Health Articles

 

The role of nutrition in mental health

Balancing Brain Chemistry to Treat Depression
By Liz Butler
This article first appeared in CAM magazine


Introduction
It is taking a long time for the scientific community to fully accept that what a person
eats can influence their mental state but in the last few decades progress in this area has
been rapid. Taking a very basic view of the subject there can be no doubt that nutrition is
intimately involved with mental health as the brain and its chemical messengers are
ultimately derived from food. Convincing doctors used to the traditional approach of
treating mental disturbance and depression (drugs or psychotherapy) to consider the
nutritional treatment approach is more difficult than simply pointing out this fact.
Fortunately there is now a large amount of research supporting the view that nutrition
has a role to play in promoting mental health, this article will review some of this
research.
It is well established that neurotransmitter imbalances can lead to mental dysfunction
and depression and in fact most drugs currently being used in this area of disease aim to
restore chemical balance within the nervous system (1). As some of the research
mentioned in this review shows, certain nutritional factors may be able to promote
chemical normality in the same way as current pharmaceutical treatments but without
the side effects associated with drug therapy.
Within a discussion about depression there must be some mention of genetic factors as
there is no denying that the risk of developing depression, particularly a severe form, is
influenced by genetics (2). It is likely that certain people are born with a predisposition to
biochemical imbalances within the brain and then an inadequate nutrient intake
compounds the problem. Eventually the situation deteriorates until there is expression
of disease. What this means however, is that even disease with a genetic component
may possibly be reversed given the correct nutrients to balance brain chemistry.
Brain chemistry
The brain is composed of about 100 billion neurones, the cells of the nervous system that
communicate messages to each other, making up what is termed grey matter. The
processes that extend from the cells to meet up with other cells constitute the white
matter of the brain. Amongst the neurones are cells called neuroglia. Their role is to
support, protect, and repair the neurones.
Neurotransmitters are chemical substances that pass between neurones relaying
messages. Examples include acetylcholine, histamine, adrenaline, noradrenaline,
dopamine, and serotonin. All of these are well-studied neurotransmitters, and the
effects of too much, or too little on the mental state are well observed. In addition
neuromodulators and neurohormones are further classes of chemicals that affect
nervous function. Neuromodulators modulate signal transmission either pre- or post-
synaptically and neurohormones behave like neurotransmitters but act at a site distant
from their release. In practice it is not possible to categorise these units of chemical
communication so rigidly as many substances have actions that apply to each group.
In truth scientists have only realised relatively recently just how complex the body's
system of chemical messengers is. It is very unlikely that current knowledge describes
the full story.

Nutrients and neurotransmitter balance
The neurotransmitters most closely associated with depression are noradrenaline and
serotonin and low levels of these compounds are implicated in some forms of the
condition (3,4).
These and other neurotransmitters such as histamine and dopamine are derived from
amino acids. The precursor amino acid of serotonin, for example, is tryptophan. Other
neurotransmitters such as aspartate, glutamate and gamma-aminobutyric acid (GABA)
exist simply as amino acids without modification.
As the links between neurotransmitters and amino acids are so close it is easy to imagine
how deficiencies of these nutrients could lead to changes in the pattern of
neurotransmitter production. It is relatively rare to find general protein deficiencies in
people living in developed countries, however deficiencies of specific amino acids are
more common and could be a feature of an inadequate diet such as an ill thought-out
vegan diet.
For general good health and the prevention of depression a balanced diet providing the
full complement of essential amino acids would be recommended. For the treatment of
such conditions however, some scientists have considered the possibility of manipulating
the levels of amino acids in the brain in order to influence neurotransmitter production (5).
Tyrosine is a very important amino acid in terms of nervous function as it is required for
the formation of catecholamine-type neurotransmitters, dopamine, noradrenaline and
adrenaline. Very few studies have investigated the effects of tyrosine on depression. Of
the research that has been done, some studies suggest that tyrosine is an effective anti-
depression treatment in some individuals (6,7) others, however, suggest that it is not (8).
