Food Chemical Contaminants and Environment Pollutants. What Roles Do They Play in the Double Burden of Malnutrition?

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1 Food Chemical Contaminants and Environment Pollutants What Roles Do They Play in the Double Burden of Malnutrition?

2 Linear Growth in early childhood Linear growth in early childhood is considered as a marker of healthy growth Data from 54 developing countries showed average HAZ at birth is 0.5, and reduce to 2 at 2 years of age. An estimated 42% of African children under the age of five years have stunted growth Impaired growth has associations with risk of short term morbidity and mortality, child development, and non communicable diseases in later life.

3 Malnutrition is a multi-sectoral issue Factors can contribute to malnutrition: SES, complementary feeding and breastfeeding practices and infection, food safety e.g. food and environment toxins Multi sectoral approach nutrition sensitive programmes For example, Scaling Up Nutrition (SUN) program involves governments, civil society, businesses and citizens worldwide. In a BBSRC funded project Agricultural and Food-system Resilience: Increasing Capacity and Advising Policy (AFRICAP) lead by the University of Leeds, we are researching on whether smart climate agriculture policy may improve food security and safety, hence reducing malnutrition

4 Chemical contaminants in food Food can become contaminated with a variety of toxins via various routes, including: Naturally occurring toxins produced by plants and fungi Metals that enter the food chain via pollution Man-made chemical toxins e.g. pesticide, and illegal food additives Toxic chemicals formed during food processing

5 Exposure may occur throughout life course In utero During breastfeeding Childhood Adulthood

6 Mycotoxins (Aflatoxins and Fumonisins) in Africa Mycotoxins: toxic chemical metabolites produced by fungal species. Aflatoxins: produced by Aspergillus fungi, contaminates crops such as maize and nuts primarily, favour warm & humid climate. Aflatoxin B 1 (AFB 1 ) most potent and common. Human liver carcinogen Fumonisins: produced by Fusarium fungi, contaminates maize crop. South Africa, Tanzania have reported high fumonisin exposure via maize. Fumonisin B 1 (FB 1 ) most common, possible human carcinogen O O OH O OH OH O OH NH 2 OH CH 3 O H 3 C OH Fumonisin B1 O O OH O

7 Aflatoxin exposure high risk populations Aflatoxin-albumin (AF-alb) adduct is a biomarker for aflatoxin exposure, being tested using ELISA, or testing AF-lysine by LC- MS method If regulations are enforced, public health risk can be reduced, for example in Europe and USA Compared to the developed countries, many Africans have much higher risk of exposure

8 Aflatoxin exposure is associated with child stunting In Benin and Togo, aflatoxin exposure was found to be associated with child stunting in a cross-sectional study followed by a cohort study Gong et al. 2002,2003, British Medical Journal. 325: Gong et al International Journal of Epidemiology. 32: Gong et al Environmental Health Perspectives. 112:

9 Study Aflatoxin exposure and growth faltering in young children Gong et al Turner et al Gong et al Study design/ population characteristics - Benin and Togo - Cross-sectional study - Sample size (n=479) - aged 9 months to 5 years -Gambia -Cohort -Sample size (n=472) -aged 6-9 years -Benin -Longitudinal cohort -200 Children (16 37 mo) -3 time points over 8 mo Evidence AF-alb geometric mean was 32.8 pg/mg AF-alb was significantly associated with stunted growth in children after adjusting for age, sex, agro zone, SES and weaning status. AF-alb was weakly associated with a lower WHZ score (P = 0.034), but was not associated with HAZ or WAZ scores. After adjusting for sex, month and birth weight there was a decrease in WHZ score up to 21 pg/mg. After adjustments for sex, height, SES, village etc. significant association betweem HAZ and AF-alb Retardation in height was 1.7 cm over the 8 month period between the highest and lowest quartiles of exposure

