300 Joseph Carrier, Vaudreuil-Dorion, Québec J7V 5V5 • Tel: 450.424.9992 • Fax: 450.424.9993 • www.immunotec.com
As listed in the 2016 Physicians’ Desk Reference (PDR) Immunocal® NUTRACEUTICAL Glutathione precursor (Bonded cysteine™ supplement) Powder Sachets DESCRIPTION and CLINICAL PHARMACOLOGY IMMUNOCAL® is a specially formulated undenatured whey protein isolate. It holds several patents in the USA and worldwide and is listed by the FDA in the category of GRAS (generally recognized as safe). It assists the body in maintaining optimal concentrations of glutathione (GSH) by supplying the precursors required for intracellular glutathione synthesis. It is clinically proven to raise glutathione values. Glutathione is a tripeptide made intracellularly from its constituent amino acids L-glutamate, L- cysteine and glycine. The sulfhydryl (thiol) group (SH) of cysteine is responsible for the biological activity of glutathione.  Provision of this amino acid is the rate-limiting factor in glutathione synthesis by the cells since bioavailable cysteine is relatively rare in foodstuffs. Immunocal® is a bovine whey protein isolate specially prepared so as to provide a rich source of bioavailable cysteine.  Immunocal® can thus be viewed as a cysteine delivery system. The   disulphide   bond   in   cystine   is   pepsin   and   trypsin   resistant   but   may   be   split   by   heat,   low   pH   or mechanical   stress   releasing   free   cysteine.   When   subject   to   heat   or   shearing   forces   (inherent   in   most extraction   processes),   the   fragile   disulfide   bonds   within   the   peptides   are   broken   and   the   bioavailability of cysteine is greatly diminished. Glutathione   is   a   tightly   regulated   intracellular   constituent   and   is   limited   in   its   production   by   negative feedback   inhibition   of   its   own   synthesis   through   the   enzyme   gamma-glutamylcysteine   synthetase,   thus greatly minimizing any possibility of overdosage.
300 Joseph Carrier, Vaudreuil-Dorion, Québec J7V 5V5 • Tel: 450.424.9992 • Fax: 450.424.9993 • www.immunotec.com
Glutathione has multiple functions: 1 . It    is    the    major    endogenous    antioxidant    produced    by    the    cells,    participating    directly    in    the neutralization   of   free   radicals   and   reactive   oxygen   compounds,   as   well   as   maintaining   exogenous antioxidants such as vitamins C and E in their reduced (active) forms. 2. Through direct conjugation, it detoxifies many xenobiotics (foreign compounds) and carcinogens, both organic and inorganic. 3 . It    is    essential    for    the    immune    system    to    exert    its    full    potential,    e.g.    (1)    modulating    antigen presentation    to    lymphocytes,    thereby    influencing    cytokine    production    and    type    of    response (cellular   or   humoral)   that   develops,   (2)   enhancing   proliferation   of   lymphocytes   thereby   increasing magnitude   of   response,   (3)   enhancing   killing   activity   of   cytotoxic   T   cells   and   NK   cells,   and   (4) regulating apoptosis, thereby maintaining control of the immune response. 4 . It    plays    a    fundamental    role    in    numerous    metabolic    and    biochemical    reactions    such    as    DNA synthesis   and   repair,   protein   synthesis,   prostaglandin   synthesis,   amino   acid   transport   and   enzyme activation.      Thus,   most   systems   in   the   body   can   be   affected   by   the   state   of   the   glutathione system,   especially   the   immune   system,   the   nervous   system,   the   gastrointestinal   system   and   the lungs. INDICATIONS AND USAGE IMMUNOCAL ®    is   a   natural   food   supplement   and   as   such   is   limited   from   stating   medical   claims per   se.   Statements   have   not   been   evaluated   by   the   FDA.   As   such,   this   product   is   thus   not intended to diagnose, cure, prevent or treat any disease. Glutathione   augmentation   is   a   strategy   developed   to   address   states   of   glutathione   deficiency,   high oxidative   stress,   immune   deficiency,   and   xenobiotic   overload   in   which   glutathione   plays   a   part   in   the detoxification of the xenobiotic in question. Glutathione deficiency states include, but are not limited to: HIV/AIDS,    infectious    hepatitis,    certain    types    of    cancers,    cataracts,    Alzheimer’s    Disease,    Parkinsons, chronic   obstructive   pulmonary   disease,   asthma,   radiation,   poisoning   by   acetominophen   and   related agents,   malnutritive   states,   arduous   physical   stress,   aging,   and   has   been   associated   with   sub-optimal immune   response.      Many   clinical   pathologies   are   associated   with   oxidative   stress   and   are   elaborated upon in numerous medical references. Low   glutathione   is   also   strongly   implicated   in   wasting   and   negative   nitrogen   balance,   notably   as   seen   in cancer,    AIDS,    sepsis,    trauma,    burns    and    even    athletic    overtraining.        Cysteine    supplementation    can oppose this process and in AIDS, for example, result in improved survival rates. CONTRAINDICATIONS IMMUNOCAL® is contraindicated in individuals who develop or have known hypersensitivity to specific milk proteins. PRECAUTIONS Each   sachet   of   IMMUNOCAL®   contains   nine   grams   of   protein.   Patients   on   a   protein-restricted   diet   need to   take   this   into   account   when   calculating   their   daily   protein   load.   Although   a   bovine   milk   derivative, IMMUNOCAL®    contains    less    than    1%    lactose    and    therefore    is    generally    well    tolerated    by    lactose - intolerant individuals.
