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Tinnitus Library

Tryptophan, Serotonin and Tinnitus

The Serotonin Deficiency Syndrome and The Chemistry of Calm by Barry Keate

Tinnitus patients are often depressed. In one study, 60% of the participants had major depression compared with 7% of a control group with general hearing loss but no tinnitus. (1) In addition, depressed tinnitus patients report more severe tinnitus and related disability than people without the condition. Experts think that tinnitus may trigger depression, which in turn worsens the way tinnitus is experienced.

Depression can be modulated by serotonin, a neurotransmitter found in the human brain and gut. It is known to be a contributor to feelings of wellbeing and happiness.  While there is a certain class of popular antidepressants, which attempt to basically “extend” the effect of existing serotonin levels, there is only one way to actually increase serotonin in the brain and that is with an essential amino acid called L-Tryptophan. I will have much more on that a little later.

Many doctors believe potentiating existing serotonin effects through medication will be helpful for the treatment of people with tinnitus by lowering the anxiety attached to it. They then prescribe a serotonin activating antidepressant, Selective Serotonin Re-uptake Inhibitors (SSRI), for the tinnitus patient. The concept behind this is correct but the execution is problematic. Here’s why:

Serotonin

Serotonin is a hormone stored in the gastrointestinal (GI) tract and the central nervous system (CNS). It acts as a neurotransmitter, a chemical that transmits nerve impulses across the synapse between neurons. This allows different parts of the brain to communicate and operate as a whole.

About 90% of the human body’s serotonin is located in the GI tract, where it is used to regulate intestinal movements. The remainder is in neurons in the CNS where it has various functions. These include the regulation of mood, appetite and sleep. (2)

Sometimes referred to as the happiness molecule, serotonin has a profound effect on mood. High levels of serotonin lead to a cheerful disposition and the ability to withstand everyday stress. Too little serotonin has been shown to lead to depression, problems with anger control, obsessive-compulsive disorder, and suicide.

So, it is reasonable to expect that by optimizing serotonin in the brain, we should be able to indirectly improve tinnitus by improving mood and reducing anxiety. The implementation of this idea, however, creates as many problems as it addresses.

Serotonin Optimizing Antidepressants

The history of psychoactive antidepressant medications began in the 1950’s when researchers treating tuberculosis with a new drug found their patients with improved moods. The drug, iproniazid, became the first of the monoamine oxidase inhibitor (MAOI) class of antidepressants. They operate by inhibiting the breakdown of monoamine neurotransmitters, such as serotonin and making them more available in the brain.

Because of potentially lethal dietary and drug interactions, MAOIs were replaced by a newer class of drugs called Tricyclic Antidepressants (TCAs). These medications operated along similar lines by preventing the breakdown of serotonin so it could be used by neurons for a longer time. The primary TCA medication is amitriptyline (Elavil), which is still in use today. However, the side effects of these drugs, while improved over MAOIs, were still quite serious and many people could not tolerate them.

Enter the newest class of serotonin optimizing medications, Selective Serotonin Re-uptake Inhibitors (SSRIs). These are the most widely used antidepressants today. SSRI antidepressants include Prozac, Paxil, Zoloft, and others. They are prescribed for major depressive disorders as well as anxiety disorders, such as social anxiety, panic disorders, obsessive-compulsive disorder (OCD), eating disorder and, occasionally, for post traumatic stress disorder (PTSD).

It is very important to know that none of the above medications create or increase serotonin levels in the brain. Instead, they inhibit the uptake of serotonin by the neuron after it has been used. In this way, serotonin is maintained in the synapse for longer than it would be otherwise and is able to be reused.

