Journal of

Integrative Medicine Official Journal of the Australasian Integra�ve Medicine Associa�on

Vol 16 No 1 – March/April 2011

Complementary/ Integrative Medicine Needs Analysis

Ginger

Mangosteen Maternal Nutrition

Milk & Choc Free Diet

Australasian Integra�ve Medicine Associa�on Inc

FROM THE EDITOR

AIMA BOARD

(as of AGM 4 Sept 2010)

EXECUTIVE: AIMA PRESIDENT Prof Kerryn Phelps MBBS, FRACGP, FAMA

Welcome to our April 2011 edi�on...

My heart goes out to all those who are suffering as part of the recent disasters in Australasia. It certainly appears that the planet is trying to get our a�en�on at this �me! We are once again reminded that the force of Mother Nature is strong and powerful. This is significant not only with regards to negative environmental effects, but rather our own innate and positive abilities to heal through natural means. It is important now more than ever that we sit up and listen to what the world is trying to tell us. Indeed, the old message rings true once again, “Prevention is better than cure”, whether we are talking about detrimental environmental consequences or human forms of sickness and dis-ease. Preconception health care focuses entirely on prevention and is one of the ways that we can truly make a difference in the lives of generations to come. As such, I hope that you enjoy my article on Maternal Nutrition in this edition of JIM. Indeed, it is beautiful to see the world at large joining as one in the face of disaster. In the same vein, I believe that it is our responsibility to practice ethical health care at all times and to continue to spread the word that it is through the very same integration and amalgamation that we will ultimately create a happier and healthier world. Yours in truth,

VICE PRESIDENT Dr Lily Tomas MBBS, BSc(Med), RACGP-AIMA JWP

SECRETARY Dr Ray Mullen MBBS, FRACGP, Dip RACOG, Cert IM TREASURER Dr Vicki Kotsirilos MBBS, FACNEM, Chair RACGP-AIMA JWP, AIMA Founder and Past President

BOARD Prof Marc Cohen MBBS (Hons), PhD, BMed Sci(Hons), FAMAC Prof Avni Sali MBBS, PhD, FRACS, FACS, FACNEM Dr Kylie Dodsworth MBBS, BSC, FRACGP Dr Melinda Prince MBBS, FRACGP, M Med Hum

Lily Tomas Editor JIM Vice President AIMA

Dr Cathryn D’Cruz MBBS, FRACGP Dr Penny Caldico� BMED, FRACGP Dr Carole Hungerford BA, MB, BS, FACNEM

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2011 – JIM 1

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AIMA Melbourne Office 1 Palmerston Crescent South Melbourne Vic 3205 T: 03 8699 0582 F: 03 8699 0584 E: [email protected] Mon, Tues & Thurs 9am-5pm

AIMA Inc The Australasian Integra�ve Medicine Associa�on (AIMA) is a na�onal, voluntary nonprofit organisa�on and is the peak medical body that promotes the safe integra�on of evidence based holis�c and complementary medicine with current mainstream medical prac�ce, in pursuit of complete whole person care. See AIMA Membership form on page 32. This work is copyright. No part may be reproduced without prior wri�en permission from the Australasian Integra�ve Medicine Associa�on. The AIMA welcomes diversity of opinion on integra�ve health care issues and will publish views which are not necessarily the policy of the AIMA. Neither AIMA nor any of its Board members nor staff, accept liability for negligence, arising from the informa�on contained in the AIMA Journal.

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CONTENTS FROM THE EDITOR – Dr Lily Tomas

1

AIMA PRESIDENT’S REPORT – Prof Kerryn Phelps

3

ARTICLE Needs Analysis for Educa�on in Integra�ve and Complementary Medicine for General Prac��oners in Australia, Part 2 – by Kotsirilos V, Singleton G, Warnecke E & RACGP/AIMA Joint Working Party members

6

ARTICLE Mangosteen – Tradi�onal and Modern Uses – Shawn M. Talbo� PhD, David A. Morton PhD, & J. Frederic Templeman MD

10

ARTICLE Maternal Nutri�on – Dr Lily Tomas

12

ARTICLE Milk & Chocolate Free Diet – Dr. M.H. Garre�

20

From the Land of the Long White Cloud – Dr Tim Ewer

22

HEALTHY NEWS UPDATES – Prof Shaun Holt

24

HERB IN FOCUS Ginger – Dr Cathryn de Cruz

28

BOOK REVIEWS A Guide to Evidence-based Integra�ve and Complementary Medicine General Prac�ce – The Integra�ve Approach

30

AIMA MEMBERSHIP FORM

32

Published by the Australasian Integra�ve Medicine Associa�on Inc.

AIMA proudly announces our new Corporate Sponsor:

STIRLING PRODUCTS LIMITED 2 JIM – 2011

14

www.s�rlingproducts.net

AIMA PRESIDENT’S REPORT Preven�on must be the theme of the future, because if it does not become the focus of public health efforts, the health system as we know it will become unaffordable before the next genera�on reaches middle age.

keep people out of hospital; not because they can’t get a bed… but because they stay well. Often it means simply going back to basics. We need to begin prior to conception with nutrition and lifestyle programmes for prospective parents, which is continued throughout pregnancy and for children throughout their preschool and school years. Once upon a time, public schools had compulsory home economics classes. The term sounds archaic but it taught important life skills like how to manage a kitchen, the principles of nutrition and food preparation.

This was the theme of my presentation to the “People’s Parliament” convened in Sydney on March 1 ahead of the NSW election. There are strong signs that Australian governments are focusing on prevention, and furthermore, they are now investing in it. The National Preventive Health Agency began operations at the beginning of the year with a big Revising Curricula budget by any criteria... $872m over six From the point of view of the medical years. The money is a start. Significantly, profession, we need to make sure our this is a strong positioning signal from medical students are being taught the Federal government that lifestyle according to the philosophy that will be interventions and preventive health prevailing at the time that they are senior strategies are to be given a high priority. clinicians, and that will be Integrative I hope there will be a corresponding Medicine. commitment from State governments The RACGP is leading the way with to ensure that the funding is spent in the development of the Integrative carefully targeted ways with priorities Medicine Fellowship through the relevant to the populations at greatest RACGP/AIMA Joint Working Party. risk. “There are strong The other colleges and medical schools The Council of Australian would do well to look at the evidence signs that Australian Governments (COAG) discussions last for IM approaches and see where they governments are month provided two things: a promise can revise their curricula and up-skill of more money for growth for hospitals focusing on preven�on, clinicians in areas of primary, secondary and an in-principle agreement between and tertiary prevention so that they are and furthermore, they the States and the Commonwealth. seen as first-line therapeutics rather are now inves�ng in it.” However, it looks like this means yet than ‘optional extras’ or ‘someone else’s another bureaucracy to administer the responsibility’. funds: a bureaucracy which I suspect will be as far removed from the actual delivery of care as Individual Responsibility the current layers of red tape. By far the more important battleground is promoting We need to cut red tape, not increase it. individual responsibility for health. The sad truth is that And don’t hold your breath. The COAG reforms are an there is not, and never will be, a pill or procedure to undo in-principl, handshake deal with little detail. We have seen the damage of a lifetime of unhealthy habits. good intentions fail to resolve Commonwealth state health Prevention is the only strategy that has a chance of turning agreements before. things around, and it needs to start before conception and Hospital based care is the pointy end of healthcare and continue throughout the lifecycle. this should be properly funded. Decisions about patient Just as the causes of chronic disease are complex and care need to have the direct involvement of the clinicians multifactorial, so will be the solutions. Governments, who deliver that care and who see every hour of every day industry, schools, parents, town planners, architects, health where it goes wrong. They need to have the equipment and professionals and ultimately, individuals, all have a part to facilities to do the job, and to carry out research to keep play. Australia at the forefront of medical advances.

Chronic Disease We are not winning the battle against the tide of chronic disease. Therefore, research funding needs to be directed at better ways of managing this battle; specifically, research into clinical Integrative Medicine interventions. The system needs to support the health sector that is most involved in prevention, screening and chronic disease management: General Practice and Primary Care. Yet there was nothing in the COAG agreement for primary care. It is through prevention and new approaches to community based chronic disease management that we will

I hope to see you at the 17th annual AIMA Conference to be held this year at Manly Beach in Sydney. 

Prof Kerryn Phelps President AIMA

2011 – JIM 3

AIMA

JOIN AIMA The Australasian Integra�ve Medicine Associa�on (AIMA) is the peak medical body represen�ng the doctors and other health care professionals who prac�ce integra�ve medicine. Integra�ve medicine is a philosophy of healthcare with a focus on individual pa�ent care and combining the best of conven�onal western medicine and evidence-based complementary medicine and therapies within current mainstream medical prac�ce. AIMA is an independent not-for-profit organisa�on supported by its membership and governed by a board of voluntary doctors and academic leaders in the field of integra�ve medicine. As we expand and diversify, we remain true to our Core Mission: To act as the peak medical body promo�ng the prac�ce of evidence-based integra�ve medicine, research and educa�on as the gold standard for op�mising wellbeing, preven�on and management of disease in Australasian healthcare systems.

