Reprinted with permission of Life Extension®.

Almost everyone has, at some point in their lives, experienced "the blues." We all feel sad in the face of significant loss--loss of a job, a loved one, or an adored companion animal. Sometimes reading the morning's news about the latest economic, environmental, or natural disaster is enough to make a person want to crawl back under the covers.

True depression, however, is much more serious than a temporary disappointment or sorrow. People who are depressed can feel a profound and persistent sadness in the absence of an identifiable external cause. Also, the symptoms extend beyond melancholy mood to sleep disruption and loss of appetite and energy. In other words, depression is a "whole body" disease that skews the way we think and behave, often damaging our physical health as well as our emotional state. It is a powerful disease that can leave us debilitated, unable to work, maintain relationships, or deal with other responsibilities. Although external factors play a role, depression and other mood disorders arise primarily from subtle imbalances in brain chemicals called neurotransmitters.


Depression is an equal-opportunity disease, striking all ages and races, both sexes, and all socioeconomic groups:

  • According to the National Institutes of Mental Health, in any given year, major depression afflicts nearly 10 million Americans over the age of 18, or about 5% of the population. When dysthymia (chronic mild depression) is included in the head count, the numbers rise to 18.8 million American adults, or about 9.5% of the population (Narrow 1998).
  • Nearly twice as many women as men suffer from major depression each year (Narrow 1998).
  • If you have just one episode of major depression, there's a 50/50 chance you'll have more, perhaps as many as one or two a year. Millions of depression cases are never diagnosed or treated.
  • Untreated, major depression may last for 6 months to a year, with recurrences becoming more frequent and severe. Without treatment, dysthymic disorder (mild depression) is so persistent that periods of normal mood may last only a few weeks at a time.
  • Major depression is the leading cause of disability in the U.S. Depressed mood ranks just behind high blood pressure as the most common chronic condition doctors see (Wells et al. 1996).
  • Depression costs our society an estimated $44 billion a year, including $23 billion for lowered productivity and absenteeism at work, and $12.3 billion for medical and psychiatric care.
  • Every year thousands of people commit suicide. In 1997, 30,535 people committed suicide, partly or largely as a result of depression, costing taxpayers billions of dollars.

Depression is one of the most commonly misdiagnosed problems. Many doctors treat the obvious symptoms of depression, such as poor appetite, insomnia, and headaches, but overlook the real problem. Left untreated, depression can become more frequent and severe, leading to physical and emotional suffering, loss of job and relationships, and even to suicide.


Medical textbooks describe depression as a mood disorder, lasting at least 2 weeks, that produces exaggerated, inappropriate feelings of sadness, worthlessness, emptiness, and dejection.

"Exaggerated" and "inappropriate" are two important words to keep in mind. To feel upset because of a job layoff, a broken marriage, a bankruptcy, or the loss of a loved one is a normal response to an unhappy event. Generally, our feelings of sadness are proportional to our loss, and this "reactive depression," as doctors call it, goes away with time.

But endogenous, or major depression often strikes for no apparent reason. It doesn't seem to be caused by outside events, such as the loss of a job. Instead, the black mood grows and grips from within. This crippling darkness can last for weeks, months, or years and may make it impossible for us to carry on our normal lives. The many and varied symptoms of endogenous depression may include:

  • Profound, persistent sadness
  • Profound, persistent irritability
  • Unexplained crying
  • Loss of self-esteem
  • Feelings of hopelessness, helplessness, pessimism, worthlessness, guilt, and emptiness
  • Ruminations over the past, particularly the errors you think you've made
  • Changes in sleeping patterns
  • Changes in eating habits
  • Unexplained weight gain or loss
  • Restlessness
  • Fatigue
  • A "slow down" in physical movements
  • Inability to concentrate
  • Memory difficulties
  • Difficulty making decisions
  • Loss of interest in usually pleasurable activities
  • Loss of interest in sex
  • Social withdrawal
  • Unexplained headaches, stomach upset, or other physical problems that are not helped with standard treatment
  • Thoughts of suicide or death
  • Suicide attempts

The symptoms may come in any combination. They can build gradually or strike hard and fast. Some of the symptoms, you'll notice, may seem contradictory. Take, for example, appetite. Mildly depressed people may gain weight as they seek comfort in favorite foods, while those more profoundly depressed may lose weight as sadness deadens their appetites. Sleep patterns also may be affected this way. Some depressed people have difficulty falling or staying asleep, while others sleep more than usual, but awaken feeling tired.

