Nutraceuticals and nootropics for anti-aging

What supplements might be useful for someone with beta-thalassemia?

I’ll first discuss the causes of thalassemia, and then indicate some supplements and drugs that might be worth trying.

Thalassemia is a collection of related diseases caused by failures of the genes regulating hemoglobin production. Hemoglobin, of course, is the substance in red blood cells that carries oxygen from the lungs to all the other cells of the body.

In healthy adult humans, hemoglobin is a molecular complex composed of four protein molecules: two molecules of an "alpha-protein" and two molecules of a "beta-protein". The body normally regulates the production of these two proteins so that they are made in equal amounts.

Thalassemia occurs when the alpha- and beta-proteins are produced in the wrong proportion. Usually this is due to genetic mutations inherited from one’s parents. For example, inheriting one defective beta-gene from one parent results in a shortage of beta-protein — and the resulting condition is called ‘beta-thalassemia’.

There are a large number of other variants of thalassemia, depending on just what genetic defects happen to be present, and the symptoms can vary from being unnoticeable to being fatal. The more severe forms of thalassemia require regular blood transfusions to prevent progressive anemia and death.

Beta-thalassemia is the most common form in Caucasians. The basic problem here is that the red blood cells contain too many alpha-proteins, and the surplus alpha-proteins accumulate at the cell membrane and disrupt its functioning. Red blood cells with altered cell membranes are detected by antibodies and targeted for destruction in the spleen. Since so many of the red blood cells are defective, the spleen destroys lots of them. The bone marrow tries to replace them by making them faster, which in turn causes more work for the spleen. So the spleen enlarges.

Thalassemia causes iron absorption to increase in the digestive tract, leading to iron overload in the body. Blood transfusions also cause iron accumulation. And the destruction of red blood cells by the spleen releases large amounts of iron. Since free iron is a catalyst for oxidative reactions, its increase leads to a rise in the levels of certain free radicals. And these, of course, cause widespread damage, including damage to DNA.

The standard treatments for thalassemia (transfusions, removal of the spleen, injection of iron chelators) are crude — but are they avoidable? For now, the answer can only come from self-experimentation. The two problems that need to be solved are: how to prevent the accumulation of alpha-protein in red blood cells; and how to prevent iron-mediated oxidative damage. There is not yet an available solution to the first problem, although there’s been some preliminary work done on it. (http://rarediseases.about.com/library/weekly/blnews062302.htm [Protein Discovered That Keeps Hemoglobin In Balance; Research May Advance Treatment Of The Blood Disease Thalassemia])

As for the second problem, antioxidants and iron chelation appear to be the right approach. Antioxidants are easy to come by, and research suggests that it is useful to take a variety of them: vit C and E, selenium, molybdenum, zinc (in modest amounts), polyphenols (such as quercetin and green tea extract), and perhaps some other categories just to cover more bases (such as ferulic acid).

There are three iron chelators that would be worth trying:

1. Quercetin — a supplement that has shown promise as an iron chelator in sickle-cell disease, and would probably work similarly in thalassemia.
2. Deferiprone — a drug currently available only in clinical trials.
3. Clioquinol — a drug used widely in the 1940s, still available by prescription as a diarrhea treatment.

It would be a mistake to take iron supplements. The anemia resulting from thalassemia cannot be treated by taking extra iron. In fact, extra iron will only make the situation worse.

— Dr. Alexis Zarkov, Ph.D.

You can contact Dr. Zarkov at AskDrZarkov@yahoo.com.

Last modified 2004.Oct.29

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References

News story: Protein Discovered That Keeps Hemoglobin In Balance; Research May Advance Treatment Of The Blood Disease Thalassemia

Iron toxicity and chelation therapy. Int J Hematol. 2002 Oct;76(3):219-28.

Membrane-bound iron contributes to oxidative damage of beta-thalassaemia intermedia erythrocytes. Br J Haematol. 2001 Jan;112(1):48-50.

Pathophysiology of thalassaemia. Baillieres Clin Haematol. 1998 Mar;11(1):127-46.

An excellent website for overview of thalassemia, iron, and sickle cell

t-BOOH-induced oxidative damage in sickle red blood cells and the role of flavonoids. Biomed Pharmacother. 2003 May-Jun;57(3-4):124-9.

Iron release, oxidative stress and erythrocyte ageing. Free Radic Biol Med. 2002 Apr 1;32(7):568-76.

Effect of antioxidant flavonoids and a food mutagen on lymphocytes of a thalassemia patient without chelation therapy in the Comet assay. Teratog Carcinog Mutagen. 2001;21(2):165-74.

Metal-protein attenuation with iodochlorhydroxyquin (clioquinol) targeting Abeta amyloid deposition and toxicity in Alzheimer disease: a pilot phase 2 clinical trial. Arch Neurol. 2003 Dec;60(12):1685-91.

Ironic fate: can a banned drug control metal heavies in neurodegenerative diseases? Neuron. 2003 Mar 27;37(6):889-90.

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Disclaimer: The information provided in this Ask Dr. Zarkov article contains no medical advice whatsoever — it contains only biological information. Nothing in the article constitutes an effort to persuade readers to use, or not to use, this information as a basis for personal action.