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chapter one
Introduction
Research on the structure and function of the human brain started very early in the history of medical science. Greek doctors, in the sixth century BC, recognized the brain as the center of the highest human activities. At the time of Galen in the second century AD, brain anatomy was already known in detail, and the brain’s importance was established as the seat of intelligence, voluntary movements, and sensations. The composition of the brain generated a significant interest as early as the time of Plato (428–348 BC), who considered this body part as equal to the bone marrow, whereas Aristotle (384–322 BC) compared the brain to a fat deposit comparable to the spermaceti found in the brain of the sperm whale.
The first observations on the fatty nature of the brain were made in the seventeenth century by the Danish physician Thomas Bartholin (1616–1680), discoverer of the lymph system and of the glands present in women that were given his name (Bartholin glands), and by the Dutch inventor of the microscope and discoverer of the spermatozoids, Antoni van Leeuwenhoek (1632–1723). But it was the early work of the French chemist Michel Eugène Chevreul (1786–1889), the founder of lipid chemistry, that led the way for other researchers in the nineteenth century to provide new knowledge about the composition of brain lipids: Nicolas Vauquelin, Jean-Pierre Couerbe, Nicolas Gobley (all in France), and Johann Thudichum (in Britain). All of these researchers described the nature of brain phospholipids, and Gobley and Thudichum also revealed the presence of few simple acids (stearic, palmitic, and oleic acids).
In the 1960s, with the advent of more efficient analytical techniques, many researchers focused on the richness of the brain and retina in docosahexaenoic acid (DHA [22:6 ω-3]), a fatty acid found in 1942 in Japanese fish (see Section 7.1). This fatty acid, called “marine fatty acid,” likely appeared during the Cambrian explosion, about 600 million years ago, when its synthesis became possible because of the rising atmospheric oxygen levels above the Pasteur point responsible for aerobic life. In parallel, complex cell types also appeared that were characterized by the presence of a nucleus and several mitochondria, structures known to be common to all cellular organisms called eukaryotes.
Among the discoverers of the biochemical features characteristic of all nervous tissues, mention should also be made of John S. O’Brien (University of California–San Diego). In 1965, he was one of the first to describe accurately the fatty acid composition of several lipid fractions extracted from the white and gray substances of the human brain (O’Brien and Sampson 1965). Similar observations were made by N. C. Nielsen (Vision Research Institute, The Ohio State University) on beef retinal cells, nerve cells specialized in the perception of light (Nielsen 1979). Nielson found that the DHA content of the photoreceptor lipids was very large (36%) and higher than that measured in synaptic membranes.
Very quickly and naturally, these biochemical features led investigators to suggest that high DHA levels in brain cell membranes should correspond to a specific physiological function. One of the first assumptions was that a dietary deficiency of this fatty acid during the development of an animal or a human could hinder the formation of the myelin sheath, known to isolate nerves, thereby inducing instability in the nervous system and causing major disorders (Bernsohn and Stephanides 1967).
Subsequently and to this day, this specific affinity of the brain and retina for DHA has prompted investigations showing the plurality of functional roles for DHA in humans and animals (rat, monkey). Human clinical studies have sometimes confirmed the results found in epidemiological studies.
Despite the resistance of the nerve tissue to any change after a dietary modification, work published in 1971 first revealed that a prolonged dietary deficiency of linolenic acid (18:3 ω-3), the precursor of DHA found in plants, induced a decrease in the DHA content in rat retina (Anderson and Maude 1971). Four years later, Wheeler et al. (1975) showed that these changes were accompanied by a weakening of the electrical functioning of the retina, thereby affecting the vision of DHA-deficient animals.
Independently of this work on vision, the influence of an essential fatty acid deficiency on the general functioning of the brain was being widely explored. It seems that the subject was first described in 1966 by D. F. Caldwell in Detroit, Michigan. Caldwell and Churchill (1966) clearly demonstrated that the administration of a diet devoid of fatty acids in pregnant rats led to a serious reduction in the learning capacity of the second-generation rats. However, these investigations could not target a precise group of lipids because the food was totally delipidated.
