American Fitness Professionals & Associates

By Dr. Bill Misner Ph.D.

GLUTATHIONE DETERMINANTS

Endogenus glutathione, a tri-peptide often referred to as “Reduced Glutathione”, is composed of Three amino acids: L-Cysteine, Glycine, and L-Glutamic Acid. Smaller peptides of 2 or 3 amino acids are absorbed without further reduction or delay, but there is some debate as to the effectiveness of taking peptides as opposed to free amino acids for in enhancing endogenous glutathione stores.  Most glutathione is found in the liver where it detoxifies harmful compounds later excreted in bile. Some glutathione is found in the red and white blood cells, lungs, and Intestinal tract. The primary biological function of glutathione is to act as a non-enzymatic reducing agent to assist in cysteine thiol side chains in a reduced state on the surface of proteins. Reduced glutathione is involved in the synthesis and repair of DNA, assists the recycling of vitamins C and E, blocks free radical damage, enhances the antioxidant activity of vitamin C, facilitates the transport of amino acids, and plays a critical role in detoxification. It is the base material for several other key antioxidant enzyme systems: glutathione-peroxidase, glutathione- reductase, and glutathione-transferase. Decline in glutathione concentrations in intracellular fluids correlate directly with indicators of longevity. Decline in endurance performance may parallel decline in glutathione concentrations imposed by the aging process.

EXTREME ENDURANCE TRAINING ACCELERATES GLUTATHIONE LOSS

Researchers accessed the antioxidant status and markers of oxidative damage in the members of the U.S. Men’s Alpine Ski Team during 10 days of intense training. Seven measures of antioxidant status were determined using Trolox equivalent antioxidant capacity, uric oxidase, alpha- tocopherol, total glutathione, cytosolic glutathione peroxidase, and superoxide dismutase. The Results suggested that antioxidant status of elite alpine skiers declined during training. [1] Further studies of blood values determined the importance of glutathione upon potentiating maximal oxygen carrying capacity. Higher glutathione levels influence red blood cell count, hematocrit, and hemoglobin. Conversely when red blood cells, hematocrit, and hemoglobin are reduced during anemia, low glutathione is implicated; the addition of GSH has been shown to resolve the aforementioned low blood markers. Whether antioxidant supplementation will enhance performance remains controversial. Exercise-induced changes in antioxidant scavengers and associated enzymes (e.g., glutathione, tocopherol, and glutathione peroxidase) provide clues about demand imposed on the defense system. Exercise training is observed to result in an augmented antioxidant system and a reduction in lipid peroxidation. Supplementation with antioxidants appears to reduce lipid peroxidation but has not been shown to enhance exercise performance. [2]

REPLACING GLUTATHIONE LEVELS

Intravenous glutathione administration may provide the most direct and effective route for increasing intracellular glutathione levels. The glutathione (GSH) antioxidant system is foremost among the cellular protective mechanisms. Depletion of this small molecule is a common consequence of increased formation of reactive oxygen species during increased cellular activities. This phenomenon may occur in the lymphocytes during the development of an immune response or also in muscular cells during strenuous exercise. Time and transit of dietary oral GSH substrates may be a positive means of glutathione repletion. However, cysteine, found in milk proteins, is reported to be a crucial limiting amino acid for intracellular GSH. [3] Replenishing glutathione from dietary supplementation of Whey, N-Acetyl Cysteine, or Glutathione, are time- and dose-dependant, but may further be inhibited by the influence of age,  exercise stress, or environmental toxins. Bypassing gastric channels and hepatic intervention activity by intravenous loading protocol presents a model for resolving these deficits. Exhaustive exercise depletes glutathione and simultaneously generates free radicals. This is evidenced by increases in lipid peroxidation, glutathione oxidation, and oxidative protein damage. It is well known that activity of cytosolic enzymes in blood plasma is increased as a result of exhaustive exercise. [3]

GLUTATHIONE REPLETION

It has been reported the effects of reduced glutathione parenterally administered resolved the status in patients suffering from chronic renal failure and undergoing hemodialysis. Reduced glutathione and placebo were given for 120 days in a randomized double-blind fashion and the following measurements were performed: red blood cells reduced and oxidized glutathione, plasma reduced and oxidized glutathione, hematocrit, hemoglobin, reticulocytes, serum iron, transferrin, indirect bilirubin, urea, creatinine, calcium, phosphate, parathyroid hormone and alkaline phosphatase. In the treated group, during the supplementation period, there was an increase in the levels of red blood cells and plasma reduced glutathione, hematocrit and hemoglobin and a concomitant decrease in plasma oxidized glutathione and reticulocytes with a maximum effect on the 120th day of therapy. In the placebo-treated group there were no significant variations of the parameters considered during the study period. When the therapy, on patients undergoing treatment, was terminated there was a drop in the analyzed parameters, which fell to pretreatment values at the subsequent controls. These findings seem to indicate that reduced glutathione could represent a useful drug in the treatment and management of anemia in patients affected by chronic renal failure. [4] By increasing glutathione an enhanced blood oxygen carrying capacity following a depletion state, may induce a rebound potential for endurance performance gain proportionate to completing repletion.

GLUTATHIONE & CYCLING TIMED-TRIAL PERFORMANCE

I hypothesized that endurance performance gain would follow rapid repletion through an intravenous Glutathione does protocol [5].
A Fit 61-year old endurance cyclist completed of 1000 miles of pre-test bicycle training, performed with periodic anaerobic bouts [sprints and hill climbing intervals] once every 6 days [or 17% of pre-test training], to attain peak cycling fitness within 90-days pre-test training. For an objective measure, a timed-trial of a 30-kilometers [18.4 miles] challenging course, was determined prior to receiving the first of four intravenous glutathione treatments.  A bolus-dose of 100 mg/cc, 10cc, total 1000 milligrams-dose diluted to a total volume of 20cc with normal saline by slow IV-push, 15 minutes was administered subsequently at 7-10 day intervals for the 36 consecutive days following the aforementioned 90-day pre-test period.

