It’s great when you notice that your education follows a somewhat coherent trajectory. It’s great when you get to disprove things you once thought were true. It’s great when you look back at your work and realize that you’ve improved your writing skills. At the moment, I’m looking further into the relationship between omega-3 fatty acids and depression, something that I thought in the past was established to be inversely connected (i.e. please do eat your nuts and flax seeds; fish are friends, not food). While there does exist evidence in support of this, there are also studies that show no connection whatsoever, which underlines the importance of not being biased when you conduct your literature searches (search omega-3 PUFAs and depression rather than omega-3 PUFAs depression treatment/improves depressive state/etc)! Seems obvious perhaps, but when you’re pressed for time in writing a paper and don’t have time to properly do the research for sources, it’s an easy trap to fall into.
Anyway, being in the process of conducting a meta-analysis on the topic of omega-3 and depression reminded me of a paper I wrote about a year ago (which I copy-pasted below for your amusement). As I re-read it there were so many question marks popping into my head; what’s the purpose? What are you doing? Where’s the coherence? Focus! FOCUS! A friend dubbed it the save-the-world syndrome. One of the best things I’ve learned in school must be the ability to better restrict myself in terms of work, and to focus on the question at hand. It’s difficult though, there are so many interesting things to research and learn about.
I’m procrastinating… Peace out.
From belly to brain:
The Neuroscience of Nutrition
Contents | 2 Introduction
3 1. Systems and services
4 1.2 The enteric nervous system
5 1.3 Peptides and proteins
6 2. Dysfunctions and gut related treatments
7 2.2 The role of nutrition
7 2.3 The example of omega-3
8 Conclusion and discussion
Introduction | The requirement of having access to ample nutrition and energy is one that we humans share with all other animals. Because it is such a vital need in order for us to keep our bodies functioning, the regulation of our behaviors regarding food intake and metabolism involves many physiological mechanisms, including some that are related to the mere anticipation of future needs (Breedlove et al., 2010).
That the food we consume directly affects our physical and mental well-being is easily observed; one only needs to think of the effects that more or less appreciated smells and flavors induce in us. An extreme example of a long-term imbalance in this system is the problem of obesity, where affected individuals seemingly cannot regulate their food intake, even though it can be assumed that the majority of those individuals do not find obesity to be a preferrable state. There seems to be some degree of automaticity involved in their behavior of consumption; an imbalance between the estimated magnitude of a particular reward and the genuine feeling that follows from obtaining it, which may lead to unwanted effects that stretch further than the acquisition of excess weight. For instance, obesity is linked to diabetes, heart disease, and cancer (Volkow et al, 2011), to name a few, as well as an impaired social life (Lewis et al., 2011). This, in turn, can be suspected to exacerbate the problem of overeating, as social interaction is tightly wound to positive emotions relating to the gut, and vice versa; social withdrawal is related to negative gut feelings and emotional states (Mayer, 2011).
The ways through which the viscera and the encephalon communicates are complex as well as extensive, and the problem of obesity is merely one result out of many that can arise from various disturbances of this system, or the development thereof. While the social aspect further complicates the topic, and is more difficult to measure than physiological responses, it can be stated that we live in a world of abundance yet employ an attitude of lack. This, in combination with corporate financial interests, has caused something that was once beneficial to us in an evolutionary sense (a heightened sensitivity to particular foods) to become a major responsibility for public health (Volkow et al., 2011).
Fortunately, food is not only guilty of causing ill health, but is increasingly recognized as an easily modifiable factor that can protect against diseases, both physical and mental, throughout the life cycle. Considering the great financial, social, and personal costs that are associated with sub-optimal health, there is a need to elucidate the ways in which nutrition can be used in treatment as well as prevention. This review will explore the dynamics between a selection of internal processes related to nutrition and their corresponding influences on health, and combine these findings with thoughts on how we can use this knowledge in a beneficial way.
