Pyroluria

Pyroluria is a familial disorder which occurs with stress, where an above-average amount of a substance consisting of “kryptopyrroles” circulate in the body. The substance is harmless in itself, but high levels of these pyrrolles systemically bind with B6 and zinc, preventing the use of these essential nutrients in the brain and body. The result is a myriad of symptoms, including severe inner tension, ongoing anxiety, poor stress control, fearfulness, and sometimes episodic anger.

Often such people have pale skin that easily burns, eyes that are sensitive to light, white flecks/marks on their nails, and stretch marks on their skin. They tire easily, are anemic, have poor dream recall, prefer not to eat breakfast, notice upper abdominal pain when stressed, and experience a “stitch” in their side if they run. They have a tendency to become loners as they age. Mental symptoms are aggravated when undergoing stress. In fact, pyroluria flares up when the individual is undergoing prolonged stress, such as during a chronic and debilitating illness.

Pyroluria may occur along with other imbalances as seen in some subtypes of schizophrenia such as histapenia (low histamine), histadelia (high histamine), high copper levels or cerebral allergies. It is the primary imbalance for 20% of schizophrenics.

Alcohol use is one way for pyrolurics to shut off their anxiety, feel more sociable, de-stress, and experience a short time when they feel more normal. Without a knowledge of this chemical imbalance, those who try to quit alcohol use must face coexisting with their symptoms. If additional antianxiety support is needed, GABA, tryptophan, chromium and inositol should be considered.

There is a urine lab test available which measures levels of kryptopyrroles. Any alcoholic, or anyone with symptoms indicating the possibility of this condition should have the lab test done.

Pyroluria is treated by restoring levels of vitamin B6 and zinc so that this double deficiency is corrected. Supplementation with vitamin B6 until daily dream recall returns (a normal phenomenon) as well as with zinc and manganese needs to be continued daily. With zinc, manganese and vitamin B6 therapy the pyroluric patient may start to respond in 24 hours and certainly some progress is noted within one week. However, total recovery may take three to four months. The biochemical imbalance and symptoms will usually recur within one to two weeks if the nutritional program is stopped. [Pfeiffer, 1974]

If a patient has a pyrrole disorder he/she likely would have at least half of the following symptoms:

Poor stress control

Sensitivity to bright lights and/or loud noises

Preference for spicy or heavily flavored foods

Significant growth after age 16

Morning nausea

Tendency to skip breakfast

Poor dream recall

Emotional outbursts

Poor short-term memory, perhaps coincident with excellent L.T. memory

Diagnosis of “rapid-cycle” bipolar

Much higher capability & alertness in the evening, compared to mornings

Dry skin

Reading disorder. (March 27, 2003) [Willam Walsh, Ph.D., past senior scientist, Pfeiffer Treatment Center www.hriptc.org]

 


Signs, symptoms & indicators of Pyroluria

Ayurvedic Typing  

High tolerance of spicy foods



Childhood  

Having late growth



Lifestyle  

Being prone to 'stitches'



Symptoms - Environment  

Rapid sunburning tendency



Symptoms - Food - General  

Weak appetite



Symptoms - Food - Preferences  

Never/rarely eating breakfast or regular avoidance of breakfast



Symptoms - Gas-Int - General  

Unexplained nausea



Symptoms - General  

Fatigue on light exertion



Symptoms - Head - Eyes/Ocular  

(High) sensitivity to bright light



Symptoms - Mind - Emotional  

Adverse reaction to stress

Pyrolurics are devastated by stresses including physical injury, emotional trauma, illness, sleep deprivation, etc.



 

Impatient/hostile disposition



 

Emotional instability



Symptoms - Mind - General  

Short-term memory failure



 

Being an antisocial person



Symptoms - Nails  

White spots on fingernails

Leukonychia punctata (white spots) are a sign of pyroluria.



Symptoms - Skeletal  

Joint pain/swelling/stiffness



Symptoms - Skin - General  

Lighter/paler skin color



Symptoms - Sleep  

Forgetting dreams




Conditions that suggest Pyroluria

Addictions  

Alcohol-related Problems

As many as one-third to one-half of alcoholics have the genetic, chemical imbalance called pyroluria.



Allergy  


 


Circulation  

Anemia (Uncommon Nutritional)

Pyrolurics are generally anemic.