Sport science consensus dictates the sport-specificity principle that to improve existing performance, athletes must impose increased training intensity “stress” well above present training level. The training alone, as continued unchanged by this athlete, should therefore not have caused gains in performance. [6] Constant aerobic protocols do not contribute to time trial performance outcome, therefore they were imposed, as controls with the intent to maintain, not increase performance outcome. Objective criteria were then selected by timing performance on the same 30k, 18.4-mile on a challenging loop course. Training distances averaged 77-80 miles per week 90-days prior to and during the timed tests, and were limited to 6 training days per week for 36 consecutive days. Performance-enhancing anaerobic sessions were not allowed, to avoid potential changes from that source.

Constant aerobic cycling training did not exceed 75% maximum heart rate or maximum oxygen consumption. Dietary and supplemental protocols were also held as constants prior to and during the test period.  To evaluate the influence of IV-Glutathione on performance outcome, a cycling timed trial was pre-dose recorded, then compared to a second time trial which was recorded between IV-doses Glutathione #1 and #2, then again recorded after all doses Glutathione. A comparison of timed-trials recorded on the same 30-kilometer 18.4-miles course, using the same bicycle, under similar conditions follows in TABLE I.

TABLE I*

TEST    TIME-MIN:SEC    AVERAGE MPH     PERCENT [+/-]
TEST    TIME/MIN:SEC    AVERAGE MPH     PERCENT+/-
PRE-TREATMENT   57:30   19.0    -0-
POST-#1 RX      56:10           19.4                    +2.1%
RX # 2-3-4              NO TEST NO TEST NO TEST
POST-RX #4      52:21   21.0    +7.2%

*LEGEND

TESTS: Pre-treatment training consisted of cycling 1000 miles in 90 days, 83% at aerobic pace and 17% of the miles at anaerobic pace rate. Four treatments Rx #1, 2, 3, 4 of intravenous glutathione, 100 mg/cc, 10cc [total 1000 milligrams] dose diluted to a total volume of 20cc with normal saline by slow IV-push over a 15-minute time period every 7-10 days during a 36 day period.

TIME MIN/SECS: Time in minutes and seconds were recorded prior to treatment, after treatment #1, and after treatments # 2-3-4 treatments over an 18.4 mile undulating asphalt road course using same bicycle under similar weather conditions.

AVERAGE MPH: The average miles per hour recorded for each timed trial.

PERCENT [+/-]: Gain and/or loss in performance as compared to the “pre-treatment” timed trial.

CONCLUSION

Performance gain 7-10 days after treatment #1 was significant [+2.1%] with total performance gain from intravenous glutathione +7.2% over 36 days [57:30 TO 52:21 Minutes:Seconds], averaging a remarkable +1.8% per treatment administered. The only variable to account for the improvement in performance was four glutathione injections. A measure of the efficiency of oxygen metabolization is closely tied to the restoration of glutathione levels for resolving depletion. By increasing GSH serum levels, enhanced performance may result. Further research is needed with more aging, fit, healthy subjects, measuring a variety of physiologic and metabolic endpoints to determine if the results of this case study prevail, and if so, the mechanism of any such benefits achieved.

REFERENCES

[1] Subudhi AW, Davis SL, Kipp RW, Askew EW. Antioxidant status and oxidative stress in elite alpine ski racers. Int J Sport Nutr Exerc Metab. 2001 Mar;11(1):32-41.
[2] Clarkson PM.Antioxidants and physical performance. Crit Rev Food Sci Nutr. 1995 Jan;35(12):131-41.
[3] Bounous G. Whey protein concentrate (WPC) and glutathione modulation in cancer treatment. Anticancer Res. 2000 Nov-Dec;20(6C):4785-92.
[3]-Vina J, Gomez-Cabrera MC, Lloret A, Marquez R, Minana JB, Pallardo FV, Sastre J. Free radicals in exhaustive physical exercise: mechanism of production, and protection by antioxidants. IUBMB Life. 2000 Oct-Nov;50(4-5):271-7.
[4] Costagliola C, Romano L, Scibelli G, de Vincentiis A, Sorice P, Di Benedetto A. Anemia and chronic renal failure: a therapeutical approach by reduced glutathione parenteral administration. Nephron 1992;61(4):404-8.
[5] Stanley B. Covert M.D., advised, designed, and administered the glutathione protocol in this open label experimental trial. Dr. Covert is the Medical Director, High Road Clinic, North 42207 Sylvan Road, Elk, Washington, 99009,  (509) 292-2748.
[6] Noakes TD. Sportscience Consensus dictates sport-specificity principle that to improve existing performance, athletes must impose increased training stress above present training level. in The Lore of Running. Leisure Press, Champaign, IL, 1991, 18-23.

DISCLOSURE: As the subject of this trial, the placebo effect and my personal bias were not eliminated from tainting the results reported; though I have no competing interests in IV-Glutathione.

Dr. Bill Misner, Ph.D. is the full time Nutritionist for E-CAPS INC. & HAMMER NUTRITION.
He is a former 2-time U.S.A. 50-Mile National Masters Champion. In 1998-1999, he established two “World Records” completing the first-ever 10,000 miles and 20,000 kilometers ever run in an organized footrace.
The above article is reprinted by permission of the Endurance Marketing Group, E-CAPS INC. & HAMMER NUTRITION LTD.

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Dr. Bill Misner, Ph.D.
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