Soy Isoflavones Benefit Breast Health

[Dave]

It's been known for some time that soy isoflavones have a
great benefit on breast health for those with malignant
tumors. However, this updated research now shows that
isoflavones may extend a benefit for women beyond malignant
tumors . . . the new study suggests a lower incidence of
benign breast cysts as well.

The study, published in the December 2007 issue of "Cancer
Epidemiology Biomarkers & Prevention," adds to an ever-growing
body of studies linking these phytochemicals to improved
breast health. Dr. Johanna Lampe and her team from the Fred
Hutchinson Cancer Research Center (Seattle) writes that
benefits may also extend to fibrocystic breast conditions, a
very common and benign condition characterised by lumpiness
and discomfort in one or both breasts.

Population studies from heavy soy use countries have shown
that a diet rich in soy is associated with fewer cases of
breast cancer. This has been linked to the presence of soy
isoflavones. In this case, the study was conducted in China
where the researchers recruited 196 women with breast cancer,
304 women with benign breast condition, and 1,002 healthy,
breast cancer-free age-matched controls from the Shanghai
region. The benign conditions were further classified as
proliferative (173 women) or nonproliferative (131 women).

Increased plasma levels of the isoflavones were associated
with a reduced risk of both types of benign conditions, in
addition to breast cancer. Indeed, the highest plasma levels
(more than 76.95 nanograms per millilitre) were 74 per cent
less likely to have breast cancer, and 60 per cent less likely
to have benign conditions relative to women with the lowest
average levels (less than 9.42 ng/mL).

"Isoflavone exposure was inversely associated with fibrocystic
breast conditions and breast cancer, and the results suggest
that effects on cancer risk occur early in carcinogenesis,"
wrote Lampe.

Dave

Full text article above extracted from
http://shamvswham.blogspot.com/

[trigonomet]

What I will add is that soy isoflavones both slow the
breakdown of activated vitamin D and help upregulate the VDR
which in turn will help maintain cellular differentiation. The
following abstracts relate to the prostate but in principle
should apply to breast health and disease as well.

1: Postepy Hig Med Dosw (Online). 2007;61:253-60.

[The influence of isoflavonoids on the antitumor activity
of vitamin
D3]

[Article in Polish]

Wietrzyk J.

Laboratorium Doswiadczalnej Terapii Przeciwnowotworowej
Instytutu Immunologii i Terapii Doswiadczalnej PAN im. L.
Hirszfelda we Wroclawiu, Poland. wietrzyk@iitd.pan.wroc.pl

Isoflavonoids exert a regulatory function on the expression of
cytochrome P450 enzymes and also up-regulate the vitamin D(3)
receptor (VDR) on cancer cells, which increase their
sensitivity to 1,25-dihydroxyvitamin D(3) , the hormonally
active form of vitamin D(3) . Isoflavonoids are also able to
raise the serum level of the active form of vitamin D(3) due
to their inhibitory activity on CYP24, the enzyme involved in
the degradation of 1,25-dihydroxyvitamin D(3) and its
precursor 25-OH-D(3) to inactive compounds. Another enzyme,
CYP27B1, involved in the synthesis of 1,25-dihydroxyvitamin
D(3) , is stimulated by isoflavonoids, and this may result in
a similar effect of increasing in the serum level of
1,25-dihydroxyvitamin D3. CYP27B1 and CYP24 were found in
kidneys (the main location of 1,25-(OH) (2)D(3) synthesis) and
also in brain cells, osteoclasts, keratinocytes, macrophages,
intestine epithelial cells, and in some cancer cells. The
expression of VDR was detected not only in the cells primarily
targeted by 1,25-dihydroxyvitamin D3, but also in epithelial
and mesenchymal cells. Therefore, combined treatment with
isoflavonoids and 1,25-dihydroxyvitamin D3 might be effective
in both cancer prevention and treatment.

PMID: 17507873

1: J Nutr. 2007 Jan;137(1 Suppl):205S-210S.

Calcitriol and genistein actions to inhibit the
prostaglandin pathway: potential combination therapy to
treat prostate cancer.

Swami S, Krishnan AV, Moreno J, Bhattacharyya RB, Peehl DM,
Feldman D.

Department of Medicine, Division of Endocrinology, Stanford
University School of Medicine, Stanford, CA 94305, USA.

