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This section, which was started at the end of July 2008, is intended as a supplement to Part I. It highlights some of the writer's unanswered questions and thinking regarding optimal dosing issues, and it updates people who may have initially read Part I many months ago, but who have not revisited it lately.

(1) A recent post by this writer on our Message Board delineates some of the questions: 

I am, of course, not sure that "my guidelines" are optimal. Time will tell.

There is a lot of nonsense being circulated even in high places about ART. Just a few days ago, for example, I heard that artemether is better because it has a half-life of over 12 hours, when its half life, I have otherwise heard, is a mere four hours. Of course, I could indeed have been previously misinformed.

I heard from the same source that the half-lives of artemisinin and artesunate were a lot shorter than four hours, when I was told by another reliable source they were [also] four hours [confirmed in a printed article].

I've heard an authoritative source encouraging use of vitamin C and E in taking ART, stating they function as pro-oxidants as well as anti-oxidants (that much is true, with a lot of caveats relating to iron levels), and that the anti-oxidant effect of these vitamins wouldn't interfere with the super-oxidant effect of ART (it needs that effect to do its work). I'd want to verify that before acting on this premise, however.

I've heard that use of butyric acid is a good thing in that it potentiates the ART, but yes, that same source has acknowledged that butyric acid smells horribly and lingers, if made volatile in the air [for months]. The stomach is said to be exempt, but I'd need to check this out through several independent sources before acting on it.

Separating fact from fiction, as you can see, very formidable.

(2) Additionally, one person (Randy) claimed excellent results when, instead of two two initial ~week-long pulsings, he used artemisinin and artesunate for a week--same dosing level this writer used--then off for a week, then on for another week. He repeated this over 3-4 months.

Another person (Jennifer) appears to have gotten excellent results (pulmonary papillomas disappeared) with every other day dosing with artemisinin (she was using other things, but there is reason to suppose the effect was due to the ART).

(3) It is important that note that in RRP ISA's initial remarks on ART, concern was expressed about whether ART might not kill infected cells through the biological process of necrosis. If that occurred, it was reasoned, an inflammatory reaction would occur. No such reaction was observed thus far, but cautions were suggested regarding the need to monitor ART in young children with RRP, since this set of patients has a narrow airway that can't afford to be seriously inflamed, etc.

This writer has since learned, from N. Singh of Univ. of Washington's School of Bioengineering,  that ART's mode of action is not through necrosis, but apoptosis. Dr. Singh has further characterized ART as anti-inflammatory.

This is reflected now on Part I of the Guidelines, but it seemed advisable to create an "addendum page" (Part II) where readers could update their knowledge without having to wade through the entirety of Part I. 

(4) We have received several inquiries as to sourcing of ART. Our sources are cited in the second and third sentences of Guidelines, part I. One source (Holley) was used in Georgetown's study with dogs. It is reported to be HPLC tested. The Hepalin/Wellcare source is cited by Dr. N. Singh from the University of Washington, who also works with ART. There is reciprocal reference to Dr. Singh by Holley. We have indicated previously that we would not be making sourcing recommendations, but people should note that ART often comes in from China, and even in areas where malaria has been treated, there have been serious issues raised in connection with sourcing, QA, etc.

We are not going to say that sourcing outside these two companies is bad, or that these companies are necessarily good. We've attempted to apply certain standards to the best of our ability, however, and this is what we've been able to come up with. In two years, our sources haven't changed. If we learn something adverse about either source, we will let people know.

If people want to get bargain basement prices for ART somewhere else, have at it, but please notate that in any reports back to our community. You may not be getting ART, or you may be getting something you do not want. Given the toxicity issues with artemether beyond a certain dosing level, you might even be permanently injuring yourself.

(5) Somewhere in an initial version of Part I, it was suggested that patients may want to wait a week after surgery before starting ART.  This writer initially did, and it was suggested that if people wanted to follow what he did--because we cannot write guidelines for others--this is the route they may wish to consider.

Our reasoning in waiting a week was to mitigate any "unknown effects" from the ART as it might have (??) adversely affected the healing process following surgery. Dr. Singh has, however, indicated that it is his belief the dosing level we have put forward is well within reasonable limits. Assuming one does not exceed it, unknown effects would probably be minimal. Medical supervision is of course still indicated, and this writer still thinks children and toddlers may need to be monitored even more meticulously, but this writer currently thinks that earlier concerns are probably unwarranted. Since ART's mechanism of action is through the technical process of apoptosis, not necrosis, he now believes that it is probably safe for him to take ART immediately after surgery, in an effort to kill as many infected cells that remain.

