Infant Rhesus Macaque Brain α-Tocopherol Stereoisomer Profile Is Differentially Impacted by the Source of α-Tocopherol in Infant Formula.


Journal

The Journal of nutrition
ISSN: 1541-6100
Titre abrégé: J Nutr
Pays: United States
ID NLM: 0404243

Informations de publication

Date de publication:
01 09 2020
Historique:
received: 13 01 2020
revised: 17 04 2020
accepted: 27 05 2020
pubmed: 3 7 2020
medline: 17 12 2020
entrez: 3 7 2020
Statut: ppublish

Résumé

α-Tocopherol (αT) in its natural form [2'R, 4'R, 8'R αT (RRR-αT)] is more bioactive than synthetic α-tocopherol (all rac-αT). All rac-αT is widely used in infant formulas, but its accretion in formula-fed infant brain is unknown. We sought to compare αT and stereoisomer status in infant rhesus macaques (Macaca mulatta) fed infant formula (RRR-αT or all rac-αT) with a reference group fed a mixed diet of breast milk and maternal diet. From 1 d after birth until 6 mo of age, infants (n = 23) were either nursery reared and exclusively fed 1 of 2 formulas by staff personnel or were community housed with their mothers and consumed a mixed reference diet of breast milk (69 mL/d at 6 mo) transitioning to monkey diet at ∼2 mo (MF; n = 8). Formulas contained either 21 μmol RRR-αT/L (NAT-F; n = 8) or 30 μmol all rac-αT/L (SYN-F; n = 7). Total αT and αT stereoisomers were analyzed in breast milk at 2, 4, and 6 mo and in monkey plasma and liver and 6 brain regions at 6 mo of age. α-Tocopherol transfer protein (α-TTP), lipoprotein αT, and urinary α-carboxyethyl-hydroxychroman (α-CEHC) were measured. One-way ANOVA with Tukey's post-hoc test was used for analysis. At study termination, plasma, liver, lipoprotein, and brain total αT did not differ between groups. However, the NAT-F-fed group had higher RRR-αT than the SYN-F-fed group (P < 0.01) and the MF group (P < 0.0001) in plasma (1.7- and 2.7-fold) and brain (1.5- and 2.5-fold). Synthetic αT 2R stereoisomers (SYNTH-2R) were generally 3- and 7-fold lower in brain regions of the NAT-F group compared with those of the SYN-F and MF groups (P < 0.05). SYNTH-2R stereoisomers were 2-fold higher in MF than SYN-F (P < 0.0001). The plasma percentage of SYNTH-2R was negatively correlated with the brain percentage of RRR-αT (r = -0.99, P < 0.0001). Brain αT profiles were not explained by α-TTP mRNA or protein expression. Urine α-CEHC was 3 times higher in the NAT-F than in the MF group (P < 0.01). Consumption of infant formulas with natural (NAT-F) compared with synthetic (SYN-F) αT differentially impacted brain αT stereoisomer profiles in infant rhesus macaques. Future studies should assess the functional implications of αT stereoisomer profiles on brain health.

Sections du résumé

BACKGROUND
α-Tocopherol (αT) in its natural form [2'R, 4'R, 8'R αT (RRR-αT)] is more bioactive than synthetic α-tocopherol (all rac-αT). All rac-αT is widely used in infant formulas, but its accretion in formula-fed infant brain is unknown.
OBJECTIVE
We sought to compare αT and stereoisomer status in infant rhesus macaques (Macaca mulatta) fed infant formula (RRR-αT or all rac-αT) with a reference group fed a mixed diet of breast milk and maternal diet.
METHODS
From 1 d after birth until 6 mo of age, infants (n = 23) were either nursery reared and exclusively fed 1 of 2 formulas by staff personnel or were community housed with their mothers and consumed a mixed reference diet of breast milk (69 mL/d at 6 mo) transitioning to monkey diet at ∼2 mo (MF; n = 8). Formulas contained either 21 μmol RRR-αT/L (NAT-F; n = 8) or 30 μmol all rac-αT/L (SYN-F; n = 7). Total αT and αT stereoisomers were analyzed in breast milk at 2, 4, and 6 mo and in monkey plasma and liver and 6 brain regions at 6 mo of age. α-Tocopherol transfer protein (α-TTP), lipoprotein αT, and urinary α-carboxyethyl-hydroxychroman (α-CEHC) were measured. One-way ANOVA with Tukey's post-hoc test was used for analysis.
RESULTS
At study termination, plasma, liver, lipoprotein, and brain total αT did not differ between groups. However, the NAT-F-fed group had higher RRR-αT than the SYN-F-fed group (P < 0.01) and the MF group (P < 0.0001) in plasma (1.7- and 2.7-fold) and brain (1.5- and 2.5-fold). Synthetic αT 2R stereoisomers (SYNTH-2R) were generally 3- and 7-fold lower in brain regions of the NAT-F group compared with those of the SYN-F and MF groups (P < 0.05). SYNTH-2R stereoisomers were 2-fold higher in MF than SYN-F (P < 0.0001). The plasma percentage of SYNTH-2R was negatively correlated with the brain percentage of RRR-αT (r = -0.99, P < 0.0001). Brain αT profiles were not explained by α-TTP mRNA or protein expression. Urine α-CEHC was 3 times higher in the NAT-F than in the MF group (P < 0.01).
CONCLUSIONS
Consumption of infant formulas with natural (NAT-F) compared with synthetic (SYN-F) αT differentially impacted brain αT stereoisomer profiles in infant rhesus macaques. Future studies should assess the functional implications of αT stereoisomer profiles on brain health.

Identifiants

pubmed: 32614402
pii: S0022-3166(22)02301-X
doi: 10.1093/jn/nxaa174
pmc: PMC7467853
doi:

Substances chimiques

Carrier Proteins 0
Chromans 0
Propionates 0
alpha-tocopherol transfer protein 0
2,5,7,8-tetramethyl-2-(2'-carboxyethyl)-6-hydroxychroman 4072-32-6
alpha-Tocopherol H4N855PNZ1

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2305-2313

Subventions

Organisme : NIH HHS
ID : P51 OD011092
Pays : United States

Commentaires et corrections

Type : ErratumIn

Informations de copyright

Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.

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Auteurs

Matthew J Kuchan (MJ)

Abbott Nutrition, Columbus, OH.

Katherine M Ranard (KM)

Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, IL.

Priyankar Dey (P)

Human Nutrition Program, The Ohio State University, Columbus, OH.

Sookyoung Jeon (S)

Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, IL.

Geoff Y Sasaki (GY)

Human Nutrition Program, The Ohio State University, Columbus, OH.

Karen J Schimpf (KJ)

Abbott Nutrition, Columbus, OH.

Richard S Bruno (RS)

Human Nutrition Program, The Ohio State University, Columbus, OH.

Martha Neuringer (M)

Division of Neuroscience, Oregon National Primate Research Center, Beaverton, OR.
Casey Eye Institute, Oregon Health & Science University, Portland OR.

John W Erdman (JW)

Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, IL.
Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL.

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