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What happens when an individual is depressed, and antidepressants do not work? Typically, another type of antidepressant will be prescribed, but the new pill is often found to be of no more benefit than the first pill. Eventually, it is on to a third pill with some hope in sight, but the prospects of getting well fades into a cruel illusion, a mirage that is seem far off in a distance. This scenario need not be the case if the actual cause and type of depression are discovered, and treated appropriately. In this article, intended for the healthcare provider who addresses the patient’s issues from a natural perspective, I will address one type of depression that is almost always overlooked, rarely diagnosed, does not respond well to antidepressants, and has a very simple solution.
Depression has many causes. Some causes of depression have a physiological basis, other causes have dietary, environmental, social or psychological factors involved. Objective evidence is rarely, if ever, present in most forms of depression. Subjective evidence supporting the diagnosis is, on the other hand, almost always present. No specific laboratory tests are diagnostic of depression. Laboratory tests, however, are often performed specifically to identify any potential illnesses or disorder that may be causing the associated symptoms of depression. In some cases, the diagnosis of depression is offered on the basis of exclusion, based purely on patient history and current subjective complaints. A diagnosis of exclusion is issued when no other explanation for the signs and symptoms can be found. In many cases, the cause is not searched for following the diagnosis of depression. If the cause of depression can be discovered, elimination of the causative factors would cause the depression to cease, and is the only logical treatment leading to a cure.
Depression can often be linked to scarce or missing nutrients in the diet. One common dietary cause of depression is a reduced level of Omega-3 fatty acids. This is largely due to the lack of these essential fatty acids in the modern day diet. Another dietary cause of depression is a nutritional deficiency of the amino acid tryptophan, which is the precursor to the neurotransmitter serotonin. If tryptophan levels are low, serotonin levels subsequently decrease.
Certain nutrients must be present in order for the brain to synthesize neurotransmitters. In order for the body to synthesize serotonin and melatonin, the amino acid tryptophan must be present. For the synthesis of the neurotransmitters dopamine and norepinephrine, the amino acid tyrosine must be present. Another neurotransmitter, Gamma Amino Butyric Acid (GABA), is synthesized from the amino acid glutamine. The presence of these amino acids, however, is not sufficient in itself to guarantee that the neurotransmitters are synthesized in normal levels in the brain. Pyridoxine (vitamin B6) and zinc are two important nutrients that must be present for the body to synthesize serotonin, dopamine, norepinephrine, and GABA. Without B6 and zinc, conversion of the aforementioned amino acids to the respective neurotransmitters cannot occur.
Some people have a marked deficiency of vitamin B6 and zinc due to a specific genetic cause. In these people, insufficient amounts of vitamin B6 and zinc are available to allow for the synthesis of normal levels of neurotransmitters. The genetic condition is called pyroluria, which is a genetically based abnormality involving hemoglobin synthesis. Pyrrole, a by-product of hemoglobin synthesis, is found in remarkably high levels in the person with pyroluria. The astute practitioner would recognize pyrrole as the simplest compound from the imidazole family. Pyrrole binds to pyridoxine (vitamin B6) and zinc, forming kryptopyrrole. Kryptopyrrole, when literally translated, means “hidden pyrrole.” Kryptopyrrole is excreted in the urine. When the pyrrole binds with B6 and with zinc, marked depletion of vitamin B6 and zinc occurs within the body, resulting in a severe deficiency of these two nutrients. Individuals with pyroluria become deficient in vitamin B6 and zinc, therefore subsequently deficient in the neurotransmitters serotonin, melatonin, dopamine, norepinephrine and GABA.
Signs and symptoms of pyroluria are simply those of a severe combined zinc and B6 deficiency. If one would to look up the symptoms of pyroluria, the psychological symptoms will be listed to be the inability to handle or manage stress, depression, anxiety, fearfulness, nervousness, mood swings, severe inner tension, and intermittent anger. Other symptoms would include increased sensitivity to sounds or noise, increased sensitivity to light, poor dream recall, and avoidance of social interaction. Signs, or that which can readily be observed by another individual, are often reported to be pale skin that easily burns, white marks on their nails (from zinc deficiency), and stretch marks on the skin. Other characteristics of pyroluria include avoidance of breakfast, impaired glucose tolerance, fatigue, poor sleep quality, and, occasionally, increased weight. In severe cases, hallucinations, delusions, paranoia, and loss of contact of reality may be evidenced. The symptoms of pyroluria are increased when the individual is under stress. Remember, however, that when neurotransmitter levels drop or are out of balance with each other, just about any psychological or neurological symptoms can be experienced by the patient.
A urine test is often prescribed to determine the level Kryptopyrrole being excreted. The test, however, is highly subject to false negatives. Kryptopyrrole is very sensitive to oxidation and should not be exposed to air. Pyrrole darkens on exposure to light, especially when exposed to direct sunlight. The darkened color is due to the polymerization of pyrrole upon exposure to light. Any urine sample should be stored in sealed darkened glass tubes without air entrapment in the tube. Unless the levels of Kryptopyrrole in the urine are very high, Kryptopyrrole will most likely be oxidized by the time the urine is prepared to be sent off to the lab. This will lead to a possible false negative test. Serum levels of B6 and Zinc provide a better diagnosis, but vitamin and mineral supplements must be avoided for three to four days before the test.