Other common mood disorders include:

  • Dysthymia: low-grade depression that lasts at least 2 years.
  • Mania: periods of elevated, expansive, or irritable mood that last at least one week. During this time, the person becomes very active (including involvement in risky behaviors), restless, grandiose, distractible, and talkative, with racing thoughts.
  • Bipolar disorder: recurrent cycles of depression and mania. Also known as manic-depressive illness.
  • Seasonal affective disorder: mild to moderate depression with carbohydrate cravings, headaches, low energy, and fatigue occurring regularly in the fall or winter.
  • Premenstrual dysphoric disorder: depression, irritability, and anxiety limited to the few days before the onset of menses.


Although we're only beginning to pull back the curtains that hide the inner workings of the human brain, we do know that several neurotransmitters (chemical messengers) including dopamine, norepinephrine, and serotonin, help to regulate our moods and keep us happy. Depressed people tend to have lower levels of norepinephrine, dopamine, and serotonin. If, for any reason, the amounts of these key neurotransmitters drop below critical levels, the result may be an endogenous depression that seems to come from nowhere, lingers forever, saps energy, and ruins lives.

Why do brain levels of mood regulators fall in some people, but not in others? We can't fully answer that question, although we know that genetics plays a major role. Depression, like other mood disorders, tends to run in families. Depression is even more likely to be shared by identical twins: If one is depressed, there's a better than 50% chance that the other will be, too.

Dutch researchers have found more symptoms of depression and lower serotonin levels in men with chronic low cholesterol, as compared with men with normal cholesterol. Cholesterol may affect the metabolism of serotonin, causing the depression (Ainiyet et al. 1996).

A great deal of research has looked into possible environmental or psychological causes of depression. Some investigators believe that people who are pessimistic, often feel overwhelmed by life, or have low self-esteem, are more likely to suffer from depression. It may be that some of us are lucky enough to have large reserves of "happy" neurotransmitters in our brains, but others have just enough to barely keep a smile on their faces.

Although biochemistry is the biggest factor in major depression, we're also affected by what happens to us in our lives. We're all hit by unpleasant events that may cause brain levels of norepinephrine and dopamine to fall temporarily. People with naturally large reserves usually get through the troubling times with minimal difficulties, but those with low chemical levels to begin with are more likely to lapse into depression. Stress has been linked to depression as well; stress increases the production of the immunological signaling chemicals IL-1beta and TNF-alpha and decreases the level of IL-2, IFN-gamma, MHC II, and NK cell activity. Both depression and cancer are linked to this shift in the chemical signals in the body (Maddock et al. 2001; Raison et al. 2001).

Women, moreover, seem to suffer more from depression than men. Some researchers argue that this disparity is caused by gender hormonal differences; others suggest that the difference is due to socialization. Girls in our society are taught to monitor their feelings and to ask for help when they are troubled. Boys, on the other hand, are encouraged to ignore their feelings. It may be that men and women are equally likely to become depressed, but that men are more reluctant to admit that they are down. In any case, it seems clear that biochemistry is the major cause of endogenous depression, with psychology and hormones playing supporting roles.


Several types of medical professionals treat depression, including family doctors, internists, psychiatrists, psychologists, and social workers. The therapies they offer are numerous, but are of three main types: psychotherapy, or "talk therapy;" drugs; and electroconvulsive shock therapy. These treatments may be used alone or in combination.

Types of psychotherapy include behavioral therapy, cognitive therapy, and psychodynamic therapy. These treatments help people learn to restructure the way they behave, think, and relate to others to better improve mental well being.

