Phenylalanine – The Pain Reliever
Phenylalanine is an essential amino acid and the precursor for the amino acid tyrosine. Like tyrosine, it is the precursor of catecholamines in the body (tyramine, dopamine, epinephrine and norepinephrine). The psychotropic drugs (mescaline, morphine, codeine, and papaverine) also have phenylalanine as a constituent.
Phenylalanine is a precursor of the neurotransmitters called catecholamines, which are adrenalin-like substances. Phenylalanine is highly concentrated in the human brain and plasma. Normal metabolism of phenylalanine requires biopterin, iron, niacin, vitamin B6, copper and vitamin C. An average adult ingests 5 g of phenylalanine per day and may optimally need up to 8 g daily.
Phenylalanine is highly concentrated in high protein foods, such as meat, cottage cheese and wheat germ. A new dietary source of phenylalanine is artificial sweeteners containing aspartame. Aspartame appears to be nutritious except in hot beverages; however, it should be avoided by phenylketonurics and pregnant women. Phenylketonunics, who have a genetic error of phenylalanine metabolism, have elevated serum plasma levels of phenylalanine up to 400 times normal. Mild phenylketonuria can be an unsuspected cause of hyperactivity, learning problems, and other developmental problems in children.
We have found that about 10 percent of depressed patients have low plasma phenylalanine, and phenylalanine is an effective treatment in these cases. Elevated phenylalanine levels occur during infection. Phenylalanine levels are lowered by caffeine ingestion.
Phenylalanine can be an effective pain reliever. Its use in premenstrual syndrome and Parkinson’s may enhance the effects of acupuncture and electric transcutaneous nerve stimulation (TENS). Phenylalanine and tyrosine, like L-dopa, produce a catecholamine effect. Phenylalanine is better absorbed than tyrosine and may cause fewer headaches.
Low phenylalanine diets have been prescribed for certain cancers with mixed results. Some tumors use more phenylalanine (particularly melatonin-producing tumors called melanoma). One strategy is to exclude this amino acid from the diet, i.e., a PKU diet. The other strategy is just to increase phenylalanine’s competing amino acids, i.e., tryptophan, valine, isoleucine and leucine, but not tyrosine.
Form and Absorption of Phenylalanine
Phenylalanine is available as D, L or DL form; this refers to right (D) or left (L) forms of spatial orientation of the molecules. DL-phenylalanine is a 50/50 (equimolar) mixture of D-phenylalanine and L-phenylalanine. D forms of amino acids are not normally used in humans. D-phenylalanine and D-methionine are the only known D amino acids that can be converted to their natural L forms by the action of liver
In sum, phenylalanine is an antidepressant and pain reliever with many potential therapeutic roles.
Tyrosine – The Antidepressant
Tyrosine is an essential amino acid that readily passes the blood-brain barrier. Once in the brain, it is a precursor for the neurotransmitters dopamine, norepinephrine and epinephrine, better known as adrenalin. These neurotransmitters are an important part of the body’s sympathetic nervous system, and their concentrations in the body and brain are directly dependent upon dietary tyrosine.
Tyrosine is not found in large concentrations throughout the body, probably because it is rapidly metabolized. Folic acid, copper and vitamin C are cofactor nutrients of these reactions. Tyrosine is also the precursor for hormones, thyroid, catecholestrogens and the major human pigment, melanin. Tyrosine is an important amino acid in many proteins, peptides and even enkephalins, the body’s natural pain reliever. Valine and other branched amino acids, and possibly tryptophan and phenylalanine may reduce tyrosine absorption.
A number of genetic errors of tyrosine metabolism occur. Most common is the increased amount of tyrosine in the blood of premature infants, which is marked by decreased motor activity, lethargy and poor feeding. Infection and intellectual deficits may occur. Vitamin C supplements reverse the disease. Some adults also develop elevated tyrosine in their blood. This indicates a need for more vitamin C.
Tyrosine therapy is very useful in a variety of clinical situations. An average human equivalent dose of 2 to 6 g intravenously can raise the blood pressure in hemorrhagic shock (extreme blood loss) in experimental animals. An average human dose equivalent of 500 mg of tyrosine given intravenously reduces susceptibility to life-threatening ventricular fibrillation in experimental animals.
More tyrosine is needed under stress, and tyrosine supplements prevent the stress-induced depletion of norepinephrine and can cure biochemical depression. However, tyrosine may not be good for psychosis. Many antipsychotic medications apparently function by inhibiting tyrosine metabolism.
L-dopa, which is directly used in Parkinson’s, is made from tyrosine. Tyrosine, the nutrient, can be used as an adjunct in the treatment of Parkinson’s. Peripheral metabolism of tyrosine necessitates large doses of tyrosine, however, compared to L-dopa. When combined with the drug Sinemet, tyrosine’s effectiveness is increased.
