May 2016: Issue 114

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ZINC-NET: Studying the role of zincin public health

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The hypothesis that saturated fat was a causative factor in cardiovascular disease (CVD) arose in the 1970s with the publication of the Seven Countries Study.1 This multi-centred longitudinal survey found statistically significant associations between CVD risk and serum cholesterol, leading to total and saturated fat being identified as likely risk factors. Keys’ hypotheses were later criticised, as they were based solely on observational findings and failed to account for potential confounders, such as trans fats and sugars. Some scientists claimed that Keys had pre-selected a limited range of countries that proved his hypothesis. Indeed, subsequent studies found that subjects with a similar serum cholesterol level nevertheless had widely different CVD outcomes,2 suggesting an indirect or non-causative relationship between serum cholesterol and CVD risk. This has been confirmed in sub-sequent studies such as the Minnesota Coronary Survey3 which tested the efficacy of a reduced saturated fat/reduced cholesterol diet on a randomised sample of 4,393 institutionalised adults over a 4.5 year period. Despite a fall in serum cholesterol in the reduced fat group, there were no significant changes in the incidence of myocardial infarctions, sudden deaths, or all-cause mortality. A meta-analysis found

contradictory evidence for the apparent CVD benefits of dietary fat reduction, except when polyunsaturated fat was increased at the expense of saturated fat.4 More recently, a Cochrane analysis concluded that, while saturated fat reduction lowered the cardiovascular events by 17%, the impact on total and cardiovascular mortality was less clear and statistically non-significant in many cases.5

Dairy benefitsOnce branded as a high fat food category to eat with caution, dairy has been revolutionised as a result of processing techniques which allow varying amounts of fat to be removed, as well as growing evidence that the types of fatty acids in dairy foods may not pose a major health risk. Emerging research on dairy protein and satiety has indicated potential weight management benefits. Saturated fat is a collective term for more than 30 individual fatty acids with single bonds in their chemical structure. Around 60% of the fatty acids in dairy foods are saturated with the most predominant being palmitic acid (16:0; making up 30% of the fatty acids), myristic acid (14:0) and stearic acid (18:0). Uniquely among animal foods, milk fats exist as globules with an oil-in-water emulsion, which may influence

TRENDS IN DAIRY FATS WITH A FOCUS ON YOGHURT

Carrie ruxton PhD, freelance Dietitian

Dr Carrie Ruxton is a freelance dietitian who writes regularly for academic and media publications. A contributor to TV and radio, Carrie works on a wide range of projects relating to product development, claims, PR and research. Her specialist areas are child nutrition, obesity and functional foods.

When I was a newly qualified dietitian in the 1990s, the demon nutrients were definitely saturated fat and sugar. Now, more than a quarter of a century later, sugar is still on the hit list, but saturated fat seems to be heading for a reprieve. A beneficiary of this revised thinking is dairy, with milk and yoghurt emerging as healthier options whether or not they are fat-free. This article will look at the thinking behind this interesting trend and highlight research on yoghurt.

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how they are absorbed by the human gut.6 Studies suggest that dairy fatty acids are less likely than others to impact on CVD risk while specific dairy fatty acids, i.e. pentadecanoic acid (15:0) and margaric acid (17:0), could lower risk. A cohort of 2,837 US adults7 found that intakes of 14:0 and 16:0 were not associated with CVD risk, but each incremental increase of 15:0 in the diet lowered CVD risk by 19% on average. In addition, two reviews of the literature8,9 confirmed that the majority of observational studies do not link dairy food consumption with increased risk of CVD, coronary heart disease or stroke, regardless of milk fat level. Protein is known to induce satiety and increase diet-induced thermogenesis which

could theoretically support weight management. A review10 collated studies on dairy protein (which is 80% casein and 20% whey) finding that whey in particular exerted metabolic effects which could promote satiety. These included stimulating the secretion of the hormones GLP-1 and glucose-dependent insulinotropic polypeptide. However, there was no clear evidence that dairy protein was superior to other sources of protein in relation to thermogenesis or other hormones, such as ghrelin, CCK or PYY.

fOCus On yOghurtYoghurt is a traditional fermented food made using bacterial cultures such as Lactobacillus bulgaricus or Streptococcus thermophilus. Ferment-

table 1: summary of recent studies

Population/studies Type of study Outcome

1,868 adults (55-80 years) with high risk of CVDinvolved in european PreDiMeD study

Longitudinal with 3.2-year follow up15

higher consumption of yoghurt (low-fat and whole-fat) associated with reduced risk of metabolic syndrome

