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WWW.IHPMAGAZINE.COM SEPTEMBER 2015

Doctors going digital

Natural Medicine in Europe

CANCERAn Integrative Approach

001.IHP Cover_noimages.indd 7 2015-08-20 10:09 AM

contents

DEPARTMENTS

FEATURES

SEPTEMBER 2015 • IHPMAGAZINE.COM 6

9 Publisher’s Letter

10 Editorial Board

12 Bits and BitesIndustry and Research News

26 Product Pro�les

30 Clinic Pro�leIntegrative Health Institute

50 Post Scriptum

34 Doctors going digitalSocial 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 EuropeSearching for adequate methodology

�nd us on3430

38

IHP Contents.indd 6 2015-08-20 9:59 AM


publisher’s letter

A ccording to Canadian cancer statis-

tics, the number of new cancer cases

will increase approximately 40 per

cent for Canada. Integrative approach to

treating and preventing cancer is now being

actively explored. We interviewed Dr. Dugald

Seely, executive director of the Ottawa

Integrative Cancer Centre to get some

updates on the current state of cancer

research from the integrative perspective.

In this issue, you can also find a European

perspective on the methodology currently

used by the naturopathic profession. On

page 48, president of the Association of

Natural Medicine in Europe shares her

opinion on the effectiveness of the evi-

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 indus-

try with the Ontario Association of

Naturopathic Doctors (OAND) holding their

2015 Convention and Tradeshow: Maximizing

the Power of the Mind in Total Wellness: Mind/

Body Medicine, Disease Management, and

Treatment Alternatives. We are expecting a

wonderful event on the body-mind connec-

tion in naturopathic medicine and we are

honoured to be media partner with the

OAND. Everyone attending the event will

have a chance to win a clinic makeover by

Melissa David, top Toronto designer, known

for her creative design and reno work pro-

duced for a number of HGTV shows.

If you have not done it yet, please

download your IHP App where you

have access to exclusive content and

full-length reference material.

Founder Sanjiv Jagota

Publisher & Editor-in-Chief Olivier Felicio

Managing Editor Inna Levchuk

Art Director Scott Jordan

Graphic Designer Kaitlin Yep

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

IHP Magazine Inc.

President Olivier Felicio

General Manager Melanie Seth

General Customer Care Manager Lucy Holden

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Canada Post Canadian Publication Mail Agreement Number 4067800 The pub-lisher does not assume any responsibility for the contents of any advertisement and any and all representations or warranties made in such advertising are those of the advertiser and not of the publisher. The publisher is not liable to any advertiser for any misprints in advertising not the fault of the publisher and in such an event the limit of the publisher’s liability shall not exceed the amount of the publisher’s charge for such advertising. No portion of this publication may be reproduced, in all or part, without the express written permission of the pub-lisher. ihp magazine is pleased to review unsolicited submissions for editorial consideration under the following conditions: all material submitted for edito-rial consideration (photographs, illustrations, written text in electronic or hard copy format) may be used by ihr Media Inc. and their af�liates for editorial pur-poses in any media (whether printed, electronic, internet, disc, etc.) without the consent of, or the payment of compensation to, the party providing such mate-rial. Please direct submissions to the Editor, ihp magazine.

Published by IHP Magazine

CirculationIHP Magazine Inc.1235 Bay St., suite 400; Toronto, Ontario, M5R 3K4Email: [email protected]

Advertising Olivier Felicio(416) 203-7900 x [email protected]

SEPTEMBER 2015 • Volume 8 Issue 4

Olivier Felicio

Publisher/Editor-in-Chief

IHP PubLetter.indd 9 2015-08-20 9:59 AM


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)

IHP CoverStory.indd 38 2015-08-20 10:00 AM


B reast cancer is the most diagnosed cancer for

women over 20, and is the second leading cause

of cancer deaths in women, second to lung cancer

(CCDP, 2005-2010). It is thought that 24,000 Canadians

will be diagnosed with breast cancer this year and 5000

will die from it, as stated by the Canadian Breast Cancer

Foundation (Coles 2013). Given these alarming statistics,

along with the side effects of conventional treatment (i.e.

fatigue, nausea, lymphedema, nerve damage and more),

there has been an increasing interest in the use of natural

supplements to prevent and treat cancer alone or alongside

conventional options. This growing interest has included

the controversial but promising use of phytoestrogens

found in soy and red clover. The study of soy as a therapeutic

ingredient has increased over the last decade. It has been

researched for its use in alleviating menopausal hot flashes,

diminishing bone loss, reducing cholesterol levels and in

cancer prevention (Messina 2010). There was a perceived

notion that soy phytoestrogens were weak estrogen ago-

nists/antagonists with molecular characteristics similar to

synthetic endocrine disruptors that could theoretically

disrupt hormones and promote cancer, however, this claim

has not been confirmed in human studies. In fact, soy may

have a real role in the prevention and treatment of breast

cancer.

