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 persons feeling of depression. Well 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, Ive 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?

Lets say youre 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. Johns Wort, SAMe (S-adenosyl methionine), L-tryptophan, 5HTP (5-hydroxy-tryptophan), omega-3 fatty acids, or magnesium? Before exploring which approach to take, lets 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 5HTP, 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 Ltyrosine and L-tryptophan, are the input side to brai n 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, youre deficient in serotonin. Lets 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 Ill 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 Ill want to confirm that with the organic acid test. If 5-HIAA, the breakdown product of serotonin, is deficient, you have a serotonin deficiency. Theres a mathematical equation that tells us the likelihood of L-tyrosine or Ltryptophan 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 brains 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 Ill 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. Ill go this route if I think someone migh t 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, its 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 youre 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 cant 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. Johns 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 its not a first line treatment. Lets summarize the initial supplements for treating depression:

1) L-tyrosine, L-tryptophan or both - depending on what the lab data indicates. 2) P5-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 weve 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 dont all have a clear sense of purpose, Wayne Dyer has explained that, for some, beginning to inquire about ones purpose is ones purpose. So, dont wait to get that horse in place. My goal is to empower pe ople 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 www.aminoacidpower.com and www.imagerynet.com.

Tyrosine
Overview:

Tyrosine is a nonessential amino acid the body makes from another amino acid called phenylalanine. It is a building block for several important brain chemicals called neurotransmitters, including epinephrine, norepinephrine, and dopamine. Neurotransmitters help nerve cells communicate and influence mood. Tyrosine also helps produce melanin, the pigment responsible for hair and skin color. It helps in the function of organs responsible for making and regulating hormones, including the adrenal, thyroid, and pituitary glands. It is involved in the structure of almost every protein in the body. It's rare to be deficient in tyrosine. Low levels have been associated with low blood pressure, low body temperature, and an underactive thyroid. This does not mean, however, that taking tyrosine supplements will help any of these conditions. Phenylketonuria (PKU) This serious condition occurs in people whose bodies can't use the amino acid phenylalanine. It can lead to brain damage, including mental retardation. People with PKU must avoid any phenylalanine in their diets. Because tyrosine is made from phenylalanine, people with PKU can be deficient in tyrosine. Tyrosine is used in protein supplements for people with PKU, but most doctors don't recommend more tyrosine supplements. If you have PKU, your doctor will determine if you need more tyrosine and how much. Stress Tyrosine is involved in the production of the stress hormones epinephrine and norepinephrine. Some researchers believe that, under stress, the body isn't able to make enough tyrosine from phenylalanine. Some animal and human studies suggest that tyrosine supplements may help improve memory and performance under psychological stress, but more research is needed. Sleep deprivation One study suggests that taking tyrosine may help you be more alert after sleep deprivation, but more research is needed.

Other Some athletes claim that tyrosine helps their performance. However, there is no proof that this claim is true or safe. Because tyrosine helps the body produce the mood-influencing chemical dopamine, and because people who are depressed often have low levels of tyrosine, researchers thought that tyrosine might help treat depression. However, studies have found that it has no effect.
Dietary Sources:

Tyrosine is found in soy products, chicken, turkey, fish, peanuts, almonds, avocados, bananas, milk, cheese, yogurt, cottage cheese, lima beans, pumpkin seeds, and sesame seeds.
Available Forms:

Tyrosine is also available as a dietary supplement, in capsule or tablet form.

How to Take It:

Take tyrosine supplements at least 30 minutes before meals, divided into 3 daily doses. Taking vitamins B6, B9 (folate), and copper along with tyrosine helps the body convert tyrosine into important brain chemicals. Pediatric Don't give tyrosine supplements to a child without first asking your doctor. Adult Doses vary. Talk to your nutritionist or doctor about what dose is right for you. To treat symptoms of sleep deprivation, one study used 150 mg per kilogram of body weight per day.
Precautions:

Because of the potential for side effects and interactions with medications, you should take dietary supplements only under the supervision of a knowledgeable health care provider. People who have migraine headaches should avoid tyrosine, as it can trigger migraine headaches and stomach upset. People with hyperthyroidism or Graves disease should avoid tyrosine supplements because tyrosine may increase levels of thyroid hormone.

