Robert A. Jacob

The integrated antioxidant system

Abstract The diversity and depth of the bodys antioxidant protection system is reviewed. Components of both endogenous and exogenous origins contribute protection, and new data suggests that some components interact to spare or replace each other. Evidence from both animal and human studies shows that glutathione and vitamin C can act in concert to alleviate a variety of oxidant stresses. Results from in vitro and animal studies indicate that vitamin C regenerates tocopherol in the lipid phase, but this interaction has not yet been shown to be important to human nutrition and metabolism. Newer evidence suggests that β-carotene and tocopherol may act synergistically against lipid peroxidation, and that polyphenols, such as flavonoids provide antioxidant protection which is enhanced by vitamin C. The diverse roles of iron and copper in redox biochemistry is illustrated by their incorporation in protective metalloenzymes and by some proposed interactions with vitamins. The emerging picture of synergisms and interactions suggests that antioxidant protection may be more flexible and efficient than indicated by studies of single nutrient effects. The apparent versatility of the oxidant defense system implys that it is capable of taking advantage of diverse antioxidants provided by the diet, as well as excesses of a particular antioxidant nutrient.

Plasma Antioxidant Capacity Changes Following a Meal as a Measure of the Ability of a Food to Alter In Vivo Antioxidant Status

Objective: Determine 1) if consumption of a meal of different fruits or berries increases plasma hydrophilic (H-) or lipophilic (L-) antioxidant capacity (AOC) measured as Oxygen Radical Absorbance Capacity (ORACFL); 2) if including macronutrients in the meal alters postprandial changes in AOC; and 3) if preliminary recommendations can be developed for antioxidant intake. Methods: Changes in plasma AOC following consumption of a single meal of berries/fruits (blueberry, dried plum, dried plum juice, grape, cherry, kiwifruit and strawberry) were studied in 5 clinical trials with 6–10 subjects per experiment. In two studies with blueberry or grape, additional macronutrients (carbohydrate, fat, protein) were included in the control and treatment meals. Blood samples collected before and after the meal were analyzed for AOC. Results: Consumption of dried plums or dried plum juice did not alter either the H- or L-AOC area under the curve (AUC). Consumption of blueberry in 2 studies and of mixed grape powder [12.5 (Study #1), 39.9 (Study #4) and 8.6 (Study #5) mmole Trolox Equivalents (TE) AOC, respectively] increased hydrophilic AOC AUC. L-AOC increased following a meal of blueberry containing 12.5 mmole TE AOC (Study #1). Consumption of 280 g of cherries (4.5 mmol TE AOC) increased plasma L-AOC but not H-AOC. The AOC in the control groups in which additional macronutrients (Studies #4 and #5) were added decreased from the postprandial baseline AOC measurement. Conclusion: We have demonstrated that consumption of certain berries and fruits such as blueberries, mixed grape and kiwifruit, was associated with increased plasma AOC in the postprandial state and consumption of an energy source of macronutrients containing no antioxidants was associated with a decline in plasma AOC. However, without further long term clinical studies, one cannot necessarily translate increased plasma AOC into a potential decreased risk of chronic degenerative disease. Preliminary estimates of antioxidant needs based upon energy intake were developed. Consumption of high antioxidant foods with each meal is recommended in order to prevent periods of postprandial oxidative stress.

'Spontaneous' genetic damage in man: evaluation of interindividual variability, relationship among markers of damage, and influence of nutritional status.

The spontaneous frequency of genetic damage (normal background) and the possible relationship of this damage to nutritional variables in humans were investigated in 22 subjects using several indices of genetic damage. The subjects were chosen, out of 122 initially analyzed, for being at the extremes of the highest and lowest values of one index of genetic damage, the frequency of micronucleated erythrocytes in peripheral blood. This index reflects chromosomal damage and loss in bone marrow erythropoietic cells. The assay for micronuclei is convenient but is restricted to splenectomized individuals because the human spleen removes micronucleated cells. The initial 122 subjects were splenectomized, but all were normal and healthy at the time of this study and none had a previous history of neoplastic disease. Factors investigated were stability of micronucleus frequency as a function of time, correlations among multiple markers of genetic damage, and influence on damage indices of nutritional variables, including blood levels of folate, B12 and antioxidant vitamins. Among different individuals, the range of values was 10-fold or more in the erythrocyte micronucleus, glycophorin A, plasma ascorbate and urinary 8-hydroxydeoxyguanosine (oxo8dG) assays, was approximately 6-fold in the lymphocyte micronucleus assay, and was 2-fold in the lymphocyte sister chromatid exchange (SCE) assay. Red blood cell folate and plasma folate, B12 and alpha-tocopherol values varied by up to 10-fold among individuals. Micronucleus frequencies in erythrocytes and peripheral blood lymphocytes ranged from < 0.3 to 16.9/1000 in mature red blood cells, < 1 to 33/1000 in reticulocytes, and 2.5 to 15/1000 in binucleate lymphocytes. Frequencies of glycophorin A variant erythrocytes ranged from 5.6 to 77.3 x 10(6) N/0 cells and 3.2 to 16.2 x 10(6) N/N cells, and oxo8dG excretion varied from 32 to 397 pmol/kg/day. Although a wide range of values was observed in each genetic endpoint, the extreme values for various endpoints of genetic damage were not observed in the same individuals. The frequency of micronucleated erythrocytes varied over time within individuals and indicated that individuals with the highest levels of damage exhibit greater variability than those with lower levels. In some subjects, frequencies of micronucleated erythrocytes changed dramatically over an interval of 2-3 years: four subjects with initial micronucleated reticulocyte frequencies of 20.4, 5.9, 6.4 and 33/1000 changed to 2.5, 20.5, 18.5 and 12/1000, respectively. Among more than 150 individuals we have studied, including the 64 individuals studied by Everson et al. [(1988) J. Natl. Cancer Inst., 80, 525-529] and Smith et al. [(1990) Cancer Res., 50, 5049-5054], the seven individuals with the highest observed frequencies of micronucleated erythrocytes all had exceptionally low values of plasma folate, red cell folate, or plasma B12, suggesting that folate and B12 status are the major determinants of the types of damage that lead to spontaneous micronucleus formation in erythrocytic cells.

Influence of dietary fiber on trace element balance.

Five adult male volunteers were fed a diet containing (as percent of calories) 16% protein, 40% fat, and 44% carbohydrate, a diet similar to that consumed by many American males. Twenty-six grams of soft white wheat bran or corn bran were added to the daily bread, and the effects on zinc, iron, and copper balance were assessed during the last 12 days of each 30-day study period. The soft white wheat bran appeared to decrease retention of zinc in four subjects but not significantly so. Iron retention was similar in all three treatments. Copper balance was improved by addition of soft white wheat bran and to a lesser degree by corn bran. An apparent copper requirement of 1.28 mg/day for the volunteers was calculated by regression analysis.