NUTRITION AND BEHAVIOUR Andrée G. Roberge, Ph.D. President and CEO Brain is Highly Susceptible to Nutritional Environment It is commonly known that the brain is like a computer – it receives, integrates, programs and transmits all sensory-motor information. We also know that it manages all physiological and psycho-affective behaviour. Many studies have, in fact, demonstrated the importance of nutrition during children’s physical growth and mental development1,2,3. More recently, however, we have begun to realize that the developed brain too, is highly susceptible to its nutritional environments. For example, although still in its preliminary stages, a role for nutrition is currently being developed in the etiology and treatment of neurological and psychiatric behaviour. It is now known that the activity of neurons is influenced by different rhythms (circadian, monthly and seasonal) and is influenced by factors as variable as meal times, choice of food and chemical constituents of foods 4. Not surprisingly, then, nutrients can be instrumental in determining: physiological and psychoaffective behaviour; the organism’s capacity to adapt to different environmental situations; and hunger and satiety. CONTROL OF NEUROTRANSMITTER SYNTHESIS The key link between brain function and diet lies in the neurotransmitters. Since the 1959’s, it has been demonstrated that catecholamines and serotonin play an important role in both humans and animals in several physiological states. Serotonin, for example, has been associated with the sleep cycle and noradrenaline with awake and vigilance states. These neurotransmitters are also involved in thermoregulation, mechanism of hunger and satiation, and in the process of learning and memory. Neurotransmitters exert their action in nerve endings after release into the spaces or synapses, between cells. The pre-synaptic cell which releases the neurotransmitter, thus communicates with receptors on the post-synaptic cell. As a result, pathways throughout the brain serve as communication lines controlling brain function. A neurotransmitter never acts alone, it is always in metabolic or physiological relation with one or many neurotransmitters5. The neuroanatomical systems (motor or limbic systems) serve as supports and intermediaries for the transmission of information. Serotonin and catecholamines are readily affected by diet. Synthesized in the brain, they are formed when tryptophan and tyrosine undergo an initial transformation (hydroxylation) by two different enzymes sharing the same nutrient cofactors (pteridine, vitamin C and iron). After hydroxylation both amino acids are then decarboxylated by a vitamin B6 dependent enzyme to form the neurotransmitters dopamine and serotonin. This step in the conversion of the amino acids to the neurotransmitters is metabolically significant because it appears to assure a biochemical balance between the synthesis of the dopamine (DA) and that of serotonin (5-HT)6,7. An administration of tryptophan, therefore, will provoke an increase of serotonin and a decrease of dopamine, whereas an administration of L-DOPA8, used in the control of Parkinson’s disease will generate an increase of dopamine and a decrease of serotonin. This is only one example of biochemical balance generated in the brain to allow neurotransmitters to receive and organize information. Under normal concentrations of brain tryptophan and tyrosine, the hydroxylases, which are the rate limiting enzymes in both pathways, are not saturated by substrate. This means that diet induced changes in blood amino acid concentrations, and as a result in the brain, will influence the brain synthesis of these two important neurotransmitters. It is probable that these simple relationships between the diet plasma and brain neuro-chemistry allow the brain to gather information on diet composition and the metabolic state of the body and to use this information in the regulation of many of its functions. BRAIN DISTINGUISHES BETWEEN NUTRIENTS It is through this system that the brain can distinguish a carbohydrate meal from a protein meal. Carbohydrate consumption increases plasma tryptophan relative to the competing neutral amino acids. This happens because the release of insulin which occurs after carbohydrate is consumed causes rapid uptake of amino acids, except tryptophan, by tissues9. When the amino acids pass through the brain capillaries, tryptophan has an advantage for uptake. As a result, brain tryptophan and serotonin levels increase. The opposite happens to brain serotonin when proteins consumed. Proteins are relatively low in tryptophan, but high in the amino acids which compete for its uptake by the brain. Thus a meal of protein decreases the plasma tryptophan to competing neutral amino acid ratio, and the brain is informed that protein is consumed. Dopamine, the immediate precursor of