This was a crucial article I published on my site Nat_anti_hiv on Yahoo groups:

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ASCORBATE-STABILIZED QUERCETIN THERAPY (ASQ)

IS POTENTIALLY VERY DANGEROUS.

IT HAS NOT BEEN TESTED PROPERLY

DO NOT ATTEMPT IT WITHOUT MEDICAL

SUPERVISION.

IT IS ENTIRELY AT YOUR OWN RISK

THE FOLLOWING DISCUSSION IS BASED ON THE PRELIMINARY EXPERIENCE OF JUST ONE PER PERSON

POSSIBLE LONG-TERM TOXICITIES ARE NOT KNOWN.

INTERACTIONS WITH OTHER MEDICATIONS ARE NOT

KNOWN

CONSULT YOUR DOCTOR

Refer to article "CK-II Inhibitor Abstracts" in association with

this article.

CK-II Inhibitors

The existing approved HIV anti-viral drugs inhibit either one or the other of two viral enzymes - either the reverse transcriptase or the protease enzyme.

The names of these two classes of drugs are reverse transcriptase inhibitors and protease inhibitors. The reverse transcriptase inhibitors are divided into two sub-classes - nucleoside analogues and non-nucleoside analogues.

There seems to be a new class of plant-derived compounds that function by inhibiting the activated human casein kinase II enzyme - CK-II. One example of this class is Quercetin. In the literature (see abstracts article) these substances have been called CK-II inhibitors. It is interesting that CK-II is not a viral enzyme, it is a human enzyme.

The following sections are my understanding of the science of HIV and Quercetin. It is all "in my opinion". I am only a layman, so they could easily be partially or wholly incorrect. I have reported my personal experience honestly and as accurately as I can.

My combination therapy includes Combinivir 1 tablet twice a day, Ritonivir 1 capsule (100mg) twice a day, Indinivir 2 capsules (400mg each) twice a day, Efavirenz 3 capsules (200mg each) once a day. The Quercetin tablets I use have 200mg Quercetin, 500mg Rutin and 50mg Ascorbic Acid. I have to cut them up into 8 little pieces to get 25 mg Quercetin doses! I use Calcium or Sodium Ascorbate powder for Vitamin C.

Absorption

The majority opinion seems to be that the glycoside form of Quercetin is absorbed through the glucose transport mechanism.

Perhaps the agyclone form of Quercetin reacts with ascorbate in the gut to produce the glycoside form, which is then readily absorbed. Onions contain a significant amount of Ascorbic Acid, and both agyclone and glycoside forms of Quercetin. Ascorbic Acid is similar to glucose.

From personal experience the use of high-dose acorbate with Quercetin resulted in high absorption. I realized this, because I experienced side effects from a single dose at what is generally regarded as low dose.

The other possibility is not that I'm getting more absorption, only that in the body Quercetin is being stabilized by high-levels of ascorbic acid, and thus becomes an active anti-viral with associated side effects at higher doses.

Half-Life

In the literature, is generally claimed to be 17-28 hours. It's not clear what the effect of ascorbate and ritonivir may be, but they would probably both contribute to a much longer half-life.

Consequently, only a once a day dose may be necessary, preferably in the morning, because of the stimulating effect of ASQ.

It may also be possible to skip days occasionally, if side effects, e.g. sleeplessness becomes too much of a problem.

Side Effects

Casein Kinase II is reported to be important in the nervous system. See Abstracts section.

This agrees with my experience of side effects, presumably from Quercetin inhibition of CK-II.

From first dose (600mg) of Quercetin and 7 grams ascorbate (Overdose)

Headache
Fast heart rate
Hyperventilation.
Severe dry mouth
Severe sleeplessness
From one lower dose (25mg and 7 grams ascorbate)
Mild Dry mouth
Improved energy level
Milder Sleeplessness
"Ringing" in the head, particularly noticeable at night.

Quercetin appears to be "stimulating".

Mechanism of Inhibition

I understand the sequence of steps that leads the Rev gene to upregulate viral enzyme production, via CK-II is as follows:

1. The Rev gene after integration into the host cell nucleus along with the rest of the viral genes, produces the Rev protein.
2. The Rev protein "activates" some amount of CK-II protein in the cell, dependent on the amount of Rev protein released. Presumably some amount of the CK-II protein in the cell is not activated. If it were all activated, it seems to me that the cell would immediately malfunction. Thus there are two kinds of CK-II. Normal CK-II and activated CK-II
3. The activated CK-II protein then functions to phosphorylate various viral enzymes, which are consequently upregulated, 2-4 fold.
4. This CK-II phosphorylation includes the Rev protein itself. This results in positive feedback.

CK-II inhibitors may selectively inhibit the two forms of CK-II. This would probably be dependent on concentration of the inhibitor. In other words in a given zone of CK-II inhibitor concentration, activated CK-II would be inhibited, but the inactivated (normal) CK-II would be only mildly inhibited or not at all and would then be able to continue its functions in the cell. Mild side effects may occur in this zone e.g. mild and occasional dry mouth. Thus inhibition of Rev upregulation of viral production, without too much harm to the cell would occur.

If the concentration of CK-II inhibitor went beyond the efficacious zone of selective inhibition, probably both forms of CK-II would be inhibited, and serious side effects would result. Or it could be that only the normal CK-II is inhibited. It's unknown at this time. Side effects would become severe, and suffering would successively increase, because large amounts of normal CK-II protein, which are essential for cell function would be inhibited. Since CK-II is important in the nervous system, nervous system side effects would be expected.

