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

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What Roles Do They Play in the Double Burden of Malnutrition?

Food Chemical Contaminantsand Environment Pollutants

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 growthImpaired growth has associations with risk of

short‐term morbidity and mortality, child development, and non‐communicable diseases in later life.

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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

Malnutrition is a multi-sectoral issue

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Chemical contaminants in foodFood 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

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Exposure may occur throughout life course

In utero During breastfeeding Childhood Adulthood

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Mycotoxins (Aflatoxins and Fumonisins) in AfricaMycotoxins: 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 B1(AFB1) 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 B1 (FB1) most common, possible human carcinogen

NH2

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Fumonisin B1

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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

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Aflatoxin exposure is associated with child stunting

• Gong et al. 2002,2003, 2004. British Medical Journal. 325: 20-21.• Gong et al 2003. International Journal of Epidemiology. 32: 556-562.• Gong et al. 2004. Environmental Health Perspectives. 112: 1334-1338.

In Benin and Togo, aflatoxin exposure was found to be associated with child stunting in a cross-sectional study followed by a cohort study

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Aflatoxin exposure and growth faltering in young children

Study Study design/ population characteristics

Evidence

Gong et al. 2002

‐ Benin and Togo‐ Cross‐sectional study‐ Sample size (n=479)‐ aged 9 months to 5 years

• 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.

Turner et al. 2003

‐Gambia‐Cohort‐Sample size (n=472)‐aged 6‐9 years

• 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.

Gong et al. 2004

‐Benin‐Longitudinal cohort‐200 Children (16 – 37 mo)‐3 time points over 8 mo

• 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

Aflatoxin (Fumonisin) exposure and growth faltering in young children

Study Study design OutcomeWatsonet al,2018

‐ Gambia. Longitudinal‐ 374 children growth 6 to 18 mo‐ serum at 6, 12 and 18 months

• 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)

Leroyet al,2018

Mexico. Longitudinal‐355 children serum at 12 mo‐ height and HAD change at 8, 12, 18 months

• 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

Shirima et al, 2015

‐ Tanzania. Longitudinal‐ 166 children ‐ aged 6‐14 mo at baseline‐ Serum AF‐alb & urinary FB1 at baseline, 6 & 12 mo+

• 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 monthsChen et al,2018

‐ Tanzania. Longitudinal‐ serum AF‐lys (n = 60)‐ urinary FB1 (n = 94)

• 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)

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Study Study design OutcomeDevries et al., 1989

‐ Kenya‐ Longitudinal‐ 125 pregnant women)‐ Maternal and cord blood

• Females born to aflatoxin positive mothers had a mean birth weight 225g lower than those born to mothers free from aflatoxins

Abdulrazzaqet al., 2004

‐ Middle East‐ Cross‐sectionalMaternal and cord blood

• High aflatoxin levels in maternal and cord blood samples were significantly related to lower birth weights (r = ‐0.654, p = 0.0001 and r = ‐0.565, p = 0.001, respectively)

Turner et al., 2007

‐Gambia; n = 138‐Longitudinal cohort‐Maternal blood samples‐ Children up to 1 year‐ Followed up in regular intervals for 1 year

• 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.

Shuaib et al., 2010

‐ Ghana, n=785‐ Cross‐sectional study‐ females (mean age 26.8 yrs) and pregnant‐ Maternal blood samples

• 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, 1.19–3.68)

Aflatoxin in utero exposure and growth faltering

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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..

Limit of the study is that baseline body weight was not measured.

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Variable Control group Intervention group

Aflatoxin intake (ng/kgbw/day)

63 ± 59 14 ± 13

Fumonisin intake (ng/kgbw/day)

6.0 ± 9.4 2.0 ± 3.2

Weight for age Z score (WAZ)

‐0.47 ± 1.30 0.12 ± 1.10

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Low mid-low mid-high highUrinary fumonisin B1 quartile groups

Urinary fumonisin B1 level inversely correlated with child growth

Shirima et al, 2015 Environmental health Perspectives

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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 28TLR2Toll‐like receptor 2TGF‐β1Transforming growth factor‐β1

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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

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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)

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

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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

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• 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 ‐glucuronide2019-01-08 School of Food Science and Nutrition

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

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Adverse health effects were reported in non‐environmentally low dose exposed people

Obesity association (human studies)• Serbian (Milosevic et al, 2017): a cross‐sectional study

103 women aged 19‐53• 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): 1326 9‐12 year olds• BPA associated with obesity in girls not boys

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Hao et al 2017Urinary [BPA] & central obesity

[BPA] tertile cases/participants OR (adjusted) 95% CI

low 32/296 1

medium 47/297 1.73 1.04‐2.88

high 45/295 1.81 1.39‐3.78

Continuous 1 unit log [BPA] 124/888 2.30 1.39‐3.78

888 middle aged men & women in Shanghai, non‐obese at start of studySpot urine for BPA analysis at startFollowed over a four year period

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Several mechanisms explored

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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):779-794. doi:10.1210/en.2017-00711

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

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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

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Summary – obesogen

BPA obesogenic in rats at low doses but not high dosesEpidemiology open to confounders; conflicting

findings reported, but Shanghai study interesting.Possible mechanisms have been suggested ‐ In vitro

evidence of adipogenesisPotential obesogenic chemicals such as BPA may

contribute to the global epidemic in obesity, both in children and adults

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