WHY JOIN AIMA? As well as assis�ng the good work of AIMA, your membership benefits include: • Representa�on of members to the AMA, RACGP/AIMA Joint Working and other medical educa�onal and government bodies. The RACGP & AIMA Joint Working party was formed in 2004 as an expert Commi�ee on Integra�ve and Complementary Medicine to provide advice and work closely with the RACGP President and Council. • Representa�on of AIMA in the Media, par�cularly with current President, high profile spokesperson, Prof Kerryn Phelps. • Networking and lobbying with medical and government organisa�ons and other stakeholders to promote the prac�ce of integra�ve medicine. • AIMA provides support network forum for doctors and other health care prac��oners interested in integra�ve medicine, including peer group support of like-minded prac��oners and support for AIMA/Medical Student Associa�ons. • Posi�on Statements across different areas of integra�ve medicine. • AIMA Board and JWP Board members are regular writers for leading medical publica�ons such as AusDoc & Australian Family Physician and other publica�ons, as experts in the area of Integra�ve Medicine. They are also invited to present at leading medical and natural health conferences both in Australia and interna�onally. • Free Subscrip�on to the AIMA Journal of Integra�ve Medicine. • Free Subscrip�on to the AIMA E-Newsle�er, twice-monthly, full of up-to-date informa�on regarding Integra�ve Medicine. Free access to an informa�ve AIMA Website: www.aima.net.au – offering members: • up-to-date integra�ve medicine informa�on. • latest research and healthy news updates. • Free access to current AIMA Posi�on Statements across different areas of Integra�ve Medicine. • Useful databases, educa�on needs and more. • Free general prac��oner lis�ng on the AIMA Website – Help us help the public to find you! • Discounted rates to the popular AIMA Annual Interna�onal Integra�ve Medicine Conference. This is the benchmark conference in Integra�ve Medicine which highlights a stunning line-up of expert speakers; Scien�fic Abstract Presenta�ons; a Medical Student Scholarship and a large exhibit area showcasing the latest products in the field of Integra�ve Medicine.

We invite you to play an ac�ve part in the change in healthcare and in shi�ing the medical paradigm! We look forward to you joining AIMA and encourage you to join us as a leader in this area in promo�ng the safe, effec�ve and evidence-based use of Integra�ve Medicines and Therapies. Please see the Membership Form on Page 32. Please contact the Melbourne AIMA office for further informa�on. 2011 – JIM 5

Needs Analysis for Education in Integrative and Complementary Medicine for General Practitioners in Australia – Part 2 Dr Kotsirilos V, Singleton G, Warnecke E & RACGP/AIMA Joint Working Party

by

The purpose of the Needs Analysis document is to clarify the need for ongoing educa�on for general prac��oners in the field of Integra�ve Medicine. Part 1 (see last issue) of this document summarises: the various defini�ons, General Prac��oner prescribing and use of CM, consumer a�tudes and needs towards CM, and prevalence of use of CMs. Part 2 of this document addresses the doctor-pa�ent rela�onship, the need for more scien�fic evidence in CM, adverse reac�ons and risks of CMs and currently available CM resource informa�on.

The Doctor-Pa�ent rela�onship

T

he doctor patient relationship may be affected when patients choose to use CMs. A legal article by Brophy suggests the doctor has a duty of care to ‘provide information about reasonably available complementary and alternative medicine treatments where that information would be material to the particular patient … given the high rate of patient self-prescribing, it is necessary for a doctor to open a dialogue with a patient about complementary and alternative medicine to address safety concerns’. In a discussion paper published in the Medical Journal of Australia, the authors emphasised when doctors are faced with patients wanting to trial CM they should be: • honest with patient’s direct questioning about CM • establish the patient’s understanding of CM and why they use it • take into account the burden of their illness and provide information on their expressed preferences • discuss the risks and benefits of both CM and orthodox treatment • adequately inform patients about available CM that has been shown to be safe and effective, and those that are shown to be ineffective • become familiar with qualified and competent

6 JIM – 2011

complementary medicine practitioners (both medical and non-medical) to whom referrals are made • continue the relationship with the patient and provide ongoing monitoring of their health. These points serve as a useful ethical framework and guidelines for doctors when faced with patients wanting to integrate CM into their healthcare. It is vital to empower patients to be active participants in their healthcare, to promote self-care and help them make well informed decisions and choices. It is also important doctors respect choices made by patients and maintain honesty regarding their own limitations such as knowledge of CM. When considering initiating any new therapy (orthodox or CM), it is important to understand and consider: • the risks versus the benefits • the scientific evidence • the clinical relevance and potential outcome • the costs to the patient • the available alternatives, for example other therapies or doing nothing

The scien�fic evidence Scientific evidence is the basis of and is essential to the practice of Medicine. Evidence on efficacy and safety should be the basis of defining which CMs are useful and which are not. To date research in CM has been limited due to a number of factors such as; lack of adequate funding, the type of CM used, difficulty extrapolating results to similar therapies with subtly different formulations, the variable quality of the studies and lack of patency rights to draw any firm conclusions about their potential role in health care. In saying this, there is also a large body of scientific evidence emerging for CM world-wide. This evidence should be made accessible to the health profession and public, and also integrated into recommended national guidelines of treatment for specific health conditions. Once a therapy or

“...the doctor has a duty of care to ‘provide informa�on about reasonably available complementary and alterna�ve medicine treatments where that informa�on would be material to the par�cular pa�ent …” medicine, be it orthodox or complementary, has a good basis of scientific evidence to prove its efficacy and safety, then the medical practitioner has a legal and ethical obligation to use the best treatment possible which is most suitable for the individual patient. There are many CMs that are not evidence-based to date. This may not mean that they are ineffective for the reasons outlined above. These CMs obviously need to be used cautiously risk until they are adequately tested and their potential benefits weighed against any potential risks. The primary aim of AIMA and the IM network is to provide education about the evidence base and risk factors of common CM and therapies used by the community.

Adverse reac�ons and Risks of CMs Compared to pharmaceuticals, the overall risk associated with the use of CMs is low. Australian TGA data from adverse events reported to the Australian Drug Reactions Advisory Committee (ADRAC) arising from the use of listed CMs from 2004 to 2008, shows that there were a total of 656 total reports where a CM was the sole suspected possible, probable or certain cause of an adverse patient reaction, with 7 possible death outcomes associated with a CM. During the same period there were 38,337 cases where a medicine (prescription, over the counter medication and other products registered on the Australian Register of Therapeutic Goods (ARTG) was the sole suspected possible, probable or certain cause of an adverse patient reaction, and there were 1014 possible death outcomes. In many cases the contribution of the suspected medicine to the death is uncertain, however based on the information reported it

is not possible to entirely exclude the possibility that the suspected medicine contributed to the fatal outcome. An NPS study discussed in detail in Part 1 of this analysis showed it is clear there is an urgent need for GPs to learn more about adverse reactions with CMs. The study revealed about 40% of general practitioners reported having minimal or no knowledge about black cohosh and ginkgo biloba, and less than 40% of the surveyed GPs were aware of some potential side effects and drug–CMs interactions of ginkgo biloba, glucosamine and black cohosh. Only 38% of GPs were aware that black cohosh has been linked to liver damage despite an ADRAC report published in 2005. This highlights a concern that needs to be addressed through better education about risks associated with CMs and the need to report adverse events possibly associated with CMs to ADRAC. A new Advisory Committee on the Safety of Medicines will commence from 2010. ‘In line with the world-wide trend of placing greater emphasis on monitoring and managing the safety of medicines after they have been registered, the TGA will from 2010 replace ADRAC with an expert advisory committee established in its own right under the Therapeutic Goods Act. This new statutory expert committee – the Advisory Committee on the Safety of Medicines (ACSOM) will encompass the activities and functions of ADRAC but will have broader terms of reference commensurate with the increasing prominence of pharmacovigilance in Australia and world-wide.’ Based on the statistics above, the level of reporting for CMs is relatively low compared with pharmaceuticals, considering the widespread usage of CMs in Australia. There may be a number of factors contributing to this, other than CMs having a relatively favorable safety profile, including significant under-reporting due to patients failing to communicate adverse events to their medical practitioner about the use of CMs and medical practitioners failing to report adverse events to ADRAC. Reports can easily be made electronically on the TGA website or by filling in the blue card and posting to ADRAC. Furthermore, the ADRAC bulletin regularly reports common or serious adverse reactions to CM. Subscribers to the ADRAC-Bulletin email list will receive an email notifying them when the latest issue of the Australian Adverse Drug 2010 – JIM 7 2011

>>

Needs Analysis for educa�on in Integra�ve and Complementary Medicine for general prac��oners in Australia

Reactions Bulletin is available on the TGA Internet site (normally once every two months) or to subscribe, go to: http://www.tga.gov.au/adr/adrac-bulletin-subscribe.asp [accessed 23 December 2009]. The new advisory committee will continue this role from 2010.

