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TitlePersonalized Nutrition: Translating Nutrigenetic/Nutrigenomic Research into Dietary Guidelines
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Page 1

Personalized Nutrition
Translating Nutrigenetic/Nutrigenomic Research into Dietary Guidelines

Page 2

World Review of Nutrition
and Dietetics

Vol. 101

Series Editor

Artemis P. Simopoulos

The Center for Genetics, Nutrition and Health, Washington, D.C., USA

Advisory Board

Regina C. Casper USA Marjanne Senekal South Africa
Uri Goldbourt Israel Leonard Storlien Australia
C. Gopalan India Changhao Sun China
Tomohito Hamazaki Japan Antonio Velazquez Mexico
Federico Leighton Chile Mark L. Wahlqvist Australia
Michel de Lorgeril France Paul Walter Switzerland
Edwin C.M. Mariman The Netherlands Bruce A. Watkins USA
Victor A. Rogozkin Russia

Page 100

80 Zeisel

1 Chanock SJ, Manolio T, Boehnke M, et al: Replicating

genotype-phenotype associations. Nature 2007;447:

655–660.

2 Teo YY: Exploratory data analysis in large-scale

genetic studies. Biostatistics 2010;11:70–81.

3 Zeisel SH: Choline: critical role during fetal devel-

opment and dietary requirements in adults. Annu

Rev Nutr 2006;26:229–250.

4 Niculescu MD, Zeisel SH: Diet methyl donors and

DNA methylation: interactions between dietary

folate methionine and choline. J Nutr 2002;132:

2333S–2335S

5 Finkelstein JD: Pathways and regulation of homo-

cysteine metabolism in mammals. Semin Thromb

Hemost 2000;26:219–225.

6 Kim Y-I, Miller JW, da Costa K-A, Nadeau M, Smith

D, Selhub J, Zeisel SH, Mason JB: Folate deficiency

causes secondary depletion of choline and phos-

phocholine in liver. J Nutr 1995;124:2197–2203.

7 Selhub J, Seyoum E, Pomfret EA, Zeisel SH: Effects

of choline deficiency and methotrexate treatment

upon liver folate content and distribution. Cancer

Res 1991;51:16–21.

8 Varela-Moreiras G, Selhub J, da Costa K, Zeisel SH:

Effect of chronic choline deficiency in rats on liver

folate content and distribution. J Nutr Biochem

1992;3:519–522.

9 Pomfret EA, da Costa K, Zeisel SH: Effects of cho-

line deficiency and methotrexate treatment upon

rat liver. J Nutr Biochem 1990;1:533–541.

offspring. Choline supplementation during this period enhanced visuo-spatial and

auditory memory in the adult rats throughout their life-span [63–67]. It also enhanced

a property of the hippocampus, long-term potentiation [46, 68, 69]. The offspring from

mothers fed a choline-deficient diet manifested opposite outcomes [64, 68].

Implications for Human Brain Development

It is always difficult to extrapolate findings reported using animal models to humans.

However, limited data are available to support the hypothesis that similar mechanisms

are involved in humans. Due to ethical constraints, no studies are available in children

or pregnant mothers to validate the rodent model. Because the 2005 National Health

and Nutrition Examination Survey (NHANES) data suggests that pregnant women do

not consume adequate amounts of choline [18], and case-control studies in California

suggest that women eating lower choline diets are at increased risk for giving birth to

babies with neural tube defects [70] and cleft palate [71], the recommendation that

pregnant women should attempt to consume diets adequate in choline seems reason-

able. In addition, because half of the population has gene polymorphisms that affect

choline and folate metabolism [52, 72], it is likely that different individuals may have

different dietary requirements for choline and may need to pay special attention to

choline intake during pregnancy.

Acknowledgments

This work was funded by grants from the National Institutes of Health (DK55865, AG09525).

Support for this work was also provided by grants from the NIH to the UNC Nutrition & Obesity

Research Center (DK56350).

References

Page 101

Clinical Nutrigenomics Approaches to Choline Functions and Requirements 81

10 Zeisel SH, Zola T, daCosta K, Pomfret EA: Effect of

choline deficiency on S-adenosylmethionine and

methionine concentrations in rat liver. Biochem J

1989;259:725–729.

11 Varela-Moreiras G, Ragel C, Perez de Miguelsanz J:

Choline deficiency and methotrexate treatment

induces marked but reversible changes in hepatic

folate concentrations serum homocysteine and

DNA methylation rates in rats. J Amer Coll Nutr

1995;14:480–485.

12 da Costa KA, Gaffney CE, Fischer LM, Zeisel SH:

Choline deficiency in mice and humans is associ-

ated with increased plasma homocysteine concen-

tration after a methionine load. Am J Clin Nutr

2005;81:440–444.