Several researchers then showed that this lipid deficiency not only decreased the learning ability of the rats, but also induced a large drop in the DHA content in specific brain phospholipids (Lamptey and Walker 1976). Similar results were described in monkeys (Fiennes et al. 1973). In France, Bourre et al. (1989) confirmed that a diet without linolenic acid, but rich in linoleic acid, induced a significant decrease in learning ability in rats. All this research finally allowed for the determination that ω-3 fatty acids, and particularly their precursor linolenic acid, were responsible for these physiological disorders. Using a fortification of the food given to pregnant rats with a fish oil rich in DHA and eicosapentaenoic acid (EPA [20:5 ω-3]), Yonekubo et al. (1994) in Japan demonstrated an improvement of learning capacities in young rats born from these mothers, compared with animals ingesting no fish oil. In addition, this DHA and EPA intake had no effect when fed during the postpartum period. From these investigations, it can be considered that surely DHA and probably its precursor EPA are among the several components involved in the “noblest” and most vital functions of the brain.
What could be the role of these particular fatty acids of marine origin in brain function? The problem is very complex, but one of the mechanisms underlying the behavioral problems observed after a linolenic acid deficiency was proposed by Delion et al. (1994) via work done in Tours University, France. They showed that a linolenic acid deficiency was able to induce important changes in neurotransmission pathways involving dopamine- and serotonin-secreting cells in various regions of the rat brain, changes likely interfering with the animal behavior.
Work on determining the major role of ω-3 fatty acids and especially long-chain DHA in brain function, as demonstrated by Michael Crawford of the Brain Chemistry and Human Nutrition Institute in London, promoted with some success the hypothesis of their decisive intervention in the anatomical and functional development of the human brain during its development.
Indeed, from the anthropological studies we know that bipedalism, present in Homo habilis 2 million years ago, was contemporaneous with a significant increase in brain volume, a phenomenon likely accompanied by the adoption of a meat-rich diet. These changes were favored by the migration of this prehistoric early-human ancestor to aquatic areas rich in land animals where DHA-concentrated prey could be found. Later, about 100,000 years ago, a further increase in brain volume led to modern humans (Homo sapiens); this brain volume increase was contemporaneous with a new migration toward East Africa in lakeshore areas or countries close to marine environments. There, these humans found prey that supplied all of the long-chain ω-3 fatty acids (EPA, DHA) needed to build the brain. In addition, this migration was accompanied by a cultural explosion, marked by the emergence of arts, religions, and unfortunately wars. This development may ultimately be characterized more by higher brain functions than by an increased brain volume (Horrobin 1998). As emphasized by Horrobin, a prolific and popular English author, the differentiation of humans and great apes can only be based on lipid metabolism, if one considers the richness of these organic compounds in the brain and the importance of the neuronal connections.
Just as past trends have been influenced by a steady and increasing supply of DHA, it is likely that the intellectual evolution of current humans will depend on the consumption of foods rich in ω-3 fatty acids. The depletion of marine animals suitable for human consumption, as a result of intensive fishing and contamination by pesticides or heavy metals, should encourage the development of a controlled aquaculture of fish or algae producing DHA: this approach may be the only way to ensure good physical and mental health for future generations.
The role of fatty acids in the functioning of the nervous system of laboratory animals has been the subject of much research. Although a direct link has not yet been established, the effects of these fatty acids on behavior and cognitive abilities of these animals are no longer questionable. This zoopsychological approach is necessary, but the transposition of the findings from rat or even chimpanzee to the human cognitive domain remains questionable. Despite the complexity of such research, it is not surprising that neurophysiologists and psychiatrists were interested in these topics, with some of them being already investigated in animals. Much epidemiological research was recently undertaken, along with some therapeutic trials. Thus, various aspects of child development, aging, neurological disorders, or mood (or affective) disorders have been considered for therapeutic or preventive actions. Although the mechanisms involved remain poorly understood, applications of some of this research are beginning to be successfully exploited in various situations.