Possible Interactions:

If you are being treated with any of the following medications, you should not use tyrosine supplements without first talking to your health care provider. Monoamine Oxidase Inhibitors (MAOIs) -- Tyrosine may cause a severe increase in blood pressure in people taking antidepressant medications known as MAOIs. This rapid increase in blood pressure, also called "hypertensive crisis, can lead to a heart attack or stroke. People taking MAOIs should avoid foods and supplements containing tyrosine. MAOIs include:

Isocarboxazid (Marplan) Phenelzine (Nardil) Tranylcypromine (Parnate) Selegiline

Thyroid hormone -- Tyrosine is a precursor to thyroid hormone, so it might raise levels too high when taken with synthetic thyroid hormones. Levodopa (L-dopa) -- Tyrosine should not be taken at the same time as levodopa, a medication used to treat Parkinson's disease. Levodopa may interfere with the absorption of tyrosine.
Alternative Names:

L-tyrosine

Reviewed last on: 7/17/2011 Steven D. Ehrlich, NMD, Solutions Acupuncture, a private practice specializing in complementary and alternative medicine, Phoenix, AZ. Review provided by VeriMed Healthcare Network.

Read more: http://www.umm.edu/altmed/articles/tyrosine-000329.htm#ixzz28FitjoJl

Tyrosine is one of the amino acids, which are the building blocks of protein. The body makes tyrosine from another amino acid called phenylalanine. Tyrosine can also be found in dairy products, meats, fish, eggs, nuts, beans, oats, and wheat. Tyrosine is used in protein supplements to treat an inherited disorder called phenylketonuria (PKU). People who have this problem cant process phenylalanine properly, so as a result they cant make tyrosine. To meet t heir bodies needs, supplemental tyrosine is given. People take tyrosine for depression, attention deficit disorder (ADD), attention deficit-hyperactivity disorder (ADHD), the inability to stay awake (narcolepsy), and improving alertness following sleep deprivation. It is also used for stress, premenstrual syndrome (PMS), Parkinson's disease, Alzheimer's disease, chronic fatiguesyndrome (CFS), alcohol and cocaine withdrawal, heart disease and stroke, ED (erectile dysfunction), loss of interest in sex, schizophrenia, and as a suntan agent and appetite suppressant. Some people also apply tyrosine to the skin to reduce age-related wrinkles.

How does it work? The body uses tyrosine to make chemical messengers that are involved in conditions involving the brain such as mental alertness.

Tyrosine is LIKELY SAFE in food amounts and POSSIBLY SAFE when taken by adults short-term in medicinal amounts or applied to the skin. Tyrosine seems to be safe when used in doses up to 150 mg/kg per day for up to 3 months. Some people experience side effects such as nausea, headache, fatigue, heartburn, and joint pain. There isn't enough information available to know if tyrosine is safe for children to use in medicinal amounts. Dont give it to children without the advice of your healthcare provider until more is known. Special Precautions & Warnings:

Pregnancy and breast-feeding: Not enough is known about the safety of using tyrosine during pregnancy and breast-feeding. Stay on the safe side and avoid use. Overactive thyroid (hyperthyroidism) or Graves disease: The body uses tyrosine to make thyroxine, a thyroid hormone. Taking extra tyrosine might increase thyroxine levels too much, making hyperthyroidism and Graves disease worse. If you have one of these conditions, dont take tyrosine supplements.

Levodopa interacts with TYROSINE Tyrosine might decrease how much levodopa the body absorbs. By decreasing how much levodopa the body absorbs, tyrosine might decrease the effectiveness of levodopa. Do not take tyrosine and levodopa at the same time.

Thyroid hormone interacts with TYROSINE The body naturally produces thyroid hormones. Tyrosine might increase how much thyroid hormone the body produces. Taking tyrosine with thyroid hormone pills might cause there to be too much thyroid hormone. This could increase the effects and side effects of thyroid hormones.

Tyrosine plays a large part in the making of the body's hormones. Adrenal hormones, thyroid hormones and melanin (skin hormone) are all made with tyrosine. These chemicals are the essential building blocks for the central nervous system, and maintain our overall bodymetabolism function. As brain neurotransmitters, these hormones work to regulate our moods and emotions. Moodregulating transmitters like dopamine, epinephrine and norepinephrine all depend on adequate amounts of tyrosine to function. During times of stress, the body converts the thyroid hormone into adrenalin. As such, healthy levels of tyrosine are needed for healthy brain function.

