US Pharm. 2009;23(11):HS-7-HS13. 

While the connection between nutritional deficiencies and physical illness is more obvious, few people see the connection between nutrition and depression. This is because depression is more typically thought of as either biochemicaly based or emotionally rooted. It is now proven that nutrition can play a key role in the onset, as well as severity and duration, of depression. Nutritional neuroscience is an emerging discipline that is shedding light on the link between nutritional factors and human cognition, behavior, and emotions.1

There are two types of depression. Behavioral depression or "the blues" results from various causes, and most people experience it at some point in their lives. Clinical depression, on the other hand, is much more serious. It is usually caused by a chemical imbalance in the brain and requires medical attention.2

Nutrition plays an important role in every aspect of well-being, and improper nutrition can lead to poor bodily function. There are many reports that people with clinical depression also suffer from malnutrition. The dietary habits of the general population in the United States and many Asian countries reveal that people are often deficient in many nutrients, especially essential amino acids, vitamins, minerals, and omega-3 fatty acids.  People who are depressed often lose all sense of self and stop eating and caring. Food alone cannot prevent depression, but poor nutrition makes the body incapable of healing itself. Supplements containing amino acids have been found to reduce symptoms of depression, as they are converted to neurotransmitters, which in turn alleviate depression and other mental health problems.3

Since most antidepressant prescription drugs have side effects, it is possible that some patients who are not being observed by psychiatrists will skip taking their medications. Such noncompliance can put patients at a higher risk for committing suicide or being hospitalized. An alternate and effective way for psychiatrists to circumvent noncompliance is to familiarize themselves with alternative or complementary nutritional therapies. Psychiatrists can recommend doses of dietary supplements based on efficacious studies and adjust the doses based on the results obtained by closely observing the changes in the patient.4

If a person with depression suffers from loss of sleep, clinicians will either increase the amount of amino acids in their diet or add iron for loss of appetite. There are foods that should be included in the diet of a person with clinical depression. Meat and amino acids such as phenylalanine, tryptophan, choline, and tyrosine--which help the nervous system function properly--should be added to the diet. Choline and tryptophan can be found in many freshwater fish, and tyrosine can be found in cheese.5 Foods that should be avoided are alcohol and caffeine. Alcohol acts as a central nervous system depressant, which makes the situation worse, and caffeine interferes with sleep and promotes nervousness. 

Signs and Symptoms of Depression

Many people attribute the feelings induced by depression to other causes such as inability to handle stress, social stigma, and alcoholism. However, depression is not difficult to spot, and specific signs and symptoms exhibited by a person are helpful in identifying its presence (see TABLE 1).6  

Brain Biochemical Imbalance

Neurotransmitters are the natural biochemicals that facilitate communication between brain cells. These substances control our emotions, memory, moods, behavior, sleep, and learning abilities. Neurotransmitters are manufactured in the brain from the amino acid precursors we receive from food. Without adequate amino acid conversion, sufficient amounts of neurotransmitters are not produced.7 Alcohol destroys these essential precursor amino acids, which is probably why alcoholics seem so emotionally down and depressed.

The two major neurotransmitters involved in preventing depression are serotonin (from the amino acid L-tryptophan) and norepinephrine (from the amino acids L-phenylalanine and L-tyrosine). It is interesting that the depressive symptoms exhibited indicate which amino acids are lacking: If the symptoms are sleeplessness, anxiety, or irritability, then L-tryptophan is low; if the symptoms are lethargy, fatigue, sleeping too much, or feelings of immobility, L-tyrosine or L-phenylalanine is lacking.7  

Conversion of Amino Acids to Neurotransmitters

The amino acid tyrosine, found in large amounts in cheese, has an amazing effect on depression. Tyrosine is a nonessential amino acid that is synthesized in the body from phenylalanine. As a building block for several important brain chemicals, tyrosine is needed to make epinephrine, norepinephrine, serotonin, and dopamine, all of which work to regulate mood. Tyrosine also aids in the production of melanin (the pigment responsible for hair and skin color) and in the function of organs responsible for making and regulating hormones, including the adrenal, thyroid, and pituitary glands. Tyrosine is also involved in the synthesis of enkephalins, substances that have pain-relieving effects in the body.8

