LA or QA Guai:  Which Kind is Right for Me?
Written for the Guai-Support Network by Val Barnes, December 16, 2002

Since Tesa published the Product Troubleshooter FAQ, many list members have been asking this question.  The purpose of this discussion is to provide some background information that may help you to make the choice, working with your personal physician/healthcare provider.

Principles of drug action  For those who want to bend their minds to the technicalities of the body's management of drugs, click here for a 'starter' link.  But be warned, this is a seriously addictive journey, with no end in sight for those who have embarked on it.  And for those who want more: Summary of Interactions with Vitamins, Herbs, and Foods

On p.65 of the book, Dr St Amand states, "Any pure guaifenesin which has no added pseudoephedrine, dexromethorphan, or any of the other compounds that may cause side effects is recommended."

and

"Guaifenesin is available in 200 mg tablets over the counter, but I do not recommend self-treatment."

Tesa  asked Dr. St. Amand in November 2001 if OTC 200 mg Guai needed to be taken more often because it was not LA (she related that HPE had developed 2, 3 and 400 mg which was said to have a 6 to 8 hour half life) and he replied, "There will be no difference with twice daily dosing. The reason is that the guaifenesin will impact for whatever hours it sits in the body and, though a few hours in between may provide lower blood levels, the next dose will again purge heavily. It doesn't matter that it not be perfectly smooth." (Dr St Amand Fri, 30 Nov 2001 100814 EST)

What do some of these terms I've been reading about mean?

To help you understand the information that will be discussed here, it may be useful to understand some of the terms that will be used:

Absorption - In layperson's terms, when we take a pill, this is the action of our digestive systems (mostly our intestines) that moves a substance we have ingested out of our digestive tract into our bloodstream.  To be effective at reversing fibromyalgia, the guaifenesin in a pill must be absorbed before it can enter our bloodstreams and be transported to our kidneys, the site of it's action.  Absorption into the bloodstream can also occur through the skin, in which case our digestive systems are not involved.

Active ingredient - The drug of interest when you take a pill, put on a skin patch, or rub a cream or gel into the skin -- in our case, guaifenesin.  This is the substance contained in a capsule/tablet/syrup/cream/gel that has the effect(s) we're looking for when we take it.

Additives (inactive ingredients) - These are the other chemical compounds that are added to a capsule/tablet/syrup for various purposes.  Additives will be discussed in some detail below.

Dissolution - This term refers to the extent to which a tablet (or any substance we ingest) dissolves in our intestinal tracts.  A tablet of guai has to dissolve before the guai can be absorbed.

Half-life - The half-life of an active ingredient is the length of time it takes for the ingredient in our bloodstream to be reduced by one-half of the original amount that was administered.  It can be used to calculate how much of the ingredient is still in the bloodstream after a period of time.  For example, the amount of a drug remaining in our bloodstream 1 hour after an injection of 100mg of the drug, if it had a T1/2 (the abbreviation for half-life) of 1 hour, would be reduced to 50mg.  After 2 hours, the amount remaining would be 25mg, and, after three hours, only 12.5mg would still be in our bloodstream.  The half-life of guai is 1 hour.

Long-acting (LA) - In our case, this refers to the characteristics of a tablet that are designed to delay the release of the guaifenesin into your system for a period of time.  Although we use the term, "LA guai," it is somewhat inaccurate, because it sounds like we are talking about the drug, guaifenesin, itself.  But we're not.  Guaifenesin always has a half-life of 1 hour.  Rather, when we say, "LA guai," we're actually talking about how the guaifenesin tablets are constructed so that only a little guai is released into your system at a time, over a period of time (12 hours in most cases).  A more accurate term for these tablets is "sustained or extended release."  "LA" refers to a dosage form, not the drug itself.  Long-acting drugs usually have active metabolites (break-down products).

Quick-acting (QA) - Again, this term refers to how a dose of guai is delivered to your system, not to the guai, itself.  In one sense, all guai is "quick-acting," because it has a relatively short half-life, compared to other drugs.  But we use the term, "QA guai," to refer to forms of taking it that do not substantially delay the release of the guai over time because of how they are constructed.