We present an overview of the prostaglandin (PG) pathway as a
novel target for the treatment of prostate cancer (PCa) using
a combination of calcitriol and genistein, both of which have
known antiproliferative properties. Calcitriol inhibits the PG
pathway in PCa cells in 3 separate ways: by decreasing
cyclooxygenase-2 (COX-2) expression, stimulating
15-hydroxyprostaglandin dehydrogenase (15-PGDH) expression,
and decreasing EP (PGE2) and FP (PGF(2alpha)) receptors. These
actions of calcitriol result in reduced levels of biologically
active PGE2, leading ultimately to growth inhibition of the
PCa cells. We also demonstrate the advantages of using
calcitriol in combination with genistein for the treatment of
PCa. Genistein, a major component of soy, is a potent
inhibitor of the activity of CYP24, the enzyme that initiates
the degradation of calcitriol. This leads to increased
half-life of bioactive calcitriol, thereby enhancing all of
calcitriol's actions including those on the PG pathway. In
addition to inhibiting CYP24 enzyme activity, genistein has
its own independent actions on the PG pathway in PCa cells.
Like calcitriol it inhibits COX-2 expression and activity,
leading to decreased synthesis of PGE2. It also inhibits the
EP and FP receptors, thereby reducing the biological function
of PGE2. Thus, the combination of calcitriol and genistein
acts additively to inhibit the PG pathway. Both calcitriol and
genistein are relatively safe and have little toxicity
associated with their intake. We postulate that the
combination of calcitriol and genistein is an attractive
therapeutic option for the treatment of PCa.

PMID: 17182827

Endocrinol. 2006 Nov;191(2):387-98.

Phytoestrogens regulate transcription and translation of
vitamin D receptor in colon cancer cells.

Gilad LA, Tirosh O, Schwartz B.

Faculty of Agricultural, Food and Environmental Quality
Sciences, Institute of Biochemistry, Food Science and
Nutrition, The Hebrew University of Jerusalem, Rehovot
76100, Israel.

The present study assesses the effects of two isoflavones,
genistein and glycitein, and equol - a product of intestinal
bacterial metabolism of dietary isoflavones, on vitamin D
receptor (VDR) expression in an intestinal HT29 cell line.
Genistein and glycitein significantly upregulated the VDR
transcription and translation in HT29 cells. The effect of
equol was less pronounced. Treating HT29 cells transfected
with a vector containing the VDR promoter next to a luciferase
reporter with genistein or glycitein resulted in significant
upregulation of VDR promoter activity, in a manner similar to
that induced by 17beta-estradiol (E2). Again, the effect of
equol was less pronounced. VDR luciferase promoter activity
was upregulated most by genistein, then by glycitein and least
by equol when the VDR promoter was cotransfected with estrogen
receptor beta. Reporter gene and chromatin immunoprecipitation
(ChIP) assays demonstrated that E2 upregulates AP-1 and Sp-1
sites present on the VDR gene. In contrast, the same assays
demonstrated that the Sp-1, but not AP-1, site is induced by
the phytoestrogens. Similar to E2, genistein, glycitein and
the isoflavonoid metabolite equol induced higher
concentrations of intracellular free calcium, an event that
could provide the upstream mechanism(s) induced by E2 and
phytoestrogens that initiates the signaling cascade which
results in the activation of extracellular signal-regulated
kinase (ERK) signaling pathways and modulation of Sp-1 sites
of the VDR gene, and culminates in enhanced VDR expression.

PMID: 17088408

[Dave]

On Dec 18, 11:00 am, trigonometry1...@gmail.com wrote:
> What I will add is that soy isoflavones both slow the
> breakdown of activated vitamin D and help upregulate the VDR
> which in turn will help maintain cellular differentiation.
> The following abstracts relate to the prostate but in
> principle should apply to breast health and disease as well.

Thanks Trig. Good stuff. With regards to the prostate, men
interested in child-bearing need to watch the amount of soy
isoflavones in their diet because it has been shown, in some
studies, to decrease sperm count. But that's not likely to be
an issue for older guys who are having prostate issues and who
are past an interest in kids!

Dave

[trigonomet]

It also suggests to me, simply dialing up one's vitamin D
intake instead of the soy flavone maybe the best way to go.
When I speak of dialing up intake. I am thinking in terms
of 5000 or even 10 000 IU daily doses of D3 not of 800
instead of 400 IU. Granted a blood test of two maybe
warrented in this context. And then one should know what
they want as an optimal serum level of 25 OH vitamin D, so
some ill informed GP wouldn't snow them some assuring
falsehood or sneering put down.