Low levels of tyrosine have been associated with low blood pressure, low body temperature, and an underactive thyroid. Because tyrosine binds to free radicals, it is considered a mild antioxidant. Thus, tyrosine may be useful for individuals who have been exposed to harmful chemicals (such as from smoking) and radiation. The usual dose is 3 to 6 g per day, taken on an empty stomach. Vitamins B6 and C need to be taken to facilitate the conversion of tyrosine to norepinephrine.8

An alternative to tyrosine is the amino acid L-phenylalanine, which can also be converted into norepinephrine. L-phenylalanine is converted to a substance called 2-phenylethylamine (2-PEA). Low brain levels of 2-PEA are also responsible for some depression. 2-PEA is converted to tyrosine, which then converts to norepinephrine. L-phenylalanine is a better start than tyrosine, but if it causes the brain to race due to the formation of 2-PEA, the patient should start with tyrosine. A disadvantage to taking L-phenylalanine is its slight potential for raising blood pressure.

There is also some evidence that excess L-phenylalanine can cause headaches, insomnia, and irritability. For these reasons, it is important to start with a low dose. L-phenylalanine doses can range from 500 mg to 1,500 mg daily and should be taken on an empty stomach.8

The FDA prohibited the manufacture and sale of tryptophan in the United States in the fall of 1980. Although the FDA continues to enunciate its concern about the use of L-tryptophan as a single product and related compounds such as L-5-hydroxytryptophan, the agency does not prohibit the marketing of dietary supplements that contain lower doses of L-tryptophan. 5-hydroxytryptophan (a direct precursor to serotonin) has been offered as an alternative. The amino acid tryptophan is the precursor for serotonin and it is found in large amounts in milk and turkey (see TABLE 2). Serotonin controls mood, sleep, sexual ability, appetite, and pain threshold. Increasing serotonin can lift depression and end insomnia.8

 

Prostaglandin E1 and Depression

Another biochemical cause of depression is a genetic inability to manufacture enough prostaglandin E1 (PGE1), an important brain metabolite derived from essential fatty acids (EFAs). The problem is the result of an inborn deficiency in omega-6 essential fatty acids. Alcohol stimulates temporary production of PGE1 and lifts the depression. When drinking is stopped, PGE1 levels fall again and depression returns. To banish it, the patients turn again to alcohol. Thus, a downward spiral toward alcoholism begins.

During the past 15 years, researchers have found that if they restore the PGE1 levels to normal range in patients suffering from alcoholism, they can eliminate both the depression and the need to drink for relief. This can be achieved with a substance called gamma-linolenic acid, which can be easily converted to PGE1.9  

The Effect of Nutrition

Research shows that nutritional deficiencies in brain chemistry can result in depression, anger, hopelessness, and paranoia. This is because the connection between depression and vitamin and mineral deficiencies is often missed. A closer look at the diet of patients suffering from depression indicates that their nutrition is far from adequate. They make poor food choices and frequently select foods that contribute to depression.10

The B-complex vitamins are essential to mental and emotional well-being. They cannot be stored in our bodies, so we depend entirely on our daily diet to supply them. B vitamins are destroyed by alcohol, refined sugars, nicotine, and caffeine. Continued vitamin C deficiency causes chronic depression, fatigue, and vague ill health, and insufficient amounts of minerals also cause mental problems. The relationship between vitamins B and C and minerals and depression is shown in TABLE 3. 

Carbohydrates

Carbohydrates, or polysaccharides, play an important role in the structure and function of an organism. In humans, they have been found to affect mood and behavior. Food rich in carbohydrates triggers the release of insulin in the body. Insulin facilitates the release of blood sugar into the cells, where it can be used for energy, and simultaneously triggers the entry of tryptophan to the brain. Tryptophan in the brain affects neurotransmitter levels.