306 incident cases of metabolic syndrome occurring in the spanish sun cohort

Cohort with six-year follow up16

no significant association between yoghurt consumption and metabolic syndrome, but central obesity lower in high consumers of yoghurt

2,636 adults involved in us framingham heart study Offspring Cohort

Cohort with 17-year follow-up17

each additional serving of yogurt/day was associated with a 6% reduction in the risk of hypertension

>3,000 adolescents (12-18 years) involved in heLena study

Pan european cross-sectional18

higher consumption of milk and yoghurt associated with lower body fat, lower risk for CVD, and higher cardio fitness

3,786 children (8-18 years) from us nhanes survey

Cross-sectional19

yoghurt intake associated with lower total fat and saturated fat intakes and lower body fat

all rCt on using yoghurt to treat antibiotic associated diarrhoea

Meta-analysis which involved two trials due to lack of data20

no consistent effect of yoghurt consumption for preventing diarrhoea

72 children (1-12 years) prescribed antibiotics

rCt giving 200g probiotic yogurt daily for duration of antibiotic treatment21

yoghurt effectively controlled diarrhoea

1,861 older adults involved in study on nutrition and Cardiovascular risk in spain

Cohort with four-year follow-up22

Participants consuming seven+ servings of low-fat milk and yoghurt per week had a 48% lower incidence of frailty

4,445 adults (>18 years) in spain Cohort with 3.5 year follow-up23

habitual yoghurt consumption did not show an association with improved quality of life

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ation alters the carbohydrate composition of milk to convert lactose to lactic acid, glucose and galactose, which explains why yoghurt is often tolerated by people with lactase deficiency.11 Yoghurt may also contain probiotic bacteria which is known to have a beneficial influence on the gut microbiota. A review published last year in NHD12 identified several areas where yoghurt consumption appears to have a positive impact on health, such as CVD, bone health, Type 2 diabetes and weight management. However, most research arose from observational studies which cannot determine cause and effect. Since then, two reviews and nine studies have been published. Glanville et al13 carried out a scoping exercise to examine the evidence-base for yoghurt health benefits. Focusing on randomised controlled trials (RCT), the review located 213 studies, mostly on nutrition or weight management outcomes, but including bone health, heart disease, cancer, diabetes, metabolic health and gut health. This highlights

the breadth of health outcomes that may be influenced by yoghurt consumption and bodes well for future meta-analyses. A second review,14 focused on weight management, noting that yoghurt appears to facilitate the regulation of energy balance. Mechanisms were proposed, including the impact of protein and calcium on satiety as a consequence of the faster absorption rate of milk proteins, and the impact of milk constituents on hunger and satiety hormones, e.g. GLP-1 and PYY. Yoghurt may also have an impact on satiety due to interactions between culture bacteria and the host microbiota. It was also noted that consumption of yoghurt and lower fat dairy foods may displace less healthful, energy dense foods. Other studies are summarised in Table 1, which add to previous evidence suggesting modest, consistent benefits for regular yoghurt consumption in relation to heart and metabolic health, as well as weight management. More emerging areas, such as tackling antibiotic-associated diarrhoea, require further work.

References1 Keys A (Ed) (1970). Coronary heart disease in seven countries. Circulation 41): I 1-2002 Ravnskov U (1995). Quotation bias in reviews of the diet-heart idea. J Clin Epidemiol 48: 713-93 Frantz Jr ID et al (1989). Test of effect of lipid lowering by diet on cardiovascular risk. The Minnesota Coronary Survey. Arteriosclerosis 9: 129-1354 Mozaffarian D et al (2010). Effects on coronary heart disease of increasing polyunsaturated fat in place of saturated fat: A systematic review and meta-

analysis of randomised controlled trials. PLoS Med 7: e10002525 Hooper L et al (2015). Reduction in saturated fat intake for cardiovascular disease. Cochrane Database of Systematic Reviews 6: CD0117376 Mansson HL (2008). Fatty acids in bovine milk fat. Food Nutr Res 52: 107 de Oliveira Otto MC et al (2013). Biomarkers of dairy fatty acids and risk of cardiovascular disease in the Multi-ethnic Study of Atherosclerosis. J Am

Heart Assoc 2: e0000928 German JB et al (2009). A reappraisal of the impact of dairy foods and milk fat on cardiovascular disease risk. Eur J Nutr 48: 191-2039 Huth PJ and Park KM (2012). Influence of dairy product and milk fat consumption on cardiovascular disease risk: a review of the evidence. Adv Nutr

