Mediterranean Diet and Its Impact on Mental Health

Introduction

Mental health refers to an individual’s emotional, social and psychological well-being (1). The importance of mental health is constantly being highlighted in the media and people are beginning to be more open when talking about their mental health. Due to this, research into the aetiology of the disease is progressing. It’s found that food contributes strongly to mental health, with a 2014 discovery finding that increasing the amount of fruit and vegetables you eat can increase your overall well-being (2). This essay will focus on how the nutrients in the different foods we eat can affect mental health, and whether the Mediterranean diet is the most beneficial for getting these nutrients.

Over time, western diets have migrated towards foods that are dense in calories and packed full of concentrated fats and sugars. In past times, evolutionary biologists believe that sugar and fat cravings are due to humans wanting to get as many calories as they can in uncertain environments (3). Now that these conditions are no longer around for the majority of people in the western world, these high-calorie foods are often overeaten leading to many obesity-related problems, including mental health issues. The UK government has started to realise the risk to the population of high-calorie diets, and so has started to implement changes. For example, a sugar tax in 2018 helped decrease the UK consumption of sugar, reducing the rate of obesity. This consequently helped increase mental health in the UK population, as obesity (particularly severe obesity in females) has been strongly linked to depressive conditions (4). Sugar has been shown to increase inflammation in the body, with a 2014 study showing that when eating a 50-gram dose of fructose, the level of CRP in the body increases after 30 minutes and remains high for another 2 hours after that (5). In a 2019 review, it was shown that increased inflammation in the body (of which CRP is a marker of body inflammation), is associated with severe mental illnesses (6). In addition to the sugar tax, a more direct way that the government has recognised the importance of mental health, is that in the 10-year plan launched in early 2019 there will be a £2.3 billion increase in mental health funding per year by 2023/24 (7).

Nutrients are also thought to be very closely related to good mental health. These most beneficial ones are…

1. Polyunsaturated fats (omega 3)
2. Minerals (zinc, magnesium, iron)
3. Vitamins (folate, B vitamins, antioxidants).

Throughout the essay, I will mostly focus on the impact certain nutrients have on mental health conditions, whether the food included in the Mediterranean diet is best for this, and will discover if food timings have any effect on mental state.

Explaining the Mediterranean Diet

This is a diet that focuses on consuming large amounts of fresh fruit, vegetables, legumes, and fish with eating poultry, eggs, and yogurt in moderation. Red meat is very rarely eaten. Alcohol consumption is in moderation, with around 1 glass of red wine a day. When cooking meals, olive oil is the go-to whether that is to dip wheat bread in it for a starter, or whether it’s for cooking the main course. The monounsaturated fats contained in olive oil differ greatly from the saturated fats contained in western diets, which are well known to be a detriment to overall health. As a result, high sugary foods and processed meats are strongly avoided, instead of having crisps or chocolate as a snack, the Mediterranean diet focuses on snacking on almonds or olives. Fish consumption makes up a large proportion of this diet and gives the body omega-3 and omega-6 fatty acids that humans can’t synthesize themselves.

Two essential fatty acids (EFAs) that the body has to get from external sources, is the omega-6 fatty acid ‘linoleic acid’ & omega-3 fatty acid ‘α-linoleic acid’ (8). Linoleic acid is digested to form arachidonic acid (ARA), which increases inflammation in the body by increasing the number of pro-inflammatory eicosanoids (9). Luckily, eicosapentaenoic acid (EPA) & docosahexaenoic acid (DHA) is taken in from eating fish, and these are both anti-inflammatory eicosanoids. DHA is found in higher concentrations than EPA in the brain, largely in the neuronal membranes where it’s needed for normal neuronal development and behaviour, as shown in a 2011 animal study (10). The effect of DHA on cognitive function is also suggested in a 2009 mice study, showing DHA is linked with an increase in neurogenesis in the hippocampus, increasing memory and learning function (11). Note that this experiment was on mice, so we don’t know if the effect will be the same on humans.

