The Effects of Nutrition on Mental Health

Brett A. Fields, MS4

Mental illness accounts for a significant proportion of global disability

and poses a substantial social, economic, and heath burden. Perhaps one of

the reasons for this is the expansive variability of factors that contribute to

mental illness. Current treatment strategies largely utilize pharmacotherapy

and psychotherapy in an effort to reduce these disparities. However, in the

case of depression, recent studies have shown that these approaches avert

less than half of the disease burdeni. The complexities of mental illness seem

to necessitate additional comprehensive tactics. Fortunately, there have

been consistent observational and interventional studies indicating that diet

quality may be a significant modifiable risk factor for mental illness.

For example, a 2014 systematic review examining the association

between diet and common mental disorders showed that healthy dietary

patterns are inversely associated with the probability of developing

depressionii. Such diets were characterized by the high intake of vegetables,

fruit, whole grains, nuts, seeds and fish, with limited processed foods. In

contrast, unhealthy diets high in processed, high-fat, high-sugar foods in

adolescence and adulthood were shown to be positively associated with the

common mental disorders, depression and anxiety. Similar evidence for the

importance of diet exists in early childhood, where poor maternal nutrition

status and early-life diet is associated with childhood emotional and

behavioral deregulationiii.

It isn’t surprising that diet seems to have such a profound impact on

mental state. The drive for food is one of the most primal instincts that

animals posses. One of the major neurotransmitters involved in the gut is

serotonin, a chemical also known to be a modulator of mood, sleep, memory,

and cognition. This overlap presents clinically in trends of mental illness;

patients with eating disorders are more likely to present with comorbid mood

disordersiv. Perhaps this is why we see an increasing need for mental health

services alongside increasing availability of processed, unhealthy foods.

As our society becomes increasingly urbanized, there are certainly

some notable benefits such as commerce, trade, education,

communications, and the efficient delivery of government and healthcare

services. However, among the population, we also see diminished levels of

physical activity, compromised sleep, and higher consumption of energy-

dense, nutrient-poor foods and beverages. This dietary skew is purposeful by

the food industry due to the higher costs that are associated with nutrient-

rich fruits and vegetables and quality protein sources such as fish and lean

meat. Moreover, research suggests that sugar, fat, and sodium have a

positive feedback effect on the hypothalamic drive to eat such foods v.

Escaping the biochemical pull of unhealthy foods seems to be an

overwhelmingly challenging task.

Yet, this makes sense from an evolutionary perspective; the pleasure

associated with energy-dense food consumption in the ancestral

environment could have acted as a means of offsetting periods of food

scarcity. However, in modern urbanizing civilization, access to food is at an

all-time high. Evolutionary biologists refer to this as ‘mismatch theory’, which

suggests that there are gaps between the physiological and psychological

requirements of individuals. The likelihood of mismatch is increased,

according to the theory, when culture and technology change more rapidly

than human biological evolution.

In addition to these biologic factors, modern marketing magnifies the

allure of these inexpensive, widely available foods, making it difficult for the

average person to make healthy dietary choices. These physiological

responses to the consumption of energy-dense comfort foods are even more

likely to be behaviorally reinforced in people with underlying mental health

disorders who often struggle with self regulation. For these reasons, research

efforts have been aimed at identifying potential neurobiological mechanisms

related to mental disorders including inflammation, oxidative stress,

neuroplasticity, the gut microbiome, and epigenetic modifications.