In addition to fatty acids, many observations have indicated that other lipids such as vitamins (A, D, and E), cholesterol, and some carotenoids could contribute to maintenance of the noble functions of the brain in aged people and also prevent serious neurological disorders such as epilepsy or multiple sclerosis.
Similarly, many mood disorders, as classified in psychopathology, seem to be under the control of these lipids. Numerous clinical studies and some experimental interventions now suggest that supplementation with some of these lipids may improve depressive and bipolar disorders, schizophrenia, autism, and attention-deficit disorders and also contribute to reduction in the intensity of aggressive or suicidal impulses.
If new results confirm the initial assumptions of the involvement of ω-3 fatty acids in brain function, and also other related compounds and vitamins belonging to the lipid group, it will be important to promote the consumption of these natural substances, the supply of which should be sufficient from a diversified diet. As suggested by D. Horrobin in 2003, the deficiencies observed in a population at risk with an unbalanced diet should be quickly filled by a supplementation with simple nutrients.
The treatment of mental disorders using a dietary approach is not yet common among the public or medical doctors. It is significant that a recent report by the Montaigne Institute in Paris evoked only the possibility of vitamin D to counteract the environmental effects on mental illness. Undoubtedly, lipid administration will gain momentum when patients realize that the current research is usually performed by government teams receiving no aid from the pharmaceutical industry. This independence may encourage a pragmatic and sympathetic consideration from the public because all of the nervous disorders described in this book could potentially be diminished without risk by a moderate dietary change or by a simple supply of an appropriate supplementation. Although this cognitive impairment approach in no way excludes modern medical therapy, patients should be aware that any alternative or at least complementary treatment already exists. This topic should be mentioned in the interview between doctor and patient, especially after taking into account the documents related to the involved problems.
These encouraging results offer the potential for a new and important treatment of many mental conditions that are currently a heavy burden on social budgets. Indeed, the World Health Organization (WHO) found that more than 450 million people suffer from behavioral or mental disorders worldwide. In the European Union, a recent analysis has shown that 27% of individuals aged 18–65 years suffered from psychiatric troubles during the past year. In France, 1 in 5 people currently suffers from a mental disorder (12 million for the whole country), compared with 1 in 10 for cancer.
The Montaigne Institute and the “FondaMental Foundation” in France estimated that in 2014 the costs associated with mental illness would reach nearly 110 billion euros per year or 5.8% of the gross domestic product. In comparison, the cost of cancer for the society was estimated at 60 billion euros and that of cardiovascular diseases at 30 billion euros. As emphasized in the Montaigne Institute report, only 2% of the budget of biomedical research is actually devoted to these problems. It is thus time to make the fight against mental diseases a public health priority. Taking into account the steady lengthening of the “total” life expectancy and the incidence of mental diseases related to old age, the main challenge of medicine in this twenty-first century is to increase the “healthy” life expectancy. Failure to achieve this ambitious goal will lead to formidable economic challenges for all nations in the management of an increasing number of frail or dependent older people.
The purpose of this book is to focus on the most important and recent work on food lipids and human health, placing the work in a historical context. Such research has provided some indisputable evidence of the beneficial effects, even for a moderate intake, of some specific lipids, sometimes absent or introduced at too low amounts in the normal diet. It is hoped that this information could be propagated widely to more easily preserve and improve brain development in young people and mental health of some adults, with only slight dietary modifications. Furthermore, these improvements involve only natural products that are much cheaper than the current traditional drugs. Despite the lack of support by pharmaceutical companies, the advances of these “nutritional treatments” as highlighted in this book may be immediately applied by healthcare personnel for the greatest benefit of patients and the global health budget.
It is regrettable that the basic rules of nutrition and dietetics are not part of the general culture, a likely consequence of the absence of education in these matters at all levels of schooling. Hopefully, the recent relationships noted between mental or neurological troubles and food lipids will spur people to take responsibility for their health status. The information in this book details how to live to old age in good health and in full autonomy, particularly by slowing the inevitable decline of the upper brain functions and by trying to avoid the development of the most disabling n...
