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Imagine if a simple, well-researched nutrient protocol could prevent cognitive decline in millions of people worldwide. Imagine further that this protocol has been known for years, supported by multiple clinical trials and global experts, yet systematically ignored by the very institutions meant to protect public health. That is precisely the case when it comes to homocysteine, B vitamins, and dementia.

Last year, the UK-based Lancet Commission on Dementia Prevention, Intervention and Care released its third major report, once again omitting any mention of homocysteine as a modifiable risk factor. This was despite direct submissions of evidence and letters from leading scientists demonstrating that lowering homocysteine with B vitamins can slow brain shrinkage and cognitive decline.

Now, in response to this silence, six of the leading dementia researchers, Professors Joshua Miller (Rutgers), David Smith (Oxford), Helga Refsum (Oslo), Jin-Tai Yu (Fudan), Babak Hooshmand (Karolinska), and Andrew McCaddon (Wrexham), have published a powerful rebuttal in the Journal of Alzheimer’s Disease. Many of these experts serve in the Alzheimer’s Prevention Expert Group (APEG) at Food for the Brain.

They wrote:

“In 2018, we published an ‘International Consensus Statement on Homocysteine and Dementia’ in this journal, in which we concluded that elevated plasma total homocysteine is a modifiable risk factor for the development of cognitive decline, dementia, and Alzheimer’s disease (AD) in older persons. (1)

We further stated that intervention trials in elderly people with cognitive impairment show that homocysteine-lowering treatment with B vitamins markedly slows the rate of both wholeand regional brain atrophy, and also slows cognitive decline. We were therefore puzzled as to why the Lancet Commission on Dementia Prevention, Intervention and Care, failed to discuss the possible role of homocysteine and B vitamins in any of their three reports, including the most recent one.” (2)

A Systematic Omission

The UK-based Lancet Commission on Dementia Prevention is meant to objectively consider the evidence on dementia prevention. Yet each edition, despite being sent the relevant papers, has ignored the evidence concerning homocysteine.

Furthermore, it’s expected to uphold the standards for critical debate which allows for experts to question Published findings. That is exactly what these experts did – yet it declined to publish their letter, instead printing a rebuttal from its own Commission while refusing to let readers see the original letter. (3, 4)

The experts wrote to The Lancet again to respond to the Commission’s letter, but their second letter was also rejected. 

Thatetter has now been published in the leading Alzheimer’s journal where the authors finally have their rightful say. It includes the following:

“We wish to reply to the Commission and continue the debate with the aim of reaching a common view on homocysteine, B vitamins and dementia. This is an important matter of public health.”

In other words, The Lancet published the ‘case for the defence’ for the exclusion of homocysteine without allowing readers to even read the ‘case for the prosecution’. (5)

So, what was The Lancet’s case against B vitamins? It rested on three criticisms – each of which these leading dementia researchers refute with scientific precision in their recent journal paper.

Criticism 1: Misunderstanding Who Benefited in the VITACOG Trial

The Lancet Commission questioned the relevance of the VITACOG trial, arguing that the results “do not show benefits in populations already consuming B vitamins in their food or through supplements.” But this fundamentally misrepresents the study population.

In the VITACOG trial, participants with mild cognitive impairment were given high doses of B6, B12, and folic acid for two years. The result was a 31% reduction in whole brain shrinkage and significantly slower rate of cognitive decline in those with raised homocysteine (6). In participants with levels above 11.3 μmol/L – the median – both cognitive and clinical improvements were observed. Importantly, key Alzheimer’s-related brain regions shrank seven times more slowly in these individuals (7, 8).

The Lancet Commission implied that participants were already supplementing, but that is incorrect. The study excluded anyone taking more than 300 mcg of folic acid, 3 mg of vitamin B6, or 1.5 mcg of vitamin B12 – doses lower  than those found in many common multivitamins. Only 16 to 20 percent were taking low-dose supplements, while the majority were not.. No one was excluded based on their dietary intake of B vitamins.

The experts respond:“The Commission authors’ comment is analogous to expecting additional drug treatment to provide benefits over and above the benefits being obtained in people already taking a high dose of the drug, which is why it puzzles us.”