What he wishes is to kill as many previously infected cells that survived the surgery and that might otherwise replicate rapidly through the wound-healing phase immediately following surgery. (If you read this website's FAQ, you would know that is a critical phase, and it is right AFTER surgery that there is always a proliferation of RRP, though at first it is usually not visible.)

A surgery would ideally first debulk the gross papillomas, and the ART might then be used to immediately "mop up" remaining infection that escaped the debrider or laser--cells that might otherwise multiply during the wound-healing phase, and would later become full-blown papillomas over weeks or months were they not killed through apoptosis from the ART.

This is, for now, only a hypothesis. It is currently being tested by the writer of this section.

(6) In the initial versions of Part I, it was stated that no serious side-effects seemed to be attached to artemisinin and artesunate, with certain caveats (e.g., anemia) and in the dosing range that was used.

We are NOT suggesting that serious side-effects are impossible, however. After taking a week of ART, one may feel it. After two weeks of ART (a week on, off and on again), that sense can be accentuated.

This writer has observed in himself upon taking the ART--and this appears to be idiosyncratic--some minor irritability, minor insomnia, etc. There could have also been some increased photo-sensitivity, but that went away as soon as the dosing stopped, and it was never dramatically noticeable. It may have been imagined.

What of the patient, however, who is already predisposed to schizophrenia, major depression,  bipolar disorder, serious panic attacks, anger management problems or insomnia?

This writer knows of no authoritatively documented studies suggesting this kind of psycho-mental side-effect profile--ART has been used on millions of people for malaria and is recommended for children as young as two years old by the World Health Organization, for goodness sake--but he thinks it is presumptuous to confidently say that dosing with ART for a length of time could not exacerbate a psychological disorder of this nature.

We would hypothesize that for someone who is already very "tippy" psychologically, ART might introduce an unpredictable variable with unpredictable results. Of course, the same thing could be said for antihistamines,  antibiotics or shellfish. In the end all that we can say is that no one should attempt to predict idiosyncratic reactions.

Now, there are those who would try to close down the Gardasil immunization effort because their teenage daughters fainted when the injection was given in the school nurse's office. We don't mean to be disrespectful, but some serious question needs to be asked and answered: Was this because GARD is inherently unsafe or because a set of adolescent patients were already "primed" to react in an over-emotional manner?

Our point is that one cannot always tell what is happening from surface-data alone. That certainly applies to Gardasil. It probably also applies to ART.

If there were a serious side-effect profile for ART, however, one would think it would have shown up in the literature, much of which is sited under the Learn>Novel Therapy section of this website. This body of literature suggests that the use of ART, when taken appropriately and in coordination with your physician, is usually safe, at least for most people.

(7) We initially suggested that it was probably best that ART (artemisinin and artesunate) be taken with a meal. Dr. Singh says that is not optimal, and his reasoning makes sense. We've just changed the guidelines relating to this issue in Part I, and we wish to call your attention to this in Part II.

Dr. Singh writes in an e-mail:

[Take ART] 3 to 4 hours after [a meal] with a cup of milk or spoonful of ice cream (without flavors or additives e.g. Breyers natural vanilla). . . .The purpose of giving a 3-4 hour interval. . .is to make sure [the] stomach is almost empty, as the drug interacts with the iron contents of food.

NOTE: Dr. Singh speaks largely to the question of artemether and Artemix. Artemether is fat soluble, but artemisinin is water soluble.This writer would add water to the milk/ice cream. Artemisinin is not fat soluble, it is water soluble. Other forms of ART are fat soluble. This writer takes water + a small amount of fat, as suggested immediately above).

Needless to say, this amount of wait-time makes "splitting the doses" a lot more troublesome.  Still, these recommendations seem well-reasoned, even compelling.

We are guessing that one may safely eat again from ~60-90 minutes after dosing with ART, since taking ART on an otherwise empty stomach should not take 3-4 hours to be absorbed. (It may be absorbed within 30 minutes, but it probably wouldn't hurt to add another 30-60 minutes on top of that.)
 

7-31-08: In closing, this writer previously described that after more than two years following the commencement of ART--as previously stated in the patient reports section--a small papilloma was found on his left vocal cord. It has remained relatively small, growing very slightly over the past few months. It has NOT affected his voice significantly (still VERY much stronger than anytime over the previous decades with RRP), but in the interest of testing his current line of thinking on dosing, he just had a surgical procedure. It took all of 15 minutes, with the microdebrider and also a low-power lasering of one ventricle). 

Given the enormous unknowns relating to  optimal dosing guidelines, we see the process of acquiring solid and accurate information as being evolutionary in nature, not revolutionary.

Nonetheless, it's slowly coming together. Please stay tuned.