ACNEM Journal June 2018, Vol 37 No 2
ACNEM Journal June 2018
ACNEM Journal June 2018
Create successful ePaper yourself
Turn your PDF publications into a flip-book with our unique Google optimized e-Paper software.
<strong>Journal</strong><br />
<strong>ACNEM</strong><br />
<strong>Vol</strong> <strong>37</strong> <strong>No</strong> 2 – <strong>June</strong> <strong>2018</strong><br />
ISSN 1839 2695<br />
ASSOCIATION OF SERUM VITAMIN<br />
D CONCENTRATIONS WITH<br />
DIETARY PATTERNS IN CHILDREN<br />
AND ADOLESCENTS<br />
ALZHEIMER'S DISEASE:<br />
A NUTRITIONAL AND<br />
ENVIRONMENTAL PERSPECTIVE<br />
RE-INTEGRATING MEDICINE PART<br />
2: RECLAIMING SCIENCE
Specialists in Functional Medicine<br />
Spectrumceuticals<br />
For practitioner dispensing only<br />
OUR FORMULAS INCLUDE SOME OF THE MOST CLINICALLY<br />
STUDIED PROBIOTIC STRAINS IN BROAD SPECTRUM,<br />
D-LACTATE FREE AND INFANT FORMULATIONS<br />
Australian Practitoner wholesale orders available only through Spectrumceuticals<br />
CONTACT US FOR MORE INFORMATION<br />
Live Chat<br />
Mon-Fri<br />
1300 852 775<br />
Mon-Fri<br />
Fax orders<br />
02 9475 5310<br />
Email orders<br />
orders@spectrumceuticals.com<br />
Online<br />
Express Delivery<br />
Flate Rate<br />
Spectrumceuticals Pty Ltd Unit 10/5 Narabang Way Belrose, NSW, 2085<br />
For New Zealand orders contact Nutrisearch toll free 0800-88-44-33
<strong>ACNEM</strong> <strong>Journal</strong> <strong>Vol</strong> <strong>37</strong> <strong>No</strong> 2 – <strong>June</strong> <strong>2018</strong><br />
Contents<br />
Editorial 3<br />
Penelope Griffiths<br />
Association of serum vitamin D concentrations with dietary patterns in 7<br />
children and adolescents<br />
Vijay Ganji, Bernadette Martineau and William Edmund Van Fleit<br />
Alzheimer's Disease: a nutritional and environmental perspective 19<br />
Dr Inanch Mehmet<br />
Re-integrating Medicine Part 2: Reclaiming Science 28<br />
John Smartt<br />
College News 33<br />
Awards and Recognition 36<br />
Editorial<br />
Penelope Griffiths ( <strong>Journal</strong> Production)<br />
Prof Neil Mann (Associate Editor) BAppSc, BSc(Hons), Dip Ed,<br />
PhD, FNSA<br />
Dr Braham Robinov (Associate Editor) MBBS, F<strong>ACNEM</strong>, Dip<br />
Health Education<br />
Dr Christabelle Yeoh (Associate Editor) MBBS, MRCP, MSc<br />
Natasha Bassett (Layout Editor)<br />
<strong>Journal</strong> of the Australasian College of Nutritional and<br />
Environmental Medicine Inc (<strong>ACNEM</strong>)<br />
Suite 10, 23-25 Melrose Street, Sandringham, VIC 3191, Australia<br />
Phone: (03) 9597 0363<br />
Fax: (03) 9597 0383<br />
Email: mail@acnem.org<br />
Web: www.acnem.org<br />
<strong>ACNEM</strong> Board of Management<br />
Dr Christabelle Yeoh (President)<br />
Dr Nadine Perlen (Secretary)<br />
Dr Kamal Karl (Treasurer)<br />
Dr Braham Rabinov<br />
Dr Kim Hayes<br />
Dr Jim Parker<br />
Joanne Ford<br />
Caryl Hertz<br />
The College, <strong>Journal</strong>, and its Editorial Board do not take<br />
responsibility for or necessarily agree with opinions or claims of<br />
authors or advertisers. All reasonable care is taken to select responsible<br />
and well-researched material for the <strong>Journal</strong>. Guidelines for authors<br />
are available on request and may also be viewed at www.acnem.org.<br />
The Editorial Board reserves the right to accept or reject content or<br />
advertising material without giving reasons for any decisions made.<br />
This <strong>Journal</strong> is copyright of <strong>ACNEM</strong>. All rights reserved. The<br />
College’s written permission must be obtained prior to using<br />
or reprinting any part of this <strong>Journal</strong>. The <strong>ACNEM</strong> logo is a<br />
registered trademark of the Australasian College of Nutritional and<br />
Environmental Medicine Inc, and all parts of the logo are protected,<br />
including its graphic elements and the word ‘<strong>ACNEM</strong>’. <strong>ACNEM</strong> Inc.<br />
is an incorporated association under the laws of Victoria, Australia.<br />
Reg: A0022218W. ABN: 18 776 847 535.<br />
1
<strong>ACNEM</strong> <strong>Journal</strong> <strong>Vol</strong> <strong>37</strong> <strong>No</strong> 2 – <strong>June</strong> <strong>2018</strong><br />
about acnem<br />
The Australasian College of Nutritional and Environmental Medicine (<strong>ACNEM</strong>) Inc,<br />
is a not-for-profit medical college established in 1982, offering postgraduate training and<br />
education for doctors and other graduate healthcare professionals in Nutritional and<br />
Environmental Medicine.<br />
what is nem?<br />
Nutritional and Environmental Medicine (NEM) is concerned with the interaction<br />
of nutritional and environmental factors with human biochemistry and physiology, and the<br />
resulting physiological and psychological symptoms and pathology. NEM is evidence-based,<br />
drawing on the latest biomedical and genetic science and research to develop new treatment<br />
approaches to illness and disease, for primary prevention and to promote optimal health<br />
and well-being.<br />
Nutritional deficiencies, imbalances, or the presence of environmental toxins in the body<br />
can result in cellular dysfunction, illness or disease. Treatment is aimed at<br />
correcting underlying causes as well as providing symptomatic relief. This may involve<br />
removal of certain foods from the diet or toxins from the patient’s environment, or prescription<br />