Currently available CM resource informa�on Recently the NPS commissioned a review of CMs information resources aimed at identifying high quality resources for use by Australian health professionals and consumers. A variety of information sources about CM are available to consumers and health professionals but these sources are of variable quality. The review was conducted by a consortium of researchers from the National Prescriber Services, Mater Hospital Pharmacy Services in Brisbane, the University of Queensland and Bond University. CM information resources were tested against a broad range of criteria encompassing currency, coverage, transparency and content quality to produce a short-list of resources. These resources were evaluated across three domains: technical quality, content quality and clinical utility. Resources were then ranked according to whether their total scores and the scores for each of the three domains were above the upper 95% confidence interval for the mean scores for all the individual resources. The top 6 identified as the highest quality (Tier 1), based on their total score, and scores for all three domains (technical quality, content quality and clinical utility) being above the upper 95% confidence interval of the mean of all short-listed resources are listed in Table 2. Three resources were identified as high quality (Tier 2) based on their total score, and two of the scores for the three Table 2. NPS Complementary Medicines Informa�on Resources. Top 6 resources iden�fied (�er 1)7 Natural Standard Professional Database package Natural Medicines Comprehensive Database (Health Professional Edi�on) Natural Standard Professional Database – Professional monographs Herbal Medicines & Dietary Supplements package Natural Standard Professional Database – Bo�om line monographs MedlinePlus: Drugs, Supplements & Herbal Informa�on domains being above the upper 95% confidence interval of the mean of all short-listed resources. They are included in Table 3. The NPS recommended that organisations responsible for providing information to consumers and health professionals Table 3. NPS Complementary Medicines Informa�on Resources. Top 3 resources iden�fied (�er 2)7 Barnes et al. Herbal Medicines. 3rd ed. 2007. Natural and Alterna�ve Treatments: EBSCO. Braun and Cohen. Herbs and natural supplements. An evidence-based guide 2nd ed. 2007.

8 JIM – 2011

“...there is a great need to further educate the medical profession on the efficacy and safety of CM and to encourage prac�ce of integra�ve medicine in order to provide, safe, holis�c care to pa�ents.” about CMs such as drug information services have access to one or both Natural Standard Professional Database or the Natural Medicines Comprehensive Database (Health Professional Edition) and to the high quality resources (Tier 1 and 2).7

Conclusion Integrative Medicine provides a holistic approach to health care which is essentially patient-centred. Ideally any form of CM to be considered by a patient and treating doctor should be evidence-based and safe, and that all care should be well coordinated and patient-centred. Care of any patient needs to be flexible, respectful of their individual needs and choices. It does require that the GP/medical practitioner have a basic understanding of CMs, know where to access any information from reliable sources, be honest about the level of knowledge in this area and consider referral to a trusted health practitioner (medically or non-medically trained) if their knowledge is limited. The GP needs to weigh the benefits of any CM therapy with any risks associated with its use. Also it is vital to monitor the patient carefully for any response to the use of CMs, report any adverse reactions and clearly document if a patient is refusing any orthodox or conventional treatment. The evidence presented previously clearly demonstrates that there is a great need to further

educate the medical profession on the efficacy and safety of CM and to encourage practice of integrative medicine in order to provide, safe, holistic care to patients. * * * * * * * * Education need is based on the findings summarized throughout this document that include: • Widespread use of CM by 2/3rds of Australians, yet a significant proportion do not tell their doctors they are using CMs.8,9,10,11 • Consumer preference to discuss the use of CMs with their doctors.10,11 • Widespread prescribing of CMs by GPs yet only 38% of GPs felt they were confident discussing CMs with patients.4 • Potential risks and adverse reactions associated with CMs.12 • More than half of the GPs seek information on CMs information about safety (interactions, adverse effects and contraindications), evidence of effectiveness, dose and indications for use, highlighting the need for education in this area.4 • Little knowledge in adverse reactions in risks associated with CM. For example less than 40% of the surveyed Australian GPs were aware of some potential side effects and drug–CMs interactions of commonly used CMs such as Ginkgo biloba, glucosamine and black cohosh, and that black cohosh has been linked to liver damage.4 • GPs are interested in professional development in CM and Integrative Medicine. They would prefer to attend seminars and workshops, and read paper versions of peer-reviewed medical journals. Over 50% of GPs are interested in attending seminars and workshops organised by an authoritative body such as NPS, the Divisions of General Practice or the RACGP.4 • Availability of high quality CM information resources for use by Australian health professionals and consumers.7  References 1.

Brophy E. Does a Doctor Have a Duty to Provide Informa�on and Advice about Complementary and Alterna�ve Medicine? Journal of Law and Medicine. 2003 Feb;10:271-84.

2.

Kerridge I, McPhee J. Ethical and legal issues at the interface of complementary medicine and conven�onal medicine. Medical Journal of Australia. 2004;181.

3.

Sta�s�cs provided by the Office of Medicines Safety Monitoring at the Therapeu�c Goods Administra�on. 25th March 2009.

4.

Brown J, Morgan T, Adams J, Grunseit A, Toms M, Roufogalis B, Kotsirilos V, Piro�a M and Williamson M. Complementary Medicines Informa�on Use and Needs of Health Professionals: General Prac��oners and Pharmacists. Sydney: Na�onal Prescribing Service, 2008. Updated April 2009. Available at:

h�p://www.nps.org.au/research_and_evalua�on/research/current_research/ complementary_medicines/cms_health_professionals_research [Accessed 3 December 2009] 5.

Australian Drug Reac�ons Advisory Commi�ee. Black cohosh and liver toxicity – an update. Australian Adverse Drug Reac�ons Bulle�n. 2007 June;26(3):11.

6.

Australian Adverse Drug Reac�ons Advisory Commi�ee (ADRAC). A new Advisory Commi�ee on the Safety of Medicines from 2010. Australian Adverse Drug Reac�ons Bulle�n. 2009 December;28(6):22.

7.

McGuire T, Walters J, Dean A, Van Driel M, Del Mar C, Kotsirilos V, Moses G, Chong S, Deed G, Eldred B, Hardy J, Heussler H, Hollingworth S, Marron L, Mendel J, Pache D, Steadman K, Trenerry H, Brown J Williamson M. Review of the Quality of Complementary Medicines Informa�on Resources: Summary Report. Sydney: Na�onal Prescribing Service March 2009.

8.

MacLennan A, Myers S, Taylor A. The con�nuing use of complementary and alterna�ve medicine in South Australia: costs and beliefs in 2004. Medical Journal of Australia. 2006;184(1):27-31.

9.

Williamson M, Tudball J, Toms M, Garden F, Grunseit A. Informa�on Use and Needs of Complementary Medicines Users. Sydney: Na�onal Prescribing Service; December 2008.

10. Easton K. Complementary medicines: a�tudes and informa�on needs of consumers and healthcare professionals - prepared for the Na�onal Prescribing Service Limited (NPS). Sydney; July 2007. 11. Williamson M, Toms M, Garden F, editors. What consumers want to know about CMs. 3rd Interna�onal Congress on Complementary Medicine Research; 2008. Na�onal Prescribing Service. 12. Australian Bureau of Sta�s�cs. Australian Social Trends; 23rd July 2008. Document No.: 4102.0

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Mangosteen Traditional and Modern Uses by Shawn M. Talbott PhD, David A. Morton PhD, & J. Frederic Templeman MD

Introduc�on – Tradi�onal Use

M

angosteen (Garcinia mangostana) is a tropical fruit that has been traditionally used as an indigenous medicine across Southeast Asia (Thailand, Malaysia, Taiwan, Philippines, Indonesia and Sri Lanka) for treatment of a wide range of ailments including fighting infections, healing wounds and treating diarrhoea and related gastrointestinal complaints. Mangosteen is known to contain a wide range of naturallyoccurring polysaccharide and xanthone compounds within the fruit, leaves, heartwood, and especially the pericarp (rind/ peel/hull) with widespread biological activities, including anti-inflammatory,1,2,3,4,5,6,7 and antibacterial/antiviral effects in a number of experiments.6,8 The pleasant taste (sweet and slightly acidic) and medicinal qualities of the reddish-purple mangosteen fruit has led to its common name as ‘Queen of Fruits’.4 The demonstration of widespread biological effects of mangosteen-derived compounds, and especially of the family of bioactive xanthones (polyphenolic compounds, of which more than 1,000 have been described in nature, 18 isolated from mangosteen fruit, and 60 from the pericarp), suggest a scientific basis for the historical medicinal use of mangosteen preparations in Southeast Asian traditional medicine systems, including Ayurvedic medicine.6 More ‘modern’ health benefits of mangosteen preparations have been described in cases of arthritis,9 cancer,10 wounds,11,12 inflammation,13 ulcers,14 eczema,15 acne,2 allergies,16 and abdominal pain,17,18 among many others.6

