Order copies  

Rewritten and reposted May 31, 2011

Disclaimer Regarding Recommendations:

As of June 22, 2010, this page was deactivated. As of May 31, 2011, it has been reactivated and there are a few new updates. RRP ISA is offering the following material as information that patients might consider but it is not intended not as medical advice. What follows should be reviewed with your personal physician.

In the interest of even greater clarity, not to mention its pun-value, RRP ISA is now calling its artemisinin usage guidelines (first developed in 2006 and published in 2008) the WMD Guidelines, or the "What-Michael-Did Guidelines."

These are not guidelines that we're actually recommending, but if you're doing it differently, then it isn't an apples to apples comparison. You're following the What-You-Did (WYD) guidelines. That's not necessarily a bad thing, but it isn't WMD. That needs to be clarified in reporting both your side-effects and your results.

RRP ISA would ideally like to contact each and every RRP patient following this approach. There are many ways of inadvertently sabotaging it and we would like to control for that through case management and some extensive telephone and/or Skype-based work. This is not a drug which should just be given to patients with unlimited confidence that it will be administered correctly.

The dosing schedule in the "WMD Guidelines" is well-reasoned (and has been used for years) but is probably not optimal. This is because the research required to determine optimal dosing has not yet been done. Much more study needs to be done to establish the best dosing schedule, which is why RRP ISA strongly encourages the otolaryngological community to begin clinical trials as soon as possible.

ART Sourcing:

Artemisinin itself may be acquired through Holley Pharmaceuticals at a 30% price reduction for RRP patients. It is called "ArteMin." Please remind Holley that you are an RRP patient. It claims its artemisinin has been tested by HPLC, and this was the original source of Dr. Schlegel's artemisinin, as described in Learn>Novel Therapies.

Sourcing of artesunate has been through Hepalin/Wellcare (this firm calls it "Hepasunate" and describes it as artesunate). No price drop is offered. Hepalin claims it tests by HPLC, melting point, etc. Spot-testing (University of Washington staff) of Hepalin's ART products for purity and dose has reportedly checked out in the past. It needs to be noted, however, that no one at the University of Washington serve as a quality assurance agent for Hepalin/Wellcare.

No physician's prescription is required for either of these products.

Artemisinin and its analogues (henceforth abbreviated ART) are imported, and much of it comes from mainland China. RRP ISA cannot vouch for product purity or quality, and we are not "recommending" these two sources over any other. There is a lot of counterfeit artemisinin being sold on the internet, however. Moreover, tens of thousands of malaria patients are dying each year because they are getting counterfeit artemisinin. After doing its own due diligence, these are the sources through whom staff at RRP ISA have ordered. If one wishes to follow the WMD guidelines, however, these were his two most reliable sources for ART.

Those patients or physicians who choose to order are advised to do their own due diligence. One strong recommendation is to put quality and reputation above price. Take care in your selection of source. Do not try eBay, and do not assume that "cheap is better." It probably isn't and if you do that, you may be getting a counterfeit.

By way of a disclaimer, RRP ISA, its staff and its board does not assume responsibility for how you use the information provided here about dose and administration of ART, sourcing of this group of medications and/or how others have used this medication.

More to the point, artemisinin treatment is very easy to inadvertently sabatoge. If you're not prepared to carefully pay attention to the WMD-guidelines and adhere to what is said there, this approach is probably not for you. Moreover, it could be dangerous.

RRP ISA is not just offering to speak personally with every RRP patient who follows the WMD-guidelines, but tacitly requesting it. We need to talk about your vitamins while on ART, your diet, even your frying pan. We'd like to do this ideally through Skype, less ideally by phone. We strongly believe that it will help maximize your chance of success, radically reducing your chance of failure, side-effects or danger.

We don't want to have to rewrite (or reinterate) the website for you, however. That said, we expect you to be fully aware of what is said here and what the reasoning is behind our assertions.