of supplements such as vitamins, minerals, trace elements and essential fatty acids where diet<br />
and lifestyle alone cannot rectify physiological imbalances.<br />
acnem membership<br />
Professional Membership of the College is open to doctors and dentists. Associate<br />
Membership is available to graduate and practising affiliated healthcare professionals.<br />
Membership benefits include free online lectures selected from <strong>ACNEM</strong> Online Learning,<br />
the <strong>ACNEM</strong> <strong>Journal</strong>, a regular email newsletter, and discounts on education and training.<br />
Members of the public are also invited to become <strong>ACNEM</strong> Community members to<br />
support the work of the College.<br />
acnem training<br />
<strong>ACNEM</strong> training programs are designed for practitioners wanting to learn effective ways<br />
of treating their patients. Content is strongly referenced and presented by some of Australia<br />
and New Zealand’s leading clinicians. The emphasis is always on ‘putting it into practice’,<br />
with guidelines and practical tools to aid implementation. Training is held throughout the<br />
year at locations around Australia and New Zealand, and also by online learning.<br />
acnem education<br />
<strong>ACNEM</strong> training optionally leads to Certification in NEM Parts 1 & 2 and Fellowship<br />
in NEM. The <strong>ACNEM</strong> Primary Modules in NEM are the starting point for <strong>ACNEM</strong><br />
Education and can be completed face-to-face, online or a combination of both.<br />
cpd/cme points<br />
<strong>ACNEM</strong> is an accredited RACGP QI&CPD training provider for the 2017-2019 Triennium<br />
with 40 Category 1 points allocated to most training programs. ACRRM, RNZCGP and<br />
CPD/CME points from other professional organisations may also be available.<br />
2
<strong>ACNEM</strong> <strong>Journal</strong> <strong>Vol</strong> <strong>37</strong> <strong>No</strong> 2 – <strong>June</strong> <strong>2018</strong><br />
Editorial<br />
Penelope Griffiths<br />
<strong>ACNEM</strong> Chief Executive Officer<br />
WORK-LIFE BALANCE – CAN IT REALLY EXIST?<br />
The theme of this editorial came to me when I saw a news<br />
feature recently on an organisation in Australia that has<br />
adopted a 25-hour work week. The organisation is in the<br />
finance sector and all staff have the option of either starting<br />
at 8 or 9 am and the hours are limited to five hours a day.<br />
Rules have been established to ensure that the required work<br />
is done without the ‘extra’ non-essential things that happen<br />
in a workplace. The premise of this is to try and get a strong<br />
definitive ‘Work-Life Balance’ within that organisation. This<br />
made me think of the question of whether a true work-life<br />
balance is really possible in this era of technology, work<br />
expectations and family responsibilities.<br />
Work-Life balance is the term used to describe the balance<br />
that an individual needs, between time allocated for work and<br />
other aspects of life 1 . It doesn’t mean that it needs to be an<br />
equal balance, but a balance that is right for each of us. The<br />
term has been in existence for close to 50 years and originated<br />
in the United Kingdom with other countries adopting its use.<br />
<strong>No</strong> matter what our job is, or in what industry sector we<br />
work, or our own personal circumstances (ie married,<br />
in a relationship, single, children, parental and/or carer’s<br />
responsibilities), many of us struggle with the feeling of being<br />
time poor and stressed as we face difficult challenges every<br />
day of finding that right balance.<br />
Some media headlines in recent times in Australia and New<br />
Zealand all highlight this struggle for work-life balance:<br />
• Australians Struggling to Achieve Work-Life Balance2<br />
• Australians lagging behind OECD countries in work/life<br />
balance, home 3<br />
• More Australians worried about work-life balance,<br />
wellbeing report4<br />
• Managing work-life balance a matter for policy, not just<br />
individuals 5<br />
• Kiwis look for better work-life balance⁶<br />
• Work life balance still a struggle for NZ⁷<br />
• Work life balance a challenge for NZ businesses 8<br />
So what can we conclude from these headlines and studies.<br />
That we all feel overworked with never enough time in the<br />
day to do all that you want to do. I know I do! In fact I didn’t<br />
need a headline or study to tell me that!<br />
Flexible working arrangements are common place – fivehour<br />
days as mentioned above (on full pay I should add), 40<br />
hour weeks over four days, 36 hour weeks over three days<br />
and so the options go on. In Canada, some organisations<br />
have adopted shorter work weeks over the summer months<br />
(known as summer hours), where some organisations close<br />
for a half day on a Friday afternoon or employees have a day<br />
off a fortnight to take advantage of the good weather.<br />
Working from home is obviously a flexible option that is<br />
widely available, however I think while good in theory and<br />
can work well in some situations, it is perhaps not the answer<br />
to achieving a work-life balance unless there are very clear<br />
and known boundaries on when somebody is at work and<br />
when they are not. This is not possible in a great number of<br />
sectors.<br />
The Australian Work and Life Index (AWALI) is a survey<br />
that measures work-life interference, or the tendency for work<br />