The central idea of drug treatment is to boost levels of neurotransmitters thought to be low in depression. State of the art treatment has evolved a great deal since the 1950s, when doctors gave depressed patients stimulants such as amphetamines. Though stimulants can boost mood, they also carry serious side effects, including nervousness, increased blood pressure, rapid heartbeat, and irregular heart rhythms. Over time, the drugs have been refined to act more selectively to alleviate depression, but with fewer adverse reactions.

Although not as gruesome as it is in movies, electroconvulsive therapy (ECT) is not a pleasant experience. Electricity shot though the brain can sideline a bout of depression, but it is only a temporary measure. It does not cure the disease and often it destroys parts of the memory.

Which treatment works best? That answer isn't clear. Some research shows that about half of depressed patients will respond to either psychotherapy or drug therapy (Keller et al. 2000). Other research indicates that drug therapy has an advantage over psychotherapy (Thase et al. 2000).

The initial choice depends both upon the individual's preference and the severity and duration of his or her depression. People with mild to moderate depression may find that psychotherapy alone does the trick. For people with chronic or severe depression, a combination of psychotherapy and medications may be the best option. Electroconvulsive therapy, while effective, is generally reserved for people with chronic depression unresponsive to medication.


Today, physicians and psychiatrists have numerous drugs at their disposal. Tricyclic antidepressants (TCAs) include Tofranil (imipramine) and Elavil (amitriptyline). Called tricyclics because of their three-ringed chemical structure, they work by altering the way the brain responds to norepinephrine and serotonin. Hundreds of clinical studies involving tricyclic antidepressants have produced only moderate results. In only about 60% of these tests have the tricyclics proved to be more effective than placebos such as sugar pills.

Monoamine oxidase inhibitors (MAOIs), such as Nardil (phenelzine) and Parnate (tranylcypromine), act as "shields" to norepinephrine and dopamine, preventing their breakdown by enzymes. MAOIs can have serious side effects if mixed with certain foods (Sullivan et al. 1984; Walker et al. 1984; Mirchandani et al. 1985; Gardner et al. 1996).

Selective serotonin reuptake inhibitors (SSRIs) include Zoloft (sertraline), Paxil (paroxetine), Celexa (citalopram), and Prozac (fluoxetine). These widely prescribed drugs (the SSRIs) enhance or increase serotonin levels by preventing the hormone from being reabsorbed and "taken out of circulation."

The medications have helped many people to regain their sense of equilibrium, but they have potentially serious side effects and must be used with caution. Fortunately, the more serious adverse effects are rare. Common side effects include:

  • Tricyclics: headache, dry mouth, constipation, diarrhea, nausea, indigestion, fatigue, weakness, drowsiness, nervousness, anxiety, excessive sweating, tremor, insomnia, weight gain, "sweet tooth."
  • MAOIs: dizziness, restlessness, tremors, dry mouth, constipation, difficult urination, blurred vision, "sweet tooth."
  • SSRIs: nausea, diarrhea, nervousness, anxiety, drowsiness, insomnia, headache, increased sweating, increased or decreased appetite, and decreased sexual drive (Most of these symptoms wane or disappear with time. Celexa [citalopram], a newer SSRI, seems to be better tolerated.)

In the 1960s, doctors started using lithium to treat bipolar disorder. Potential side effects of lithium--marketed as Carbolith, Euralith, Lithane, and Lithonate--include dizziness, dry mouth, increased urination, lack of appetite, vomiting, diarrhea, stomach pain, irregular heartbeat, shortness of breath, swelling of hands and feet, slurred speech, headaches and muscle aches, weakness, sleepiness, and confusion. Newer medications, such as the anticonvulsant drug gabapentin (Neurontin), are under investigation as mood stabilizers.

Some medications may contribute to depression. Examples include ibuprofen, Benadryl, Xanax, Valium, Librium, Klonopin, Butisol, Fiorinal, Inderal, Lopressor, Seconal, Halcion, Compazine, Thorazine, Percodan, Darvocet, Percocet, and Dalmane. If you are taking any of these medicines, ask your physician to review with you all of the potential side effects. If you or anyone in your family has or has had problems with depression, make sure your doctor knows about this before he or she writes you a prescription.