Phenylalanine is a precursor of tyrosine and has proved to be more successful in the
treatment of depression than tyrosine (9,10). This is probably due to the fact that, aside
from its role in catecholamine synthesis, this amino acid can be decarboxylated to
phenylethlamine (PEA) (11). This compound has amphetamine-like stimulant properties
and is suggested to be an endogenous stimulatory or antidepressive substance in
humans. Low urinary levels have been found in depressed patients (11,12,).
Tryptophan is another amino acid that has been used to manipulate neurotransmitter
levels as it is the precursor to serotonin (13,14). Tryptophan is not available to buy as a
supplement because of a contamination incident that occurred in the 1980s however 5-
hydroxytryptophan (5-HTP), which is a compound occurring further along the serotonin
pathway, is available. 5-HTP has shown more consistent positive results in the treatment
of depression compared with tryptophan (15-18). 5-HTP's increased effectiveness is
probably due to the fact that it does not require a transport molecule to cross the blood-
brain barrier, unlike tryptophan. Also not all tryptophan is converted to serotonin, some
follows an alternative biochemical pathway and is converted to a compound called
kynurenine. 5-HTP is not converted to kynurenine and therefore more is available for
serotonin production. Double-blind studies have shown 5-HTP to have ‘equipotency'
with serotonin reuptake inhibitors (SRIs) and tricyclic antidepressants in terms of
effectiveness and to offer several advantages in that it is less expensive, better tolerated
and associated with fewer and much milder side effects. (16,18).
Based on findings that a high carbohydrate meal induces feelings of calm and reduced
tension compared to a high protein meal, R. J. Wurtman proposed that the levels of
serotonin in the brain could be influenced by the proportions of carbohydrate and protein
in the diet.
Wurtman suggested that a high carbohydrate diet increases the ratio of the plasma
concentration of tryptophan relative to the other large neutral amino acids e.g. tyrosine,
phenylalanine, leucine, isoleucine and valine (19). This occurs because insulin released in
response to the carbohydrate load facilitates uptake of most amino acids into peripheral
tissues, but not tryptophan. Since tryptophan and the other large neutral amino acids
compete for entry into the brain, and the rate limiting enzyme for serotonin production
(tryptophan hydroxylase) is not fully saturated with substrate under normal conditions,
an increase in the plasma ratio of tryptophan to the other large neutral amino acids leads
to an increase in brain serotonin synthesis. In contrast, consumption of a meal high in
protein can be expected to have the opposite effect, primarily because most dietary
proteins contain relatively little tryptophan.
This theory is the most prominent and extensively tested idea concerning the effects of
food on mood. The results however have not been consistent. One study found that
individuals highly prone to stress who were subjected to uncontrollable stress situations
were less likely to show signs of stress such as depression, decline in vigour and cortisol
elevation if they were following a carbohydrate rich, protein poor diet compared with a
carbohydrate poor, protein rich diet (20). Similar results have been obtained in several
other trials (21,22,23). On the other hand another study comparing the effects of a high
protein breakfast, a high carbohydrate breakfast and no breakfast found that the group
of people consuming the high protein breakfast felt more contented, interested, sociable
and out-going than those in the other two groups (24).
At present it is still not clear whether a high carbohydrate diet can lead to a reduction in
depression and although it is established that carbohydrate can have an effect on brain
tryptophan and serotonin levels, some scientists believe that this effect is not sufficient
to alter mood (25). Also adding to the argument is the issue of hypoglycaemia, which is
implicated in depression (26,27). Hypoglycaemia may be aggrevated by a high
carbohydrate diet.
Hypoglycaemia
In normal subjects, consumption of a solution containing 50g of glucose is associated
with a rapid rise in blood glucose and a large insulin response. The latter stimulates
peripheral glucose uptake to such an extent that the rate of glucose use exceeds the rate of absorption and the blood glucose concentration falls below the fasting level 2-4 hours after the glucose load (28). High blood glucose levels are associated with increased energy and decreased tension (26), however as glucose levels fall mood alters as low blood glucose levels are associated with tension, depression and other negative mood states (27).