Persons with pyroluria cannot efficiently synthesize serotonin, dopamine, norepinephrine, or GABA. This is due to the significantly decreased levels if B6 and zinc in the body. Many of these persons have been prescribed selective serotonin reuptake inhibitors (SSRI’s), which may have only marginal benefit for a limited time. In order to reuptake a neurotransmitter, existence of a sufficient amount of the neurotransmitter must be present in order to achieve the desired results. You simply cannot reuptake that which is not there. Monoamine oxidase inhibitors (MAOIs) are also prescribed for depression. MAOI’s work by inhibiting the breakdown of Monoamine oxidase, thus prolonging the action of the monoamine neurotransmitters dopamine, norepinephrine and serotonin at the sympatic junction. Attempting to prolong the action of drastically deficient levels of neurotransmiters with an MAOI is of not much help, and is often worse than the SSRI for the patient with pyroluria. In some cases, MAOI’s often make the patient with pyroluria worse, instead of better, but that is a whole other topic.
The notion that health can be restored or every disease can be cured by ingesting chemical compounds manufactured in a chemistry lab is actually quite absurd. To believe that chemicals can cure a disease requires us also to believe that the reason the disease was allowed to occur in the first place is because of a deficiency in the body of some manufactured chemical. That notion is equally absurd, and is nothing more than ad ridiculum. Logic would dictate that restoration of deficient neurotransmitter levels through appropriate nutrient supplementation is the only sound approach for the patient with pyroluria.
Persons with pyroluria are often under chronic stress. Cortisol is produced by the adrenal glands when the body is under stress. Biochemically and physiologically, the body does not see any difference between chemical, physical, or emotional stress. Cortisol is released as a response to chronic stress, no matter the source of the stress. Cortisol is also known to be elevated in depression and sleep disturbances. An elevated cortisol level activates a liver enzyme called tryptophan pyrrolase, which breaks down the amino acid tryptophan, decreasing the amount available by the body to make serotonin. Chronic stress therefore leads to reduced serotonin levels because of tryptophan being broken down by tryptophan pyrrolase. Because of the actions of the enzyme tryptophan pyrrolase, tryptophan supplementation may be indicated in some cases of pyroluria.
In some cases, patients with pyroluria may develop tardive dyskinesia. Tardive dyskinesia is generally characterized by repetitive and involuntary movements involving the facial muscles. These movements include grimacing, tongue protrusion, lip smacking, puckering and pursing of the lips. Tardive dyskinesia is most commonly seen in some psychiatric patients who have been taking dpoamine-blocking agents for a prolonged period. In the patient with pyroluria, tardive dyskinesia is most likely a result of a manganese deficiency. Manganese supplementation may be indicated in these cases.
In order to properly address pyroluria, supplementation of vitamin B6 and the mineral zinc is in order. B vitamins should be taken as a group since the ingestion of an excess of one vitamin in the B group could cause a deficiency of other vitamins in the group. The RDA of B6 is 2 mg, which is totally inadequate for the person with pyroluria. The B-complex used to treat pyroluria should typically contain at least 50 mg. of vitamin B6. In some cases, additional vitamin B6 in addition to that found in the B-complex may be necessary. The preferred form for the mineral zinc is zinc picolinate. The RDA of zinc is 15 mg., again inadequate for the person with pyroluria. 30 to 60 mg. would be more appropriate when treating pyroluria. Results are generally seen rapidly, generally within a few days. Complete balancing of the involved neurotransmitter systems generally takes 30-45 days.
In the patient with pyroluria, vitamin B6 and zinc supplements are used to ensure that adequate amounts of these nutrients are present for the biochemical reactions that they support. If the appropriate levels of vitamin B6 and zinc are not present, the associated biochemical reactions involved in neurotransmitter production cannot go to completion, therefore cannot produce the neurotransmitter. A biochemical reaction that cannot go to completion is essentially “hung” in that state, awaiting some nutrient to become available. When the nutrient becomes available, the hung reaction then can proceed toward completion. When vitamin B6 and zinc are available again, the cascade of biochemical reactions involved in neurotransmitter synthesis will occur quite rapidly by the unsaturated enzymes associated with the hung reactions. Obtaining adequate levels of vitamin B6 and zinc will virtually eliminate these hung reactions, therefore, eliminating the causative factor in the development of pyroluria.
Hung biochemical reactions, however, are not limited to vitamin and mineral deficiencies. Other nutrients involved in neurotransmitter production, such as amino acids, may also be deficient. Amino acid deficiencies are often seen among persons taking antacids and medications designed to suppress hydrochloric acid secretion in the stomach. These medications are commonly prescribed for ulcers and acid reflux disease. Unfortunately, these medications also inhibit protein digestion by either neutralizing the acid medium of the stomach or suppressing the secretion of the acid required by the enzymes that perform protein digestion. As a result, amino acids, which are the products of protein digestion, become scarce. If an amino acid deficiency is suspected, supplementation with appropriate free-form amino acids would enhance neurotransmitter production. Supplementation with free-form amino acids should, however, be done with care. An understanding of the psychological profile of an individual would be desirable when choosing the appropriate amino acid supplements.
Should vitamin B6 and zinc supplements be used by the patient taking antidepressants, it should be done under the close supervision of a qualified practitioner. The patient with pyroluria will most likely experience rapid production of neurotransmitters when beginning vitamin B6 and zinc supplementation. Any medications may have to be adjusted quickly to account for the rapidly changing biochemistry of the brain. The patient should be familiarized with the signs and symptoms of Serotonin Syndrome, a rare, but potentially serious side effect of marked increase of serotonin activity.
It is quite sad when someone finds out too late that something could have been done earlier to restore their health. Years of accumulated damage, years of pain, and years of lost enjoyment could have been averted if only the right information or the right health care practitioner were only found earlier.