Initial use of ART (first three weeks):

Artemisinin can only be absorbed continuously for 6-7 days. In this initial phase, ART is given for a week on, a week off, and another week on. Note that this is the only time anyone will take ART for more than 3 days in a row, using the guidelines in this section.

Continuation Dosing:

Whether ART actually kills HPV-infected cells is open to doubt. Papillomas may still recur, though the overall virulence of the virus seems greatly reduced.

As to how much it helps? Anecdotally, this writer had previously used cidofovir, MMR, photo-dynamic therapy, retinoic acid(s), interferon(s), and even acyclovir and acupuncture. ART's effect seems to be many times greater than any of these.

This writer has used it monthly for over six years, based on his reasoning that ART's efficacy requires periodic refreshment (see below).

Following the loading dose phase, described above, he has used it for 3 days a month only, however, on a once-a-month basis.

For people wishing to replicate his approach (WMD Guidelines=What-Michael-Did), this once a month continuation dosing schedule will commence after the initial dosing is over (that's the week on, a week off and another week on).

Thus we have (day 1) an initial dosing schedule lasting around two weeks with another week off. On day 21 (three weeks), the clock for the continuation schedule begins.

A month from that day, it's appropriate to take artemisinin and artesunate together again, but this time only for about three days. Wait yet another month and you may take it again for three days. This cycle will continue indefinitely.

Summary (Initial and Continuation Dosing):

7 days on (artemisinin plus artesunate)
7 days off (no usage)
7 days on
21 days off
3 days on
27 days off
3 days on
27 days off
(Continue the "3 days on, 27 days off" as a maintenance regimen)

How Much To Take:

Dosing at about 7 mg/kg a day of body weight for the artemisinin from Holley and about 4 mg/kg a day for the artesunate from Hepalin/Wellcare seemed to work without any side-effects for this writer.

He's also used Artemix from Wellcare containing artemether. Artemether, however, can be hazardous at high dose levels, and generally speaking, it isn't safe for most patients for that very reason. Patients often think "more is better," but that may result in irreversible neurological damage where artemether is concerned (as shown in animal studies involving artemether only). No such dire warnings were attached to artesunate or artemisinin, but don't increase their dosing either since that doesn't mean there are no dangers in doing so.

Your first task, therefore, is to figure your weigh in kg. To do that, you divide your weight in pounds by the the number 2.2. EXAMPLE: If you weigh 165 pounds, your weight in kg is 75 kg (165 divided by 2.2=75).  ANOTHER EXAMPLE: A 40 pound patient weighs 18 kg (40 divided by 2.2=18).

Once you know the weight of the patient in kg, you're half-way there. If you follow the 7 mg per kg rule, a 165 patient would take 525 mg of artemisinin a day (7 X 75=525). The same patient would take 300 mg of artesunate (4 X 75=300).

Rounding up or down is ok, as the capsules are offered in increments of 50 mg. Thus a 165 pound, 75 kg patient might wish to take 500 mg of artemisinin and 300 mg of artesunate.

The question of rounding up or down often arises. Following these guidelines, an 18 kg child, for example, would be taking 126 mg of artemisinin and 72 mg of artesunate, based on the 7/4 dosing ratio. These size capsules aren't made, however, so the patient's parents will need to decide whether to round up (150/100 mg) or down (100/50 mg).

We can't advise on this, but we can say that while slightly exceeding the 7/4 level seems to be ok, greatly exceeding these 7/4 dosage schedule is probably not a good thing. What is small, what is great? This is a question each person must answer for him/herself, and RRP ISA wishes to steer clear of offering advice.

If it's more than 10% to get a "round number in increments of 50 mg and this writer himself were doing it, he'd be inclined to round downwards. Otherwise, he might round up. If you feel like following what he did more to the letter, you may wish to consider breaking the capsules and dividing the ingredients by eye.

