Factsheet: Kryptopyrrolurie (KPU)

The unknown metabolic disorder

What is KPU in Horses?

Kryptopyrroluria (KPU) is not a disease, but rather a metabolic disorder.

Symptoms of KPU

This metabolic disorder can lead to a range of diseases and symptoms. The visible symptoms vary, including digestive issues such as diarrhoea, FFWS, or recurring colic, as well as skin conditions like mud fever, Mallendar/Sallendar, nettle fever episodes, eczema, allergies, chronic respiratory diseases, laminitis, tendon or suspensory ligament damage, performance loss, and much more. Because the clinical presentation is so inconsistent, the underlying disorder was not properly recognised for a long time, with only the visible disease being treated in isolation. Accordingly, the affected horses have a long history of suffering and are ‘multimorbid,’ meaning they suffer from multiple simultaneous conditions, such as chronic cough, summer eczema, and FFWS, as examples of possible symptom combinations. Or they are so-called “non-responders,” meaning horses that do not respond, or only respond weakly, to medications and therapies. Moreover, these horses tend to have severe reactions after receiving medication and develop intolerances to worming treatments or vaccine side effects. For many horses, the symptoms are less pronounced in summer during turnout but become more pronounced in winter when being fed haylage.

How does KPU develop?

To understand this, we need to look at the processes in the horse’s liver. This is where detoxification takes place, meaning that all waste products produced in the body, as well as all toxins ingested—such as mycotoxins from mould in forage, medications, or poisonous plants—must be neutralised by the liver.

Detoxification in the Liver: Phase 1

This detoxification occurs in two phases. In Phase 1, the substances are initially modified. At the end of this phase, intermediate products are formed, which are sometimes more toxic than the original substances. Therefore, it is crucial that Phase 2 begins immediately.

Detoxification in the Liver: Phase 2

In this phase, the toxins are further neutralised and altered so that they can later be excreted. After this step, the waste product is released from the liver into the bloodstream, where it can then exit the body via the kidneys and urine. For Phase 2 of detoxification to occur, a catalyst is required. In horses, this catalyst is Pyridoxal-5-Phosphate, or P5P for short. It is an activated form of vitamin B6.

When the Catalyst P5P is missing

If P5P is absent, the detoxification process is halted after Phase 1, and the body carries a transformed, yet still highly toxic substance that it cannot excrete. In healthy horses, sufficient amounts of P5P are provided by the gut flora. As horses and their gut flora live in symbiosis, the horse is usually sufficiently supplied with P5P from this source. Over the course of evolution, it appears that horses have lost the ability to activate vitamin B6 into P5P on their own. This is a major difference compared to humans, who can produce P5P from vitamin B6 on their own. However, Kryptopyrroluria or Hämopyrrolactamuria (HPU) also occurs in humans, when a genetic mutation prevents them from being able to produce P5P themselves. People with KPU or HPU must take P5P for their entire lives to compensate for the deficiency. However, in horses, the deficiency is usually caused by damage to the gut flora.

Trace element deficiency due to a defective detoxification cascade*

If P5P is missing to allow Phase 2 of detoxification to proceed normally, the liver begins to bind waste products to certain trace elements in order to eliminate at least part of them. These primarily include zinc, selenium, and sulfur. However, manganese or iron can also be used. Since horses are very sensitive to zinc deficiency in the blood, but are tolerant of selenium or manganese deficiency, the latter are more commonly seen in blood tests.

Cascade = In biochemistry, a sequence of reactions in a metabolic pathway.

Selenium deficiency – a widespread phenomenon

Many horses show signs of selenium deficiency in their bloodwork. The cause is often attributed to selenium-poor soils. However, more commonly, it is not a lack of supply but rather the high consumption due to a defective detoxification cascade. Supplementing with selenium preparations may temporarily raise the selenium level in the blood plasma, but shortly after stopping these supplements, the selenium deficiency can be detected again. This is not a true deficiency. The selenium deficiency actually masks a zinc deficiency, which results from a lack of P5P. The cause of P5P deficiency and thus dysfunctional detoxification lies in a disruption of the gut flora.