to have a negative impact on other areas of life. It shows that<br />
certain groups are more affected than others by work-life<br />
interference. They include:<br />
• women (who generally have worse work-life outcomes<br />
than men, and do around twice as much caring and<br />
domestic work);<br />
• parents (particularly mothers, and even more so single<br />
mothers);<br />
• people who are caring for others, such as sick, elderly or<br />
disabled relatives;<br />
• the ‘sandwich generation’ (women who care for children<br />
as well as elderly or sick relatives have the worst work-life<br />
outcomes); and<br />
• people in certain occupations, including managers,<br />
professionals and those in the mining industry 8 .<br />
However, on the flip side we all know how important work<br />
is in terms of good mental and physical health and wellbeing.<br />
The benefits of work include:<br />
• providing a daily structure,<br />
• provides challenges,<br />
• a sense of meaning, purpose and pride,<br />
• social interaction, including professional relationships,<br />
• helps us to feel part of a community, and of course<br />
• financial benefit.<br />
There is no doubt though, that certain aspects of work<br />
can have a negative impact on a person’s well-being – both<br />
physical and mental. Job stress, isolated working conditions,<br />
psychological demands, lack of rewards for effort, job<br />
insecurity and a lack of control in a job can all contribute to a<br />
lack of balance.<br />
The role of technology needs to be addressed in the worklife<br />
balance scenario. I often yearn for the days of pre-mobile<br />
3
<strong>ACNEM</strong> <strong>Journal</strong> <strong>Vol</strong> <strong>37</strong> <strong>No</strong> 2 – <strong>June</strong> <strong>2018</strong><br />
phone, pre-email, pre-laptops and where the only people<br />
that had your phone number was HR (which was used<br />
for emergency purposes only!). Mail came by the post and<br />
you waited for it to be sorted and then you dealt with it in<br />
a logical and methodical order! There was no need to run,<br />
as there is now, training courses on how to handle receiving<br />
100 plus emails a day (I have been on such a course!). I must<br />
admit I do contact staff out of hours although I do try and<br />
keep this to a minimum and will try, if possible, to do this by<br />
text message.<br />
The blurring of societal behaviours also contributes to this<br />
expectation of being available for work 24/7. When growing<br />
up, I was told it was rude to phone anyone after 9.00pm unless<br />
it was an emergency. <strong>No</strong>w my phone ‘buzzes’ day and night!<br />
We also need to look at the impact that stress and burnout<br />
has. If you can’t switch off or are never given the opportunity<br />
to switch off how does this affect a person’s wellbeing, both<br />
physical and mental. With <strong>ACNEM</strong>’s membership focused<br />
on healthcare, you see all of this in your everyday life. In<br />
fact, I would suggest that many of you also have trouble with<br />
balancing work and life.<br />
Do I have the answers? Is flexibility in working arrangements<br />
the key to getting the balance right between work and home?<br />
Or are there other factors we need to be considering? Perhaps<br />
as practitioners you are able to help provide the answers<br />
either by guiding your patients or leading the way in ‘walking<br />
the talk’. If you have the answer – can you please let me<br />
know? I quite like the sound of summer work hours though!<br />
References<br />
1. Delecta, P. Work Life Balance. International <strong>Journal</strong> of Current<br />
Research. 2011:3:186–189.<br />
2. Australia's welfare 2017. Australian Institute of Health and<br />
Welfare. October 2017. https://www.aihw.gov.au/reports/<br />
australias-welfare/australias-welfare-2017/contents/table-ofcontents<br />
3. Passmore, D. Australians lagging behind OECD countries in<br />
work/life balance, home ownership and safety. The Courier-Mail,<br />
19 October 2017.<br />
4. Jean, P. More Australians worried about work-life balance,<br />
wellbeing report shows. The Advertiser. 19 October 2017<br />
5. Taylor, T. Managing work-life balance a matter for policy, not just<br />
individuals, economist, ABC News, 1 February 2017. http://<br />
www.abc.net.au/news/2017-02-02/work-life-balance-policy-notindividual-actions-economist/8235030<br />
6. Cann, G Working 9-5, it's no way to make a living as Kiwis<br />
look for better work-life balance 27 December 2016. https://<br />
www.hrmonline.co.nz/news/work-life-balance-still-a-struggle-fornz-245580.aspx<br />
7. Diversity Works NZ. Work life balance a challenge for NZ<br />
businesses. 15 January <strong>2018</strong>. https://diversityworksnz.org.nz/<br />
work-life-balance-a-challenge-for-nz-businesses<br />
8. The Australian Work and Life Index (AWALI). 2010. http://<br />
www.unisa.edu.au/Research/Centre-for-Work-Life/Our-research/<br />
Current-Research/Australian-Work-And-Life-Index/<br />
4
Register online at<br />
www.acnem.org<br />
<strong>ACNEM</strong>’s revised cancer care module will explore the speciality area of integrative oncology, showcasing a variety of<br />
therapeutic tools and techniques.<br />
Our experienced presenters will share their working clinical knowledge of hyperbaric oxygen use and hyperthermic<br />
treatments, as well as bringing you up to date on the latest research and use of intravenous vitamin C in this field.<br />
