nac detox regulators...glutathione synthesis as measured in the red blood cells.9 in adults, nac...

NAC Detox Regulatorswith SelenoExcell®

INGREDIENTSDoctor’s Best NAC Detox Regulators supports the body’s natural biochemical pathways for neutralizing and excreting toxins. The three nutrients in this product—NAC (N-AcetylCysteine) and the essential minerals Selenium (Se), and Molybdenum (Mo)—sustain glutathione, the body’s most important antitoxin, along with many enzymes that use glutathione to neutralize toxins and clear them from the body.

These nutrients are all naturally integral to the body’s biochemistry. They are therefore ortho molecules, or right molecules for the body, following the idea of “the right molecules in the right amounts” for optimal health as conceived by two-time Nobel Prizewinner Professor Linus Pauling.1

NAC is the nutrient best proven to sustain the body’s glutathione stores.2,3 Glutathione is concentrated in all human cells. Detoxification (“detox”) enzymes in the liver, kidneys, lungs, and other organs use glutathione to bond with (“conjugate”) toxins and thereby make them able to mix into water for excretion (usually via the urine).

The Se and Mo in this formulation each have unique properties that power detox enzymes. The detox system has considerable overlap with the antioxidant defense (“antiox”) and redox regulatory (“redox”) systems. Selenium is required by a variety of enzymes that are detox, antiox and redox regulators.4 Molybdenum is indispensable for enzymes that detoxify sulfur compounds.5 This product’s combination of NAC plus Se plus Mo supports a diverse collection of detox enzymes that dispose of natural and man-made toxins (refer to the Table, Factors That Deplete Glutathione).

BENEFITSNAC Supports Numerous Detox FunctionsNAC’s detox value is grounded in its rapid conversion to cysteine that protects the blood and body fluids; the cells’ need for cysteine to make glutathione; and direct antitoxin effects by NAC itself.2,3,6-8

Supplies Cysteine To Make Glutathione. Taken by mouth, NAC elevates cysteine in the blood. Cysteine is the predominant antitoxin and antioxidant of the blood and other body fluids.3 Taking NAC is

* These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease.

actually a better way to get cysteine than cysteine itself (l-cysteine), which is too unstable to be used in dietary supplements.2 NAC’s acetyl group keeps it stable for its absorption into the blood, then subsequently its acetyl group is removed (mostly by liver enzymes) and the molecule becomes cysteine.3

Cysteine may be a conditionally essential nutrient.2 The diet of some human populations may be relatively deficient in cysteine, and (beginning around the fourth decade of life) glutathione levels decline with age.2 A pioneering cysteine researcher (W. Droge) strongly advocated taking NAC to support healthy aging, suggesting “Everybody is likely to experience a cysteine deficiency sooner or later.”

Sustains The Body’s Glutathione Status. Glutathione is the most highly concentrated antitoxin and antioxidant within human cells, and adequate glutathione is a must for good health.2,3 Glutathione is used to neutralize toxins, whether these originate outside the body or are naturally produced by the body.

Healthy cells continually “top up” their glutathione stores by importing cysteine from the blood (not glutathione), then making new glutathione from scratch.2 The supply of cysteine is normally the limiting factor for the cells to make glutathione. Supplementing with NAC therefore helps sustain both cysteine levels in the blood, and glutathione levels inside the cells.

Potent Direct Antitoxin and Antioxidant. NAC, and the cysteine it delivers into the blood, have sulfur groups with electrons that can directly neutralize “free radical” and other electron-hungry toxins (collectively called oxidants).2,3 Many prominent environmental toxins as well as cigarette smoke and other “lifestyle” toxins are oxidants (refer to the Table). Further,

Supplement FactsServing Size 1 Veggie CapsuleServings Per Container 60 & 180

Amount Per Serving % Daily Value

Selenium 50 mcg 90% (from SelenoExcell® High Selenium Yeast)(Saccharomyces cerevisiae)Molybdenum 50 mcg 110% (from molybdenum glycinate chelate)

N-Acetylcysteine (NAC) 600 mg †

† Daily Value not established.

Other Ingredients: Hypromellose (vegetarian

Suggested Adult Use: Take 1 capsule twice daily with food, or as recommended by a nutritionally- informed physician.WARNING: Consult your physician before using NAC if you are pregnant, nursing, have a history of stomach ulcers, cardiovascular or kidney problems. Non-GMO / Gluten Free / Soy Free / Vegetarian Store in a cool dry place.