You will almost certainly need to do that anyway, since you will not be giving anyone a full day's dosing all at once. You will need to divide the daily dose, as described in the section below called When To Take It.

This amount will be the patient's standard daily-dosing amount, although as previously stated, you will not take it every day. You will take it a week on, a week off (no ART whatsoever), and another week on. From that point, you will move to the continuation dosing schedule.

Use With Children:

Reports on safety in children deserve special mention.

ART is an anti-inflammatory and works through apoptosis. If that is true, some of the speculations below may be unwarranted. If inflammation were to result, however, could it not cause a potential airway obstruction in very young children?

Anyone using ART with kids needs to be especially careful. There may indeed be no cause for concern, but we think that physician supervision and close monitoring is absolutely indicated and required in the case of toddlers and young children with small airways.

Artemisinin and artesunate generally appear safe for children, at least when used at the initial WND-Guidelines dosing level, which Dr. N. Singh and others described as appearing quite safe. We cannot offer medical advice, but we can say that several sources, including the World Health Organization, have recommended ART for children with malaria.

But what about chronic use over months or years? Here, we have little or no data. This writer knows of no clinical trials for chronic use of ART, whether in children or adults. Are there hidden toxicities? We don't know. We would at the least suggest frequent blood chemistry panels, until more is known.

As in most things, you need to do your own due diligence. Having said that, we suggest reading from the material cited here (on all pages associated with Learn>Novel Therapies. That should allay most anxiety concerns for both prospective patients and health care professionals.

What To Take:

Note that these guidelines call for the taking of BOTH artemisinin AND artesunate. Not just artemisinin.

On the plus side, artemisinin has a longer half-life over artesunate. On the other side, Dr. Tomikazu Sasaki, who is an expert on artemisinin at the University of Washington, writes in an email (4/22/09): 

Again, more studies need to be done to determine the optimum combination and dosing for artemisinin and artesunate (ART).

When to Take It:

It's been reported that the artemisinin and artesunate have only about a 2-4 hour half-life, which is short. You may therefore wish to divide the total dosage, spacing the smaller dosings at 4 hour intervals. You needn't be obsessive, however. This writer "fudged" during sleep and you may wish to do likewise, or during school hours.

We would emphatically warn against taking all the capsules at once. That would almost certainly constitute an overdose. This writer spaced the usage of ART throughout the day. He never took all the artesunate in the morning, for example, and the artemisinin in the evening. Every few hours, he would take a prorated amount of artemisinin and artesunate. In following these guidelines, you would want to do likewise.

Because of the short half-life, you would do well to think of taking ART the last thing before retiring for sleep and early in the morning as well. This writer took it (both artemisinin and artesunate) no less than four times a day.

Storage of ART:

Both artemisinin and artesunate are light sensitive, yet they come bottled in white plastic bottle that, while semi-opaque, still allow light to get in. You may want to wrap the bottles with tin foil so as to prevent light from entering, or else you will want to ensure that they are kept in a dark closet. You can carry a daily dose of capsules around with you, but you should be cautious about keeping the bottle unprotected in an open cupboard, etc.

Antioxidants And Other Medications:

ART works by superoxidizing so-called "active" iron (ferrous form) inside diseased cells. This writer strongly suggests not taking any supplemental antioxidants within 12 hours of starting to dose with artemisinin or artesunate. This includes vitamins C, D, E, A, etc. It also includes multivitamins, powerful food-based antioxidants like blueberries. Please educate yourself on your food-sources and use your common sense.

Because of the pro-oxidant mechanism of action for the ART, antioxidants tend to defeat the ART. This admonition is as significant as the one on the importance of taking the artemisinin with fat-containing food and the artesunate with water. If you also take powerful antioxidants at the same time as you are taking ART and you get no measurable results, please do not blame the ART. 

The problem is that you have taken the ART on one hand and unknowingly worked to defeat it on the other. This is absolutely not an approach that is likely to result in positive results.

