L-Glutamine in Sickle Cell Disease

Ify Osunkwo, MD, MPH: Biree, L-glutamine was recently approved by the FDA, in 2017, for the treatment of sickle cell disease. Can you share with us, how does it work? What does it do? How effective is it? Is it used alone with hydroxyurea? Is it for all genotypes, sickle cell hemoglobin SS? What are your thoughts about Endari?

Biree Andemariam, MD: Based on the clinical trial results that were published, I think, last year, it was a randomized controlled, placebo-controlled clinical trial, a couple of hundred patients, randomized either to placebo or daily L-glutamine. What they showed was there was a reduction in the median annualized frequency of pain crises by about 25% over placebo. On that basis they got FDA approval, also on the basis of that in the study they saw very little toxicity. I guess commonly reported adverse effects have included some nausea, some dyspepsia. It’s important that people know that this is not a pill. Even though it’s an oral formulation, it’s a powder that has to be mixed and ingested twice a day.

Ify Osunkwo, MD, MPH: In cold or in room temperature?

Biree Andemariam, MD: You can imagine there might be some dyspepsia associated with that. It got FDA approval for its indication, and I’ve personally seen that in some patients it really works to reduce their pain crisis frequency. I think what has been challenging for some patients is the formulation and having to drink something twice a day and remember to do it is a burdensome in the GI [gastrointestinal] adverse effects.

The mechanism of action is a little unclear, and I know that there’s some work being done to fine-tune that a little more, but it works as an antioxidant. It is pharmaceutical-grade L-glutamine. A lot of people ask, “Well, can’t I just get this from my local GNC?”

Ify Osunkwo, MD, MPH: Amazon?

Biree Andemariam, MD: If you talk to the manufacturer they’ll say, “You know, this was developed in a pharmaceutical-grade fashion, tightly regulated. Every patient is getting the same exact dose.” I think in some patients it really works, and in some patients I think the jury is still out.

Ify Osunkwo, MD, MPH: It’s important to know that it’s heat sensitive. If you put it in a place where it gets exposed to heat, it deactivates the medication.

Transcript edited for clarity.