(P17-015-24) Maternal Dietary Vitamin B12 Restriction Promotes Insulin Resistance in the Offspring

Objectives: Veganism, especially among young Americans, is becoming increasingly popular. While often considered healthy, a vegan diet (VD) lacks vitamin B12, an essential micronutrient that is absent in plant foods. The impact of this deficiency on the metabolic health of pregnant women and their offspring remains unclear. This study investigated the intergenerational effects of a VD on the metabolic health of female C57BL/6 mice.

Methods: Female mice (4 wks-old, n=12-18/group) were individually housed and fed either a control diet (CD) or a diet with reduced vitamin B12 levels to mimic a VD for 18 weeks (wks). After 4 wks (attempt#1) and 12 wks (attempt#2) on diet, mice were bred with male colony mice and maintained on their respective diets through pregnancy, lactation, and after that. Body weight and food consumption were monitored regularly. Oral glucose tolerance tests (OGTT) and plasma homocysteine (tHcy) levels were measured at various time points in mothers and female offspring from both breeding attempts. Additionally, a subset of female VD pups was switched to CD after weaning and monitored for 8 wks.

Results: VD-fed mothers consistently showed elevated tHcy levels (a marker of B12 insufficiency) compared to CD-fed mice, but no significant differences were observed in food consumption, body weight, or glucose tolerance. B12 insufficiency persisted in VD pups, who, also exhibited glucose intolerance and were heavier than CD pups. Notably, the mothers' VD duration correlated with the extent of metabolic effects on the pups. VD-pups from the first breeding attempt showed significant glucose intolerance at wk12, while VD-pups from the second breeding attempt showed differences as early as at wk 4. Interestingly, even after switching to CD, VD pups maintained their glucose intolerance and significantly higher body weights than CD pups.

Conclusions: The metabolic effects of B12 deficiency are amplified in the F1 generation. These findings underscore the importance of considering the intergenerational impact of VD on humans.

Funding Sources: Penn State University SEN Summer 23 grant to KK. DP was supported by NIH grant T32DK120509.