of glucosamine (an inhibitor of endothelial NO synthesis) in endothelial cells. In addition, through stimulating the mammalian target of rapamycin signaling pathway and thus protein synthesis, leucine may enhance GFAT protein expression. Thus, among BCAAs, leucine is unique in inhibiting the synthesis of nitric oxide (NO, a major vasodilator and a mediator of insulin actions in skeletal muscle) from arginine in endothelial cells, and may modulate cardiovascular homeostasis via insulin resistance. In support of this view, dietary supplementation with BCAAs has been reported to promote the development of insulin resistance in both rats and humans. Conversely, reducing the circulating levels of L-leucine or endothelial GFAT activity may provide a potentially novel strategy for preventing and/or treating cardiovascular disease in obese and diabetic subjects. Such means may include: (1) dietary supplementation with (a) α-ketoglutarate to enhance BCAA catabolism in the small intestine and other tissues, (b) N-ethyl-L-glutamine to inhibit GFAT activity in endothelial cells, and (c) arginine to overcome the inhibitory effect of leucine on endothelial NO synthesis; and (2) oral administration of interferon tau, an inhibitor of oxidative stress. Preventing leucine-induced activation and expression of GFAT by nutritional

supplements or pharmaceutical drugs may help to ameliorate the metabolic syndrome in obese subjects. In conclusion, leucine is a biomarker of metabolic defects in obesity, and lowering its concentrations in blood may improve NO generation by the vasculature and enhance the sensitivity of tissues (such as skeletal muscle, heart, liver, and adipose tissue) to insulin. (Supported by AHA and NIH grants).

**Keywords:** Branched-chain amino acids, nitric oxide, obesity

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# NEW TOOLS FOR NUTRITIONAL ASSESSMENT IN EARLY LIFE: HOW TO MANAGE THEM

## GESTATIONAL WEIGHT GAIN STANDARDS IN THE INTERGROWTH 21ST PROJECT: IMPLICATION TO POLICY MAKERS

Kac, Gilberto.

Professor, Institute of Nutrition, Federal University of Rio de Janeiro. Brazil.

The aim of this abstract is to describe the methodology of the INTERGROWTH-21st gestational weight gain (GWG) standard implementation on the Brazilian Health Unified System. This is a work in progress. The Intergrowth 21st GWG standard was constructed based on a prospective, longitudinal, multi-center study. The study was conducted on eight diverse urban regions in Brazil, China, India, Italy, Kenya, Oman, United Kingdom and United States. The sample comprised healthy, well-nourished women, enrolled in the Fetal Growth Longitudinal Study, a component of the INTERGROWTH-21st Study. Maternal weight was measured every 5 weeks starting with <14 weeks of gestation until delivery. A multi-level, mixed effect, linear regression analysis for repeated measures, adjusted for gestational age was employed to produce the GWG values. The standard was constructed for women with normal weight (body mass index (BMI) ≥18.50-24.99 kg/m2 at the first trimester. doi: https://doi.org/10.1136/bmj.i555. BMJ 2016;352:i555). A reference was also constructed for overweight women (25.0-29.99 kg/m2, not published yet). Smoothed GWG centiles were fitted for the 3rd, 10th, 25th, 50th, 75th, 90th, and 97th for each week of gestation. Additionally, equations for the mean and standard deviation to calculate any desired centiles according to gestational age can be found on the INTERGROWTH-21st dedicated website. The implementation of the INTERGROWTH-21st GWG standard on the Brazilian Health Unified System will be conducted in steps and has been organized as several sub-studies aimed to surpass several difficulties initially identified when the INTERGROWTH-21st GWG standard was released. The main technical issues comprise the lack of GWG data for the first trimester and for the extremes of the pre-gestational weight gain BMI distribution (<18.5 and ≥30 kg/m2). The first sub-study will comprise an extensive literature review dealing with (i) manuscripts that have tested the use of the INTERGROWTH-21st
GWG standard; (ii) manuscripts that have compared measured versus reported pre-gestational weight and (iii) manuscripts that discusses the first trimester GWG estimates. The second sub-study will comprise the validation of the INTERGROWTH-21st GWG standard. This component will focus on testing different cut-off points and ranges of GWG to predict selected maternal and infant outcomes, such as small for gestational age; large for gestational age, postpartum weight retention among others. A third sub-study will seek strategies to evaluate GWG on the extremes of the body mass index distribution. This component will look into for particular prospective cohort studies during pregnancy that may be meta-analyzed to produce GWG estimated for those BMIs not included on the INTERGROWTH-21st. A fourth sub-study will have as objective a reliability study between reported and measured pre-gestational weight. Finally, a fifth sub-study will deal with issues related to the first trimester GWG gain estimates. As a final product, we expect to be able to evaluate INTERGROWTH-21st validity and to assess how useful it can be as a tool to monitor GWG at the Brazilian Health Unified System and if this standard can be used as a substitute of the actual GWG monitoring system in place.

**Keywords:** Gestational weight gain; Intergrowth 21st; Policy makers; Standard; Surveillance

## INTERGROWTH 21 ST PROJECT: WHAT IS NEW FOR NEWBORN ANTHROPOMETRIC ASSESSMENT?

Medina, Mercedes

MSc. Nutritionist. Interdisciplinary Group of Family Studies, Universidad de la República. Uruguay.

The impact of different situations in the early stages of life on infant development, cognitive development and the consequences of life, which is not enough to consider only the size of the child, but requires a broader assessment of the result of pregnancy. According to the need to optimize fetal development, the concept encompasses a broad set of considerations, such as: maternal health before and during pregnancy, duration of this, size of the neonate for gestational age and The possibility that fetal development has been disturbed or that the nutritional, physical and emotional factors of the infant's environment exist that maximize their ability to grow, develop and have a healthy life (WHO 2006)

INTERGROWTH-21st is an international, multicentre, population-based project consisting of a number of components, including the Fetal Growth Longitudinal Study (FGLS) and INTERBIO- 21st Fetal Study (FS).

The INTERGROWTH-21st Project provides standards for early human growth based on populations that conform to the prescriptive approach recommended by WHO 21,52. By prescriptive, we mean we have observed a cohort of prospectively enrolled women whose risk of adverse maternal and perinatal outcomes (including fetal growth restriction) was low based on their individual clinical profiles and the socioeconomic and demographic characteristics of the underlying geographically diverse popula-

tions. In fact, the INTERGROWTH-21st Project is unique because it has produced, for the first time, fetal ultrasound, newborn size and preterm postnatal growth data set that have all been collected from the same underlying populations using the same rigorously applied methodologies.

**Objective:** To evaluate the birth weight of the Uruguayan children who participated in the National Survey of health, nutrition and development(ENDIS) in 2011 with Intergrowth project.

The information on weight and height of newborns in Uruguay extracted from a representative sample of 3000 children under 4 years old was processed by the information from the 21st intergrowth Project. This project used information from the same countries of the new anthropometric references of children under 6 years of WHO. And the exclusion criteria in that Project were:

- women under 18 and over 35 y.o

- Mother's height under 1,53 m.

- BMI < 18.5 ó >30

- Somokers

- History of children with <2500 g. Ó> 4500 g., Or children born dead.

- Less than 14 weeks gestation

Birth weight was analyzed below the 10th percentile with a lower than expected value of 4.5%, while children born with a weight above the 90th percentile exceeded 9% (19%), As for birth size, children below the 10th percentile were 11.5% and above the 90th percentile, 7.8%

The difference in gramas terms were from 100 to 220 gs. < P10, and > P90 from 130 to 300 gs. All evaluated by the gestational age.

The difference in centimeters of heigth were from 110 to 225 cm. < P10, and > P90 from 120 to 350 cm, all evaluated by the gestational age.

**Keywords:** Birth weight, birht height, intergrowth Project.

**Further collaborators:**

Cecilia Severi. Interdisciplinary Group of Family Studies, Universidad de la República. Uruguay. Proffesor of Preventive Medicine. Universidad de la República.

## EPIDEMIOLOGICAL IMPLICATIONS OF THE NEW WHO ANTHROPOMETRIC REFERENCES AND THEIR LIMIT VALUES AND THE IMPLEMENTATION PROCESS IN ARGENTINE

Abeyá Gilardon, Enrique O.

MD. MPH. Nutrition Area Coordinator. Mother & Child Health. Ministry of Health. Argentina.

Since 1982 in Argentina, Ministry of Health used local references to evaluate children growth, to select food programs beneficiaries and estimate prevalences of malnutrition (stunting and ematiation). In 2007, Ministry of Health adopted the Multicenter Growth Reference Study curves (launched by WHO in 2006) for weight for age, length/height for age, head circumference for age and body mass index for age for all children less than five years replacing local references. By September 2012 all 23 country prov-
inces and Buenos Aires Autonomous City had adopted the WHO standards (10 before 2009; 9 from September 2009 to March 2010; 3 from April 2010 to September 2010; 2 from October 2010 to September 2012). Time delay from adoption to implementation was partially due to existing stock of printed material (mainly, growth charts and sanitary booklets).

Implementation of new curves was performed in coordination with Sociedad Argentina de Pediatría through local seminars and training workshops. This process was supported by providing an ad-hoc handbook and growth charts.

Ministry of Health selected 8 graph: weight for age (first semester, birth to 24 months and birth to 5 years), height for age (birth to 24 months and birth to 5 years), BMI for age (1 to 5 years), head circumference (first trimester and birth to 5 years). All curves are for percentiles 3, 10, 25, 50, 75, 90 y 97 except BMI for percentiles 85 instead of 90. Also it were included three tables of weight increments for first two years.

The weakness of the MGRS is that all programs include children up to 6 years, therefore it was necessary to include a handed curve for this temporal segment from WHO growth curves not included in MGRS.

**Keywords:** Children Growth, Implementation, Argentina, Nutrition Policy, MGRS WHO

PS_144/45

# ADVANCEMENT OF GLOBAL FOOD COMPOSITION DATABASES

## FOOD COMPOSITION DATABASES ACROSS THE GLOBE: AN OVERVIEW

(1)McLean, Morven; (2)Christianson, Karin; (3)Leet, Whitney; (4)Bennett, Laurie.

(1)PhD. Executive Director. International Life Sciences Institute Research Foundation. Washington. DC. USA.; (2)MS MPH. Program Associate. International Life Sciences Institute Research Foundation. Washington. DC. USA; (3)MS RD. PhD Student. Nutrition and Health Sciences. Emory University. Atlanta. Georgia. USA; (4)Program Manager. International Life Sciences Institute Research Foundation. Washington. DC. USA.

In 2017, the ILSI Research Foundation launched the Catalogue of Food Composition Databases and Tables (or CatFCDB), a curated clearinghouse of information about food composition databases and tables. Designed with researchers, dietitians, students, government officials, and database managers in mind, CatFCDB serves to aide users in their initial assessment of the scope and depth of nutritional composition data available for certain countries and regions. It is displayed as an interactive map that enables users to explore, analyze and filter 90 FCDBs from 92 countries and regions. CatFCDB is meant to be a starting platform for users to learn about available food composition databases and tables to determine which may suit their needs, and it provides hyperlinks

to direct the user to the source databases and tables (when these are available). An overview of CatFCDB demonstrating its functionality will be provided.

The ILSI Research Foundation also maintains the ILSI Crop Composition Database (ILSI-CCDB), an open-access source of comprehensive nutritional composition data for eight conventionally bred crops: canola, cotton, field corn, potato, rice, sorghum, soybean, and sweet corn. Data in the CCDB are derived from numerous samples of hybrids and/or varieties cultivated in controlled field trials using standard commercial cultivation practices at various locations throughout the world. Representative plant samples are obtained from field-grown crops with known production locations and dates. The analytical methods used to generate the composition data must be indicated, validated, and use certified or historically verified standards. Users can query the database to generate mean levels and ranges of nutritional components in various crop species. Environmental factors such as soil type and temperature can impact the levels of important nutrients in plants, and the moisture content can vary based on field conditions at harvest and when samples are handled. The database includes features that allow the user to retrieve a subset of data for samples produced in a specific year or location, and the analyte search filter can be applied to retrieve a pre-determined subset of data. Version 6 of the ILSI-CCDB was released in October 2016, and Version 7, which will include apple for the first time, is targeted for release before the end of 2017.

One of the strengths of the ILSI-CCDB is the completeness and quality of the data sets for each crop. However, the analytical rigor required for data submitted to the ILSI-CCDB means that sample testing is expensive, and so it is not surprising that most data have been donated by the private sector, and for a very limited range of crops. The ILSI Research Foundation is committed to including data for other crop species, particularly important staple foods. For such data to become available, public sector breeding programs, as well as breeding programs run by small and medium enterprises, must be able to submit data, but it is also essential to ensure that data for new crops are verifiable and robust. Resolving how to balance these imperatives remains a significant challenge.

**Keywords:** Food composition, crop composition, open data

## NEW DEVELOPMENTS IN FOOD COMPOSITION PROGRAMMES IN SOUTH-EAST ASIA: ASEANFOODS

(1)Tee, E-Siong; (2)Judprasong, Kunchit; (3)Puwastien, Prapasri.

(1)PhD. ASEANFOODS Advisor. President. Nutrition Society of Malaysia. c/o Institute for Medical Research. Kuala Lumpur. Malaysia; (2)PhD. Assoc Prof. ASEANFOODS coordinator. Institute of Nutrition. Mahidol University. Nakhon Pathom. Thailand; (3)PhD. Assoc Prof. ASEANFOODS Advisor. Institute of Nutrition. Mahidol University. Nakhon Pathom. Thailand.

The Association of Southeast Asian Network of Food Data systems (ASEANFOODS) was established in 1986 consisting of 10 member countries, namely Brunei Darussalam, Cambodia,
Indonesia, Laos, Malaysia, Philippines, Singapore, Thailand, and Vietnam. To coordinate the ASEANFOODS activities, the Institute of Nutrition, Mahidol University (INMU) was chosen as the Regional Centre in 1986 and INFOODS Regional Database Centre in 1991. The goal and objectives are to strengthening the development of national and regional food composition data (FCD) with high quality, adequate quantity and accessibility to the users. The first ASEAN FCTs was published in 2000 and was available in ASEANFOODS website. A number of proficiency testing schemes for laboratories were organised and few reference materials for food analysis were developed.

