Sickle Cell and Hydroxyurea

Hydroxyurea has been advocated as a treatment for Sickle cell crises in adults but because of it’s potential side effects it has yet to be approved for use in children. The side effects include:

• drowsiness,
• nausea,
• vomiting
• diarrhea,
• constipation,
• mucositis,
• anorexia,
• stomatitis,
• bone marrow toxicity (which may take 7–21 days to recover after the drug has been discontinued),
• alopecia (hair loss),
• skin changes,
• abnormal liver enzymes,
• creatinine and blood urea nitrogen

Due to its effect on the bone marrow, regular monitoring of the full blood count is vital, as well as early response to possible infections. In addition, renal function, uric acid and electrolytes, as well as liver enzymes, are commonly checked.

On a positive note a 2005 study with sickle cell patients indicated that long-term hydroxyurea treatment can improve height, weight, and spleen function, and reduce episodes of acute chest syndrome. Patients in the study started the treatment as babies, and most patients took the drug for at least 4 years.

Hydroxycarbamide has been used primarily for the treatment of myeloproliferative diseases, which has an inherent risk of transforming to acute myeloid leukemia. There has been a longstanding concern that hydroxycarbamide itself carries a leukemia risk, but large studies have shown that the risk is either absent or very small. Nevertheless, it has been a barrier for its wider use in patients with sickle-cell disease.

One of the main reasons that Hydroxyurea has been recommended for sickle cell is that there is evidence to show that it increases the production of fetal haemoblobin (HbF) which appears to be able to carry more oxygen. The mechanisms are not fully understood but would appear to revolve around breaking down sickle cells and increasing the production of Hb.

I’d always prefer to look for non pharmaceutical lifestyle changes first and that has taken me in the direction of the following.

Cytidine Analogues. Cytidine analogues increase HbF production by affecting the genes that regulate it. Decitabine is one such drug that was developed to treat leukemia and other blood malignancies. Early studies are suggesting that it significantly increases HbF production, even in patients who have failed hydroxyurea. Only minor toxic side effects have been reported to date. So my question is where could the body get naturally occuring cytidine precursors. The answer is from eating meat from organs such as liver, kidney, heart etc. These are rich in Dietary sources of cytidine and include foods with high RNA (ribonucleic acid) content, such as organ meats, Brewer’s yeast, as well as pyrimide-rich foods such as beer. During digestion, RNA-rich foods are broken-down into ribosyl pyrimidines (cytidine and uridine), which are absorbed intact. In humans, dietary cytidine is converted into uridine, which is probably the compound behind cytidine’s metabolic effects.

Butyrates. Butyrates are natural fatty acids, which are the end-products of fermented carbohydrates in the intestinal tract and they are also metabolized from fiber. One derivative, arginine butyrate, has been under investigation for some time in sickle cell for its role in stimulating production of HbF. Intermittent therapy using intravenous administration has achieved increased levels. In a promising 2002 study administering arginine butyrate improved ulcer healing by ten-fold. Because its actions are different from hydroxyurea, experts hope the two drugs may eventually be used in combination. However, arginine butyrate is difficult to administer, and experts are looking for different forms that might make it simpler to use.

So my advice is to eat food before resorting to drugs. Eating a diet with plenty of liver and kidney could be beneficial. Try for yourself and let us know how you get on.