Antidepressant medications, while helpful to many people, are not panaceas. Some studies have shown that drugs are of no value in treating about 33% of depression cases. In another 33% of cases, the drugs were only a little more effective than placebos. In addition, they can cause side effects. On the other hand, depression itself is unpleasant and carries the life-threatening risk of suicide (Shea et al. 1992; Emslie et al. 1997; Tanghe et al. 1997).

Caution: If you are already on an antidepressant, do not stop treatment without consulting your physician. Abrupt discontinuation of some of these drugs can lead to unpleasant symptoms such as nausea, vomiting, tremor, fatigue, and headache, not to mention re-emergence of depression. Also know that several of the natural supplements listed below can interact with drug treatment.


  • Alcohol
  • Caffeine
  • Sugar

Hippocrates, the great Greek physician and Father of Medicine, said: "From the brain, and from the brain only, arise our pleasures, joys, laughter, and jests, as well as our sorrows, pains, griefs, and tears."

It's startling to learn that there are 15 trillion neurons (nerve cells) in the human brain. There are far more glial cells (neuroglia) that fill the spaces between the neurons, Schwann cells, and miles of blood vessels to nourish the three or so pounds of brain tissue in the average head.

Three pounds isn't much: only 2% of the body weight of a person weighing 150 pounds. Brain cells are hungry cells, demanding nourishment from as much as 30% of circulating blood. We used to think that the brain could somehow protect itself from nutrient deficiencies, but today we know that the brain requires specific nutrients. If the brain doesn't get them, its biochemistry changes, resulting in fatigue, depression, irritability, and other symptoms.

For example, the brain needs a good supply of B vitamins to act as coenzymes (catalysts) for many functions, including converting nutrients from food to fuel that our bodies can use. Glucose is the brain's primary fuel. If glucose levels fall, we may feel depressed, tired, or unable to think clearly.

B vitamins also are needed to help the brain make neurotransmitters, the "messengers" that enable brain cells to communicate with each other. Vitamin B6 is needed to manufacture serotonin, a neurotransmitter that produces feelings of well-being. Without proper supplies of vitamin B12, the brain could not make acetylcholine, an important neurotransmitter involved in learning and memory. The B vitamin known as folate (folic acid) is needed to make an important group of mood-regulating chemicals called catecholamines, including dopamine, norepinephrine, and epinephrine (Bukreev 1978; Carney et al. 1990; Carney 1995; Fujii et al. 1996; Masuda et al. 1998; Bottiglieri et al. 2000; Zhao et al. 2001).

In many cases, depressed people with blood levels indicating that they lacked key nutrients respond quite well to supplements. Unfortunately, most physicians do not prescribe natural supplements to treat depression (Carney et al. 1990; Carney 1995).

In general, people who are depressed should follow these dietary guidelines:

Avoid Alcohol. It may make us feel giddy at first, but that's only because it's dulling our inhibitions. In the long run, alcohol is a depressant, which is the last thing depressed people need. If you must drink, limit yourself to one drink a day. (One drink means a single serving of a single alcoholic beverage a day, either one ounce of hard liquor, straight or mixed, four ounces of wine, or 12 ounces of beer.)

Quit Caffeine. Caffeine can leave you mentally and physically drained. Avoid the caffeine in coffee, tea, soft drinks, chocolate, and cocoa, as well as the "hidden" caffeine in Excedrin, Midol, Anacin, and many other medicines. (Ask your physician or pharmacist if the medicines you are taking contain caffeine. If they do, talk to your physician about switching to other medications.)

Avoid Sugar. Sugar jolts us with a burst of energy which can make us feel excited, talkative, and ready to take on the world. However, when the body responds by snatching the excess sugar out of circulation, it often takes too much, leaving us tired and depressed. Some depressed patients experience wild, sugar-induced fluctuations in their moods. Convincing them to stay away from cakes, candy, soda, and refined and processed foods often solves the problem.

Continued . . .

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