What are the different ways to take guai?
As we all know, there are a variety of ways to take guaifenesin. All of these use guai powder that comes from the producers of  "raw" guaifenesin in various places around the world.  The most familiar ways to take guai include taking the guai powder in capsules, compressed into tablets, suspended in a syrup, or in pediatric sprinkles on food.  There are other, less familiar methods of taking it that are also effective in getting guai into our bloodstreams and to our kidneys.  These include sprinkling guai powder on food or absorbing it through our skin with a cream, gel or patch.

With the exception of tablets that are specifically constructed not to dissolve right away (LA guai), all of these guai-delivery methods release the full dose of guai in a relatively short time after taking the dose.  For example, when we swallow a gel cap, our digestive systems first have to dissolve the gel cap and then absorb the guai powder that was contained inside it.  With syrup, our digestive systems don't have to first dissolve a gel cap before the guai is available to be absorbed, so the guai may hit our bloodstreams sooner than with gel caps.  But, there could possibly be inactive ingredients in the syrup that could somewhat delay absorption of the guai for some people.  With QA tablets, our digestive systems have to first break down the tablet before the guai is available for absorption, so it might take a little longer for the guai to be released and absorbed than with a gel cap or syrup.  With guai cream or gel, the digestive tract is avoided altogether and the guai goes directly into our bloodstream.  With LA tablets, it SHOULD take a long time before the entire tablet dissolves and the full dose of guai has been released for absorption.  The LA tablets are designed so that they dissolve slowly and release only a little guai at a time.

Are there different types of guai?
Nope.  There will be some variations in the "purity" of the "raw" guai powder that is put into capsules or that is used in manufacturing tablets or syrup.  And, the big lots of "raw" guai powder that come from the producers may include other substances.  But, the US and other governments have set standards for how many and what kind of impurities are allowed, and each lot of raw powder is required to be assayed (tested to see how pure it is) before it is certified.  Some manufacturers of guai tablets, capsules, and syrups are very picky about the raw guai that they buy.  Others may be less so.  We've found that it takes a lot of work to obtain information about the source and purity of the guai powder used by big manufacturers, but that they generally WILL help you.  At this time, however, we believe that the variability that is allowed in the purity of the raw guai is so small that it's probably not worth the effort required to track down the information.  If you are concerned about the purity of the guai that is used in what you are taking, you may want to choose a brand or source of guai that makes this information easily available to you.

Is absorption important?
Yes!  For guai to work in reversing fibromyalgia, it must be absorbed from your digestive tract, enter your bloodstream, and travel to your kidneys.  If something interferes with the ability of your digestive tract to absorb the guaifenesin, the dose of guai that actually makes it to your kidneys will be very low with the result that you may have to increase your dose significantly to cycle effectively.  For example, if you have an absorption problem and you are taking a 1200mg pill twice a day, but there is something interfering with your ability to absorb the guai in the pills, your kidneys will not receive the full benefits of a 1200mg dose.  Instead, they may only be getting 200mg of guai or less, depending upon just how much interference there is.

What can affect absorption?
Many factors can affect absorption.  These include characteristics of the drug itself, characteristics of any additives used in manufacturing the tablet/capsules we take, the characteristics of how your own digestive tract works, and the form in which we take the drug.  We know that guaifenesin itself, in general, is a very easily absorbed drug, compared to other types of drugs, so we won't talk any further about the characteristics of guaifenesin itself.   

Ansel, Popovich, & Allen (1995), on p. 75 of 'Pharmaceutical Dosage Forms and Drug Delivery Systems' (published by Williams & Wilkins: Media, PA) state, "The variables that can contribute to the differences between products are many.  For instance in the manufacture of a tablet, different materials or amounts of such formulative components as fillers, disintegrating agents, binders, lubricants, colorants, flavorants and coatings may be used...  The tablets may vary in shape, size, and hardness, depending upon the punches and dies elected for use by the manufacturer and the compression forces utilized in the process.  During packaging, shipping and storage the integrity of the tablets may be altered by physical impact, or changes in conditions of humidity, temperature, or through interactions with the components of the container.  Each of the factors noted may have an effect on the rates of tablet disintegration, drug dissolution, and consequently on the rate and extent of drug absorption."

