Abstract
Antioxidants come in many varieties such as complex protein compounds called Enzymes, and non-enzymatic antioxidants including: Alpha-Lipoic Acid, Carotenoids, Tocopherals, and Vitamins (Refer to Section, “What are Antioxidants?”). Dietary antioxidants, such as the foregoing with some emphasis on Flavonoids, and particularly Vitamin C, reveal additional biological effects which might be of importance in context with the prevention of degenerative diseases (Stahl et al, 2002). Additional current studies continue to reinforce the popular notion that a direct correlation exists between the increased intake of antioxidants, and wellness across the board, resulting in prolongation of life span (Sueoka et al, 2001), and increased quality of life—especially in the latter years.
Enzymatic Antioxidants
There are dozens if not hundreds of reports providing ample data and findings in support of what now seems to be approaching conclusive evidence rather than mere hypothesis. In the instance of enzymatic antioxidants we have several good authorities upon which we may rely. For example, Coenzyme Q10 has been shown to be an endogenous enzyme cofactor which may provide protective benefits as an antioxidant (Miles, 2004). Another study examined the fact that Mitochondrial dysfunction contributes to the neurodegenerative process in Huntington disease (HD), and Coenzyme Q10 enhances mitochondrial complex I activity; therefore providing a possible therapeutic benefit in HD (Andrich, 2004). This is particularly interesting in light of features of Parkinson's disease (PD) also associated with coenzyme Q(10) deficiency (Muller et al, 2003). We know Parkinson’s disease also as a degenerative neurological disorder. Coenzyme Q10 was tested (testing and evaluation occurred over a 16 month period followed by a 16 month follow-up period) and proved safe, and well-tolerated at dosages of up to 1200mg/d. At this level it appeared to slow the progressive deterioration of function in PD…(Shults et al, 2002). Another enzymatic substance, Ubiquinone (Coenzyme Q), in addition to its well-established function as a component of the mitochondrial respiratory chain, during the last decade, has acquired increased attention as an antioxidant (Ermster, 1995).
In the non-enzymatic camp we find a model compound in Alpha-Lipoic Acid which influences a number of cell processes. These include:
· Direct radical scavenging
· Recycling of other antioxidants
· Accelerating GSH synthesis
· Modulating transcription factor activity especially that of NF-kappa B (Packer, 1998)
In particular, four antioxidant properties of lipoic acid have been studied [the kind of oxidizable substrate (e.g., DNA, lipid protein) determine its reactions]:
In vitro studies also have shown that alpha-lipoic acid (LA) is an antioxidant. LA oral supplementation decreases plasma-and LDL oxidation and urinary isoprostanes (Marangon et al, 1999). Finally, a decrease in the activity of plasma glutathione peroxiadase (an oxidant) observed in the glucose-fed rats was prevented by lipoic acid treatment (El Midaoui & de Champlain, 2002). This final study indicates that the possibility of its use proactively, merits our attention.
Carotenoids, especially made up of phytochemicals (which give produce its bright colors) are great allies in keeping the body healthy. In a medical journal just last year it was explained, “The intake of 400-600 g/d of fruits and vegetables is associated with reduced incidence of many common forms of cancer. Diets rich in plant foods are also associated with a reduced risk of heart disease and many chronic diseases of aging. These foods contain phytochemicals that have anti-cancer and anti-inflammatory properties which confer many health benefits.” (Heber, 2004)
Red foods contain lycopene, the pigment in tomatoes, which is localized in the prostate gland and may be involved in maintaining prostate health, and which has also been linked with a decreased risk of cardiovascular disease. Growing evidence suggests that lycopene has significant in vitro antioxidant potential. A study involving 39,876 middle-aged and elderly women initially free of cardiovascular disease and cancer was recently concluded. Conclusions drawn from this study confirmed that higher plasma lycopene concentrations are associated with a lower risk of cardiovascular disease in women. (Sesso et al, 2004). In an earlier study it was observed that tomato products may reduce the susceptibility of lymphocyte DNA to oxidative damage. (Riso et al; April, 1999). Later, an evaluation in nine adult women of whether the consumption of 25g of tomato puree for 14 consecutive days increased plasma and lymphocyte carotenoids concentration was conducted. The conclusion of this study is that small amounts of tomato puree added to the diet over even a short period can increase carotenoid concentrations and the resistance of lymphocytes to oxidative stress. (Porrini & Riso, 2000) Watermelon has also been show to offer significant amounts of lycopene (Edwards et al, 2003).
