expert opinion

Successful intervention with B vitamins to help prevent mild cognitive impairment is shown to be enhanced by a superior marine omega-3 fatty acid status

February 15, 2016


Professor Celeste de Jager, Division of Geriatric Medicine, University of Cape Town, South Africa

Some nutrients, including B vitamins and marine omega-3 fatty acids, have been demonstrated to have a positive effect on cognition in humans. When an individual has a low vitamin B status, the result is an accumulation of homocysteine. Highplasma homocysteine (tHcy) levels are a known, modifiable risk factor for cognitive impairment and Alzheimer’s Disease (2).

Professor Celeste de Jager of the Division of Geriatric Medicine at the University of Cape Town in South Africa specializes in the effect of nutrition on cognitive decline in the elderly. In recent years, she has been closely involved in the VITACOG randomized controlled trial which found that a vitamin B intervention (specifically folic acid, vitamins B6 and B12) reduced circulating homocysteine levels, leading to a reduced rate of cognitive decline. The VITACOG study involved a two-year intervention of the B vitamin mix in 266 participants who were aged 70 years or over and had been diagnosed with mild cognitive impairment. The intervention was found to slow brain atrophy, both overall and in specific regions (3, 4). The intervention also helped maintain memory functions, specifically verbal episodic memory, semantic memory and overall cognitive performance as measured by the Mini-Mental State Examination (MMSE). However, the benefits only occurred in those individuals who had high tHcy levels at the start of the trial. Impressively, when rated using the Clinical Dementia Rating (CDR), more than half of the individuals reverted from mild cognitive impairment to normal control status after the two-year intervention (5).

Consumption of fish rich in marine omega-3 fatty acids has been recognized as being protective against the onset of cognitive decline and dementia (6). However, as with vitamin B, the results of direct intervention trials have been inconsistent. Interestingly, tHcy is involved in the methionine cycle that regulates both omega-3 distribution and phospholipid synthesis.

In a paper published in 2015, Professor De Jager’s team reported that a good omega-3 status enhanced the protective effect of B vitamins on brain shrinkage in the VITACOG cohort (7). In her latest paper on the VITACOG cohort (1), she found that 33% of the participants with a good marine omega-3 status had clinical dementia ratings of more than zero, compared with 59% of participants who had low levels (at the end of the two-year vitamin B intervention). Verbal delayed recall and global cognition were also better in the high omega-3 status group. The beneficial effect was largely attributed to the specific omega-3 fatty acid, docosahexaenoic acid (DHA). The paper also demonstrated that for the participants who had low circulating marine omega-3 levels, the vitamin B intervention had no effect in delaying the onset of mild cognitive impairment.


  1. Oulhaj A, Jernerén F, Refsum H, Smith AD & De Jager CA; “Omega-3 Fatty Acid Status Enhances the prevention of cognitive decline by B vitamins in Mild Cognitive Impairment”; Journal of Alzheimer’s Disease 2016”, accessed 20th January 2016: DOI 10.3233/Jad-150777
  2. Hooshmand B, Polvikoski T, Kivipelto M, Tanskanen M, et al.; “Plasma homocysteine, Alzheimer and cerebrovascular pathology: A population-based autopsy study. Brain 2013; 136, 2707-2716.
  3. Smith AD, Smith SM, De Jager CA, Whitbread P et al.; “Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment. A randomized controlled trial. PLoS One 2010; 5, e12244.
  4. Douaud G, Refsum H, De Jager, CA, Jacoby R et al.; “Preventing Alzheimer’s disease related gray matter atrophy by B-vitamin treatment” ; Proc Natl Acad Sci USA 2013; 110, 9523-9528.
  5. De Jager CA, Oulhaj A, Jacoby R, Refsum H & Smith AD; “Cognitive and clinical outcomes of homocysteine lowering B-vitamin treatment in mild cognitive impairment: A randomized controlled trial”; Int J Geriatr Psychiatry 2012; 27: 592-600.
  6. Beydoun MA, Beydoun HA, Gamaldo AA & Teel A; “Epidemiologic studies of modifiable factors associated with cognition and dementia: Systematic review and meta-analysis. BMC Public Health 2014; 14: 643.
  7. Jernerén F, Elshorbagy AK, Oulhaj A, Smith SM, Refsum H & Smith AD (2015) Brain atrophy in cognitively impaired elderly: The importance of long-chain omega-3 fatty acids and B vitamin status in a randomized controlled trial”; Am J Clin Nutr 2015; 102: 215-221.