Selenium Activates Glutathione Enzymes, Other Redox ProteinsThe selenium atom’s unique electronic properties are specifically required by at least 25 “selenoproteins,” including the four glutathione peroxidase enzymes that use GSH to provide protection against oxyradicals.7,26 Several other Se proteins are redox enzymes that help regulate a complex web of redox-sensitive proteins involved in gene activation, protein synthesis and cell to cell communication.2,7,26

Another Se protein family includes several enzymes that regulate iodine metabolism and healthy thyroid hormone production.4 Other Se proteins regulate muscle development and sensitivity to calcium. Still others support and regulate healthy immunity.27 Altogether, the Se proteins have complex functional interrelationships with cysteine, glutathione, and other substances with active sulfur groups, as well as with the Mo enzymes, to protect and regulate a broad swath of life processes.

Molybdenum Enzymes Detoxify Sulfur ToxinsMolybdenum’s electronic properties are required by sulfite oxidase (SO) and at least 3 other enzymes that detoxify various sulfites and bisulfites.5 These potentially toxic sulfur compounds are generated from breathing sulfur dioxide, a common environmental air pollutant, but also from the body’s normal metabolism of the sulfur in proteins and other biomolecules.28 Sulfites also are sprayed onto vegetables at salad bars to prevent spoilage, used as preservatives in wines, vinegars, and other foods, and also employed to preserve medical products. Inadequate functioning of SO results in difficulties from sulfite buildup in the blood and tissues.5

Sulfite buildup can initiate toxic reactions that especially target energy production by the mitochondria.28 The body’s four molybdenum enzymes work to detoxify a variety of potentially toxic substances produced from sulfur. Among the substances they help detoxify are “free radical” combinations of sulfur with oxygen or nitrogen that potentially could deplete glutathione.5,28 Molybdenum is a crucial dietary component of the glutathione redox system.

These Detox Regulators Are Also Antiox and Redox RegulatorsNAC, Se and Mo support, enhance and promote not just detoxification but also the interconnected metabolic webs of antioxidant defense and redox regulation.

Antioxidant Defense Centers On Mitochondria. Cysteine and lesser amounts of other antioxidants in the blood provide help defend against newly absorbed toxins.2,3 Those toxins that penetrate into cells can be neutralized by glutathione, which occurs in high concentrations in the cell interior.2 But the mitochondria need glutathione to cope with the ongoing toxic challenge that they themselves create.29

As the cells’ microelectric generators, the mitochondria generate our life energy by using oxygen to “burn” our foods. But oxygen is highly reactive and is continually generating oxyradicals within the mitochondria. These oxyradicals can generate “downstream” oxidants

In the blood, it is reduced cysteine that mainly determines the redox balance, but inside the cells glutathione predominates.2,3 By supplying cysteine, both to sustain blood cysteine and for the cells to make glutathione, NAC is the body’s premier redox support nutrient.

NAC and cysteine also help neutralize potentially toxic “free radicals” and other oxidants that the body itself naturally and continually produces. These include oxygen free radicals (oxyradicals), nitrogen free radicals, and free radicals of sulfur.2,3,6-24

NAC Has A Wide Scope Of Clinical BenefitMore than 30 controlled clinical trials with NAC have established a broad range of clinical benefits for this versatile nutrient.

Protects Against Oxidative Stress. The condition of oxidative stress occurs when “free radical” oxidative activity is abnormally high or antioxidant capacity is abnormally low. If prolonged, oxidative stress can lead to tissue and organ damage.2 Taking NAC helps counter oxidative stress, both by lowering oxidative activity and by raising antioxidant capacity.

One very intense oxidative stressor is cigarette smoke. In a double-blind trial with smokers, NAC (1200 mg daily for 6 months) significantly lowered DNA damage in lung cells.10 A more subtle cause of oxidative stress is heavy exercise in untrained individuals, which markedly elevates oxygen metabolism and causes a surge in oxidative stress that can damage the muscles.2 NAC countered such oxidative stress in a double-blind trial, also increasing muscle endurance.11

Emotional stress can translate into oxidative stress, as with medical students studying for finals.16 These students showed not only GSH depletion but also sperm abnormalities. In a controlled trial, men with poor sperm quality who received NAC (600 mg per day) had significantly lower oxidative stress markers in the blood after 3 months, and their semen volume, motility and viscosity also were significantly improved.17

Benefits The Brain And Other Organs. NAC has shown strong benefits for mood, function and behavior in multiple controlled clinical trials.7,12-15 NAC supported healthy mood stability, insight, self-care, motivation, clarity of thought, and social interaction.12-14 Used in combination with B vitamins, NAC also helped stabilize memory in elderly individuals.15 Animal experiments suggest NAC may support certain brain transmitter systems by actions different from its usual detox and antiox actions.7