My experience is this overdose zone can result in a very high viral load (750,000). It is possible to recover very rapidly from this, because as concentration of inhibitor (Quercetin) falls into the efficacious zone, if the zone is maintained and combination therapy is in place, potent viral suppression can occur. Based on my experience, viral load can by reduced by 99%, in less than a week (down to 7000). T4 cell count improved by 50 in the same week from 320 to 370. Liver and kidney function were still O.K. Quercetin is paradoxical.

Anti-viral activity Dependency

A report on the use of Quercetin with Polio virus, (see abstract below) stated that the Quercetin must be ascorbate stabilized to obtain optimum anti-viral function. The same is probably true for HIV. This would imply that levels of ascorbate in the body must be maintained continuously at a high level. (Mega-dosing ascorbate - Vitamin C). This is what I did, using ascorbate powder at 5-7 grams every 3-4 waking hours. Ritonivir may serve to stabilize Quercetin blood levels, but I believe the ascorbate is also necessary for anti-viral activity of Quercetin.

Viral Resistance

1. Since the CK-II enzyme is not a viral enzyme, and it is the activated form of this enzyme that is inhibited by the CK-II inhibitor, viral mutation will be irrelevant, except perhaps the Rev gene.
2. The Rev gene produces the Rev protein, which activates CK-II. Once again, because CK-II is a human protein it is unlikely to mutate, and any mutation of the Rev gene to produce a different Rev protein will be thwarted, because it will no longer be able to activate CK-II. In any case, Rev must activate CK-II one way or another. Once activated, the consequent process of phosphorylation of viral enzymes is performed by the activated CK-II protein, which is unlikely to mutate. This is the process that is inhibited by CK-II inhibitors. For the virus it becomes a case of "resistance is futile".
3. In fact the host selective pressure would be for CK-II not to mutate. In other words to maintain sensitivity to CK-II inhibitors, so that some defense against the virus is possible, with the help of the inhibitors. These inhibitors do seem to be fairly common in plants. Maybe plants have had to deal with retroviruses in their time too!

It would be interesting to know how plants regulated their levels of CK-II inhibitor. Perhaps by levels of ascorbate. Most animals manufacture their own Vitamin C in the liver. Humans are one of the few that do not. When an animal becomes sick, the liver produces large amounts of vitamin C. If there is a CK-II inhibitor in the body from food (e.g. Quercetin), it would then become activated - just when it's needed.

The virus's hi-jacking of the human CK-II protein for one of its most destructive functions (up-regulation), is it's strength, but also it's weak point, it's Achilles heel.

In effect activated CK-II has become part of the viral production machinery. Because it is a human protein, it is the one part of the virus production machine that is not subject to rapid mutation. The plant strategy of using CK-II inhibitors to inhibit this one part of the viral machine that is both very damaging and not subject to rapid mutation, is an example of the finesse of Mother Nature. If you prefer a more scientific statement, it is the finesse that results from millions of years of evolution.

Combination Therapy

CK-II inhibitors only inhibit up-regulation. There remains the possibility of low-level viral replication. (See Abstracts) Current standard of care is combination therapy anyway, but this low-level viral replication would also dictate additional treatment with direct inhibitors of viral enzymes. For example, the currently approved anti-virals. Viral resistance to combination therapy would be retarded, because a CK-II inhibitor has inhibited up-regulation of viral production. Low-Dose Ritonivir (100mg twice a day) may be an essential element of combination therapy to stabilize Quercetin. My doctor pointed this out to me. It is not clear what the effect of higher dosage Ritonivir might be.

There is the definite possibility of interaction with Efavirenz at least, because it also has effects on the nervous system. I take Efavirenz, and once at a higher dosage (25mg Quercetin each day for three days in a row) I had very disturbing dreams, which I had not had previously with Efavirenz.

There is a THEORETICAL possibility, that if response to this new combination, which includes a CK-II inhibitor, is very good - low viral load, high T4 cell count, combination therapy may be possible with fewer anti-virals and thus less drug load.

Conclusions:

It appears that ascorbate stabilized Quercetin:

1. Indirectly inhibits only one viral enzyme, a crucial one - Rev by inhibiting activated CK-II. Quercetin appears to inhibit many viral enzymes, because Rev upregulates several viral enzymes, via activated CK-II. The name is appropriate. Rev "revs up" viral production.
2. Quercetin itself is virtually immune to viral resistance - because of indirect mechanism of inhibition - of the human protein, activated CK-II.
3. Is a potent anti-viral in combination therapy
4. Reduces viral opportunity for resistance to existing anti-virals, by inhibiting up-regulation of viral production.
5. Is non-toxic at efficacious doses. Since my preliminary experience indicates that results can be fast and dramatic, possible strategy may be to use ASQ with combination therapy for 1-4 weeks, then drop ASQ and simply continue combination therapy, or at this time switch to new combination therapy. ASQ could be repeated as needed, or maintained if tolerable.

It seems to me that the current treatment strategies, though they have served well so far, are ultimately a losing game, because of CK-II mediated up-regulation of HIV.

Perhaps if up-regulation of HIV can be reduced or prevented by CK-II Inhibitors, the game may be winnable.