During 2015-2016, ASEANFOODS collaborated with and supported by International Life Sciences Institute South East Asia (ILSI-SEA) Region in organising two workshops in Thailand. The specific objectives of the first workshop, from 17-18 December 2015, were to develop a quality evaluation system (draft guideline) for assessing the quality of published national FCTs in ASEAN countries and to develop action plan for succeeding workshop and future activities. The specific objectives of the second workshop, 30-31 March 2016, were 1) to review the proposed plan/strategies for updating of ASEAN FCTs/FCDBs and organising Food-Comp-ASEAN course, 2) to discuss the feasibility of incorporating nutrient data of pre-packaged foods (branded food products) into national FCDBs. The latter activity has commenced in Thailand, to be followed by Malaysia and Philippines.

At the national level, most ASEAN countries have been actively working on generating new data. Recent activities are as follows: Malaysia continued with its new phase of compilation and documentation of the laboratory analyses of nutrients by participating institutions through a web-based system for data generators, data compilers and data users. This online FCDB publishes partial releases of the Malaysian FCD websites since 2015. Facilitated by ILSI-SEAR, a project to analyse the sugar content of commonly consumed foods and beverages is being planned. Philippines: Current activities are on updating FCTs and web-based PhilFCT. New food data, focusing on indigenous fruits and vegetables, are being generated, compiled, checked and evaluated until the end of the 3rd quarter of 2017. Thailand: The hard copy of the new version Thai FCT was published in September 2015. The on-line Thai FCDB is available since April 2016 at the INMU website. Food composition data for new food items and missing data are being developed. Vietnam: Activity on updating the Vietnam FCDB is at the final preparation and is expected to be published by 2017. A strategic plan for updating the ASEAN FCDB has been developed for possible implementation in 2018 when there is sufficient progress of FCDB in the main member countries.

The main activity of the ASEANFOODS Regional Centre in 2017 will be to strengthen the competence of young staffs in ASEANFOODS member countries by collaborating with the area experts in organising the FoodComp-ASEAN 2017 in Thailand.

**Keywords:** ASEANFOODS, Food composition databases

## WHAT'S NEW: THE USDA BRANDED FOOD PRODUCTS DATABASE

Many current and important public health challenges are linked to food and nutrition. Obesity and associated co-morbidities, a primary public health concern, is diet/food related. The risks for some cancers may be decreased by dietary patterns and cardiovascular disease is associated with many specific nutrients as well as dietary patterns. The USDA is the primary department with farm-to-fork oversight of the U.S. Food Supply, and the USDA conducts much work in the areas of nutrition and dietary guidance. Central to accomplishing this task is tracking the nutritional status of Americans, and this requires knowledge of the composition of the food system. Although the USDA has maintained food composition records since the early twentieth century, the task today is greatly complicated by the volume and fluidity of the food supply. Today there are more than 25,000 food manufacturers in the US who produce more than 20,000 new food and beverage products each year. The average grocery store has more than 36,000 individual items and there are more than 400,000 items in the food supply additionally, meals away from home are increasing and now account for over 50% of total food spending in the United States. All these factors results in limited knowledge of current intake of calories and nutrients by the America people.

The USDA Agricultural Research Service (ARS) maintains a program for monitoring food composition and nutrient intake of the nation; this program has two components: Provide U.S. food composition data and Determine food consumption and dietary patterns of Americans as part of the National Health and Nutrition Examination Survey (NHANES). Electronic records and databases are essential to this mission. For over thirty years this program has maintained the National Nutrient Database for Standard Reference (SR). Until October, 2016, this database contained information on approximately 9,000 foods and many of the items have complete analyses (of up to 146 nutrients) conducted by analytical laboratories. More recently, however, a public-private partnership between the USDA, the International Life Sciences Institute - North America (ILSI-NA), GS-1, One World Sync and Label Insight has resulted in creation of the Branded Food Products Database (BFPD). This partnership enables the flow of manufacturers label data into the ARS Nutrient Database significantly increasing the database to more than 170,000 foods within 4 months, with the anticipation of many more to be placed in the system. These data represent a tremendous increase in the amount of knowledge but

<footnote>(1)Starke-Reed, Pamela; (2)Krestor, Alison; (3)Fernandez, Angela;</footnote>

<footnote>(4)Gilchrist, Graig; (5)Xavier, Dagan; (6)McKillop, Kyle; (7)Murphy, Delia.</footnote>

<footnote>(1)PhD. Deputy Administrator. USDA Agriculture Research Service. Beltsville. Maryland. USA; (2)MS, RD. Director Science Programs. ILSI North America. Washington, DC 20005; (3)vice president of retail grocery and foodservice. GS1 US. Lawrenceville New Jersey, USA; (4)Strategic Account Executive. !WorldSync. Lawrenceville. New Jersey. USA; (5)VP Data Intelligence. Label Insight. Chicago. Illinois. USA; (6)Director of Food Safety Informatics Program. University of Maryland. College Park, MD USA; (7)Science Program Associate. ILSI North America. Washington.D.C. USA.</footnote>
many gaps remain before the full potential of the Branded Foods
Products Data can be realized.

**Keywords:** Nutrition, Branded Foods, Database

PS_144/163

# WHO/CDC SYMPOSIUM ON THE ASSESSMENT OF VITAMIN A STATUS IN POPULATIONS

## WHO PROCESS FOR DEVELOPING GUIDELINES FOR VITAMIN A INDICATORS RETRIEVAL, SUMMARIZING AND ASSESSING THE EVIDENCE

Rogers, Lisa Marie.

PhD. Technical Officer. World Health Organization. Geneva, Switzerland.

Indicators to assess the micronutrient status in populations are important for determining the magnitude and distribution of deficiency as a public health problem, for choosing the most appropriate intervention, and for monitoring and evaluating the impact and safety of public health programmes. The assessment of micronutrient status is often complex, as indicators can be affected by other conditions such as age, sex, disease, smoking, infection and inflammation; and the use of appropriate indicators must feasible at the population level. The World Health Organization (WHO) previously convened a meeting on Priorities in the assessment of vitamin A and iron status in populations to discuss and initiate the work of updating WHO guidelines on indicators for the assessment of vitamin A status, indicators considered to be of highest priority to undergo review were: 1) retinol (serum or plasma obtained from venous or capillary blood); 2) retinol-binding protein (RBP; serum or plasma obtained from venous or capillary blood); 3) breast milk retinol; 4) relative dose response (RDR) tests; and 5) modified RDR (MRDR) tests. Additional indicators identified since the previous consultation are retinyl esters and isotope dilution for use in select populations. As guidance on the use of specific biomarkers of vitamin A status and redefinition of thresholds for vitamin A deficiency will have implications for public health and research around the world, this work must be consultative, transparent, methodical, and use the best available scientific and statistical methods. WHO has adopted internationally recognized methods and standards for guideline development to ensure that its guidelines are of the highest quality. The general process includes: (i) identification of key questions and critical outcomes; (ii) retrieval of the evidence; (iii) assessment and synthesis of the evidence; (iv) formulation of the recommendations; and (v) planning for dissemination, implementation, impact evaluation and updating of the guideline.

**Keywords:** Vitamin A, retinol, status, assessment, indicators

## BIOLOGICAL EVIDENCE FOR OR AGAINST HIGH DOSE SUPPLEMENTATION

Tanumihardjo, Sherry.

University of Wisconsin-Madison. USA.

The World Health Organization (WHO) recommends high dose capsules of retinyl palmitate be orally administered to children between 6 and 59 months of age for the prevention of mortality. Infants less than 12 months are to receive 100,000 IU and those 12-59 months receive 200,000 IU. These capsules should be targeted in areas of the world that are at risk for vitamin A deficiency based on a variety of factors. Other high dose supplementation programs in different age- or vulnerable groups have been tested and sometimes implemented in many countries. However, currently evidence on their efficacy to improve infant and childhood mortality is not supported by reviews of randomized controlled trials. One of the most debated interventions is neonatal supplementation. Trials indicated mixed results on infant mortality, and a meta-analysis of human trials indicated no overall effect of neonatal supplementation on death within 6 mo of birth. High dose supplements have transient effects on serum retinol and tissue stores of vitamin A, with the exception of the liver where increases may last for several months on the background of low dietary intake in humans. In swine models, vitamin A is well-absorbed, appears in serum primarily as retinyl esters, and is taken up dose dependently in all tissues. Nonetheless, enhancement in piglets did not persist in serum, lung, kidney, spleen, or adrenal gland. It has long been considered that circulating retinyl esters disrupt membranes and are the major cause of symptoms of hypervitaminosis A or toxicity. After high-dose supplements, elevated esters persisted for approximately 12 hours before being sequestered in the liver for storage. Elevated circulating esters were associated with hypervitaminosis A in Zambian children at a cutoff of 5% of total vitamin A, but the current cutoff used in adults, i.e., 10% retinyl esters of total vitamin A, has not been validated.

In piglets, vitamin A storage was enhanced for more than 10 days after high-dose supplements compared with placebo. In the same study, once liver reserves reached 0.7 micromol/g liver, vitamin A concentrations plummeted. It is not known whether this was due to the high dose capsule administered 7 days prior or if it reflects a biological response at this liver reserve, which was referred to as excessive vitamin A status in the past. No group of piglets reached a mean concentration of >1 micromol/g liver, which currently defines hypervitaminosis. Short-term impacts of retinoid signaling and longer follow-up after high dose supplements need to be evaluated.

**Keywords:** Animal models, catabolism, circulating retinyl esters, hypervitaminosis, supplementation
# SUMMARY OF INDICATORS OF VITAMIN A STATUS AND THEIR INTERPRETATION IN A POPULATION SETTING

Tanumihardjo, Sherry.

University of Wisconsin-Madison. USA.

Vitamin A, which includes circulating retinol, retinal in the eye, storage retinyl esters, and the hormone retinoic acid, is an essential nutrient because humans must consume it in the diet either in the preform or as provitamin A carotenoids. Provitamin A carotenoids are produced in plants and provide vitamin A after enzymatic cleavage. Vitamin A deficiency continues to burden the global diseases, particularly in resource-poor countries. The most severe indicator of vitamin A deficiency is xerophthalmia and increased risk of death from infectious diseases, especially in children. Serum retinol concentrations are under homeostatic control due to its essential role in growth and cellular differentiation, which requires constant levels. At high concentrations, the vitamin is toxic. Because retinol-binding protein is a negative acute phase reactant, serum retinol concentrations are depressed during inflammation. Therefore, population status assessment needs to account for inflammation using acute phase markers (C-reactive protein and alpha-acid-1-glycoprotein). A serum retinol concentration of <0.7 micromol/L is considered deficient. However, in some population groups, this concentration may be adequate on the background of inflammation. Other indicators that have been used include breast milk retinol, which is unique to lactating women, doses response tests, isotope dilution methodology, and serum retinyl esters. These biomarkers can be related to liver vitamin A concentrations, which are considered the gold standard for vitamin A status. Breast milk concentrations <1 micromol/L are inadequate. Breast milk has two sources of retinol, i.e., retinol bound to retinol-protein and chylomicra. Therefore, they have utility in defining vitamin A exposure. Dose response test require an analog of retinol be administered and a waiting time of 4 to 6 hours before blood drawing. If retinyl acetate is administered a baseline blood is also required and an increase of 20% is considered abnormal. If 3,4-didehydroretinyl acetate is given, a single blood sample is needed and a ratio of 3,4-didehydroretinol to retinol of >0.06 signifies inadequacy. In the past, the World Health Organization (WHO) considered a 20% prevalence of inadequacy as a severe public health problem. Isotope dilution testing also requires analog administration, blood draws, and a waiting period. However, they are usually considered good estimates of total body stores of vitamin A and have been validated against liver reserves of vitamin A in animals and humans. WHO has not considered a prevalence definition for public health significance when isotope dilution testing is used. This is likely because most studies are stratified across population cohorts. Vitamin A indicators are best used together to best define where along the vitamin A status continuum the population lies. Serum retinol concentrations alone have limited utility, yet other tests are more expensive to implement. The best scenario is likely that serum retinol be measured on the population and then randomly selected subsets of individuals be administered either the dose response or isotope dilution test.

This would allow a more informed interpretation of the serum retinol distribution.

**Keywords:** Biomarkers, dose response test, inflammation, isotope dilution, serum retinol.

# EXPERIENCES AND LESSONS LEARNED WHEN THE MODIFIED RELATIVE DOSE RESPONSE TEST WAS INCLUDED IN POPULATION-BASED SURVEYS TO ASSESS VITAMIN A STATUS

WHO defines vitamin A deficiency (VAD) as serum retinol <0.70 µmol/L, but this indicator is homeostatically controlled, influenced by inflammation, costly to assess, and requires a venous blood specimen. Retinol binding protein (RBP) is often collected instead because it is less costly and can be collected with a capillary sample, but a standard cut-off for VAD using RBP is not defined. In each survey collecting RBP, a subsample of retinol should also be collected in order to calculate the RBP cut off equivalent to serum retinol <0.70 µmol/L. The modified relative dose-response (MRDR) test is a qualitative indicator of vitamin A liver stores. MRDR is not homeostatically controlled and less influenced by inflammation than retinol or RBP. During the analysis of MRDR, a value for serum retinol is also generated, which can be used to calibrate the RBP cut off values for defining VAD. MRDR requires consuming a small challenge dose of a vitamin A analog (A2) along with a fatty snack and collecting a blood sample 4-6 hours later, increasing the survey complexity. Using examples from Nepal, we describe experiences planning large scale population-based vitamin A assessments including subsamples of MRDR/retinol, determining RBP cut-offs for VAD, and prevalence estimates.

Describe planning and logistical implications for large scale surveys including young children. Use linear regression to examine the retinol-RBP relationship and determine the RBP cut-off that corresponds to the retinol cut-off of 0.70 µmol/L. Describe the RBP cut-offs calculated from the surveys for young children, including pre- and post-vitamin A2 dosing.

