Re: High Levels of Vitamin E Fractions Linked to Reduced Risk of Prostate Cancer

[Guest guest]

Hi Al:

Thanks for that heads up. That is a pretty interesting result. If

the difference for tertiles is that big, how big would the difference

be for quintiles? Presumably larger.

The study abstract can be found at PMID 15741576:

" Serum alpha-tocopherol and gamma-tocopherol in relation to prostate

cancer risk in a prospective study.

Weinstein SJ, ME, Pietinen P, King I, Tan C, PR,

Virtamo J, Albanes D.

Division of Cancer Epidemiology and Genetics, National Cancer

Institute, NIH, DHHS, Bethesda, MD 20892, USA.

The Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study

demonstrated a 32% reduction in prostate cancer incidence in response

to daily alpha-tocopherol supplementation. We examined baseline serum

concentrations of alpha-tocopherol and gamma-tocopherol to compare

their respective associations with prostate cancer risk. From the

ATBC Study cohort of 29 133 Finnish men, 50-69 years old, we randomly

selected 100 incident prostate cancer case patients and matched 200

control subjects. Odds ratios and 95% confidence intervals (CIs) were

estimated for the serum tocopherols (measured by high-performance

liquid chromatography) using logistic regression models. All P values

were two-sided. Odds ratios for the highest versus the lowest

tertiles were 0.49 (95% CI = 0.24 to 1.01, P(trend) = .05) for alpha-

tocopherol and 0.57 (95% CI = 0.31 to 1.06, P(trend) = .08) for gamma-

tocopherol. Further analyses indicated that the association of high

serum tocopherols with low prostate cancer risk was stronger in the

alpha-tocopherol-supplemented group than in those not receiving alpha-

tocopherol. Participants with higher circulating concentrations of

the major vitamin E fractions, alpha-tocopherol and gamma-tocopherol,

had similarly lower prostate cancer risk. "

Rodney.

--- In , " Al Young " <acyoung@r...>

wrote:

>

>

> NEW YORK (Reuters Health) Mar 02 - High circulating levels of the

major

> vitamin E fractions, alpha- and gamma-tocopherol, seem to cut the

risk of

> prostate cancer by about 50% each, according to a report in the

Journal of

> the National Cancer Institute (NCI) for March 2.

>

> The findings are based on a case-control analysis of 100 prostate

cancer

> patients and 200 controls randomly selected from the Alpha-

Tocopherol,

> Beta-Carotene Cancer Prevention (ATBC) Study, which included nearly

30,000

> Finnish men.

>

> Men in the highest tertile for alpha-tocopherol levels at baseline

were 51%

> less likely to develop prostate cancer than those in the lowest

tertile, Dr.

> Demetrius Albanes, from the NCI in Bethesda, land, and

colleagues note.

> Similarly, the highest tertile for gamma-tocopherol levels cut the

risk by

> 43% compared with the lowest tertile.

>

> Further analysis showed that the link between high tocopherol

levels and low

> cancer risk was stronger among subjects using alpha-tocopherol

supplements

> than among non-users, the investigators point out.

>

> " The antioxidant activity of vitamin E may be particularly

important to the

> observed associations because oxidative stress has been implicated

in

> prostate carcinogenesis, " the authors note. However, alpha-

tocopherol has

> other non-antioxidant properties, such as enhancement of the immune

> response, which may also play a role in the benefits seen, they add.

>

> J Natl Cancer Inst 2005;97:396-399.

[Guest guest]

Hi All,

In the post:

http://lists.calorierestriction.org/cgi-bin/wa?A2=ind0503 & L=crsociety & P=R22070 & X\

=0A0A1518BF43099461 & Y=old542000

vitamin E subtypes with respect to prostate cancer risks were discussed by

Rae.

The below may be pertinent.

There is a not in Medline pdf-avaialble article that appeared to report that the

combination of vitamin E succinate, selenium and lycopene is effective in

anti-prostate cancer regimens. The main focus appears to be on the pdf-avaiable

paper:

Venkateswaran V, Fleshner NE, Sugar LM, Klotz LH.

Antioxidants block prostate cancer in lady transgenic mice.

Cancer Res. 2004 Aug 15;64(16):5891-6.

PMID: 15313934

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=pubmed & dopt=Abstra\

ct & list_uids=15313934 & query_hl=22

The report not in Medline is:

Vitamin E and Prostate Cancer: Is Vitamin E Succinate a Superior Chemopreventive

Agent?

By: Basu, Arpita; Imrhan, Victorine.

Nutrition Reviews, Jul2005, Vol. 63 Issue 7, p247, 9p; DOI:

10.1301/nr.2005.jul.247-251; (AN 17549038)

PDF Full Text (142K)

Its abstract is:

There is convincing evidence that vitamin E succinate significantly reduces

human

prostate cancer growth in experimental models compared with ?-tocopherol or

tocopheryl acetate. Its intact delivery to cancer cells is questionable when

administered orally; however, a study in transgenic mice showed a synergistic

inhibitory effect of dietary vitamin E succinate, selenium, and lycopene on

prostate

cancer incidence. Clinical trials have yet to confirm this effect.

In the text are the below results that are reviewed. It seemed that the levels

of

anti-oxidants used in the animal studies was exceedingly high, compared to

normal

levels provided as human recommended daily allowances.

How effective might the combination of anti-oxidants be if it contains all

vitamin E

forms that are present in the normal ratio found in the human diet and were used

in

such human studies?

.... VITAMIN E AND PROSTATE CANCER: ANIMAL STUDIES

Male Lady transgenic mice spontaneously develop local-

ized prostate cancer and metastasis,which mimics the

progression of human prostate cancer in many respects.