Drugs like yohimbine which prolong the effects of tyrosine products have been used as an aphrodisiac. Tyrosine supplements in large doses may stimulate sex drive by raising blood pressure and catecholamine levels.
Tyrosine, like amphetamines, in large doses will reduce appetite, but in low doses tyrosine stimulates appetite. Tyrosine therapy may be useful in drug addiction; temporarily replacing codeine and amphetamines as methadone does for heroin addicts.
Physicians at Harvard Medical School have pioneered the use of 1 to 6 grams of tyrosine for the effective treatment of medication-resistant depression. Many antidepressants work by prolonging the action of tyrosine metabolites. Tyrosine is safer, although the results may be less dramatic in the short term than the antidepressants. Lower doses, as little as 1000 to 2000 mg, have been found to be effective clinically, as well as experimentally in animals. The minimum daily requirement for adults of tyrosine and its precursor, phenylalanine, is 16 mg/kg a day or about 1000 mg total. Hence, 6 g is at least six times the minimum daily requirement.
Tyrosine can be used as a safe and lasting therapy, useful in a variety of clinical situations-depression, hypertension, Parkinson’s disease, low sex drive, appetite suppression and therapy for cocaine addicts (pioneered at Fair Oak hospital in New Jersey). Tyrosine, like the branched chain amino acids, fights all kinds of stress because it is the precursor of adrenalin, which is used up during stress.
Tryptophan – The Sleep Promoter
Tryptophan is an essential amino acid which is the precursor of serotonin. Serotonin is a brain neurotransmitter, platelet clotting factor and neurohormone found in organs throughout the body. Metabolism of tryptophan to serotonin requires nutrients such as vitamin B6, niacin and glutathione. Niacin is an important metabolite of tryptophan. High corn or other tryptophan-deficient diets can cause pellagra, which is a niacin-tryptophan deficiency disease with symptoms of dermatitis, diarrhea and dementia.
Inborn errors of tryptophan metabolism exist where a tumor (carcinoid) makes excess serotonin. Hartnup’s disease is a disease where tryptophan and other amino acids are not absorbed properly. Tryptophan supplements may be useful in each condition, in carcinoid replacing the over-metabolized nutrient and in Hartnup’s supplementing a malabsorbed nutrient. Some disorders of excess tryptophan in the blood may contribute to mental retardation.
Assessment of tryptophan deficiency is done through studying excretion of tryptophan metabolites in the urine or blood. Blood may be the most sensitive test because the amino acid tryptophan is transported in a unique way. Increased urination of tryptophan fragments correlates with increased tryptophan degradation, which occurs with oral contraception, depression, mental retardation, hypertension and anxiety states.
The requirement for tryptophan and protein decreases with age. Adults’ minimum daily requirement is 3 mg/kg/day or about 200 mg a day. This may be an underestimation, for there are 400 mg of tryptophan in just a cup of wheat germ. A cup of low fat cottage cheese contains 300 mg of tryptophan and chicken and turkey contain up to 600 mg per pound.
Tryptophan supplements of up to 3 g a day have been used to control intractable pain in various conditions. Furthermore, tryptophan supplements decrease aggressive behavior. Abnormalities in tryptophan metabolism occur in aggressive mentally retarded patients. Increased violent crimes occur in areas where tryptophan-deficient corn is a major dietary staple. Vitamin B6 and tryptophan supplements can correct some of the biochemical disorders related to aggression. Drugs which increase the opposite neurotransmitter, dopamine-i.e., Nardil or bromocriptine—can produce rage reactions, as do drugs which inhibit vitamin B6, i.e., isoniazid, which inhibits metabolism of tryptophan to niacin.
Tryptophan is also a useful treatment for insomnia; significantly reducing the time needed to fall asleep. Effective doses range from 500 to 2000 mg. Disorders of REM sleep may require doses of 3 to 15 g.
Suicidal patients show a significant decrease in serotonin levels. These patients, as well as agitated, depressed patients, do well with tryptophan supplements. Most antidepressants prolong the effects of serotonin by preventing reuptake of this neurotransmitter, as well as the reuptake of catecholamine; Tryptophan at night and tyrosine in the morning can probably mimic the effects of most antidepressants. Levels of the neurotransmitters are directly dependent on dietary tryptophan and other amino acids.
Tryptophan has many other reported desirable effects. Appetite for carbohydrates is decreased and blood sugar is raised by tryptophan supplements. It stimulates growth hormone and prolactin, which is the basis of some of tryptophan I s therapeutic effects.
Tryptophan is also beneficial in some forms of schizophrenia; it probably acts by balancing dopamine excess. In Parkinson’s it inhibits tremor, and possibly also in progressive myoclonic epilepsy. Patients with kidney failure, on birth control pills, or with Down’s syndrome may need more tryptophan.
Chronic tryptophan supplementation (minimum 2 g daily), like supplementation with other amino acids, raises many plasma amino acids besides tryptophan itself. This is positive and exciting because many amino acids tend to decrease with age.