Consumption of diets low in carbohydrates tends to precipitate depression, since the production of the brain chemicals serotonin and tryptophan, which promote the feeling of well-being, is reduced. It is suggested that low glycemic index (GI) foods such as some fruits and vegetables, whole grains, and pasta are more likely to provide a moderate but lasting effect on brain chemistry, mood, and energy level than the high GI foods.10

Proteins and Amino Acids

Many of the neurotransmitters in the brain are made from amino acids. Proteins are made up of amino acids and are important building blocks of life. As many as 12 amino acids are manufactured in the body and the remaining eight (essential amino acids) must be supplied through diet. A high-quality protein diet contains all of the essential amino acids. Foods rich in high-quality protein include meat, milk and other dairy products, and eggs. Plant proteins in beans, peas, and grains may be low in one or two essential amino acids.

Protein intake and in turn the individual amino acids can affect the brain function and mental health. The neurotransmitter dopamine is made from the amino acid tyrosine, and the neurotransmitter serotonin is made from tryptophan. If there is a lack of either of these amino acids, there will lack of neurotransmitter synthesis, which is associated with low mood and aggression in patients. The excessive buildup of amino acids may also lead to brain damage and mental retardation. For example, excessive amounts of phenylalanine in individuals with the disease called phenylketonuria can cause brain damage and mental retardation.10 

Omega-3 Fatty Acids

The brain is one of the organs with the highest level of lipids (fats). Brain lipids are composed of fatty acids and are a major part of its membranes. It has been estimated that gray matter contains 50% fatty acids that are polyunsaturated in nature (about 33% belong to the omega-3 family) and hence are supplied through the diet. In one of the first experimental demonstrations of the effect of nutrients on the structure and function of the brain, the omega-3 fatty acid alpha-linolenic was found to have a major role. An important trend has been observed from the findings of some recent studies that lowering plasma cholesterol by diet and medications might increase depression. Among the significant factors involved are the quantity and ratio of omega-6 and omega-3 polyunsaturated fatty acids (PUFAs) that affect serum lipids and alter the biochemical and biophysical properties of cell membranes. It has been hypothesized that sufficient long-chain PUFAs, especially DHA, may decrease the development of depression.15

The glycerophospholipids in the brain consist of a high proportion of PUFAs derived from the essential fatty acids, linoleic acid, and alpha-linolenic acid. The main PUFAs in the brain are DHA, derived from the omega-3 fatty acid alpha-linolenic acid, arachidonic acid, and docosatetraenoic acid, both derived from the omega-6 fatty acid and linoleic acid. Experimental studies have also revealed that diets lacking omega-3 PUFAs lead to considerable disturbance in neural function.16  

Age, Depression, and CAM

Anorexia in the elderly may play an important role in precipitating depression, either by reducing food intake directly or in response to such adverse factors as age-associated reductions in sensory perception (taste and smell), poor dentition, use of multiple prescription drugs, and depression. Currently, to tackle the problem of depression, many people are following the complementary and alternative medicine (CAM) interventions. CAM therapies are defined by the National Center for Complementary and Alternative Medicine as "a group of diverse medical and health systems, practices, and products that are not considered to be a part of conventional medicine."17 Mental health professionals need to be aware that it is likely that a fair number of their patients with bipolar disorder might use CAM interventions. Some clinicians judge these interventions to be attractive and safe alternatives or adjuncts to conventional psychotropic medications.

Current research in psychoneuroimmunology and brain biochemistry indicates the possibility of communication pathways that can provide a clearer understanding of the association between nutritional intake, the central nervous system, and immune function, thereby influencing an individual's psychological health status. These findings may lead to greater acceptance of the therapeutic value of dietary intervention among health practitioners and health care providers in addressing depression and other psychological disorders.18 

The Safety of Vitamin Supplements

Vitamin C and the B-complex vitamins, discussed above, are all water soluble; therefore, they cannot accumulate in the body or be stored for future use. Amounts above and beyond current nutritional needs are excreted through urine. As a result, there is little danger of overdosing. Unlike water-soluble vitamins, lipid-soluble vitamins and minerals can be stored in body tissues. For therapeutic doses of these compounds, the advice of a qualified nutrition consultant is required. Do not exceed the recommended therapeutic doses, since accumulation of certain minerals in the body can be dangerous.19 

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