If taking statins or other medications, we again emphasize the need to coordinate our WMD usage guidelines with your physician, who may have also asked you to take Co-Q10. The WMD-guidelines call for no Co-Q10 whatsoever within 24 hours of taking ART.

Most foods contain some amount of antioxidants. There is no need to be obsessive, just reasonably mindful. Yes, you can eat an orange. It probably isn't such a good idea to eat blueberries, however. If you have heard of a food-source just brimming with antioxidants, it probably isn't good for you to ingest that during the time you're dosing with ART. Think about what you're eating, but again, don't imagine that you have to eliminate every antioxidant from your diet. Eat balanced meals during this time and use your common sense. Under WMD, you can drink coffee, eat nuts, no chocolate though but we’re not sure the latter is really an issue (even if it is an antioxidant). It certainly isn’t in the blueberry-class.

Ingestion of Ferrous-Containing Food

While two ART researchers at the University of Washington have all but dismissed the possibility that taking food with the ART could interfere with it, one researcher believes it might very well happen. There is reason to believe that he may be right.

It isn't about "food" so much as it's about the artificial spiking of food with ferrous-supplementation.

For example, most cereals and breads--even organic bread flour--contain the active form of iron (ferrous, which is the target of artemisinin). There is no reason to suppose that ingesting ART in the presence of ferrous-supplemented food couldn't cause the ART to prematurely react in the gut, rather than remain inert until it has entered the cells containing RRP.

The stomach is known to be a caldron of extreme complexity relative to iron metabolism, and there are indeed some serious unpredictables (thanks to Dr. Tom Broker for his insights here).

For what it's worth, the "WMD guidelines" calls for curtailing the ingestion of all forms of active (ferrous-based) iron during the several days that ART is to be taken. This means no cereals or pastries, little bread (even organic bread) and minimal processed foods. Finally, if you don't know what's in it, you probably shouldn't eat it during the time you're taking ART.

How Does It Work On HPV Tumors and RRP?

The form of the iron that freely circulates in the blood (a ferric form) is converted into the ferrous form, used inside cells. The HPV virus needs that particular form of iron to replicate and create papillomas. Transferrin receptors appear to play a role here, as discussed elsewhere. ART enters the cell and superoxidizes the ferrous form of iron--it doesn't normally affect the form of iron in the blood or the stomach. It creates apoptotic intracellular conditions that Dr. Tom Broker described as "spectacular." Even if it doesn't appear to kill all of the virus, it seems to down-regulate RRP radically, at least in many patients.

Should I Take It With Iron Supplements:

That could cause problems if the supplement contains the ferrous form of iron that ART reacts with. If ART reacted to the form of ferrous iron in the supplement, it may cause nausea and, more ominously, it could be expected to eliminate or greatly reduce the ability of ART to work on RRP. Used with a chelated or succinate form of iron, ART might be shown to even be helpful, but if one choose to do that, they should probably use no more than the RDA. It would be an experiment; research on that is still out.

Cooking Utensils:

Same precautions apply here as with iron supplements. Cast iron utensils may (?) leach ferrous-based iron into one's food. That could be expected to eliminate or potentially reduce the ability of the ART to work on RRP. Take great care to note these concerns. ART works by selectively "attacking" certain forms of iron. If you ingest ferrous-based forms of iron during your dosing days, you will probably get little or no benefit from ART.

Whether To Take It With Or Without Food:

Dr. Sasaki, a expert in artemisinin and chemistry at the University of Washington confirms that artemisinin is partially fat soluble--mostly dissolved by albumin, however--not water soluble. Artemisinin is not very bioavailable because it is only partially soluble.

Dr. Singh at the Univ. of Washington recommended that the stomach contents be emptied of food when taking ART. He suggests waiting 3-4 hours after a meal. He affirmed the importance of fat in the absorption process, so he suggested taking ART with a glass of whole milk (milk contains very little iron) + some water as well.

