Gender, antioxidants and cancer

[Guest guest]

Hi All,

The below and the article referred to in the same issue of Br. J. Nutr. that is

pdf-available seem to suggest that, if you get a normal healthy diet, than

taking

them as supplements is a waste of time and money. Sex differences in cancer

incidence and effect of antioxidant levels are variable, it seems.

Gender, antioxidants and cancer

Hi All,

The below and the article referred to in the same issue of Br. J. Nutr. that is

pdf-available seem to suggest that, if you get a normal healthy diet, than

taling

them as supplements is a waste of time and money. Sex differences in cancer

incidence and effect of antioxidant levels are variable, it seems.

Jane V. Higdon and Balz Frei

British Journal of Nutrition (2005), 94, 139–140 Invited commentary

Is there a gender difference in the effect of antioxidants on cancer risk?

Prior to the publication of the SUpplementation en VItamines et

Mine´raux AntioXydants (SU.VI.MAX) study results last year

(Hercberg et al. 2004), the findings of most randomized con-trolled

trials did not support the hypothesis that antioxidant nutri-ent

supplementation reduces total cancer incidence or mortality

(reviewed in Higdon & Frei, 2005). The only exception was a

trial conducted in a nutritionally deficient population in China

(Blot et al. 1993). Evidence from randomized controlled trials

for a cancer protective effect of antioxidant supplements in nutri-tionally

sufficient populations has been limited to prostate cancer.

Supplementation of Finnish smokers with 50 mg a-tocopherol/d

for 6 years was associated with a 32 % decrease in prostate

cancer incidence (Heinonen et al. 1998). In a US study, sup-plementation

with 200 mg Se/d for 7 years was associated with

a 51 % decrease in prostate cancer incidence, but the protective

effect was limited to those with lower plasma Se levels at baseline

(Duffield-Lillico et al. 2003). Similarly, supplementation of

American physicians with b-carotene (50 mg on alternate days)

for 12 years was associated with a 32 % reduction in prostate

cancer incidence only in those with lower baseline plasma b-car-otene

concentrations (Cook et al. 1999).

In the SU.VI.MAX study, daily supplementation with a mixture

of antioxidant nutrients (120 mg vitamin C, 30 mg vitamin E,

6mg b-carotene, 100 mg Se and 20 mg Zn) for more than 7

years was associated with a significant 31 % reduction in total

cancer incidence in men but not women (Hercberg et al. 2004).

However, the protective effect in men did not appear to be related

to a substantial decrease in prostate cancer incidence. In the pre-sent

issue of the British Journal of Nutrition, additional analysis

of data from the SU.VI.MAX study provides evidence of an

inverse association between baseline serum antioxidant concen-trations

and total cancer incidence in men but not women,

suggesting that the lack of effect of antioxidant supplementation

on cancer risk in women cannot be entirely explained by higher

baseline antioxidant levels or higher antioxidant nutrient con-sumption

in women (Galan et al. 2005).

Differences in relationships between antioxidant status and the

risk for gender-specific cancers may have contributed to the

observed gender differences in total cancer risk. Prospective

studies provide some evidence that low antioxidant status in

men is associated with increased prostate cancer risk. Three pro-spective

studies found that low Se status was associated with sub-stantially

increased prostate cancer risk, and another found a

similar relationship in current and former smokers (reviewed

in Waters et al. 2004). Serum vitamin E concentrations were

inversely associated with prostate cancer risk in two cohorts of

smokers (Eichholzer et al. 1996; Weinstein et al. 2005), and

plasma g-tocopherol but not a-tocopherol concentrations were

inversely associated with prostate cancer risk in a prospective

study of American men (Helzlsouer et al. 2000). An interaction

between Se and vitamin E status was suggested by the finding

that higher levels of Se and a-tocopherol were associated with

a significant decrease in prostate cancer risk only when g-toco-pherol

levels were also high. In contrast, prospective studies

have not generally found plasma vitamin C, vitamin E or Se con-centrations

to be associated with breast cancer risk in women

(Waters et al. 2004; Higdon & Frei, 2005). Plasma b-carotene

concentrations were inversely associated with breast cancer risk

in several prospective studies. However, each study found that

serum concentrations of other carotenoids, such as lycopene or

a-carotene, were also inversely related to breast cancer risk,

suggesting that increasing consumption of a number of dietary

carotenoids, instead of b-carotene in isolation, may offer some

protection from breast cancer (Higdon & Frei, 2005; Tamimi

et al. 2005).

Even for cancers that affect both men and women, there may be

gender differences with regard to the influence of antioxidant

nutrient status. A number of prospective studies suggest that

low plasma Se and vitamin C concentrations are associated with

increased total cancer risk in men but not women. Of six prospec-tive

studies that examined the relationship between serum Se con-centrations

and total cancer incidence, four found a significant

inverse association in men, but none found a significant associ-ation

in women (reviewed in Waters et al. 2004). All three pro-spective

studies that examined the relationship between plasma

vitamin C concentrations and total cancer risk in men found a sig-nificant

inverse relationship (Eichholzer et al. 1996; Loria et al.

2000; Khaw et al. 2001), but neither of the two studies that

also examined plasma vitamin C concentrations in women

found these concentrations to be related to cancer risk (Loria

et al. 2000; Khaw et al. 2001). Although plasma vitamin C con-centrations

were generally higher in women than men, even

women with very low plasma vitamin C concentrations were

not at increased risk for cancer (Loria et al. 2000; Simon et al.

2001).

DNA contains reactive groups in its bases that are susceptible

to attack by reactive oxygen and nitrogen species. It has been pro-posed

that oxidative damage to DNA occurs in vivo at a rate of

10^4 oxidative hits per cell per d (Woodall & Ames, 1997). At

least fourteen clinical trials have examined the effect of some

type of antioxidant supplementation on oxidized pyrimidines

using the modified Comet assay, which measures strand breaks

induced by treatment of DNA with endonuclease III. Interest-ingly,

six of the seven trials that found antioxidant supplemen-tation

to be beneficial in lowering oxidized pyrimidine levels

were conducted in men only, while only one of the seven trials

that found antioxidant supplementation to be of no benefit was

conducted exclusively in men (Moller & Loft, 2004). Although

this observation may reflect a shortage of female participants, it

highlights the possibility of a gender difference with regard to

the effect of antioxidant supplementation on oxidative DNA

damage in vivo.

The study of antioxidant nutrients and carcinogenesis is com-plicated

by the fact that different types of cancer vary in their

aetiology and pathology. Moreover, antioxidant nutrients, such

as vitamin C, vitamin E, carotenoids and Se, vary considerably

in their chemistry, metabolism and biological activities, not all

of which are related to their ability to act directly as antioxidants.

In order to make antioxidant nutrient recommendations based on

chronic disease prevention, it is important to understand the

extent to which gender influences relationships between antioxi-dant

status and disease risk. Future prospective and supplemen-tation

studies should be designed with adequate power to detect

gender differences in the effects of antioxidant nutrients on

specific types of cancer and other cancer-related endpoints. Inves-tigators

should report the results of gender-specific analyses even

when no significant differences are found. In addition to examin-ing

individual and synergistic effects of antioxidant nutrients on

different types of cancer, mechanistic studies should also address

potential interactions with gender-related factors.

Galan P, c¸on S, Favier A, et al. (2005)

Antioxidant status and risk of cancer in the SU.VI.MAX study: is the effect of

supplementation dependent on baseline levels?

Br J Nutr 94, 125–132.

Al Pater, PhD; email: old542000@...

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