A 2018 report by the WHO states : ‘Vitamins B and E, PUFA and multi-complex supplementation should not be recommended to reduce the risk of cognitive decline and/or dementia.’
Please note that this is not a statement saying ‘not enough evidence’ or that the evidence is divided. It is a positive statement telling people to NOT do something, akin to not smoking, not drinking too much alcohol.
First, let’s look at the evidence they cite to support this and what they did not consider, back in 2018when this was written (and repeated in a published paper is 2020). This 2018 WHO review makes no reference at all to the effect of B vitamins in slowing brain atrophy (1) and in improving cognition (2) in the rather large sub-group, estimated to be up to half of those over 65, with raised homocysteine. After all, why would B vitamins be expected to have an effect in those not deficient?
On closer inspection, three of the four cited studies in the WHO document are actually one meta-analysis primarily of cholinesterase inhibitors, which cites only one paper of B vitamins, that one part-funded by ARUK, which showed a clear effect of B vitamins in improving cognition in those with raised homocysteine, and one study on omega-3 DHA, which also shows clear benefit as stated in the studies abstracts. Thus, it misrepresented the study that ARUK part funded on B vitamins as negative when it had a clearly positive effect.
The only cited B vitamin study (how one does a meta-analysis and systematic review on one study is a mystery) states (De Jäger at el 2012, https://pubmed.ncbi.nlm.nih.gov/21780182/) “The mean plasma total homocysteine was 30% lower in those treated with B vitamins relative to placebo. B vitamins stabilized executive function (CLOX) relative to placebo (P = 0.015). There was significant benefit of B-vitamin treatment among participants with baseline homocysteine above the median (11.3 µmol/L) in global cognition (Mini Mental State Examination, P < 0.001), episodic memory (Hopkins Verbal Learning Test-delayed recall, P = 0.001) and semantic memory (category fluency, P = 0.037). Clinical benefit occurred in the B-vitamin group for those in the upper quartile of homocysteine at baseline in global clinical dementia rating score (P = 0.02) and IQCODE score (P = 0.01). In this small intervention trial, B vitamins appear to slow cognitive and clinical decline in people with MCI, in particular in those with elevated homocysteine.’ In other words, B vitamins work in those who are deficient in them, as establisahed by a homocysteine test. Above 11mcmol/l the brain shrinks faster as a clear indicator of deficiency.
The only cited study on omega-3 fish oils (Lee et al 2013 – https://pubmed.ncbi.nlm.nih.gov/22932777/) states “The fish oil group showed significant improvement in short-term and working memory (F = 9.890; ηp (2) = 0.254; p < 0.0001), immediate verbal memory (F = 3.715; ηp (2) = 0.114; p < 0.05) and delayed recall capability (F = 3.986; ηp (2) = 0.121; p < 0.05). The 12-month change in memory (p < 0.01) was significantly better in the fish oil group. This study suggested the potential role of fish oil to improve memory function in MCI subjects.” Once again, a positive study somehow used to imply a negative.
So, even based in its own cited evidence, the benefit of both B vitamins and omega-3 fish oils is supported.
How the WHO statement then recommends the opposite ‘Vitamins B and E, PUFA and multi-complex supplementation should not be recommended to reduce the risk of cognitive decline and/or dementia.’ beggars belief.
Also, much has been learnt, and published, since 2018. There is now evidence that homocysteine lowering B vitamins are most effective in those with sufficient omega-3 status and omega-3 fish oils are most effective in those with low homocysteine, thus confirming clinically the known mechanism of co-dependence, is an example as to why the WHO document is now out of date. We prefer published, peer-reviewed reviews such as the editorial in the the American Journal of Clinical Nutrition in 2021 (3) and a meta-analysis in 2023 (4).
Also, since 2018 there have been at least 17 studies (5-21), both randomised controlled trials and cohort studies which show benefit of either omega-3 fish oil supplementation, or higher intake from seafood or higher blood levels, in reducing risk for and incidence of dementia or cognitive decline. This is a another example why the WHO document is no longer current and relevant.
Regarding multivitamins the latest meta-analysis states: The meta-analysis of COSMOS substudies showed clear evidence of MVM benefits on global cognition and episodic memory; the magnitude of effect on global cognition was equivalent to reducing cognitive aging by 2 y.
In conclusion the 2018 WHO report is so sloppy, and out of date, it would be wise for WHO to withdraw this misleading report and certainly for both ARUK and the Alzheimer’s Society and any other Alzheimer’s or dementia organisations to stop referring to it in the context of omega-3, B vitamins or multivitamins if they are to maintain credibility in being remotely science-based.
Note: Many people are not aware that the WHO is no longer only funded by donations from countries but is now privately funded with the second largest funder, accounting for 10% of its budget, as the Bill Gates Foundation which influence its agenda.
References
1. Smith AD, Smith SM, de Jager CA, Whitbread P, Johnston C, Agacinski G, 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(9):e12244.
2. 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. International journal of geriatric psychiatry 2012;27(6):592-600.
3. Smith AD, Jernerén F, Refsum H. ω-3 fatty acids and their interactions. Am J Clin Nutr 2021;113(4):775-8.
4. Fairbairn P, Dyall SC, Tsofliou F. The effects of multi-nutrient formulas containing a combination of n-3 PUFA and B vitamins on cognition in the older adult: a systematic review and meta-analysis. The British journal of nutrition 2023;129(3):428-41.
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