The training will include sessions on how to apply ketogenic diets in clinical practice and how this can benefit your patients,<br />
as well as how all of these tools and techniques can be used with other cancer treatments such as chemotherapy and<br />
radiation.<br />
You will also hear about the metabolic management of cancer, immune modulating nutraceuticals and cancer<br />
pain management. Bring your tricky case questions and build your network with like-minded practitioners.<br />
2 days face-to-face + required activities<br />
For more information and to register online visit acnem.org<br />
Learning Outcomes<br />
Describe the metabolic theory of cancer and the<br />
impact of inflammation on the pathogenesis of<br />
cancer<br />
Outline the detrimental influence of the modern<br />
environment, diet and lifestyle on the development<br />
of specific cancer types<br />
Identify the role of diet and nutrition in the<br />
prevention and management of cancer<br />
Communicate the importance of early intervention<br />
for cellular health and a systems biology approach to<br />
management<br />
Formulate a systematic integrative approach to<br />
making dietary and lifestyle recommendations for<br />
patients in the primary prevention and supportive<br />
management of patients with cancer<br />
Register online at acnem.org<br />
speakers<br />
EARLY BIRD<br />
AND MEMBER<br />
DISCOUNTS<br />
APPLY<br />
Dr Taufiq Binjemain<br />
MBChB(UK), MRCGP(UK), MRCS(Edin),<br />
CCFP(Canada), FRACGP.<br />
Experienced Integrative GP and Clinical<br />
Director of NIIM Gold Coast.<br />
Cliff Harvey<br />
Registered Clinical Nutritionist, PhD Candidate<br />
and Researcher in Nutrition (AUT University).<br />
Published author, presenter and researcher in<br />
the area of low-carbohydrate and ketogenic diets.<br />
Dr Damian Wojcik<br />
MBChB, FRNZCGP, F<strong>ACNEM</strong>, FFCFM (RCPA) M<br />
Forensic Medicine (Monash)<br />
Founder and director of the <strong>No</strong>rthland<br />
Environmental Health Clinic.<br />
AUSTRALASIAN COLLEGE OF NUTRITIONAL AND ENVIRONMENTAL MEDICINE<br />
PROVIDING POST GRADUATE EDUCATION TO DOCTORS AND HEALTHCARE PROFESSIONALS FOR OVER 30 YEARS.<br />
ONLINE COURSES ALSO AVAILABLE - VISIT <strong>ACNEM</strong>.ORG FOR MORE INFORMATION | +61 3 9597 0363 | MAIL@<strong>ACNEM</strong>.ORG<br />
© Australasian College of Nutritional and Environmental Medicine Inc, Australia, <strong>2018</strong>
<strong>ACNEM</strong> <strong>Journal</strong> <strong>Vol</strong> <strong>37</strong> <strong>No</strong> 2 – <strong>June</strong> <strong>2018</strong><br />
Australia's<br />
Leading<br />
Compounder<br />
PERSONALISED MEDICINE<br />
Our compounding solutions involve the creation of medicines in<br />
quality controlled labs that are specifically made for your patients.<br />
SUPPORT<br />
HOTLINE<br />
Created<br />
Allergy Free<br />
Broader Treatment<br />
Options<br />
Optimised for<br />
Highest Quality<br />
Our highly qualified Pharmacists and<br />
Nutritionists are dedicated to supporting<br />
Medical Practitioners, Allied Health<br />
Practitioners and their patients.<br />
Call 1300 564 799 today!<br />
All compounds can be made<br />
free from ingredients that<br />
cause adverse effects or<br />
allergic reactions.<br />
Doses can be reduced,<br />
placed in various forms or<br />
medicines combined to<br />
ensure compliance.<br />
Our medicines are created<br />
in industry leading,<br />
dedicated clean rooms and<br />
compounding labs.<br />
HIGH QUALITY MEDICINE<br />
We have dedicated labs, using the highest quality equipment,<br />
ingredients and raw materials available.<br />
ORDERING<br />
Ordering from us is simple, you can fill out our<br />
mobile friendly online prescription order form<br />
OR<br />
email scripts to<br />
compounding@kingswaycompounding.com.au<br />
OR<br />
fax your script to 1300 564 899.<br />
It’s that easy!<br />
DELIVERY<br />
Temperature<br />
Controlled<br />
Pressure<br />
Controlled<br />
Humidity<br />
Controlled<br />
Extensive<br />
Testing<br />
Standard<br />
Operating<br />
Procedures<br />
Stringent control<br />
& Performance<br />
Logging<br />
We have established strong and reliable<br />
partnerships with national fulfilment suppliers<br />
that follow special instructions required for the<br />
handling of medicine. We deliver locally and<br />
internationally.<br />
GET IN TOUCH WITH US<br />
Ph: 1300 564 799 Fax: 1300 564 899<br />
Email: compounding@kingswaycompounding.com.au<br />
40/9 Powells Rd, Brookvale NSW 2100 Australia<br />
www.kingswaycompounding.com.au<br />
WE DELIVER AUSTRALIA WIDE<br />
AND INTERNATIONALLY<br />
QUALITY CERTIFIED<br />
COMPOUNDED MEDICINE<br />
6
<strong>ACNEM</strong> <strong>Journal</strong> <strong>Vol</strong> <strong>37</strong> <strong>No</strong> 2 – <strong>June</strong> <strong>2018</strong><br />
Association of serum<br />
vitamin D concentrations<br />
with dietary patterns in<br />
children and Adolescents<br />
Authors:<br />
Vijay Ganji1, Bernadette Martineau2 and William Edmund Van Fleit3<br />
1Human Nutrition Department, College of Health Sciences, Qatar University, Doha, Qatar. 2Children Healthcare of Atlanta, Emory<br />
University, Atlanta, GA, USA. 3Georgia State University, Atlanta, GA, USA.<br />
ABSTRACT<br />
Background: Because children have been advised on the<br />
dangers of sun exposure, diet is an important contributor of<br />
serum 25 hydroxyvitamin D [25(OH)D] concentrations.<br />
