developed by: Dietrich Klinghardt, M.D.

Dr. Klinghardt's The Core mineral supplement for HPU/KPUDr. Dietrich Klinghardt is a physician specializing in neurological diseases such as autism and lyme, practicing out of Kirkland, Washington. Over the years, he has found that the lyme and autism patients who did not progress in their recovery many times had an underlying condition known as hemopyrrollactamuria (HPU), also known as kyptopyrroluria (KPU). HPU is a severe but reversible deficiency of zinc, biotin, manganese, vitamin B6 (or P5P), and arachidonic acid. When treated for this condition, his patients were then able to move forward in their treatment with success.

Dr. Klinghardt has found that HPU occurs in Lyme disease around 80% of the time (or more), and it occurs in over 75% of patients with heavy metal poisoning. The incidence of HPU in children with autism is over 80%.

What Is It?
HPU is an abnormality in heme synthesis. Hemoglobin is the substance the holds iron in the red blood cells. Hydroxy-hemopyrrolin-2-one (HPL) is a byproduct of hemoglobin (heme) synthesis and can be identified in the urine. HPLs bind to zinc, biotin, manganese, vitamin B6, arachidonic acid and other vitamins and minerals and lead to a significant depletion of these compounds in the brain and body.

Potential symptoms says many symptoms can result, “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.”1

How does one get tested/diagnosed?
Scott Forsgren writes in his Public Health Alert (May 2010) article Kryptopyrroluria (aka Hemopyrrollactamuria): A Major Piece of the Puzzle in Overcoming Chronic Lyme Disease, that “HPL levels can be measured from urine through the laboratory Vitamin Diagnostics. The test costs approximately $55 dollars. A lab kit is ordered and the urine sample is returned to the lab by the patient. It is important that the patient follow the instructions as Dr. Klinghardt outlines and not the directions that come with the test kit from the lab.

Until recently, Vitamin Diagnostics offered a test for the related compound called kryptopyrrol only. Recently, they began to offer a test for the hydroxy-hemopyrrolin-2-one (HPL) compound. When filling out the requisition, the practitioner can now select HPL in addition to kryptopyrrol. The HPL test results in a much higher yield.

Dr. Klinghardt finds that in order to get the best possible insight into the patient’s condition, it is best to avoid all supplements, especially those containing zinc, biotin, and vitamin B6, for 5-7 days before the urine sample is collected. He suggests that patients use a 24-hour urine collection as opposed to first morning urine as the release of HPL complex into urine is not consistent and might be missed in a single urine collection. The sample should be shielded from light. 500mg ascorbic acid should be added to each liter of urine as a preservative.

To further maximize the benefit of testing for the condition, it is best for the patient to be under stress at the time the test is being performed as HPL excretion is known to increase during times of stress.

Dr. Klinghardt has found that Vitamin Diagnostics has the best test for HPU available in the United States. In some circumstances, however, patients may still test negative even when the condition is suspected. In those cases, an empiric trial of the HPU protocol may still be warranted.

Other laboratory results that may be suggestive of HPU include:
• WBC < 5000/mcL (due to low levels of zinc) • High LDL / Low HDL • Low normal alkaline phosphatase (<60U/L) • Low omega-6 fatty acids in red cell membrane test • Low taurine in amino acid profile • High MCV • WBC and RBC zinc and manganese levels may be normal while biopsies from bone and CNS are completely deficient Bone biopsies are a reliable predictor of HPU. Severe deficiencies of zinc, manganese, lithium, calcium, magnesium, and molybdenum are often found."2

What is the treatment?
Scott Forsgren’s comprehensive article goes on to detail the treatment that Dr. Klinghardt uses for HPU (dosages for adults):

Before Breakfast

Zinc 27-40mg elemental zinc per day (as Picolinate, Gluconate or Sulfate; liquid is more effective). Initially, up to 
240mg of elemental zinc may be used under the care of a doctor in those with metal toxicity and chronic infections. Nausea after zinc supplementation may be a sign of hypochlorhydria or low stomach acid. This tends to resolve after 2-4 months on the protocol. 

Manganese 5mg per day (initially up to 20mg per day in those patients with joint and ligament weakness.)