Scien�fic Evidence Extensive laboratory and human clinical research has suggested a strong link between the mechanisms by which oxidative stress leads to chronic inflammation, which in turn may mediate a wide array of chronic diseases of ‘aging’ including cancer, obesity, diabetes, and diseases of the cardiovascular, pulmonary, and neurological systems.19 Oxidative stress is known to activate numerous inflammatory pathways and transcription factors, including those for growth factors, cytokines, and cell cycle regulatory

10 JIM – 2011

molecules, which may lead to transformation of a normal cell to a tumour cell.19 Reducing inflammation in overweight and obese individuals may be valuable in preventing the progression to metabolic syndrome with associated risks for heart disease and diabetes.20 Inflammatory conditions are typically multi-factorial in their etiology. In obesity, for example, central adipose tissue is known to produce inflammatory cytokines including CRP and IL-6, which further influence insulin activity and glucose homeostasis.21 Systemic chronic inflammation has emerged as a significant and specific predictor of cardiovascular disease, risk for myocardial infarction and the development of metabolic syndrome. Therefore the ability to reduce inflammation with mangosteen/xanthones may be an important and valuable preventive measure against the development of diabetes,22,23 heart disease,24,25,26,27 arthritis,28,29,30 and inflammatory diseases of the lungs,31,32 digestive tract,33 and skin.34,35 The pharmacological options for treating inflammation are numerous, including steroids and non-steroidal antiinflammatory drugs, such as aspirin, ibuprofen, and naproxen – but their long-term use is associated with a range of potential adverse side effects including reduced resistance to infection and gastrointestinal bleeding.36 As natural anti-inflammatory agents, mangosteen-derived xanthones, particularly alpha- and gamma-mangostins, are supported by a large body of scientific literature for their effects in various inflammatory pathways, including: • Inhibition of both IgE-mediated histamine release and prostaglandin E2 synthesis from arachidonic acid as well as COX-2 activity in rat cancer cell lines.36,37,38 • The major xanthone in mangosteen, alpha-mangostin, has shown antiplasmodial activity39 and anti-larval activity40 in vitro. • Various extracts of mangosteen (water, ethanol, ethyl acetate, methanol) have demonstrated antioxidant and neuroprotective activity in cell culture.41 • Antioxidant activity of mangosteen-derived xanthones has been demonstrated in direct free

“The mangosteen is one of the few natural therapeu�cs from ancient tradi�onal medicine systems that has stood the scru�ny of modern scien�fic evalua�on.” radical scavenging,42 decreasing the oxidation of human low density lipoproteins (LDL) induced by peroxyl radical,43 and prevention of alpha-tocopherol consumption during LDL oxidation.44 Such antioxidant effects have also been linked to neuroprotective activity.41 • Mangostin has shown antibacterial effects (in vitro) against staphylococcus aureus,45,46 Enterococci,45 and Mycobacterium tuberculosis47 as well as a range of antibiotic-resistant strains of bacteria including methicillin-resistant S. Aureus (MRSA) and vancomycin resistant Entercocci (VRE).45,48 • Chemopreventive effects of mangosteen extract have been demonstrated against rat colon carcinogenesis49 and against various human cell cultures of hepatic, lung, and gastric carcinomas.10 • In cell culture, alpha-mangostin induces apoptosis in a variety of human cancer cell lines,17,18,50,51 possibly due to antioxidant and/or anti-inflammatory activities.18 • Direct anti-inflammatory activities of xanthones have been shown in rats challenged with the carrageenaninduced paw oedema,52 and in cell cultures where both alpha- and gamma-mangostins inhibit histamine release.53

application of mangosteen xanthones has been shown to reduce acne2,13 and eczema.15 A recent human feeding trial evaluated the effects of a proprietary mangosteen (fruit plus pericarp) juice blend (Xango, Xango LLC) on markers of inflammation (highlysensitive C-reactive protein, hs-CRP levels). The study was an 8 week randomised, double-blind, placebo-controlled design of 40 obese subjects that showed a significant change from baseline values (reduced CRP) in the subjects consuming mangosteen juice (Xango) compared to placebo.20

Conclusions This brief overview of the traditional use and scientific evidence for mangosteen and mangosteen-derived xanthones demonstrates a long history of use of the fruit in traditional medicine systems around the world, as well as a detailed and extensive profile of the phytochemical constituents and pharmacological effects of the bioactive xanthone components that are richly and widely distributed in the mangosteen fruit and pericarp. The emerging clinical data suggests that whole mangosteen fruit preparations (fruit plus pericarp) containing a family of xanthone compounds may have important and considerable clinical potential in treating inflammation and a range of inflammatory conditions in human subjects. As such, the mangosteen is one of the few natural therapeutics from ancient traditional medicine systems that has stood the scrutiny of modern scientific evaluation. Further research should help elucidate and extend the health benefits of mangosteen to a wider population.  References available from [email protected]

• Interestingly, a mouthwash containing mangosteen extract was found to reduce levels of volatile sulfur compounds associated with bad breath54 and topical 2011 – JIM 11

Maternal Nutrition by

Dr Lily Tomas MBBS.,BSc(Med.)

Chronic Disease and Obesity

G

ood maternal nutrition is exceptionally important throughout both pregnancy and lactation, for if a mother’s diet is inadequate, her baby is not protected from a multitude of potentially preventable problems.1 There is growing evidence that specific nutrients such as those listed below are vital to the health and wellbeing of our future generations.2 Indeed, women of childbearing age should achieve and maintain good nutritional status through dietary guidelines and supplement regimes advised by their health care providers during preconception counselling.3 Much recent work has provided evidence that preconceptual nutritional conditions and the periconceptual environment not only influences healthy birth outcomes but also plays a major role in long-term health outcomes, including a role as an antecedent to adult diseases.4,5,6 The “Developmental Origins of Adult Health and Disease” (DOHAD) hypothesis states that environmental factors, especially maternal under-nutrition, act in early life to programme the risk for adverse health outcomes, such as cardiovascular disease, infertility, obesity and the metabolic syndrome in adult life. Evidence suggests that the foetal environment can programme the developmental trajectory of the stress axis and the systems that maintain and regulate arterial blood pressure.7 Maternal obesity alters renal and adipose tissue, resulting in chronic kidney disease and insulin resistance, respectively, whereas maternal nutrient restriction during pregnancy has also been shown to result in marked attenuation of cellular stress and inflammation in renal and adipose tissue of ovine juvenile offspring.8 Indeed, maternal under-nutrition is associated with shorter adult height, less schooling, reduced economic productivity and, for women, lower offspring birthweight. In turn, lower birthweight and under-nutrition in childhood are risk factors for high glucose concentrations, blood pressure and harmful lipid profiles. Birthweight has also been positively associated with lung function and the incidences of some cancers, and under-nutrition could be associated with mental illness.2 Furthermore, animal studies have shown that nutrient restriction over the period

12 JIM – 2011

of foetal brain development contributes to a profoundly different adaptation in energy balance which may result in an increased risk of Type II diabetes.9 While the DOHAD hypothesis has focussed primarily on the impact of maternal under-nutrition, an increase in maternal nutrient intake and body mass has become more prevalent in developed countries. Exposure to over-nutrition in foetal life results in a series of central and peripheral neuroendocrine responses that programme development of the fat cell and of the central appetite regulatory system. Such outcomes emerge in childhood and adolescence and can therefore directly contribute to intergenerational cycles of obesity and poor reproductive fitness.7 Both under-nutrition and over-nutrition of the mother during pregnancy and lactation can produce a syndrome of altered energy balance in the offspring and have long-lasting consequences on the regulation of food intake, metabolism and food rewards.10 Indeed, many chronic diseases have been found to be particularly common in undernourished children who experience rapid weight gain after infancy.2 Epigenetic mechanisms, which may be mediated by macro and micronutrients, endocrine status and oxidative stress, are the focus of many recent studies aimed at understanding the processes involved in these effects.5

Both under-nutri�on and over-nutri�on of the mother during pregnancy and lacta�on can produce a syndrome of altered energy balance in the offspring and have long-las�ng consequences on the regula�on of food intake, metabolism and food rewards.

