While nearly 45 million Americans will attempt to follow some sort of diet each year, most will not experience long-term benefits and weight loss [12
]. Many factors impact obesity including genetics, socioeconomic status, and behavioral and environmental issues. There are still, however, ways to help prevent obesity and the resulting chronic diseases. It is important to start preventative measures at a young age in order that children not develop into obese adults. The most effective ways to prevent obesity are decreased daily caloric intake, increased exercise, and appetite suppression medications; however, the most effective method may come from a combination of the three.
Decreasing daily caloric intake can be done many different ways. Portion control is a very effective way to decrease caloric intake. By reducing the portion size, you automatically reduce the number of calories you consume. Smaller portions and frequent snacking can also help to avoid over eating. Also, by choosing lower caloric foods and beverages than higher ones, overall caloric intake is also decreased. Drinking water is another great way to help promote satiety since it does not contain any calories.
Appetite suppressants have recently been found helpful to jumpstart weight loss and some have been shown to be a safe method of weight loss by health professionals [13
]. Such suppressants work through the glands of the hypothalamus, which leads to a suppressed appetite, thereby leading to lower food consumption and ultimately weight loss [14
]. “Appetite” as defined by the Miller-Keane Encyclopedia and Dictionary of Medicine, is “the psychological desire for food.” Since appetite is a psychological factor, suppressant medications such as Phenylpropanolamine, Phentermine and Diethylpropion have been the most effective [14
]. Obesity is often linked to over eating due to feelings of stress, anxiety, and sadness. By controlling these psychological feelings, appetite can be controlled. Suppressant medications are most effective when combined with a diet and exercise program under the supervision of a physician. Appetite suppressants can have mild side effects such as thirst, fatigue, and irritability. Rarely, people experience more severe side effects including cardiac arrhythmias, cerebral arthritis, and cerebral hemorrhage, which can ultimately lead to death.
Severe side effects such as those listed above are often a major deterrent to taking a medication. Recently a new phenomenon of “prescription medical foods” has emerged. According to the FDA, a medical food is defined as "a food which is formulated to be consumed or administered enterally under the supervision of a physician and which is intended for the specific dietary management of a disease or condition for which distinctive nutritional requirements, based on recognized scientific principles, are established by medical evaluation." People with chronic diseases have different nutritional needs than those without them. If these needs, such as neurotransmitter deficiencies, are not addressed, then oftentimes the overall health issue cannot be resolved.
Neurotransmitters control appetite, satiety, and carbohydrate cravings. It has been observed that obese patients have an increased need for these transmitters and neurotransmitter levels are often found to be depleted in these patients [16
]. Thus, by increasing the amount and efficient turnover of neurotransmitter precursors, it is possible to increase the concentration and function of neurotransmitters, which as a result might help control obesity.
There are several amino acid precursors that produce the neurotransmitters that control appetite and satiety. Histidine functions as the amino acid precursor to the excitatory neurotransmitter and anorexigenic agent, histamine [8
]. Histamine is an important regulator of food intake and body weight. This neurotransmitter functions in the posterior hypothalamus by stimulating effects on the central nervous system. During the appetite phase, histamine works by suppressing appetite by stimulating Corticotropin-Releasing Hormone (CRH) and Corticotropin-Releasing Factor (CRF), both of which limit the production of Neuropeptide Y (NPY). By inhibiting NPY, an energy regulator, increased food take is reduced and physical activity levels are increased. Thus by increasing the amount of histamine produced, there is an overall decrease in food intake.
Glutamate is an excitatory neurotransmitter that has been shown to have effects on appetite. Increased intake of glutamate leads to stimulation of brain nuclei that help to control appetite [17
]. On the other hand, low levels of glutamate have been connected with imbalances of serotonin levels, another neurotransmitter that affects appetite.
Tryptophan functions as the neurotransmitter precursor for serotonin, an excitatory neurotransmitter that helps suppress appetite. Many obese patients have lower levels of serotonin than non-obese patients [18
]. As a result, obese patients experience carbohydrate cravings and increased appetite. Another factor that influences serotonin levels is protein. For patients on a low calorie diet, if protein intake is also significantly decreased, a serotonin deficiency can arise. A serotonin deficiency as a result of low protein levels can occur because low protein levels limit the amount of tryptophan available for serotonin synthesis.