Soy is a complete protein as it contains all the essential

amino acids including histidine. It is known to be low in

cysteine, which is required for infants, and therefore not

recommended for use in infancy. Food sources of soybeans

include soy milk and tofu. Fermented foods with soy are

natto and fermented bean paste. The form and type of soy

consumed should also be noted, as this has an impact on

absorption after consumption. For instance, it is known

that majority of the isoflavones in soy milk are glycosides,

but they are converted to aglycones by fermentation

(Takagi 2015). Isoflavone absorption is increased in

fermented soy milk beverage (in which the isoflavones are

largely converted to aglycones) in comparison to regular

soy milk. Some consideration should be given to the fact

that 93 per cent of soy is now a genetically modified

organism (GMO), and that it can cause allergic reactions

in some, however, further studies are needed to assess the

full effects of this (Kelly, 2015). Until this can be done, it is

best to use non-GMO soy and to avoid usage if allergic.

It should be noted that people metabolize soy phy-

toestrogens differently. Soy contains isoflavones, such as

genistein and daidzein. It also contains glycitein, an

O-methylated isoflavone that makes up 5–10% of the total

isoflavones in soy food (Song 1999). Equol is a gut bacterial

metabolite of the isoflavone daidzein, and has been asso-

ciated with beneficial health effects (Törmälä, 2007). Those

with the intestinal capacity to convert daidzein to equol

can change steroid metabolism and estrogen bioavailabil-

ity, and thus have an advantage using soy.

Red clover is a plant that has been used in traditional

medicine for centuries. It has phytoestrogens coumestrol

(CM) and formononetin (FM). It has been known for its use

in asthma, cholesterol reduction, hot flashes, indigestion

and cancer prevention. Recently, more research has been

done on the use of red clover in female conditions, including

menopause and cancer, alongside soy. The value of the

use of phytoestrogens (found in soy and red clover) to

combat cancer is now being assessed. For instance, one

source suggests a therapeutic dose of 40-50mg of isofla-

vones (biochanin A, daidzein, formononetin and genistein)

as daily dose for cancer prevention and additional health

benefits, and this is derived from the traditional Japanese

diet (Beck 2005).



feature

MOLECULAR MECHANISMS OF SOY PHYTOESTROGENSSoy phytoestrogens are thought to be involved in breast

cancer prevention through certain mechanisms of action.

Genistein, for example, is believed to be involved in the

modulation of different signaling pathways associated with

the growth of cancer cells through pleiotropic actions includ-

ing inhibition of tyrosine kinases, DNA topoisomerase II,

5α-reductase, galectin-induced G2/M arrest, protein histidine

kinase, and cyclin-dependent kinases (Varinska 2015).

Another in vitro and in vivo study showed that genistein

reduced MCF-7 cell proliferation and induced the inactivation

of IGF-1R and p-Akt and downregulated the Bcl-2/Bax protein

ratio (Chen 2014). Overall, these mechanisms have shown

potential in breast cancer prevention.

MOLECULAR MECHANISMS OF RED CLOVER PHYTOESTROGENSMouse models and in vitro evidence have both shown inter-

esting ways in which red clover isoflavones, like formononetin

(FM) can be preventative in breast cancer. Cells treated with

FM have demonstrated reduced migration and invasion of

MDA-MB-231 and 4T1 cells in a wound healing assay, chamber

invasion assay, and an in vivo mouse metastasis model. In

vitro, FM inhibited breast cancer cell migration and invasion

by decreasing the expression of matrix metalloproteinase-2

(MMP-2), MMP-9 and increased the expression of tissue

inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2 (Zhou

2014). This finding, while preliminary, suggests that FM may

have anti-invasive properties for breast cancer, and that

red clover deserves further evaluation in this context.

