Hookworms and Haemachromatosis or hemachromatosis


A brief discussion of the potential for hookworm therapy as a passive treatment for excessive iron diseases

Hookworms consume blood from their hosts

Haemochromatosis (American spelling is hemochromatosis) is a genetic disease that causes an unhealthy accumulation of iron in the body.
To levels that can cause a variety of serious symptoms and disorders:

Fatigue, weakness and lethargy
Joint pains leading to osteoarthritis
Abdominal pain
Diabetes
Liver disorders; enlarged liver, cirrhosis
Sexual disorders; loss of sex drive in both male and female, impotence in men, absent or scanty menstrual periods and early menopause in women
A decrease in body hair
Discolouration or bronzing of the skin (hence its archaic name of Bronze diabetes)
Cardiomyopathy; disease of the heart muscle
Neurological/psychiatric disorders; impaired memory, mood swings, severe irritability, depression.
[1]

Currently, there are two treatments, the most common is the removal of large quantities of blood when first diagnosed if iron and ferritin levels are high enough to be causing organ damage, see above.

Or drugs that help the body excrete iron without metabolising it. [Management of Haemochromatosis in General Practice]

If phlebotomy (bleeding, venesection or exsanguination) is used once a healthy baseline is attained bleeding is less frequently required but suffers from being episodic and involving the taking of relatively large quantities of blood.

Like insulin injections for diabetes, which replace a dynamic system for regulating insulin levels finely tuned in relation to blood sugar levels, the removal of large quantities of blood periodically suffers similar problems, being a crude approximation of a natural process.

As with insulin injections for diabetes, the large swings of in this case iron means that one is rarely at a healthy, optimal level of iron saturation in one’s tissues.

Far better, as witnessed by efforts to develop insulin pumps to deliver smaller doses more frequently in response to frequent blood sugar tests, is a system whereby a subject could be bled on a minute-by-minute basis.

Nature has provided just such a pump for iron removal in the form of hookworms, which are tiny (1.4 cm by half a mm) roundworms that feed on the blood of their hosts, drawing very small amounts per organism.

This characteristic would allow a very fine tuning of the resident population in any subject, probably after phlebotomy had been used to resolve the excess of iron in the tissues of the newly diagnosed.

Producing an optimal population easily titrated for each individual should be relatively easy, particularly as experience using this approach is accumulated, or after a brief dosing trial in a range of haemochromatosis types.

The idea of using hookworms to treat haemochromatosis NOT an original one, it was tried in ten subjects in 1965, however, the paper is French and does not appear to be available online. [2]

It was also described in a letter to the BMJ in 1991, so the idea of using hookworms to treat haemochromatosis has been around for a very long time. [3]

Hookworms, in my opinion, are a very safe option for use in this way. That opinion is supported by the Centers for Disease Control (CDC) in America which recommends US doctors not treat light to moderate infections with hookworms.

That recommendation is likely made because hookworms are a self-limiting (they die of old age) infection. They do not proliferate in the host, they don’t represent an infection risk in developed countries, nor do they mismigrate, and they are easy to eliminate with drugs that in most countries are available over the counter.

The light to moderate part of their recommendation springs from their potential to cause iron deficiency anaemia in normal subjects in large numbers.

This is their only potential negative health impact*, one only possible when the number of adult hookworm in an adult male opmnivore who was not supplementing with iron exceeds 300 (me, I only have myself to experiment on).

This is the reason hookworms represent such a good candidate for treating haemochromatosis, as in normal subjects they can cause anaemia if present in significant numbers.

Other advantages would appear to be that it is a passive system for reducing iron stores, so that it would not require regular visits to facilities for phlebotomy/venesection. So compliance would be a given once the subject had been infected with sufficient organisms. Given they live for three years in most subjects redosing would at most have to be an annual occurrence.

After a year hosting any number of hookworm the immune response of the subject would be sufficient moderated to allow large top-up doses of up to 100 without any side effects (there are some exceptions to this rule), and it is a way to constantly remove relatively small amounts of iron on a daily basis avoiding the side-effects of the removal of large amounts of blood on an episodic basis.

Because iron removal would be continuous and consistent the problems of organ damage that attend the episodic removal of large volumes of blood when iron saturation levels were or were approaching pathological levels using conventional treatments should be eliminated or reduced.

Given the effectiveness of helminthic therapy based on hookworms for treating such a large variety of chronic inflammatory, autoimmune, allergic and other immunological disorders a prophylactic effect for a very large variety of such conditions would likely be a consequence.

There are two species of hookworm that commonly infect humans and which have humans as their definitive host.