Inflammation is defined as elevation in pro-inflammatory cytokines and

acute phase proteins. Chronic low-grade exposure to these chemicals is

implicated in the development of depression, schizophrenia and bipolar

disordervi. The causes of chronic inflammation are multifaceted and include

several lifestyle factors, such as psychological stress, smoking, obesity, lack

of sleep and, of particular relevance, poor diet. Results from large

observational studies suggest that healthy dietary patterns, such as the

Mediterranean diet, significantly improve markers of inflammation in

intervention studiesvii.
 Oxidative stress has been implicated in several chronic diseases and

appears to be relevant to mental illness as well. Schizophrenic populations

have demonstrated decreased brain glutathione levels, disordered glutamate

metabolism, and increased oxidative stress. Similar results are reported in

depressed populations, with higher levels of oxidative stress markers

observed, as well as lower levels of antioxidants, such as vitamin E, vitamin

C, coenzyme Q10 and glutathione, when compared with healthy controls viii.

Given the abundance of antioxidant compounds present in foods such as

fruit and vegetables, it follows that this pathway could be modulated through

dietary means.

The generation of neural pathways is an essential component of

learning, memory, and mood regulation. Altered neurogenesis, particularly

within the hippocampus, has been implicated in mental illness. Brain-derived

neurotrophic factor (BDNF) and other neurotrophins have been suggested to

mediate hippocampal neurogenesis. Although there is presently limited

clinical investigation of the effect of diet on this pathway, preliminary

evidence supports the role of diet in improving BDNF levelsix. This suggests

that healthy dietary options could lead to increased memory and learning

ability in addition to improving mood regulation.

One of the most promising new areas of research in the field of

nutritional science has been the role of the gastrointestinal microbiome on

chronic disease. Compelling evidence indicates the gut floura can affect

mental health-related behaviors via multiple pathways. For example,

microbiota-deficient germ-free mice exhibit an exaggerated stress response

as well as lower BDNF and serotonin receptor levels in the cortex and

hippocampus of the brain when compared with normal gut colonized micex.

Interestingly, some of these pathways appear to be bidirectional, with the

hypothalamic–pituitary–adrenal axis acting to modulate microbial

composition in rats.

One application of this gut flora research has been fecal transplants.

Transplantation of fecal microbes from depressed patients into rodents

resulted in depression-related behaviors. Conversely, altering gut flora

through probiotic supplementation or food products was shown to positively

influence depression-related behavior in animalsxi. The impact of bacteria on

the rest of the body is hard to deny, especially considering that bacterial

cells are estimated to outnumber human cells by a ratio of 3:1xii.

Diet also seems to have an effect on overall intestinal permeability.

Compromised integrity of the gut epithelial barrier seems to be associated

with depression, according to a 2013 studyxiii. It has been theorized that this

increased permeability may allow bacteria-derived lipopolysaccharides to

activate immune cells within the intestinal wall, promoting the production of

inflammatory cytokines as well as activation of oxidative stress pathways,

resulting in elevated systemic inflammation. This further emphasizes the

complicated, integrated relationship between the gut and the mind.

In the age of genetic medicine, it is also important to discuss the

epigenetic mechanisms by which genes and nutrition interact to modify

mental status. The plasticity and reversibility of these mechanisms suggests

that the nutritional environmental is constantly modulating an individual’s

health. Epigenetic mechanisms, such as DNA methylation and histone

modification, have been implicated in cognition, eating disorders,

depression, autism, and schizophreniaxiv. Since the nutritional environment

seems to be constantly rearranging molecular structure, it is even more

paramount for physicians to stress the importance of diet amongst patient

populations.

Applying this research in a clinically relevant way remains to be an

elusive challenge, but dietary interventions are feasible and can provide

significant benefit. One area that merits further investigation is

nutraceuticals, food-derived microproducts that have demonstrable health

benefits. Compounds such as n-3 fatty acids, folate, S-adenosylmethionine,

N-acetyl cysteine, and probiotics have been shown to have a positive effect

on patients with schizophrenia, bipolar and anxiety disordersxv. Encouraging

the consumption of foods with these neutroceuticals could have lasting

impacts on daily well-being.