Read more: What Does Tyrosine Do? | eHow.com http://www.ehow.com/about_4614938_what-doestyrosine-do.html#ixzz28Fjq2tM4

Tyrosine-Derived Neurotransmitters
The majority of tyrosine that does not get incorporated into proteins is catabolized for energy production. One other significant fate of tyrosine is conversion to the catecholamines. The catecholamine neurotransmitters aredopamine, norepinephrine, and epinephrine (see also Biochemistry of Nerve Transmission).
Norepinephrine is the principal neurotransmitter of sympathetic postganglionic endings. Both norepinephrine and the methylated derivative, epinephrine are stored in synaptic knobs of neurons that secrete it, however, epinephrine is not a mediator at postganglionic sympathetic endings. Tyrosine is transported into catecholamine-secreting neurons and adrenal medullary cells where catechaolamine synthesis takes place. The first step in the process requires tyrosine hydroxylase, which like phenylalanine hydroxylase requires tetrahydrobiopterin (H4B, or written as BH4) as cofactor. The dependence of tyrosine hydroxylase on H4B necessitates the coupling to the action of dihydropteridine reductase (DHPR) as is the situation for phenylalanine hydroxylase and tryptophan hydroxylase (see below). The hydroxylation reaction generates DOPA (3,4-dihydrophenylalanine). DOPA decarboxylase converts DOPA to dopamine, dopamine -hydroxylase converts dopamine to norepinephrine and phenylethanolamine N-methyltransferase converts norepinephrine to epinephrine. This latter reaction is one of several in the body that uses SAM as a methyl donor generating S-adenosylhomocysteine. Within the substantia nigra and some other regions of the brain, synthesis proceeds only to dopamine. Within the adrenal medulla dopamine is converted to norepinephrine and epinephrine.

Synthesis of the Catecholamines from Tyrosine.

Once synthesized, dopamine, norepinephrine and epinephrine are packaged in granulated vesicles. Within these vesicles, norepinephrine and epinephrine are bound to ATP and a protein called chromogranin A. The actions of norepinephrine and epinephrine are exerted via receptor-mediated signal transduction events. There are three distinct types of adrenergic receptors: 1, 2, . Within each class of adrenergic receptor there are several sub-classes. The 1 class contains the 1A, 1B, and 1D receptors. The 1 receptor class are coupled to Gq-type G-proteins that activate PLC resulting in increases in IP3 and DAG release from membrane PIP2. The 2 class contains the 2A, 2B, and 2C receptors. The 2 class of adrenergic receptors are coupled to Gi-type G-proteins that inhibit the activation of adenylate cyclase and therefore, activation results in reductions in cAMP levels. The class of receptors is composed of three subtypes: 1, 2, and 3 each of which couple to Gs-type Gproteins resulting in activation of adenylate cyclase and increases in cAMP with concomitant activation of PKA. Dopamine binds to dopamineric receptors identified as D-type receptors and there are four subclasses identified as D1, D2, D4, and D5. Activation of the dopaminergic receptors results in activation of adenylate cyclase (D1 and D5) or inhibition of adenylate cyclase (D2 and D4).

Epinephrine and norepinephrine are catabolized to inactive compounds through the sequential actions of catecholamine-O-methyltransferase (COMT) and monoamine oxidase (MAO). Compounds that inhibit the action of MAO have been shown to have beneficial effects in the treatment of clinical depression, even when tricyclic antidepressants are ineffective. The utility of MAO inhibitors was discovered serendipitously when patients treated for tuberculosis with isoniazid showed signs of an improvement in mood; isoniazid was subsequently found to work by inhibiting MAO.

Metabolism of the catecholamine neurotransmitters. Only clinically important enzymes are included in this diagram. The catabolic byproducts of the catecholamines, whose levels in the cerebrospinal fluid are indicative of defects in catabolism, are in blue underlined text. Abbreviations: TH = tyrosine hydroxylase, DHPR = dihydropteridine reductase, H2B = dihydrobiopterin, H4B = tetrahydrobiopterin, MAO = monoamine oxidase, COMT = catecholamine-O-methyltransferase, MHPG = 3-methoxy-4-hydroxyphenylglycol, DOPAC = dihydroxyphenylacetic acid.