Green foods, including broccoli, Brussel sprouts and kale, contain glucosinolates which have also been associated with a decreased risk of cancer. Other bioactive substances in green tea and soybeans have health benefits as well. White-green foods like garlic and others in the onion family contain allyl sulphides which may inhibit cancer cell growth. Consumers are advised to ingest one serving of each of the seven color groups daily. The recommendation of the National Cancer Institute and American Institute for Cancer Research provides guidelines of five to nine servings per day (Heber, 2004). Another independent study indicated that the consumption of fruits and vegetables reduces the risk of major chronic degenerative diseases. Among individual food groups, coffee, wine, and vegetables were significantly correlated with dietary Zeaxanthin, Beta-carotene, and Alpha-carotene. These data agree with the hypothesis that dietary antioxidants other than the well-known antioxidants contribute to our antioxidant defense. Surprisingly, the single greatest contributor to the total antioxidant intake was coffee (Svilaas et al, 2004).
Beta-carotene from juice has been shown to enhance immune functions in humans. Increased plasma carotenoid concentrations after vegetable juice consumption are accompanied by a time-delayed modulation of immune functions in healthy men consuming a low-carotenoid diet. Juice consumption resulted in relatively fast responses in plasma carotenoid concentrations (Watzl, 2003).
How all of this works may be explained by the following statements: The antioxidant action of carotenoids is believed to involve quenching of singlet oxygen and scavenging of reactive oxygen radicals. It was found that Zeaxanthin-supplemented cells, in the presence of either Alpha-tocopherol or Ascorbic Acid, were significantly more resistant to photoinduced oxidative stress. Such a synergistic action of Zeaxanthin and Vitamin E or C indicates the importance of the antioxidant interaction in efficient protection of cell membranes against oxidative damage induced by photosensitized reactions. (Wrona et al, 2004). It has been known for some time that Beta-carotene can act synergistically with Alpha-tocopherol as an effective radical-trapping antioxidant in membranes. (Palozza & Krinsky, 1992). Thus, synergistic relationships between carotenoids and vitamins apparently exist, each enhancing the contribution of the other, independently.
In another test volunteers consumed a daily supplement (for 3 weeks in a randomized crossover design separated by a 12 week washout phase) comprising either capsules containing just fish oil (4 x 1 g) or fish oil (same dosage), but also containing a natural carotenoid mixture (4 x 7.6 mg). The carotenoid mixture provided a daily intake of Beta-carotene (6.0 mg), Alpha-carotene (1.4 mg), Lycopene (4.5 mg), Bixin (11.7 mg), Lutein (4.4 mg) and paprika carotenoids (2.2 mg). Consumption of the natural carotenoid mixture lowered the increase in oxidative stress induced by the fish oil. The carotenoid mixture also enhanced the plasma triglyceride-lowering effect of the fish oil. (Kiokias & Gordon, 2003). These findings are extremely encouraging for cancer patients. The relation between lung cancer risk and intakes of Alpha-carotene, Beta-carotene, Lutein, Lycopene, and Beta-cryptoxanthin in 2 large cohorts was studied. In the pooled analyses, Alpha-carotene and Lycopene intakes were significantly associated with a lower risk of lung cancer (Michaud et al, 2000).
Also, foods and beverages rich in phenolic compounds, especially flavonoids, have often been associated with decreased risk of developing several diseases. Alleged health-promoting effects of flavonoids are usually attributed to their powerful antioxidant activities. Phenols might exert direct effects within the gastrointestinal tract, because of the high concentrations present (Halliwell et al, 2005).
Further, tocopherols and tocotrienols may also exert direct beneficial effects in the gastrointestinal tract and that their return to the gastrointestinal tract by the liver through the bile may be physiologically advantageous (Halliwell et al, 2005).
Some of the most promising yet readily available carotenoids are in the form of tea catechins. The anticancer properties of tea catechins are most frequently attributed to the principal catechin, (-) epigallocatechin-3-gallate (EGCg). Efficacy was evaluated studying growth of cultured HeLa cells and inhibition of the enzymatic activity. Various synthetic mixtures based on purified catechins and decaffeinated tea extracts treated enzymatically to reduce the ester bond-containing catechins varying in EGCg content were of comparable efficacy to decaffeinated green teas extracts. The mixtures’ advantages stem appear to be lowered toxicity of the mixture to normal cells and a more efficient blood delivery of orally-administered catechins to a tumor sight (Morre et al, 2003).
