**5. References**

568 Selected Topics in DNA Repair

(Modulates Growth Arrest and Cell Survival and DNA repair) (70-2000 mg/day)

(Enhances DNA repair by increasing tryptophan uptakr, and also providing anti-

7. DO SUPRA-PHYSIOLOGIC LEVELS OF DIETARY SUPPLEMENTS AUGMENT DNA REPAIR CAPACITY. The ingredients identified above with the exception of Resveratrol were known to be effective in vivo at the indicated doses above, which were in turn above normal physiologi occurring levels . However, metabolic competition between some agents can seriously alter their bioavailability to the extent that when administered in combination they are no longer efficacious (Sheng et al 1998, Pero 2000). It was hypothesized that this could be the case with resveratrol and the other agents in Nutra-Reveratrol. Hence, they were pre-screened before formulation to avoid any metabolic competition originating from their DNA repair mechanism of action

Weight regulates essentially all aspects of a disease-free life via nutrition and metabolism balances/imbalances that can be estimated reproducibly by assessment of dehydration (Cheuvront et al 2010). Primary causes of everyday ill health from weight gain are bodily fluctuations in water balance (hydration) (Manz 2007). Moreover, it is a very large market since 27% of American adults have metabolic syndrome (i.e. disturbances in hydration), while 85% of overweight people do (Ford et al 2004, Grundy et al 2005). Your lifestyle demands you to react to your environment, and metabolic hydration is the gage of how

Lifestyle factors are key to generation of oxidative stress, aging, and dehydration in turn is the dominant cause behind weight generated ill health, because weight gain also co-varies with the lifestyle changes associated with the obese. Examples are narcotics (smoking, alcohol consumption, drugs, binge over-eating), diet (fats, proteins, carbohydrates, fiber, vitamins, minerals) exercise, weight gain, sleep (psychotropic stress). Hence, treating dehydration with re-hydration, and anti-DNA damaging agent metabolism also optimizes a

There is another important link between essential amino acid metabolism and DNA repair capacity. It is based on the discovery of a previously unappreciated metabolic connection between naturally occurring hippuric acid and quinic acid. Hippuric acid is not found in plant material nor is it metabolized by higher plants (Reviewed in Pero 2010b). Hippuric acid is known to be catabolically synthesized from benzene-type aromatic compounds usually believed to be originating from environmental exposures, or from the cyclic sugar type-compound quinic acid. Quinic acid is ubiquitous especially in healthy foodstuffs which in turn can lead to aromatic plant biosynthesis *via* the microbial shikimate pathway existing in the human gastrointestinal tract. Consequently, Pero (2010a) reasoned that if the urinary level of hippuric acid co-varied and increased in proportion with urinary quinic acid levels as they in fact did, then it follows then that the primary levels of these metabolites (i.e hippuric and quinic acids) are coming from the diet and not environmental exposures. Hence, because the GI tract was primarily responsible for this metabolism and not the liver,

successful you have managed health risk from exposure to these factors.

first good line of defense against age-associated diseases in general.

3. CAROTENOIDS (CANTAXATHIN) INGREDIENT

(Reduces Neurological Stress) (100-200 mg/day) 6. QUINIC ACID ANALOG OR EXTRACT INGREDIENTS

infective properties (350-700 mg/day)

4. RESERVATROL INGREDIENT

5. DMAE (Deanol) INGREDIENT

(Pero and Garret 2010).

(Powerful water soluble antioxidant carotenoid) (100-200 mg/day)


Enhancing DNA Repair by Combining only Dietary Supplement

filing date 16.03.2006, Publication date 28.09.2006

Pharmacology *5:* 67-73, 2010a

Publication Date Aug. 26, 2010

236, 2010b.

346, 2009b

Ingredients that do not Metabolically Compete in Order to Achieve Synergism 571

Pero, RW. Method of preparation and composition of a water soluble extract of the plant

processes of warm blooded animals. US 6,238, 675 B1, Issued May 29, 2001 Pero, RW. Method of preparation and composition of a water soluble extract of the plant

repair processes of warm blooded animals US 6,361,805 B2 Mar. 26, 2002 Pero, RW. Method of preparation and composition of a water soluble extract of the bioactive

acid analog preferably quinic acid lactone) US 6,964,784 . Issued Nov. 15, 2005 Pero, RW. Medicinal compositions of salts, chelates and/or free acids of alpha hydroxyl

Pero, RW. A method of increasing tryptohan and nicotinamide levels in vivo. WO/2008/008837. International filing date 11.07.2007, Publication date 17.01.2008 Pero, RW. Method of preparation and composition of a water soluble extract of the bioactive

isolating a quinic acid analog). US 7,579,023 B2, Issued Aug. 25, 2009a Pero, RW. Method of preparation and composition of a water soluble extract of the bioactive

Pero, RW. Historic development of Uncaria preparations and their related bioactive

Pero, RW, Garret, S. Nutritional Supplement. US 2010/0215768 A1, filed Feb. 24, 2010,