EPA & DHA also affects the omega-3 fatty acid inflammation pathway. Due to the pathway starting with arachidonic acid, EPA & DHA can combine with it to create membrane-bound phospholipids, consequently decreasing the overall concentration of arachidonic acid. EPA can also act as a competitive inhibitor with arachidonic acid, decreasing the amount of pro-inflammatory eicosanoids made. In a 2015 study, it was also proposed that DHA had a differential effect on some patients with IL-6 gene expression, affecting the cytokine TNFα by partially inhibiting the NFκB signalling pathway(12). It is suggested that inflammation increases immune activation, as the brain translates this as being a ‘stressor’ which can increase the likeliness of getting depression (13). In depressed patients the levels of BDNF (brain-derived neurotrophic factor) decrease, but then patients are treated with anti-depressants (which decrease inflammation), the level of BNDF expression and mood of the patient both increased (14).

In the Mediterranean diet, seafood isn’t the only place that we can get omega-3 fatty acids from. ALA (α-linoleic acid) is present in a lot of leafy vegetables, whereas linoleic acid is found in a lot of vegetable or nut oils. The conversion of ALA to EPA & DHA is extremely low, and therefore the best consumption for these omega-3 fatty acids is directly from seafood, particularly salmon. This could well be the reason for a 2014 study showing that marine sources of omega-3 fatty acids show a decrease in inflammatory markers (i.e. CRP, TNFα & IL-6) in the blood of none-obese patients (15).

However, although a lot of studies have shown there to be an association between omega-3 fatty acids and mood, the strength of this link can come under question. For example, a report about how omega-polyunsaturated fats affect depression produced mixed results (16). This isn’t the only report showing the same outcome, with a Bloch & Hannestead (17) report stating that omega-3 supplementation had no significant benefit compared with the placebo. This report did attract some scrutiny, however, as another paper released in 2011 reported a clear benefit between omega-3 supplementation and the alleviation of depression symptoms (18). This report, along with other ones before (19) gives evidence to the idea that EPA is the effective omega-3 component for treating depression. The authors of these papers provided ideas as to why this could be but provide no evidence, showing more research is needed.

We have to look at how much omega-3 fatty acid we would have to consume to be effective. According to a 2009 study (20), the recommended intake of EPA & DHA is 250-500mg a day, whereas the western diet gives us an average intake of 100-135mg a day. The Mediterranean diet easily meets this recommended daily value. The amount recommended then increases in pregnant women, with a 70mg/day increase for pregnant women in the last 3 months of pregnancy (21). This is mainly due to placental transfer to the foetus, putting the mother at risk.

In one placebo study (22), the authors compared two omega preparations enriched with EPA and one with DHA. They found that none of them were superior to the placebo in monotherapy for major depressive disorder. However, in another study (23) it was found that giving EPA-rich omega-3 fatty acids with citalopram greatly decreased the symptoms, as compared with Citalopram and the placebo. Consequently, different studies that give conflicting results about what impact omega-3 fatty acids have on depression. For example, in a study that looked at the effects of omega-3 fatty acids on the effect of depression after an MI, no effects on the symptoms of depression were reported (24), with lots more literature giving the same conflicting results. One reason for this could be due to depression is a multifactorial disease, and so is affected by genetics, age, environment, etc. As well as this even though studies have shown that omega-3 fatty acids can decrease the amount of inflammation in the brain, we still do not know the science behind this, which has led to some controversy as to whether it is true or not (25).

The evidence for omega-3 fatty acids affecting different mental health conditions is less researched than depression. However, in a study about dementia (26) it was found that an increased dietary intake of DHA decreased the risk of getting Alzheimer’s Disease (AD), as long as you didn’t have the ApoE4 genotype as this limit’s protection. This isn’t the same for all mental health conditions, however, as in a study about finding new treatments for schizophrenia, Ethyl-EPA was used to see if it had any impact on treatment, and not much was found (27).