noradrenaline (NA), is derived from the amino acid tyrosine. However, its synthesis is not directly influenced by plasma and brain concentration of tyrosine, as is the saturation describing the relationship between tryptophan and serotonin. The synthesis of noradrenaline, from dopamine is limited by the biochemical properties of the synthesis enzyme (dopamine-B-hydroxylase) and by the location of this enzyme in the nerve cell. Consequently, an increase in the dopamine content does not necessarily correspond to an increase in noradrenaline content on the neuroanatomical and neuro-physiological levels. It is interesting to note that in certain regions of the brain such as the cortical regions, the synthesis of dopamine is to serve almost exclusively for the synthesis of noradrenaline, whose role as a neurotransmitter is dominant. REGULATION OF FOOD INTAKE: RECENT THEORIES Food intake regulation is a good example of behavioural response. Many theories have tried to explain how the brain controls food intake and is responsible for hunger and satiation mechanisms. The theories of the control of blood glucose and of lipid reserves are described as the glucostatic and lipostatic hypotheses. According to the glucostatic hypothesis, appetite control is determined by the use of glucose by brain cells. If utilization is low, neurons would be activated and hunger increases. Conversely, when the rate of glucose utilization is high, the activity of the brain cells sensitive to glucose would be diminished, and the sensation of satiation attained. Unlike peripheral tissues, such as muscle, the brain does not need insulin to metabolize glucose and cannot store the glucose, suggesting further that the metabolism of glucose may have a unique place in the regulation appetite. The lipostatic hypothesis suggests that the size of fat deposit in the organism is connected to the neuronal or hormonal control of appetite. Temperature changes affect degree of appetite, possibly by affecting energy storage. Thus in humans, a cold environment stimulates appetite, whereas a warmer environment diminishes appetite. An hypothesis suggests that changes in plasma amino acids patterns and brain uptake of amino acids after food ingestion provide signals which allow the regulation of appetite10,11. Both the catecholamines and serotonin neurotransmitters systems are known to be involved in appetite regulatory mechanisms. The control of their synthesis by the availability of their amino acid precursors, therefore, suggests that appetite regulation may be achieved by this mechanism. Other hypothesis exist for the regulation of appetite, but their physiological and biochemical significance are yet to be specified. The brain may possess many mechanisms capable of modulating the functional use of nutrients. PSYCHO-AFFECTIVE BEHAVIOURS The importance of macro-and micro-nutrients in psycho-affective disorders is recognized more and more. For example, it has been demonstrated that the circadian rhythm of free tryptophan but not that of tyrosine in plasma was perturbed in depressive subjects maintained on a controlled diet 12. Furthermore, an abnormality in the metabolism of tryptophan has also been described to cause emotional instability, irritability, fatigue, perturbed sleep, loss of libido and relatively depressive state. In subjects using oral contraceptives, a disturbance in the metabolism of tryptophan was corrected using a vitamin B 6 supplement13. PSYCHO-AFFECTIVE FOOD-INTAKE BEHAVIOUR Anexoria nervosa is a disease primarily of young women characterized by the pursuit of a thin body and a dread of weight-gain. It is an example of food-intake behaviour thought to be of psycho-affective origin, and may be reflected in a diet which shows a selective privation of certain macro-nutrients and a very restrictive energy intake, significantly lower than the norm causing excessive weight loss 11. Anorexic14,15 subjects select their food according to mood, expectations or deceptions and generally eat in a disorderly fashion. Often the preferred hypocaloric diet is relatively high in proteins, low in carbohydrate and lipids and rich in fibber. Consequently, the individual’s nutritional state deteriorates and the subject will show man symptoms of nutrient deficiency including lack of menstruation, hypothermia, bradycardia, hypertension, constipation, anxiety, and depression. In all these cases, a biochemical imbalance appears to exist between the brain’s neurotransmitters and the limbic system’s functions. Therefore, the first nutritional step to be undertaken in the treatment of affected individuals should be aimed at weight gain as well as at stabilizing the psychoaffective state. As discussed earlier the brain can distinguish a carbohydrate meal from a protein meal. An increase in brain serotonin after a glucose carbohydrate meal reduces mental activity