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An Integrative Approach

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SEPTEMBER 2015

Doctors going digital Natural Medicine in Europe

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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

find us on

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34 SEPTEMBER 2015 • IHPMAGAZINE.COM

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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

download your IHP App where you

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

Circulation

Publisher & Editor-in-Chief Olivier Felicio

IHP Magazine Inc. 1235 Bay St., suite 400; Toronto, Ontario, M5R 3K4 Email: circulation@ihpmagazine.com

Managing Editor Inna Levchuk Art Director Scott Jordan Graphic Designer Kaitlin Yep

Advertising

Olivier Felicio (416) 203-7900 x 6107 olivier@rivegauchemedia.com

Contributors

Jason Boxtart, Denise Cheung, Rochelle Fernandes, Eric Forget, Nora Laubstein, Dugald Seely, Jill Shainhouse

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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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