Although these studies above may show conflicting evidence about whether omega-3 fatty acids can improve mental health, due to the limited side effects of getting to a healthy level of 250-500mg/day of EPA & DHA (20), there is little evidence showing harm in eating a Mediterranean diet. There has, however, proved that there is a link between inflammation and omega-3 fatty acids, demonstrating that this diet may have mental health benefits depending on a variety of factors e.g. age, sex & genotype.

Zinc in the Mediterranean Diet

Zinc is an essential trace element that we consume in our diet, with a recommended dose being 11mg per day for adult males and 8mg for females, rising to 13mg in pregnancy (28). A high amount of zinc is found in oysters, chickpeas, lentils, and beans (foods that are eaten in high amounts in the Mediterranean diet). It is thought that one of Zinc's main responsibilities is to bind to transcription factors on DNA creating Zinc finger (ZnF) proteins, which affect gene expression in the CNS. In a mice study (29), it was then shown that the highest level of zinc is found in the adult hippocampus, one of the main places for adult neurogenesis. In a collective review of different experiments (30), it was found that there is strong evidence to suggest that a lack of adult neurogenesis has an impact on mental health, including depression, anxiety, and schizophrenia.

The role that zinc has in the progression of Alzheimer’s Disease (AD) is controversial. One study (31) shows a significant increase of zinc in the hippocampus in patients with AD (with age-matched controls), while another shows the level of blood zinc decreases in patients with AD in similar control groups (32). These conflicting results show more research is needed into the physiology of zinc in the brain. Nevertheless, ideas between zinc and AD keep coming forward, with one prominent theory suggesting that zinc helps the phosphorylation serine 214 in tau proteins causing hyperphosphorylation of tau (33).

Many studies have shown that zinc plays an important role in the treatment of Depression. For example, results from a Treatment-Resistant Depression (TRD) study found that lower serum zinc is a marker of TRD and the inflammatory response in depression (34). Although the science behind this is not fully understood, a 2002 report found evidence to suggest that low levels of zinc increase the amount of Mitochondrial Reactive Oxygen Species (ROS) in the brain (35), which can cause inflammation. In a rat study, it was also shown that low levels of Zinc serum can lead to TRD, as zinc levels appear to be lowest in the rats that didn’t respond to antidepressant drug treatment (36). Interestingly, it has been shown that zinc affects depression for women more than it does for men, with a 2012 population study finding that zinc had a much bigger reduction of depressive symptoms on women than men (37). Additional research is needed to understand the causation of this.

Magnesium in the Mediterranean Diet

Magnesium supplementation has also been shown to be beneficial to mental health. In a 2006 study, it was shown that magnesium can be used in the treatment for major depression, as low magnesium levels could damage neuronal calcium channels (38). Other studies have also demonstrated that magnesium deficiencies are found in other disorders, for example a study that looked at children with ADHD found that magnesium deficiency in the ADHD children occurred more frequently than healthy children (39). Magnesium deficiencies have also become more common over the last 20 to 30 years, as the highly processed foods in western diets contain very little magnesium, opening the idea that this could potentially be a reason for many studies showing dramatic increases in the case of ADHD (40). There hasn’t, however, been that much research into the negative side effects of magnesium for healthy people, but research shows patients with severe renal disease should be cautious and monitored if taking magnesium supplements (41). All this supports the argument for eating a Mediterranean diet, as seafood, vegetables, and fruit all contain high levels of magnesium.

Iron in the Mediterranean Diet

Iron deficiency is the world’s most common food deficiency, mostly occurring due to bleeding or breastfeeding. As well as causing anaemia, iron has a big impact on neurology. There are many theories as to how low iron concentration impacts the brain, with one review suggesting that the main reason is due to slow neuronal processing (42). Like magnesium, iron deficiency has been linked to children with a range of psychiatric disorders, including ADHD and autism (43). However, if iron supplements were taken, the patient would have to be definitely iron deficient, as Hemochromatosis and cirrhosis can occur if iron levels get too high. Therefore, a diet such as the Mediterranean diet that’s full of green vegetables (a high source of iron) can achieve the recommended daily intake of 8.7mg for adult males & 14.8mg a day for adult females (44), without taking supplements.