Vitamin A2 is not commercially available and must be synthesized. Data collection was planned to start 30 days after bivalent vitamin A supplementation (VAS) campaigns because VAS influences circulating retinol. Among children 6-23 months, the

<footnote>(1)Jefferds, Maria; (2)Whitehead, Jr., Ralph D.; (3)Mei, Zuguo;</footnote>

<footnote>(4)Tanumihardjo, Sherry; (5)Chitekwe, Stanley; (6)Dahal, Pradiumna;</footnote>

<footnote>(7)Paudyel, Naveen; (8)Pokharel, Rajkumar; (9)Joshi, Nira; (10)Flores-Ayala, Rafael.</footnote>

<footnote>(1)Centers for Disease Control and Prevention. USA.; (2)PhD. Division of Nutrition, Physical Activity and Obesity. Centers for Disease Control and Prevention. USA; (3)MD. Division of Nutrition, Physical Activity and Obesity. Centers for Disease Control and Prevention. USA; (4)PhD. Department of Nutritional Sciences. University of Wisconsin-Madison. USA.; (5)Nutrition Unit. UNICEF. Nepal; (6)MSc, MA. Nutrition Unit. UNICEF. Nepal; (7)BS. Nutrition Unit. UNICEF. Nepal; (8)MPH, PG-Dip (Epid.); (9)MA, ARPH. New Era, Nepal; (10)DrPH. Division of Nutrition, Physical Activity and Obesity. Centers for Disease Control and Prevention. USA.</footnote>
calculated RBP cut-off to define VAD was RBP<0.84 µmol/L and RBP<0.59 µmol/L, respectively, in two surveys collected four years apart.

Including a subsample of MRDR/retinol is feasible with plan-
ning. More information is needed to understand the factors influ-
encing RBP calculated cut-offs equivalent to retinol <0.70 µmol/L
and the best methods to assess vitamin A status.

**Keywords:** Vitamin A deficiency, RBP, MRDR, retinol

PS_144/1039

PATHS TO NOURISHING MILLIONS WITH BIOFOR-
TIFICATION

SCALING UP BIOFORTIFICATION: PROGRESS TO
DATE, SUCCESS FACTORS AND THE CHALLENGES

(1)Mudyahoto, Bho; (2)Foley, Jen; (2)Boy, Erick; (2)Birol, Ekin; (2)Asare-Marfo, Dorene; (2)Lividini, Keith.

(1)HarvestPlus. International Food Policy Research Institute.
Kampala, Uganda.; (2)HarvestPlus. International Food Policy
Research Institute. Washington, D.C., USA.

During the past 15 years, HarvestPlus and its partners have
made tremendous progress in the development, release and dis-
semination of biofortified crop varieties. Biofortification is the
process of increasing the density of vitamins and minerals in a
crop through conventional plant breeding or agronomic practices.
Varietal development is jointly led by CGIAR centers in collab-
oration with National Agricultural Research Institutes, with sup-
port from donors and national governments. Over 140 varieties of
10 crops have been released as public goods in over 30 countries
worldwide, and are being tested and grown in over 60 countries
in Sub-Saharan Africa, Asia and Latin America. The adoption
and consumption of biofortified crops is ever increasing. In 2016,
over 7 million households (35 million people) were estimated to
be growing and consuming biofortified crops. It is estimated that
by 2030, about 1 billion people will be growing and consuming
biofortified high pro-vitamin A maize, cassava, and sweet potato;
high iron beans; sorghum and pearl millet; and high zinc wheat
and rice, globally. While the pathways to develop, deploy and scale
up biofortified crops are country and context specific, a robust
evidence base of the effectiveness of biofortification, continued
investment in product (varietal) development, standards for bi-
ofortification, strategic partnerships, relevant national policy in-
struments, private and public sector, and donor investment across
the value chain of biofortified crops and, robust monitoring, eval-
uation and information sharing systems, are all crucial for sustain-
able scaling up of this technology, regardless of the context. There
is robust evidence on the acceptability, efficacy and effectiveness
of biofortification, and new research is published on an ongoing
basis. For example, a recent systematic review of three randomized
iron-biofortified efficacy trials further confirmed that iron-biofor-
tified interventions significantly improve iron status—particular-

ly among women and children under 5 (Finkelstein et al. 2017). Additionally, an effectiveness study carried out in Uganda showed that among recipients of Orange Sweet Potato (OSP) vines: (a) there was sustained adoption 2-4 seasons after delivery; (b) vita- min A intakes of children and women significantly increased, with OSP accounting for 53% of vitamin A intake for children under 5; and (c) the prevalence of low serum retinol was reduced by 9.5 percentage points among children under 5 (Hotz et al. 2012). In addition, a WHO Cochrane review committee was assembled in 2016 to review the scientific evidence and country experiences of scaling up biofortification. This paper summarizes the progress and challenges of scaling up biofortification and the existing evi- dence focusing on: varietal development and release; biofortifica- tion standards and enforcing compliance; HarvestPlus' scaling up strategy, priority countries and global targets; the entry points and strategies at national, regional and international levels; the role of strategic partnerships in scaling up biofortification; M&E systems for biofortification initiatives; lessons learned and challenges.

**Keywords:** Biofortification, Scaling-up, Global strategies, Ag-
riculture, Partnerships

SCALING UP BIOFORTIFICATION: DELIVERY OF
BIOFORTIFIED CROPS AND FOODS IN NIGERIA
- PROGRESS AND LESSONS

(1)Ilona, Paul; (2)Pfeiffer, Wolfgang; (3)Boy, Erick; (3)Foley, Jen; (1)Umeze, Gerald; (1)Okonkwo, Ifeoma.

(1)HarvestPlus. International Institute of Tropical Agriculture.
Ibadan, Nigeria.; (2)HarvestPlus. International Centre for Tropical
Agriculture. Cali, Colombia.; (3)HarvestPlus. International Food
Policy Research Institute. Washington, D.C., USA.

New agricultural technologies are seldom able to propagate
themselves because adoption by farmers and consumers is often
influenced by a myriad of factors other than the improved charac-
teristics in the new technologies. Biofortification is one such new
technology in Nigeria, with the primary objective to increase the
levels of essential micronutrients in staple crops as a sustainable
and complementary strategy to reduce micronutrient malnutri-
tion among vulnerable populations. Seventeen biofortified varie-
ties (six of pro-vitamin A cassava, seven of pro-vitamin A maize,
two of orange sweet-potato and two of iron sorghum) have been
officially released for production in Nigeria during the past six
years. The journey of delivering biofortified varieties to farmers
started in 2011, soon after the first set of three biofortified varieties
of cassava were officially released to farmers by the government.
HarvestPlus has since innovated and deployed several tools and
channels that were initially slow but gradually picked up momen-
tum to reach an estimated two million farmers by the end of 2016.
This did not go without challenges considering the diversity in cul-
ture and agro-climatic conditions, initial need for evidence, con-
fusion of our crops with GMO's, and socio-political and economic
instability. There were shifts from: a single crop approach in the
early years to multiple crop approach; social to commercial seed
delivery; single field demonstrations to model village concepts; specific component interventions to value chain models; conventional marketing to dedicated and online markets; single to multimedia communication including movies; direct to partner-led delivery; manual to electronic data collection; zero to three policy support documents; zero to over 2,000 small- and medium-sized enterprises; and, finally, special activities to mainstream biofortification such as quiz competitions, national nutrition platforms, educational curriculum and school feeding programs. This paper reviews the different strategies and channels employed in reaching Nigerians with more nutritious crop and food options. It presents coverage data and analyses the lessons learned, suggests new strategies for scaling and predicts the potential reach by 2020.

**Keywords:** Biofortification, Scaling-Up, Agriculture, Nigeria.

## PRIVATE PUBLIC PARTNERSHIPS: A DELIVERY MODEL FOR BIOFORTIFIED IRON PEARL MILLET IN INDIA

Cherian, Binu.

HarvestPlus. International Center for Tropical Agriculture. c/o International Crop Research Institute for the Semi-Arid Tropics. Patancheru. Telangana. India.

Despite India's tremendous economic growth and agricultural production in recent decades, levels of iron deficiency anemia and zinc deficiency have not significantly improved. Yet, agriculture is a sustainable and affordable source of nutrition and through biofortification—the conventional breeding of food crops with higher micronutrient levels—a measurable impact on nutrition and food security is achievable in populations that consume these nutrient-rich foods daily. Pearl millet (Pennisetum glaucum (L) R. Br.) is a climate resilient crop and major source of food and nutrition security for millions in the semi-arid tropics. Biofortified iron pearl millets are not only high in iron and zinc content, but are higher yielding, more disease resistant, tolerant to drought, heat and soil salinity, and include other agronomical traits preferred by farmers. In India, strong pearl millet breeding programs exist in both the public and private sectors. Seed companies have a well-developed, vertically integrated research and development to distribution and retail chain. Therefore, to promote the scale-up of nutrient-dense biofortified crops, HarvestPlus established partnerships with public and private seed companies. This has facilitated the rapid commercialization of products and engagement of farmers in delivery activities by leveraging their efficient and extensive distribution touch points. For example, farmers' engagement during participatory variety selection informs them of biofortified product characteristics at an early stage and encourages adoption. Public-private partnerships have been a successful strategy to increase the reach of biofortified crops in India: by the end of 2016, an estimated 375,000 people were consuming iron pearl millet. Market research results helps to understand key consumer insights and motivations towards biofortified crops. Collaborative promotion campaigns are organized with partners, such as on-farm

product demonstrations, farmers' field days, mobile campaigns, and engagements at the point of sales, help create further demand. Product information regarding the nutritional and agricultural benefits of iron pearl millet are made available through training sales personnel, retailers, and distributors of seed companies who remain one of the first points of contact of farmers. Collectively, through these private-public partnerships and other market-based approaches, HarvestPlus aims to reach 3 million people in India by 2030 with biofortified pearl millet. In partnership, HarvestPlus' advocacy strategy shall focus on some of the challenges of linking biofortified pearl millet to existing public food programs in the country. These linkages may help to increase demand for biofortified pearl millets and add nutrition components to existing food interventions that reach pregnant and nursing mothers, children under the age of six, school children, and families above and below the poverty line.

**Keywords:** Biofortification, Scaling-Up, India, Private-Public-Partnerships, Agriculture.

PS_144/119

## IMMUNONUTRITION IN HEALTH AND DISEASE: EVALUATION OF BIOMARKERS

### LIFESTYLE HABITS AND IMMUNONUTRITION

Marcos, Ascensión.

Research Professor at the Spanish National Research Council (CSIC). President of the International Society for Immunonutrition (ISIN).

Immunonutrition is the subject that studies the interrelationship between nutrition and the immune system. However, in the last decade, Immunonutrition also includes an interdisciplinary space in the research field, being related to other tissues and systems of the organism, such as the nervous, digestive and endocrine systems, as well as the gut microbiota that has been recently defined as a “new” organ. Therefore, the study of Immunonutrition acquires a great interest in the assessment of the nutritional status through the evaluation of certain biomarkers capable to detect situations of malnutrition and also the risk of suffering from eating disorders, metabolic syndrome, cardiovascular diseases, neurological disorders, allergies or infections. Lifestyle includes diet and other determinants, such as body fat composition, physical activity, sedentary habits, sleep profile, stress situations and psychological status, as well as tobacco and alcohol consumption. Although the Mediterranean diet (MD) has been promoted at an international level as a consequence of the scientific evidence about its benefits, especially for cardiovascular diseases, chronic degenerative diseases and some cancers, unfortunately, even in the Mediterranean countries, this type of diet is losing its leading role due to globalization effects across the world. The MD is mainly characterized by an elevated consumption of plant based foods, such as fruits and vegetables, a low intake of red meat and the use
of olive oil as the main source of fat food. Indeed, the studies on the adherence to the MD has been positively associated with performance in youth, independently of potential confounders, including body mass index, physical activity, fitness and sedentary behavior. In addition, there are several plausible mechanisms that can explain the protective effect of the adherence to the MD not only on cognition, but also including antioxidative and anti-inflammatory effects and the reduction of vascular comorbidities. In fact, the higher adherence to the MD is associated with lower levels of C-reactive protein and interleukins; thus, an underlying neuroprotective effect could be due to its vascular properties and its ability to reduce inflammation and oxidative stress, which are also associated with neurodegeneration. Regarding body fat composition, several biomarkers, such as leptin, cortisol and insulin have been confirmed as essentially included into the assessment of inflammation-related biomarkers. Fitness has also been confirmed as a useful tool to evaluate cardiometabolic profile. In addition, regular physical activity has been shown to develop a positive impact on the immune system by promoting mechanisms of action to defend the organism, in contrast with a high and intense physical exercise that can lead to immunosuppression with a high risk to suffer from infections. Moreover, the sleep profile has been defined as another important determinant to evaluate, due to its relationship with inflammatory patterns. In summary, the study of the different determinants included into the lifestyle habits and their relationship with the assessment of immunological biomarkers should be taken into account to evaluate the nutritional status in order to detect metabolic alterations and to prevent risk and development of diseases from the beginning of the onset.

**Keywords:** Mediterranean diet, physical activity, Fitness, sleep profile, immunological biomarkers

## BIOCHEMICAL MARKERS IN IMMUNE-DEPRESSED SUBJECTS

Slobodianik, Nora H.

PhD. University of Buenos Aires, School of Pharmacy & Biochemistry. Dept. Nutrition & Food Science. Argentina.

The aim of this lecture is to show the most important preliminary results obtained in our laboratory, related to the nutritional status evaluated through the use of biochemical parameters in 19 children suffering from cystic fibrosis (CF). The patients were treated and recruited at the Nutrition Service of Pedro Elizalde Hospital, Buenos Aires, Argentina. The study was approved by the University of Buenos Aires Ethics Committee, and all participants' parents agreed to sign the written consent before recruitment. The results were compared with reference values obtained from healthy children matched by age and gender.

