It is widely accepted that a well-balanced diet and good nutrition are necessary to ensure normal growth, prevent disease, and maintain physical performance. Despite much speculation and some important early findings about general malnutrition, relatively little is known about how specific nutrients affect the brain and other organ systems in relation to mental activities, emotional states, and behavior in healthy individuals. With few exceptions (for example, vitamin B12 and iron), the behavioral consequences of deficiency are not presently considered as criteria when establishing recommended dietary allowances. However, the involvement of a broader range of disciplines and recent methodological advances have led to the reemergence of studies on brain function and behavior in relation to nutrition. This area of research represents a unique approach to assessing the functional consequences of altered nutrition.
This chapter focuses on this nutrition research; describes current methods of assessing nutrition, brain function, and behavior; highlights several interesting findings; and discusses future challenges.
Why Study Brain Function and Behavior?
Among the public, there is a strong and persistent belief that what we eat affects our mental and emotional states and, in general, our ability to perform day-to-day activities and to meet life’s demands. It seems we all have theories, or at least suspicions, about the functional importance of this or that food or specific nutrient. In fact, some of us alter our diets and take supplements and freely advise others to do likewise, with the firm belief that such changes will improve the way we feel and our ability to perform.
This belief often creates a psychological environment amenable to food faddism and uncritical acceptance of claims made by self-styled “nutritionists.” Today’s “smart” foods, promoted as a way to increase “brain power” and enhance memory, are a recent example. Scientific evidence to support most of these claims of the beneficial effects of specific nutrients or diets is at best conflicting and, more typically, simply lacking. The study of nutrition, brain function, and behavior responds to public interest and will, with time, produce the experimental data needed to assess the legitimacy of health claims and provide reliable criteria useful for evaluating nutritional status and making recommendations for dietary intakes.
The consumption of nutrients (biologically active chemicals), in the form of foods or supplements, affects body chemistry which, in turn, affects brain chemistry and function. Neural impulses are largely the result of sodium and potassium exchange, but numerous other minerals, carbohydrates, amino acids, proteins, and vitamins affect cell membrane permeability, neurotransmitter metabolism, and the glial cells that provide structural and nutritional support to neurons.
The delicate chemical balance of the brain is somewhat protected by the blood-brain barrier, which restricts entry of certain chemicals to the brain via the blood. Nevertheless, the brain is highly susceptible to changes in body chemistry resulting from nutrient intake and deficiency.
The brain receives, stores, and integrates sensory information and initiates and controls motor responses. These functions correspond to mental activities and form the basis for behavior. Thus, theoretically, there is a direct connection between nutrition, brain function, and behavior. Furthermore, behavior may be unique as a criterion for establishing nutritional adequacy, in that it represents the functional integration of all biological systems, including homeostatic and other compensatory mechanisms that determine the practical importance of a nutritional deficit or excess.
Who Studies Brain Function and Behavior?
In the United States, studies on nutrition and brain function are conducted at private laboratories and hospitals, academic institutions, and government research laboratories. Government-supported research in this area is concentrated in the Department of Defense (DOD), USDA, and the National Institutes of Health (NIH). DOD nutrition programs focus on enhancing performance during combat and in other stressful environments, while NIH nutrition programs focus on the brain and behavior related to disease states and drugs used in treating disease. Only USDA addresses the relationships among nutrition, brain function, and behavior in the population as a whole.
One of the six principal objectives stated in USDA’s 1992-98 Agricultural Research Service (ARS) Program Plan is to “develop the means for promoting optimal human health and well-being through improved nutrition” and to “define adequate and safe ranges of intake for nutrients.” To meet this objective, the plan explicitly recognizes the need to acquire “information about the effects of foods and nutritional adequacy on behavior and performance.”
Within ARS, the Grand Forks Human Nutrition Research Center, in North Dakota, has been a leader in studying the effects of nutrition on brain function and behavior in both humans and animals for more than a decade. The human nutrition research centers located in San Francisco, CA, Boston, MA, Beltsville, MD, and Houston, TX, have also conducted studies in this area.
The need for broad institutional support is clear because this research is truly multidisciplinary, drawing heavily from the fields of biochemistry, physiology, neuroscience, psychology, and medicine, and, less frequently, from epidemiology, sociology, and anthropology. Technological and analytical advances have further involved the fields of biotechnology, computer science, and multivariate statistics. Coordinating and integrating the activities of scientists from these diverse fields is a significant challenge and key to successful research on nutrition, brain function, and behavior.