In numerous other clinical trials, NAC benefited the liver,8,18 lungs,19 colon,20 pancreas,3 immune system,3,21 circulation,22 and skin.23 NAC also supported healthy growth in children,9 improved skeletal muscle mass and function in elderly individuals,2,24 and provided nutritional support for wellbeing all across the lifespan.6,7,9,16,24

NAC effectively repletes glutathione in individuals who have sustained depletion. In a clinical study on severely depleted children, NAC restored glutathione synthesis as measured in the red blood cells.9 In adults, NAC also effectively repleted glutathione in immune cells.3 NAC is widely accepted as a safe and effective means to replenish glutathione.2,3,8,9

NAC Is The Premier Nutrient For Redox Support. “Redox” stands for “reduction-oxidation.” Reduction indicates relative electron abundance, which is good for health, and oxidation indicates relative electron scarcity, which is bad for health. The healthy body has sufficient reducing power to keep oxidative challenges under control. The body under oxidative stress typically has less reducing power, with fewer electrons available to cope with oxidative challenge. Maintaining redox balance on the side of electron abundance is crucial to health.

Redox regulating enzymes maintain the necessary balance by drawing electrons from cysteine or glutathione, then positioning them on redox-sensitive enzymes and other proteins (such as receptors, transporters, and gene regulators). Redox-sensitive proteins typically have sulfur groups that must be kept loaded with electrons in order for the molecule to work.25 NAC, the cysteine it provides, and the glutathione made from cysteine all have sulfur groups available to donate electrons to those proteins that need them.2,3


such as nitrogen radicals, sulfur radicals, and peroxides. The mitochondria cannot make their own glutathione, and instead use energy to import glutathione from the cell cytoplasm into their interior.29 They also use Se and Mo enzymes for additional protection.4,5 Supplementing the diet with NAC, Se and Mo helps the mitochondria avoid self-destruction from their own free radical production.

Redox Regulates Life. In the healthy body, an overall reducing redox balance, i.e., relative abundance of electrons, helps keep the sulfur groups of proteins saturated with electrons and fully active. Such redox-sensitive proteins make up the vast majority of the cell’s proteins, and collectively ensure healthy production and utilization of DNA, RNA, phospholipids, proteins, hormones, and thousands of other essential biomolecules. Healthy redox balance also is essential to regulate energy generation, gene and chromosome activities, cell growth and proliferation, cell-to-cell coordination, electrical activity, wound healing and regeneration, detox and antiox defense, and practically all the other life processes.2,3,25,26

By simultaneously enhancing the body’s detox, antiox and redox systems, this product’s nutrient combination is a boon to anyone striving for optimal health or seeking additional nutritional insurance against the hazards of living and working in the modern world.

Factors That Deplete the Body’s Glutathione Stores

• Acetaminophen, an OTC pharmaceutical8,30

• Acrylamide, used in the plastics industry and naturally occurring in foods31

• Aging32

• Alcohol33

• Cement dust34

• Cigarette smoke10

• Emotional stress, as in medical students studying for exams.16

• Heavy metals arsenic, cadmium, lead, mercury35,36

• Inhaled fibers37

• Malnutrition in children9

• Methacrylates, used in dental work and other applications38

• Methyl mercury, ubiquitous environment pollutant39

• Octachlorostyrene, industrial byproduct of chlorine processing40

• Oxygen deficit (hypoxia)41

• Paraquat42 and phosphamidon, common pesticides43

• Polychlorinated biphenyls (PCBs), ubiquitous pollutants44

• Styrene, used in plastics45

• Surgery, other illness46

• Thimerosal, mercury compound currently uses as medical preservative36

• Ultraviolet23

• X-rays, occupational exposure in radiology technicians47

SAFETYNAC, Se, and Mo are all well tolerated and safe to take long-term. These three functionally linked nutrients render Doctor's Best NAC Detox Regulators well suited for an exceptionally wide range of dietary supplement applications.


Mitochondrial glutathione, a key survival antioxidant. Antiox Redox Signal 2009;11:2685-2700.

30. Mitchell SJ, Kane AE, Hilmer SN. Age-related changes in the hepaticpharmacology and toxicology of paracetamol. Curr Gerontol Geriatr Res 2011;V2011, Article ID 624156: 14 pages.

31. Park J, Kamendulis LM, Friedman MA, Klaunig JE. Acrylamide-induced cel-lular transformation. Toxicol Sci 2002;65:177-183.