What additives are typically used in manufacturing tablets and capsules?
Surprisingly, there are quite a few!  Not all of these are used in manufacturing LA or QA guai tablets, but additives that are frequently used in manufacturing tablets include:

Tablet antiadherents - These are substances, such as magnesium stearate or talc, that prevent the ingredients of a tablet from sticking to the machines used to make them.

Tablet binders - These are substances, such as methylcellulose or povidone, that are used to "glue" the ingredients in a tablet together.  (In LA guai tablets, methycellulose is most often used to "hold" the guai powder so that it is released very slowly.)

Tablet or capsule fillers - These are substances, such as lactose, cellulose or dibasic calcium phosphate, that are used to increase the bulk (amount) of the ingredients or to change the compression characteristics of the ingredients used to manufacture a tablet or capsule. 

Tablet coating agents - These include substances used to coat a tablet so that it is resistant to heat, humidity, or air, so that the tablets don't break down when they are exposed to the environment.  Other coatings, such as sugar, may be used to improve the taste of a tablet.  Or, enteric coatings may be used that prevent the tablet from breaking down until it reaches your intestines (will pass through your stomach) to help with gastrointestinal upsets.

Tablet excipient - Dibasic calcium phosphate is often used in making guai tablets to help compress the powder ingredients into a tablet form.

Tablet disintegrants - Used to promote the breaking up of a tablet into smaller particles that are more readily dissolved.  Disintegrants include alginic acid, carboxymethylcellulose calcium, and starches.

Tablet and capsule glidants - These help improve the "flow" characteristics of a powder mixture, and include colloidal silica, cornstarch or talc.

Tablet lubricants - These are used to reduce friction when making a tablet, and include calcium stearate, mineral oil or stearic acid.

Flavors and colors - These include natural and artificial flavors, and dyes.

Are different additives used in LA vs. QA guai tablets and capsules?
Yes.  The LA tablets are constructed so that they dissolve slowly over time, which means that the manufacturers include additives in the tablets to delay the rate at which the tablets dissolve over time.  The effect of the additives is that they slow the rate at which the guai is released from the tablets into our digestive tracts where it is then absorbed.  So, oversimplifying once again, if your digestive tract is working normally, when you take a 600mg LA tablet in the morning, you will receive something less than 50mg of guai per hour over the course of the day. 

Quick-acting guai capsules and tablets do not include the delaying additives that are used to construct the LA pills.  This means that when you take a 600mg QA tablet in the morning, for example, and your digestive tract is working normally, the full 600mg dose of guai will be released into your digestive tract as soon as the capsule or tablet dissolves, and all of the guai in the tablet or capsule will enter your bloodstream in a much shorter period of time.

Other than the delaying additives, however, LA and QA tablets may include many of the same additives needed to manufacture the tablets.  Binders, antiadherents, excipients, and fillers, for example, may be used in manufacturing both LA and QA tablets.  Dyes and flavors may also be used in tablets or syrup.  Guaifenesin powder in gel caps usually does not include any additives. 

What differences between people affect how well guai is absorbed?
Many of us have gastrointestinal problems that may affect our ability to dissolve the guai tablets and to absorb the guai in our intestines, whether we are taking LA or QA guai.  For example, some people are hypersensitive to some of the additives listed above.  The pH in your digestive tract may also interfere with your intestines' ability to dissolve the guai tablets.  These kinds of problems will decrease the amount of guai that we absorb.  If you have absorption problems, you may either need to take more guai than someone with a "normal gut" to compensate, in order to reach your cycling dose, or change to a different brand that contains different or no additives.  When you find a form of guai and a brand that you absorb well -- be prepared to notice the difference! 