Tea drinking has been associated with decreased occurrence of cancer and heart disease. One potential mechanism for these findings is the strong antioxidant effect of tea polyphenols. In one randomized study it was observed that plasma and urinary levels of catechins rose significantly in the green tea group compared with drinkers of black tea or water, only (Hakim et al, 2003). Green tea is one of the most practical cancer preventives as has been shown in various in vitro and in vivo experiments, along with epidemiological studies. In Hangzhou, China 254 patients recruited during 1999-2000 with histopahtologically confirmed epithelial ovarian cancer were followed up for a minimum of three years. Close relatives were also traced. The variables examined included their survival time and the frequency and quantity of tea consumed post-diagnosis. The survival experience was different between tea drinkers and nondrinkers. 78 % of the tea-drinkers survived to the time of the interview compared to 48% of the non-tea-drinkers. This equates to brewing one batch or more of green tea per day of approximately 2 g of dried tea leaves per batch (Zhang et al; November, 2004). Both increased dosages and tea delivered in supplemental form seem to increase its effects. In a separate study in Saitama Prefecture, Japan, people found consuming over 10 cups of green tea a day suffered almost no cardiovascular disease. These data suggest that green tea has preventive effects on both chronic inflammatory diseases and lifestyle-related diseases (including cardiovascular disease and cancer), resulting in prolongation of life span (Sueoka et al, 2001). Green and black tea polyphenols have been extensively studied as cancer chemopreventive agents. Many in vitro experiments have supported their strong antioxidant activity. Flavanol absorption was enhanced when tea polyphenols were administered as a green tea supplement in capsule form and led to a small, but significant increase in plasma antioxidant activity compared with just teas themselves. These observations suggest that green tea extract supplements retain the beneficial effect of green tea…without the side effects of caffeine associated with the green and black tea beverages (Henning et al, 2004).
Vitamins
It has been recognized for years that an adequate consumption of vitamins is vital in order to promote good general health. Two hundred twenty free-living, healthy women aged 60-91 years (median 63 years) were recruited by newspaper advertisement in Hanover, Germany and its environs. Subjects were randomly assigned to receive either a multivitamin/mineral or placebo capsule with identical appearance for six months containing 36 mg 36mg vitamin E, 150 mg Vitamin C, and 9 mg beta-carotene. A six-month supplementation with physiological doses of antioxidant vitamins improves the blood concentration of these nutrients even in relatively well-nourished elderly women or, as seen for Vitamin C, prevents reduction of serum concentrations (Wolters, Hermann, & Hahn, 2004). Military personnel and other subjects living under conditions comparable to military recruits were analyzed in a series of tests. The conclusion of those findings was that Vitamin C supplementation clearly reduced the incidence of respiratory disease (Hemila, 2004).
But, perhaps arguably greater results, surprisingly, have also been collated regarding the proper administration of vitamins to combat even more insidious diseases. In 1980 an investigation of 85,118 female nurses who completed a detailed questionnaire commenced that assessed their consumption of Vitamin C and other nutrients and was followed up for 16 years. It was concluded in that study that users of Vitamin C supplements apparently are at lower risk for coronary heart disease (Osganian, 2003). Vitamin C-enhanced effects of Vitamin E in supplement form was studied and in relation to mortality risk in 11,178 persons aged 67-105. All participated in the Established Populations for Epidemiologic Studies of the Elderly in 1984-1993. Use of Vitamin E reduced the risk of all-cause mortality and the risk of coronary disease mortality (Losonczy et al, 1996). Older persons are at risk of both poor nutrition and increased oxidative stress. Plasma ascorbate concentrations fall with increasing age, and concentrations of other antioxidants may also be reduced. The test results indicated that low blood Vitamin C concentrations in the older British population are strongly predictive of mortality. In other words, in general terms the higher the ascorbate concentrations the lower the cardiovascular disease mortality and all-cause mortality. (Fletcher et al, 2003). Vitamin C has been shown to have important roles in cell performance and vascular function. In a study of 15 stroke victims it was found that their systems had lower plasma levels of Vitamin C than did non-stroke patients (Sanchez-Moreno et al, 2004.