Vitamins in the Diet

Vitamins play an important role in mental health. For example, a case study about a 29-year-old male reported that OCD symptoms were presented in the early manifestations of B12 deficiency (45), with similar studies in the elderly showing similar outcomes (46). In another study that looked at case reports, it was then shown that cobalamin (vitamin B12) deficiency is linked to Psychosis and folate deficiency is linked to depressive disorders (47). It often takes 3-5 years for a B12 deficiency to affect the body due to the liver having a large supply, so it is usually the elderly who have B12 deficiencies. Therefore, it is important elderly patients get enough folate and B12, not only for mental health but a deficiency can lead to anaemia. It is recommended that adults have 200mg of folate a day and 1.5micrograms of B12 (48). These can both be achieved by eating a Mediterranean diet, as the green vegetables will provide lots of folate, and salmon and cod will provide B12.

Fasting & Caloric Restriction

In addition to the foods we eat, it also appears that fasting calorie restriction and timing of eating can also affect mood. For example, in a 2003 study it was shown that in diets that short term fast, the quality of sleep and daytime performance are increased (49).

Many studies have shown that a prolonged calorie deficit has been shown to increase mood, consequently decreasing depressive symptoms. For example, a study on the FCR (Fasting and calorie regime) in ageing men for 3 months found that the regime was beneficial in decreasing negative moods such as anger and anxiety, promoting calmer and better moods instead (50). In a longer study, the same findings were shown in a more varied age group and showed no side effects (51). In a mice study, it was found that calorie restriction also helped prevent neurodegeneration, opening the idea that this regime may be beneficial in the prevention of Alzheimer’s (52).

We only have suggestive evidence for these results above. For example, in a mice study (52) it was found that during the 10-day fast, mood was improved through orexin signalling activation. This increases arousal, appetite, and alertness. In a different report on mice (53), it was found that the level of p-CREB (phosphorylated-cAMP responsive element binding) was also increased. This plays an important role in the neuronal transcription regulation, an area that a lot of anti-depressants affect. Ketones may also play a big part in improving mood. In the first 24hrs of fasting there will be the lipolysis of fat, producing ketones. According to a 2009 study (54), this can cause a noticeable increase in the mitochondrial function and neurotrophic factors, with a decrease in the inflammatory mediators. There is no evidence, however, as to which one of these factors cause the neuroprotective effects of ketones.

However, not all of the studies surrounding FCR support it. In a 4-week mice study (55), it was found that a calorie deficit with a 34% decrease in calories caused an increase in corticosterone levels (which increases with stress). In a separate mice study (56), it was shown that the corticosteroid increase due to calorie deficit can induce neuronal damage. Although these tests were done on mice and not humans, it shows contrasting evidence to the FCR regime. In addition to this, there is conflicting evidence towards whether calorie restriction during fasting in Ramadan improves mood. For example, in a study that looked at alertness and mood at different times during the day (57), these were lowest at 09:00 and 16:00, and then highest at 23:00. There is no evidence to support the reasons for this as this was observational study, so therefore more research is needed. In opposition to this point, a different study looked at the adverse effects of a 12-hour fast for Ramadan on the mental health of bipolar patients (58). They found no rise in lithium blood levels and no effect on mental state. These results conclude that much more research is needed to understand the reasoning behind how a fasted body affects brain function.

Conclusion

Overall, the Mediterranean diet provides a perfectly adequate supply of the nutrients needed for healthy brain function. Although each of the nutrients has had a lot of individual research, there is only enough evidence that suggests a correlation between nutrient deficiency and mental health disorders, so more research is needed on the theories about the physiological effect of nutrients on the brain. However, the overall results for following the Mediterranean diet seem promising for not only the prevention of mental health disorders but also the eradication. A study found that the current treatments for depression leave 20%-40% of patients with persistent depressive symptoms (59), perhaps the efficacy of the treatment would be improved for these patients if they followed the Mediterranean diet whilst receiving treatment. 

References

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