Molecular evidence from Chen et al found that FM prevented

the proliferation of MCF-7 cells and arrested the cell cycle

in comparison to controls (Chen 2011). Levels of p-IGF-1R,

p-Akt, cyclin D1 protein expression, and cyclin D1mRNA

expression were also downregulated. FM also prevented

tumor growth of human breast cancer cells in nude mouse

xenografts in the same study. Overall, these results show

that FM halts the cell cycle at the G0/G1 phase by inactivating

IGF1/IGF1R-PI3K/Akt pathways, which demonstrate its poten-

tial in preventing breast cancer carcinogenesis (Chen 2011).

HUMAN STUDIES OF THE PROTECTIVE EFFECT OF RED CLOVER AND SOYThere are many epidemiological studies that support the

effects of soy and, a study for red clover, in either breast

cancer prevention or treatment alongside other therapies.

A recent systematic review suggested that soy food intake,

similar to a traditional Japanese diet (2-3 servings daily,

containing 25-50mg isoflavones) may be protective against

breast cancer and its recurrence (Fritz 2013). One study,

done on WHO-CARDIAC study populations, demonstrated

that the lower mortalities of breast cancers were inversely

related to the 24-h urinary isoflavone excretion (Yamori

2006). Another interesting, longitudinal, prospective study

of breast cancer patients in China noted that soy food intake

was safe and associated with a lower mortality and

recurrence of breast cancer in patients (Shu 2009). A meta-

analysis of breast cancer risk in Chinese women showed

that soy was a relevant factor in reducing the risk of breast

cancer development; significant differences were also found

between those who consumed soy foods, OR = 0.68 (95%

CI 0.50-0.93) and those who ate a high-fat diet, OR = 1.15

(95% CI 1.01-1.30) (Wu 2015). One study proposed that soy

should be used only in indicated patients and not in receptor

It should be noted that people metabolize soy phytoestrogens differently. Soy contains

iso�avones, such as genistein and daidzein.



positive females. Woo et al. found that high intake of soy

isoflavones increased the risk of cancer recurrence in HER2-

positive breast cancer patients (Woo, 2012), however,

majority of the evidence proposes that soy is still protective.

Other convincing evidence comes from systematic

reviews and meta-analyses, such as the one by Liu et al.,

which concluded that consumption of both soy and fruit was

significantly associated with a decreased risk of breast

cancer, with summary ORs of 0.65 (95% CIs: 0.43-0.99;

I2=88.9%, P<0.001; N=13) and 0.66 (95% CIs: 0.47-0.91;

I2=76.7%, P<0.001; N=7), respectively (Liu 2014). A case control

study support this finding in Korean women; among soy

foods, a high intake of cooked soybeans, including yellow

and black soybeans, had an association with diminished

risk of breast cancer (OR=0.67; 95% CI=0.45-0.91; P<0.02)

(Do 2007). A case control German study showed that high

and low consumption of soybeans, as well as of sunflower

and pumpkin seeds were associated with significantly

reduced breast cancer risk compared to no consumption

(OR = 0.83, 95% CI = 0.70-0.97; and OR = 0.66, 95% CI =

0.77-0.97, respectively) (Zaineddin 2012).

Research on red clover is limited, however, it still gives

hope that could ease controversial claims that phytoestro-

gens, such as those found in red clover, may contribute to

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.

CONCLUSIONOverall, molecular and human studies support the position

that soy based phytoestrogens do not promote nor cause

breast cancer; rather, studies have shown that soy may

decrease breast cancer risk, as well as protect against

recurrence. Red clover is thought to act via similar mecha-

nisms, however, requires further human study. For soy (pref-

erably non GMO), supplementation has been thought to be

more beneficial in equol producers. It has also been found

that breast cancer mortality was decreased in those with

increased excretion of phytoestrogen metabolites (i.e. in

the urine). There are some challenges in current research,

such as a need to bridge the findings of observational studies

to individual patient care (i.e. to address issues of intake

and heterogeneity), however, a start would be to utilize

doses with significant results in current studies and move

towards creating more structured, double-blind, placebo

controlled trials whenever possible (Ballard-Barbish, 2009).

A careful review of the evidence is required alongside a

specific tailored regimen for each case and patient. It is

important to consider the study population (Asian or other),

estrogen receptor status and the presence or absence of

menopause. Although interventional clinical trials are needed

to conclusively assess the role of soy and red clover, the

existing research suggests that red clover and soy may have

an important role to play in the prevention and treatment

of breast cancer when used in the right context.

View the references on your tablet.


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