Pyroluria and Adrenal Fatigue Syndrome – Part 2

By: Michael Lam, MD, MPH; Justin Lam, ABAAHP, FMNM; Dorine Lam, RDN, MS, MPH

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Pyroluria and Adrenal Fatigue Syndrome

Pyroluria affects the endocrine systemAdrenal Fatigue Syndrome (AFS) is a stress induced neuro-endocrine dysfunction of the body. The hallmark symptom is fatigue of unknown origin despite normal medical investigation. There are four clinical stages of clinical progression, from mild to severe. In advanced stages, one can be incapacitated and housebound, unable to work or lead a normal social life. In some of these stages, the effects include symptoms similar to pyroluria.

Most people with AFS carry on a normal life and are thus unaware of the potential natural progression of this condition until quite late. Allopathic physicians are ignorant of this condition and thus reject its notion. Do not be surprised if your doctor tells you AFS does not exist.
Many symptoms of pyroluria and AFS are similar because both have close ties to the psycho-neuro-endocrine system. The key symptoms include fatigue, insomnia, irritable bowl, anxiety and nervousness, depression, increase in sensitivity or intolerance to temperature change or external stimuli, anxiety, depression, brain fog, low tolerance to stress, and sensitivity to medications and supplements.

Pyroluria Treatment and Maximum Tolerance Level

Once pyroluria is suspected or confirmed by laboratory testing, most are started on Vitamin B6 and zinc therapy by their physician with high hopes. From our experience, it is rare that B6 and zinc therapy alone lead to an immediate, sustained, and complete recovery of all symptoms of pyroluria when AFS is present or when the body is very weak from other chronic conditions. Obviously, something is amiss.

With concurrent AFS, the body clinically responds to vitamin B6 and zinc therapy with heightened sensitivity similar to how it reacts when the external substrate approaches its internal maximum tolerance level (MTL). Substrates can be medications, nutritional supplements, and selected types of food. The body has a pre-established MTL for each compound. Once reached, the body will try to get rid of the excess automatically. For example, in the case of magnesium or Vitamin C, loose bowel can ensue as the body tries to get rid of it. Different substrates are cleared through different mechanisms. The liver is largely responsible for this job. If not cleared or at least cleared in a timely fashion, say in the case of liver congestion or extracellular matrix pollution, metabolic by products can accumulate in the body and become toxic. Circulation of such toxic compounds to the various parts of the body can lead to brain fog, joint pain, irritability, anxiety, insomnia, and cramps.

The body’s overall sensitivity to substrates increases as it gets closer to the MTL. There may be subtle signs of intolerance such as bloating, loose stools, feeling jittery, and insomnia. These are warning signs. If exceeded, the MTL then activates the body’s alert system and initiates steps to rid itself of the excess aggressively. In this alert process, the autonomic nervous system is usually involved, triggering the release of norepinephrine and adrenaline (epinephrine). These powerful hormones lower the threshold for paradoxical reaction and tolerance to stress, medications and supplements.

Forcing more Vitamin B6 and zinc without consideration to the MTL will only worsen the situation as they will wire the body internally and trigger worsening fatigue, anxiety, insomnia, and other undesirable symptoms.

Vitamin B6 must be taken cautiously in cases of pyroluriaCompounds that can potentiate the stimulatory effect of B6 and zinc include selenium, copper, manganese, calcium, kelp, iodine, high dose amino acid, and other members of the Vitamin B family. Also included in this effect are adrenal and thyroid glandular, adaptogenic herbs such as ashwagandha, licorice, and rhodiola, which can compound the problem. Those on thyroid hormone replacement therapy, testosterone, DHEA, pregnenolone and bioidentical hormonal therapy need to be extremely careful as well. The addition of Vitamin B6 and zinc to the regiment may hasten sensitivity and can lead to overstimulation and ultimately therapeutic failure.

Therefore, despite high hopes of successful pyroluria treatment, the vast majority will find their clinical outcome less than ideal and sub-optimal, especially if they are already on a basket of different nutritional supplements mentioned above as stimulatory. The more advanced the AFS, the greater the risk of therapeutic failure.

While those in mild AFS may experience consistent benefit, most in advanced stages will feel only a slight improvement of energy at best after a few weeks or months of therapy, with their energy rise plateauing as fatigue resurges. Energy recovery generally falls below expectations and targets for these. Many in advanced AFS do not improve at all and feel no difference. Some in fact feel worse right from the start or soon afterwards, especially those who are very weak, incapacitated, or in catabolic state. The overall clinical picture is often muddy at best over time.

