Lipids in the functioning of our brain: contribution of data obtained in humans
Does it make sense to talk about a link between lipids and the brain?
It is important to know that lipids represent 60% of the dry weight of the brain. They are essential for its development and lifelong functioning.
Lipids play major functional and structural roles. Among these lipids, we should mention the omega-6 and omega-3 fatty acids, the majority of which are very important because of their properties, which are described as being rather opposite at the vascular and inflammatory levels. In addition, these fatty acids are the source of derivatives (eicosanoids, resolvins, protectins) which play fundamental roles in the brain.
Can the lipids in our diet modulate the lipid content of our brain?
Food is a major environmental factor for our brain, to which we are exposed throughout our lives.
The omega-6 and omega-3 fatty acids found in the brain are long-chain fatty acids. Our body can synthesise them from precursor fatty acids, respectively linoleic acid (LA) for omega-6 and alpha-linolenic acid (ALA) for omega-3, which must be strictly supplied by the diet. They are therefore present in vegetable oils, such as sunflower oil for LA and rapeseed oil for ALA.
It should be mentioned that the conversion of the precursor fatty acids LA and ALA into long-chain fatty acids occurs in the body with a low yield. In addition to vegetable oils, it is therefore also necessary to consume foods that directly provide these long-chain fatty acids, such as oily fish, which are sources of omega-3 fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).
With age, the conversion efficiency of precursor fatty acids into long-chain fatty acids decreases. It is therefore important to balance the intake of LA and ALA precursor fatty acids through the combination of different vegetable oils, and also to consume the long-chain fatty acids EPA and DHA directly from food.
Therefore, the fat in our diet can actually affect the functioning of our brain.
Is there any evidence that dietary fat has a beneficial impact on our brain function?
The modifiable nature of diet makes it a major avenue for the prevention of cognitive disorders, for which there is still no curative treatment today.
The contribution of observational data
In addition to the studies carried out on animals, there is indeed a certain amount of observational data from nutritional epidemiology.
Our first work on this lipid/brain theme dates back to the early 2000s, in particular with the data from thePAQUID[1]studycarried out on subjects aged over 65 years living in the general population. We showed a relationship between the level of consumption of certain foods and the risk of dementia: namely that the highest consumers of fish had a lower risk of developing dementia. From these data came the interest in omega-3 fatty acids with regard to brain ageing.
Overall, epidemiological data obtained in the general population show that the higher the consumption of omega-3 fatty acids, the lower the risk of dementia or Alzheimer's disease.
However, there is some conflicting data, especially when exposure is concerned with circulating fatty acids, suggesting the involvement of metabolism, or an individual genetic susceptibility, as well as the role played by different environmental factors.
This is why, today, we are focusing on dietary profiles. For example, if we take the case of omega-3 fatty acids (which are peroxidisable due to their structure), we have put forward the hypothesis that the consumption of antioxidants would be more protective of these fatty acids.
Indeed, we find that people who eat fish also eat more fruit and vegetables. In the3-Cities study[2 ], which since 2000 has been looking at the brain ageing of people aged 65 and over living at home, we observed that the highest consumers of fish and fruit and vegetables, which are sources of antioxidants, have a reduced risk of dementia.
From fish, a source of omega-3 fatty acids, we have expanded our research to include other nutrients such as omega-6 fatty acids and monounsaturated fatty acids, such as oleic acid.
In general, dietary profiles such as the Mediterranean diet or those that follow the recommendations of the PNNS are described as favourable for the brain. Concerning the Mediterranean diet in particular, we observed in the 3-Cities cohort that the consumption of olive oil, rich in oleic acid, was associated with a lower incidence of stroke.
Research is now moving towards so-called omics approaches: these are non-targeted exploratory approaches that make it possible to identify the health impact of metabolites in our diet. These approaches make it possible to identify strong or weak metabolizers of these different metabolites and to make the link to health events. This new strategy offers interesting avenues for new modes of action for food.
The contribution of intervention data
In addition to these observational data, there are also data from intervention studies, namely supplementation trials.
These supplementation trials can be carried out in primary prevention in the general population or in secondary prevention in so-called fragile subjects at risk, who report a spontaneous cognitive complaint for example.
As in the case of observational studies, we have moved from an isolated nutrient approach to a more pragmatic dietary profile approach. An example of secondary prevention is thePREDIMED study, which demonstrated a beneficial effect of the Mediterranean diet with added extra virgin olive oil or walnuts on the brain of subjects at high cardiovascular risk and at risk of dementia.
Overall, the data from intervention trials are contradictory and only partially reflect the results of observational studies, due to methodological pitfalls: studies conducted with supplements that do not take into account the participant's spontaneous diet, the problem of targeted populations in a context of heterogeneous and asymptomatic brain ageing. For example, giving omega-3 fatty acids to people who already spontaneously eat fish twice a week does not seem appropriate.
Secondly, these trials generally have very short supplementation durations, preventing the demonstration of a possible longer-term effect. The question of the time window during which supplementation might be most effective is not yet known.
Finally, some of these trials are conducted on subjects with memory complaints. However, in these subjects, the cerebral ageing process seems to have already begun. The complaint is probably a symptom of structural alterations already taking place in the brain, before the appearance of more conclusive clinical signs.
In conclusion, what should we remember?
The evidence from observational studies supports the consumption of long-chain omega-3 fatty acids such as those found in oily fish and monounsaturated fatty acids, such asoleic acid found in olive oil, to support brain function.
On the more specific question of the impact on the brain of consuming vegetable oils other than olive oil, there is little evidence to date. The intake of fatty acids from these oils should play a more important role in this type of study, as we are seeing more and more consumers of these oils.
Catherine Féart is a member of the "Lifelong Exposures, Health and Aging" team in which she coordinates the "Nutrition, Health and Aging" thematic axis. Her research focuses on the relationship between diet and the onset of geriatric syndromes, and on the mechanisms underlying these associations. His approach, which combines epidemiology and biology, has shown, for example, that a greater Membership adherence to a Mediterranean diet is associated with slower cognitive decline in the elderly, and that an adequate vitamin D status is a preventive strategy against Alzheimer's disease. A mechanism involving LPS, partly regulated by the quantity and quality of lipids, and linked to the intestinal microbiota, could explain these associations. Most of her work is based on the large 3-Cities cohort (http://www.three-city-study.com/) and on national and international collaborations. She is currently supervising 2 PhD students and co-directing a thesis in partnership with the University of Toulouse. (http://cvscience.aviesan.fr/cv/2147/catherine-feart).
In parallel to her research activities, Catherine Féart is involved in teaching as head of the DU "Nutritional Epidemiology, teaching via the Internet" (http://www.isped.u-bordeaux.fr/), and of the teaching unit "Nutritional Epidemiology and Clinical Research in Nutrition" of the Master in Food Science and Nutrition at the University of Bordeaux.
[1] https://epidemiologie-france.aviesan.fr/ccontent/pdf/(ObjectId)/88475