1. Systems and services
As the gut- and brain activity that are involved in our feeding behaviors are under autonomic regulation, we cannot excert voluntary control over these matters in the same fashion as we can concerning movement (Breedlove et al., 2010). However, through learning about the ways in which these systems work, it could in many cases be possible to produce desirable effects by prospectively planning what inputs we deliver to the relevant systems. Such a topdown approach could have far reaching effects; for example, if the altered innervation of a specific region in the gut causes some emotion to arise, then the responses that are consequently sent from the brain can also be expected to change. If the stimulus is applied for a certain duration of time, or at a certain level of intensity, then this could possibly induce permanent changes in synaptic activity (Mayer, 2011).
1.2 The enteric nervous system
Many emotional states and their associated physiological responses are influenced by the nerves in our gut; examples of this can be found in the expression “to make decisions based on gut feelings”, and in the tickling feeling of “having butterflies in one’s stomach” when nervous or stressed. Scientific theories concerning visceral involvement in emotional states were being developed already at the end of the nineteenth century, by William James and Carl G. Lange (Breedlove et al., 2010).
The enteric nervous system (ENS) – the branch of the autonomic nervous system that resides in our gut – has sometimes been referred to as the “second brain”, owing to its similarity to the brain in terms of complexity and use of specific transmittor molecules (Mayer, 2011). The ENS may contain as many as 600 million neurons, which is not so surprising considering that its area of concern (the intestinal surface area, from the esophagus to the end) has a surface span about 100 times as greater as that of the skin, and contains an unfathomable number of microorganisms (roughly 100 trillion – about ten times the number of cells in the human body) from 40,000 species (Kurokawa et al., 2007). Furthermore, considering the brain’s great need for energy relative to the rest of the body, it seems logical for the processes involved in this to be extensive, and to some extent even redundant (Gomez-Pinilla, 2008).
The gut and the brain communicates via several parallel pathways that are innervated subcortically mainly by the amygdala and the hypothalamus, which in turn are subject to stimulation from the medial prefrontal cortex (PFC), and the anterior cingulate cortex (ACC); areas that also are involved in reward processing (Volkow et al., 2011). Many projections between these areas and the intestines are part of the vagal complex, which, among other effects, mediates the release of serotonin (5-HT), and responds to feelings of hunger and satiety by means of various peptides (Mayer, 2011). This information is then conveyed to the hypothalamic system for integration.
1.3 Peptides and proteins
In addition to influencing our feeding behavior to preserve homeostasis through feelings of reward and satiation (for example by acting on dopaminergic pathways), multiple neuropeptides have been found to possess the capacity to stimulate mechanisms relating to cognition, such as synaptic plasticity and learning (Gomez-Pinilla, 2008; Mayer, 2011; Volkow et al., 2011).
Ghrelin is a hormone (peptide) that upon secretion by an empty stomach stimulates the appetite by binding to orexigenic (hunger inducing) receptors, and has also been found to be involved in the generation of rewarding feelings associated with food (Volkow et al., 2011). Orexin is another peptide that cause appetite to increase. It is released from the hypothalamus, and it has been suggested that leptin (discussed next) excerts a regulatory effect over this peptide (Breedlove et al., 2010).
Leptin, which is synthesized in fat tissue, has the opposite effect on appetite as that of ghrelin and orexin; it tells the brain to reduce appetite by binding to receptors in the hypothalamus, and might facilitate learning, as receptors have also been found in the hippocampus (Gomez-Pinilla, 2008).
Yet another hormone that binds to receptors at the hypothalamus, is insulin. It is secreted from the Islets of Langerhans when a meal is anticipated (referred to as the cephalic phase of insulin release; its release can be triggered by other factors as well), and is among other things crucial for the conversion of glucose into glycogen (Breedlove et al., 2010).
As it appears, metabolic and synaptic functions are closely tied together. A final example of this relationship to be mentioned here is the multiple signalling protein BDNF, or brain-derived neurotrophic factor, which excert effects on neurogenesis (both prenatal and adult), synaptic plasticity, insulin sensitivity, appetite regulation, and energy metabolism (Vaynman et al., 2006; Gomez-Pinilla, 2008). It is furthermore a crucial component of the processes involved in memory, learning, and cognition, and can affect cognitive function through metabolic signals. BDNF expression is influenced by for instance physical exercise, but is also elevated in the hypothalamus by leptin (Gomez-Pinilla, 2008).