Aim of this study was to determine whether serum<br />
25(OH)D concentrations were associated with any specific<br />
dietary patterns in US children.<br />
Methods: Data from 2 cycles of National Health and<br />
Nutrition Examination Survey (NHANES) 2003–2004<br />
and 2005–2006 for individuals aged 2 to ≤19 y, were<br />
used to study relation between dietary patterns and serum<br />
25(OH)D. We derived 2 major dietary patterns based on<br />
the food frequency questionnaire data. These were labeled<br />
as High-Fat-Low-Vegetable Dietary (HFLVD) pattern and<br />
Prudent Dietary (PD) pattern.<br />
Results: In multivariate adjusted analysis, there was<br />
no significant relationship between serum 25(OH)D<br />
concentrations and tertiles of HFLVD and PD dietary<br />
pattern scores in all subjects, boys, and girls. When dietary<br />
patterns scores were used as a continuous variable in adjusted<br />
analysis, children (all) with higher PD contribution scores to<br />
overall diet showed a significant positive relation with serum<br />
25(OH)D (ß = 59.1, P = 0.017). When data were stratified<br />
by sex, a significant positive relation was observed in girls<br />
between serum 25(OH)D concentration and PD pattern<br />
scores (ß =82.1, P = 0.015). A significant negative relation<br />
was observed in girls between serum 25(OH)D and HFLVD<br />
pattern scores (ß = − 88.5, P = 0.016).<br />
Conclusion: Overall, serum 25(OH)D were associated<br />
with PD pattern but not with HFLVD pattern in US<br />
children. In public health perspective, it is important to<br />
encourage children, especially girls who are consuming<br />
HFLVD pattern to shift to healthier diet.<br />
BACKGROUND<br />
A classical function of vitamin D is to regulate extracellular<br />
calcium and phosphorus. Current evidence suggests that<br />
vitamin D may play a role in various non-bone diseases<br />
such as autoimmune disease 1,2 , cardiovascular disease 3,4 ,<br />
type-2 diabetes mellitus (T2DM)5, depression6, and<br />
cancer7. Dietary vitamin D sources include oily fish such<br />
as salmon, mackerel, bluefish, sardines and tuna, shiitake<br />
mushrooms (fresh or sundried), and egg yolks. Fortified<br />
dietary sources of vitamin D include milk, orange juice,<br />
infant formulas, yogurts, butter, margarine, cheeses, and<br />
breakfast cereals8.<br />
Serum 25-hydroxyvitamin D [25(OH)D] is a<br />
commonly used marker of vitamin D nutritional status.<br />
Hypovitaminosis D is a widespread problem in the US,<br />
specifically in children and adolescents 9–12 . Prevention of<br />
suboptimal vitamin D status in childhood may reduce<br />
future adverse health conditions. The contribution of<br />
dietary sources to vitamin D status is not clearly known<br />
in children. Some studies have shown that dietary intake<br />
of certain vitamin D rich foods had a significant positive<br />
influence on serum 25(OH)D concentrations 13,14 , whereas<br />
other studies have shown that vitamin D intake did not<br />
affect serum 25(OH)D concentrations 15 . While sunlight<br />
exposure is the major source of circulating serum 25(OH)<br />
D 16 , children and adolescents have been advised on the<br />
dangers of sun exposure 17 and are exposed to increased use<br />
of sunscreen lotions and time spent indoors which has likely<br />
contributed to the increasing prevalence of low vitamin<br />
D status 18 . Therefore, diet is an important contributor of<br />
circulating serum 25(OH)D in the absence of or in the<br />
presence of reduced sunlight exposure.<br />
To our knowledge, no data are available on the relation<br />
7
<strong>ACNEM</strong> <strong>Journal</strong> <strong>Vol</strong> <strong>37</strong> <strong>No</strong> 2 – <strong>June</strong> <strong>2018</strong><br />
between dietary patterns and serum 25(OH)D in US<br />
children and adolescents. Studies that have looked at<br />
diet and vitamin D status have addressed associations<br />
between individual food sources such as fortified milk or<br />
fatty fish. However, people consume a variety of foods<br />
in combination9. Dietary pattern analysis, an alternative<br />
approach to traditional single nutrient epidemiology, takes<br />
into account all nutrient interactions and allows for a more<br />
comprehensive approach to study the relation between<br />
disease and dietary intake 19 . Therefore, the objective of<br />
this study was to determine whether serum 25(OH)D<br />
concentrations were associated with any specific dietary<br />
patterns in US children and adolescents using assayadjusted<br />
data from the National Health and Nutrition<br />
Examination Survey (NHANES) 2003–2006.<br />
METHODS<br />
Brief NHANES survey methods<br />
The National Center for Health Statistics (NCHS)<br />
conducts large, nationally representative, sample surveys<br />
known as NHANES on the noninstitutionalized US<br />
civilian population. A sample representative of individuals<br />
aged > 2 months was selected by using a stratified,<br />
multistage, probability sample survey design. Beginning<br />
in 1999, NHANESs were conducted as annual surveys<br />
and data are released in 2-y cycles for public use. Certain<br />
subgroups including low-income persons, adolescents,<br />
persons aged ≥60 y, non-Hispanic black (NHB), and<br />
Hispanic/ Mexican American (H/MA) are oversampled<br />
to yield more reliable estimates for these specific groups.<br />
The detailed descriptions of the survey design and<br />