Lower plasma fractions related to the nutritional status (apoB, Transferrin, Transthyretine) meanwhile higher levels of CRP and Fibrinogen were found in CF children in comparison with the healthy group. In addition, 30% of the CF children showed CPR levels higher than 0.3 mg/dL, concomitant with Fibrinogen levels

higher than 288 mg/dL, and 78% showed HDL levels lower than 35 mg/dL, these values being associated with cardiovascular risk. Moreover, a significant reduction of complement factors (C3c and C4c) was found which is related to a higher plasma ceruloplasmin concentration and Adenosine Deaminase activity (T lymphocyte-associated enzyme). Moreover, changes in the plasma fatty acids profile were found. In conclusion, nutrition is a critical component of the management of cystic fibrosis, and nutritional status is directly associated with both pulmonary status and survival. The results obtained in this paediatric population point out the requirement to include biochemical and functional parameters in the evaluation of patients suffering from CF. Specific nutritional support should be established and adjusted to individual needs.

**References:**

Fatty acid profile in children suffering from Cystic fibrosis. PD Perris, MS Feliu, S Giacomino, S Barbeito, A Franchello I Ruiz-Pugliese, A Caamaño, M Ferraro, NH Slobodianik. Proc Nutr Soc, 2001;72, Issue OCE1, E11

Inflammatory biomarker profile in children with cystic fibrosis: preliminary study NH Slobodianik, MS Feliu, P Perris, S Barbeito, I Strasnoy, A Franchello and M Ferraro. Proc Nutri Soc 2010;69:354-56.

**Keywords:** Cystic Fibrosis, Biochemical markers, Specific plasma proteins, Immune System

**Further collaborators:**

M. Susana Feliu, Paula Perris, Susana Barbeito, Irene Strasnoy, Alejandra Franchello, Mabel Ferraro, Olga Ramos.

## HEPCIDIN AND IRON IN INFLAMMATION

Solano, Liseti.

Professor. Nutrition Research Institute. Faculty of Health Sciences. Carabobo University. Valencia. Venezuela.

Hepcidin has emerged as the central regulatory molecule of systemic iron homeostasis. It is a 25-amino acid peptide hormone, produced and secreted predominantly by hepatocytes, circulates in the bloodstream, and excreted by kidneys. By binding to ferroportin and inducing its internalization and degradation, hepcidin regulates cellular iron efflux, controlling absorption of dietary iron from the intestine and release of recycled iron derived from senescent erythrocytes. Hepcidin levels are reduced in iron deficiency, and measurement of blood or urine hepcidin levels may enable evaluation of iron requirements providing a powerful indicator of physiological iron deficiency. Hepcidin measurement in patients have been proposed, as for anemia of chronic disease, anemia associated with chronic kidney disease and hemodialysis, genetic hemochromatosis, and iron deficiency diagnosis. Its concentrations are decreased in situations that require increased concentrations of circulating iron. In case of increased erythropoiesis, as in response to hypoxia, anemia, iron deficiency, or conditions of ineffective erythropoiesis, a decreased hepcidin concentration will result in the release of stored iron and in an increase in the dietary iron absorption. On the other hand, infection and inflammation cause an increase in hepcidin synthesis, resulting in decreased
availability of circulating iron, which is considered to represent a defense mechanism of the human body against extracellularly proliferating (irondependent) pathogens. In chronic (low-grade) inflammatory states, this ultimately leads to a deficiency of iron available for erythropoiesis called anemia of chronic disease, especially in obesity due to adipose tissue enlargement.

**Keywords:** Hepcidin, Iron concentration, Iron deficiency anemia, Chronic disease anemia, Inflammation

## THE IMMUNOINFLAMMATORY PROCESS IN TYPE 2 DIABETES MELLITUS. HOW CAN WE HELP?

Valdes-Ramos, Roxana.

Faculty of Medicine, Universidad Autónoma del Estado de México.

**Introduction:** Type 2 diabetes mellitus (T2DM) is considered the epidemic of the 21st century, with more than 220 million sick people worldwide. It is calculated that this number will triplicate by 2030. It is present mainly in subjects over the age of 40, however, its association with obesity has increased its prevalence in younger subjects. The nutritional transition in which many countries are immersed, with a rapid change in family income, the adoption of inadequate lifestyles and very low levels of physical activity, have led to an increase in prevalence of diabetes. Its aetiology involves the immune system in a very important way. **Objectives:** To review the conditions in the immunoinflammatory process that lead to the development of T2DM and its complications, in search of ways to improve the condition. **Development:** T2DM is a pathology resulting from two main conditions in glucose metabolism, a decrease in the production of insulin or an increased resistance to it. Diabetes is closely related to an alteration of the innate immune system, with the production of pro-inflammatory cytokines and adipokines in a chronic way. Insulin resistance develops before the increase in some inflammatory markers such as C-reactive protein and plasminogen activator 1, among others. Tumor necrosis factor alfa, interleukins 1 alfa and beta, interleukin 6, interferon gamma, retinol binding protein and resistin are increased in type 2 diabetes mellitus. On the other hand, we can find decreases in adiponectin, leptin, ghrelin, visfatin and omentin production. The immunoinflammatory process is responsible for the complications such as retinopathy, nefropathy, neuropathy, cardiovascular and peripheral vascular diseases, as well as periodontal pathologies. There are several low-cost and widely available interventions that may be useful in decreasing or controlling the inflammatory process, such as supplementation with various vitamins, polyunsaturated fatty acids, etc. **Conclusions:** T2DM is a pathology, where cause and effect are related to the innate immune system, thus, by controlling this inflammatory process, we can avoid the consequent complications of the disease.

## References:

1. Guadarrama-López AL, Valdés-Ramos R, Martínez-Carrillo BE. Type 2 Diabetes, PUFAs and Vitamin D: their relation to

inflammation. J Immunol Research 2014; Article ID 860703. 13 pages.

2. Valdés-Ramos R, Guadarrama-López AL, Martínez-Carrillo BE, Benítez-Arciniega AD. Vitamins and Type 2 Diabetes Mellitus. Endocrine, Metabolic and Immune Disorders -Drug Targets (EMIDDT) 2015; 15: 54-63.

3. Guadarrama-López AL, Valdés-Ramos R, Kaufer-Horwitz M, Harbige LS, Contreras I, Martínez-Carrillo BE. Relationship between fatty acid habitual intake and early inflammation biomarkers in individuals with and without type 2 diabetes in Mexico. Endocrine, Metabolic and Immune Disorders -Drug Targets (EMIDDT) 2015 (15): E-pub ahead of print.

4. Jacobo-Cejudo G, Valdés-Ramos R, Guadarrama-López AL, Pardo-Morales RV, Martínez-Carrillo BE, Harbige LS. Effect of n-3 Polyunsaturated Fatty Acid Supplementation on Metabolic and Inflammatory Biomarkers in Type 2 Diabetes Mellitus Patients. *Nutrients* 2017, 9:573. Doi: 10.3390/nu9060573.

5. Hamid I, Masoodi SR, Mir SA, Nabi M, Ghazanafar K, Ganai BA. Tyoe 2 diabetes mellitus: From a metabolic disorder to an inflammatory condition. *World J Diabetes* 2015; 6(4): 598-612.

**Keywords:** Type 2 Diabetes Mellitus, Inflammation, Immunity, Nutrition

## PS_144/1048

### BIOMARKERS REFLECTING INFLAMMATION AND NUTRITION DETERMINANTS OF ANEMIA (BRINDA 2) PROJECT

### OVERVIEW OF PHASE 2 OF THE BIOMARKERS REFLECTING INFLAMMATION AND NUTRITION DETERMINANTS OF ANEMIA (BRINDA) PROJECT

(1) Suchdev, Parminder A.; (2) Young, Melissa; (3) Williams, Anne; (4) Addo, Yaw; (5) Engle-Stone, Reina; (6) McDonald, Christine; (2) Guo, Junjie;

(2) Ismaily, Sanober; (3) Flores-Ayala, Rafael.

(1) MD, MPH. Departments of Pediatrics and Global Health. Emory University. Nutrition Branch. Centers for Disease Control & Prevention; (2) Hubert Department of Global Health. Emory University; (3) Nutrition Branch. CDC; (4) Hubert Department of Global Health. Emory University. Nutrition Branch. CDC; (5) PhD Nutritionist. Department of Nutrition. University of California Davis; (6) Deputy Director of IZiNCG at Children's Hospital Oakland Research Institute.

The Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project is a multi-agency and multi-country collaboration formed in 2012 in an effort to improve micronutrient assessment and anemia characterization globally. BRINDA's overall goal is to refine approaches to estimate the prevalence of micronutrient deficiencies and thus improve the targeting, design and effectiveness of nutrition research and programs. BRINDA phase 1 was recently completed with key findings on approaches to adjust biomarkers of iron and vitamin A status
for inflammation, as well as factors associated with anemia in both
high and low inflammation settings.

BRINDA phase 2 activities build on the success of BRINDA 1 by expanding the scope of countries included in analysis and answering new key research questions including: 1) approaches to address the association between inflammation and zinc in pre-school children (PSC) and women of reproductive age (WRA); 2) approaches to address the association between inflammation and vitamin B12 and folate in PSC and WRA; 3) role of stunting and inflammation on micronutrient deficiencies in PSC; and 4) relationships between the double burden of malnutrition (e.g., coexistence of undernutrition and overweight/obesity), inflammation and micronutrient status among PSC and WRA. To address these questions, an expanded harmonized dataset was created, containing 24 cross-sectional nutrition surveys, representing 36,360 PSC and 41,881 WRA from all six WHO geographic regions. Survey prevalence estimates took into account complex survey design and weights, where appropriate. Overall prevalence was defined using the median prevalence estimates across surveys.

The overall prevalence of inflammation in PSC was 30.8% (either CRP > 5mg/L or AGP >1 g/L), ranging from 6.0% (US) to 67.3% (Cote d'Ivoire). In WRA, the prevalence of inflammation was 15.3%, ranging from 6.6% (Vietnam) to 36.8% (Cambodia). In PSC, stunting prevalence (height-for-age z-score <-2) was 26.7%, ranging from 3.6% (US) to 50.8% (Laos), and overweight/obesity prevalence (BMI-for-age z-score >2) was 6.2%, ranging from 0.6% (Laos) to 19.5% (Georgia). In WRA, the prevalence of BMI > 25 kg/m2 was 48.3%, ranging from 8.0% (Vietnam) to 71.7% (Mexico), and BMI <18.5 kg/m2 was 6.0%, ranging from 1.4% (Mexico) to 20.5% (Vietnam). Zinc deficiency in PSC (serum zinc <57 ug/dL in afternoon or <65 ug/dL in morning) was 44.7% overall, ranging from 10.3% (Ecuador) to 78.7% (Cameroon). In WRA, zinc deficiency [serum zinc <59 ug/dL in afternoon or < 66 ug/dL in morning (non-fasting), <70 ug/dL in morning (fasting)] was 52.9%, ranging from 28.8% (Mexico) to 82.2% (Cameroon). The prevalence of zinc, B12 and folate deficiencies by inflammation adjustment approach will be analyzed.

Conclusions: Findings from BRINDA will be used to inform
international guidelines on the appropriate interpretation of mi-
cronutrient biomarkers in settings of inflammation as well as ap-
proaches to address the double burden of malnutrition in various
settings.

**Keywords:** Nutrition assessment, inflammation, zinc deficiency, folate deficiency, double burden

**Further collaborators:**

Supported by the Bill & Melinda Gates Foundation, Centers for Disease Control and Prevention, Global Alliance for Improved Nutrition, and Eunice Kennedy Shriver National Institute of Child Health and Human Development. Work presented on behalf of the BRINDA working group.

INTRODUCTION TO THE WORK OF THE IAEA IN
THE FIELD OF NUTRITION

Loechl, Cornelia.

PhD. Seciton Head. Nutritional and Health-Related
Environmental Studies Section. International Atomic Energy
Agency (IAEA). Austria.

The IAEA's programme in nutrition supports the use of stable (non-radioactive) techniques to combat malnutrition in all its forms. Stable isotope techniques play an important role in understanding the mechanisms of malnutrition and as a reliable tool in designing and evaluating the impact of nutrition interventions. They improve specificity and sensitivity of nutritional evaluations such as the assessment of fat and lean body composition, energy expenditure, breastfeeding patterns, body vitamin A stores, and factors affecting absorption and retention of essential minerals such as iron and zinc in the body. The IAEA fosters its use to generate evidence for informed nutrition programming across the life course, from infant and young child feeding, to maternal and adolescent nutrition, to healthy ageing, and to track progress towards achieving World Health Assembly targets. This complements the efforts of other UN agencies, NGO's and Government Institutions in nutrition. The IAEA provides support and training to build the capacity to use stable isotope techniques in nutrition through a) national and regional nutrition projects via its Technical Cooperation Programme with governments of Member States as well as b) coordinated research conducted by individual investigators to address specific problems. In the area of nutrition and aging, the IAEA supports the application of stable isotope and other nuclear techniques to measure changes in body composition (normally loss of muscle mass and increase in body fat) and physical activity, bone health, and micronutrient bioavailability. An example includes a regional project in 12 countries in Latin America and the Caribbean with the aim of standardizing techniques for the early diagnosis of sarcopenia (age-related loss of skeletal muscle mass and strength) and raising awareness of this important issue for the quality of life of older people in the region. Body composition by deuterium dilution technique in relation to the loss of functionality is assessed in the older population with the aim to determine cut-off values for the determination of sarcopenia in order to improve early diagnosis. A database of fat-free body mass will be compiled, which will allow the development of easier field methods to measure body composition based on anthropometry and bioelectrical impedance. As the basal metabolic rate and thus energy requirements decline with age, the doubly labeled water technique is used to measure total daily energy expenditure in older adults undergoing their normal daily activities in order to determine caloric needs with or without sarcopenia. The project will provide a tool for the health sector to allow for early detection of sarcopenia and ensure early interventions can delay physical disability and improve the quality of life in the elderly. This will also help to reduce health-related costs of the elderly population.
# PREVALENCE AND FUNCTIONAL IMPACT OF SARCOPENIA

Ferriolli, Eduardo.