Other ART experts at the Univ. of Washington vigorously disputed any need for the fasting-period, contending that the iron in food is typically well-chelated and does not react to the ART.

Thus it is that we have a friendly contradiction going. One published study showed that the presence of food didn't seem to interfere with ART absorption, but, of course, absorption isn't the same as effect. Also, we don't fully understand what will happen to the ART after a multitude of chemical operations on the food in the stomach (stomach acid changes many food-based molecular bonds).

At the time of this latest writing, no solid evidence has come to our attention suggesting that one approach is better than the other but do be careful of what you eat, as stated above. Taking ART with foods that have been artificially supplemented with ferrous (that's true of many cereals and of most organic/inorganic flour). Finally, milk itself contains relatively little fat, so it may well be that taking ART with fat-containing food (assuming there is no processed food containing ferrous) is best.

The most important thing is to take both the artemisinin and artesunate with something that has some sort of fat content (e.g., whole milk, eggs, oils, toast and peanut butter or regular butter, cheese, meat, etc.). One probably should also drink a few ounces of water at the same time.

If you are using just water, then you are not properly absorbing the artemisinin. In that case, your trial with ART will almost certainly fail.

What Not To Do (Mixing Treatment Modalities):

ART is not a vitamin. While is may not be regulated by the FDA in America, it is considered a potent medicine elsewhere in the world. It saves lives. You want to treat it with respect.

People have taken ART with DIM (though not taken at the exact time) with no apparent problems but no studies on this have been reported. We would discourage the use of I3C and ART, partly because I3C is an old technology that doesn't work as well as DIM, partly because it's very unstable and leads to several very toxic byproducts. Likewise, we don't know if there are any interactions with other medications such as DIM, cidofovir, RRP, interferon or other medications you may be taking.

You may also wish to limit the use of unnecessary medications while using ART in that the use of several medications at once makes assigning credit in case of a good response impossible. Was it the ART? Or something else you were doing at the same time?

There should be no problem taking Gardasil (three systemic injections) with ART assuming they were dosed according to Merck's timelines (the third dose being at six months).

Unless you know how another drug will interact with it, however, we think that it would be prudent to avoid introducing a lot of unknown variables unless your physician says otherwise.

Treatment Effects:

In many of those patients reporting in, the use of ART appears to have profoundly altered the course of RRP. In one case, there were reported CT scans and other data points that suggested in might also have a beneficial effect in pulmonary/tracheal cases involving both RRP or cancer.

Side-Effects (General):

Some patients report a sense of malaise, photosensitivity, slight (temporary) cognitive fogging or minor digestive issues. A few of these reports may also be connected with idiosyncratic dosing patterns, etc.

In any event, this section should not be considered exhaustive or relied on for predictive purposes. You may have no side-effects or they may be different from those of other patients who have reported them.

We have heard reports of gastric disturbance and a metallic taste affecting a few people. It again highlights the need for research. Perhaps inert iron, normally bound as such to food, is undergoing a conversion to the active form in the stomach of a subset of patients. That could explain the subsequent metallic taste in the mouth, nausea, etc. Inadvertently ingesting active iron (ferrous) might (?) also result in these side-effects.

Most people, however, have reported no such reaction. If patients experience this, they stop taking ART immediately and discuss this matter with their physician.

Experts discourage taking ART within six weeks of radiation and there may be concerns involving chemo. Both modalities can kill affected cells. You probably do not want to create an additive effect, since that hasn't been well-studied, at least not to the best of our knowledge. 

RRP ISA strongly suggests that everyone wishing to use ART obtain a baseline blood test (e.g, the usual liver enzymes, iron levels, renal function, etc.). Discuss it with your physician, and get it done regularly. The writer has been taking ART for over six years with no discernable ART-related abnormalities.