Perhaps an even more effective dietary intervention would simply

center around patient education. Dr. Joel Fuhrman, an advocate for

evidence-based, nutrient-rich foods, uses the acronym ‘G-BOMBS’ (Greens,

Beans, Onions, Mushrooms, Berries, and Seeds) to give patients an easy

reference of foods around which to base their dietxvi. Simple educational tools

such as these make the complicated world of food selection less

overwhelming and give power back to the consumer.

Nutritional psychiatry is a rapidly growing field of research that has the

potential to provide clinically meaningful interventions to both prevent and

manage mental illness. Observational research has demonstrated a

consistent relationship between diet quality and common mental illnesses

and biological pathways including inflammation, oxidative stress, gut flora,

and neurogenic factors provide viable mechanisms of action for this

observed effect. Such findings only add to the urgency of further evaluating

the importance of nutritional variables.

References
i
Casacalenda N, Perry JC & Looper K (2002) Remission in major depressive disorder: a comparison of pharmacotherapy,
psychotherapy, and control conditions. Am J Psychiatry 159, 1354–1360.
ii
Lai JS, Hiles S, Bisquera A et al. (2014) A systematic review and meta-analysis of dietary patterns and depression in
community-dwelling adults. Am J Clin Nutr 99, 181–197.
iii
O’Neil A, Quirk SE, Housden S et al. (2014) Relationship between diet and mental health in children and adolescents: a
systematic review. Am J Public Health 104, e31–e42.
iv
Sloan E, Hall K, Moulding R, Bryce S, Mildred H, Staiger PK. Emotion regulation as a transdiagnostic treatment construct across anxiety, depression,
substance, eating and borderline personality disorders: a systematic review. Clin Psychol Rev. (2017) 57:141–163. doi: 10.1016/j.cpr.2017.09.002
v
Morgan D, Sizemore GM: Animal models of addiction: fat and sugar. Curr Pharm Des 2011, 17:1168–1172.
vi
Fernandes BS, Steiner J, Molendijk ML et al. (2016) C-reactive protein concentrations across the mood spec- trum in
bipolar disorder: a systematic review and meta-analysis. Lancet Psychiatry 3, 1147–1156.
vii
Schwingshackl L & Hoffmann G (2014) Mediterranean dietary pattern, inflammation and endothelial function: a
systematic review and meta-analysis of intervention trials. Nutr Metab Cardiovasc Dis 24, 929–939.
viii
Moylan S, Berk M, Dean OM et al. (2014) Oxidative & nitrosative stress in depression: why so much stress? Neurosci
Biobehav Rev 45, 46–62.
ix
Guimaraes LR, Jacka FN, Gama CS et al. (2008) Serum levels of brain-derived neurotrophic factor in schizophrenia on a
hypocaloric diet. Prog Neuropsychopharmacol Biol Psychiatry 32, 1595–1598.
x
Sudo N, Chida Y, Aiba Y et al. (2004) Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system
for stress response in mice. J Physiol 558(Pt 1), 263–275.
xi
Zheng P, Zeng B, Zhou C et al. (2016) Gut microbiome remodeling induces depressive-like behaviors through a pathway
mediated by the host’s metabolism. Mol Psychiatry 21, 786–796.
xii
American Academy of Microbiology FAQ: Human Microbiome January 2014
xiii
Maes M, Kubera M, Leunis JC et al. (2013) In depression, bacterial translocation may drive inflammatory responses,
oxidative and nitrosative stress (O&NS), and autoimmune responses directed against O&NS-damaged neoepitopes. Acta
Psychiatr Scand 127, 344–354.
xiv
Tsankova N, Renthal W, Kumar A et al. (2007) Epigenetic regulation in psychiatric disorders. Nature Rev Neurosci 8,
355–367.
xv
Firth J, Stubbs B, Sarris J et al. (2017) The effects of vitamin and mineral supplementation on symptoms of schizophre-
nia: a systematic review and meta-analysis. Psychol Med 47, 1515–1527.
xvi
https://www.drfuhrman.com/library/eat-to-live-blog/62/the-healthiest-anti-cancer-foods-g-bombs