Breast-Feeding, Chronic Disease and Obesity Several recent systematic reviews and meta-analyses suggest that breast-feeding, in addition to its well-established beneficial effects during the lactation period, also provides beneficial long-term effects such as protection against

infectious and immune-related diseases, better cognitive development and a decreased risk of metabolic syndrome and obesity.11,12,13,6 There is also evidence that breast-feeding has a beneficial effect on other major components of the metabolic syndrome such as blood pressure, cholesterol metabolism and insulin resistance, thereby profoundly affecting risk factors of cardiovascular disease.14 Breast-feeding has been found to reduce the odds ratio for obesity at school age by about 20% compared with formula-feeding, when adjusted for biological and sociodemographic confounding variables.15 The mechanisms involved, although poorly understand as yet, are likely to involve the benefits of relative under-nutrition and slower growth associated with breast rather than formula feedingthe “Growth Acceleration Hypothesis”.16 Protein intake per kilogram body weight is 55-80% higher in formula-fed infants and it is also hypothesised that high early protein intakes in excess of metabolic requirements may enhance weight gain in infancy and later obesity risk – the “Early Protein Hypothesis”.15 Human milk is exquisitely fitted for optimal infant growth and development and may uniquely modulate neuroendocrine and immunologic pathways involved in the regulation of body weight.12 Hormones in breast milk such as leptin, ghrelin, insulin, IGF-1(insulin-like growth factor) and adiponectin play roles in food intake regulation, metabolism and body composition.6,11 Serum leptin has been found to be higher in breast-fed compared with formulafed infants which may provide a physiological explanation for a number of advantages seen in reaching proper growth and energy balance.11 In contrast, formula-fed infants at 45 months show higher plasma levels of IGF-1 and certain amino acids than breast-fed infants.17,13 A recent study involving 1823 subjects has compared the duration of breast-feeding with BMI levels at 60 years. This study demonstrated that breast-feeding for 8 months was associated with an increased BMI and % body fat in later life. It was concluded that breast-feeding for < 2 months was deleterious, possibly due to lack of exposure to protective factors in breast milk, and breastfeeding for > 8 months was possibly deleterious because the mother’s hormones in breast milk reset the infant’s hypothalamic-pituitary-thyroid axis.18 Despite breast-feeding having a protective effect against obesity, it is imperative to remember that other genetic and environmental determinants such as socioeconomic status and parental obesity, may have a greater effect as risk factors for childhood obesity.12

Omega-3 Essen�al Fa�y Acids Fatty acids are essential to normal growth and development through their roles as membrane lipids, as ligands for receptors and transcription factors that regulate gene expression, as precursors for eicosanoids, in cellular communication and through direct interactions with proteins. Inadequate supplies of fatty acids during foetal and child development subsequently alter the fatty acid composition of membrane phospholipids and storage triglycerides, having

the potential to disrupt cellular environments and alter the structure and function of biological programmes.19 Because DHA is critical for the development of the nervous system, particularly during the first year of life, the content of DHA in breast milk is vital for the well-being of exclusively breast-fed infants.20 Indeed, stores of essential fatty acids in the foetus are entirely dependent upon maternal fatty acid intake during pregnancy and lactation, highlighting the need for educating lactating women about the importance of DHA in foods and/or supplements.20 Human have a perinatal brain growth spurt, selectively accumulating DHA and other long-chain polyunsaturated fatty acids (LCPUFAs), from the 3rd trimester through the 2nd year of life.21 Supplementation in pregnancy (2.2g DHA, 1.1g EPA/ day in one study) has been shown to significantly increase Omega 3 LCPUFAs in breast milk, particularly in early lactation, and has been positively associated with infant DHA status at 1 year.22,23,24

Vision and Cogni�on Docosahexaenoic acid (DHA), the most important omega-3 fatty acid, is a vital component of both neural and retinal membranes and rapidly accumulates in the brain during gestation and the post-natal period. Higher maternal DHA intake in pregnancy and in lactation is associated with positive infant neurodevelopmental outcomes. Women of reproductive age should achieve a minimum dietary intake of 200mg DHA/day.25,26 Children whose mothers received DHA supplementation during pregnancy and lactation scored better in mental processing tests carried out at 4 years than children whose mothers received placebo or omega-6 fatty acids.24,27 Maternal accumulation of DHA during pregnancy has also been shown to positively correlate to sequential processing at 7 years age. However, no significant effect has been shown on global IQs.27 Evidence shows that a higher maternal DHA intake during pregnancy may also be favourable for visual development of infants. Electroretinogram data obtained during the first week of life and pattern-reversal visual evoked potentials performed at 50 and 66 weeks postconception were significantly associated with the DHA 2011 – JIM 13

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Maternal Nutri�on

status of the infant at birth.24,19 Furthermore, both EPA and DHA in breast milk have been positively correlated with Griffith’s developmental scores, including hand and eye coordination.22

Immunity – Allergies, Infec�ons and Asthma Optimal foetal nutrition via the mother is definitely an important prerequisite for the establishment of a functional immune system with normal immune responses. Omega3 LCPUFAs exert their immunomodulatory activities at various levels. Fatty acids and their derivatives are known to regulate numerous metabolic processes, induce eicosanoid production, regulate gene expression of important proteins such as enzymes and cytokines and alter T-cell signalling. (28) It is important to note that the effect of the omega3 LCPUFAs on the immune system of infants may vary according to dose, time of exposure and profile of the immune system (ie. T-helper, Th1/Th2).29 An intact gut barrier forms a prerequisite for protection against infection and allergy. Both allergic and inflammatory mediators (eg. IL-4, IFN-gamma) are known to compromise the epithelial gut barrier integrity by enhancing permeability. LCPUFAS, EPA and DHA are effective in supporting the barrier integrity by improving resistance and reducing IL-4 mediated permeability.30 Recent evidence suggests that the increased prevalence of childhood allergy and asthma may be linked to deviations in foetal immune development.28 A RCT involving 533 women with normal pregnancies were randomly assigned to receive either 2.7g omega-3 PUFAs, olive oil or no oil capsules daily from gestation week 30 until delivery. During the 16 years that passed since childbirth, it was demonstrated that the hazard rate of “asthma” was reduced by 63% and the hazard rate of “allergic asthma” was reduced by 87% in the fish oil group.31 Thus, supplementation of the maternal diet in pregnancy with Omega-3 LCPUFAs is potentially a non-invasive intervention strategy to prevent the development of allergy, asthma, infection and possibly other immune-mediated diseases.29

Cardiovascular Disease Early nutrition may programme obesity and cardiovascular risk later in life, and one of the potential agents is omega3 LCPUFAs.32 There have been a multitude of studies demonstrating beneficial cardiovascular effects of fish oils in adults, however, there is currently a paucity of studies on infants. One recent study has demonstrated that fish oil supplements may affect heart rhythm in a positive manner in infants similar to that observed in adults. This may then imply that low omega-3 PUFA levels in late infancy may contribute to disturbances in heart rate and heart rate variability.33 Another recent study, however, has demonstrated a 6mmHg higher diastolic and mean arterial pressure in 7 year old boys of mothers who were supplemented with 1.5g/day fish oil during the first 4 months of lactation. Further studies are, of course, required.32

14 JIM – 2011

Human Milk Oligosaccharides as Prebio�cs There is growing evidence of the local effects within the gastrointestinal tract and the systemic functions of human milk oligosaccharides (HMO).34 Despite the role of milk to serve as a sole nutrient source for infants, most of these oligosaccharides are actually not able to be digested by human infants. This apparent paradox raises many questions regarding the functions of HMO.35 The nutritional function most attributed to HMO is to serve as prebiotics – a form of indigestible carbohydrate that is selectively fermented by desirable intestinal microflora.35 The microflora of breast-fed infants is an important physiological factor in gut function and the development of the immune system. Many studies have shown that HMO selectively stimulate the growth of Bifidobacteria and Lactobacilli in the intestine.34,35,36,37,38,39

Low B12 and high folate in mothers could be contribu�ng to the epidemic of adiposity and Type II diabetes. Such prebiotic characteristics of the HMO may contribute to protection against infectious agents as the intestinal mucosa acts as a barrier against harmful dietary and microbial antigens.40,30 The ability of HMO to protect the neonate seems to be due primarily to their inhibition of pathogen binding to their host cell target ligands through various processes. HMO strongly attenuate inflammatory processes in the intestinal mucosa and are able to induce growth inhibition in intestinal cells by inducing differentiation and/or by influencing apoptosis.41 Thus, oligosaccharides and other such glycans are the main components of an innate immune system of human milk whereby the mother protects her infant from enteric and other pathogens through breast-feeding. This may be the underlying aetiology as to why infants that are not breastfed have a higher incidence of diarrhoea and respiratory disease than those that are.40,34,38 Several recent studies have also demonstrated a relationship between gut microflora in infancy and subsequent development of allergic disease. Further larger studies are required regarding this significant connection.42