Pero, RW, Holmgren, K, Persson, L. Gamma-radiation induced ADP-ribosyl tansferase

Pero, RW, Hoppe, C, Sheng, Y. Serum thiols as a surrogate estimate of DNA repair correlates to mammalian life span. Jour Anti-Aging Med 3 (3): 241-249, 2000 Pero RW and Lund H. In Vivo Treatment of Humans with Quinic Acid Enhances DNA

Pero, RW, Lund H. Dietary quinic acid supplied as the nutritional supplement AIO + AC-11

Pero RW, Lund H, Leanderson T. Antioxidant metabolism induced by quinic acid. Increased

Repair and Reduces the Influence of lifestyle Factors on Risk to Disease. ISSN 0973-

leads to induction of micromolar levels of nicotinamide and tryptophan in the

urinary excretion of tryptophan and nicotinamide. Phytotherapy Research 23: 335-

activity and mammalian longevity. Mutation Res 142: 69-73, 1985

2691. Int. J. Biotech. and Biochem. 5 (3): 293–305, 2009a

urine. Phytotherapy Research in press, 2011

species Uncaria for enhancing immune, anti-inflammatory, and anti-tumor

species Uncaria for enhancing immune, anti-inflammatory, anti-tumor and DNA

component of the plant species Uncaria for enhancing immune, anti-inflammatory, anti-tumor and DNA repair processes of warm blooded animals (Isolation of a quinic

organic acids and related processes and methods. WO/2006/101922 International

component of the plant species Uncaria for enhancing immune, anti-inflammatory, anti-tumor and DNA repair processes of warm blooded animals (a method of

component of the plant species Uncaria for enhancing immune, anti-inflammatory, anti-tumor and DNA repair processes of warm blooded animal (a method of isolating a quinic acid salt or chelate or free acid). US 7,595,064 B2, Issued Sept. 29, 2009b. Pero, RW. Health consequences of catabolic synthesis of hippuric acid. Reviews in Clinical

components. Chap.9. In Allison E. Thomas (ed). DNA repair, damage repair mechanisms and aging, Nova Science Publishers, ISB 978-1-61668-914-8. pp 223-


Dawat P, de Oliveira R, Ehrlich D, Boiteux, S. Repair of oxidative DNA damage in Gram

de Murcia G, Ménissier-de Murcia J, Schreiber V. Poly(ADP-ribose) polymerase: molecular

Feng YH , Jian-Ping Z, Xiao-Yu L. Effects of resveratrol and ethanol on production of

Ford ED, Giles WH, Mokad AH. Increasing prevalence of the metabolic syndrome among

Fu CS, Swendeid ME, Jacob RA, Mckee YW. Biochemical Markers for Assessment of Niacin

Gatz SA , Keimling M, Baumann C, Thilo, Dörk T, Debatin K-M, Fulda S, Wiesmülle, L.

Grossman R. The role of dimethylaminoethanol (DMAE) in cosmetic dermatology. Am J

Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, Gordon DJ, Krauss

institute scientific statement statement. Circulation 112(17): 2735-2752, 2005 Jacobson, E. et al., IN: ADP-Ribosylation Reactions (Poirier, G. G. and Moreau, P., eds.), pp.

Matsuda T, Saijo, M, Kuraoka I, Kobatashi T, Nakatsu, Y, Nagal A, Enjoji, T, Massuta C,

Mazen A, Menissier-deMurcia J, Molinete M, Simonin F, Gradwohl, G, Poirier, G, deMurcia,

Nagy I, Nagy K. On the role of cross-linking of cellular proteins in aging. Mech Ageing Dev

Olsson A, Olofsson T, and Pero, RW. Specific binding and uptake of extra cellular nicotinamide in human leukemic K-562 cells. Biochem. Pharmacol. 45(6):1191-1200 (1993) Payette H, Rola-Pleczcynski, M, Ghadirin P. Nutrition factors in relation to cellular and

Pero, RW. Carotenoid-nicotinamide-zinc compositions and methods of treatment using

Pero, RW. Method of preparation and composition of a water soluble extract of the plant

Sugasawa, K, Hanaoka, F. DNA Repair protein XPA binds replication protein A

G. Poly(ADP-ribose)polymerase: a novel finger protein. Nucleic Acid Res. 17:4689-

regulatory immune variables in a free-living elderly population. Am. J. Clin. Nutr.

Lieber, DC Antioxidant reactions of carotenoids. Ann. N. Y. Acad. Sci. 691: 20-31, 1993 Manz, F. Hydration and disease. Journal of the American College of Nutrition. 26(9005):

developmental biology13 (9):455-62 (1991).

Tryptophan. J. Nutr. 123: 1349-1355, 1993.

