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

Overview

Journal J Nutr

Publisher Elsevier

Specialty Nutritional Sciences

Date 2020 Jul 3

PMID 32614402

Citations 6

Authors

Matthew J Kuchan

Katherine M Ranard

Priyankar Dey

Sookyoung Jeon

Geoff Y Sasaki

Karen J Schimpf

Richard S Bruno

Martha Neuringer

John W Erdman

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Associations between Brain Alpha-Tocopherol Stereoisomer Profile and Hallmarks of Brain Aging in Centenarians.

Chan J, Tanprasertsuk J, Johnson E, Dey P, Bruno R, Johnson M Antioxidants (Basel). 2024; 13(8).

PMID: 39199242 PMC: 11351880. DOI: 10.3390/antiox13080997.

Human-to-monkey transfer learning identifies the frontal white matter as a key determinant for predicting monkey brain age.

He S, Guan Y, Cheng C, Moore T, Luebke J, Killiany R Front Aging Neurosci. 2023; 15:1249415.

PMID: 38020785 PMC: 10646581. DOI: 10.3389/fnagi.2023.1249415.

Carotenoids improve the development of cerebral cortical networks in formula-fed infant macaques.

Miranda-Dominguez O, Ramirez J, Mitchell A, Perrone A, Earl E, Carpenter S Sci Rep. 2022; 12(1):15220.

PMID: 36076053 PMC: 9458723. DOI: 10.1038/s41598-022-19279-1.

Role of Vitamin E in Neonatal Neuroprotection: A Comprehensive Narrative Review.

Kolnik S, Wood T Life (Basel). 2022; 12(7).

PMID: 35888171 PMC: 9316652. DOI: 10.3390/life12071083.

Vitamin E Levels in Preterm and Full-Term Infants: A Systematic Review.

Assuncao D, Silva L, de Araujo Santos Camargo J, Cobucci R, Ribeiro K Nutrients. 2022; 14(11).

PMID: 35684057 PMC: 9183035. DOI: 10.3390/nu14112257.

References

Leal L, Jensen S, Bello J, Den Hartog L, Hendriks W, Martin-Tereso J . Bioavailability of -tocopherol stereoisomers in lambs depends on dietary doses of - or RRR--tocopheryl acetate. Animal. 2018; 13(9):1874-1882. DOI: 10.1017/S1751731118003373. View

Brigelius-Flohe R, Traber M . Vitamin E: function and metabolism. FASEB J. 1999; 13(10):1145-55. View

Kuchan M, Jensen S, Johnson E, Lieblein-Boff J . The naturally occurring α-tocopherol stereoisomer RRR-α-tocopherol is predominant in the human infant brain. Br J Nutr. 2016; 116(1):126-31. DOI: 10.1017/S0007114516001719. View

Teller I, Schoen S, van de Heijning B, van der Beek E, Sauer P . Differences in Postprandial Lipid Response to Breast- or Formula-feeding in 8-Week-Old Infants. J Pediatr Gastroenterol Nutr. 2016; 64(4):616-623. DOI: 10.1097/MPG.0000000000001341. View

Hymoller L, Lashkari S, Clausen T, Jensen S . Distribution of α-tocopherol stereoisomers in mink (Mustela vison) organs varies with the amount of all-rac-α-tocopheryl acetate in the diet. Br J Nutr. 2018; 120(12):1332-1337. DOI: 10.1017/S0007114518002878. View

Niki E, Traber M . A history of vitamin E. Ann Nutr Metab. 2012; 61(3):207-12. DOI: 10.1159/000343106. View

Weiser H, Vecchi M . Stereoisomers of alpha-tocopheryl acetate. II. Biopotencies of all eight stereoisomers, individually or in mixtures, as determined by rat resorption-gestation tests. Int J Vitam Nutr Res. 1982; 52(3):351-70. View

Mah E, Pei R, Guo Y, Ballard K, Barker T, Rogers V . γ-Tocopherol-rich supplementation additively improves vascular endothelial function during smoking cessation. Free Radic Biol Med. 2013; 65:1291-1299. DOI: 10.1016/j.freeradbiomed.2013.09.016. View

Lashkari S, Jensen S, Bernes G . Biodiscrimination of α-tocopherol stereoisomers in plasma and tissues of lambs fed different proportions of all-rac-α-tocopheryl acetate and RRR-α-tocopheryl acetate1,2. J Anim Sci. 2019; 97(3):1222-1233. PMC: 6396261. DOI: 10.1093/jas/skz011. View

10.