A diet that promotes steady blood sugar levels is one that consists of foods with a low
glycaemic index, the glycaemic index (G.I) being a way of ranking foods based on their
overall effects on blood sugar levels. Although it is not always as straightforward as
classing all refined carbohydrate foods as those with a high glycaemic index, this does
work as a general guideline. A blood sugar-friendly diet would also be free of stimulants
such as caffeine, which lead to an adrenaline rush and therefore cause a rapid rise in
blood glucose. It is thought that a diet with moderate levels of protein will lead to
steadier blood sugar levels as protein does not stimulate insulin release in the same way
as carbohydrate (29). For this reason a diet combining moderate levels of protein with low
G.I. foods may be the best option for someone trying to combat depression.
The link between the brain and the immune system
Carl Germano, one of the authors of ‘The Brain Wellness Plan' (30), believes that brain
diseases require treatment of the immune system as well as the brain itself. He states
that ‘there exists a complex communication pathway that connects your brain with your
endocrine, cardiovascular, and immune system via neurotransmitters and
immunotransmitters (chemical messengers produced from the immune system)'. It is
true that neurotransmitters have receptors on various components of the immune
system and are therefore able to influence the immune response. It seems that the
reverse is also true, that in certain areas of the brain, neurones have receptors for
immunotransmitters (cytokines) (31).
Cytokines are to the immune system what neurotransmitters are to the brain. They are
crafted to deliver warnings to speed up or slow down the immune system's response.
Three of the most important cytokines are interleukins, tumor necrosis factor, and
interferon. Research suggests that these chemicals can profoundly alter the way
neurotransmitters are released or inhibited (31). Strong evidence now exists indicating
that certain cytokines are ‘offensive' to the immune system and brain, causing fatigue,
slowed thinking, and depression (32,33).

The links between the brain and the gut
The gut is very intimately involved with the nervous system and in fact, unlike any other
organ, it contains an intrinsic nervous system. In other words the gut is home to a part of
the nervous system that is able to mediate reflexes in the complete absence of input
from the brain or spinal cord (34). This part of the nervous system is known as the enteric
nervous system. This is not a small proportion of the nervous system, in fact there are
more nerve cells in the gut than in the entire remainder of the peripheral nervous system.
In addition each one of the classes of neurotransmitter found in the brain is also present
within the gut (34).
One of the neurotransmitters present in large amounts in the enteric nervous sysytem is
serotonin. In fact a far greater amount of this neurotransmitter is present in the enteric
nervous system than in the brain (34). It is currently not known the extent to which and
exactly how neurotransmitters released in the gut affect the brain but it is known that a
steady stream of messages flows back and forth between the gut and the brain via the
vagus nerve (34).
Allergic reactions
There is another way that the gastrointestinal tract can influence mental function. This
phenomenon involves the immune system as well. More and more scientists and doctors
are recognising the condition known as ‘Leaky Gut Syndrome', which basically describes
a hyperpermeable intestinal lining.
A healthy intestinal tract provides an effective barrier against excessive absorption of
food antigens. However, increased gut permeability allows greater quantities of
antigens to penetrate the intestinal lining resulting in an overly sensitised, reactive
immune system (35). As already mentioned cytokines released during an immune reaction
can disrupt brain function. Research data confirms that those suffering from allergies
often experience depression (36).
There is also evidence that partially digested proteins passing from the gut into the blood
stream can have a direct effect (without the involvement of the immune system) on the
nervous system leading to depression and other mental dysfunction (37,38). These
peptides have the ability to act on brain opiate receptors and have been named
exorphins (exo = exogenous, orphin = morphin, an opium), the opposite of endorphins
(39). Much of the work carried out in this area has been conducted by Fukudome and
Yoshikawa, in the last decade (40,41), who have identified and characterised five distinct
exorphins in the pepsin digests of gluten. Eight distinct exorphins have also been
identified in the pepsin digests of milk (42).
