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June 2011

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Natural Treatment
of Depression

With depression and mood disorders rising to epidemic levels, we need to move beyond the initial treatment options of psychiatry, namely medication, and embrace a more natural and complete treatment approach. Whether someone is clinically depressed or has a bad case of the blues, the keys are two neurotransmitters, namely norepinephrine and serotonin.

Mainstream medicine has lost sight of the fact that nutrients in our diet are the precursors of neurotransmitters, just as nutrients make up 100% of the body. Amino acids are the precursors to every neurotransmitter, with the exception of acetylcholine.

There are several ways to test for neurotransmitters to find out which ones are deficient, and which ones are causing a person’s feeling of depression. We’ll get to lab testing later. Medicine and psychiatry have assumed that serotonin is the main problem in depression, and so their first treatment approach is with an SSRI antidepressant (like Prozac, Paxil and Zoloft) to raise serotonin levels. After testing people for neurotransmitters since 1982, I’ve found that at least 65% of depressed people are deficient in norepinephrine and not serotonin. Some depressed people are deficient in serotonin and some are deficient in both norepinephrine and serotonin.

How can you tell if your feeling of depression or the blues is a serotonin or norepinephrine problem? When norepinephrine is deficient, the person will feel depressed, and generally has an array of cognitive problems, such as decreased memory and concentration, brain fog, indecision, irritability, increased worry, anger, and insomnia.

Serotonin deficiency is associated with depressed mood and insomnia. There can be some cognitive problems, but they are much less frequent and intense than in norepinephrine-related depression.

Which Natural Way To Turn?

Let’s say you’re feeling depressed due to a serotonin deficiency, and you want a natural approach (or you want a natural approach to help you get off medications). Do you supplement with St. John’s Wort, SAMe (S-adenosyl methionine), L-tryptophan, 5-HTP (5-hydroxy-tryptophan), omega-3 fatty acids, or magnesium?

Before exploring which approach to take, let’s look at the biochemistry. The amino acid L-tyrosine enters the brain and is converted into the neurotransmitter dopamine, which then converts into norepinephrine. For an adult, 1000 mg of L-tyrosine twice a day will bring results. Tyrosine must be taken 45 to 60 minutes before or after breakfast and lunch. Protein is made up entirely of amino acids, and several amino acids will compete with tyrosine to cross the blood-brain barrier to get into the brain.

L-tyrosine requires pyridoxal-5-phosphate, P-5-P, to get converted into norepinephrine. P-5-P is the active form of vitamin B6, pyridoxine, and must be taken as an enteric-coated capsule. If you purchase P-5-P in a capsule, it will do little good, for it will be broken down by stomach acids and rendered useless.

The biochemistry that increases serotonin is similar to that of norepinephrine. The amino acid L-tryptophan, on an empty stomach, enters the brain, and in the presence of P-5-P, gets converted into 5-HTP and then serotonin. There is no controversy about whether L-tryptophan turns into serotonin, but there is debate about the efficacy of 5-HTP, which is unpredictable in getting into the brain.

The simple equation is this: L-tyrosine, in the presence of P-5-P, increases norepinephrine brain levels. L-tryptophan, in the presence of P-5-P, increases brain serotonin levels. The total biochemistry is a long chain of events in which a weakness in any part of that chain will interfere with the goal of increasing a deficient neurotransmitter.

In addition to L-tyrosine and L-tryptophan, other amino acids are implicated in mood. A study of 500 depressed people revealed a deficiency in the amino acid L-glutamine in 50% of the subjects.

Lab Testing

The most important lab test for depression is amino acid analysis. Amino acids, like L-tyrosine and L-tryptophan, are the “input” side to brain chemistry. Because almost all neurotransmitters are made from amino acids, treatment with amino acids is the first step in a natural approach.

The second important lab test is for urine organic acids. These are the breakdown products of 40+ important biochemical processes. This is the “output” side of brain chemistry. The organic acid test includes testing for the breakdown products of catecholamines (norepinephrine and dopamine) and serotonin. If your VMA (from organic acid testing) is quite low, I know that you are deficient in norepinephrine. On the other hand, if your 5-HIAA (5-hydroxy-indolacetic acid) is low, you’re deficient in serotonin.

Let’s look at how to understand the lab work. On amino acid testing, if L-tyrosine is low, chances are extremely high that you are deficient in norepinephrine, but I’ll want to look at the results of organic acid testing for confirmation. If L-tyrosine is low, VMA, the breakdown product of norepinephrine, is usually deficient.

Similarly, on amino acid testing, if L-tryptophan is deficient, chances are very high that you are deficient in serotonin, but I’ll want to confirm that with the organic acid test. If 5-HIAA, the breakdown product of serotonin, is deficient, you have a serotonin deficiency.

There’s a mathematical equation that tells us the likelihood of L-tyrosine or L-tryptophan working. To find out if L-tyrosine will work, taking the numerical values from the test, divide L-tyrosine by the denominator, which is leucine plus isoleucine plus valine plus phenylalanine plus tryptophan. If that number is .15 or less, chances are 80% that you will have a good response to treatment with L-tyrosine. A similar equation exists to predict the response to treatment with L-tryptophan. The science of treating depression by normalizing the brain’s nutritional deficiencies has been established for more than 40 years.