methodologies are described elsewhere 20 .<br />
NHANES 2003–2004 was conducted between January<br />
2003 and December 2004 in 12,761 individuals [9643 were<br />
examined in the Mobile Examination Centers (MEC)] and<br />
NHANES 2005–2006 was conducted between January<br />
2005 and December 2006 in 12,862 individuals (9950 were<br />
examined in the MECs). Participants were interviewed<br />
in their homes to gather information on demographic<br />
characteristics, diet, and health. Additional health data<br />
were collected during a medical examination conducted in<br />
MECs. At the MECs, a physical exam, blood and urine<br />
sample collection, and other diagnostic measurements were<br />
performed. All NHANES protocols were approved by<br />
the NCHS Ethics Review Board prior to data collection.<br />
Detailed description of these protocols is found elsewhere 21 .<br />
Households were randomly selected and all members<br />
within the household were screened for demographic<br />
characteristics. One or more individuals within the<br />
household were then selected for sample based on age, sex,<br />
and race-ethnicity. NHANES 2003–2006 sample included<br />
individuals ≥2 mo old. Race-ethnicity was categorized as<br />
non-Hispanic white (NHW), NHB, H/MA, and Other.<br />
Participants self-reported their race-ethnicity status. Poverty<br />
income ratio (PIR) was calculated as the ratio of income to<br />
the family’s appropriate poverty threshold. To avoid damage<br />
to the MECs, examination data in the <strong>No</strong>rth were collected<br />
in spring/summer (May 1–October 31) and in South were<br />
collected in fall/winter (<strong>No</strong>vember 1–April 30). Data for<br />
body mass index (BMI) were obtained from the medical<br />
examination component of NHANES. Supplement users<br />
were defined based on participants who answered ‘yes’<br />
to the question “Did you take supplements in the past<br />
30d?” Participants were asked about hours spent watching<br />
television, playing video games, and using the computer.<br />
Blood samples were collected by venipuncture from<br />
participants in MECs according to standard protocols.<br />
Detailed specimen collection and processing methods<br />
have been previously reported 22,23 . Serum 25(OH)<br />
D concentrations were analyzed and determined at the<br />
National Center for Environmental Health, Centers<br />
for Disease Control and Prevention using the Diasorin<br />
Radioimmunoassay (Stillwater, MN).<br />
Periodically, NHANES data files are updated by the<br />
NCHS, replacing previous data files. In <strong>No</strong>vember 2010,<br />
an update occurred for serum 25(OH)D data because of<br />
changes and drifts in serum 25(OH)D assay over time.<br />
This was likely due to method variation that resulted from<br />
reagent and calibration lot-to-lot variation. The NCHS<br />
released a data advisory for vitamin D and recommended<br />
use of the assay-adjusted data by investigators rather than<br />
previously available unadjusted data. A detailed description<br />
of this data advisory for serum 25(OH)D is described<br />
elsewhere 24 .<br />
A 216-item food frequency questionnaire (FFQ)<br />
component was newly added to NHANES 2003–2004<br />
and was used to gather information on the frequency of<br />
food consumption of participants over the past 12 months.<br />
The questionnaire was developed, tested, and validated<br />
by the National Institutes of Health, National Cancer<br />
Institute. Participants were asked the average number of<br />
times foods were consumed over the past 12 months and<br />
for certain types of foods, their seasonal intake were also<br />
gathered. Participants reported the number of times/d, wk.,<br />
mo, or never that a food was consumed. All foods’ frequency<br />
of consumption was standardized to a monthly intake by<br />
using a conversion factor of 30.4 d/mo as this is the number<br />
of days in an average month. Frequency of consumption was<br />
collected for dairy products, meat, fish and seafood, poultry,<br />
eggs, fruits and juices, vegetables, grains and legumes, snacks<br />
and sweets, beverages, and added fats. Those participants<br />
who did not answer the FFQ were excluded from this study.<br />
Study sample<br />
Two cycles of NHANES 2003–2004 and 2005–2006<br />
were used in this study. Although serum 25(OH)D<br />
concentrations are available publically in NHANES 2001–<br />
2002, this survey was not included in this current study<br />
because FFQ data were not collected. Data on children<br />
between ages 2 to ≤19 y from NHANES 2003–2004 and<br />
2005–2006 were concatenated into one master analytic<br />
database, NHANES 2003–2006 (n = 8747). Subjects with<br />
serum 25(OH)D concentration data were then selected to<br />
include in this study (n = 7172). Of the remaining 7172<br />
8
participants, children < 2 y old were excluded from the<br />
data analysis due to lack of completed FFQ (n = 2572).<br />
Of the remaining 4600 children, 71 were excluded because<br />
they reported that they were lactating or pregnant, 45 were<br />
excluded due to lack of BMI measurement, 4 were excluded<br />
due to lack of calorie intake data, 3 were excluded due to<br />
lack of supplement use data, and 73 were excluded due to<br />
lack as of thiscreen the viewing number response. of days Thus, in an the average final analytic month.<br />
sample Frequency consisted of consumption of 4404 children was collected and adolescents for dairy(Fig. products,<br />