MD, PhD, Department of Internal Medicine, Ribeirao Preto Medical School, University of Sao Paulo.

The prevalence of sarcopenia in different studies varies significantly, depending on the population studied, definition adopted, method used for the measurement of muscle mass and function. It varies, in different populations, from 1 to 29% in the community and from 14 to 33% in institutions. Recently, a meta-analysis was published (Diz et al., 2016) showing a prevalence of 17% in Brazil. Another meta-analysis of general population studies found a prevalence of 10% in men and women worldwide (Shafiee et al., 2017). Sarcopenia has been associated with negative metabolic and clinical outcomes, including increased insulin resistance, lower energy expenditure, lower resistance for aerobic activities, increased number of falls, increased incidence of reduced mobility, disability, dependencies and death. Considering the ageing of the world population, and, especially, of the developing countries, these numbers show the importance of this condition as a serious public health problem. Being sarcopenia defined as low muscle mass associated with low muscle strength or function, the diagnosis is clearly dependent on cut-off points for the different assessments and these will vary depending on the population studied. Lourenço et al. (2015) verified the performance of the European Working Group on Sarcopenia in older people and their findings showed that the adoption of the original cut-off points in Spanish, Mexican and Brazilian cohorts would define 83.4% of the total cohort as suspects for having sarcopenia, indicating muscle mass assessment; assuming adapted cut-off values, this proportion decreased to 34.2%. In Brazil, the Frailty in Older People Study (FIBRA-BR) found cut-off points considerably lower than the ones originally proposed, considering the 20th percentile of the performance of the studied population. A Latin America Regional Project funded by the International Atomic Energy Agency (IAEA) is verifying the association between low muscularity and function in 12 Latin American and Caribbean countries, aiming to determine tools and standards for the diagnosis of sarcopenia and to increase awareness of this condition in this region. Body composition was measured by the deuterium dilution method, bioimpedance analysis, anthropometry and dual-energy X-ray absorptiometry when available; function and strength by the measurement of walking speed, handgrip strength, timed up-and-go test and six-minute walking test. A sub-group had energy expenditure measured by the doubly labeled water method and physical activity pattern by an accelerometry based physical activity recording system. New parameters for the association between muscularity and physical performance in the Latin America and Caribbean region will be defined and the results will be discussed during this symposium.

# DIETARY FACTORS CONTRIBUTING TO SARCO-PENIA SYNDROME

Aleman Mateo, Heliodoro.

PhD. Nutritionist. Nutrition and Metabolism Department, Coordination of Nutrition, Research Center for Food and Development. Carretera a La Victoria, Km 0.6 Hermosillo, Sonora, CP 83304. Mexico.

Sarcopenia is a progressive, chronic clinical condition associated with the aging process characterized by the loss of skeletal muscle mass, muscle strength and functionality. In older adult populations, this condition increases the risk of adverse outcomes, such as physical disability, poor quality of life, and increased morbidity and mortality rates. The concept of sarcopenia has evolved significantly from the original definition proposed by Irwin Rosenberg (1989). Recently, the European Working Group on Sarcopenia in Older People published a consensus on the definition of sarcopenia and the diagnostic criteria for sarcopenia syndrome. Regarding the factors that contribute to the loss of skeletal muscle and development of sarcopenia syndrome, the literature now recognizes the role of such elements as pro-inflammatory cytokines, vitamin D deficiency, anabolic hormone deficiency, insulin resistance and hyperinsulinemia, anabolic resistance to nutrition and exercise, chronic illness, sedentarism, as well as other lifestyle factors, including low or poor dietary protein intake and the non-homogeneous distribution of protein at mealtimes. More recently, other dietary factors have been reported as contributing factors for sarcopenia and sarcopenia syndrome, though most current evidence highlights the role of low dietary protein intake as the main alimentary factor that exacerbates the loss of skeletal muscle mass in older adult populations. This presentation reviews cross-sectional and cohort studies on the association between high dietary protein intake and sarcopenia and analyzes the main results of some published studies of clinical trials on dietary protein supplementation. Finally, the main challenges involved in satisfying the current recommendations for dietary protein in older people in Latin American countries are discussed briefly.

**Keywords:** Loss of skeletal muscle mass, sarcopenia syndrome, dietary protein intake, aging, physical disability
# DIAGNOSIS AND PREVENTION OF MUSCLE LOSS; CHALLENGES IN LATIN AMERICA

Márquez, Carlos.

MSc. Nutritionist. Public Nutrition Unit. Institute of Nutrition and Food Technology (INTA). University of Chile. Santiago. Chile.

Latin America (LA) is experiencing demographic, epidemiological and nutritional transitions. There is an increase in total aging population in LA which has an impact on many aspects of society. Aging is associated with important physiological changes that should be considered by health care systems. One of the highly relevant age-induced condition is the decline in neuromuscular performance. The loss of skeletal muscle mass and the changes in the structure and function associated to aging are clinically important because they are responsible for decreasing muscle strength and the capacity to perform physical activity. Therefore, it is necessary to be able to diagnose loss of muscle early and to implement effective interventions to prevent it. There are different techniques available to diagnose loss of muscle mass. Simple assessment methods to reflect muscle loss include weight loss and decrease in calf and mid-arm muscle circumference. More accurate estimations of muscle mass can be gained by bioelectrical impedance analysis (BIA), dual-energy X-ray absorptiometry (DXA), and the reference method of deuterium dilution technique to determine total body water (TBW) and calculate fat-free mass. Predictive models of appendicular skeletal muscle mass have also been developed in Chile, based on anthropometric measurements and functional tests in the elderly.

The prevention of the loss of muscle mass in the elderly will be influenced by socioeconomic factors such as income, education, existence of support networks and general health status (nutritional status, pathologies and integrity of their denture). Diet quality is important for the prevention of skeletal muscle loss. High quality, easy digestible protein in sufficient amounts is needed to maintain the muscle mass and vitamin D status and intake need to be considered. Physical activity also has positive effects on the overall health of the elderly and may prevent muscle loss. Studies have shown that the prescription of supervised muscle strength training for elderly people counteract or at least attenuate the decline in neuromuscular function.

The challenge for LA is to establish population specific cutoff points for muscle mass loss and to develop screening tools to identify early muscle loss in the elderly to ensure interventions can be implemented. A group of researchers is finalizing a project whose objectives are to develop an anthropometric model of prediction of skeletal appendicular muscle mass in Latin American elders and establish cutoff points for healthy muscle mass.

**Keywords:** Elderly, muscle loss, nutrition, physical activity.

### VITAMIN D STATUS AROUND THE WORLD: EPI-DEMIOLOGICAL DATA AND DIAGNOSIS

González-Gross, Marcela.

Pharm D. Professor. Department of Health and Human Performance. Universidad Politécnica de Madrid. Vice-President of the Spanish Nutrition Society. CIBERobn. Spain.

Low vitamin D concentration is an increasing public health problem around the world, contributing to the double burden of malnutrition as defined by WHO. Serum or plasma 25-hydroxyvitamin D [25(OH)D] continues to be the optimal marker of vitamin D status because its long half-life and because it reflects both D2 and D3 levels.

The debate regarding optimal cut-offs for diagnosis is still open. In the last years, and for better comparison among studies, international guidelines have been accepted to define sufficiency/optimal levels ≥75nmol/l (30ng/ml); insufficiency <75 nmol/l; deficiency <50 nmol/l (20 ng/ml) and severe deficiency <27.5 nmol/l (10.8 ng/mL). This last cut-off is the most controversial one, as some authors propose <30 nmol/l (12ng/ml) as deficient, and others go down to 20 nmol/l (8 ng/ml).

Identified risk factors include restricted diets, insufficient sunshine exposure, sunscreen use, darker skin pigmentation, high latitude, full-body clothing cover, season, air pollution, age, efficiency of absorption in the gut, liver and kidney disease, and medication use (notably anticonvulsants, corticosteroids).

Deficiency affects mainly all population groups and is present in all continents. In infants, highest prevalence of rickets, the clinical manifestation of vitamin D deficiency have been observed in North America, South America, Europe and parts of the Middle East. Concentrations <30nmol/l have been observed in Iran (86%), Kuwait (66%) or India (61%). Lowest prevalence in Argentina (3%) and China (0.4%). High prevalence of deficiency (<30 nmol/l) has been observed in children i.e. from Afghanistan (73%) and Malaysia (35%); in female adolescents from Saudi Arabia (81%). In fact, being a female is a risk factor in certain countries. Concentrations <50nmol/l were observed e.g. in adults from Jordan (14% of females vs. 2% males), Sri Lanka (59% vs. 34%) and Nigeria (34% vs. 5%). Elderly people are especially at risk because with aging there is an important change in lifestyle like less solar exposure and less outdoor activity. A high prevalence of concentrations <30nmol/l have been observed in Germany (67%), India (62%), Morocco (52%; females) or Australia (22-45%).

Within the EU-funded ODIN study, applying vitamin D Standardization Program (VDSP) protocols to serum 25(OH)D data from representative childhood/teenage and adult/older adult European populations, an overall pooled estimate, irrespective of age group, ethnic mix, and latitude of study populations, showed that 13.0% of the 55,844 European individuals had serum 25(OH) D concentrations <30 nmol/L on average in the year, with 17.7% and 8.3% in those sampled during the extended winter (Octo-
ber-March) and summer (April-November) periods, respectively. The prevalence of <50 nmol/L I was 40.4%. In a study we performed on non-supplemented Spanish elite athletes, apart from seasonal variations, a significant difference was observed between those training indoor and outdoor, especially in winter around a mean 20nmol/l difference. Even sunny countries are at risk for vitamin D deficiency during the winter months.

**Keywords:** Vitamin D deficiency. Rickets. Calcidiol. Public health.

**Further collaborators:**

References:

Cashman KD, Dowling KG, Škrabáková Z, Gonzalez-Gross M, et al. Vitamin D deficiency in Europe: pandemic? Am J Clin Nutr. 2016 Apr;103(4):1033-44. Muscogiuri G. Vitamin D and chronic diseases: the current state of the art. Arch Toxicol. 2017 Jan;91(1):97-107. Palacios C, Gonzalez L. Is vitamin D deficiency a major global public health problem? J Steroid Biochem Mol Biol. 2014 Oct; 144PA: 138-145

## VITAMIN D: CLASSIC AND NOVEL ACTIONS

Gil, Ángel.

PhD. Prof. Department of Biochemistry and Molecular Biology. Institute of Nutrition and Food Technology. Centre of Biomedical Research. University of Granada. CIBERobn. Spain.

Vitamin D has a key role in calcium homeostasis. Indeed, vitamin D participates actively in calcium intestinal absorption, renal excretion and bone synthesis and remodelling. In addition, vitamin D also affects the absorption and excretion of phosphate. Vitamin D is mainly produced by photobiogenesis at the skin by the action of ultraviolet radiation B on 7-dehydrocholesterol, but it can also be derived from a number of dietary sources i.e. ergocalciferol (vit D2) from plants and cholecalciferol (D3) from animal foods, mainly fatty fish, eggs, meats and dairy products. D3 is by far the most important source of vitamin D. Vitamin D requirements ranges from 400 to 600 IU/d (10-15 µg/d), depending on age, sex and lifecycle conditions.

Vitamin D is transported from the intestine to the liver and rapidly hydroxylated to 25(OH)D2 and 25(OH)D3 by a cytochrome P450 dependent enzyme. Those metabolites reach the systemic circulation and later are hydroxylated in the renal cortex to render calcitriol (1-25(OH)2D), the active vitamin D. Alternative 24-hydroxylation of 25(OH) D renders 24-25(OH)2D, which is inactive, this compound contributing to the regulation of calcitriol levels in plasma. Blood and adipose tissue are well known stores for vitamin D, and plasma 25(OH)D3 is recognised as the best biomarker of vitamin D status.

The regulation of calcitriol synthesis relies on the activity of both 1-α-hydroxylase (CYP27B1) and 24-hydroxylase (CYP24A1). Increased levels of parathormone (PTH) due to vitamin D insufficiency or hypocalcemia, lead to increased expression of 1-α-hydroxylase, which results into increased synthesis of calcitriol. Opposite, high levels of plasma calcitriol and calcium inhibit the secretion of PTH. In addition, calcitriol inhibits its own synthesis

through the modulation of the renal hydroxylases. In addition, when calcium levels increase thyroid C cells produce calcitonin, blocking calcium bone mobilization and stimulating calcium and phosphorus renal excretion.

In addition to the classic roles of vitamin D in increasing intestinal calcium and phosphate absorption and increased bone synthesis and remodelling, novel roles of vitamin C affecting cell proliferation, differentiation and apoptosis, as well as increasing innate immunity and decreasing adaptive immunity have been recognised. Moreover, vitamin D is involved in the protection of cardiovascular system through the regulation of the renin-angiotensin system, PTH secretion, adipocyte apoptosis and insulin secretion.

The action of vitamin D in the immune system is mainly mediated by the increased phagocytic capacity of antigen presenting cells (dendritic cells and macrophages) against microbes. This action is due to calcitriol which enhances the expression of cathelicidins, one particular type of antimicrobial peptides. In addition calcitriol inhibits the production of the granulocyte and macrophage colony stimulating factor (GM-CSF). Moreover, calcitriol inhibits the expression of major proinflammatory cytokines e.g IL-1, IL-6. IL-12 and TNF-α, and the development of Th1 cells, differentiation of B lymphocytes and antibodies production.

**Keywords:** Bone metabolism. Calcitriol. Immune system. Photobiogenesis. Vitamin D

## VITAMIN D LEVELS DURING PREGNANCY AND FETAL IMPLICATIONS

(1) Larqué, Elvira; (2) Blanco-Carnero, José Eliseo.

University of Murcia. Spain.; (2) Hospital Virgen de la Arrixaca, University of Murcia, Spain.