SSRI antidepressants are recommended by the National Institute for Clinical Evidence (NICE) as a first-line treatment of severe depression and for the treatment of mild-to-moderate depression that persists after conservative measures have failed. (3)

However, the effectiveness of these medications is controversial. Two meta-analysis of clinical trials published in 2008 and 2011 found that in mild and moderate depression, the effect of SSRIs is small or none compared to placebo, while in very severe depression the effect of SSRIs is between “relatively small and substantial.” (4) (5)

There are two primary problems associated with these medications, especially as they concern people with tinnitus. The first is the list of side effects. These include, but are not limited to, nausea, drowsiness, headache, bruxism (grinding the teeth), insomnia, diarrhea, weight loss/gain, sexual dysfunction, increased depression and anxiety, suicidal thoughts, and tinnitus.

That’s correct: tinnitus. Tinnitus is listed as a frequent side effect for all SSRI antidepressants. Not everyone who uses these will develop or worsen existing tinnitus but a significant percentage of them will. So here we have a condition where some doctors prescribe a medication to help with tinnitus when the medication may very well make it worse!

There are other, rare side effects that are much more serious. A couple of years ago, in 2011, my wife was prescribed Prozac for depression. After a few months on the drug, she started developing muscle stiffness in her legs. It slowly worked its way up her body and into her back and sides. She was becoming unable to walk. We were very worried and thinking she might be developing Muscular Sclerosis (MS). One day I saw a TV ad for one of these medications. Among the list of side effects mentioned was muscle stiffness. We had never thought it could be the Prozac but I looked it up and, sure enough, one of the potential side effects listed was the quite chilling effect called Neuroleptic Malignant Syndrome. This was listed as a rare but potentially life threatening side effect that had the effect of freezing the muscles. We immediately discontinue the medication but it took several months before her muscles started loosening up.

In addition to the side effects, SSRI antidepressants have serious withdrawal problems. This is similar to Benzodiazepine Withdrawal Syndrome where the brain stops making GABA, the inhibitory neurotransmitter, because it is fooled by the tranquilizing medication into thinking there is plenty. When trying to withdraw, the lack of GABA leads to a super-excitatory condition that is much like, or even worse than, the symptoms for which the drugs were started in the first place.

SSRI antidepressants cause the brain to think there is plenty of serotonin so it stops making it. When withdrawing, serotonin levels drop precipitously and disturbing withdrawal symptoms appear which may be indistinguishable from the reoccurrence of the original illness. (6)

As in Benzodiazepine Withdrawal Syndrome, doctors will change the SSRI prescription to one with a long half-life and go on an extended, slow reduction in the dosage to prevent the worst of the effects. However, many people are simply unable to withdraw from these drugs and are effectively sentenced to using them for the rest of their lives.

Tryptophan

As stated above, antidepressant medicines do not create serotonin. There is one way, and one way only, to create serotonin in the brain. That way is with the serotonin precursor, L-Tryptophan. This amino acid crosses the blood-brain barrier and creates serotonin, melatonin and niacin within the human brain.

L-Tryptophan is an essential amino acid. This means that the body cannot produce it and it must be obtained from the diet. It is found in most protein-based foods, most notably turkey, but is also found in oats, dried dates, chickpeas, pumpkin seeds, bananas, peanuts, milk, yogurt, cottage cheese, red meat, eggs, fish, and poultry.

While the amount of tryptophan in a typical diet meets basic metabolic requirements, it often fails to provide optimal brain serotonin levels. The reason for this is tryptophan is the least plentiful amino acid and it competes with other amino acids for transport through the blood-brain barrier. When a variety of amino acids are consumed together, tryptophan is at a disadvantage and often does not transport through the barrier.

As we age, tryptophan levels decline. This leads to a spectrum of mood disorders, often called “Grumpy Old Man (or Woman) Syndrome”, that include irritability, stress and anxiety. More serious symptoms, such as sleep disorders, depression, aggressive behaviors, even suicide, have all been traced to reduced levels of tryptophan causing a decrease in serotonin levels. (7)

Boosting and balancing brain serotonin through tryptophan supplementation, as opposed to drug therapy, is an innovative approach to depression that is gaining more and more traction, especially with the discovery that patients with major depression have low levels of tryptophan. (8)

Supplementing with L-Tryptophan is helpful for reducing PMS, reducing carbohydrate cravings and loosing weight, improving sleep and mood, and increasing endurance.