U,S. adult. Diabetes Care 24 (10): 2735-2752, 2004

153-162, Springer Verlag, New York, N.Y., 1992

(RPA). J. Biol. Chem. 270(8):4152-4157, 1995

same. US 6,020,351, Issued Feb. 1, 2000

species Uncaria. US 6,039,949. Issued Mar. 21, 2000

Pharmacol Sin 23(10): 893-897, 2002

Clin Dermatol 6:39–47, 2005

535S-541S, 2007

4698, 1989

14(1–2):245–251, 1980

52:927-932, 1990

1995

positive bacteria: the Lactococcus lactis Fpg protein.Microbiol. 141 (Pt 2):411-417,

biological aspects. BioEssays: news and reviews in molecular, cellular and

proinflammatory factors from endotoxin activated murine macrophages Acta

Status in Young Men: Levels of Erythrocyte Niacin Coenzymes and Plasma

Resveratrol modulates DNA double-strand break repair pathways in an ATM/ATR–p53- and –Nbs1-dependent manner. Carcinogenesis 29(3):519-527, 2008

RM, Savage, PJ, Smith SC jr, Spertus JA, Costa F. Diagnosis and management of metabolic syndrome: An American Heart/National Heart, Lung, and Blood


Pero, RW, Olsson, A, Sheng, Y, Hua, J, Moller, C, Kjelle'n, E, Killander, D, Marmor, M.

Regnault C, Postaire ER, Rousse GJ, Bejot M and Hazebroucq, GF Influence of beta carotene,

Riso P, Pinder A, Santangelo, A, Porrini, M. Does tomato consumption effectively increase

Sheng Y., Pero, R.W., Olsson, A.R., Bryngelsson, C. and Hua, J. DNA repair enhancement by

Sheng , Akesson, C. Holmgren K, Bryngelsson C, Giampapa V, Pero, RW. An active

Regnault C, Postaire ER, Rousse GJ, Bejot M and Hazebroucq, GF Influence of beta carotene,

Stoner DS, Li-Shu Wang L-S , Casto BC. Laboratory and clinical studies of cancer chemoprevention by antioxidants in berries. Carcinogenesis 29(9): 1665-1674, 2008 Terman A, Brunk UT. Oxidative stress, accumulation of biological "garbage," and aging.

Weitberg, AB. Effect of nicotinic acid supplementation in vivo on oxygen radical-induced genetic damage in human lymphocytes. Mutational Res. 216:197-201, 1989 Valenzano DR, Terzibasi E,Genade T, Cattaneo A, Domenici L , Cellerino A. Resveratrol

Whyte L, Huang YY, Torres, K, Mehta, RG. Molecular mechanisms of reservatrol action in

Williams, RO, Loeb L A. Zinc requirement for DNA replication in stimulated human

WIN/NIDDK, Weight-Control Information Network/National Institute of Diabetes,

http://win.niddk.nih.gov/publication/health risk.htm. December 31, 2010 Wood, RD, Mitchell, M. , Sqouros, J, Lindahl, T. Human DNA repair genes. Science 16: 291

Zhang J, Henning, SM, Swendseid AE Poly(ADP-Ribose) Polymerase Activity and DNA

Zhang YH, Kramer, TR, Taylor, PR, Li, JY, Blot, WJ, Brown, CC, Guo, W, Dawsey, SM, LI, B.

measurements of poly ADP-ribosylation. Biochimie 77:385-393 (1995) Rawling JM, Jackson TM, Drisscol ER, Kirkland, J. Dietary Niacin Deficiency Lowers Tissue

1603, 1994

718, 1999

12007–17, 2007

(5507) : 128 4-9, 2001

Clin. Nutr. 62:1477S-1482S, 1995

1355, 1993

Pharmacotherapy 27(11):1349-1350, 1993

Ethanopharmacology 96(3):577-584, 2005

Pharmacotherapy 27(11):1349-1350, 1993

Antioxid Redox Signal 8(1–2):197–204, 2006

Vertebrate. Current Biology 16 (3): 296-300, 2006

lymphocytes. J. Cell Biol. 58:594-601, 1973

Prevent. 22(4): 284-292 (1998)

Progress in identifying clinical relevance of inhibition, stimulation and

Poly(ADP-Ribose) and NAD+ Concentrations in Fischer 344 Rats J. Nutri. 124:1597-

vitamin E, and vitamin C on endogenous antioxidant defenses in erythrocytes Ann.

the resistance of lymphocyte DNA to oxidative damage. Am J. Clin Nutr 69(4): 712-

a combined supplement of carotenoids, nicotinamide, and zinc. Cancer Det.

ingredient of Cat's Claw water extracts. Identification and efficacy of quinic acid. J

vitamin E, and vitamin C on endogenous antioxidant defenses in erythrocytes Ann.

Prolongs Lifespan and Retards the Onset of Age-Related Markers in a Short-Lived

lung cancer cells using dual protein and microarray analyses. Cancer Res 67(24):

Digestive and Kidney Disease. Do you know the health risks of being over weight.

Strand Breaks Are Affected in Tissues of Niacin-Deficient Rats. J. Nutri. 123:1349-

Possible immunologic involvement of antioxidants in cancer prevention. Am. J.
