Supplementation of Betaine and Creatine to Neonatal Parenteral Nutrition Lowers Telemetric Blood Pressure in Adult Yucatan Miniature Pigs.

BACKGROUND

Developmental programming is a key determinant of adult hypertension. Total parenteral nutrition (TPN) can exert nutritional stress during development and cause irreversible programming of metabolism via epigenetic modifications, often caused by imbalances in dietary methyl nutrients. Betaine and creatine (B + C) can increase the availability of methyl groups, but they are not included in commercial TPN formulations.

OBJECTIVES

We hypothesized that receiving TPN during early life would increase blood pressure (BP) in adulthood and that supplementing TPN with B + C (TPN-B + C) would prevent this programming. Intrauterine growth-restricted (IUGR) neonates have been shown to develop hypertension in adult life; thus, we hypothesized that IUGR would exacerbate the TPN effect.

METHODS

We used 7-d-old normal birth weight female Yucatan miniature piglets (n = 24) that were randomly assigned to the following diets: sow-fed (SowFed), TPN control (TPN-control), and TPN-B + C, with 8 IUGR piglets fed TPN as a fourth group (TPN-IUGR). After 2 wk of the experimental diets, all pigs were fed a grower diet until adulthood. At 8 mo, a telemeter was implanted to measure 24-h BP before and after a 2-wk high salt diet.

RESULTS

Although BP was not different between TPN-control and SowFed adult pigs, the addition of B + C to neonatal TPN reduced mean (by 9.5 mmHg) and systolic (by 7.1 mmHg) arterial pressure (P < 0.05; analysis of variance, Dunnett's comparison to TPN-control) in adulthood. However, the expression of key renin-angiotensin system genes was not altered in adult pigs. The BP parameters increased in response to a high salt challenge in all pigs (by 6.2-15.4 mmHg; P < 0.05; paired t-tests), but the neonatal diet did not affect the response.

CONCLUSIONS

These data collectively suggest that TPN feeding in early life does not alter adult BP but supplementing B + C in TPN may reduce risk of hypertension.