300 Joseph Carrier, Vaudreuil-Dorion, Québec J7V 5V5 • Tel: 450.424.9992 • Fax: 450.424.9993 • www.immunotec.com
WARNINGS Patients   undergoing   immunosuppressive   therapy   should   discuss   the   use   of   this   product   with their    health    professional.        Individuals    with    the    autosomal-recessive    metabolic    disorder cystinuria, are at higher risk of developing cysteine nephrolithiasis (1-2% of renal calculi). ADVERSE REACTIONS Gastrointestinal   bloating   and   cramps   if   not   sufficiently   rehydrated.   Transient   urticarial-like   rash in   rare   individuals   undergoing   severe   detoxification   reaction.   Rash   abates   when   product   intake stopped or reduced. OVERDOSAGE Overdosing on IMMUNOCAL® has not been reported. DOSAGE AND ADMINISTRATION For   mild   to   moderate   health   challenges,   20   grams   per   day   is   recommended.   Clinical   trials   in patients   with   AIDS,   COPD,   cancer   and   chronic   fatigue   syndrome   have   used   30-40   grams   per   day without   ill   effect.   IMMUNOCAL®   is   best   administered   on   an   empty   stomach   or   with   a   light   meal. Concomitant intake of another high protein load may adversely affect absorption. RECONSTITUTION IMMUNOCAL ®    is   a   dehydrated   powdered   protein   isolate.   It   must   be   appropriately   rehydrated before   use.   Ideally   consumed   after   mixing.   If   it   is   premixed   for   later   consumption,   it   should   be refrigerated   and   consumed   shortly   after   mixing.   DO   NOT   heat   or   use   a   hot   liquid   to   rehydrate the   product.   DO   NOT   use   a   high-speed   blender   for   reconstitution.   These   methods   will   decrease the activity of the product. Proper mixing is imperative. Consult instructions included in packaging. HOW SUPPLIED 10 grams of bovine milk protein isolate powder per sachet. 30 sachets per box. STORAGE Store in a cool dry environment. Refrigeration is not necessary.