13 Zeisel SH, Mar M-H, Howe JC, Holden JM:

Concentrations of choline-containing compounds

and betaine in common foods. J Nutr 2003;133:1302–

1307.

14 Ilcol YO, Ozbek R, Hamurtekin E, Ulus IH: Choline

status in newborns, infants, children, breast-feeding

women, breast-fed infants and human breast milk. J

Nutr Biochem 2005;16:489–499.

15 Holmes-McNary MQ, Cheng WL, Mar MH, Fussell

S, Zeisel SH: Choline and choline esters in human

and rat milk and in infant formulas. Am J Clin Nutr

1996;64:572–576.

16 Blusztajn JK, Zeisel SH, Wurtman RJ: Developmental

changes in the activity of phosphatidylethanolamine

N-methyltransferases in rat brain. Biochem J 1985;

232:505–511.

17 Institute of Medicine and National Academy of

Sciences USA: CholineIn Dietary Reference Intakes

for Folate Thiamin Riboflavin Niacin Vitamin B12

Panthothenic Acid Biotin and Choline. Washington,

National Academy Press, 1998, vol 1, pp 390–422

18 Jensen HH, Batres-Marquez SP, Carriquiry A,

Schalinske KL: Choline in the diets of the US popu-

lation: NHANES 2003–2004. FASEB J 2007;21:

lb219.

19 Cho E, Zeisel SH, Jacques P, et al: Dietary choline

and betaine assessed by food-frequency question-

naire in relation to plasma total homocysteine con-

centration in the Framingham Offspring Stud. Am J

Clin Nutr 2006;83:905–911.

20 Busby MG, Fischer L, Da Costa KA, et al: Choline-

and betaine-defined diets for use in clinical research

and for the management of trimethylaminuria. J

Am Diet Assoc 2004;104:1836–1845.

21 da Costa KA, Badea M, Fischer LM, Zeisel SH:

Elevated serum creatine phosphokinase in choline-

deficient humans: mechanistic studies in C2C12

mouse myoblasts. Am J Clin Nutr 2004;80:163–

170.

22 Fischer LM, da Costa K, Kwock L, et al: Sex and

menopausal status influence human dietary require-

ments for the nutrient choline. Am J Clin Nutr 2007;

85:1275–1285.

23 Resseguie M, Song J, Niculescu M, da Costa K,

Randall T, Zeisel S: Phosphatidylethanolamine

n-methyltransferase (PEMT) gene expression is

induced by estrogen in human and mouse primary

hepatocytes. FASEB J 2007;21:2822–2832.

24 Walter P, Green S, Greene G, et al: Cloning of the

human estrogen receptor cDNA. Proc Natl Acad Sci

USA 1985;82:7889–7893.

25 Lopez D, Sanchez MD, Shea-Eaton W, McLean MP:

Estrogen activates the high-density lipoprotein

receptor gene via binding to estrogen response ele-

ments and interaction with sterol regulatory ele-

ment binding protein-1A. Endocrinology 2002;143:

2155–2168.

26 Agarwal A, Yeung WS, Lee KF: Cloning and charac-

terization of the human oviduct-specific glycopro-

tein (HuOGP) gene promoter. Mol Hum Reprod

2002;8:167–175.

27 Xie T, Ho SL, Ramsden D: Characterization and

implications of estrogenic down-regulation of

human catechol-O-methyltransferase gene tran-

scription. Mol Pharmacol 1999;56:31–38.

28 Sarda IR, Gorwill RH: Hormonal studies in preg-

nancyI: total unconjugated estrogens in maternal

peripheral vein cord vein and cord artery serum at

delivery. Am J Obstet Gynecol 1976;124:234–238.

29 Adeyemo O, Jeyakumar H: Plasma progesterone

estradiol-17beta and testosterone in maternal and

cord blood and maternal human chorionic gonado-

tropin at parturition. Afr J Med Med Sci 1993;22:55–

60.

30 Sweiry JH, Yudilevich DL: Characterization of cho-

line transport at maternal and fetal interfaces of the

perfused guinea-pig placenta. J Physiol 1985;366:

251–266.

31 Sweiry JH, Page KR, Dacke CG, Abramovich DR,

Yudilevich DL: Evidence of saturable uptake mecha-

nisms at maternal and fetal sides of the perfused

human placenta by rapid paired-tracer dilution:

studies with calcium and choline. J Devel Physiol

1986;8:435–445.

32 McMahon KE, Farrell PM: Measurement of free

choline concentrations in maternal and neonatal

blood by micropyrolysis gas chromatography. Clin

Chim Acta 1985;149:1–12.

33 Zeisel SH, Wurtman RJ: Developmental changes in

rat blood choline concentration. Biochem J 1981;

198:565–570.

34 Ozarda IY, Uncu G, Ulus IH: Free and phospho-

lipid-bound choline concentrations in serum dur-

ing pregnancy after delivery and in newborns. Arch

Physiol Biochem 2002;110:393–399.