Mental  

Schizophrenia

Approximately 20% of all schizophrenics have pyroluria as their primary imbalance. Symptoms are many including a sweet, fruity breath and body odor. The affected person has a tendency to have insight (understand they have mental problems).



 

Bipolar Disorder, Manic-Depressive

About 18% of those with bipolar disorder are also pyroluric.



 

Anxiety

Pyroluria is a known biochemical marker for life long anxiety symptoms. According to one alcoholism treatment center, one-third to one-half of alcoholics treated have this marker. High levels of pyrrolles systematically bind to B6 and zinc, preventing the use of these nutrients in the body and brain. The result is a myriad of symptoms, including severe inner tension, ongoing anxiety, poor stress control, fearfulness, and sometimes episodic anger.



 


 


 


Metabolic  


Nervous System  


Nutrients  

Zinc Requirement

Pyroluria is caused by an overproduction of kryptopyrrole during hemoglobin synthesis, which chemically combines with vitamin B6 and zinc, resulting in their excretion and a deficiency of both of these essential nutrients.



 

Vitamin B6 Requirement

A functional pyridoxine deficiency is common in pyroluria (often seen in alcoholics), due not so much to inadequate intake as impaired conversion to its active form, pyridoxal-5-phosphate, and enhanced degradation.



Skin-Hair-Nails  


Symptoms - Mind - General  

Having dyslexia




Risk factors for Pyroluria

Symptoms - Food - Beverages  

Moderate/low/high alcohol consumption

A higher than normal anxiety level leads many with pyroluria to drink alcohol. As many as one-third to one-half of alcoholics have this genetic chemical imbalance.



Symptoms - Gas-Int - General  

History of unexplained nausea



Symptoms - Mind - Emotional  

Small social support group size or no social support group




Pyroluria suggests the following may be present

Nutrients  

EFA (Essential Fatty Acid) Type 3 Requirement

Omega 3 fatty acids are potentially harmful supplements in someone with pyroluria. Omega 3s can worsen mental symptoms in bipolar or schizophrenic patients, if they have a pyrrole disorder.

Normally the desaturase enzymes which metabolize EFAs have a higher affinity for the n3 (Omega3) series. It has been proposed that in schizophrenia mutant desaturases are present which prefer the n6 series. This change would account for the low levels of linoleic acid, dihomogammalinolenic acid and 1 series prostaglandins which have been reported in schizophrenia. It would also explain the high levels of arachidonic and alpha-linolenic acids and the recently described therapeutic response to alpha-linolenic acid. The abnormal pattern in n6 series EFAs in schizophrenics can almost exactly be imitated in rats by depriving them of n3 EFAs. This is the nearest experimental equivalent to an inability to metabolize EFAs because of an enzyme defect. Heterozygotes carrying such a mutant gene would have an advantage over either form of homozygote since they would be better able to cope with variations in dietary intake of n3 and n6 EFAs. [Schizophrenia: the role of abnormal essential fatty acid and prostaglandin metabolism. Horrobin DF, Huang YS. Med Hypotheses. 1983 Mar;10(3): pp329-36]

Pyroluric mental patients will usually get worse if given fish oils, DHA, EPA, etc (alpha-linolenic acid metabolites). They thrive on Primrose Oil, a good source of AA and other omega 6s.




Pyroluria can lead to

Circulation  

Anemia (Uncommon Nutritional)

Pyrolurics are generally anemic.



Mental  


Nutrients  

Zinc Requirement

Pyroluria is caused by an overproduction of kryptopyrrole during hemoglobin synthesis, which chemically combines with vitamin B6 and zinc, resulting in their excretion and a deficiency of both of these essential nutrients.



 

Vitamin B6 Requirement

A functional pyridoxine deficiency is common in pyroluria (often seen in alcoholics), due not so much to inadequate intake as impaired conversion to its active form, pyridoxal-5-phosphate, and enhanced degradation.



Skin-Hair-Nails  



Recommendations for Pyroluria

Amino Acid / Protein  


Lab Tests/Rule-Outs  

Test for Urine Kryptopyrroles

People with pyroluria produce excess amounts of a byproduct from hemoglobin synthesis, called kryptopyrrole (2,4-dimethyl-3-ethylpyrrole) or hemepyrrole. In these people an excess amount of kryptopyrrole is found in the urine. The most accurate test for pyroluria directly measures urine kryptopyrrole’s.