Important Issues To Consider
Several considerations are common to most studies of nutrition, including those on brain function and behavior. Inadequate dietary intakes result in deficiency states that occur by degree, ranging from suboptimal to marginal to severe. By definition, a severe clinical deficiency in any essential nutrient is going to have profound effects, particularly during periods of early development. However, cases of marginal or subclinical deficiencies are far more common (at least in the United States) and thus probably merit greater attention by researchers and a larger share of experimental resources.
Optimal intakes for all nutrients are difficult to determine and have not yet been established. This issue of optimal intakes is particularly important to the study of brain function and behavior, and interest arises in part from the increasing emphasis of medical and allied professionals on promoting health rather than treating illness and in part from the belief that brain function and behavior within the normal range can and should be improved.
The choice of an animal or human model is important. Animal studies permit greater control over genetic and environmental variation, assessment of effects over an entire life span and even across generations, and extensive analysis of brain chemistry and anatomy. They can also be useful in assessing brain physiology, mental processes, and some emotional responses, such as anxiety. However, there are often significant differences between humans and animals in nutrient metabolism; human brain function and cognition are considerably more complex, and the behavioral repertoire of humans, including speech, greatly exceeds that found in animals. Thus, the ability to generalize findings from animal studies to humans is limited and many aspects of function simply cannot be studied in animals.
Even within a healthy population, nutritional effects on brain function and behavior must be studied separately in numerous distinct groups. These groups may be defined by characteristics such as age, sex, body composition, exercise, stress, and dietary choices including consumption of vegetarian and other restricted diets, caffeine, and alcohol. The overwhelming majority of existing studies on nutrition, brain function, and behavior were conducted on children.
The diet contains both nutrients and non-nutrients. Examples of the latter are preservatives, artificial sweeteners, and substances like caffeine and alcohol. Studies that assess the effects of excessive amounts of either nutrients or non nutrients may be considered toxicological rather than nutritional in nature. When nutrient intakes are manipulated by supplementation, amounts can be at either physiologic (appropriate to the body’s normal functioning) or pharmacologic amounts. Although pharmacologic or therapeutic amounts may be required for a brief period to remedy a severe deficiency, they are in excess of amounts that can be reasonably acquired from the typical diet.
Methods of Assessment
In experimental studies, nutrient intakes are manipulated, selected responses are measured, and other potential factors are controlled. Intakes may be modified in an acute or chronic fashion. Single-meal and short-term (weeks) supplement studies exemplify acute modifications, while long-term (months) supplement studies are examples of chronic approaches. In correlational studies, nutritional intakes and status and response variables are measured and statistically interrelated. Because intakes and thus status are not under experimental control in these studies, other factors that naturally change with intake and status may confound results and make them uninterpretable. It is essential, therefore, that experimental studies be used in nutrition research on brain function and behavior.
Nutritional status is determined by biochemical assay of biological samples (blood, urine, feces, menses, sweat, and hair) to validate the effectiveness of manipulating nutrient intakes via the diet or supplementation. In correlational studies, an estimate of intakes can be made using diaries of food consumption or recall and, along with nutritional status, serve as a predictor variable.
Brain function is assessed biochemically, physiologically, and behaviorally. Biochemical assays of blood and urine for carbohydrates, proteins, amino acids, and neurotransmitter precursors and metabolites provide indices of changes in brain biochemistry relevant to nutritional intake and status.
The electrical activity of the brain is measured by using the electroencephalogram (EEG) under conditions of rest (the subject is given no explicit task demands) and while the subject is engaged in some mental activity, such as counting backward by 7’s. EEG data are long-latency responses of the brain (greater than 1 second) and provide a measure of background rhythmic activity at rest and during task performance.
Brain electrical activity is also measured in response to auditory, visual, and somatosensory stimulation. Data collected in response to sensory stimulation are short-latency responses (less than 1 second), referred to as evoked or event-related potentials (EPs), and they index how rapidly the central nervous system responds to information-processing demands. If the subject is instructed to respond (press a button) to some stimuli but not others, the EPs index the subject’s expectation, decisionmaking, and response preparation.
Behavior is assessed by measuring accuracy and response times during performance of cognitive tasks. Cognition is simply the collection of psychological processes involved in sensing, attending to, perceiving (attributing meaning), encoding, and retrieving information and using that information to solve problems, make decisions, and execute controlled responses. Cognitive processes occur in the context of and are affected by emotional or mood states, which are themselves the result of a complex interaction between physiological activation and cognitive appraisal. Although performing any activity involves most, if not all, cognitive processes, a well-designed task with multiple stimulus or response conditions or both can emphasize a single process. Different cognitive processes are associated with different patterns of electrical activity and with different regions of the brain. Therefore, performance on cognitive tasks indirectly assesses brain function while providing a direct assessment of behavior relevant to real-world activities.