Maternal vitamin D insufficiency during pregnancy is a common issue and a significant public health problem globally. The circulating 25(OH)D concentration sufficient to meet the physiological needs of humans is an ongoing subject of debate, which affects the prevalence of vitamin D deficiency/insufficiency estimated around the world. Since evidence is lacking regarding appropriate cut-points to define vitamin D status during pregnancy, levels used to establish intake recommendations and vitamin D content of prenatal vitamin supplements are quite conservative.

During pregnancy, maternal hemodilution is accompanied by a number of physiological changes to both vitamin D metabolism and maternal body composition; such adaptations might lead to differences in the determinants of response to vitamin D supplementation between pregnant and non-pregnant women. Maternal 1,25-dihydroxyvitamin D concentrations increase during the third trimester, and it can be synthesized by the placenta since it contains the enzyme 1-α-hydroxilase.1 Furthermore, it is possible that vitamin D increases the synthesis of various calcium-binding proteins in the placenta. Clinically, understanding how individuals respond could lead to individualized antenatal counselling regarding vitamin D supplementation to ensure vitamin D repletion without increasing the risk of vitamin D toxicity.
The importance of vitamin D in pregnancy for maintaining maternal calcium homeostasis and there for fetal bone development is well recognized; moreover, there is a large discussion on potential maternal detrimental effects of vitamin D deficiency on perinatal outcomes, fetal development and the long-term skeletal health of children. Recent studies are also evaluating its effects on asthma fetal programming.

Risk factors for vitamin D insufficiency are well described, and include ethnicity, extensive skin covering and liberal use of sun protection, overweight/obesity, low dietary vitamin D intake, and smoking, in addition to the seasonal variation that is observed at temperate latitudes. The increasing obesity rates in young women enhance the prevalence of vitamin D deficiency, due to vitamin D storage in adipose tissue, reducing its maternal blood levels and fetal availability. Moreover, gestational diabetes risk is higher in obese mothers which may affect the associations with vitamin D levels.

Pregnant women require at least 400-600 IU per day of vita-
min D. It has been proposed by The Endocrine Society that at least
1500-2000 UI/ of vitamin D may be needed to maintain a blood
level of 25(OH)D above 30 mg/dl. A recent randomized trial of
1000 IU of vitamin D supplementation during pregnancy found
no effect on offspring bone health in infants born in the summer
but did find enhanced fetal bone mineral accretion in infants born
during the winter months.2 The benefits of vitamin D supplemen-
tation during pregnancy should be evaluated through rigorous in-
tervention studies.

**Keywords:** Vitamin D, gestation, pregnancy, supplementa-
tion, perinatal outcomes

VITAMIN D AND OBESITY

Aguilera, Concepción María.

PhD. Department of Biochemistry and Molecular Biology,
Institute of Nutrition and Food Technology, University of
Granada. CIBERobn. Spain.

Vitamin D (vitD) adequate concentration is essential for
growth, development and health. It plays a relevant role in the reg-
ulation of calcium levels and bone metabolism. In addition, recent
studies indicate that hypovitaminosis D compromises long-term
condition as a consequence of its non calciotropic effects, such as
the implication/regulation of immune system, endocrine pancre-
as, liver, skeletal muscle and adipocytes. In fact, vitD insufficiency
is associated with a wide range of chronic disease and conditions,
including obesity, and several types of cancers. Suboptimal vitD
status has also been associated with increasing severity of metabol-
ic dysregulation (insulin resistance, hyperlipidemia, liver disease
and hypertension) in children and adults with obesity. In the last
years the prevalence of overweight and obesity in Spanish children
and adolescents has highly increased. Therefore, the identification
of associated factors and risk groups related to hypovitaminosis
D is critical. In this context, we have characterized vitD status in
471 children and adolescents (2 to 18 years age) and analyzed its
correlation with gender, pubertal period, age and Body Mass In-

dex (BMI). An inverse lineal effect of BMI and age on 25(OH)D
concentrations was observed in children, 39.6 % of vitD levels var-
iability was explained by BMI. Therefore, understanding the un-
derlying contribution of suboptimal vitD status to the metabolic
dysregulation disorders in obese subjects is important.

Recently, several studies have attempted to establish the mo-
lecular mechanism of the relation between vitD levels and obe-
sity. Some of these studies suggest that vitD, due to its fat-soluble
characteristic, is retained by the adipose tissue. In addition, it has
been described that adipose tissue has the capacity to metabolize
vitD locally, and this can be dynamically altered during obesity.
Considering the importance of low grade chronic inflammation
in metabolic syndrome and obesity, many authors hypothesized
the involvement of the vitD in the pathogenesis of these diseases
altering the balance between pro and anti-inflammatory cytokines
and thus affecting insulin action, lipid metabolism and adipose
tissue function and structure. Indeed, VitD increases the produc-
tion of some anti-inflammatory cytokines and reduces the release
of some pro-inflammatory cytokines. The association of the vitD
pathway gene variants with anthropometric measurements and li-
pid profile has also been investigated. Polymorphisms in the vitD
receptor (VDR) gene have been shown to be associated with the
components of metabolic syndrome, obesity and type 2 diabetes
mellitus in different populations. There are some reports of asso-
ciations between the retinoid X receptor gamma gene variants and
lipid and anthropometric parameters. And polymorphisms at the
vitD-binding protein gene have been associated with body-fat per-
centage and obesity.

VitD supplementation in obese subjects showed controversial
effects: with some studies demonstrating improvements in insulin
sensitivity, glucose and lipid metabolism while others showing no
beneficial effect on glycemic control and on inflammation. In con-
clusion, despite of the evidences of a significant role of VitD in the
pathogenesis of obesity, metabolic syndrome and type 2 diabetes,
its potential function in treatment and prevention of these diseases
is unclear.

**Keywords:** Obesity, Vitamin D, Child, Molecular

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NUTRITION DATA LIFE-COURSE: HARMONIZATION
AND MANAGEMENT

CURRENT AND NEW INDICATORS FOR SMART
SURVEYS, DEVELOPMENT AND APPLICATION

Sauveplane, Victoria.

Action Against Hunger.

According to recent global data from UNICEF, WHO and the World Bank, 50 million children are suffering from acute malnutrition and 159 million children are stunted. Availability of high quality nutrition data is essential in understanding the extent of nutritional needs and how to best develop programs to most ap-
propriately address those needs, especially during emergencies and large scale responses. The availability of timely and credible nutrition data, presented in accessible ways at national and sub-national levels, can help governments and other actors to be responsive to these challenging circumstances, guide nutrition and health programming in-country and help prioritize support globally. Valid nutrition data and evidence make the difference.

SMART (Standardised Monitoring and Assessment of Relief and Transitions) is recognised as the standard methodology for nutrition and mortality surveys at national and sub-national level by decision makers in the international nutrition community, including government ministries (e.g., national Ministries of Health), institutes of statistics, national and international NGOs, organizations, UN agencies, academia, and consultants. Endorsed by the Global Nutrition Cluster, most nutrition surveys in Sub-Saharan Africa are conducted using the SMART Methodology. The high quality data collected with SMART feed into national and regional nutrition information systems for effective and coordinated decision-making, particularly in times of emergencies when data is critical for resource allocation. SMART tools are also critical for the preparedness of governments and other actors gathering and utilizing data of various population groups, geographic levels and contexts allowing comparability across countries and over the course of multiple years.

Given the standardization of data collection tools, comparability across countries and contexts, adaptability with mobile technology, and data quality checks, Nutrition International approached the SMART team at Action Against Hunger to ultimately increase availability of consistent and reliable data for the monitoring of nutrition indicators based on the SMART tools for their cross-country nutrition and health programming.

**Keywords:** Nutrition, assessment, standardization, surveillance, quality.

**Further collaborators:**

Sara Wuehler from Nutrition International (swuelher@nutritionintl.org)

Daniel Sellen from University of Toronto (dan.sellen@utoronto.ca)

# NUTRITION INTERVENTION MONITORING SURVEYS (NIMS) – A STORY OF HARMONIZING DATA INDICATORS AND METHODS ACROSS MULTIPLE COUNTRIES

Nutrition International (NI), formerly the Micronutrient Initiative, has been working to reduce malnutrition in vulnerable populations for 25 years. In part this has involved improving government monitoring and reporting to ensure that nutrition programs are reaching vulnerable populations with interventions that achieve desired results. In reviewing the multiple surveys and monitoring tools that NI has developed and implemented, NI recognized the need for harmonized surveillance methods and tools to (i) obtain and store uniformly collected data to facilitate quality assurance and cross-country analyses; (ii) ensure indicators are consistent across multiple interventions, (iii) establish harmonized electronic data collection tools to facilitate concurrent external survey monitoring and speed survey feedback and final reporting; (iv) potentially adapt these tools for use during supervisory visits to improve regular program monitoring and reporting; and (v) inform other similar global nutrition surveillance efforts.

NIMS tools were initiated in collaboration with Action Against Hunger (ACF) to build on their SMART approach of harmonized data collection for nutrition status indicators. NIMS collects indicators of program related knowledge, attitudes and practices (KAP) as well as facility stocks and provider KAP; related modules currently address maternal iron and folic acid (IFA) and antenatal care, intermittent IFA, infant and young child nutrition, micronutrient powders for young children, delivery and newborn care, zinc and oral rehydration for treating diarrhea, and facility-related issues for each of these topics. NIMS also includes external monitoring tools, being developed and tested in collaboration with the University of Toronto, to provide simultaneous data-cleaning and related feedback to survey teams.

Based on NI's experience while implementing NIMS in four countries, this presentation will summarize the key discoveries and recommendations related to: 1) developing harmonized indicators, 2) ensuring consistency during contextualization, 3) optimizing training and implementation, 4) relative inputs compared

<footnote>(¹)Wuehler, Sara; (²)Rowe, Sarah; (³)Gupta, Payal; (⁴)Schmidt, Kasper;</footnote>

<footnote>(⁵)Kung'u, Jacqueline; (⁶)Raut, Manoj Kumar; (⁷)De-Regil, Luz Maria.</footnote>

<footnote>(¹)Senior Technical Advisor. Global Technical Services. Nutrition International. Ottawa. Canada; (²)Program Manager, Monitoring & Reporting. Program Operations Unit. Nutrition International. Ottawa. Canada; (³)Regional Senior Manager, Monitoring & Reporting. Program Operations Unit, Asia Regional Office.</footnote>

<footnote>Nutrition International. Delhi. India; (⁴)Program Officer, Monitoring, Reporting and Knowledge Sharing. Program Operations Unit. Nutrition International. Ottawa. Canada;</footnote>

<footnote>(⁵)Regional Advisor. Research and Monitoring & Evaluation, Africa Regional Office. Nutrition International. Nairobi. Kenya;</footnote>

<footnote>(⁶)Regional Manager. Research & Evaluation, Asia Regional Office. Nutrition International. Delhi. India; (⁷)Director, Research and Evaluation/ CTA. Global Technical Services. Nutrition International. Ottawa. Canada.</footnote>
to individually developed surveys, 4) potential use for supervisory monitoring visits, and 5) implications for future updates.

**Keywords:** Nutrition, surveillance, harmonization, quality, standardization.

**Further collaborators:**

Action Against Hunger
University of Toronto

## EXTERNAL MONITORING OF NUTRITION SURVEYS – EXPERIENCES FROM DEVELOPING AND IMPLEMENTING MONITORING TOOLS IN TWO MULTI-COUNTRY SURVEY CONTEXTS

(1)Sellen, Daniel; (2)Owais, Aatekah; (3)Begum, Khadija; (4)Kekre, Priya.

(1)PhD. Director. The Joanna and Brian Lawson Centre for Child Nutrition. University of Toronto. Canada.; (2)PhD. Nutrition epidemiologist. University of Toronto. Toronto. Canada.; (3)MD, PhD. Nutritionist. University of Toronto. Toronto. Canada.; (4)MSc. Nutritionist. University of Toronto. Toronto. Canada.

The University of Toronto (UofT), like other academic institutions, partners with implementing agencies to develop scientifically rigorous methods for measuring nutrition-specific and nutrition-sensitive indicators at individual, household and population levels and robust study designs for effective, accurate and interpretable impact evaluation of large-scale interventions aimed at maternal, newborn and child nutrition and health. Recent external monitoring efforts have included: (a) a series of baseline assessments using a quasi-experimental design in four countries as part of Enhancing Nutrition Services to Improve Maternal and Child Health in Africa and Asia (ENRICH), a multi-country, broad-spectrum and integrated intervention program funded by Global Affairs Canada (GAC) and implemented by World Vision Canada (WVC), and partners; and (b) Nutrition International's (NI) Nutrition Intervention Monitoring Surveys (NIMS) conducted in several countries. Both sets of surveys employed SMART approaches and tools embedded within larger household survey (HHS) tools, which were developed to ensure consistency in target indicators, component variables and response sets across settings while accommodating local contextualization, adaptation and translation by in-country research partners (CRPs) in each of the participating countries.

Based on UofT's experiences in support of external monitoring of nutrition surveys in two multi-country survey contexts, this presentation will summarize the key discoveries and recommendations related to: (i) developing English and predominant local language Open Data Kit (ODK) templates for field-based data collection at multiple sites on android devices; (ii) remote coordination with in-country local teams to pre-test, correct and adapt draft tools on very short timelines; (iii) daily monitoring and quality assurance during data collection using rapid analysis and feedback on primary data uploaded to cloud servers. We focus on lessons learned from multiple challenges encountered and met across settings. We highlight the advantages of ODK approaches

when development is controlled centrally, and some specific difficulties that can arise when it is not. Our experience indicates that ODK can be highly effective and efficient when sufficient time and money is invested to make it work smoothly form the first day of data collection, and that it is also flexible, allowing rapid resolution of logistical and technical difficulties in the field when best approaches are applied.

**Keywords:** Harmonization of data collection, maternal and child nutrition, nutrition intervention program, ODK, multi-country

**Further collaborators:**

World Vision Canada, Aga Khan University Pakistan, James P Grant School of Public Health, BRAC University, Egerton University, Muhimbili University of Health and Applied Sciences, Nutrition International

PS_144/150

## GLUTAMATE A SIMPLE MOLECULE WITH SEVERAL FACES

### WHY DO WE LIKE THE UMAMI TASTE OF GLUTAMATE?

San Gabriel, Ana.