10 Aflatoxin (Fumonisin) exposure and growth faltering in young children Study Study design Outcome Watson et al, 2018 Leroy et al, 2018 Shirima et al, 2015 Chen et al, Gambia. Longitudinal children growth 6 to 18 mo - serum at 6, 12 and 18 months Mexico. Longitudinal -355 children serum at 12 mo - height and HAD change at 8, 12, 18 months - Tanzania. Longitudinal children - aged 6-14 mo at baseline - Serum AF-alb & urinary FB1 at baseline, 6 & 12 mo+ - Tanzania. Longitudinal - serum AF-lys (n = 60) - urinary FB1 (n = 94) Mean AF-alb 55 pg/mg at 18 m Inverse relationship between AF-alb and LAZ, WAZ & WLZ from 6 to 18 months (p<0.05) Low AF-lys (0.82 pg/mg albumin) Height and Height for age-difference (HAD) positively associated with AF-lys after 4 months but not 10 months Mean AF-alb 24 pg/mg at 12 months Negative but non-significant association between AF-alb and growth FB1 negatively associated with mean length gain over 12 months Mean AF-lys 5.1 pg/mg at 24 months No association of AF-lys with HAZ, WAZ or WHZ FB1 negatively associated with WAZ (p = 0.005)

11 Aflatoxin in utero exposure and growth faltering Study Study design Outcome Devries et al., 1989 Abdulrazzaq et al., 2004 Turner et al., 2007 Shuaib et al., Kenya - Longitudinal pregnant women) - Maternal and cord blood - Middle East - Cross-sectional Maternal and cord blood -Gambia; n = 138 -Longitudinal cohort -Maternal blood samples - Children up to 1 year - Followed up in regular intervals for 1 year - Ghana, n=785 - Cross-sectional study - females (mean age 26.8 yrs) and pregnant - Maternal blood samples Females born to aflatoxin positive mothers had a mean birth weight 225g lower than those born to mothers free from aflatoxins High aflatoxin levels in maternal and cord blood samples were significantly related to lower birth weights (r = , p = and r = , p = 0.001, respectively) AF in maternal blood was a strong predictor of both weight (P=0.012) and height (P= 0.044) gain, lower gain in those with higher maternal exposure. After adjustments for gender, age, placental weight, maternal weight, gestation time and season. There was an increased odd of delivering a baby who is SGA, low birth weight, preterm or still born with aflatoxin levels in the highest quartile. Women with AFB1-lysine level >11.34 pg mg were more likely to have low birth weight babies (OR, 2.09; 95% CI, )

12 Improving post-harvest practices reduced mycotoxins intake in Tanzanian children- a cluster randomized control trial (Kamala et al, 2018) Intervention practices: thoroughly drying before storage, hand sorting, pesticide use, improve storage facility.. Variable Control group Intervention group Aflatoxin intake (ng/kgbw/day) Fumonisin intake (ng/kgbw/day) 63 ± ± ± ± 3.2 Weight for age Z score (WAZ) ± ± 1.10 Limit of the study is that baseline body weight was not measured.

13 Urinary fumonisin B 1 level inversely correlated with child growth Mean body height gain (cm) over 12 months Low mid-low mid-high high Urinary fumonisin B1 quartile groups Shirima et al, 2015 Environmental health Perspectives

14 Possible mechanisms It has been suggested that mycotoxins may damage intestinal cell absorption and cause nutrients leaking leading to a compromised immune system, more susceptible to environmental enteropathy Possible impact through IGF axis proteins- conflicting data from young and old children Aflatoxin related changes in DNA methylation in immune genes (Hernandez-Vargas et al 2015) CCL28Chemokine (C-C motif) ligand 28 TLR2Toll-like receptor 2 TGF-β1Transforming growth factor-β1

15 Summary - undernutrition High prevalence of aflatoxins/fumonisin exposure and child malnutrition (co)exist in many developing countries. In addition to their carcinogenetic risk, evidence suggests aflatoxin and fumonisin exacerbate slowed child growth Some inconsistent findings on aflatoxin indicate the effect may have a dose threshold. Further characterisation is required Interaction between aflatoxin and fumonisin, and other toxic chemical in diet need further study

