Effect of vitamin B12 and omega-3 fatty acid supplementation on brain neurotrophins and cognition in rats: A multigeneration study

Biochimie. Sep-Oct 2016;128-129:201-8. doi: 10.1016/j.biochi.2016.08.009. Epub 2016 Aug 26.


Vitamin B12 and omega-3 fatty acids are important nutrients required for neuronal functioning. We have demonstrated the beneficial effects of vitamin B12 and omega-3 fatty acid supplementation on brain neurotrophins and cognition in the first and second generation offspring. However, there is a need to examine if the effects are sustained in the third generation offspring. This study reports the effects of vitamin B12 and omega-3 fatty acid supplementation across three consecutive generations on brain neurotrophins like brain derived neurotrophic factor (BDNF); nerve growth factor (NGF) and cognitive performance in the third generation male offspring. Three successive generations of Wistar rats were assigned the following groups throughout pregnancy, lactation and adulthood: i) Control, ii) vitamin B12 deficient (BD), iii) vitamin B12 deficient + omega-3 fatty acid (BDO), iv) vitamin B12 supplemented (BS) and v) vitamin B12 supplemented + omega-3 fatty acid (BSO). The BD group demonstrated lower (p < 0.01) NGF in the cortex but not BDNF levels although the cognition was impaired (p < 0.01). In contrast, in the BDO group, higher NGF levels were observed in the hippocampus and animals demonstrated improved (p < 0.01) cognitive performance. Vitamin B12 supplementation showed comparable BDNF levels in the hippocampus while their levels were lower in the cortex as compared to the control (p < 0.05). These animals showed more reference and working memory errors (p < 0.01) as compared to the control group. A combined supplementation of vitamin B12 and omega-3 fatty acid showed higher (p < 0.01) levels of DHA and NGF in the hippocampus, higher BDNF in both hippocampus and cortex and improved cognitive performance. Our findings have implications for fortification of foods with vitamin B12 and omega-3 fatty acids in improving brain development.

Keywords: BDNF; Cognition; DHA; Omega-3 fatty acids; Vitamin B(12).

MeSH terms

  • Animals
  • Brain / drug effects*
  • Brain / metabolism
  • Brain / physiology
  • Brain-Derived Neurotrophic Factor / metabolism
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / physiology
  • Cognition / drug effects*
  • Cognition / physiology
  • Dietary Supplements
  • Fatty Acids, Omega-3 / administration & dosage
  • Fatty Acids, Omega-3 / pharmacology*
  • Female
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Hippocampus / physiology
  • Male
  • Maze Learning
  • Memory / drug effects
  • Memory / physiology
  • Nerve Growth Factor / metabolism
  • Nerve Growth Factors / metabolism*
  • Pregnancy
  • Rats, Wistar
  • Vitamin B 12 / administration & dosage
  • Vitamin B 12 / pharmacology*
  • Vitamins / administration & dosage
  • Vitamins / pharmacology


  • Brain-Derived Neurotrophic Factor
  • Fatty Acids, Omega-3
  • Nerve Growth Factors
  • Vitamins
  • Nerve Growth Factor
  • Vitamin B 12