Neurotoxicities, including irreversible hearing loss, have been reported to be associated with very high doses of artemether (a different drug from artemisinin or artesunate) that were administered systemically (not orally) into animal models. Again, remember that these side effects were only in animal models and only with very high doses of artemether, not with artemisinin or artesunate.

Artemisinin has been used VERY widely for malaria. Many consider it and artesunate to be a treatment of choice, although multiple agents are usually used in order to prevent malaria resistance to artemisinin.

It is widely regarded as extremely safe even in children but that is for malaria dosing, not for chronic dosing (once or more monthly). There have been virtually no clinical trials of ART for chronic use, therefore we have little to no hard data. That said, we've been informed that the dosing levels are still relatively low, even lower on a per day basis than for malaria.

For chronic dosing, we again suggest coordinating with your physician and getting regular liver chemistry panels, etc. Used of ART with anemia and certain other diseases affecting blood iron levels may be counterindicated although we know of one patient with borderline-anemia who has used it without any adverse tipping toward anemia. Again, ART is not supposed to react with the form of iron in the bloodstream. Exceptions may exist, however, and this should be your doctor's call. The writer has not experienced significant side-effects at the dosing levels mentioned here. You or your child could be different, however, and you should not take any medications, including ART, without your physician's knowledge.

For more on side-effects, see Learn>Novel Therapies>Artemisinin Safety and Pharmacokinetics.

Cautionary Comments for Pregnant Women

Taking ART when one is pregant may not be such a good thing. No negative data exists, but we know artemisinin crosses the blood-brain barrier. Small amounts of ferrous exist in all cells, though in the target cells (cancers or RRP) that artemisinin selects, it exists in huge amounts. The question is whether superoxidation of even small amounts of ferrous in embryonic brains might be damaging. No one knows, but I did find an interesting article on ferrous and brains relating to a drug called deprenyl at http://www3.interscience.wiley.com/journal/104543109/abstract?CRETRY=1&SRETRY=0 and also at http://www.benbest.com/lifeext/deprenyl.html.

From the latter: 

"The breakdown products of dopamine resulting from MAO-B degradation are hydrogen peroxide, ammonia and an aldehyde. Aldehydes are highly reactive compounds that can modify proteins. Ammonia is also toxic, particularly to glia (non-neuron brain cells). Hydrogen peroxide in the presence of ferrous iron ion can lead to hydroxyl radicals, the most toxic of all free radicals. Hydrogen peroxide can easily pass into the cell nucleus where it can encounter iron ions to produce hydroxyl radicals that damage and mutate DNA. The combination of deprenyl and melatonin has been shown to counteract hydroxyl radical production due to dopamine autoxidation in the brain significantly more than either agent alone [JOURNAL OF PINEAL RESEARCH; Khaldy,H; 29(2):100-107 (2000)]. (Carnosine, which has been shown to reduce cellular senescence, also inhibits MAO-B free radical generation.)"

One person at the University of Washington says that butyric acid (butyrate) potentiates the ART up to tenfold--allegedly without any toxic side-effects. Two other ART expert at the University of Washington, however, have said that they do not believe butyric acid has been properly tested with ART, and they do not think it's needed.

This question is interesting, but until more is known, this writer will not use it, and RRP ISA has explicitly asked Holley management and staff NOT to steer RRP patients and doctors toward butyrate, assuming the person(s) calling in have identified themselves RRP patients/physicians in order to get the 30% discount. We are emphatic at this juncture in suggesting that until more is known, patients think twice before adding it to their regimen.

Concluding Remarks:

Again, what is written here is offered only for its informational value, not as medical advice. The specific course any patient follows should be at the advice of his or her personal physician. Your following this approach may complement, but emphatically must not take the place of, regular medical care by a qualified physician. If you need surgery, get it. Same with anything else that is medically recommended, etc.

If you try this approach, please read this material several times over, so you thoroughly understand what is said here. Please also let us know how it works.

We wish you the very best of luck.