• Nutrients Duo form Powerful Therapy against Brain Shrinkage
    Professor David Smith
  • Patrick Holforth

News & Views

Nutrients Duo form Powerful Therapy against Brain Shrinkage

Mar 24 2023

“The effect is greater than that of any drug treatment to date - with no adverse effects” David Smith

A combination of B vitamins and omega-3 has been hailed as the next major step towards Alzheimer’s prevention following new studies showing that a mixture of the two nutrients can stop brain shrinkage.The discovery was first made at the University of Oxford, but has now been confirmed by research groups in Holland, Sweden and China.

Headed by Professor David Smith, former Chair of Pharmacology and Deputy Head of the Division of Medical Sciences at Oxford and director of the Oxford Project to Investigate Memory and Ageing (OPTIMA), the research has found that giving older people with the first signs of cognitive impairment supplemental B vitamins (B6, B12 and folic acid) at higher levels than can be achieved through diet to those with sufficient omega-3 fats, produced 73% less brain shrinkage in a year compared to placebo(1). 

This reduction brought brain shrinkage down to the level found in those elderly with no cognitive decline(2). “The effect is greater than that of any drug treatment to date - with no adverse effects.” said Professor Smith. In contrast the recent trials of anti-amyloid drugs only show an insignificant reduced brain shrinkage of 4%.

Three other research groups, in Holland, China and Sweden, have confirmed the combined effect of omega-3 and B vitamins is far greater than either nutrient on its own.

B-Proof Trial

In Holland, a major trial called B-proof found no benefit at all from the B vitamins in those with low omega-3 status, but a massive improvement in cognition in those with sufficient omega-3 levels (3).

A Swedish trial that had given older people omega-3 fish oils but found no significant cognitive benefit reanalysed their results splitting the participants into thirds – from the lowest to highest B vitamin status. The group with sufficient vitamin B, indicated by a low level of blood homocysteine, showed three times the clinical improvement reported from the recent Lecanemab anti-amyloid drug trial(4). 

Meanwhile a trial in China gave those with pre-dementia either the B vitamin folic acid, or omega-3, or both, compared to placebo. Although B vitamin treatment and omega-3 treatment did slightly improve cognitive cores, the improvement was much greater in those given both of these nutrients(5). 

China’s leading dementia prevention expert, Professor Jin-Tai Yu at Shanghai’s Institute of Neurology at Fudan University, carried out one of the most thorough reviews of all risk factors for Alzheimer’s to date(6) concluding that “Lowering blood homocysteine levels, an established indicator of Alzheimer’s risk, with B vitamins is a most promising treatment.”

UK Bio Bank provides data

He was also given access to the UK’s Bio Bank data of almost half a million people “Our current research, using data from the UK Bio Bank, shows that having higher blood levels  of omega-3, and supplementing fish oils, is associated with less risk of dementia(7).  Moreover, recent studies suggest these two factors - homocysteine lowering B vitamins, and omega-3 - may, in combination, be potentially more beneficial. They are easy to implement. This is worthy of further research.”

The US National Institutes of Health research confirms this, attributing almost a quarter (22%) of the risk for Alzheimer’s to lack of B vitamins and raised homocysteine levels and the same (22%) to a lack of omega-3 and seafood intake(8). Almost half of all people over 65 have raised homocysteine(9) which increases risk for dementia by up to 10 times, according to Chinese research published last year(10).

Food Charity needs volunteers

Professors Yu and Smith are advisors to the Alzheimer’s prevention charity, Food for the Brain. The charity is looking for volunteers to take their free on-line Cognitive Function test and Dementia Risk Index questionnaire, including B vitamins and omega-3, and have a pin prick blood test to determine their status.

“These are the two easiest, and evidence-based risk factors anyone can eliminate.” said Patrick Holford who directs the Food for the Brain Alzheimer’s Prevention project. “Brain shrinkage is the hallmark of Alzheimer’s, so this is a vital discovery. Right now the evidence suggests we could cut the average person’s risk of developing Alzheimer’s by up to two thirds and the number of people developing dementia by a third if these and other risk factors were targeted. This could save some 70,000 people a year in the UK from developing dementia. Now we need to test this in a real-life situation.”

If you’d like to test your cognitive function and find out how to reduce your risk visit Food for the Brain website(below) and join their citizen science campaign.

More information online 

1. Jernerén F., et al. Am J Clin Nutr. 2015 Jul;102(1):215-21.

2. Oulhaj A., et al. J Alzheimers Dis. 2016;50(2):547-57.

3. van Soest APM., et al. Am J Clin Nutr. 2021 Apr 6;113(4):801-809.

4. van Dyck CH., et al. N Engl J Med. 2023 Jan 5;388(1):9-21.

5. Li M., et al. Eur J Nutr. 2021 Jun;60(4):1795-1808.

6. Yu JT., et al. J Neurol Neurosurg Psychiatry. 2020 Nov;91(11):1201-1209.

7. Huang Y., et al. Front Neurosci. 2022 Sep 7;16:910977.

8. Beydoun MA., et al. BMC Public Health. 2014 Jun 24;14:643.

9. Pfeiffer CM., et al. Clin Chem. 2008 May;54(5):801-13.

10.  Teng Z., et al. Front Aging Neurosci. 2022 Jul 15;14:868777.


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