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An Integrative Approach
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contents
FEATURES 34
Doctors going digital
Social media: friend or foe
36
Doctor’s Choice
38
Therapeutic and molecular evidence for the use of soy and red clover in breast cancer
44
An integrative approach to cancer in Canada
48
Natural Medicine in Europe
Searching for adequate methodology
38 DEPARTMENTS 9 10 12 26 30 50
Publisher’s Letter Editorial Board Bits and Bites
Industry and Research News
Product Profiles Clinic Profile
Integrative Health Institute
Post Scriptum
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publisher’s letter
A
ccording to Canadian cancer statis-
the Power of the Mind in Total Wellness: Mind/
tics, the number of new cancer cases
Body Medicine, Disease Management, and
will increase approximately 40 per
Treatment Alternatives. We are expecting a
cent for Canada. Integrative approach to
wonderful event on the body-mind connec-
treating and preventing cancer is now being
tion in naturopathic medicine and we are
actively explored. We interviewed Dr. Dugald
honoured to be media partner with the
Seely, executive director of the Ottawa
OAND. Everyone attending the event will
Integrative Cancer Centre to get some
have a chance to win a clinic makeover by
updates on the current state of cancer
Melissa David, top Toronto designer, known
research from the integrative perspective.
for her creative design and reno work pro-
In this issue, you can also find a European
duced for a number of HGTV shows.
perspective on the methodology currently used by the naturopathic profession. On
If you have not done it yet, please
page 48, president of the Association of
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Natural Medicine in Europe shares her
have access to exclusive content and
opinion on the effectiveness of the evi-
full-length reference material.
dence-based system and its application in the naturopathic medicine research. In our recently introduced section, we will be talking about social media and what you should know to use it professionally. September is a busy month for our industry with the Ontario Association of Naturopathic Doctors (OAND) holding their
Olivier Felicio
2015 Convention and Tradeshow: Maximizing
Publisher/Editor-in-Chief
SEPTEMBER 2015 • Volume 8 Issue 4 Founder Sanjiv Jagota
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feature
Therapeutic and molecular evidence for the use of soy and red clover in breast cancer By Rochelle Fernandes, MSc., ND (cand.) Peer-reviewed by Jason Boxtart (ND), Dugald Seely (ND, MSc), Jill Shainhouse (ND, FABNO), Denise Cheung (ND, cand)
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B
reast cancer is the most diagnosed cancer for
but they are converted to aglycones by fermentation
women over 20, and is the second leading cause
(Takagi 2015). Isoflavone absorption is increased in
of cancer deaths in women, second to lung cancer
fermented soy milk beverage (in which the isoflavones are
(CCDP, 2005-2010). It is thought that 24,000 Canadians
largely converted to aglycones) in comparison to regular
will be diagnosed with breast cancer this year and 5000
soy milk. Some consideration should be given to the fact
will die from it, as stated by the Canadian Breast Cancer
that 93 per cent of soy is now a genetically modified
Foundation (Coles 2013). Given these alarming statistics,
organism (GMO), and that it can cause allergic reactions
along with the side effects of conventional treatment (i.e.
in some, however, further studies are needed to assess the
fatigue, nausea, lymphedema, nerve damage and more),
full effects of this (Kelly, 2015). Until this can be done, it is
there has been an increasing interest in the use of natural
best to use non-GMO soy and to avoid usage if allergic.
supplements to prevent and treat cancer alone or alongside
It should be noted that people metabolize soy phy-
conventional options. This growing interest has included
toestrogens differently. Soy contains isoflavones, such as
the controversial but promising use of phytoestrogens
genistein and daidzein. It also contains glycitein, an
found in soy and red clover. The study of soy as a therapeutic
O-methylated isoflavone that makes up 5–10% of the total
ingredient has increased over the last decade. It has been
isoflavones in soy food (Song 1999). Equol is a gut bacterial
researched for its use in alleviating menopausal hot flashes,
metabolite of the isoflavone daidzein, and has been asso-
diminishing bone loss, reducing cholesterol levels and in
ciated with beneficial health effects (Törmälä, 2007). Those
cancer prevention (Messina 2010). There was a perceived
with the intestinal capacity to convert daidzein to equol
notion that soy phytoestrogens were weak estrogen ago-
can change steroid metabolism and estrogen bioavailabil-
nists/antagonists with molecular characteristics similar to
ity, and thus have an advantage using soy.
