GSH Augmentation Therapy in CF: An Initial Protocol for Interested

Physicians


Note: These recommendations are based upon the theory that CF persons have a
glutathione transport problem. Most of the cells in their body are able to
make enough glutathione for cellular needs, but are unable to export
glutathione to the extracellular environment, where a severe deficit of GSH
develops over time. However, immune system cells, hepatic cells, and all
other cells with a redundant anion channel to the CFTR which is
missing/defective in cystic fibrosis, *are* able to export GSH. However,
since they are the minority of cells in the body, they will quickly become
depleted of GSH in the attempt to make up for the extracellular deficit.
This state of chronic depletion of GSH in the immune system cells causes
chronic inflammation and immunodeficiency. (See
http://members.tripod.com/uvicf/mediainfo/hudsonlong.pdf for further details.)

 Warning: The protocol given below is not authoritative! It was drawn up as
an initial protocol for interested physicians! You should not
begin this therapy without the consent and supervision of your doctor! Do
not make any changes to your medical treatment without consulting with your
doctor first!

 

  NOTE:  It is Dr. Bishop's opinion that GSH use should not be attempted in CF patients who culture Burkholderia cepacia, or who have a history of hemoptysis/pneumothorax, or whose FEV1 is less than 30% predicted, or who have undergone a lung or other type of transplant, until such time as research has been performed to decide whether use under such conditions is safe.

The following protocol was recommended by Dr. Clark Bishop, M.D. and board-certified pulmonologist.  You or your doctor can reach him at clark.bishop@imail.org 

1. When the patient wakes in the morning, have them take a cysteine donor such as NAC (n-acetyl cysteine), 250-600 mg.

2. Have them follow that with the first dose of GSH. (Dosing is described in #10 below.)

3. Have them continue to take their GSH dose every 3-4 waking hours.

4. We recommend a mix of oral GSH dosing and inhaled GSH dosing during the patient's waking hours, and further recommend that the patient have at least one oral dose and one inhaled dose every day. The specific mix of doses over the course of the day, e.g., 3 oral, 1 inhaled; 2 oral, 2 inhaled, etc. is up to you.

5. It is not necessary for a patient to take both an oral dose and an inhaled dose during the same 3-4 hour period.

6. We recommend that CF persons start out at a very low dose, about one fourth the recommended dose (see #10 below), and *gradually* increase that dose until the desired total daily dose is achieved. We recommend at least a one week period at one dose before increasing to the next step. The patient may not reach the desired level for almost a month, but this should allow for maximum toleration.

7. GSH that is inhaled should be both buffered and isotonic when in solution. We recommend the product GSHPlus (Reduced L-Glutathione Plus Sodium Bicarbonate) by Theranaturals, Inc. ( theranat@fiber.net ) and their website is http://www.theranaturals.com  Each capsule of GSHPlus contains about 210 mg of buffered GSH, and when dissolved in 3-4 ml of sterile or distilled water (not saline!), this will yield a roughly isotonic solution of pH 6, suitable for nebulizing.  How many capsules to use will vary by weight of the patient, see #10 below.  If using more than one capsule or less than one capsule, the amount of water should be adjusted proportionately to maintain approximate isotonicity. (Some users do use regular or hypertonic saline, or use a smaller amount of water per capsule. Some persons may not be able to tolerate such a hypertonic solution, so it is best to start with an isotonic solution and then adjust according to one's individual toleration of hypertonic solutions.)

8. GSH to be taken orally should ideally have ascorbic acid with it. We recommend two formulations by Theranaturals 1) the first, called "GSH-Curc Caps," contains 300 mg of pharmaceutical grade glutathione, plus curcumin, NAC, ascorbic acid, and a small amount of selenium, and 2) the second, called "GSH Caps," which each contain 500 mg of pharmaceutical grade glutathione.  Their email is theranat@fiber.net and their website is http://www.theranaturals.com  There is also another company called  HMP, Inc., which sells oral glutathione mixed with ascorbic acid called Ultrathione-250 and Ultrathione-500. ( http://www.hmpscience.com or 1-800-362-8673), though we have received a few complaints about HMP's shipping and billing.  No member of UVICF has any financial connection to any company selling glutathione.

9. There may be some initial slightly negative tranistory side effects, such as transitory sulphur-smelling flatulence, lightheadedness, transitory slight aggravation of asthma. These effects will disappear in 7-10 days. However, if the patient notices any negative side effects that you feel are harmful, have them cease taking GSH! Remember that GSH is a vasodilator, so if a patient is prone to bleeds, be very careful when you are using GSH with them.

10. Desired total daily dose is currently an art, not a science. Dr. Bishop used the following formula in his 2002 clinical trial: the formula for total daily dose is 30 mg/pound body weight/day. This formula yields a total daily dose, and must be divided by the number of times that GSH is given during the day to get the dose per dosing period.  Most persons take 4 doses per day, so, for example, if the formula yields 2000 mg per day as the total dose, then each of the 4 daily doses would be 500 mg.  Remember that a CF person must work up to these doses gradually over time! Also remember that there is no evidence in the scientific literature that taking a larger dose than that recommended here would result in any harm. There is no "overdose" level for GSH, because GSH is non-toxic. Please see the Investigator's Brochure of our IND for a full literature search on this issue (accessible from the previous page).

11. Make sure the patient does not take acetaminophen or drink alcohol when on glutathione augmentation therapy, as these will strip GSH from the body.  Other substances, such as morphine, will do the same.