Tyrosine is the neurotransmitter precursor for the neurotransmitters norepinephrine and epinephrine
, both of which function as appetite suppressants [18
]. With a greater amount of tyrosine available the production of dopamine and norepinephrine are quicker. In addition, norepinephrine helps increase serotonin levels by increasing the tryptophan uptake by the brain, which as previously stated helps to suppress appetite. Lower norepinephrine levels have been reported in obese individuals.
Choline serves as the precursor to the both inhibitory and excitatory neurotransmitter, Acetylcholine, the main neurotransmitter of the autonomic nervous system. Acetylcholine regulates insulin
and glucose levels in the blood. Additionally, Acetylcholine is involved in food intake by controlling activity in the sympathetic nervous system [19
]. One way it does this is by binding to receptors on postganglionic neurons, which triggers the release of norepinephrine. This in turn activates the sympathetic nervous system, which might be one way to explain the increase in leptin, the hormone which regulates energy intake and expenditure.
Lastly, L-serine activates the neurotransmitter D-serine, which is the precursor for the production of a few amino acids, including tryptophan. Ultimately, the production of serine is vitally important to the production of serotonin and appetite suppression [20
Medical foods and the treatment of obesity focus on treating the dietary deficiencies that is present in a disease state by correcting neurotransmitter deficiencies and restoring the homeostatic mechanisms that work to control appetite. By controlling appetite, satiety is increased, leading to decreased caloric intake. This may be achieved by providing the neurotransmitter precursors which have been noted to be involved in the neural pathway that controls appetite, specifically tyrosine, tryptophan, choline, glutamate and histidine.
Recent research has noted nutritional deficiencies in obese patients requiring more amino acids and minerals than are obtained in a normal daily diet [21
]. The systemic supplementation of certain amino acids may facilitate the regulation of the obese patient’s appetite. Flavonoids may also have therapeutic benefits, as they are found in all vascular plants, and are responsible for some of the health benefits associated with naturally brightly colored foods.
As previously discussed, neurotransmitters are intimately involved in the feedback mechanisms that regulate appetite and satiety and subsequently body weight. These neurotransmitters are made of amino acids precursors. Some of the amino acids are non-essential and some are essential, meaning the essential amino acids must be derived from our diet. When there is a depletion of these key amino acids the result is often times insatiable cravings. The most common cravings are for sugars, sweets and carbohydrates. One recent study demonstrated that supplementation with glutamine reduced sugar cravings and resulted in a loss of body fat [22
] therefore, firmly establishing glutamate as a primary neurotransmitter that mediates body weight regulation.
If there is an imbalance of these neurotransmitters there will be a disruption in weight, appetite and satiety. Imbalances in neurotransmitters may occur for several reasons such as genetics, metabolic disorders, nutritional deficiency, digestive imbalances or medication use. It has also been noted that obese individuals had fewer neurotransmitter for certain receptors than normal weight subjects [23
]. The lack of receptors may also play a role in the disruption of signaling that is present in obese individuals.
It is often an imbalance of serotonin and catecholamine, which include dopamine, norepinephine and epinephrine that can cause inappropriate hunger, cravings and binging behavior. Interestingly, these amino acids levels are low in obese individuals despite excessive calorie intake and could not be corrected with administration of a protein rich supplementation. This nutrient deficiency points to a possible metabolic problem that is also present in obese populations [24
When normal serotonin levels are present, satiety normally occurs. A serotonin deficiency has been associated with carbohydrate binging that result in weight gain. As serotonin is derived from tryptophan, low blood levels of tryptophan have been found in obese individuals, which indicate that their overeating patterns may be related to a serotonin deficiency [25
These findings illustrate that the cause and treatment of obesity is a complex matter. Further understanding of the amino acid deficiencies and the metabolic pathways are keys to understanding the treatment of the distinct nutritional needs that are present in obese subjects.