synthetic endocrine disruptors that could theoretically
Red clover is a plant that has been used in traditional
disrupt hormones and promote cancer, however, this claim
medicine for centuries. It has phytoestrogens coumestrol
has not been confirmed in human studies. In fact, soy may
(CM) and formononetin (FM). It has been known for its use
have a real role in the prevention and treatment of breast
in asthma, cholesterol reduction, hot flashes, indigestion
cancer.
and cancer prevention. Recently, more research has been
Soy is a complete protein as it contains all the essential
done on the use of red clover in female conditions, including
amino acids including histidine. It is known to be low in
menopause and cancer, alongside soy. The value of the
cysteine, which is required for infants, and therefore not
use of phytoestrogens (found in soy and red clover) to
recommended for use in infancy. Food sources of soybeans
combat cancer is now being assessed. For instance, one
include soy milk and tofu. Fermented foods with soy are
source suggests a therapeutic dose of 40-50mg of isofla-
natto and fermented bean paste. The form and type of soy
vones (biochanin A, daidzein, formononetin and genistein)
consumed should also be noted, as this has an impact on
as daily dose for cancer prevention and additional health
absorption after consumption. For instance, it is known
benefits, and this is derived from the traditional Japanese
that majority of the isoflavones in soy milk are glycosides,
diet (Beck 2005).
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feature
It should be noted that people metabolize soy phytoestrogens differently. Soy contains isoflavones, such as genistein and daidzein.
MOLECULAR MECHANISMS OF SOY PHYTOESTROGENS
in comparison to controls (Chen 2011). Levels of p-IGF-1 R,
Soy phytoestrogens are thought to be involved in breast
p-Akt, cyclin D1 protein expression, and cyclin D1 mRNA
cancer prevention through certain mechanisms of action.
expression were also downregulated. FM also prevented
Genistein, for example, is believed to be involved in the
tumor growth of human breast cancer cells in nude mouse
modulation of different signaling pathways associated with
xenografts in the same study. Overall, these results show
the growth of cancer cells through pleiotropic actions includ-
that FM halts the cell cycle at the G0/G1 phase by inactivating
ing inhibition of tyrosine kinases, DNA topoisomerase II,
IGF1/IGF1R-PI3K/Akt pathways, which demonstrate its poten-
5Îą-reductase, galectin-induced G2/M arrest, protein histidine
tial in preventing breast cancer carcinogenesis (Chen 2011).
kinase, and cyclin-dependent kinases (Varinska 2015). Another in vitro and in vivo study showed that genistein
HUMAN STUDIES OF THE PROTECTIVE EFFECT OF RED
reduced MCF-7 cell proliferation and induced the inactivation
CLOVER AND SOY
of IGF-1R and p-Akt and downregulated the Bcl-2/Bax protein
There are many epidemiological studies that support the
ratio (Chen 2014). Overall, these mechanisms have shown
effects of soy and, a study for red clover, in either breast
potential in breast cancer prevention.