In 2004,Venkateswaran et al.5 showed a signi & #64257;cant

reduction in prostate cancer incidence in male Lady

transgenic mice fed a standard-fat (25%kcal from fat)or

a high-fat (40%kcal from fat)diet with antioxidant

supplementation compared with the controls.The anti-

oxidant supplement included a daily dietary dose of a

combination of 800 IU of VES,200 µg of seleno-dl-

methionine,and 50 mg of lycopene.This was the & #64257;rst in

vivo study showing the inhibitory effects of VES,in

combination with selenium and lycopene,on the inci-

dence of prostate cancer.

In this study,5 transgenic animals were divided into

four main groups:group 1 animals were fed a standard

(25%kcal from fat)diet;group 2 animals were fed a

standard diet with antioxidant supplementation;group 3

animals were fed a high-fat (40%kcal from fat)diet;and

group 4 animals were fed a high-fat diet with antioxidant

supplementation.At the end of 28 to 32 weeks,the

prostate tumor incidence was approximately 11%in

group 2 and approximately 16%in group 4.This was a

striking reduction compared with the controls,which had

a tumor incidence of about 74%in group 1 and 100%in

group 3.These investigators also measured the protein

expression of cytoplasmic p27 and proliferating cell

nuclear antigen (PCNA)in prostate tissue sections using

immunohistochemistry.The tumor suppressor gene p27

is an important regulator of cell cycle progression from

the G 1 to the S phase,and works by binding and inhib-

iting the cyclin E-/cyclin-dependent kinase 2 complex.

PCNA serves as a critical marker for increased prolifer-

ation of DNA polymerase-driven DNA synthesis.5 Thus,

both p27 and PCNA expression serve to elucidate pos-

sible mechanisms by which antioxidant supplementation

could lead to a reduction in the incidence of prostate

cancer.Venkateswaran et al.5 reported that PCNA ex-

pression was markedly reduced in prostate sections from

both of the antioxidant-supplemented groups (groups 2

and 4)compared with the untreated controls,while p27

scoring was increased in the antioxidant-treated animals,

which is consistent with a reduction in the incidence of

prostate tumors.

Fleshner et al.6 previously reported an in vivo study

using dietary supplementation of dl-alpha tocopheryl acetate

on the growth of human prostate LNCaP xenografts in

nude mice.The human prostate LNCaP cell line (from

lymph node metastasis)expresses androgen receptors

and also produces prostate-speci & #64257;c antigen (PSA).Once

implanted into nude mice,it undergoes local growth

without metastases,making it well suited to studying

tumor growth rates.In this study,6 following subcutane-

ous inoculation of the LNCaP cells,animals were ran-

domly assigned to four groups:group 1 animals were fed

a diet with 40%kcal from fat;group 2 animals were fed

a diet with 40%kcal from fat supplemented with dl-alpha

tocopheryl acetate;group 3 animals were fed a diet with

20%kcal from fat;and group 4 animals were fed a diet

with 20%kcal from fat supplemented with dl-alpha tocoph-

eryl acetate.The level of dl-alpha tocopheryl acetate in-

cluded in the diets of groups 2 and 4 was 11.4 IU/kg/d.

This 15-week study revealed a signi & #64257;cant reduction in

LNCaP tumor size in group 2 compared with group 1.

However,there was no signi & #64257;cant difference between

group 3 and group 4.Animals in group 1 had the highest

tumor growth,and 50%of the animals in this group

attained the target tumor size (0.1 cm 3 )in 6 weeks.

Tumor growth was signi & #64257;cantly slower in group 2 ani-

mals and in the animals fed low-fat diets (groups 3 and

4)with or without vitamin E supplementation.

Both Venkateswaran et al.5 and Fleshner et al.6

reported in vivo data emphasizing the fact that a high-fat

diet promotes the incidence and growth of prostate can-

cer,and that vitamin E alone (as dl-alpha tocopheryl acetate)

or in combination with other antioxidants (as VES plus

selenium plus lycopene)ameliorates this high-fat-asso-

ciated prostate cancer effect.Interestingly,Venkateswa-

ranetal.5 reported a marked decrease in prostate cancer

incidence even in the group fed the standard diet (25%

kcal from fat)with antioxidant supplementation com-

pared with the corresponding untreated controls,whereas

Fleshner et al.6 showed no difference between the groups

fed 20%kcal from fat,with or without vitamin E sup-

plementation.This difference could be attributed to a

different vitamin E derivative,a higher amount of vita-

min E,or the longer period of vitamin E supplementation

in the study reported by Venkateswaran et al.5 compared

with Fleshner et al.6 (800 IU of VES/d for 32 weeks

versus11.4IUofdl-alpha tocopheryl acetate/kg/d for 15

weeks,respectively).

.... vitamin E (50 IU of

dl-alpha tocopheryl acetate)was administered by the well-

known Alpha-Tocopherol,Beta-Carotene (ATBC)cancer

study,which resulted in a one-third reduction in prostate

cancer incidence and a 41%reduction in prostate cancer

mortality among Finnish male smokers.17 While the

ATBC study showed a protective effect of vitamin E

supplementation on prostate cancer entirely among

smokers,the US Health Professional Study (USHPS)

revealed a slightly reduced risk among smokers but none

among non-smokers taking regular vitamin E supple-

ments (50,200,400,or 800 IU).18 Thus,studies in

human subjects have been inconsistent in establishing

the chemopreventive action of vitamin E,either alone or

in combination with other antioxidants,on prostate can-

cer incidence in the non-smoking,healthy male popula-

tion.The choice of the form of vitamin E,its dose,and

duration may be determining factors in relation to its

chemopreventive action. ...

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

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