32. Samiec PS, Drews-Botsch C, Flagg EW, others. Glutathione in humanplasma: decline in association with aging, age-related macular degenera-tion, and diabetes. Free Radic Biol Med 1998;24:699-704.

33. Joshi PC, Guidot DM. The alcoholic lung: epidemiology, pathophys-iology, and potential therapies. Am J Physiol Lung Cell Mol Physiol2007;292:L813-L823.

34. Orman A, Kahraman A, Cakar H, others. Plasma malondialdehyde anderythrocyte glutathione levels in workers with cement-dust exposure.Toxicol 2005;207:15-20; Erratum in Toxicol 2005;215:170.

35. Jomova K, Valko M. Advances in metal-induced oxidative stress and hu-man disease. Toxicology 2011;283:65-87.

36. Makani S, Gollapudi S, Yel L, others. Biochemical and molecular basis ofthomerosal-induced apoptosis in T cells. Genes Immunity 2002;3:270-278.

37. Abbate C, Giorgianni C, Brecciaroli R, others. Changes induced by expo-sure of the human lung to glass fiber-reinforced plastic. Environ HealthPerspec 2006;114:1725-1729.

38. Chang HH, Guo MK, Kasten FH, others. Stimulation of glutathione deple-tion, ROS production, and cell cycle arrest of dental pulp cells and gingi-val epithelial cells by HEMA. Biomaterials 2005;26:745-753.

39. Shenker BJ, Guo TL, Shapiro IM. Induction of apoptosis in human T-cells by methyl mercury: temporal relationship between mitochondrial dysfunc-tion and loss of reductive reserve. Toxicol Appl Pharmacol 1999;157:23-35.

40. Park EJ, Park K. Induction of oxidative stress in human Chang liver cells by octachlorostyrene, the persistent and bioaccumulative toxicant. Toxicol In Vitro 2008;22:367-375.

41. Tissot van Patot MC, Serkova NJ, Haschke M, others. Enhanced leukocyte HIF-1 alpha and HIF-1 DNA binding in humans after rapid ascent to 4300 m. Free Radic Biol Med 2009;46:1551-1557.

42. Zhang J, Lv G, Zhao Y. The significance of serum xanthine oxidase andoxidation markers in acute paraquat poisoning in humans. Clin Biochem 2011;44:221-225.

43. Ahmed T, Tripathi AK, Ahmed RS, Banerjee BD. Assessment of phospha-midon-induced apoptosis in human peripheral blood mononuclear cells. J Biochem Mol Toxicol 2010;24:286-292.

44. Xie W, Wang K, Robertson LW, Ludewig G. Investigation of mechanism(s) of DNA damage induced by 4-monochlorobiphenyl (PCB3) metabolites.Environ Int 2010;36:950-961.

45. Sati PC, Khaliq F, Vaney N, others. Pulmonary function and oxidativestress in workers exposed to styrene in plastic factory: occupation-al hazards in styrene-exposed plastic factory workers. Hum Exp Toxicol 2011;30:1743-1750.

46. Liu J-L, Hammarqvist F, Andersson K, Wernerman J. Surgical trauma de-creases glutathione synthetic capacity in human skeletal muscle tissue.Am J Physiol Endocrinol Metab 1998;275:E359-E365.

47. Akkose A, Omer B, Yigitbasi A. DNA damage and glutathione content inradiology technicians. Clin Chim Acta 2003;336:13-18.

supplementation on seleno-protein gene expression and re-sponse to influenza vaccine chal-lenge. PLoS ONE 2011;6:e14771 (9 pages).

28. Zhang X, Vincent AS, HalliwellB, Wong KP. A mechanism ofsulfite neurotoxicity. J Biol Chem 2004;279:43035-43045.

29. Mari M, Morales A, Colell A, others.

SCIENTIFIC REFERENCES

1. Pauling L. Orthomolecular psychiatry. Science 1968; 160:265-271. 2. Droge W. Oxidative stress and aging: is aging a cysteine deficiency syn-

drome? Phil Trans R Soc B 2005;360:2355-2372. 3. Atkuri KR, Mantovani JJ, Herzenberg LA, Herzenberg LA. N-acetylcyste-

ine-a safe antidote for cysteine/glutathione deficiency. Curr Opin Phar-macol 2007;7:355-359.

4. McCann JC, Ames BN. Adaptive dysfunction of selenoproteins from theperspective of the triage theory: why modest selenium deficiency mayincrease risk of diseases of aging. FASEB J 2011;25:1793-1814.