cancer prevention or treatment alongside other therapies. A recent systematic review suggested that soy food intake,
MOLECULAR MECHANISMS OF RED CLOVER
similar to a traditional Japanese diet (2-3 servings daily,
PHYTOESTROGENS
containing 25-50mg isoflavones) may be protective against
Mouse models and in vitro evidence have both shown inter-
breast cancer and its recurrence (Fritz 2013). One study,
esting ways in which red clover isoflavones, like formononetin
done on WHO-CARDIAC study populations, demonstrated
(FM) can be preventative in breast cancer. Cells treated with
that the lower mortalities of breast cancers were inversely
FM have demonstrated reduced migration and invasion of
related to the 24-h urinary isoflavone excretion (Yamori
MDA-MB-231 and 4T1 cells in a wound healing assay, chamber
2006). Another interesting, longitudinal, prospective study
invasion assay, and an in vivo mouse metastasis model. In
of breast cancer patients in China noted that soy food intake
vitro, FM inhibited breast cancer cell migration and invasion
was safe and associated with a lower mortality and
by decreasing the expression of matrix metalloproteinase-2
recurrence of breast cancer in patients (Shu 2009). A meta-
(MMP-2), MMP-9 and increased the expression of tissue
analysis of breast cancer risk in Chinese women showed
inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2 (Zhou
that soy was a relevant factor in reducing the risk of breast
2014). This finding, while preliminary, suggests that FM may
cancer development; significant differences were also found
have anti-invasive properties for breast cancer, and that
between those who consumed soy foods, OR = 0.68 (95%
red clover deserves further evaluation in this context.
CI 0.50-0.93) and those who ate a high-fat diet, OR = 1.15
Molecular evidence from Chen et al found that FM prevented
(95% CI 1.01-1.30) (Wu 2015). One study proposed that soy
the proliferation of MCF-7 cells and arrested the cell cycle
should be used only in indicated patients and not in receptor
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positive females. Woo et al. found that high intake of soy
breast cancer; rather, studies have shown that soy may
isoflavones increased the risk of cancer recurrence in HER2-
decrease breast cancer risk, as well as protect against
positive breast cancer patients (Woo, 2012), however,
recurrence. Red clover is thought to act via similar mecha-
majority of the evidence proposes that soy is still protective.
nisms, however, requires further human study. For soy (pref-
Other convincing evidence comes from systematic
erably non GMO), supplementation has been thought to be
reviews and meta-analyses, such as the one by Liu et al.,
more beneficial in equol producers. It has also been found
which concluded that consumption of both soy and fruit was
that breast cancer mortality was decreased in those with
significantly associated with a decreased risk of breast
increased excretion of phytoestrogen metabolites (i.e. in
cancer, with summary ORs of 0.65 (95% CIs: 0.43-0.99;
the urine). There are some challenges in current research,
I2=88.9%, P<0.001; N=13) and 0.66 (95% CIs: 0.47-0.91;
such as a need to bridge the findings of observational studies
I2=76.7%, P<0.001; N=7), respectively (Liu 2014). A case control
to individual patient care (i.e. to address issues of intake
study support this finding in Korean women; among soy
and heterogeneity), however, a start would be to utilize
foods, a high intake of cooked soybeans, including yellow
doses with significant results in current studies and move
and black soybeans, had an association with diminished
towards creating more structured, double-blind, placebo
risk of breast cancer (OR=0.67; 95% CI=0.45-0.91; P<0.02)
controlled trials whenever possible (Ballard-Barbish, 2009).
(Do 2007). A case control German study showed that high
A careful review of the evidence is required alongside a
and low consumption of soybeans, as well as of sunflower
specific tailored regimen for each case and patient. It is
and pumpkin seeds were associated with significantly
important to consider the study population (Asian or other),
reduced breast cancer risk compared to no consumption
estrogen receptor status and the presence or absence of
(OR = 0.83, 95% CI = 0.70-0.97; and OR = 0.66, 95% CI =
menopause. Although interventional clinical trials are needed
0.77-0.97, respectively) (Zaineddin 2012).
to conclusively assess the role of soy and red clover, the
Research on red clover is limited, however, it still gives
existing research suggests that red clover and soy may have
hope that could ease controversial claims that phytoestro-
an important role to play in the prevention and treatment
gens, such as those found in red clover, may contribute to
of breast cancer when used in the right context.
breast cancer or recurrence. One systematic review suggests that it may not promote breast cancer (Fritz 2013). Further studies for red clover are required to support the dietary use of phytoestrogens from this source and others. View the references on your tablet.
CONCLUSION Overall, molecular and human studies support the position that soy based phytoestrogens do not promote nor cause SEPTEMBER 2015 â&#x20AC;˘ IHPMAGAZINE.COM
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