Food and Mood: Evaluating the Role of High-Fat Food in Causing Depression

A healthy body is a healthy mind. Did you know that your favorite fast-foods can get you depressed? Current studies have established a link between the type of food consumed and the mood of an individual [1,2]. One of the severe mood disorders influenced by diet is depression which is defined as a “persistent feeling of sadness and loss of interest” according to NCBI [3]. It has been implicated that depression arises due to a disturbance in the activity of a chemical substance called “serotonin” [3]. This is also more commonly known as the “happy chemical [4]”. So, the food you call “comfort food” is actually not so comforting. It is important to note that there might be a bidirectional link between diet and depression that has not been completely evaluated [5]. However, currently, studies suggest that a high-fat diet including high amounts of red meat, processed or refined food and sweets, along with a low intake of fruits and vegetables can cause increased risk of depression [6]. Whereas eating foods like fruits and vegetables, seeds and nuts, lean protein and yogurt is considered healthy and is associated with a lower risk of depression [6]. 

High-fat diet causes inflammation

Human studies: 

Various studies performed across different populations of the world have shown that high-fat diet causes increased risk of “systemic inflammation” which means an overall inflammation in the body resulting from chemical messengers that can cause unfavorable changes. Hence, some of our favorite foods such as cup noodles, French fries or burgers are classified as inflammatory foods [7]. Studies have shown that such a ‘pro-inflammatory’ diet leads to increased risk of depression especially in people who are over-weight or obese [8]. This establishes a clear link between the type of diet and depression. Another important link between diet and depression was established by two trials where the participants were asked to stick to a healthy Mediterranean diet full of fruits, vegetables and whole grains. It was observed that when the participants ate healthy and reduced their intake of high-fat food, the depressive symptoms were reduced by 1.68-fold [9]. 

Rodent models: 

There are plenty of studies performed in rats and mice to examine the effect of diet on depression. For instance, two studies performed by Yang, Hassan and their colleagues show that a high-fat diet is associated with a depressive phenotype in mice [10, 11]. However, one major problem with these studies is that the type of ‘high-fat diet’ they use varies from study to study [12]. This makes the results slightly unreliable as there is no standardization of the procedure [12]. Even though the protocols are different, the effect of high amount of fat in the diet remains the same throughout all studies. The studies performed by these researchers show that this observed depression might be a result of changes in inflammatory processes induced by diet. Some of these processes link saturated fatty acids to brain inflammation and some link it to the changes in microbiota ultimately causing mood disorders [13].

Saturated fatty acids and brain inflammation

Saturated fats are classified as the ‘bad kind of fats’ and are obtained from foods like cakes, butter, oil, cheese etc. [13]. Some studies show that these saturated fatty acids can activate a particular protein in the brain called the “Toll-like receptor 4” and cause release of certain chemicals called cytokines which cause inflammation in the brain [14]. Some other studies describe the importance of a brain region called ‘hippocampus’ which is very sensitive to changes in these cytokine levels. They show that long term exposure of mice to high fat diet causes alteration in the cytokine levels leading to memory defects, cognitive impairments and depression [10]. One of the studies also describes the role of a molecule called “Tetrahydrobiopterin or BH4” which plays a major role in formation of dopamine which is our ‘motivation chemical’. Brain inflammation leads to formation of harmful substances called “reactive oxygen species” which can inactivate BH4 and hence hinder the production of dopamine and even serotonin to some extent [15].

These effects don’t exist just in rodents, in fact, when some studies examined post-mortem tissues from patients with depression, they found similar evidence suggesting that these fatty acids might be responsible for altered brain function and mood disorders [16]. 

Gut microbes and mood disorders

The gut of a human consists of trillions of microorganisms which form a complex ecosystem that’s unique to each and every human [17]. This is called the gut microbiome, the composition of which is most easily modifiable and influenced by diet [17]. 

The microbes in the gut relay various types of signals to the brain via a connection known as the “gut-brain axis” [18]. This communication is bidirectional and involves various other systems of the body [18]. These microbes can affect the brain through the vagus nerve which is responsible for relaying signals of hunger and satiety or even through altering the nutrient availability in the gut [19, 20]. Certain bacteria can influence the gut-brain axis through their metabolites which possess the ability to act as hormones and through the ability to modulate the immune pathways [21].  Hence, the type of diet modulates the gut microbiome which in turn modulates mood and behavior in an individual. 

Daniel and his colleagues used mouse models to show that a high fat diet causes the whole microbiome ecosystem to shift [22]. Various populations of microbes affect the gut-brain axis differently. Hassan and his colleagues showed that the mice that presented with depressive symptoms had a reduced population of Bacteriodetes and increased population of Firmicutes and Cyanobacteria as compared to normal control mice [23]. In support of this, Zhang and his colleagues showed that when the fecal microbiota from patients with depression was transplanted into normal mice, the mice started showing depression like symptoms as well [24]. This proved that the microbiome plays an important role in mood disorders like depression. 

Apart from these, there are various other factors influenced by high fat diet causing changes in the mood of an individual. For instance, some studies have also established a link between insulin and dopamine where the mice who ate a high fat diet had an impaired insulin signaling in the brain which in turn also reduced dopamine signaling in the brain causing a depression [25]. On the other hand, some studies have also discussed the importance of “anti-oxidative nutrients” which are nutrients that can reduce or prevent harmful oxidative reactions that may otherwise cause inflammation [26].

Nutrients and depression

It has been reported that the intake of antioxidants is lower in people with depression as they consume lower amounts of “healthy food” [27]. Studies have evaluated the role of antioxidative nutrients such as folic acid or vitamin B9 and vitamin B12 in mediating depression. One of the studies performed by Gilbody and colleagues found that lower levels of vitamin B9 were associated to a higher risk of depression [28]. Moreover, some other studies also found that lower levels of vitamin B12 were also associated to increased risk of depression [29]. It has been proposed that low levels of these vitamins cause increased levels of a molecule called “homocysteine” which is considered toxic and can increase oxidative reactions further damaging the DNA. There are some studies that found no correlation between lower levels of B9 and depression but found a strong correlation between lower B12 levels and depression [30]. However, as vitamin B9 and B12 are closely related and are a part of the same family of vitamins, B9 supplements have been used as a means to treat depression for a long time [31].  

This brings to the conclusion that diet plays a major role in influencing our mind. Depression, although being common, is a disorder that should be taken seriously as it has affected about 264 million people of all ages in the world [32]. Although there are various factors other than diet influencing this disorder, food is something that we eat every day. Hence, making changes to our diet can play a major role in modulating the mood disorders. Moreover, at least 30% of the people with depression do not respond to anti-depression therapies [33]. This makes dietary changes a potential target for treating or reversing mood disorders. 

However, we know that a specific diet causes specific changes but we still have to know the complete mechanism of action by which food causes these changes in the brain. This way, we can combine dietary intervention with pharmacological treatments to manage such disorders. For the time being, you might want to make the hard decision of choosing salad over pizza and fruits over fries. 

References: 

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