16 Double burden of malnutrition Some environmental agents may impact growth, contributing to undernutrition (malnutrition) Others may promote obesity Endocrine disrupting agents (EDA) and obesity: mycotoxin Zearalenone and DDT(see Eze et al presentation) Focus on the review of evidence on Bisphenol A (BPA)

17 Veiga-Lopez A 2018 Trends in Endocrinology & Metabolism 29 no. 9

18 BPA exposure: where from? Almost 2 million tons of BPA used per year worldwide Plastics manufacture; Epoxy resins in a variety of products Paper on which receipts are printed Food packaging; Lining of food & drink cans Occupational exposure showed strongest contribution Adverse health effects were reported in non-environmentally low dose exposed people, more often the case Breast milk/milk can be a source of exposure for infants

19 BPA is an endocrine disruptor; Binds to oestrogen receptors BPA is absorbed quickly in gut, metabolized primarily as glucuronide form present in blood and excrete in urine Oral route possibly has less risk to free BPA exposure than subcutaneous administration as the result of metabolism in GI Large body of evidence links BPA to adverse health effects in various species of animals and in vitro Toxicity exhibits non-monotonic dose response as most EDAs do Bisphenol A Bisphenol A -glucuronide

20 Maternal exposure to BPA & child health Authors Journals published Health outcomes reported Suiura-Ogasawa et al 2005 Human Reproduction 20, 2325 Recurrent mis-carriage Braun et al 2009 Environ Hlth Persp 117, 1945 Early childhood behaviour Cantowine et al 2010 Environ Health 9; 62 Pre-maturity Braun et al 2011 Pediatrics 128, 873 Behaviour & executive function Miao et al 2011 Reproductive Toxicol 32, 64 Birthweight Perera et al 2012 Environ Hlth Persp 120, 1190 Child behaviour Spanier et al 2012 Environ Hlth Persp 120, 916 Child wheeze from birth to 3 y Chevrier et al 2013 Environ Hlth Persp 121, 138 Thyroid function Adverse health effects were reported in non-environmentally low dose exposed people

21 Obesity association (human studies) Serbian (Milosevic et al, 2017): a cross-sectional study 103 women aged Association of BPA in urine with obesity USA (Song et al 2014): 977 women Association of BPA in urine with modestly faster weight gain USA (Hoepner et al, 2016): 369 pregnant women BPA in women associated with fat mass index, waist circumference and body fat in children at age 7 but not birthweight China (Li et al, 2013): year olds BPA associated with obesity in girls not boys

22 Hao et al 2017 Urinary [BPA] & central obesity 888 middle aged men & women in Shanghai, non-obese at start of study Spot urine for BPA analysis at start Followed over a four year period [BPA] tertile cases/participants OR (adjusted) 95% CI low 32/296 1 medium 47/ high 45/ Continuous 1 unit log [BPA] 124/

23 Several mechanisms explored

24 A study in mice showed that in utero exposure to BPA led to increased obesity in offspring. The effect was higher at the low dose and was associated with a change in DNA methylation that led to increased expression of the fggy carbohydrate kinase gene that may be relevant to obesity From: Prenatal Exposure to Bisphenol A Disrupts Naturally Occurring Bimodal DNA Methylation at Proximal Promoter of fggy, an Obesity-Relevant Gene Encoding a Carbohydrate Kinase, in Gonadal White Adipose Tissues of CD-1 Mice. Endocrinology. 2018;159(2): doi: /en

25 Modulation of a range of hormone receptors are involved in BPA mechanism pathway GR = glucocorticoid receptor; ER = Oestrogen receptor; EpR = endoplasmic reticulum Veiga-Lopez A 2018 Trends in Endocrinology & Metabolism 29 no. 9

26 Summary obesogen BPA obesogenic in rats at low doses but not high doses Epidemiology open to confounders; conflicting findings reported, but Shanghai study interesting. Possible mechanisms have been suggested - In vitro evidence of adipogenesis Potential obesogenic chemicals such as BPA may contribute to the global epidemic in obesity, both in children and adults

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