B Vitamins Nutrients implicated in healthy reproduction and lifelong health also include B vitamins, particularly B6, B12 and folate.43 An inadequate maternal dietary intake of B vitamins may increase the expression of potentially harmful genes.44 Balance between the B vitamins is also important as demonstrated by a recent study of 700 pregnant women in India. The offspring of mothers with a combination of low Vitamin B12 and high folate status were found to be the most insulin resistant at 6 years of age. As such, it was concluded that low B12 and high folate in mothers could

be contributing to the epidemic of adiposity and Type II diabetes.45 It has also recently been found that neural tube defects and other congenital anomalies may not only be due to nutritional deficiencies in the mother, but also due to deficiencies in the father. Fathers of children with neural tube defects were found to have significantly lower Vitamin B12 and folate levels (and, in turn, higher homocysteine) than controls. It has been postulated that congenital anomalies may be due to more complex gene-nutrient interaction defects in affected families, probably through abnormal folate/homocysteine metabolism.46 Futhermore, elevated homocysteine has been shown to be a possible risk factor for preeclampsia.47 In developed countries, Vitamin B12 deficiency usually occurs in exclusively breast-fed babies whose mothers are vegetarian as the newborn’s Vitamin B12 storage comes exclusively from placental transfer.48 Symptoms of B12 deficiency include irritability, anorexia, anaemia, failure to thrive, lethargy, hypotonia and arrest or regression of developmental skills.49,50,51 These symptoms respond remarkably to supplementation, however, if not treated, Vitamin B12 deficiency can cause lasting neurodisability.52 In such cases, cerebral imaging demonstrates diffuse cortical atrophy.48 Approximately 50% infants exhibit abnormal movements before the start of treatment with intramuscular cobalamin, which disappear 1-2 days after.53 B12 deficiency may cause these symptoms through delayed myelination or even demyelination of nerves, alteration in the S-adenosylmethionine: S-adenosylhomocysteine ratio, through imbalances of neurotrophic and neurotoxic cytokines and/or accumulation of lactate in brain cells.49 Efforts should therefore be directed to preventing deficiency in pregnant and breast-feeding women, particularly if they are vegetarians, by giving them Vitamin B12 supplements as required. If preventative supplementation has failed, one should recognise and treat quickly an infant presenting with failure to thrive and delayed development.53,54 There have been limited studies regarding maternal B6 deficiency alone, however, research has shown that poor Vitamin B6 status appears to decrease the probability of conception and may contribute to the risk of early pregnancy loss.55 It has also been associated with an increased risk for cleft lips with or without cleft palate.56

Folic Acid There have been a multitude of studies regarding the protective effects of folate on neural tube defects, such that health agencies in the early 1990’s began advising all women of childbearing age to consume 400ug folate daily. Subsequently, many common foods have been fortified with folic acid in order to achieve this.57 More recently, prenatal supplementation of folic acid has been shown to decrease the risk of several congenital malformations and possibly certain paediatric cancers as folate deficiency induces DNA breaks and may alter cellular capacity for mutation and epigenetic methylation.58,59 MTHFR (5-methylenetetrahydrofolate reductase) is the

key enzyme required to activate folate for methylation in neurodevelopment. A particular polymorphism of this enzyme has been found to occur in a significantly higher frequency in autistic individuals. An interesting hypothesis has recently been put forward as to whether enhancement of maternal folate status before and during pregnancy has altered the natural selection by increasing survival rates of infants possessing this MTHFR C677T polymorphism. Such infants also have higher post-natal requirements for folic acid for methylation during the critical neurodevelopmental period. Detection of this polymorphism and other methionine cycle enzymes as part of newborn screening could determine which newborns need to monitored and maintained on diets and/or supplements that ensure adequate folate status during this critical time.57

Vitamin D and Calcium During pregnancy and lactation, mothers require significantly higher amounts of calcium to pass on to baby. Given the dependence of adult calcium levels and bone metabolism on Vitamin D, it seems highly probable that adequate amounts of Vitamin D are even more critical during pregnancy and lactation. However, it appears that maternal and foetal adaptations provide the necessary calcium to the neonate relatively independent of Vitamin D status, with possible consequences to maternal health.60 Vitamin D deficiency has been widely reported in all age groups in recent years.61 In particular, low Vitamin D status during pregnancy has been found to be common in many studies from different countries. Consequent Vitamin D insufficiency in the neonate can lead to hypocalcemia, rickets, dental problems, reduced intrauterine long bone growth, shorter gestation, decreased birth weight and reduced childhood bone mineral/mass accumulation.62,63,61 The functions of Vitamin D also include immune system regulation and anti-proliferative effects on cells. Thus, early life Vitamin D deficiency has been implicated not only in bone disease, but also auto-immune disease, such as Type I 2011 – JIM 15

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rickets in developed countries, however higher doses may be required in order to achieve optimal levels of both maternal and neonatal Vitamin D status in order to prevent other important consequences of Vitamin D deficiency.61,69 Several studies have concluded that the incidence of Vitamin D deficiency in infancy is rising and that adequate intake of Vitamin D cannot easily be met with human milk as the sole source of Vitamin D.70 Research has shown that during lactation, supplements administered directly to the infant can easily achieve appropriate levels. One study has shown that 400IU/day maintains 25(OH)VitD concentrations higher than 50nmol/L.71 The mother needs much higher doses (4000IU/day) to achieve equivalent concentrations in her exclusively breast-fed infant.60,69 No toxicity has been reported at these levels.72 It has also been shown that women who restrict milk intake < 250mL during lactation compromise protein, Vitamin D and calcium intakes. Vitamin and mineral supplements have been shown to improve these levels.73 Furthermore, in situations of low calcium intake, Vitamin D requirements may be even higher than normal.74 This is imperative as nutrient intake during breast-feeding may have a long-lasting effect on the baby’s future health.75

An�-Oxidants – Vitamin A, C and E diabetes, and certain cancers later in life. More long-term interventional studies are required.60,61 There has been a moderate amount of research of late regarding the association between maternal Vitamin D deficiency and autism in the offspring. Animal studies have shown that Vitamin D deficiency during gestation results in the dysregulation of numerous proteins involved in brain development with increased brain size and enlarged ventricles, similar to those found in autistic children. Oestrogen and testosterone have profoundly different effects of the metabolism of calcitriol and may explain the striking male:female autistic ratios. Furthermore, calcitriol down-regulates the production of inflammatory cytokines, cytokines that have been associated with autism. Consumption of Vitamin D containing fish during pregnancy has been shown to reduce autistic symptoms in offspring.64,65,66 A recent systematic review has shown that calcium supplementation during pregnancy can reduce the incidence of hypertension in the mother and offspring blood pressure. Further studies are required, however, it was concluded that calcium supplementation is simple and inexpensive and may be an easy way to reduce the risk of hypertension and its sequels in the next generation.67 Current recommendations for Calcium intakes during pregnancy and lactation are……. Adequate serum concentrations of 25-hydroxyvitamin D and consequently appropriate doses of Vitamin D during pregnancy and lactation, are still being debated.68 There is evidence to show that current Vitamin D guidelines for the neonatal period, 200-400IU/day, prevents full-blown

16 JIM – 2011

Supplementing women with antioxidants during pregnancy may help to counteract oxidative stress.76 Maternal Vitamin A deficiency during pregnancy is known to be widespread in developing countries. However, a recent study of pregnant women in developed countries with short birth intervals or multiple births demonstrated that almost 1/3 women had borderline Vitamin A deficiency.77 Vitamin A and its analogues are important regulators of cell proliferation, differentiation, immune function and apoptosis. Because Vitamin A regulates nephron mass, maternal Vitamin A status profoundly affects kidney organogenesis of the newborn. In adult humans, nephron numbers vary between 0.3 and 1.3 million per kidney, which is accepted as normal. Animal studies indicate that Vitamin A deficiency results in a 20% reduction in nephron number and further recent studies have shown that humans at the low end of nephron number are predisposed to primary hypertension. Thus, those infants with low levels of retinoic acid may require heightened surveillance for BP later in life.78,79 Vitamin A also plays an important role in foetal lung development and maturation. Indeed, the American Pediatrics Association cites Vitamin A as one of the most critical vitamins during pregnancy and lactation, especially in terms of lung function and maturation. If the Vitamin A supply of the mother is inadequate, the supply to her foetus will be inadequate, as will later be her milk. The German Nutrition Society (DGE) recommends a 40%increase in Vitamin A intake during pregnancy and a 90% increase during lactation.77 A recent Cochrane review has also indicated that Vitamin A supplementation in pregnancy improves infant birthweight.80