Criticism 2: No Benefit in the Hong Kong Trial?

The Commission’s response also cited a Hong Kong trial that reported no benefit of B vitamins over two years in people with mild cognitive impairment (MCI) (9). However, this overlooks several important confounders.

Firstly, 22% of participants were taking aspirin, which the study authors themselves found to impair the effect of B vitamins. This interference has since been confirmed in further research (10).

Secondly, the authors of The Lancet response failed to consider another critical factor: omega-3 status. Numerous studies show that B vitamins only deliver cognitive benefits when omega-3 fatty acid levels are sufficient. The Hong Kong study did not measure or control for omega-3 status, which likely explains the lack of consistent benefit over the two-year period.

Thus, the absence of effect in this trial does not disprove the role of B vitamins.  The experts go on to demonstrate in their article the overwhelming body of evidence –  reported by us – that homocysteine-lowering B vitamins do not work optimally in individuals with low omega-3 status.

Criticism 3: No Benefit in the VITAL Trial in Alzheimer’s Patients?

The Lancet authors also referenced the VITAL trial, which reported no overall cognitive benefit from B vitamins in patients already diagnosed with Alzheimer’s disease (11). But again, this conclusion overlooks key details.

In a subgroup analysis, those in the early stages of Alzheimer’s disease did show significant benefit (12). The authors of the VITAL trial themselves highlighted this in their paper, suggesting that earlier intervention is more effective. This finding aligns with multiple other studies showing that B vitamin treatment is most effective in the pre-dementia stages (13).

Furthermore, participants in the VITAL trial began with an average homocysteine level of 9 μmol/L, which is below the threshold (>10–11 μmol/L) associated with brain atrophy.  It is extremely rare to find a group of people with Alzheimer’s disease that start with such a low homocysteine level.  While the B vitamins did reduce homocysteine further to 7μmol/L, there was no overall cognitive benefit observed. But this is akin to giving painkillers to people who are not in pain and then reporting no change in pain levels. At Food for the Brain, we consider a homocysteine level above 10μmol/L as in need of correction with B vitamins.

There are also concerns about conflicts of interest. The lead author, Paul Aisen, is described as “a consultant to the following pharmaceutical companies involved in the development of potential treatments for Alzheimer’s disease”. with more than a dozen firms listed. These companies would certainly favour a trial designed to fail – especially if it were widely publicised.

Additionally, when an anti-amyloid drug trial for lecanemab was published – now licensed in the US and UK – the names of Paul Aisen and Christopher Van Dyck appeared once again as lead authors. In other words, the paid pharmaceutical consultants, responsible for running the drug trial were also tasked with overseeing a trial – designed to fail – on a competing approach: lowering homocysteine with B vitamins. The conflict of interest here is both clear and concerning.

What Does the Evidence Really Say?

You can read the full expert response published in the Journal of Alzheimer’s Disease here. 

Their conclusion is clear:

“We hope that the Lancet Commission will consider the substantial existing evidence of raised homocysteine as an important risk factor for dementia and the possibility of modifying its harm by supplementation with B vitamins.”

They emphasise that the evidence for B vitamin intervention is as strong – or stronger than –  many of the risk factors the Commission did include in its 2024 report. To continue ignoring the proven impact of homocysteine, and the benefits of lowering it through B vitamins is not merely a scientific oversight –  it is a missed opportunity with major implications for medicine and public health.

Remember, prevention is better than cure, and there is so much you can do to protect your brain health

The perfect time to start? Today.

What Can You Do?

Test your homocysteine (and omega-3 status) TODAY –  especially if you’re over 50 or at risk of cognitive decline. At Food for the Brain, we offer an accurate at-home test kit that reliably measures plasma homocysteine reliably. 

You can order your single Homocysteine test here or save money and test both omega-3 index and homocysteine (plus other markers) as part of our DRIfT tests here. International shipping available.

Act on your results –  if your level is above 10 μmol/L, supplementation with vitamin B6 (20 mg), methylfolate (400 µg), and vitamin B12 (500 µg) is recommended.
Read more on supplements and homocysteine here.

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