 


 


Mineral  

Zinc

Kryptopyrrole is a reacting agent which combines irreversibly with active vitamin B6. The resulting molecule then chelates zinc, the combined product appearing in the urine. The whole syndrome is stress-induced so the susceptible patient, when stressed, quickly becomes vitamin B6 and zinc deficient.



 

Manganese

Manganese is poorly absorbed, so the oral administration of large doses of manganese gluconate daily for a long period of time may be required. Manganese levels can be tested for in red blood cells. Daily doses of 50mg or more may be required over a long period to bring these levels to within the normal range.



 


Vitamins  

Vitamin B6 (Pyridoxine)

Pyrolurics commonly respond within a few months to B6, zinc and manganese. The nutrient dosage usually must be increased when the pyroluric patient is under increased stress.



Key

Weak or unproven link
Strong or generally accepted link
Strongly counter-indicative
Likely to help
Highly recommended
May have adverse consequences

Glossary

Pyroluria

This condition is caused by an overproduction during hemoglobin synthesis of kryptopyrrole, which chemically combines with vitamin B6 and zinc, resulting in their excretion and a severe deficiency of both of these essential nutrients. Most pyroluric individuals never develop schizophrenia symptoms.

Vitamin B6

Influences many body functions including regulating blood glucose levels, manufacturing hemoglobin and aiding the utilization of protein, carbohydrates and fats. It also aids in the function of the nervous system.

Zinc

An essential trace mineral. The functions of zinc are enzymatic. There are over 70 metalloenzymes known to require zinc for their functions. The main biochemicals in which zinc has been found to be necessary include: enzymes and enzymatic function, protein synthesis and carbohydrate metabolism. Zinc is a constituent of insulin and male reproductive fluid. Zinc is necessary for the proper metabolism of alcohol, to get rid of the lactic acid that builds up in working muscles and to transfer it to the lungs. Zinc is involved in the health of the immune system, assists vitamin A utilization and is involved in the formation of bone and teeth.

Anxiety

Apprehension of danger, or dread, accompanied by nervous restlessness, tension, increased heart rate, and shortness of breath unrelated to a clearly identifiable stimulus.

Stitch

A sudden sharp pain, usually in the side, that can occur during exercise such as running.

Chronic

Usually Chronic illness: Illness extending over a long period of time.

Schizophrenia

Any of a group of psychotic disorders usually characterized by withdrawal from reality, illogical patterns of thinking, delusions, and hallucinations, and accompanied in varying degrees by other emotional, behavioral, or intellectual disturbances. Schizophrenia is associated with dopamine imbalances in the brain and defects of the frontal lobe and is caused by genetic, other biological, and psychosocial factors.

Histamine

A chemical in the body tissues, produced by the breakdown of histidine. It is released in allergic reactions and causes widening of capillaries, decreased blood pressure, increased release of gastric juice, fluid leakage forming itchy skin and hives, and tightening of smooth muscles of the bronchial tube and uterus.

Copper

An essential mineral that is a component of several important enzymes in the body and is essential to good health. Copper is found in all body tissues. Copper deficiency leads to a variety of abnormalities, including anemia, skeletal defects, degeneration of the nervous system, reproductive failure, pronounced cardiovascular lesions, elevated blood cholesterol, impaired immunity and defects in the pigmentation and structure of hair. Copper is involved in iron incorporation into hemoglobin. It is also involved with vitamin C in the formation of collagen and the proper functioning in central nervous system. More than a dozen enzymes have been found to contain copper. The best studied are superoxide dismutase (SOD), cytochrome C oxidase, catalase, dopamine hydroxylase, uricase, tryptophan dioxygenase, lecithinase and other monoamine and diamine oxidases.

Allergy

Hypersensitivity caused by exposure to a particular antigen (allergen), resulting in an increased reactivity to that antigen on subsequent exposure, sometimes with harmful immunologic consequences.

GABA

The amino-acid derivative GABA (Gamma-Aminobutyric Acid) is a calming substance. Tranquilizers like Valium and Librium owe their soothing effects to the fact that they stimulate GABA receptors in the brain.

Tryptophan

Essential amino acid. Natural relaxant and sleep aid due to its precursor role in serotonin (a neurotransmitter) synthesis. Along with tyrosine, it is used in the treatment of addictions.