Vitamin A deficiency also has multiple effects on the pituitary-thyroid axis with Vitamin A status modulating thyroid gland metabolism, peripheral metabolism of thyroid hormone and production of thyrotropin by the pituitary.81 Further Cochrane reviews have determined that the antioxidant Vitamins C and E taken during pregnancy have no effect on reducing the risk of pre-eclampsia and other serious complications in pregnancy. It should be noted that no doses or specifies types of Vitamin E were cited in these reviews.76,82 An earlier review concluded that there was insufficient data available to say if Vitamin C supplementation, alone or combined with other supplements, was beneficial during pregnancy. Preterm birth may have been increased with vitamin C supplementation. Again no doses were cited.83 A very recent case-control study of 276 mothers of babies with congenital heart defects demonstrated that periconceptional use of Vitamin E supplements in addition to a dietary intake above 15mg/day was associated with a 5-9 fold higher risk of congenital heart defects when compared with controls. This risk appeared to increase with increasing doses of Vitamin E. Current Australian guidelines recommend 7mg Vit E /day during pregnancy.84

Another recent systema�c review and meta-analysis, including Cochrane databases, has demonstrated that mul�vitamin supplements provide consistent protec�on against neural tube defects, cardiovascular defects, cle� palate, urinary tract anomalies, limb defects and congenital hydrocephalus.

Vitamin K Since 1961, the Committee on Nutrition of the American Academy of Pediatrics has recommended that prophylactic Vitamin K be given to all newborn infants in order to avoid Haemorrhagic Disease of the Newborn (HDN). Vitamin K1 is present in green vegetables and Vitamin K2 is made by intestinal flora.85 Basically, HDN is a disease of exclusively breast-fed infants. As Vitamin K is undetectable in cord blood, the only source in breast-fed infants is breast milk. (86) Studies have shown that formula-fed infants have greater faecal concentrations of Vitamin K1 and K2 than breast-fed babies.85 It also appears that plasma lipids may affect the absorption of Vitamin K, and other fat-soluble vitamins may antagonise Vitamin K under different physiological conditions.87 A Cochrane review has concluded that a single 1mg i/m Vitamin K after birth is effective in the prevention of classic HDN whereas either i/m or oral Vitamin K prophylaxis improves biochemical indices of coagulation status at 17 days. Neither i/m or oral routes have been tested in randomised trials with respect to the prevention of late onset (week 2-12) HDN.88 Breast-fed infants may benefit from increased maternal Vitamin K intakes (>1ug/kg/day) during pregnancy and

lactation. A 5mg supplement given to lactating mothers has been shown to increase the Vitamin K status in human milk and significantly increase infant plasma Vitamin K.86

Mul�-Vitamins Previously, more attention has been paid to the risks of under-nutrition, however, with the growing incidences of obesity, diabetes, dyslipidaemia and cardiovascular disease, more focus is being placed on overconsumption. It is important to realise that overconsumption does not guarantee an adequate supply of critical nutrients.89 Prenatal and antenatal supplementation with multiple micronutrients has recently been associated with a modestly increased birth weight and reductions in the risk of preeclampsia, pre-term deliveries and congenital defects.90,91,92 Unexpectedly, in one study, however, the risk of perinatal death was marginally increased in the group tasking micronutrient supplementation.92 Recent studies have also indicated that prenatal multivitamin supplementation may be associated with the prevention of certain paediatric cancers and a decrease in congenital anomalies.93 A recent systematic review and metaanalysis, including Cochrane databases, has concluded that prenatal multivitamin supplementation is associated with a decreased risk for paediatric brain tumours, neuroblastoma and leukaemia. It is not currently known which constituent(s) confer this protective effect.58,93 Another recent systematic review and meta-analysis, including Cochrane databases, has demonstrated that multivitamin supplements provide consistent protection against neural tube defects, cardiovascular defects, cleft palate, urinary tract anomalies, limb defects and congenital hydrocephalus.94 A 2006 Cochrane review has also shown that multivitamin supplementation is associated with a reduction in the number of low birthweight and small-for-gestational-age babies as well as maternal anaemia. However, there appeared to be no added benefit compared with iron/folate supplementation, thus it was concluded that iron/folate should not be replaced by a multivitamin supplement.95 Recommendations have recently been made by the Society of Obstetricians and Gynaecologists of Canada that all women of reproductive age should be advised about the benefits of multivitamin and folate supplements as diet alone is now unlikely to provide levels comparable to that of supplements. Ideally, supplementation with a multivitamin and 5mg folic acid should begin at least 3 months prior to conception and continue until 10-12 weeks post conception. From this time until the cessation of breastfeeding, supplementation should consist of a multivitamin plus 0.4-1.0mg folate/day.96

Iodine Vitamin A deficiency and iodine deficiency disorders affect > 30% of the global populations and these deficiencies often co-exist in vulnerable groups.81,97 It is interesting to note, however, that 47% healthy lactating volunteers in Boston, US, were found to be providing breast milk with insufficient iodine to meet their baby’s requirements.98 2011 – JIM 17

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A recent Cochrane review has demonstrated that iodine deficiency has multiple adverse effects on growth and development due to inadequate thyroid hormone production and remains the most common cause of preventable mental impairment worldwide.99,100,101,102,103 The WHO (World Health Organization) recently increased their recommended iodine intake during pregnancy from 200 to 250ug/d and suggested that a median urinary iodine concentration of 150-249ug/L indicates adequate iodine intake in pregnant women. (81) However, extensive literature reviews demonstrate that these levels may be even higher, with antenatal requirements from 250-300ug/ d, lactation requirements being 225-350ug/d and infant requirements being 90ug/d.104 Iodine supplementation before and during pregnancy has been associated with a significant reduction in deaths during infancy and early childhood. This also decreased the prevalence of cretinism at 4 years and improved psychomotor development scores between 4-25 months of age with no adverse effects.100 In areas where

Milk & Chocolate Free Diet For the future: Some, but not all studies published in the literature would indicate that giving cow’s milk to new born infants where one or other parent had a history of milk intolerance seems to make these infants more liable to allergic problems. Recent literature seems to point to even mother taking acidophilus in late pregnancy also helps delay the onset of allergy. This is possibly because the infant is exposed to only ‘good germs’ during labour and breast feeding, and so colonisation of the infant’s gut helps the developing infant immunity and offers some protection. If the birth is difficult, ensure that your infant is NOT complemented with a cow’s milk infant formula in the nursery. Request that a nonallergic formula be used-neocate best, pregestimil satisfactory but I wouldn’t even use this in the problem family. Use Neocate where a supplement in hospital is necessary. After the birth, my own advice is that breast-feeding a new infant is the best protection that can be given and, a milk chocolate free diet for mother continued. Introduction of solids is best delayed, for about 4-6 months but there is little research on this, just a good indication that this may be best, and introduce ‘low allergy foods’ first. You should continue to use acidophilus and don’t forget the ‘cheating’ gut permeability problem. Alternative advice says that early introduction of milk and other allergenic foods

either through breast milk or directly fed, allows tolerance to develop. In short we really don’t know yet.

A2 Milk Most problems from milk are due to intolerance rather than true allergy. Allergic children react to only tiny amounts of milk and can have severe life-threatening reactions. Fortunately only about 2% of children react in this way and most children have a slower non dangerous response after some few hours to even days. These children do not have positive blood or skin tests to milk and we are unsure in many cases of the exact mechanism. I have found by experience that these late responders can mostly tolerate A2 milk which is somehow different, and there is no opiate problem. It comes from Jersey and Guernsey cows and is now available in IGA stores and most super markets. Do not use this initially. The first job is to discover the actual food causing the trouble by elimination diets before trying A2. It must never be tried in milk allergic subjects. If a nutritionist is available in your area, then it is wise to enlist their help in management.  Further Reading www.aima.net.au for integra�ve medical Drs in your area. www.acnem.org for doctors who have had extra training in allergy in your area. www.aaaai.org (American Academy of Allergy with many links). www.fan.org (Food Allergy Network). www.acaai.org ( American Academy Asthma Allergy and Immunology). www.ascia.com.au ( Australian Society Clinical Immunology and Allergy).

From the Land of the Long White Cloud Our thoughts remain with friends, family and colleagues in Christchurch as they come to terms with the sad loss of life as well as the enormous destruc�on to homes, workplace and infrastructure. Unfortunately, the aftershocks continue to place physical and psychological pressure on all remaining there, while those who have lost homes or are in urgent need of respite are being supported throughout the country. It is likely to take many months, if not longer, to regain confidence and vitality in the ‘garden city’. However, the local and international response to this disaster has been a phenomenal example of generosity, practical help and human kindness which is hugely appreciated.