The lab I use for amino acid and organic acid testing is Genova Labs. On occasion I’ll use Vitamin Diagnostics Lab, in New Jersey, to test for more than 10 different neurotransmitters. Their testing is based on research that has shown that the levels of neurotransmitters in blood platelets correlates strongly with brain levels of those neurotransmitters. I’ll go this route if I think someone might be deficient in acetylcholine, the lack of which causes severe memory problems and a feeling as if someone pulled the plug on mental energy.

Links in the Chain

The response to amino acid therapy depends on the weakest link in a chain of events. First, it’s important to identify and treat any problems with digestion and absorption from the gut. If the digestive tract is not running at 100%, absorption of nutrients declines.

B vitamins are essential for this biochemistry. Nearly every B vitamin plays a role in brain chemistry, the most important ones being biotin, folic acid, P-5-P, and B12. So supplement with a multi-B vitamin. Vitamin C is also important, and is critical for the production of serotonin, norepinephrine, and for adrenal function.

Minerals also play a role, the most important ones for neurotransmitters being magnesium, zinc, copper, and iron. Magnesium is the most important mineral for amino acid chemistry. If you’re depressed and feeling agitated, or fatigued, apathetic and slowed down, you are likely to have a magnesium deficiency.

Essential fatty acids (EFAs) are another link. Omega-3 fatty acids have been shown to alleviate depression. The balance of omega-3 and omega-6 fatty acids is important in maintaining healthy cell membranes. Given that the brain is 40% fat, we can’t ignore the role of EFAs.

SAMe has become a popular natural treatment for serotonin-related depression. SAMe, a variant of the amino acid methionine, is a cofactor in the biochemical chain that produces serotonin.

St. John’s Wort, an herb, has been found to be helpful in treating depression. There are a number of theories about how it works, and that research goes on.

Many people ask why L-tyrosine is recommended to raise norepinephrine levels, instead of using the amino acid L-phenylalanine. Phenylalanine turns into L-tyrosine and will raise norepinephrine levels, but one should first go the L-tyrosine route, along with the needed cofactors, for a couple of months. If you are still depressed, or improving but still have a way to go, then add L-phenylalanine. Phenylalanine can raise blood pressure, so it’s not a first line treatment.

Let’s summarize the initial supplements for treating depression:

1) L-tyrosine, L-tryptophan or both - depending on what the lab data indicates. 2) P-5-P, 3) B complex, 4) multivitamin, 5) multi-mineral, 6) magnesium, which needs to be taken with calcium to keep the two in balance, 7) Vitamin C, and 8) sublingual B12.

The Anxiety-Depression Connection

Many depressed people also feel anxious. For many people, correcting norepinephrine and serotonin will alleviate depression and anxiety. However, if anxiety persists, supplementing with GABA, up to 4 grams a day, is recommended. If GABA is helping you, do not think that more is better. At high doses GABA produces anxiety, rather than alleviating it.

In treating depression with or without anxiety, there are a number of issues, beyond the normal biochemistry, to look at: 1) Sugar depletes B vitamins; 2) Nicotine depletes vitamins A, C, E, and B. It decreases vitamin C by 50%; 3) Caffeine stimulates the release of norepinephrine, but in the process depletes the brain of L-tyrosine, the precursor to norepinephrine; 4) Long-term excessive alcohol use can deplete almost all neurotransmitters, including norepinephrine, serotonin, GABA, and acetylcholine. Alcohol abuse will lead to depression. Alcohol treatment involves repairing all neurotransmitters, but GABA depletion is the lynch pin.

A final consideration involves antidepressant medications. SSRIs (Paxil, etc) increase serotonin levels but, in the process, deplete the brain of L-tryptophan, which is stored in nerve endings. Bupropion (Wellbutrin), an antidepressant that increases norepinephrine levels, depletes the brain of its stores of L-tyrosine. As a result, these medications often start to lose their efficacy after many months. The usual psychiatric recommendation is to increase the dosage of that medication, rather than to supplement with the depleted amino acids.

Optimal Mind

In this series we’ve looked at conventional treatments for mood, such as medications, as well as natural ways of bringing the brain to an optimal level. A total approach also includes looking at our relationships, stressors, unresolved conflict, spiritual connection, and sense of purpose. If life is a horse and carriage, our sense of purpose is the horse, and its power will just pull our life forward automatically. Without a sense of purpose, our life is only the carriage. In that situation it takes a great deal of effort to get going, to feel happy, and motivated. While we don’t all have a clear sense of purpose, Wayne Dyer has explained that, for some, beginning to inquire about one’s purpose ——is one’s purpose. So, don’t wait to get that horse in place. My goal is to empower people by helping them develop a healthy brain, a peaceful and powerful mind, a spiritual connection, and a sense of purpose. With that holistic approach to life, people can go way beyond limiting thoughts about their potential for healing, success, and happiness.

David Gersten, M.D. practices Nutritional Medicine and Integrative Psychiatry out of his Encinitas office and can be reached at 760-633-3063. Please feel free to access 1,000 online pages about holistic health, amino acids, and nutritional therapy at and