Chromium

Chromium is a mineral that becomes a part of the glucose tolerance factor (GTF). Chromium aids in insulin utilization and blood sugar control. By controlling blood sugar, chromium helps prevent the damage caused by glucose, which is called glycation. Chromium helps maintain normal cholesterol levels and improves high-density lipoprotein levels. Chromium is also important in building muscle and reducing obesity.

Inositol

Usually considered part of the vitamin B complex. It is thought that along with choline, inositol is necessary for the formation of lecithin within the body. Involved in calcium mobilization.

Manganese

An essential mineral found in trace amounts in tissues of the body. Adults normally contain an average of 10 to 20mg of manganese in their bodies, most of which is contained in bone, the liver and the kidneys. Manganese is essential to several critical enzymes necessary for energy production, bone and blood formation, nerve function and protein metabolism. It is involved in the metabolism of fats and glucose, the production of cholesterol and it allows the body to use thiamine and Vitamin E. It is also involved in the building and degrading of proteins and nucleic acid, biogenic amine metabolism, which involves the transmitting of nerve impulses.

Nausea

Symptoms resulting from an inclination to vomit.

Short-Term Memory

Also known as immediate memory or working memory, this is a phase of memory in which a limited amount of information may be held for several seconds to minutes. In general, up to 7 'chunks' of information are stored for about 20 seconds.

pH

A measure of an environment's acidity or alkalinity. The more acidic the solution, the lower the pH. For example, a pH of 1 is very acidic; a pH of 7 is neutral; a pH of 14 is very alkaline.

Bipolar Disorder

Also known as manic-depression, this disorder is characterized by alternating periods of extreme moods, usually swinging from being overly elated or irritable (mania) to sad and hopeless (depression) and then back again, with periods of normal mood in between. The frequency of the swings between these two states, and the duration of the mood, varies from person to person.

Hallucination

A false or distorted perception of objects or events, including sensations of sight, sound, taste, smell or touch, typically accompanied by a powerful belief in their reality.

Hemoglobin

The oxygen-carrying protein of the blood found in red blood cells.

Pyridoxine

(Vitamin B-6): A B-complex vitamin that plays a role as a coenzyme in the breakdown and utilization of carbohydrates, fats and proteins. It facilitates the release of glycogen for energy from the liver and muscles. It also participates in the utilization of energy in the brain and nervous tissue and is essential for the regulation of the central nervous system.

Fatty Acids

Chemical chains of carbon, hydrogen, and oxygen atoms that are part of a fat (lipid) and are the major component of triglycerides. Depending on the number and arrangement of these atoms, fatty acids are classified as either saturated, polyunsaturated, or monounsaturated. They are nutritional substances found in nature which include cholesterol, prostaglandins, and stearic, palmitic, linoleic, linolenic, eicosapentanoic (EPA), and decohexanoic acids. Important nutritional lipids include lecithin, choline, gamma-linoleic acid, and inositol.

Enzymes

Specific protein catalysts produced by the cells that are crucial in chemical reactions and in building up or synthesizing most compounds in the body. Each enzyme performs a specific function without itself being consumed. For example, the digestive enzyme amylase acts on carbohydrates in foods to break them down.

Metabolism

The chemical processes of living cells in which energy is produced in order to replace and repair tissues and maintain a healthy body. Responsible for the production of energy, biosynthesis of important substances, and degradation of various compounds.

Essential Fatty Acid

(EFA): A substance that the human body cannot manufacture and therefore must be supplied in the diet.

Prostaglandin

Any of a class of physiologically active substances present in many tissues, with effects such as vasodilation, vasoconstriction, stimulation of the smooth muscles of the bronchus or intestine, uterine stimulation; also involved in pain, inflammation, fever, allergic diarrhea, and dysmenorrhea. A potent hormone -- similar in structure to an unsaturated fatty acid -- that acts in extremely low concentrations on local target organs; first isolated from the prostate.

DHA

Docosahexanoic Acid. A metabolite of the omega-3 fatty acid alpha-linolenic acid.

EPA

Environmental Protection Agency. Also: Eicosapentanoic Acid. A metabolite of the omega-3 fatty acid alpha-linolenic acid.

Metabolite

Any product (foodstuff, intermediate, waste product) of metabolism.

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