henry copeland:

How to increase serotonin in the human brain without drugs

Relatively few generations ago, most of the world population was involved in agriculture and was outdoors for much of the day. This would have resulted in high levels of bright light exposure even in winter. Even on a cloudy day, the light outside can be greater than 1000 lux, a level never normally achieved indoors. In a recent study carried out at around latitude 45° N, daily exposure to light greater than 1000 lux averaged about 30 minutes in winter and only about 90 minutes in summer50 among people working at least 30 hours weekly; weekends were included. In this group, summer bright light exposure was probably considerably less than the winter exposure of our agricultural ancestors. We may be living in a bright light–deprived society. A large literature that is beyond the scope of this editorial exists on the beneficial effect of bright light exposure in healthy individuals. Lamps designed for the treatment of seasonal affective disorder, which provide more lux than is ever achieved by normal indoor lighting, are readily available, although incorporating their use into a daily routine may be a challenge for some. However, other strategies, both personal and institutional, exist. “Light cafes” pioneered in Scandinavia have come to the United Kingdom,51 and an Austrian village that receives no sunshine in the winter because of its surrounding mountains is building a series of giant mirrors to reflect sunlight into the valley.52 Better use of daylight in buildings is an issue that architects are increasingly aware of. Working indoors does not have to be associated with suboptimal exposure to bright light. A third strategy that may raise brain serotonin is exercise. A comprehensive review of the relation between exercise and mood concluded that antidepressant and anxiolytic effects have been clearly demonstrated.53 In the United Kingdom the National Institute for Health and Clinical Excellence, which works on behalf of the National Health Service and makes recommendations on treatments according to the best available evidence, has published a guide on the treatment of depression.54 The guide recommends treating mild clinical depression with various strategies, including exercise rather than antidepressants, because the risk–benefit ratio is poor for antidepressant use in patients with mild depression. Exercise improves mood in subclinical populations as well as in patients. The most consistent effect is seen when regular exercisers undertake aerobic exercise at a level with which they are familiar.53 However, some skepticism remains about the antidepressant effect of exercise, and the National Institute of Mental Health in the United States is currently funding a clinical trial of the antidepressant effect of exercise that is designed to overcome sources of potential bias and threats to internal and external validity that have limited previous research.55 Several lines of research suggest that exercise increases brain serotonin function in the human brain. Post and colleagues56 measured biogenic amine metabolites in cerebrospinal fluid (CSF) of patients with depression before and after they increased their physical activity to simulate mania. Physical activity increased 5-HIAA, but it is not clear that this was due to increased serotonin turnover or to mixing of CSF from higher regions, which contain higher levels of 5-HIAA, with lumbar CSF (or to a combination of both mechanisms). Nonetheless, this finding stimulated many animal studies on the effects of exercise. For example, Chaouloff and colleagues57 showed that exercise increased tryptophan and 5-HIAA in rat ventricles. More recent studies using intracerebral dialysis have shown that exercise increases extracellular serotonin and 5-HIAA in various brain areas, including the hippocampus and cortex (for example, see58–60). Two different mechanisms may be involved in this effect. As reviewed by Jacobs and Fornal,61 motor activity increases the firing rates of serotonin neurons, and this results in increased release and synthesis of serotonin.62 In addition, there is an increase in the brain of the serotonin precursor tryptophan that persists after exercise.63 The largest body of work in humans looking at the effect of exercise on tryptophan availability to the brain is concerned with the hypothesis that fatigue during exercise is associated with elevated brain tryptophan and serotonin synthesis. A large body of evidence supports the idea that exercise, including exercise to fatigue, is associated with an increase in plasma tryptophan and a decrease in the plasma level of the branched chain amino acids (BCAAs) leucine, isoleucine and valine (see64,65 for reviews). The BCAAs inhibit tryptophan transport into the brain.66 Because of the increase in plasma tryptophan and decrease in BCAA, there is a substantial increase in tryptophan availability to the brain. Tryptophan is an effective mild hypnotic,67 a fact that stimulated the hypothesis that it may be involved in fatigue. A full discussion of this topic is not within the scope of this editorial; however, it is notable that several clinical trials of BCAA investigated whether it was possible to counter fatigue by lowering brain tryptophan, with results that provided little support for the hypothesis. Further, exercise results in an increase in the plasma ratio of tryptophan to the BCAAs before the onset of fatigue.64,65 The conclusion of these studies is that, in humans, a rise in precursor availability should increase serotonin synthesis during and after exercise and that this is not related to fatigue, although it may be related to improved mood. Whether motor activity increases the firing rate of serotonin neurons in humans, as in animals, is not known. However, it is clear that aerobic exercise can improve mood.
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