Because of their subjective nature, mood states such as anger, anxiety, confusion, depression, fatigue, and sleepiness are assessed by using self-report measures. Questionnaires and tests are also used to assess nutritional effects on stress, intellectual achievement, and social behavior. However, social behavior is most commonly measured by observing and recording the frequency, quality, and intensity of contact with others.
Highlights From Human Studies
Studies of severe protein-calorie malnutrition in children have a long history and are by far the most common of any nutritional studies. They have reliably found that malnourished children have abnormal EEG’s, reduced activity levels, and impaired attention. A variety of other behavioral consequences have been frequently, but not consistently, reported, including impaired or delayed mental (particularly verbal) and motor development, impaired intersensory integration, reduced academic performance, increased crying in infancy, hyperactivity, apathy, withdrawal, and impaired social skills. With rare exceptions, however, these studies were correlational in design such that brain and behavioral effects were confounded by an impaired interaction of the child with his or her social and physical environment.
An ongoing series of experimental studies has repeatedly shown that eating a high-carbohydrate, low-protein meal on an empty stomach increases the relative availability of the amino acid tryptophan, and promotes synthesis of the neurotransmitter serotonin. Under these conditions, several behavioral effects have been consistently observed: impaired attention and slowed reaction times, increased fatigue and sleepiness, and reduced pain sensitivity.
Severe deficiencies in several B vitamins have profound effects for brain function and behavior, including abnormal EEG’s, impaired memory, anxiety, confusion, irritability, and depression. Subclinical deficiencies in thiamin (B1), riboflavin (B2), niacin (B3), pyridoxine (B6), cobalamin (B12), and folic acid are also commonly found in elderly and psychiatric populations. However, experimental studies have not been done to determine the involvement of individual vitamins in memory processes or in thought and affective (emotional) disorders. Experimental pyridoxine and vitamin E deficiencies produce abnormal brain electrical activity in humans and animals, and vitamin C supplementation in rather large doses (1-2 grams per day) seems to influence brain activity, although in varying ways.
The relationship of iron to brain function and behavior has received considerable attention, particularly in children. Iron deficiency reliably results in impaired attention and learning, hyperactivity, and apathy, which are consistent with findings of reduced dopamine (a brain neurotransmitter) in iron-deficient animals. In several studies with young adults, iron intake and status were related to EEG and EP responses and to performance on tasks assessing short-term memory; the findings indicate that low levels of iron result in reduced alertness and impaired memory.
Supplementation and correlational studies have found increased brain and behavioral excitability with low zinc intakes and status. Subclinical experimental magnesium depletion was also found to increase brain electrical activity. Nutritional copper deficiency reduces brain excitability, consistent with reported reductions in several neurotransmitters in copper-deficient animals. Behaviorally, calcium supplementation has been related to relief of pain during menstruation.
Boron, a mineral not yet recognized as essential for humans, has shown effects on brain electrical activity and cognitive performance in several studies with older adults. When compared with higher boron intakes, EEG changes noted with low boron intake were in the direction of those found with other forms of malnutrition. Low boron intake also increased reaction times on attention, perception, memory, and motor tasks.
These highlights do not fully represent the numerous and varied studies conducted on nutrition, brain function, and behavior in humans; however, they do represent the most consistent findings. Experimental studies with animals are even more numerous, and there has been no attempt to present the findings from studies of nutritional deficiencies during pregnancy and lactation, which have profound and often lasting effects on the developing nervous system. Likewise, space limitations do not permit presentation of findings from studies on food additives, including preservatives and sweeteners, or substances like caffeine and alcohol.
The complexity of research on nutrition, brain function, and behavior is evident, but so too is its potential to generate knowledge that has broad practical application and benefits. Future studies will no doubt identify new relationships and better characterize existing ones, while attempting to discover underlying mechanisms. Although the focus of early studies was on the effects of general malnutrition in children, future studies will more likely focus on specific nutrients and their effects on brain function and behavior in adults. Experimental (in contrast with correlational) studies offer the best hope of distinguishing nutritional from nonnutritional effects on these critical aspects of function.
It is also highly probable that future research will attempt to identify nutrient intakes that will result in optimal performance (psychonutrition). To be sure, one challenge for researchers in this area will be to present findings in a manner that tempers the public’s tendency to uncritically embrace new findings before they are replicated and refined and to overgeneralize highly specific findings obtained under the controlled conditions of the laboratory.