2. Dysfunctions and gut related treatments
In 2005, it was reported that the two-year outcome of a 12 month long study of vagal nerve stimulation (VNS) in the treatment of depression was a twofold improvement in patients, compared to those who had received treatment as usual (TAU – medication and/or therapy). This alternative way of treating depression came about as it was observed that VNS in the treatment of epilepsy produced improvements in the patient’s mood (Gomez-Pinilla, 2008). While further research is needed to establish the precise mechanisms that underlie these improvements, it has been found that VNS causes an increase in BDNF levels; an effect that it shares with antidepressant treatments.
Findings such as these provide substance to the thought that our emotions are greatly influenced by signals that emanate from the gut. Furthermore, VNS might bear effects on higher forms of cognitive processing, as suggested by a separate study that reported recognition memory to be significantly enhanced following treatment (Clark et al., 1999).
2.2 The role of nutrition
What we choose to eat can affect both brain anatomy and physiology, as well as biochemistry. Gut hormones and other molecules, including those discussed earlier, are influenced by one’s energy levels and the nutrient content of the ingested food (Dauncey, 2012). While it is known that nutrition bears an effect on multiple levels of gene expression, there is still much to be discovered in the area, as the effects tend to vary between individuals. Nevertheless, some specific nutrients have been found to influence cognitive abilities, thus increasing the evidence in support of using dietary management as viable tactic to treat psychiatric disorders (Gomez-Pinilla, 2008).
2.3 The example of omega-3
A particularly important nutrient for brain development and function, that cannot be synthesized in the body and therefore is essential to obtain through one’s diet, is omega-3 (o-3) polyunsaturated fatty acids (De Souza et al., 2011). Deficits noticeably impairs signal transmission in the brain (as these lipids constitute the cell membranes and the ionic permeability thereof), and is associated with changes in learning and memory performance. The role of o-3 in memory formation is further reflected in how supplementation, in conjunction with exercise, amplifies BDNF-related effects on cognition as well as synaptic plasticity (Dauncey, 2012).
Furthermore, suboptimal levels of o-3 in humans can increase the risk of for instance ADHD, depression, schizophrenia, and bipolar disorder, and multiple studies have suggested that diets containing higher than desired levels of saturated fats and simple carbohydrates likewise have adverse effects on cognition (De Souza et al., 2011; Gomez-Pinilla, 2008). It has also been demonstrated that subliminal stimulation of the gut by means of fatty acids reduced the subject’s responses to experimentally induced sadness (Mayer, 2011). Findings such as these are worrisome considering the current composition of the standard western diet (which reflects an increase in the consumption of saturated fats, and a decrease in the consumption of o-3), which has already been suggested to be among the greatest threats to public health today (Cordain et al., 2005).
Conclusion and discussion | Despite that the scope of this review was only able to touch upon a fraction of the mechanisms involved in the interplay between the viscera and the brain, it is clear that we can significantly influence our mental states through our guts. The complex interaction between the two continues to be an exciting area for exploration, and increased knowledge about the precise mechanisms that are involved might found the basis of novel and accessible alternatives in the treatment of various diseases of the body and mind. For instance, a greater understanding of how our emotions and feeding behaviors are associated could contribute greatly in the combat against obesity and other cases where gut-based therapeutic interventions can be applied.
Future challenges also include a need to elucidate the effects of perinatal nutrition on brain development. Studies in this area would be likely to also investigate the effects of diet on epigenetics, as well as later influences on DNA expression, such as lifestyle.
Lastly, if changes in dietary habits are to have an enduring success, caution needs to be excerted when promoting them, in order for the findings to have a greater chance of being taken into permanent consideration rather than be classified as a transient trend. This will require cooperation from many stakeholders such as food producers and associated media. However, the latter is likely to pose as a challenge in itself; while good health makes a lot of sense, it does not make much money.
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