meat, fish and seafood, poultry, eggs, fruits and<br />
1).<br />
juices, vegetables, grains and legumes, snacks and sweets,<br />
beverages, and added fats. Those participants who did not<br />
Study variables<br />
answer the FFQ were excluded from this study.<br />
In this study, the foods from the FFQ were categorized into<br />
30 Study food sample groups. These 30 food groups were low-fat and<br />
high-fat Two cycles dairy products, of NHANES dairy 2003–2004 alternatives, and fish and 2005–2006 other<br />
seafood, were used eggs, inmeat, this study. processed Although meat, serum poultry, 25(OH)D creamed concentrations<br />
soups, pizza, are available mixed foods, publically cereals, in refined NHANES grains, 2001–<br />
soups,<br />
other<br />
whole 2002, grains, this survey nuts, was legumes, not included tomatoes, incruciferous, this current starchy, study<br />
and because other FFQ vegetables, data were fruit, not fruit collected. juices, snacks Data and on children sweets,<br />
butter between and ages margarine, 2 to ≤19 other y from fats, NHANES added sugars, 2003–2004 coffee/tea, and<br />
energy 2005–2006 drinks were (high concatenated or low), and into alcohol one(Table master 1). analytic Foods<br />
were database, categorized NHANES based 2003–2006 on nutrient (n profiles = 8747). or Subjects culinary with use<br />
and serum were 25(OH)D grouped similar concentration to those data used were in other thenstudies selected 25 .<br />
Frequency to includeof in dietary this study intake (n of = these 7172). 30 Of food the groups remaining for<br />
each 7172individual participants, was children used to identify < 2 y oldmajor weredietary excluded patterns. from<br />
<strong>ACNEM</strong> <strong>Journal</strong> <strong>Vol</strong> <strong>37</strong> <strong>No</strong> 2 – <strong>June</strong> <strong>2018</strong><br />
Age, sex, race-ethnicity, BMI, PIR, time of examination,<br />
use of supplements, energy intake, and screen use hours<br />
were considered as potential confounding variables as these<br />
are known to affect serum 25(OH)D concentrations 18,26 .<br />
Participants were categorized into 2–3 y, 4–8 y, 9–13 y, and<br />
14–19 y old age groups. BMI was categorized as normal<br />
weight (<br />
excluded 2.5), and because not reported. they reported Combined thattelevision, they werecomputer, lactating and<br />
orvideo pregnant, game 45 use were hours excluded were categorized due to lackas of ≤2 BMI h, 3–4 measurement,<br />
4 h/d. Smoking 4 were excluded status and due alcohol to lack intake of calorie variables intake were also<br />
h, or ><br />
data, considered 3 wereas excluded potential due confounding to lack of variables. supplement However, use<br />
data, smoking-related and 73 were excluded questions due were toonly lackasked of screen to children viewingaged<br />
response. ≥12 y and Thus, alcohol-related the final analytic questions sample were asked consisted to adults of<br />
4404 aged children ≥20 y; and therefore, adolescents both were (Fig. dropped 1). from the analysis.<br />
Ganji et al. Nutrition <strong>Journal</strong> (<strong>2018</strong>) 17:58 Page 3 of 11<br />
Study variables<br />
In this study, the foods from the FFQ were categorized<br />
Data analysis<br />
into 30 food groups. These 30 food groups were low-fat<br />
and Statistical high-fatanalysis dairy products, was performed dairy alternatives, using SAS statistical fish and<br />
other software seafood, (version eggs, 9.2, meat, SAS Institute) processedas meat, it is capable poultry, of<br />
creamed handling soups, the complex other soups, survey pizza, design mixed of NHANES. foods, cereals, The<br />
refined survey grains, analysis whole procedures grains, accounted nuts, legumes, for primary tomatoes, sampling<br />
cruciferous, unit, stratum, starchy, cluster, and and other observation vegetables, weight fruit, in the fruit<br />
juices, calculation snacksof and variances sweets, used butter for interval and margarine, estimation other and<br />
National Health and Nutrition<br />
Examination Survey 2003-2006-<br />
children 2-19 years old<br />
(n=8,747)<br />
Subjects selected with serum 25-<br />
hydroxyvitamin D concentration<br />
(n=7,172)<br />
Subjects selected with serum 25-<br />
hydroxyvitamin D concentration and<br />
food frequency data<br />
(n=4,600)<br />
Ineligible due to lack of 25-<br />
hydroxyvitamin D concentration<br />
(n=1,575)<br />
Ineligible due to lack of food frequency<br />
data (n=2,572)<br />
Excluded due to pregnancy and lactation<br />
(n=71)<br />
Excluded due to lack of data for BMI<br />
(n=45)<br />
Excluded due to lack of data for energy<br />
intake (n=4)<br />
Excluded due to lack of data for<br />
supplement use (n=3)<br />
Excluded due to lack of data for screen<br />
viewing time (n=73)<br />
Final eligible study sample: children 2-<br />
19 y old with all study variables<br />
(n=4,404)<br />
Fig. 1 Study sample derivation after removing subjects for missing data for main variables and confounding variables sequentially<br />
(weighted n = 60,274,698)<br />
9
<strong>ACNEM</strong> <strong>Journal</strong> <strong>Vol</strong> <strong>37</strong> <strong>No</strong> 2 – <strong>June</strong> <strong>2018</strong><br />
hypothesis testing. The NOMCAR option was used in all<br />
analyses so that design variables with missing values are<br />
used in the domain analysis to estimate variances using<br />
Taylor series linearization method. Detailed guidelines on<br />