Symptoms of zinc deficiency

Due to the latent or already noticeable zinc deficiency caused by KPU, secondary diseases and symptoms often arise, such as eczema, mud fever, poor hoof growth, poor coat change, thin manes and tails, a weak immune system with allergies, susceptibility to infections, or chronic coughing. The more trace elements become deficient, the more diseases and symptoms manifest, and the less the horse can respond to therapies or medications.

How does this happen?

The cause of KPU is a lack of supply of P5P. How can this happen? Most muesli, pellets, and mineral feed are heavily supplemented with Vitamin B6. However, this is the inactive form, which the horse cannot activate on its own. Brewer’s yeast is also not a good source of P5P. It is therefore important to restore the horse’s natural gut flora to its normal functioning. This way, the horse is automatically supplied with all active B-vitamins, Vitamin K, and many essential amino acids that are also produced by the gut symbionts. Additionally, anything that disrupts the horse’s gut flora should be avoided. These disruptions primarily stem from the feeding practices.

What to do about it?

If KPU is suspected, a urine test should be conducted, even if the blood work shows no abnormalities. This test is offered by the laboratory www.sension.eu.

1. Urine test

Two values are determined here: Indican as an indicator of intestinal putrefaction and Kryptopyrrole as an indicator of liver metabolism dysregulation. The Indican value is more informative for horses, as it shows the onset of KPU, even if the liver can still compensate. If the result is positive, please contact us for the necessary therapeutic and supportive measures, as these can vary in detail depending on the values, horse breed and age, and any pre-existing conditions.

2. Optimise the Diet

The first priority is always the optimisation of the diet. This includes ensuring the horse has access to good, fibrous hay 24/7 to support the gut flora. Empty periods longer than 4 hours must be avoided at all costs. Haylage and other silage products must be removed from the feeding plan, along with any other foods that are poorly tolerated, such as bread, bananas, large amounts of carrots or apples, large quantities of apple pomace, and fibre in the form of green stems or husks in concentrates.

3. Colon Restoration and Regeneration

A gut regeneration is necessary to restore the balance of the gut flora. For this, administer OKAPI Liquorice Extract for 2 weeks, take a 2-week break, and then repeat for another 2 weeks. It has anti-inflammatory properties and encourages the body to renew the intestinal lining. At the same time, feed OKAPI Bitter Herbs for 4–6 weeks, which stimulate bile production, support the intestinal muscles, and help inhibit putrefactive bacteria. If the horse is experiencing feacel water, also administer OKAPI Helianthus for 4 weeks to help bind the stool until the gut lining is restored.

4. KPU-Therapy

Horses with KPU must be provided with essential B vitamins and zinc. Both are included in OKAPI HeparKPU forte, along with plant-based active ingredients that help reduce intestinal putrefaction. Depending on urine test results, it should be administered for 6–18 months. If haylage has been fed, an additional detoxification treatment is necessary. For this, give OKAPI Prodic for 2–4 weeks to neutralise acids and support the body’s excretion process. In any case, a course of OKAPI Spirulina (as powder or pellets) should be given. This binds toxins in the body, which are primarily eliminated via the liver, gallbladder, and intestines, thus relieving the kidneys.

Long-term support

KPU horses also benefit from ongoing metabolic support after colon restoration until the body returns to balance. We recommend the use of OKAPI Seasonal Feeds, which generally serves as a healthy alternative or supplement to concentrated feed, or alternatively, a two-week rotation of OKAPI Detox Herbs, OKAPI Grazing Herbs, OKAPI Immuno Herbs, and OKAPI Bitter Herbs. Additionally, ensure proper mineral balance with OKAPI Mineral Feed. Please consult with us before starting the therapy.