Page 199

Subject Index 179

Inflammatory bowel disease, see Crohn’s

disease

Inhibin, expression in obesity 110

Leptin

gene polymorphisms in obesity 25

receptor polymorphisms and diet

interactions 28, 29

Liver carcinogenesis, see Cancer

Meat

carcinogen metabolic activation 34, 38

colorectal adenoma screening study

gene selection and genotyping 35, 36,

38–41

nitrate/nitrite intake estimation 36

population characteristics 35, 37

statistical analysis 36

cooking and carcinogen formation 34

Melanocortin receptor 3 (MC3R), gene

polymorphisms in obesity 25

Melanocortin receptor 4 (MC4R), gene

polymorphisms in obesity 22

Methionine, schizophrenia trials 143

Methylene tetrahydrofolate, metabolizing gene

polymorphisms and choline

requirements 78

Methylfolate, schizophrenia trials 145

MicroRNA

liver carcinogenesis role

dysregulated microRNA functions

125–129

methyl-deficient diet effects 125

study design 124

tumor expression 121

Milk, prodigy testing in dairy cattle 154–156

Myalgic encephalomyelitis, eicosapentaenoic

acid therapy 17, 18

Nutrigenetics/nutrigenomics

challenges

ethical and legal implications 5, 6

meeting challenges 6

polymorphism variety 75

premature health claims 5

study size 73, 74

surrogate endpoints 4, 5

choline deficiency, see Choline

dietary guidance 155, 156

genome-wide association studies, see

Genome-wide association studies

industry-academia partnerships

DuPont-Penn State partnership

163–167

learning curve 160–163

omega-3 fatty acids 160, 161

professional development and

networks 163

publications 163, 164

obesity personalized nutritional therapy, see

Obesity

opportunities 2–4

rationale for study 1, 2

Obesity

adipose tissue expression profiling in

diet-induced weight loss 105–111

candidate genes 21, 22

CIDE family expression 109, 110

definition 103

epidemiology 21

gene-nutrient interactions

interventional studies 25–28

nutritional studies concerning

gene-dependent effects on

obesity-related manifestations

28–30

observational studies 22–25

weight gain genes

adipogenesis genes 24, 25

food/energy intake genes 22, 24

lipid utilization genes 24

weight loss and maintenance genes

adipocyte metabolism genes 28

food/energy intake genes 25

lipid utilization and adipogenesis

genes 27, 28

thermogenesis genes 28

inhibin expression 110

metabolic syndrome 101

serum amyloid A expression 108, 109

treatments 21, 104

Oxidative stress, see Schizophrenia

Penn State, DuPont partnership 163–167

Perilipin, gene polymorphisms in obesity 27

Peroxisome proliferator-activated receptor-α

(PPARA), pregnancy and fetal

epigenetics 65, 66

Peroxisome proliferator-activated receptor-γ

(PPARG), gene polymorphisms in

obesity 24, 25

Page 200

180 Subject Index

Phosphatidylethanolamine-N-

methyltransferase (PEMT)

choline metabolism 76

estrogen response element 77

gene polymorphisms and choline

requirements 78

Polyphenols

histone deacetylase modulation

inhibitors 90, 91

mechanisms 91

SIRT1 89, 90

inflammation modulation

catechins 86, 87

curcumin 86

resveratrol 85, 86

overview 85

Polyunsaturated fatty acids (PUFAs),

schizophrenia trials 145, 146

Resveratrol, see Polyphenols

Schizophrenia

brain connectivity impairments 133, 134

developmental factors 132, 133

environmental factors 132

epidemiology 131

genetic factors 132

glutathione deficiency

butyl sulfoximide induction in animal

models 139

cell morphology effects 138, 139

etiology 137

glutamate receptor response effects 137

glutamate:cysteine ligase knockout

mice 140, 141

myelination defects 138

one-carbon metabolism effects 143–145

overview 134–136

parvalbumin-containing neuron

reduction in prefrontal cortex

137, 138

neurotransmission dysfunction 133

oxidative stress

developmental animal models of

dysregulation 138–141

therapeutic targeting

N-acetyl cysteine 141–143

cobalamin 145

early intervention 142, 143

methionine 143

methylfolate 145

polyunsaturated fatty acids 145, 146

vulnerability factor 134

symptoms 131

Serum amyloid A (SAA)

diet-induced weight loss effects 108

expression in obesity 108, 109

Sirtuins, see Chromatin remodeling

Sulforaphane (SFN), histone deacetylase

inhibition 90, 91, 97–99

Toxicogenomics

interpretation of adverse versus adaptive

effects 120

noise sources in expression studies

117–119

phenotypic anchoring 119, 120

reference materials for microarray

performance assessment 116, 117, 120

Uncoupling protein 3 (UCP3), gene

polymorphisms in obesity 28

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