With Breakfast

Arachidonic acid from Omega-6 oils (Ghee, Evening Primrose Oil, Black Currant, Borage, Pumpkin; 4-6 capsules of Evening Primrose Oil per day is commonly used.)

Fish oil 1 teaspoon per day


Before Bedtime

Vitamin B6/P5P 25mg B6 per day and 50mg P5P per day (Most patients do better with a combination of both B6 and P5P. Some require P5P. Approximately 10% do not tolerate P5P at all. Initially, up to 750mg per day may be used, especially in those with seizure disorders.)

Magnesium (Glycinate or Malate) 600-2000 mg per day – or titrate to bowel tolerance.

BioPure MicroMinerals 1 tablespoon per day

Biotin 10mg per day for brain, skin, hair, and nails

This is the core treatment for HPU. 


Niacinamide 1000mg three times per day for psychiatric symptoms


Taurine 500mg three times per day for brain-related symptoms such as seizures, brain fog, and memory loss. Supports elimination of neurotoxins, improves bile quality, increases glutathione, and normalizes brain rhythms


Lithium Orotate or Aspartate 60mg-240mg per day 

Chromium 500 mcg per day (initially up to 2 mg, especially in certain brain disorders and hypo/hyperglycemia and insulin resistance)

Molybdenum 300 mcg (initially much higher, especially with sulfur reactivity)

High Gamma Vitamin E 400 IU per 40lbs of body weight per day (Unique E is the brand often used)

HPU clients are also often deficient in silica, iodine, and boron.

In Europe, “Depyrrol” is a product which contains Zinc, Manganese, and a mix of vitamin B6 and P5P. It is used as a method of treating HPU. The more complete US product “Core” is available from BioPure Healing Products. Omega-6 oils must be supplemented in addition to Depyrrol or Core, but these products provide the patient the convenience of getting the key components of the protocol in one product. One potential consideration is that some patients may not tolerate both vitamin B6 and P5P; both of which are contained in Depyrrol and Core. As a result, it is occasionally necessary for patients to take each component of the HPU program separately.

It is critically important to monitor mineral levels during this treatment. Copper levels should be assessed using a red cell mineral test. Copper replacement is often necessary at a dose of 2-4mg per day due to the high zinc dosage. This is evaluated and introduced when necessary after the treatment has begun, often between months four and six. Zinc, manganese, and vitamin B6 are copper antagonists. Thus, monitoring levels of copper and supplementing where needed is an important part of the treatment protocol. Zinc and copper should not be taken at the same time of day.

Copper deficiency can lead to hemorrhoids, varicose veins, fatigue, edema, hair loss, anorexia, skin problems, osteoporosis, cardiovascular disease, aneurisms, and many other undesired conditions. Current nutritional teachings are misinformed on the topic of copper toxicity. The immune system uses copper and iron to fight infections associated with Lyme disease. As a result, oxidized copper is displaced in the connective tissue and may appear as though the patient is copper toxic by some testing methods when in fact copper supplementation may be appropriate. High dose Vitamin C has the effect of changing copper to a form that can be reused by the body.”2

The protocol is challenging to get through because once the mineral deficiencies are corrected, the body starts to dump heavy metals. It is critical to have a heavy metal detoxification protocol underway before this happens. For this reason and others, Dr. Klinghardt cautions that the HPU protocol should only be undertaken under the guidance of a qualified physician.

Sources for vitamins: iHerb (*Get $5 off your 1st order up to $40, $10 off $40 and over with coupon code “GEN582″ at checkout), VitaNet, VitaCost, BioPure (Dr. Klinghardt’s company)

1st Chinese Herbs - 10% offiHerb - $5 off 1st orderMountain Rose Herbs

Notes, Pyroluria
2Scott Forsgren, Kryptopyrroluria (aka Hemopyrrollactamuria): A Major Piece of the Puzzle in Overcoming Chronic Lyme Disease, The Public Health Alert, May 2010

Below is Dietritch Klinghardt, M.D.’s presentation on HPU, Lyme disease and autism at the LIA Foundation’s 2009 Annual Conference.

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