720 North Tustin Avenue
Suite 104
Santa Ana, CA 92705-3606
Phone: (714) 565-1032
Fax: (714) 565-1035

Jeremy E. Kaslow, MD, FACP, FACAAI Physician and Surgeon
Board Certified Internal Medicine

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PYROLURIA

Pyroluria is a genetically determined chemical imbalance involving an abnormality in hemoglobin synthesis. Hemoglobin is the protein that holds iron in the red blood cell. Individuals with this disorder produce too much of a byproduct of hemoglobin synthesis called "kryptopyrrole" (KP) or "hemepyrrole." Kryptopyrrole has no known function in the body and is excreted in urine.

Kryptopyrrole binds to pyridoxine (vitamin B6) and zinc and makes them unavailable for their important roles as co-factors in enzymes and metabolism.These essential nutrients when bound to kryptopyrrole are removed from the bloodstream and excreted into the urine as pyrroles.Arachidonic acid (an omega-6 fatty acid) also becomes deficient.

The effect of pyroluria can have a mild, moderate, or severe depending on the severity of the imbalance. Most individuals show symptoms of zinc and/or B6 deficiencies, which include poor stress control, nervousness, anxiety, mood swings, severe inner tension, episodic anger (an explosive temper), poor short-term memory and depression. Most pyrolurics exhibit at least two of these problems. These individuals cannot efficiently create serotonin (a neurotransmitter that reduces anxiety and depression) since vitamin B6 is an important factor in the last step of its synthesis. Many of these persons appear to benefit from SSRI medications such as Prozac, Paxil, Zoloft, Celexa, etc. However, as with all mind-altering drugs, side effects occur and the true cause of the mental difficulties remains uncorrected. In addition these individuals often have frequent infections and are often identified by their inability to tan, poor dream recall, abnormal fat distribution, and sensitivity to light and sound. As you can imagine an SSRI will not correct these metabolic effects. More healthful benefits may be achieved by giving the appropriate supporting nutrients.

Pyroluria is detected by chemical analysis of the abnormal pyroles in urine detectable as a purple (on testing paper) metabolite in called "the mauve factor." Most persons have less than 10mcg of KP per deciliter. Persons with 10-20 mcg/dl are considered "borderline" pyroluric and may benefit from treatment. Persons with levels above 20 mcg/dl are considered to have pyroluria, especially if the above symptoms are present. The chemical analysis for KP is difficult due to the tendency for this chemical to decompose. Sometimes it is necessary to repeat the urine test to properly determine the level of KP being excreted. To make the initial diagnosis, no vitamins or minerals should be taken for two days before the urine is collected (This is to avoid false negative results). The specimen should be handled properly as well - collected and frozen immediately and protected from any light by being placed in aluminum foil. A repeat test to determine if the condition has been improved may be helpful.

People with mild-moderate pyroluria usually have a fairly rapid response to treatment if no other chemical imbalances are present. People with severe pyroluria usually require several weeks before progress is seen and improvement may be gradual over 3 - 12 months. Features of pyroluria usually recur within 2 - 4 weeks if the nutritional program is stopped.Thus, the need for treatment is indefinite.

Pyroluria is managed in part by restoring vitamin B6 and zinc. The type of replacement therapy is very important as zinc must be provided in an efficiently absorbed form. Vitamin B6 is also available in several forms. Both zinc and B6 supplementation need to be directed by the doctor as too much can be toxic, use of the wrong form will be ineffective, and avoiding competing minerals and supplements may be necessary. Other nutrients may assist in pyroluria include niacinamide, pantothenic acid, manganese, vitamins C and E, omega-6 fatty acids and cysteine. Food sources and nutritional supplements containing copper and red/yellow food dyes should be avoided.

Because pyrolurics are stress intolerant, they seem to be especially vulnerable to cumulative stress over many days. For example, parents of a pyroluric child should use discipline that is "short and sweet" rather than "long and lingering." It is not unexpected that pyroluric patients are prone to relapses, especially during illness, injury, or emotional stress.

Much of the information we have about pyroluria is from the work of the late Carl Pfeiffer, M.D. in the 1970ís.Some references include:

Irving DG: Apparent non-indolic ehrlich-positive substances related to Mental illness. J Neuropsychiat, 1961;2:292-305.

Hoffer A, Mahon M: The presence of unidentified substances in the urine of psychiatric patients. J Neuropsychiat, 1961;2:331-397.

Irvine DG, Bayne W, et al: Identification of kryptopyrrole in human urine and its relationship to psychosis. Nature, 1969;224:811-813.

Pfeiffer CC, Lliev V: Pyrroluria, urinary mauve factor, causes double deficiency of B6 and zinc in schizophrenics. Fed Proc, 1973;32:276.

Jackson JA, Riordan HD, Neathery S: Vitamins, blood lead and urine pyrroles in Down Syndrome patients. Amer Clin Lab, 1990:Jan- Feb:8-9.

Jackson JA, Riordan HD, Neathery S, Riordan N: Urinary pyrroles in health and disease. J Orthomol Med, 1997: 12;2:96-98.

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