In 1989 there was a spontaneous outbreak of a rare and deadly disease in New Mexico called Eosinophilia-Myalgia Syndrome (EMS). The common cause was traced back to the fact that all the people who became sick had been using tryptophan as a dietary supplement. EMS caused the deaths of 37 people and permanently disabled another 1500. It was all manufactured at the Showa Denko plant in Japan.

The FDA immediately issued a recall of all tryptophan on the market and outlawed its importation and sale in 1991. At the time of the ban, the FDA did not know, or did not indicate, that EMS was caused by a contaminated batch, not the L-Tryptophan itself. Even when the contamination was discovered and the purification problem fixed, the FDA maintained the L-Tryptophan was unsafe.

In 2001, the FDA loosened the restrictions on marketing but not importation. Finally, in 2002, they removed all restrictions and L-Tryptophan has been sold in its original form since then. (10)

The nutritional requirement for L-Tryptophan is modest at 5 mg/kg of body weight, or about 375 mg for a 170 lb person. However, many adults choose to consume much more, up to 4-5 grams/day to improve mood or sleep. The only side effect of this dosage is drowsiness so it is best to start slow until you know how it affects you. Though the literature is thin for higher doses, some side effects are seen at dosages above 5 grams. These include tremor, nausea and dizziness. In rare cases, the “Serotonin Syndrome”, may occur. This is the result of too much serotonin stimulation when tryptophan is combined with serotonin drugs. Symptoms are serious and can include delirium, hyperthermia and coma. It is advisable not to combine tryptophan with prescription antidepressants. (9)

Tryptophan should always be taken on an empty stomach to prevent it competing with other amino acids for absorption.

Tryptophan may cause excessive sedation if it is taken with potentially sedating herbs such as catnip, kava kava, St. John’s wort, or valerian.

Clinical depression is a very serious condition and treatment through medication is often the right and prudent action to take. However, next time a doctor wants to write a prescription for an antidepressant, you may wish to suggest tryptophan. Or you could have another piece of turkey and a glass of warm milk.

References:

1 – “Can tinnitus be helped with antidepressants?” Consumer Reports http://consumerreports.org/cro/2012/04/can-tinnitus-be-helped-with-antidepressants/index.htm

2 – Berger M, Gray JA, Roth BL (2009) “The Expanded Biology of Serotonin”. Annu. Rev. Med. 60: 355-66.

3 - http://nice.org.uk/nicemedia.

4 – Fournier J, DeRubeis R, et al. “Antidepressant Drug Effects and Depression Severity”. Journal of the American Medical Association, 303 (1): 47-53.

5 – Kirsch I, Deacon BJ, et al. “Initial Severity and Antidepressant Benefits: A Meta-Analysis of Data Submitted to the Food and Drug Administration”. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2253608.

6 – Broekhoven F, Kan CC, Zitman FG. “Dependence Potential of Antidepressants Compared to Benzodiazepines”. Prog. Neuropsychopharmacol. Biol. Psychiatry, 26 (5): June 2002. 939-43.

7 – Sandyk R. “L-Tryptophan in Neuropsychiatric Disorders: a Review.” Int J Neurosci. 1992 Nov-Dec:67(1-4):127-44.

8 – Sa M, Ying L, Tang AG. “Simultaneous Determination of Tyrosine, Tryptophan and 5-Hydroxytryptamine in Serum of MDD Patients by High Performance Liquid Chromatography with Fluorescence Detection. Clin Chim Acta. 2012 Jun 14;413 (11-12):973-7.

9 – Fernstrom JD. “Effects and Side Effects Associated with the Non-Nutritional Use of Tryptophan by Humans”. J Nutr. 2012 Dec;142(12):2236S-2244S.

10 – http://en.wikipedia.org/wiki/tryptophan.