What about the dyes in my guai tablets?
Some people react to dyes in anything they ingest and there has been a lot of controversy in the research literature about the yellow dyes in particular.  A number of studies have shown that children with ADHD react to yellow #5 with increased behavior problems.  Some people who are aspirin-sensitive also react to yellow #5 which is chemically very similar to salicylates.  Further, the yellow dyes have also been shown to cause chronic urticaria (hives and itching) in some people.  We have always said that the itching that is such a common cycling symptom was due to "phosphates coming out of your skin," but we are now beginning to wonder if some people may be reacting to the yellow dyes that are used to color some brands of guai pills.  If you have any chemical sensitivities or find yourself itching a lot when you start taking guai, you may want to take only a dye-free guai brand.

Why are cycling symptoms sometimes more intense when taking QA guai than LA guai?
The most important reason is that the amount of guaifenesin that reaches the kidneys at one time is much larger when taking a dose of QA guai than when taking an equivalent dose of LA guai.  We know there is a clear dose-response relationship between guai and cycling symptoms, if you aren't blocking on salicylates or at your maximum dose.  That is, the more guai you take, the harder you cycle.  So, because more guai hits your system at one time from taking QA guai compared to LA guai, you will experience an hour or two of more intense symptom exacerbations on the QA guai than when taking the same dose of LA guai.  As discussed above, when you take a 600mg tablet of QA guai, it will completely dissolve within the first half-hour or so and, assuming all goes well in your intestines, a significant portion of that 600mgs of guai will enter your bloodstream relatively rapidly.  In contrast, when you take a 600mg tablet of LA guai, only a little will dissolve within the first half-hour -- possibly somewhere around 50mgs or less.  So, when the 600mg QA guai tablet dissolves, there will be 12 times MORE guai hitting your system at one time than when you take the 600mg LA tablet!

Another reason may be that some people are better able to dissolve QA tablets or capsules than LA tablets because their digestive tracts have a difficult time breaking down the LA tablets due to the additives, or because the LA tablets they were taking were very tightly compressed, or some other factor.  Or, there may be something about the additives that interferes with absorption for a particular individual.  The combination of removing any barriers to absorption and the difference in the rate at which guai is released into your system with QA guai, together, may mean that your kidneys are receiving A LOT more guai than they were before.  If you were having absorption problems with your LA guai and don't with the QA guai, the actual amount of guai hitting your system from a 600mg QA dose could be even greater than 12 times the guai you were receiving from the 600mg LA pill! 

What are the advantages of taking LA guai?
In my opinion, the biggest advantage of taking LA guai is convenience.  You only have to take your dose twice a day and can forget about it in between, knowing that the guai is present in your bloodstream and allowing your kidneys to work correctly -- if your system is able to dissolve the tablets and absorb the guai.

A second important advantage of LA guai is that you may avoid the "rollercoaster effect" that some people experience in their cycling symptoms when taking QA guai.  Because the full dose of QA guai hits your system at once, and then the amount of guai in your bloodstream decreases at a relatively rapid rate over the next few hours, you may have a couple of hours of feeling awful after taking your dose, and then a couple of hours of feeling nothing until your next dose.  Also, if you are someone who does better when maintaining a constant level of guai in your system, you may find that you begin feeling worse and worse the longer it has been since taking your last QA dose.  These kinds of ups and downs are avoided with the steady stream of guai that LA tablets deliver.

What are the advantages of using QA guai?
Well, most people KNOW that they are cycling and what it feels like more clearly when that big bolus of guai hits their systems within 20-30 minutes after taking a dose!  That can be a very useful experience for people who are just starting out and don't know what cycling feels like or whether this guai stuff is going to do anything for them at all.  And it can also be enlightening for longer-term/high-dose guaiers who aren't being mapped and have never been really sure they were cycling with LA tablets.

Using QA guai to do a blocking test is also good, because if you aren't blocking, the increased cycling symptoms from raising your dose for the blocking test will last for a much shorter period of time than if you raise your dose by taking additional LA guai.  Your response will be much more obvious regarding whether you are or are not blocked.

And, if you are someone who might have a digestive tract problem of some sort, the reduced or eliminated additives in QA guai may allow you to absorb the guai much better, so that your progress on the protocol is enhanced.