AIMA New Zealand s�ll has a wonderful programme of events planned for this year. Our first meeting on March 1st featured Pat Armistead; Nurse, Joyologist and award winning radio Improv artiste who shared stories and successes of her work, the Good Grief restorative programme, which combines casting, art, ceremony, storytelling, symbolism, music and positive psychology. We are also very honoured to have Bruce Lipton speak on Tuesday March 29th at Fairway Lodge. Bruce is very well

22 JIM – 2011

known internationally for his fascinating lectures, research and books, The Biology of Belief and Spontaneous Evolution. Bruce also presented at a number of public presentations in Auckland in recent months. AIMA New Zealand has a wide variety of speakers for the rest of the year: dates will be confirmed on our AIMA Newsletter. Cherye Roche from NZ College of Chiropractic; Jason Bennett, a dynamic speaker on nutrition, Dr Patrick Mc Hugh, Respiratory Physician on the local research in Gisborne on complementary therapies including Buteyko, Dr Fraser Burling, Consultant Rheumatologist on current evidence-based research in pharmaceuticals and nutritional supplements, and David Holden on the latest technologies for diagnosis and management in cancer are just some of the speakers presenting this year. The AIMA seminar this year is the weekend of 7th/8th May at Massey University and speakers include Petrea King from the Quest for Life Centre in Australia and Rachel Arthur, Biochemist and Naturopath, who will speak on the clinical relevance of many laboratory tests with a wide range of clinical cases for illustration and discussion. Further speakers to be confirmed. Dr Tim Ewer AIMA New Zealand

2011 – JIM 23

Healthy News Updates The following studies have been compiled with independent commentary by Dr Shaun Holt, BPharm (Hons), MBChB (Hons). [email protected]

Alexander technique is costeffec�ve for back pain The facts: • 579 patients with chronic or recurrent low back pain were enrolled in a study to evaluate the cost-effectiveness and usefulness of the Alexander technique (therapeutic massage, exercise, and lessons) for persistent back pain. • Intervention costs ranged from £30 for an exercise prescription to £596 for 24 lessons in Alexander technique plus exercise.

Zinc may be good for the common cold The facts: • A review of 15 trials involving 1360 people assessed the effects of zinc lozenges or syrup on common cold symptoms and duration.

• A combination of six lessons in Alexander technique plus exercise was the most useful and costeffective option for persistent back pain.

• When taken within a day of the onset of cold symptoms in otherwise healthy people, zinc reduced the severity and length of illness.

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The facts: • 102 adults with irritable bowel syndrome (IBS) were split into 2 groups and were instructed to either maintain their normal lifestyle or to get more exercise (up to 1 hour of moderate-tovigorous exercise for at least 3 days a week) for 3 months. • Symptoms that were assessed included cramps, bloating, constipation and diarrhoea.

• Children who took zinc for 5 months or longer caught fewer colds, took less time off school, and needed fewer antibiotics than children who didn’t take zinc. Prof Shaun Holt: Almost half of time taken off work is for the common cold and so, as zinc appears to reduce the duration of symptoms by around a day, this is an important finding. The research found that you can get this benefit if you start taking the zinc soon after symptoms start. Alternatively, if you take it every day, the research found that you will suffer around 40% fewer colds. Zinc can be taken as a syrup, tablets or lozenges. The common cold is the most widespread illness in the world and the average New Zealand adult will have around 3 episodes a year, and children tend to have more. http://dx.doi.org/10.1002/ 14651858.CD001364.pub3.

Exercise may improve irritable bowel symptoms

• At the end of the study, the exercise group reported greater improvements in symptoms than the group that carried on as normal, and were less likely to show worsening symptoms. Prof Shaun Holt: The Alexander technique has been defined as an education and guidance system to “improve posture and movement, and to use muscles efficiently”. Previous studies have suggested that it is effective for back pain, which is both common and very hard to treat. This large study, which had nearly 600 participants found that the Alexander technique was more effective than exercise and that a combination of six lessons in Alexander technique lessons followed by exercise was the most effective and cost effective option. http://dx.doi.org/10.1136/bmj. a2656

Prof Shaun Holt: Irritable bowel syndrome is a common illness that is poorly understood by doctors and consequently very difficult to treat. Could simple exercise be the answer? This smallish trial suggests it may be, with nearly half of those that did the exercise experiencing clinically important reductions in symptoms. The recommended exercise schedule was 20 to 60 minutes of moderateto-vigorous exercise – like brisk walking or biking – on three to five days out of the week. http://www.nature.com/ajg/ journal/vaop/ ncurrent/full/ajg2010480a.html

Healthy News Updates Green bananas help diarrhoea

• Compared with patients who took placebo, those who took THC reported improved and enhanced taste perception, and an improved appetite.

The facts: • This community-based trial in rural Bangladesh evaluated the effects of a green bananasupplemented diet in 2968 children with acute or prolonged diarrhoea. • For the treatment group, mothers were instructed to add cooked green banana to their child’s diet; the others were fed as normal. • The recovery rates of children with diarrhoea were much faster in those given green bananas than in those given a standard diet.

• The THC group also reported increased quality of sleep, relaxation, and improved quality of life.

8 weeks to assess the effects of the probiotic on symptoms. • Compared with placebo, LGG significantly reduced the frequency and severity of abdominal pain, even during the 2-month period after treatment was stopped. • Use of LGG probiotics significantly improved gut permeability in the children with IBS.

Prof Shaun Holt: Natural remedies are often seen as a lifestyle choice in rich, Western countries, but in the developing world, cheap and effective natural products can have enormous, even lifesaving, benefits. By way of example, diarrhoea results in 1.5 million deaths among children under the age of five each year, the second most common cause of infant death. This trial of nearly 3,000 young children in Bangladesh found that adding cooked green banana to the diets of children with diarrhoea significantly hastened recovery. http://dx.doi.org/10.1111/j.13653156.2010.02608.x

Probio�cs reduce abdominal pain in children The facts: • 141 children with IBS or abdominal pain received oral Lactobacillus rhamnosus GG (LGG) or placebo twice daily for

Prof Shaun Holt: Recurrent abdominal pain, which may or may not be diagnosed as irritable bowel syndrome, is a common complaint in children and is one of the most common reasons for referral to a specialist. As probiotics seem to be beneficial in a number of gastrointestinal disorders, it is perhaps no surprise that this small study found that probiotics reduced the frequency and severity of abdominal pain in children. The study had a number of limitations, but given the safety of probiotics supplements, a “try and see” approach can be recommended to parents of children with these symptoms. http://pediatrics.aappublications. org/cgi/ content/abstract/126/6/e1445

Cannabis ingredient restores taste in cancer pa�ents The facts: • 21 adult cancer patients with taste alterations and poor appetite after chemotherapy were given either THC (the active ingredient of cannabis) or placebo twice daily for 18 days.

Prof Shaun Holt: People with cancer face many challenges and a common one is not having a good appetite, due to the illness or the treatments. This can lead to malnutrition, which can make the person feel more sick, further reducing appetite. It can be hard to break this vicious cycle and people with cancer often use cannabis to stimulate their appetite. This study found that tetrahydrocannabinol, one of the main active ingredients in cannabis, can also actually make food taste and smell better, and thereby help to bring back a bigger appetite. http://annonc.oxfordjournals.org/ content/early/2011/02/11/annonc. mdq727.abstract

Physical ac�vity helps outcome a�er prostate cancer The facts: • 2705 men with prostate cancer were followed for nearly 20 years to determine the effects of exercise on their survival. • Men who engaged in at least 3 hours of exercise (e.g. swimming, biking, jogging, tennis) per week had a much lower risk of dying from prostate cancer than those who exercised for >

Healthy News Updates Selenium reduces PSA levels in men

Passion flower tea improves sleep quality

The facts: • 30 healthy middle-aged US men took a selenium supplement for 6 weeks to assess the effects of the mineral on prostate cancer risk.

The facts: • 41 healthy volunteers were given a cup of either passion flower or parsley tea daily for 1 week, during which time they also completed a sleep diary.

• Selenium supplementation led to a decrease in plasma levels of prostate specific antigen (PSA), an indicator of prostate cancer.

• A daily cup of passion flower tea significantly improved sleep quality compared with parsley tea.

• Reducing a marker of prostate cancer does not necessarily mean a reduction in cancer risk, but does justify further study of selenium glycinate supplementation.

• Based on these findings, further studies of passion flower are warranted, particularly in patients with insomnia.

• Men who walked for at least 90 minutes a week at a normal to brisk pace were much less likely to die from any cause than those who walked