D.V.M. M.S. Nutrition. International Glutamate Information Service.

The answer to this question lies behind the understanding of glutamate (Glu) taste properties, its function by itself as an amino acid, and the cooking processes that make Glu so abundant in the foods we eat. Taste strongly determines our food choices and their utilization in the body. Our taste papillae in the tongue express different taste receptors responsible to informing the brain of the chemical background of foods. We are programmed from birth to prefer certain tastes, sweet, umami, weak sour and moderate salty tastes, and avoid others such as very strong bitterness, sourness and saltiness. These innate behavioral responses ensure the intake of sufficient nutrients while protecting us against the ingestion of an excess of sodium, spoiled foods or plant toxic me-tabolites. In the other hand, food habits and dietary patterns are learned from our mother throughout pregnancy and lactation, and through our life eating experiences. They are strongly determined by food and cultural environment.

Glu is the representative compound for umami taste, one of the tastes we are conditioned to prefer. Abundant in breast milk, soups stocks, fermented and cured foods, this amino acid serves multiple functions. As a nutrient, Glu is part of proteins such as meats, fish, eggs, legumes, and dairy products. By itself alone, when is not bound to proteins or peptides, Glu is metabolically active and can behave as a signaling molecule. It is rich inside cells as unbound Glu also known as free Glu (FGlu) where it can be used to synthesize other amino acids or bioactive molecules like the antioxidant glutathione, to generate energy through the Krebs cycle,
or to communicate with neighboring cells. It also contributes to the nitrogen metabolism and detoxification of ammonia producing glu-tamine via glutamine synthetase. Each of these functions requires either metabolic enzymes for synthesis and degradation of FGlu, transporters for carrying Glu through cell membranes, or Glu and taste receptors for rendering information about the cellular envi-ronment or the food we ingest.

It is important to emphasize that only FGlu has taste. The Glu bound to proteins cannot interact with taste receptors and consequently is not relevant to umami, but it is still significant to our body. Many cooking or food manipulation process from many traditional cuisines such as extraction in soups, fermentation, maturation, curing or drying enhances the availability of FGlu. This is why soy or fish sauces, cheeses or soup stocks are very rich in umami. The enzymatic breakdown of proteins or cells in meats or beans releases large amounts of FGlu, which gives a very subtle, long lasting and coating sen-sation throughout the whole tongue characteristic of umami. At the end of the presentation, I will describe how FGlu could function as a general marker of familiar foods or foods that are adequate for our ingestion.

**Keywords:** Umami, glutamate, MSG, taste receptors, signaling
**Conflict of Interest disclosure:** I am employee of Ajinomoto
Company.

## UMAMI TASTE: A TOOL TO REDUCE SODIUM INTAKE

Reyes, Felix.

Prof. Food Toxicology. Department of Food Science. University of Campinas. Brazil.

Sodium chloride (NaCl) has been the most commonly used ingredient to confer salty taste to foods. However, excess sodium in the bloodstream has been associated with the development of several chronic non-communicable diseases, mainly arterial hypertension a risk factor associated to cardiovascular and kidney diseases. In addition, excessive sodium intake has also been associated with stomach cancer, osteoporosis and obesity, among others. Thus, in order to limit sodium intake to levels considered safe, the World Health Organization (WHO) recommends for adults a daily intake of not more than 5 g of NaCl (less than 2 g of sodium). According to the country, most sodium could come from processed foods (USA), or added while eating, home cooking and foods from restaurants (Brazil). As an example, in Brazil, the mean intake of NaCl is 12 g per person per day (4.7 g sodium). The Pan American Health Organization (PAHO) recommends three strategic actions to reduce sodium intake: (1) promotion of healthy eating (particularly with regard to the rational use of salt); (2) implementation of educational actions for health professionals, manipulators and manufacturers of food, and the population; and (3) reformulation of processed foods. The last recommendation indicates there is an urgent need to find salt substitutes to reduce the sodium content in the foods. Among those substitutes umami compounds have been pointed as an alternative strategy, since

they have the ability to balance the taste and harmonize the total flavor of a dish. Umami can also improve the palatability of a wide variety of foods. The umami taste also depends on the amount of salt. It was verified that soups low in salt, but with umami, were tastier than those that did not contain umami. Like salty, umami is also a basic taste and the compounds associated to umami are monosodium glutamate (MSG), guanosine-5'-monophosphate (GMP) and inosine-5'-monophosphate (IMP), mainly. GMP and IMP act synergistically with MSG, and all of them are approved to be used as food additives. Those compounds have been evaluated by scientific committees and regulatory agencies, including the Joint FAO/WHO Expert Committee on Food Additives (JECFA), the Scientific Committee on Food (SCF) of the European Commission, the United States Food and Drug Administration (US FDA), and the Federation of American Societies for Experimental Biology (FASEB). JECFA and the SCF established an acceptable daily intake (ADI) "not specified", which indicated that the substance posed no health risk to consumers when used as a food additive in amounts necessary to obtain the desired technological effect. US FDA and FASEB confirmed both the safety of MSG when used as a food additive, and classified it as a Generally Recognized as Safe (GRAS) substance. In this lecture it will be presented an overview about the safety aspects of MSG as food additive, and the potential applications of its use to reduce sodium content in specific industrialized foods, such as soups, stocks and seasonings, instant noodles, meat products, snacks and milk products.

**Keywords:** Basic test, umami, monosodium glutamate, safety evaluation, industrialized foods.

## HOW DOES GLUTAMATE WORK IN YOUR BRAIN?

Albarracín, Sonia Luz.

PhD. Chemistry. Department of Nutrition and Biochemistry.
Faculty of Sciences. Pontificia Universidad Javeriana. Bogotá.
Colombia.

One challenge of modern neurobiology is the identification of individual molecules that operate within neural circuits, regulating brain function and control synaptic plasticity. Neurotransmitters, the essential molecules for the transfer of information between neurons, are released from a presynaptic terminal into a synaptic cleft. The interaction of a neurotransmitter to its postsynaptic receptors induces an ionic flux that depolarizes or hyperpolarizes the neuron. Neurotransmitter binding also may cause metabolic changes such as the activation of second messenger systems or opening the ion channels.

The glutamate (Glu) in the central nervous system (CNS) is the main excitatory neurotransmitter, and its action depends on the extracellular concentrations being kept low. Due to the blood-brain barrier essentially preventing the entry of glutamate into the CNS, most of the glutamate must be synthetized in the brain mainly from glucose. Essentially by transamination of α-ketoglutarate in both neurons and glia. Depending on the type of neuron, Glu can be used for excitatory synaptic transmission or decarboxylated by a glutamate decarboxilase for the synthesis of GABA, the main
inhibitory neurotransmitter in GABAergic neurons. In synaptic terminals, Glu is stored in vesicles and released via a calcium-dependent mechanism. Once in the synaptic cleft, Glu binds and activates postsynaptic glutamate receptors. The action of Glu is finished by removal from the synaptic cleft by neuronal presynaptic and glial high affinity reuptake systems. Given the critical role of Glu in neural function, it is not surprising that a greater level of regulation is required of brain L-glutamate concentration than that observed in most other tissues where important roles has in the intermediary metabolism and is present at millimolar concentrations.

Astrocytes are the most important cells for controlling both the biosynthesis and turnover of glutamate and GABA. In astrocytes, glutamate is used for the synthesis of glutamine, which is catalyzed by a glutamine synthetase as an inactivating mechanism of this neurotransmitter. Then, glutamine is released and recycled to regenerate glutamate by a phosphate-activated glutaminase. The uptake of glutamate and GABA and their transformation in glutamine by astrocytes give origin to the Glutamate-GABA-Glutamine cycle operating between the nerve endings of glutamatergic or GABAergic neurons and surrounding astrocytes. In addition, the coupling between excitatory and inhibitory neurotransmission is key for maintaining the synaptic function and convert the Glutamate-GABA-Glutamine cycle as a special mechanism of protection against excitotoxicity in normal and pathological conditions such as in neurodegenerative diseases.

In this lecture, we will review the current knowledge on glutamatergic signaling in the central nervous system with a special emphasis in the coupling excitatory and inhibitory neurotransmission and the key role of the astrocytes in this process.

**Keywords:** Neurotransmission, glutamate, excitation/inhibition, metabolism

stimulation of glutamate receptor, mGluR1, within gastric epithelium releases serotonin, nitric oxide that subsequently stimulates the vagus nerve. The vagus nerve then carries information to the hypothalamic centers that control hunger and satiety. In addition, animal and human clinical studies have shown that consumption of glutamate modify body weight and food consumption. In a rat model of obesity, glutamate consumption decreased fat accumulation and leptin production. Data also show that children that drink infant formula rich in glutamate consume less milk than children who do not. Additionally, studies with adults have shown that monosodium glutamate consumption reduces energy intake from fat and sweet snacks. These studies provide evidence for dietary glutamate's role in the regulation of energy balance as a "proteostat" that limits food intake and increases energy consumption.

**Keywords:** Energy balance, food consumption, monosodium glutamate, umami

**Conflict of Interest disclosure:** I am member of "Instituto para estudio del Glutamato en Latinoamérica", Ajinomoto supports my participation in IUNS 21st International Congress

## GLUTAMATE IN THE CONTROL OF ENERGY BALANCE

Baldeón, Manuel E.

Centro de Investigaciones Biomédicas, Universidad Tecnológica Equinoccial. Ecuador.

With metabolic syndrome, overweight, and obesity on the rise worldwide, there is a need to better understand the biology that controls energy balance and regulates body weight. Several external and internal factors have been implicated in the modulation of hypothalamic neurons responsible of satiety and hunger sensations including glucose and fat metabolites; hormonal, immunological and nervous mediators. Studies considering the recognition of dietary glutamate by specific receptors in the intestinal tract have contributed to the understanding the role this amino acid has in the regulation of energy balance. Glutamate functions as a nutrient and as a dietary signal from the gastrointestinal towards the brain. At the moment, glutamate's role in umami taste upon stimulation of specific receptors on epithelial cells present in taste buds is well established. Animal studies have also shown that
# Track 6: Functional Foods and Bioactive Compounds

PS_144/141

## ESSENCE OF WASHOKU, UMAMI IS THE BASIC TASTE FOR BETTER NUTRITION?

### UMAMI: THINKING OF AN IDEAL HEALTHY DIET FROM THE UNESCO HERITAGE FOOD CULTURE, WASHOKU

Yamamoto, Shigeru.

Jumonji University. Japan.

Life-expectancy at birth for Japanese is long; the mean for women is 86 and 80 for men. Cancer and heart disease have been increasing; however, the age-adjusted death rates have been quite constant, indicating the increase has been due to the increase in the elderly population. The prevalence of obesity is the lowest in the 50 developed countries, with obesity defined as BMI over 30. The prevalence of obesity in the last 40 years has increased in the USA from 15% to more than 30%, and in England from 7% to 25%. In Japan it has also increased from 2% to 3.5%, but the increase has been small. The Japanese have maintained their lipid intake at about 55g/day for more than 40 years. World-wide the higher the income, the higher the lipid intake; however, Japan has been exceptional in this. Sugar intake is more than 100g in the USA and Holland and more than 50 g in Taiwan but only about 30 g in Japan.

The above results may be attributed to the Japanese cuisine. A special aspect of this cuisine is UMAMI seasonings. These include glutamate from sea kelp, inosinate from fish, and guanosinate from mushrooms. People may always seek tasty ingredients in meals, for example, salt, sugar, lipids and UMAMI seasonings. Japanese had been using high salt for a long time and had high blood pressure. A major cause of death until 1980 was stroke (brain hemorrhage) from high blood pressure. After the 1980's, UMAMI seasonings became more common because of low-cost commercial production and salt intake decreased. Perhaps the factors of low lipid intake over a long period and low sugar intake were also due to UMAMI seasonings.

Visual appeal may be an important factor of the Japanese cuisine providing psychological satisfaction. Gourmet Japanese cuisine is trying to express a view of nature in cooking. To that end, not only expensive ceramics and lacquer ware but also fish in a container in a boat-shaped wooden container, tree branches, grasses, flowers and even seaweed are used. Even in home situations, the presentation of food is an important consideration. The tendency to provide a number of smaller separate dishes may also contribute to the health of Japanese. Japanese cuisine tends to vary the preparation of standard ingredients (such as the diverse dishes

based on soybeans); this perhaps contributes to a feeling of novelty that reduces habituated consumption.

Does such an attempt have the potential to contribute to health? For example, if the same dish is served in a paper container or on beautiful tableware, is the effect on health the same? If food is beautifully presented in small amounts on a variety of dishes rather than in a large amount in a single dish, our eating speed will be moderate and our intake will decrease. I think that such factors may have influenced obesity prevention, health promotion, and longevity for Japanese.

**Keywords:** Washoku, Japanese cuisine, health, UMAMI, small portion

### UMAMI: ESSENCE OF WASHOKU FOR HEALTHY AGING

Uneyama, Hisayuki.

Ph.D. Executive Professortal. Global Communications Department. Ajinomoto Co. Inc.

More than 109 years ago, umami taste, the perceived taste essence of Washoku was originally discovered as a new taste quality by Japanese scientist, Professor Kinunae Ikeda with a motivation to improve the poor nutritional status of Japanese people. Finally, he contribute to develop the first umami taste seasoning, monosodium glutamate (MSG) as an affordable seasoning to make everybody able to cook delicious and tasty foods easily, cooperated with Ajinomoto Company. Today after his great work, Japan has been entered into the highest aged society with an active long-life expectancy. However, even now, many Japanese elderly faces to under-nutritional status, especially protein-energy malnutrition suffering from decrease in oral and gut functions with aging (hydro-salivation/ taste and swallowing dysfunction/dyspepsia/constipation). Using the purest umami taste substance (MSG), we has shown that umami taste could be sensed at oral tongue as well as gastrointestinal tracts and might act as an intake nutrient sensor (especially, protein) to modulate appetite and food digestion. Especially, many animal and human studies indicate that umami taste can stimulate exocrine secretions related to food digestion such as saliva and gastric juice. Now, we can know some clinical trials to examine whether umami taste has a power to improve the functional decrease of those aging-related health issues, or not. In this my presentation, I'll review the recent reports on umami taste research for improving elderly health, and discuss umami taste is how important to has been contributed to active-long life expectancy of Japanese people.

