B-vitamins and Omega-3 Fatty Acids and Biomarkers of Brain Atrophy.

B-vitamins and ω-3 Fatty Acids to Modulate Brain Ageing in European Citizens Through Improved Nutrition: the BOOMERANG Project

A poor nutrition status is a modifiable risk factor for cognitive decline and dementia. In particular, evidence links low status of certain B-vitamins and ω-3 fatty acids (ω-3 FA) with a greater risk of cognitive decline and dementia. Although these dietary components are typically investigated separately, post-hoc analyses of existing clinical trial data and experimental work indicate that B-vitamins and ω-3 FA may exert synergistic beneficial effects on processes related to brain health and cognition. However, this combination has not been tested directly in humans. In the proposed BOOMERANG project, we will study the effects of jointly supplementing with B-vitamins and a highly bioavailable ω-3 FA supplement, Lysoveta, on a robust biomarker of brain atrophy, the neurofilament light chain, in a double-blinded randomized controlled trial (RCT) over 3 months in older adults. We will also examine the secondary effects of the supplement of quality of life and cognitive function.

We will assess the effects of combined supplementation of B-vitamins and omega-3 fatty acids on neurofilament light chain (NfL), a biomarker of brain atrophy, in a group of older adults. The primary outcome is the change in plasma NfL, which is a marker related to inflammation, brain atrophy, and worsening of cognitive performance. The secondary outcomes are related to change in plasma homocysteine, B-vitamins, EPA, DHA, omega-3 index (the percentage of EPA and DHA in red blood cells), and biological age using epigenetic markers. These are biomarkers that can tell us about the effect of the supplement in the body. We also want to study the effect of the intervention on gene expression profiles and metabolite profiles. In addition, we will include secondary outcome measures of quality of life (SF-36) that include affective symptoms, as these can be a forerunner to developing cognitive impairment. We are also collecting data on their cognitive performance, as this is related to brain atrophy and neurological conditions.

Inclusion Criteria:

• Age > 65 years
• A low baseline B-vitamin status as assessed by plasma tHcy > 11 μmol/L
• Normal MMSE score (>25)

Exclusion Criteria:

• Unable to give informed consent
• Fatty fish intake > 2 times per week
• daily omega-3 supplementation
• daily B-vitamin supplementation
• history of B12-injections
• Serum creatinine > 90 μmol/L for women and > 105 μmol/L for men (above reference values)
• aspirin use
• renal disease
• active cancer
• Participants can be included if they accept to not take omega-3 supplementation or B-vitamin supplements during the study. They should stop using it and wait 12 weeks before they are invited to a screening visit.