The causes of depression may vary as much as our individuality, yet we often fail to consider our eating habits as possible culprits. With each passing year's increased understanding of the biological complexities of the human animal, more data suggesting dietary factors are unveiled. The use of drugs such as SSRIs (selective serotonin re-uptake inhibitors) and herbal extracts such as St. John's Wort (1, 2, 3) and 5-hydroxytryptophan (4) to manipulate quantities of serotonin at the synapses within the brain has demonstrated that available serotonin beyond the blood brain barrier (BBB) is an important factor in alleviating depression for many people. The brand name of one such drug, Prozac, has become a household word in our North American culture. Protein, if consumed in excessive quantity, suppresses CNS serotonin levels. Carbohydrate intake, as well as alcohol and cocaine abuse increase levels initially, but if use is chronic, such use dramatically lowers CNS serotonin, resulting in depression, carbohydrate cravings, sleep disturbances, and proneness to argumentativeness, irritability. Violence can also be used to manipulate serotonin levels. Additionally, the morphine-like substances derived from the incomplete digests of dairy and cereal grain proteins are other dietary factors which may alter mood by depressing CNS serotonin, dopamine and norepinephrine levels (5). The reduced number of platelet receptors for serotonin found in patients with celiac disease, which is also caused, at least in part, by dietary factors, again points to food as a factor in some cases of depression. Such a propensity for depression, as is now seen in our modern world, seems to run counter to the process of natural selection. It is of more than passing interest that many of the foods which seem to be implicated in depression are also foods which Humanity has had only a relatively short time, on the evolutionary calendar, to adapt to (6). And we have been consuming more and more of these new foods during this century.
Regardless of the causes of the high frequency of depression in our contemporary world, we now have fairly effective drugs to treat this condition. One such group of drugs, SSRIs, act to reduce the rate of re-uptake of serotonin at the synapses, working to conserve serotonin and increase its synaptic concentration for longer periods of time. Serotonin is an important neurotransmitter which is needed for sleep onset, mood regulation, carbohydrate craving and consumption, and a host of other functions (7). But there are other means to manipulate its presence in the brain. If we have recently digested protein, resulting in an increased level of large neutral amino acids (LNAA) in the blood stream, and we subsequently eat enough carbohydrate to induce a significant rise of circulating insulin, most of these amino acids will be transported across cell walls, for storage or energy. Due to tryptophan's resistance to insulin, this will result in an increase of circulating tryptophan. Since LNAAs compete for transport across the BBB, and since its competitors have been reduced, the relative increase in tryptophan leads to increased quantities of tryptophan being moved into the brain. Since the BBB is the primary limiting factor in conversion of tryptophan to serotonin, this results in increased levels of serotonin within the brain (8).
Since such manipulations of serotonin are difficult to regulate, and unlikely to have long-lasting effects (although some of the mystery of obesity may be revealed in this dynamic) a much more important dietary factor in depression may be the morphine-like substances which derive from the incomplete digests of proteins in cereal grains and dairy products. These were first reported by Christine Zioudrou et al. who dubbed such peptides "exorphins" (9). Further elucidation of this issue has been provided through the extensive work of Fukudome and Yoshikawa, published over the last decade (10,11) who have identified and characterized five distinct exorphins in the pepsin digests of gluten. Eight distinct exorphins have also been identified in the pepsin digests of milk (12). This work has given us a clearer sense of the morphine-like psychoactive nature of the peptides which result from the incomplete digests of these dietary proteins, as well as offering a possible explanation for some of the reported psychiatric reactions to these proteins (13,14,15) including the sense of "brain fog" that often accompanies immune reactions to these foods.