and provokes drowsiness, both well known responses after a meal. Similarly, it has been demonstrated in rats that a carbohydrate and lipidrich diet increases serotonin synthesis but decreases activity in the noradrenergic system16,17. Although it is a difficult task to change the anorexic sufferer’s protein-rich diet to a relatively carbohydrate-rich diet, these effects of protein ad carbohydrate on the brain suggest that anorexic individual might benefit from a dietary increase in carbohydrate to reverse the the neuro-chemical effects of the high protein diet. This is only one example of psycho-affective food-intake behaviour. Possibly obesity treatment by diet may be enhanced by appropriate manipulation of neurochemical systems through food composition. RELATIONSHIPS SHOULD NOT BE OVERSIMPLIFIED The effects of nutrition on behaviours linked to human mental and psychoaffective activity are numerous and complex. It is important to remember that macro and micro-nutrients are essential to the good functioning of the brain even though it is presently difficult to evaluate fully their role in origin of a cerebral malfunction. Moreover, as amino acids play an obvious role as precursors of neurotransmitters, it must no be overlooked that they are closely tied to vitamins and minerals in all their metabolic progress. It is clear that a healthy and balance diet contributes to the stable maintenance of the brain’s vital function. These relationships should not be oversimplified, however, because the link between nutrition and human behaviour constitutes a continuum of multiple well-integrated sequences capable of maintaining a homeostatic state for as long as the organism’s physiological limits have not been excessively distorted by disease or more frequently, by various stressful situation. References : 1. Roberge, A.G.O2K NEURO NUTRITION CONCEPT. Conférence présentée le 8 février 2002 à Nassau, Bahamas pour Matol Botanical International. 2. Roberge, A.G. Nutrition and Behaviour. Perspectives, Vol. 3, No 1/Spring 1985. 3. Himwich, H.E. Early studies of the developing brain. Biochemistry of Developing Brain. Ed. W. Himwich, Marcel Dekker Inc., 1973. Vol.1:1-50. 4. Moore-Ede, M.C., Sulzman, F.M. and Fuller, C.H.The Clocks That Time Us. Physiology of the Circadian Timing System. Harvard University Press, 1982. 5. Roberge, A.G., Parent, A. et Boulay, M. Démonstration d’une relation inversement proportionnelle entre la dopamine et la sérotonine dans certaines structures cérébrales :aspects neurochimique et morphologiques. J. Neurochem., 1976. 26:591-595. 6. Erickson, C.K. Functional relationship among central neurotransmitters. Review of Neuroscience, Ed. Ehrenpreis & Kopin, Raven Press, 1978. Vol. 3:1-34. 7. Roberge, A.G. A morphological and biochemical dissociation between dopamine and serotonin in cat brain. Catecholamines: Basic and Clinical Frontiers, 1978. 2:1110-1113. 8. Bouchard, S. & Roberge, A.G. Biochemical properties and kinetic parameters of DOPA/5-HTP Decarboxylase in brain, liver and adrenals of cat. Can.J. Biochem., 57(7): 1014-1018. 9. Héroux, O. and Roberge, A.G. Different influences of two types of diets commonly used for a rats on a series of parameters related to the metabolism of central serotonin and noradrenaline. Can. J. Physiol. And Pharmacol., 1981, 59(2): 108-112. 10. Altern, H., Dudel, J., Grusser, O.J., Griieser-Cornehls, U., Klinke, R., Schmidt, R.F. and Zimmerman, M. Fundamentals of sensory physiology. Ed. Schmidt, R.F., Springer-Verlag, New York, 1981. 11. Blackburn, H., Roberge, C. et Roberge, A.G. Effets d’un régime hyperlipidique et hyperglucidique et d’un régime hypocalorique sur la teneur des amines biogènes du cerveau de rat. ACFAS, Univ. du Québec à TroisRivières, 25-27 mai 1983. 12. Anderson, G.H. and Johnston, J.L. Nutrition control of brain neurotransmitter synthesis and function. Can. J. Physio. Pharmacol., 1983. 61:271-281. 13. Adams, P.W., Rose, D.P., Folkard, J., Wyne, U., Seid, M. and Strong, R. Effect of pyridoxine hydrochloride (vitamin B6) upon depression associated with oral contraception. Lancet, 1973, 897-904. 14. Thibault, L. et Roberge, A.G. The Nutritional Status of Subjects with Anorexia Nervosa. Intern. J. Vit. Nutr. Res., 57 :447-452. 15. Gillberg, C. Low dopamine and serotonin levels in anorexia nervosa. Am. J. Psychiat., 1983, 140(7): 948. 16. Pouliot, T., De la Noüe, J. & Roberge, A.G. Influence of Social Interaction on Physiological and Neurochemical Responses of Rainbow trout under Hypoxia Stress. Nanjing – The third International Symposium on Antennas and Electromagnetic Theory (ISAE’93), China, September 6-9, 1993. 17. Pouliot, T., Roberge, A.G. & De la Noüe, J. Impact of Dietary Protein Quality on the Resistance of Rainbow Trout to Chronic Hypoxia Stress. Hobart – 6th International Symposium on Fish Nutrition and Feeding, Australia, Oct. 4-7. 1993.