Each of the species of hookworms with humans as their definitive host are quite different in terms of their characteristics as a potential candidate as a therapeutic organism for haemochromatosis.

Necator Americanus is longer lived, three years in my experience except in those subjects exhibiting evidence of a strong coevolutionary effect on their genetic makeup. Those with the form of Crohn’s affecting the ileum, and a significant subset of those with an atopic disorder.

It has been demonstrated that coevolution with helminths has shaped the human immune system. [4]

The other species is shorter lived, Ancylostoma Duodenale, but it also draws up to six times as much blood.

It may be that haemochromatosis (American spelling is hemochromatosis) is an adaptation to very high hookworm burden environments.

It would be strongly suggestive that haemochromatosis is the result of coevolution with hookworms if it occurred significantly more often in those suffering from the form of Crohn’s that occurs in the ileum.

However, even if there was no correlation as described between Crohn’s of the ileum (ileocolitis sometimes) and haemochromatosis it is still possible that haemochromatosis arose from coevolution with hookworms as it may have occurred independently of the mutations which lead to Crohn’s.

It is also possible that the mutations leading to the disorder arose in an environment which provided a diet that was iron deficient, as suggested by the fact that periods of food deprivation in animal models lead to a similar response as to inflammation, where hepcidin is produced blocking iron uptake and at the same time scavenging it from circulation by conserving it in the liver and in macrophages. [5]

From Healthline: “Most types of primary hemochromatosis are caused by mutations. The HFE gene, or hemochromatosis gene, controls how much iron you absorb from food. There are two common mutations of this gene that cause hemochromatosis. They are C282Y and H63D. A person must inherit a copy of the defective gene from each parent to develop this condition. A person who inherits only one copy of a mutated gene is considered a carrier of the condition, but they may never manifest symptoms.”

That if the mutations associated with haemochromatosis are inherited from only one parent the disease does not occur suggests the mutation did arise as a result of living in an iron-deficient environment. As pathology only occurs if the mutation is inherited from both parents as is the case with similar mutations.

This is a similar situation to that which occurs in many genetic diseases, of which haemochromatosis is the most common, such as Sickle-Cell Anaemia, Taye-Sachs and Cystic Fibrosis which result from adaptations to diseases with very high morbidities.

All are genetic diseases where a single copy of the mutation confers a heightened level of immunity to a particularly lethal disease, Malaria, Tuberculosis and Cholera respectively.

One only develops the genetic disorder when one inherits the mutation from both parents.

I am not sure if the inconvenience of regular blood donations is sufficient to make hookworms an attractive alternative treatment, but based on my reading it appears that the drawbacks, including expense, of regular bleeding by phlebotomy, would make hookworms a better treatment in terms of the health of the individual, reduced need for monitoring and treatments, and potentially produce higher compliance rates and better outcomes.

*Infection with high numbers of hookworms has not been studied sufficiently to be sure of this claim, they do modulate host immune response, so there is the potential that in very large numbers individuals might be more vulnerable to infectious diseases and to cancers than the general population. For a more complete discussion of this topic please visit our Safety Page.

1. Treatment of idiopathic haemochromatosis. Lancet. 1977;1: 290–291. doi:10.1016/S0140-6736(77)91831-1

2. Deuil R, Brumpt L, Mundler B, Puech H, Liquory C, Chanu P. [THE PRACTICE OF BLEEDING IN IDIOPATHIC HEMOCHROMATOSIS. 1 CASE SUBJECTED TO INOCULATION WITH ANCYLOSTOMA DUODENALE; 10 CASES TREATED FROM 1 TO 4 YEARS]. Sem Hop. 1965;41: 259–263. Available: https://www.ncbi.nlm.nih.gov/pubmed/14259068

3. Simon D, Rose C, Bovill BA. Hookworms to treat haemochromatosis? Postgrad Med J. 1997;73: 254–255. Available: https://www.ncbi.nlm.nih.gov/pubmed/9156137

4. Fumagalli M, Pozzoli U, Cagliani R, Comi GP, Riva S, Clerici M, et al. Parasites represent a major selective force for interleukin genes and shape the genetic predisposition to autoimmune conditions. J Exp Med. 2009;206: 1395–1408. doi:10.1084/jem.20082779

5. Mirciov CSG, Wilkins SJ, Anderson GJ, Frazer DM. Food deprivation increases hepatic hepcidin expression and can overcome the effect of Hfe deletion in male mice. FASEB J. 2018; fj201701497RR. doi:10.1096/fj.201701497RR

6. You read this far, wow. I am truly impressed.

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