5. Panel on Micronutrients. Dietary Reference Intakes for Vitamin A, VitaminK, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybde-num, Nickel, Silicon, Vanadium, and Zinc. 2002; National Academies Press (http://www.nap.edu/catalog/10026.html).

6. Millea PJ. N-acetylcysteine: multiple clinical applications. Am Fam Physi-cian 2009;80:265-269.

7. Dean O, Giorlando F, Berk M. N-acetylcysteine in psychiatry: current ther-apeutic evidence and potential mechanisms of action. J Psychiatr Neurosci 2011;36:78-86.

8. Heard KJ. Acetylcysteine for acetaminophen poisoning. N Engl J Med 2008;359:285-292.

9. Badaloo A, Reid M, Forrester T, others. Cysteine supplementation [NAC]improves the erythrocyte glutathione synthesis rate in children with se-vere edematous malnutrition. Am J Clin Nutr 2002;76:646-652.

10. Van Schooten FJ, Nia AB, De Flora S, others. Effects of oral administration of N-acetyl-l-cysteine: a multi-biomarker study in smokers. Cancer Epide-miol Biomark Prev 2002;11:167-175.

11. Koechlin C, Couillard A, Simar D, others. Does oxidative stress alter quad-riceps endurance in chronic obstructive pulmonary disease? Am J RespirCrit Care Med 2004;169;1022-1027.

12. Berk M, Munib A, Dean O, others. Qualitative methods in early-phasedrug trials: broadening the scope of data and methods from an RCT ofN-acetylcysteine for schizophrenia. J Clin Psychiatry 2011;72:909-913.

13. Berk M, Copolov DL, Dean O, others. N-acetyl cysteine for depressivesymptoms in bipolar disorder—a double-blind randomized placebo-con-trolled trial. Biol Psychiatr 2008;64:468-475.

14. Magalhaes PV, Dean OM, Bush AI, others. N-acetyl cysteine add-ontreatment for bipolar II disorder: a subgroup analysis of a randomizedplacebo-controlled trial. J Affect Disord 2011;129:317-320.

15. McCaddon A. Homocysteine and cognitive impairment; a case series in a General Practice setting. Nutr Journal 2006;5:1-6.

16. Eskiocak S, Gozen AS, Yapar SB, others. Glutathione and free sulphydrylcontent of seminal plasma in healthy medical students during and afterexam stress. Human Repr 2005;20:2595-2600.

17. Ciftci H, Verit A, Savas M, others. Effects of N-acetylcysteine on semenparameters and oxidative/antioxidative status. Urology 2009;74:73-76.

18. Sotelo N, de los Angeles Durado M, Gonzalez A, Dhanakotti N. Earlytreatment with N-acetylcysteine in children with acute liver failure sec-ondary to hepatitis A. Ann Hepatol 2009;8:353-358.

19. Stav D, Raz M. Effect of N-acetylcysteine on air trapping in COPD. Chest 2009;136:381-386.

20. Guijarro LG, Mate J, Gisbert JL, others. N-acetyl-l-cysteine combined with mesalamine in the treatment of ulcerative colitis: randomized, place-bo-controlled pilot study. World J Gastroenterol 2008;14:2851-2857.

21. De Flora S, Grassi C, Carati L. Attenuation of influenza-type symptom-atology and improvement of cell-mediated immunity with long-termN-acetylcysteine treatment. Eur Respir J 1997;10:1535-1541.

22. Kudaravalli J. Improvement in endothelial dysfunction in patients withsystemic lupus erythematosus with N-acetylcysteine and atorvstatin. In-dian J Pharmacol 2011;43:311-315.

23. Goodson AG, Cotter MA, Cassidy P, others. Use of oral N-acetylcysteinefor protection of melanocytic nevi against oxidative stress. Clin Canc Res 2009;15:7434-7440.

24. Hauer K, Hildebrandt W, Sehl Y, others. Improvement in muscular perfor-mance and decrease in tumor necrosis factor level in old age after antiox-idant treatment. J Mol Med (Berlin) 2003;81:118-125.

25. Pandey KB, Rizvi SI. Markers of oxidative stress in erythrocytes and plas-ma during aging in humans. Oxid Med Cell Longevity 2010;3:2-

26. Hawkes WC, Alkan Z. Regulation of redox signaling by selenoproteins. Biol Trace Elem Res 2010;134:235-251.

27. Goldson AJ, Fairweather-Tait SJ, Armah CN, others. Effects of selenium

© Doctor’s Best, Inc. phone: 800-333-6977 • fax: 949-498-3952 • www.drbvitamins.com

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