Who Responds Well?

Those who respond positively to B6 and zinc alone usually are young, constitutionally strong, and in early stages of AFS, where fatigue is mild and not incapacitating. Positive results are usually felt within weeks and sustainable over time indefinitely. After a while, dosage can be reduced without sacrificing results.

If you are in advanced stages of AFS or internally weak, be very careful commencing zinc and B6 therapy even if your laboratory test for pyroluria is positive. Forcing zinc and B6 into the body under these circumstances is a common recovery mistake.

Unless there is primary pyroluria and no other associated chronic disease that weakens the body, healing the adrenals first can often lead to spontaneous recovery of most if not all symptoms of pyroluria. Attempts to heal the pyroluria without concurrent attention to AFS can retard the healing process of both.

When Laboratory Results can be Misleading

Relying on laboratory results alone to start treatment may be acceptable for those in early stages of AFS where symptoms are relatively mild and the body is strong. Do not embark on an aggressive treatment program by relying on laboratory results alone if you are in advanced stages of AFS. Vitamin B6 and zinc can be adrenal crash triggers in such cases.

Unless there is a very clear indication of Vitamin B6 and zinc therapy, many factors have to be considered prior to commencing aggressive therapy. Most sufferers of AFS are so eager to try Vitamin B6 and zinc that they overlook considering the potential negative outcome as part of their overall decision making. They are emotionally devastated when clinical results do not meet their expectations as they get worse overall instead of better.

When Good is Bad

Pyroluria can effect paradoxical recoveriesUsing any nutritional supplementation for AFS or pyroluria recovery should proceed slowly and under professional care. Any immediate drastic improvement of fatigue after using B6 and zinc is not necessarily a good sign. It can be a sign of impending substrate saturation as MTL is reached. Hypersensitivity, paradoxical effect, worsening fatigue, intolerance and adrenal crashes can result if advanced AFS is present.

Significant immediate positive outcome can also be, but not always, an alert of underlying liver dysfunction, extracellular matrix congestion, feedback loop dysregulation, or hypersensitivity of receptor sites as the body overreacts and amplifies the therapeutic response. Always be on the lookout for any drastic clinical change, whether it is positive or negative. Both can point to underlying dysfunction.

The Adrenals Come First

Once diagnosed or suspected of pyroluria, especially when advanced AFS is present, the temptation to start on B6 and zinc immediately should be refrained. Stabilize and strengthen the adrenals first. This will reduce the chances of adrenal crashes triggered by pyroluria therapy.

Our comprehensive total body approach can usually stabilize and bring healing to weak adrenals within weeks, though those with liver and extracellular matrix congestion may need significantly more time. Fatigue should begin to reduce once the healing process starts. If pyroluria is also present, symptoms should also subside automatically as adrenal healing progresses. No Vitamin B6 or zinc is then necessary.

Once the adrenals are stable and well-healed, a trial course of Vitamin B6 and zinc can be considered as a way to speed up the AFS recovery process, with dosage titrated carefully. If pyroluria is indeed a concurrent problem, it will be corrected automatically. B6 and zinc helps both AFS and pyroluria without the risk of adrenal crashes when given at the right time and dosage. Jumping in too early can worsen the overall fatigue.

One has closely monitored any change in clinical symptoms and made dosage and delivery system adjustments accordingly.


Pyroluria (Pyrrole disorder) is characterized by an elevated urine kryptopyrrole, which results in a dramatic deficiency of zinc and Vitamin B6. It is a blood disorder, which is genetically transmitted. Because of an abnormality in the synthesis of hemoglobin, a chemical imbalance occurs in the blood. Diagnosis can be made by urine laboratory testing. Treatment consists of Vitamin B6 and zinc. The decision of whether treatment is needed varies. The majority of sufferers are asymptomatic with no treatment needed. The symptoms of pyroluria and AFS are similar. Our clinical experience has shown that treatment for pyroluria is best deferred until the adrenals are well healed in sufferers that are in advanced stages of AFS. Too aggressive an approach with pyroluria wrongly timed can worsen AFS and trigger adrenal crashes.

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© Copyright 2016 Michael Lam, M.D. All Rights Reserved.

Exploring the commonalities and differences between Pyroluria and Adrenal Fatigue Syndrome