In a recent study it was understood that ingestion of slow release Vitamin C formulation was associated with protective effects to DNA. Overal,l the slow release tablets of Vitamin C formulation had a more pronounced and sustained protective effect on base damage compared with the plain release tablets. In conclusion, long-term Vitamin C supplementation at a dosage of 500mg together with Vitamin E of 1182 mg, decreased the steady-state level of oxidative DNA damage in mononuclear blood cells of smokers. (Moller, 2004). Another study demonstrated that gammaT and mixed Vitamin E forms induce death of prostate cancer cells (Jiang et al, 2004).
The Honolulu-Asia Aging Study is a longitudinal study of Japanese-American men living in Hawaii. Data for this study came from a study of 3,385 men, age 71-93 years, whose use of Vitamin E and C supplements had been ascertained previously. A significant protective effect was found for vascular dementia in men who had reported taking both Vitamin E and C supplements in 1988. They were also protected against mixed/other dementia. These results suggest that Vitamin E and C supplements may protect against vascular dementia and may improve cognitive function in late life (Masaki; March, 2000). Use of Vitamin E and Vitamin C supplements in combination is associated with reduced prevalence and incidence of Alzheimer’s Disease (AD). A trend toward lower AD risk was also evident in users of Vitamin E and multivitamins containing vitamin C, but we saw no evidence of a protective effect with use of Vitamin E or Vitamin C supplements alone, with multivitamins alone, or with vitamin B-complex supplements (Zandi et al, 2004).
Vitamins and Minerals
While the effects of individual vitamins and combinations of vitamins have been studied in isolation, when vitamins are taken in conjunction with minerals, the effectiveness of both seems to increase. A multivitamin and mineral supplement reduced the incidence of participant-reported infection and related absenteeism in a sample of participants with type 2 diabetes mellitus and a high prevalence of subclinical micronutrient deficiency (Barringer, 2003). The relationship of serum Vitamin E and Vitamin C with Selenium and Beta-carotene to asthma was investigated among 7,505 youth (4-16 years old) in the Third National Health and Nutrition Examination Survey. An increase in Vitamin C, Selenium and Beta-carotene, was associated with a 10-20% reduction in asthma prevalence. (Rubin, Navon, & Cassano, 2004)
Vitamins and Carotenoids
As observed in the Rubin/Navon/Cassaono study, the interplay of vitamins and minerals with carotenoids seems to enhance their effectiveness as antioxidants, collectively. Both in vivo and in vitro cell protection is demonstrated for Beta-carotene in the presence of Vitamin E and Vitamin C. A synergistic protection is observed (between Vitamins E and C)--compared either of these anti-oxidants, individually. (Bohm et al, 1998).
Data from a cross-sectional survey of 746 non-institutionalized, Boston-area elderly individuals (aged > or = 60 years old) were analyzed to assess the relation between antioxidant nutrient intake and plasma antioxidant status. These results provide epidemiologic evidence that increasing intake of either Vitamin C, Vitamin E, or carotenoids is associated with greater plasma concentrations of one or both of the other antioxidant vitamins (Jacques et al, 1995).
Finally, it is important to recognize that the different delivery sources of vitamins and carotenoids are important in order to maximize efficiency. Dietary intervention with tomato products increased Lycopene concentration both in plasma and lymphocytes. Vitamin C increased approximately 35% in plasma and by approximately 230% in lymphocytes. These results suggest that tomato products are not only good sources of Lycopene, but also sources of bioavailable Vitamin C. A regular intake of small amounts of tomato products can increase cell protection from DNA damage induced by oxidant species (Riso et al, 2004). Recently, some wonder fruits have been discovered even richer in the aforesaid combinations of vitamins, minerals and carotenoids than our more-familiar American produce. These include the Siberian Pineapple (Hippophae rhamnoides), Gâc (Momordica cochinchinensis) and Cili fruits (Rosa roxburghii), and Chinese Lycium (Lycium barbatum) (Soundconcepts, 2005)
And don’t forget minerals. Without many of the rare trace elements with their catalytic properties and the structural properties of the macro minerals, vitamins and all the rest are much less effective at doing their respective jobs. In fact the ability to absorb, uptake and assimilate most nutrients is governed by the presence of certain trace elements in mineral complexes.
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© March 2007, R. Joseph Collet JD