3:266-8510 Bendtsen LQ et al (2013). Effect of dairy proteins on appetite, energy expenditure, body weight and composition: a review of the evidence from

controlled clinical trials. Adv Nutr 4: 418-3811 European Food Safety Authority (2010). EFSA Journal 8(10): 1763-8012 Ruxton C and Phillips F (2015). Nutritional benefits of yoghurt. NHD mag 103: 25-2813 Glanville JM et al (2015). The scale of the evidence base on the health effects of conventional yoghurt consumption: findings of a scoping review. Front

Pharmacol 6: 24614 Tremblay A et al (2015). Impact of yoghurt on appetite control, energy balance and body composition. Nutr Rev 73: 23-715 Babio N et al (2015). Consumption of yoghurt, low-fat milk and other low-fat dairy products is associated with lower risk of metabolic syndrome

incidence in an elderly Mediterranean population. J Nutr 145: 2308-1616 Sayón-Orea C et al (2015). Association between yoghurt consumption and the risk of metabolic syndrome over six years in the SUN study. BMC Public

Health 15: 17017 Wang H et al (2015). Longitudinal association of dairy consumption with the changes in blood pressure and the risk of incident hypertension: the

Framingham Heart Study. Br J Nutr 114: 1887-9918 Moreno LA et al (2015). Dairy products, yoghurt consumption and cardiometabolic risk in children and adolescents. Nutr Rev 73: 8-1419 Keast DR et al (2015). Associations between yoghurt, dairy, calcium and vitamin D intake and obesity among US children aged 8-18 years: NHANES,

2005-2008. Nutrients 7: 1577-9320 Patro-Golab B et al (2015). Yoghurt for treating antibiotic-associated diarrhoea: Systematic review and meta-analysis. Nutrition 31: 796-80021 Fox MJ et al (2015). Can probiotic yoghurt prevent diarrhoea in children on antibiotics? A double-blind, randomised, placebo-controlled study. BMJ

Open 5: e00647422 Lana A et al (2015). Dairy consumption and risk of frailty in older adults: A prospective cohort study. J Am Geriatr Soc 63: 1852-6023 Lopez-Garcia E et al (2015). Habitual yoghurt consumption and health-related quality of life: a prospective cohort study. J Acad Nutr Diet 115: 31-9

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aiMs anD ObJeCtiVes Of Zn-netThe main aim of Zn-Net Action TD1304 is to establish a comprehensive understanding of the role of zinc in biology medicine and general public health and well-being by creating a multidisciplinary research platform. This platform brings together expertise from research groups throughout the COST countries and beyond to stimulate and accelerate new, innovative and high impact scientific research. Secondary objectives of Zn-Net are defragmentation of the knowledge base across scientific, clinical and industrial partners, establishment of a Pan-European Research Platform, establishment of the Virtual Institute of

Zinc Biology (VIZIBI) website, training and outreach. In terms of the reach of the Zn-Net project, there are 27 COST countries involved: Belgium, Bulgaria, Croatia, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Israel, Italy, Lithuania, Netherlands, Norway, Poland, Portugal, Romania, Serbia, Slovenia, Spain, Sweden, Switzerland, Turkey and United Kingdom. There is also one COST country international partner: Australia.

aChieVeMentsZn-Net has achieved a lot in its first two years. During the first year, a Zn-Net workshop and conference was undertaken in Budapest, Hungary and a conference and workshop on ‘Measuring Zinc’ was held in London. Also during the first year, two grants were awarded to support Zn-Net disseminations in Asilomar, USA and eight Short Term Scientific Missions (STSM) were supported. During the second year, in 2015, 21 STSMs were funded. A conference on ‘Zn Biomarkers in Human Health and Disease’ and a management committee meeting was organised in Granada, Spain, followed by a training school in Brno, Czech Republic on ‘Metallothionein and its relation to zinc (II) ions’. An opportunity to present their STSM work was given to Early Stage Researchers (ESRs) in the Conference and Workshop meeting organised in Antalya, Turkey

ZINC-NET: STUDYING THE ROLE OF ZINC IN PUBLIC HEALTH

Dr Marisol Warthon-Medinaregistered nutritionist, university Of Central Lancashire (uCLan)

Dr Marisol Warthon-Medina is a Post-Doctoral Researcher working as Project Co-ordinator for The Network for the Biology of Zinc (Zinc-Net) Jan 14-Apr 16. Marisol is based at the International Institute of Nutritional Sciences and Applied Food Safety Studies (iINSAFSs), Division of Sport, Exercise and Nutritional Sciences (SENS), School of Sport and Wellbeing, UCLAN. Her expertise is in micronutrient research and nutrition in vulnerable populations.