Further, if you end up being one of the fortunate ones who need a lower dose of QA guai than LA guai, QA guai may end up being less expensive to take.  Of course, that depends on your insurance coverage, where you buy your guai, and so on. 

But how do I handle the more intense cycling symptoms if I take QA guai?
So far, we are aware of three methods for reducing the intensity of cycling symptoms when taking QA guai:

The first method is to take smaller doses more frequently over the course of the day.  If you want to take a 600mg/day dose, you might need to take 200mg three times a day, rather than 300mg twice a day. 

The second method is to take your doses with food.  The food may slow down the rate at which your digestive tract dissolves the tablets. 

Third, (careful here) you many need to reduce your daily dose from what it was with LA tablets.  If you are dissolving/absorbing the QA guai better than the LA guai, you may be able to reduce your dose and still end up with MORE guai in your system than you were getting with the LA tablets.  If you are just starting out on the protocol and are using QA guai, it may be wiser to start out at 400mg/day or less, rather than 600mg/day with LA guai, and then titrate up from there to find the dose at which you are "significantly but tolerably worse."  If you are switching from LA guai to QA guai, and feel that you need to reduce your dose, it is very important that you are mapped regularly for at least 3 months following the dose reduction to make sure you haven't gone below your cycling dose.

Why have some people reported that their maps show significantly more deposits after switching from LA to QA guai?
There are at least three possible reasons for this. 

First, if you weren't absorbing the guai contained in your LA tablets very well, but do absorb the guai in a QA form more effectively and have stayed on the same daily dose, it's very possible that you are flooding your bloodstream with phosphates, because your dose on the QA guai is actually now too high.  When this occurs, we know that our bodies will temporarily store the phosphates in various sites (often your neck and upper back) until your kidneys can clear them out of your bloodstream.  If you continue taking the same dose of QA guai over time, the number of temporary deposits will continue to increase, until your map once again looks like you are a Dalmatian.  This result can be very upsetting, because it looks like you are going backwards and you will likely be feeling terrible.  Reducing your QA dose will stop the phosphate flooding and give the temporary storage sites an opportunity to clear.  The big problem with this process is the pain involved!!  The phosphates hurt when they come out of your tissues the first time, hurt when they go back into temporary storage, and then hurt again when they are pulled out.

The second possible reason, of course, is that if you have reduced your dose when switching, you may have gone too low and are, in fact, re-depositing phosphates in areas you previously cleared.

The third possible reason is that you might be inadvertently blocking on something you've introduced into your life since making the switch and haven't discovered it yet!

If I have switched to QA guai and my map starts showing more deposits, what can I do?
The first and most informative step is to do a blocking test.  This means raising your dose by 200-300mg to see if your cycling symptoms become more intense.  If you start feeling much worse on the higher dose, then you have at least ruled out blocking as a reason for the increased deposits.  If you feel no change, then you are likely blocking and need to go on a sal-hunt.  If some of your symptoms are exacerbated, but others are decreased at the higher dose, then you likely have been at too low a dose and will need to stay at the higher dose.  If you feel just terrible at the higher dose, then your dose of QA guai has likely been too high, and you can decrease it.

One of the ways in which you can distinguish between a too-high dose, a too-low dose, and blocking is by considering the rate at which your maps have changed.  If you have been taking a too-high dose and are flooding your system with phosphates, you should see many new deposits in a very short time, i.e., on your next map.  If your dose is too low, or you are blocking, the re-depositing seems to be slower.  Your first map after switching may show no change from your last map, then the next one three months later may start showing some new deposits, and then there will be a noticeable difference after six months that is your clue.  Most people don't want to wait this long, however, and do a blocking test, try raising their doses or switch brands of guai if they become concerned.

 Prepared by Val Barnes based on pharmaceutical textbooks  provided by Tom Slaughter of Mulberry Pharmacy, information available on Dr. Greg Penniston's website and discussions with him, information provided by Dr. Paul St. Amand in his book and in the Guai-Support archives, comments from Dr. Tom Savino, and research literature available on the web.  Reviewed for pharmaceutical accuracy by Tom Slaughter and Val's local pharmacist prior to publication on the website..
 

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