300 Joseph Carrier, Vaudreuil-Dorion, Québec J7V 5V5 • Tel: 450.424.9992 • Fax: 450.424.9993 • www.immunotec.com
REFERENCES 1. Baruchel S, Viau G, Olivier R. et al. Nutraceutical modulation of glutathione with a humanized native milk serum protein isolate, Immunocal ® : application in AIDS and cancer. In: Oxidative Stress in Cancer, AIDS and Neurodegenerative Diseases. Ed.; Montagnier L, Olivier R, Pasquier C. Marcel Dekker Inc. New York, 447-461, 1998 2. Bounous G, Kongshavn P. Influence of protein type in nutritionally adequate diets on the development of immunity. In  Absorption and Utilization of Amino Acids Vol.II.  Ed. M. Friedman. CRC Press, Inc., Fla.  2:219-32, 1989 3. Bounous G, Gold P. The biological activity of undenatured whey proteins: role of glutathione. Clin Invest Med 14:296-309, 1991 4. Bounous G, Baruchel S, Falutz J. Gold P. Whey proteins as a food supplement in HIV-seropositive individuals. Clin Invest Med. 16:3; 204-209, 1992 5. Bounous G.  Whey protein concentrate (WPC) and glutathione modulation in cancer treatment. Anticancer Res. 20:4785-4792,2000 6. Bounous G.  Immunoenhancing properties of undenatured milk serum protein isolate in HIV patients.  Int. Diary Fed: Whey: 293-305, 1998 7. Bray T, Taylor C. Enhancement of tissue glutathione for antioxidant and immune functions in malnutrition. Biochem. Pharmacol. 47:2113-2123, 1994 8. Droge W, Holm E. Role of cysteine and glutathione in HIV infection and other diseases associated with muscle wasting and immunological dysfunction. FASEB J: 11(13):1077-1089, 1997 9. Herzenberg LA, De Rosa SC, Dubs JG et al. Glutathione deficiency is associated with impaired survival in HIV disease.  Proc Natl Acad Sci 94:1967-72,1997 10. Kennedy R, Konok G, Bounous G et al.. The use of a whey protein concentrate in the treatment of patients with metastatic carcinoma: A phase 1-II clinical study. Anticancer Res. 15:2643-50,1995 11. Lands LC, Grey VL, Smountas AA. Effect of supplementation with a cysteine donor on muscular performance. J. Appl. Physiol. 87:1381-1385, 1999 12. Locigno R, Castronovo V. Reduced glutathione System: Role in cancer development, prevention and treatment. International Journal of Oncology 19:221-236, 2001 13. Lomaestro B, Malone M. Glutathione in health and disease: pharmacotherapeutic issues. Ann Pharmacother  29: 1263-73,1995 14. Lothian B, Grey V, Kimoff RJ, Lands. Treatment of obstructive airway disease with a cysteine donor protein supplement: a case report. Chest 117:914-916, 2000 15. Meister A. Glutathione. Ann Rev Biochem 52:711-60,1983 16. Peterson JD, Herzenberg LA, Vasquez KK, Waltenbaugh C.  Glutathione levels in antigen-presenting cells modulate Th1 versus Th2 response patterns.  Proc.Natl. Acad. Sci. 95:3071-3076, 1998 17. Tozer RG, Tai P, Falconer W, Ducruet T, Karabadjian A, Bounous G, Molson J, Dröge W. Cysteine- rich protein reverses weight loss in lung cancer patients receiving chemotherapy or radiotherapy. Antioxidants & redox signaling. 10: 395-402, 2008 18. Watanabe A, Higachi K, Yasumura S. et al. Nutritional modulation of glutathione level and cellular immunity in chronic hepatitis B and C. Hepatology. 24:597A, 1996 19. Witschi A, Reddy S, Stofer B, Lauterberg B. The systemic availability of oral glutathione. Eur. J. Clin. Pharmacol. 43:667-669, 1992
300 Joseph Carrier, Vaudreuil-Dorion, Québec J7V 5V5 • Tel: 450.424.9992 • Fax: 450.424.9993 • www.immunotec.com
Manufactured by Immunotec Inc. Tel: 450-424-9992 ext. 4453 www.immunotec.com Copy courtesy of Dr. Vicky Dominguez, D.Sc. www.immunotec.com/drvicky
2 0 . Grey   V,   Mohammed   SR,   Smountas   AA,   Bahlook   R,   Lands   LC.   Improved   glutathione   status   in   young adult   patients   with   cystic   fibrosis   supplemented   with   whey   protein.   J   Cyst   Fibros.   (2(4):195-8,   Dec 2003 2 1 . Baumann   JM,   Rundell   KW,   Evans   TM,   Levine   AM.   Effects   of   cysteine   donor   supplementation   on exercise-induced bronchoconstriction. Med Sci Sports Exerc. 37(9):1468-73 Sep 2005 2 2 . Chitapanarux   T,   Tienboon   P,   Pojchamarnwiputh   S,   Leelarungrayub   D.   Open-labeled   pilot   study   of cysteine-rich   whey   protein   isolate   supplementation   for   nonalcoholic   steatohepatitis   patients.   J gastroenterol Hepatol. 24(6):104550, Jun 2009 2 3 . Karelis   AD,   Messier   V,   Suppère   C,   Briand   P,   Rabasa-Lhoret   R.      Effect   of   cysteine-rich   whey   protein (Immunocal®)   supplementation   in   combination   with   resistance   training   on   muscle   strength   and lean   body   mass   in   non-frail   elderly   subjects:   a   randomized,   double-blind   controlled   study.   J   Nutr Health Aging. 19(5):531-6, May 2015