Ranard K, Kuchan M, Bruno R, Juraska J, Erdman J . Synthetic α-Tocopherol, Compared with Natural α-Tocopherol, Downregulates Myelin Genes in Cerebella of Adolescent Ttpa-null Mice. J Nutr. 2019; 150(5):1031-1040. DOI: 10.1093/jn/nxz330. View

11.

Bruno R, Dugan C, Smyth J, DiNatale D, Koo S . Green tea extract protects leptin-deficient, spontaneously obese mice from hepatic steatosis and injury. J Nutr. 2008; 138(2):323-31. DOI: 10.1093/jn/138.2.323. View

12.

Vatassery G, Angerhofer C, Knox C, Deshmukh D . Concentrations of vitamin E in various neuroanatomical regions and subcellular fractions, and the uptake of vitamin E by specific areas, of rat brain. Biochim Biophys Acta. 1984; 792(2):118-22. DOI: 10.1016/0005-2760(84)90211-x. View

13.

Lauridsen C, Engel H, Jensen S, Craig A, Traber M . Lactating sows and suckling piglets preferentially incorporate RRR- over all-rac-alpha-tocopherol into milk, plasma and tissues. J Nutr. 2002; 132(6):1258-64. DOI: 10.1093/jn/132.6.1258. View

14.

Traber M, Burton G, Ingold K, KAYDEN H . RRR- and SRR-alpha-tocopherols are secreted without discrimination in human chylomicrons, but RRR-alpha-tocopherol is preferentially secreted in very low density lipoproteins. J Lipid Res. 1990; 31(4):675-85. View

15.

Hodges J, Tan L, Green M, Ross A . Vitamin A Supplementation Increases the Uptake of Chylomicron Retinyl Esters into the Brain of Neonatal Rats Raised under Vitamin A-Marginal Conditions. J Nutr. 2016; 146(9):1677-83. PMC: 4997285. DOI: 10.3945/jn.116.233692. View

16.

Metcalfe T, Bowen D, Muller D . Vitamin E concentrations in human brain of patients with Alzheimer's disease, fetuses with Down's syndrome, centenarians, and controls. Neurochem Res. 1989; 14(12):1209-12. DOI: 10.1007/BF00965511. View

17.

Jeon S, Ranard K, Neuringer M, Johnson E, Renner L, Kuchan M . Lutein Is Differentially Deposited across Brain Regions following Formula or Breast Feeding of Infant Rhesus Macaques. J Nutr. 2018; 148(1):31-39. PMC: 6251643. DOI: 10.1093/jn/nxx023. View

18.

Han S, Pang E, Zingg J, Meydani S, Meydani M, Azzi A . Differential effects of natural and synthetic vitamin E on gene transcription in murine T lymphocytes. Arch Biochem Biophys. 2009; 495(1):49-55. DOI: 10.1016/j.abb.2009.12.015. View

19.

Jensen S, Norgaard J, Lauridsen C . Bioavailability of alpha-tocopherol stereoisomers in rats depends on dietary doses of all-rac- or RRR-alpha-tocopheryl acetate. Br J Nutr. 2006; 95(3):477-87. DOI: 10.1079/bjn20051667. View

20.

Gohil K, Godzdanker R, ORoark E, Schock B, Kaini R, Packer L . Alpha-tocopherol transfer protein deficiency in mice causes multi-organ deregulation of gene networks and behavioral deficits with age. Ann N Y Acad Sci. 2005; 1031:109-26. DOI: 10.1196/annals.1331.012. View