**3.2 The carotenoid material**

The known molecular mechanisms of carotenoids are described herein. The exact mechanism of action of carotenoids such as beta carotene is not fully understood but it is commonly accepted scientifically that one primary mechanism is to directly scavenge oxygen derived free radicals produced either as by-products of metabolism or from exogenous environmental exposures (Lieber 1993; Bohm et al 1993; Regnault et al 1993; Riso 1999). As a free radical scavenger, carotenoids can be expected to reduce or protect against the chemical damage induced in DNA, RNA and protein of cells by toxic environmental exposures or endogenous cellular metabolic errors that ultimately can result in a disease state. On the other hand, nicotinamide and zinc salts do not possess this chemical property which results in an improved biological cellular function.

#### **3.3 The nicotinamide material**

The known molecular mechanisms of nicotinamide are described herein. Nicotinamide and its metabolic equivalent nicotinic acid (niacin, vitamin B) or even tryptophan which is the synthetic precursor to niacin is the main precursor for the formation and maintenance of the cellular pool of NAD (Bernofsky 1980; Olsson et al 1993). NAD is essential for cellular ATP production and maintenance of the cell's redox potential, and it is also the substrate for the DNA repair enzyme, poly ADP-ribosyl transferase (ADPRT). Niacin deprivation decreases the NAD pools significantly both in tissue culture cells (Jacobson, E et al 1992) and animal

Enhancing DNA Repair by Combining only Dietary Supplement

**3.6 The quinic acid material** 

2009a, 2009b; Pero and Garret 2010a).

be found in Sections 3.1 to 3.6 of this review.

below together with optimal dose ranges: 1. NAD (NICOTINAMIDE) INGREDIENT

200 mg/day) 2. ZINC INGREDIENT

**4. Discussion** 

Ingredients that do not Metabolically Compete in Order to Achieve Synergism 567

A water extract of Cat's Claw (Uncaria species) called AC-11 or one of its active ingredients quinic acid are also DNA repair enhancers that do not metabolically compete with resveratrol material, carotenoid material, nicotinamide material, DMAE material or zinc material, and as such could be added to the DNA repair mixture without inducing metabolic competition and thus inhibiting DNA repair instead of being synergistic, because the mode of action of AC-11/quinic acid to increasing DNA repair is novel to inducing DNA repair by increasing uptake of urinary tryptophan and nicotinamide (Pero 2008, Pero et al 2009b, Pero and Lund 2009a , 2011). The quinic acid analog being selected for commericial development is from the group consisting of quinic acid salts, chelates, and Uncaria or other plant extracts containing quinic acid analogs (Pero 2001, 2002, 2005, 2006,

The family of dietary supplements proposed herein; e.g. Nutra-Reservatrol, ReservaQuin, AIO, or carotenoids/nicotinamide/zinc combinations (Pero and Garret 2010, Pero and Lund 2011, Sheng et al 1998) are break through products embedded in the science of synergism, often hypothesized, rarely if ever accomplished. Listed below are 6 ingredients all known to be useful in enhancing DNA repair by independent molecular mechanisms, because their interaction with the DNA repair process results in non-competitive molecular metabolism; i.e. they regulate different pathways essential to mediate successful repair of genetic lesions. In order to achieve synergism of DNA repair, it is necessary to combine at least two of this family of dietary supplements to achieve a synergistic mixture development. This fact in turn provides a great diversity to product development by providing 6 ingredients to choose from and still achieve an increased blend of efficacy for any desired clinical indication. For example, nicotinamide supplies the energy source, zinc helps bind a repair enzyme to the damaged are in DNA, carotenoids help scavenger radicals that in turn damage the DNA in the first place, resveratrol modulates growth arrest and cell survival, DMAE (deanol, dimethylaminoethanol) dietary supplement reduces the harmful health effects of neurological stress, and by increasing critical nutrient uptake such as tryptophan and nicotinamide with quinic acid analogs. The scientific basis for further substantiation can

Most anti-aging products have at least one of the following mechanisms of action that address: Inflammation, Immunity, DNA repair, Nutrition, or Oxidative stress. However, rarely do anti-aging products have most of these known modes of action present and shown to occur by simply avoiding metabolic competition the DNA repair ingredients. The logic in this case is that synergism is hypothesized to come from co-varying lifestyle factors all being simultaneously metabolically regulated by the same dehydration/rehydration properties being induced by non-competitive metabolism of a family of DNA repair enhancing dietary supplements (data in Pero 2000, Pero and Garret 2010, Pero and Lund 2011, ). They are listed

(Energy source to Enhance Repair of Cellular Damage to DNA, RNA and protein) (100-

(Helps Recognize Harmful Lesions in Genetic Material)(10-20 mg/day

systems (Zhang et al 1993) as well as humans (Fu et al 1989). The depleted cells have an increased sensitivity to DNA damage and the levels of poly (ADP-ribose) production in cultured cells (as cited by Jacobson, E L in Poirier and Moreau (eds) 1992) or in rat liver (Rawling et al 1994) were significantly lower after mild nicotinamide deficiency. On the other hand, when niacin was given as a supplement to ordinary nutrition (i.e. above known dietary levels) the NAD pool increased and the cells were less sensitive to oxygen radicals (Weitberg 1989). Therefore, it is obvious from this review of the prior art that the primary mechanism of action of nicotinamide/niacin differs from carotenoids and zinc in that the cell's potential for energy metabolism is increased by amplifying NAD and ATP pool supplies (i.e. these biochemicals are the energy sources of living organisms) which in turn is useful to cells, tissues and organs to reduce DNA damage, enhance DNA repair (i.e. poly ADP-ribosylation) and stimulate immune function where the relevance to the disease state is apparent (Pero et al 1995).