Depression is one of the most common symptoms in those with coeliac disease (43,44),
these people having an intolerance to gluten. However, this phenomenon is not limited
to those with such food intolerances. Clear evidence exists showing that exorphins can
be absorbed through the intestinal mucosa and into the circulation of a significant
minority of apparently healthy members of the general population (45).
Vitamins and minerals as biochemical cofactors
It has been known for a long time that vitamins and minerals have a part to play in
promoting and preserving mental health. The most profound demonstration of this has
been the observation of people with deficiencies in certain nutrients.
It is the famous psychiatrist Dr Carl Pfeiffer as well as others such as Dr Abraham Hoffer
that are responsible for some of the most important work in the area of nutrition and
mental health. Carl Pfeiffer identified many diseases that are related to specific nutrient
deficiencies and he developed treatment approaches for balancing nutrient levels and
correcting brain chemistry leading to great improvements in disease symptoms (46).
Neurotransmitter production is regulated by enzyme catalysts, which are dependent on
specific nutrients acting as essential cofactors. Often methylation occurs in the
neurotransmitter pathways and certain nutrients act either as methyl group acceptors, or
donators. Without these essential cofactors biochemical pathways, often involving more
than one neurotransmitter, are inhibited (47). Folic acid, vitamin B12, and a form of the
amino acid methionine known as SAM (S-adenoyl-methionine), function as ‘methyl
donors'. Supplementation of these nutrients and the promotion of methylation
reactions have been shown to increase serotonin levels (48,49) and be effective against
depression (49,50).
Vitamin B6 is another of the B vitamins closely associated with depression. It is required
for the synthesis of two neurotransmitters that are involved in the regulation of anxiety:
serotonin and GABA. Vitamin B6 is also important for its role in general amino acid
metabolism and also the metabolism of essential fatty acids. Symptoms of vitamin B6
deficiency include irritability and depression (51).
Apart from the B vitamins, deficiencies of other nutrients lead to symptoms of
depression. These include vitamin C (52) and certain minerals such as calcium and
magnesium (53,54). Magnesium has also been found in levels higher than for controls in
some with depression (55). This could be due to the fact that calcium and magnesium
have an antagonistic relationship and therefore high magnesium levels are associated
with low calcium levels. Copper is another mineral for which high levels are associated
with depression (56, 57).
It is unlikely that many doctors treating patients with depression would consider
checking a person's vitamin and mineral levels. Considering the widespread deficiencies
of many nutrients in the average UK diet (58), such a policy could prove valuable.
The importance of essential fatty acids
Essential fatty acids are the main components of cell membranes. They help hold
proteins in the membrane by the electrostatic attractive forces of their double bonds,
and thus they are involved in the traffic of substances in and out of the cells. They also
help create the electrical potentials across membranes of neurones so that electric
transmissions may occur.
The essential fatty acids are required for prostaglandin synthesis. Prostaglandins being
hormone-like substances with many functions in the body including, according to fairly
recent research, influencing the activity of neurotransmitters and their receptors (59).
Research has found that deficiencies in essential fatty acids, particularly the omega-3
type, lead to an increase in depression (60,61,62). During the famous Framingham Study,
the largest ever to examine the relationship between lowered cholesterol and decreased
heart disease, researchers made a disconcerting discovery. People participating in the
study who lowered their cholesterol did suffer less from heart disease. However, more of
the study's participants committed suicide compared to the rest of the population.
Scientists suggest that low cholesterol may be a risk factor for depression but it appears
that the lipid balance as a whole, and in particular low levels of omega-3 fatty acids are
the most important factors (62).
Conclusion
The aim of this article has not been to give advice on possible treatment protocols for
depression but to outline some of the ways in which nutrition can promote biochemical
balance within the brain and nervous system as a whole. The exciting thing is that more
and more research is showing that using these nutritional strategies can lead to positive
benefits for those with depression. With increasing research in this area expected health
professionals can look forward more extensive information to support their work in the
treatment of depression.
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