Micronutrient deficiencies of iron, zinc vitamin A, iodine, folic acid and selenium affect more than 50% of the world’s population, with infants, children and women the most high risk groups.6 Zinc deficiency, remains a widespread worldwide nutritional problem and in order to offset this problem, considerable efforts have been made to increase both the content and availability of zinc in staple crops and grains.5

NHD-eXtra: PubLiC heaLth

To date, there is no reliable, sensitive and specific biomarker of zinc status. Additionally, there are no standardisation protocols across research groups in Europe to facilitate data comparisons. To address these problems through a multidisciplinary approach, four scientists (see below) co-founded Zinc-Net (Zn-Net) based on the successful Zinc-UK network that started in 2009 led by Dr Imre Lengyel. Since its foundation, Zn-Net has become a great network of scientists, supported by the European Commission (European Cooperation in Science and Technology COST Action TD1304), which was launched in October 2013, and is expected to complete its work by October 2017. www.cost.eu/COST_Actions/fa/TD1304

in November last year. This workshop included training in mentoring, networking academic writing and grant applications, commercialisation of intellectual property and psychology bias and personality types. Currently this year, eight STSMs are being funded and a meeting in Sofia, Bulgaria was held in March with the focus on ‘Dietary supplements vs food biofortification and the gut microbiome: human and animal health outcomes’. A planning MC meeting and ISZB conference is scheduled in Istanbul, Turkey in September and five more STSMs will be supported throughout the year. The interesting theme of the Sofia Zn-Net meeting gathered excellent keynote speakers with expertise in this fascinating area. Biofortification is defined as the process of increasing the nutrition quality of foods by means of breeding of crops. Examples of zinc biofortification are on wheat, rice, beans, sweet potato and maize.7 Cereals are known to be the main staple food in large parts of the world, but have the disadvantage of being low in zinc and low in other nutrients.4 Consumption of zinc biofortified staple crops among zinc deficient populations should improve adequacy of zinc in the diet and reduce the risk of dietary zinc deficiency.3 An example of trials in biofortification can be seen in the study by Chomba et.al,1 where young Zambian children (mean age of 29 months old) met zinc requirements when they were fed with biofortified maize 34μg zinc/g grain. In this trial, zinc absorption per day was significantly higher in the biofortified maize group compared to the control group.1

The review by Welch6 suggests that the nutrition and health sectors should turn to agricultural interventions to eradicate malnutrition in the world. Food fortification and supplementation has been implemented to lessen the problem. However, this has not been proven effective, whereas the advances in biotechnology have promised improvements of the output of

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Zn-Net co-foundersProfessor Lothar Rink, RWTH Aachen University (Vice-Chair Zn-Net)Professor Nicola Lowe, University of Central Lancashire (Chair Zn-Net)Dr Imre Lengyel, University College LondonProfessor Mike Watkinson, Queen Mary University London.www.zinc-net.com/

bioavailable micronutrients from agricultural systems.6 Therefore, biofortification of edible crops through biotechnology may help to lessen malnutrition in developing countries.2 Zn-Net has gradually grown in members and continues working collaboratively to achieve the objectives of the Zn-Net project. Being part of Zn-Net is a wonderful experience to exchange zinc knowledge and work together across disciplines, to achieve overall end goals more efficiently.

This article is based upon work from COST Action TD1304 the Network for the Biology of Zinc (Zinc-Net), supported by COST (European Cooperation in Science and Technology). www.cost.eu/domains_actions/fa/Actions/TD1304

References1 Chomba E, Westcott CM, Westcott JE, Mpabalwani EM, Krebs NF, Patinkin ZW, Palacios N, Hambidge KM. Zinc absorption from biofortified maize

meets the requirements of young rural Zambian children. J Nutr 2015, 145, 514-5192 Gilani GS, Nasim A. Impact of foods nutritionally enhanced through biotechnology in alleviating malnutrition in developing countries. J AOAC Int 2007,

90, 1440-14443 Hotz C. The potential to improve zinc status through biofortification of staple food crops with zinc. Food Nutr Bull 2009, 30, S172-1784 Palmgren MG, Clemens S, Williams LE, Kramer U Borg S, Schjorring JK, Sanders D. Zinc biofortification of cereals: Problems and solutions. Trends

Plant Sci 2008, 13, 464-4735 Rouached H. Recent developments in plant zinc homeostasis and the path toward improved biofortification and phytoremediation programs. Plant

Image: Thomas Splettstoesser (www.scistyle.com) via Wikimedia Commons

representation of the zinc-finger motif of proteins

Signal Behav 2013, 8, e226816 Welch RM. Biotechnology, biofortification, and global health. Food Nutr Bull 2005, 26, 419-4217 WHO. Biofortification of staple crops www.who.int/elena/titles/biofortification/en/ (Accessed February 17th, 2016)