### Reference

1) Sasano T, Uneyama H, Hummel T., edited. Sensory Science of Oral Health for Creating New Preventive Medicines (Special Issue). Curr Pharm Design, 22, 2016.

2) Yamamoto S, Tomoe M, Toyama K, Kawai M, Uneyama H. Can dietary supplementation of monosodium glutamate improve the health of the elderly? Am J Clin Nutr. 90 844S-849S, 2009.
**Keywords:** Umami taste, elderly nutrition, oral health, gut health, monosodium glutamate

**Conflict of Interest disclosure:** The author is an employee of Ajinomoto Co., Inc.

## SUBLIMINAL IMPACT OF BASIC TASTES FOR DECISION MAKING ON FOOD SELECTIONS

Alonso-Alonso, Miguel.

MD PhD. Assistant Professor. Harvard Medical School. Director. Laboratory of Bariatric and Nutritional Neuroscience. Beth Israel Deaconess Medical Center. Boston. Massachusetts. USA.

Taste is known to play an important role in shaping food choice, and overall in the consumption of food. However, there is limited understanding of the mechanisms underlying these effects, particularly for non-sweet tastes and in the case of complex, cognitive aspects that go beyond appetite, reward or affective associations, e.g. health or dietary goals. Notably, little is known about whether taste could prime and potentially bias food choice via upstream effects, at the level of brain regions involved in cognitive executive processes that support goal-oriented, adaptive behaviors necessary for healthy eating in the current environment.

We conducted a study to explore possible associations of umami taste with brain and cognitive determinants of healthy eating. Previous experimental studies have shown that pre-meal intake of a broth or soup supplemented with monosodium glutamate, a key substance underlying the umami taste of foods, can decrease appetite and food intake, particularly in women with propensity to overeat and gain weight. Based on these data, we examined acute changes in brain and cognitive domains related to healthy eating following intake of a chicken broth alone or supplemented with monosodium glutamate in a sample of healthy young women. Subjects were evaluated with a food-modified computerized inhibitory control task, a buffet meal test with two calorically conflicting menu sets during which subjects wore eye-tracking glasses, and brain responses during a food choice paradigm evaluated with functional neuroimaging. We found evidence for improvement in key parameters related to inhibitory control following intake of the broth with monosodium glutamate, particularly in subjects with high levels of disinhibition, who also showed lower intake of saturated fat during the meal. Additionally, consumption of this broth led to a reduction in the rate of fixation switches between plates at the meal, and increased engagement of a brain region in the left lateral prefrontal cortex previously associated with successful self-control during food choice. Altogether, these results suggest potential facilitating effects of umami taste, specifically monosodium glutamate, in cognitive-executive processes that are relevant for the support of healthy eating behaviors and food choice.

**Keywords:** Umami, monosodium glutamate, neurocognition, eating behavior, food choice

**Conflict of Interest disclosure:** This study was funded by a grant from Ajinomoto

## CONTROL OF APPETITE WITH PROTEINS, PEP-TIDES AND AMINO ACIDS

Anderson, Harvey.

PhD. Director. Program in Food Safety. Nutrition Regulation Affairs. Professor Nutritional Sciences and Physiology.

Protein consumption impacts many essential physiological functions in addition to providing amino acids for protein synthesis. Appetite control is one of these functions. Consumption of proteins increase satiety and reduce food intake when consumed alone or with carbohydrate. The role of proteins in appetite control are of interest because they are more satiating than either carbohydrate or fat. They regulate food intake and metabolic functions by the combined actions of the intact protein, encrypted peptides and amino acids in the gastrointestinal tract and brain centers. The impact of consuming proteins on appetite control depends on many factors, including source, quantity, time of day, before or with a meal and age. These factors interact with the physiologic sensing of protein intake arising from the actions of peptides and amino acids released by digestion. The sensing systems include amino acid and peptide receptors in the gastrointestinal tract, and free amino acids in plasma and brain. As well the products of digestion stimulate many gastrointestinal hormones the signal the brain's food intake regulatory centers. Proteins may also increase food intake by adding palatability to foods and meals. In contrast, isolated proteins, their peptides or free amino acids are often unpleasant when consumed alone. The exception to the generally unpleasant taste of protein hydrolysates or free amino acids is monosodium glutamate, which provides the umami taste and may also provide signaling of protein ingestion via gut receptors. With the exception of glutamate, the potential of individual free amino acids to be uses as tastants or additives for regulation of appetite and food intake in humans has received little exploration. However it is clear they provide nutrient signaling via the gut. In summary, food proteins and the peptides and amino acids have many physiological functions that contribute to regulation of appetite and healthy body weight.

**Keywords:** Protein intake, appetite control, amino acids, taste, satiety
FOOD LOSSES AND WASTE (FLW) AS SOURCE OF BIOACTIVE COMPOUNDS OF NUTRITIONAL INTEREST

Polenta, Gustavo.

PhD. Biochemist. Food Technology Institute. Agro-Industry Center. Instituto Nacional de Tecnología Agropecuaria (INTA). Argentina.

In recent years, two relevant facts have emerged, which will probably have an impact on the food industry agenda in the near future. On the one hand, the estimation made by the Food and Agriculture Organization (FAO), that around one third of all food produced in the world is lost or wasted. In addition to reducing farmers' incomes and increasing consumers' expenses, FLW have also an important negative environmental impact because of the associated greenhouse gas emissions and inefficient use of water and land. On the other hand, the increasing awareness raised by consumers on the significant role that diet has in the modulation of body functions, which can contribute to improve the state of well-being, to reduce the risks associated to certain chronic diseases, and ultimately to improve the overall quality of life. Market drivers for this awareness include the ageing population, the increasing health care costs, the technological advances in the food technology field, and the progresses made in different food legislations. Within this framework, agricultural by-products, which for many years have been considered as undervalued substrates due to the problems arising from their removal from food production, and the necessity to treat them before their disposal in the environment, are now being regarded as a cheap source of highly appreciated bioactive compounds. As a consequence, an exciting new field of research has arisen, which include the development of emerging processing technologies (such as High Pressure Processing Pulsed Electric Fields, and Ultrasound), able to maximize the efficiency of extraction and the remaining bioactivity of the compounds of interest during the processing and storage of the formulated product; and to successfully deliver the desired bioactive component to the target sites in the body. Other aspects to consider are related to the challenges associated to the regulatory positioning of bioactive compounds and functional foods, to the strategies that should be deployed when launching novel foods containing the recovered compounds into the marketplace (such as Kano Method), and to the need to meet consumer expectations and acceptance, in terms of documented efficacy, food safety, organoleptic properties and price of health promoting food. Therefore, the presentation will discuss general aspects related to the state-of-the-art in the recovery technologies of the target compounds, and their successful recycling inside the food chain as functional additives, in products devoted to different population niches. Specifically, topics to be addressed will be: the recovery strategies and stages to be consider, the impact that emerging

technologies have in aspects such as nutritional value, functional properties, bioavailability and shelf-life of biocompounds, and the use of marketing methodologies leading to the success of the final food products. In addition to the positive impact that this new field will have on the reduction of FLW by recovering part of the nutritional potential of by-products, improving the competitiveness of food chains, and reducing the environmental impact, it can be also considered as a promising opportunity for the agro-industrial development of Countries like Argentina.

**Keywords:** Emerging food processing technologies, High Pressure Processing, by-products, Kano method, health promoting compounds

**Further collaborators:**

Gabriela Denoya, Mariela Maldonado, Julio Juárez, Adriana Pazos, Vanina Ambrosi

APPLIED NANOTECHNOLOGY: IMPROVEMENT OF NUTRITIONAL FOOD PROFILES

Gallardo, Gabriela.

PhD. Chemistry. National Institute of Industrial Technology (INTI). Argentina.

Nanotechnologies are considered to hold a great promise for the development of new products in almost all industrial sectors and many applications are currently marketed worldwide. The development of new products and applications involving nanotechnologies holds great promise in different industrial sectors, food not excluded.

The great advantage of materials at this dimensional state is that they show unique functional properties from bulk materials, properties that can be exploited for a wide range of applications. These properties are mainly due to a high surface to mass ratio that results in a higher reactivity for interactions.

Nanotechnology offers new opportunities also for the food and agricultural industries and several applications can be found at different stages of the food production chain.

Food additives and flavor enhancers, food supplements (e.g. to increase iron or other trace element bio-availability), novel food structure (e.g. nanoemulsion to reduce fat content), nanoparticles for selective binding and removal of contaminants and pathogens from food. Furthermore, nanotechnology has the potential to transform our future food packaging materials, as part of an active and intelligent packaging system

Despite these promises, however, nanotechnologies should be carefully applied because toxicological data on several nanaterials already in use are lacking and because the development of analytical methods able to guarantee consumer protection is still ongoing and need to face several challenges before any routine application in food control could be imagined. To be successful in the long run, proper education of the public is also paramount in the introduction and development of nanotechnology in food system. In spite of these the development of functional foods through the addition of bioactive compounds holds many technological
challenges, so the technique that industry can use is microencapsulation. It is an useful tool to improve the delivery of bioactive compounds into foods, particularly probiotics,

minerals, vitamins, phytosterols, lutein, fatty acids, lycopene and antioxidants. Several microencapsulation technologies

have been developed for use in the food industry and show
promise for the production of functional foods because the addi-
tion of bioactive ingredients should not affect the sensory proper-
ties, colour or flavour of food products. Moreover, these technolo-
gies could promote the successful delivery of bioactive ingredients
to the gastrointestinal tract. The microcapsules can release their
contents sealed at controlled rates under specific conditions, and
can protect the encapsulated product of light and oxygen. Mi-
croencapsulation is formed by a micro-porous polymeric mem-
brane of an active substance container. A microcapsule consists
of a semi-permeable membrane, spherical, thin and strong center
around a solid / liquid. The substances that can be microencapsu-
lated are vitamins, minerals, dyes, prebiotics, probiotics, flavors,
nutraceuticals, antioxidants, odors, oils, enzymes, bacteria, per-
fumes, drugs and even fertilizers.

**Keywords:** Functional food, nanotechnology, microencapsulation

PS_144/42

THE HUMAN MICROBIOME: SHARING OUR BODIES

SHARING OUR BODIES. THE SYMBIOSIS OF HU-
MANS AND OUR MICROBIOTA. A HIGHLEVEL
OVERVIEW OF RESEARCH IN THE FIELD

Hoffmann, Christian.

Food Research Center. University of Sao Paulo. Brazil.

Our knowledge about human gut microbiota, its resident species and their functional interaction capacity with its host has grown exponentially in recent years, especially due to next generation DNA sequencing technologies. These recent techniques have helped demonstrate the incredible diversity present in this ecosystem. Indeed, the adult human intestinal microbiome is considered one of the places with the highest microbial densities known. Estimations indicate that the gut microbiome has over 1800 bacterial genera and between 1500 and 3600 bacterial species, the vast majority of which has so far not been cultivated. Such estimations do not take under consideration other microbial groups which are present within the intestinal system, such as Archaea and Fungi. Several recent studies have provided important information with respect to what constitutes a 'healthy gut microbiota' while furthering our understanding of the role of gut microbes in intestinal and metabolic diseases. They have shown that the gut microbiota plays an important role in maintaining the host's overall health. For instance, nutrients such as non-digestible, fermentable carbohydrates can affect gut microbiota composition and modulate microbial-host interactions, which in turn maintain and/or pro-

mote health. Dysbiosis ensues when this relationship is disrupted. Manipulation of gut microbiome can provide new avenues for the treatment and prevention of human diseases.

**Keywords:** Human Microbiome

EXPLORING THE ROLE OF THE MAJOR GUT MI-
CROBIOTA CLUSTERS ON NUTRITIONAL AND
FUNCTIONAL BENEFITS OF NUTRIENTS AND
NON-NUTRIENTS

Rowland, Ian.

PhD. Department of Food and Nutritional Sciences. University of Reading. UK.

The biotransformation capabilities encoded in the gut micro-
biome greatly exceed that of the host genome, these include func-
tions involved in the breakdown, metabolism and absorption of
dietary components. As such, the gut microbiota is a key factor
in shaping the biochemical profile of the diet and, therefore, its
impact on host health and disease.

The ILSI Europe Functional Food Task Force set up a working
group to gain a perspective on the state of the art in this area with
a focus on the role played by the gut microbiota in metabolism
and absorption of key nutrients and non-nutrients. This has tak-
en the form of a systematic review focussing on energy and the
following candidate dietary substrates: protein, carbohydrate, fat,
resistant starch, dietary fibre and polyphenols. In reviewing the
literature, particular attention was paid to the characterisation of
the microbiotas which are predominantly implicated in each case,
and indications of the potential health impacts.

In addition to this systematic review, we have conducted a de-
tailed evaluation of the main gut microorganisms and microbial
pathways involved metabolism of these dietary components and
furthermore we have critically examined existing and novel meth-
odologies used to study diet-gut microbial interactions including
'omics' techniques, mathematical modeling, isolated microbes and
enzyme assays.

It is anticipated that a more thorough understanding of the role
the gut microbiota plays in the metabolism of dietary substrates
and of the relevant members of the microbiota and community
profiles holds considerable promise to facilitate the development
of novel health-orientated dietary strategies.

**Keywords:** Gut microbiota, microbiome, nutrient metabo-
lism, health impact

**Conflict of Interest disclosure:** Research support: Comvita
New Zealand Ltd

Scientific advisory boards: Herbalife Nutrition Institute, Mc-
Cormick Science Institute, European Natural Soybean Associa-
tion, Alpro Foundation ILSI Europe working group