the sample weighting and the proper variance estimation<br />
procedures are outlined in the NHANES Analytic and<br />
Reporting Guidelines 20 .<br />
Factor fats, added analysis sugars, (principal coffee/tea, component) energy was drinks used to (high identify or<br />
dietary low), and patterns alcohol based (Table on the 1). frequency Foods of were dietary categorized intake<br />
of based the 30 onpredefined nutrient food profiles groups. or culinary The PROC use FACTOR and were<br />
procedure grouped similar in SAS to was those used to used conduct in other this analysis. studies The [25].<br />
factors Frequency were of rotated dietary by intake orthogonal of these transformation 30 food groups to for<br />
achieve each individual a structure was of independent used to identify factors with major greater dietary<br />
interpretability. patterns. Age, The sex, number race-ethnicity, of factors BMI, that were PIR, retained time of<br />
was examination, determined use based of on supplements, an Eigenvalue energy (≥1.5), intake, explained and<br />
variance screen use (≥5%), hours and were Cattell considered scree plot. as potential The remaining confounding<br />
variables were considered as these the are main known dietary to patterns affectand serum were<br />
factors<br />
labeled 25(OH)D based concentrations interpretation [18, of 26]. the data. Participants Factor loadings were<br />
categorized into 2–3 y,4–8 y, 9–13 y, and 14–19 y old<br />
were derived for each of the 30 food groups across the<br />
extracted factors. For each dietary pattern, a factor score was<br />
calculated for each participant by combining the frequency<br />
of dietary intake of the food groups weighted by their factor<br />
loadings. Dietary pattern scores were then stratified into<br />
tertiles (low, medium, and high) based on the factor scores<br />
for each dietary pattern.<br />
ageChi-square groups. BMI tests were was used categorized to identify as associations normal weight between<br />
( serum 2.5), and 25(OH)D not reported. concentrations Combined and dietary television, patterns. computer,<br />
Associations and video were game analyzed use hours according wereto categorized the participants’ as<br />
≤2factor h, 3–4 scores h, or for > 4each h/d. dietary Smoking pattern status divided and alcohol into tertiles intake<br />
(low, variables medium, and werehigh), alsoand considered to the factor asscores potential as a<br />
confounding continuous variables. variable. This However, analysis smoking-related included sex, age, questionethnicity,<br />
were use only of supplements, asked to children time of aged examination, ≥12 y and BMI,<br />
race-<br />
alcohol-related PIR, and screen questions use hours were as asked potential to adults confounding aged ≥20<br />
y; therefore, both were dropped from the analysis.<br />
Ganji et al. Nutrition <strong>Journal</strong> (<strong>2018</strong>) 17:58 Page 4 of 11<br />
Table 1 Food groups used in the dietary pattern analysis: NHANES 2003-2006 a<br />
Food Groups b<br />
Foods from Food-Frequency<br />
Questionnaire c<br />
Low-fat dairy<br />
1, 2%, skim, nonfat, and evaporated milk; yogurt/frozen, low-fat cheese,and low-fat sour cream<br />
High-fat dairy<br />
Whole milk, cream, ice cream, pudding, cottage cheese, cheese, and sour cream<br />
Dairy alternative<br />
Soy, rice, and other milk; non-dairy creamer, and meal replacement beverage<br />
Fish and other seafood<br />
Oysters, clams, and shellfish; fish: fillets, sticks, tuna, salmon, and raw fish sushi<br />
Eggs<br />
Egg whites, whole egg, egg substitute, and egg salad<br />
Meat<br />
Beef, steak, roasts, hamburger, pork, ribs, and ham<br />
Processed Meat<br />
Bacon, Canadian bacon, sausage, hot dogs, luncheon meats, liver, and Liverwurst<br />
Poultry<br />
Chicken, all types; and turkey<br />
Creamed soup<br />
Creamed soups, all types; and chowders<br />
Other soup<br />
Broth-based soups and bean soups<br />
Pizza<br />
Pizza, all types<br />
Mixed dishes<br />
Casseroles, lasagna, macaroni and cheese, and chili<br />
Cereal<br />
Oatmeal, grits, and other cooked cereals; and cold cereal, all types<br />
Refined grains<br />
English muffin, bagel, roll, cracker, stuffing, cornbread, biscuit, pancake, waffle, pasta, and rice<br />
Whole grains<br />
Dark breads and rolls; brown rice, bulgur, cracked wheat and millet; and granola bars<br />
Nuts<br />
Peanuts, walnuts, and other nuts; seeds; and nut butters<br />
Legumes<br />
Pintos, kidney, blackeyed peas, lima, lentils, refried beans, baked beans, soybeans, and tofu<br />
Starchy vegetables<br />
White potatoes, french fries, and potato salad; squash, sweet potatoes, carrots, and yams<br />
Tomatoes<br />
Tomatoes, including fresh, tomato juice, and salsa<br />
Cruciferous and green vegetables<br />
Spinach, turnip, collard, chard, kale, broccoli, cabbage, cauliflower, Brussel sprouts, and lettuce<br />
Other vegetables<br />
Pickles, green beans, peas, peppers, onion, cucumber, corn, and mixed Vegetables<br />
Fruit<br />
Apples, pears, peaches, bananas,melons, strawberries, grapes, pineapple, and dried fruit<br />
Fruit juices<br />
Orange juice, grapefruit juice, apple juice, grape juice, and prune juice<br />
Sweets and Snacks<br />
Donuts, danish, cookie, brownie, cake, pie, cobbler, popcorn, pretzels, tortilla chips, and candy<br />
Butter and Margarine<br />
Butter and margarine, all types<br />
Other fats<br />
Olive oil, corn oil, canola oil, salad dressings, mayonnaise, and gravies<br />
Condiments<br />
Maple syrup, honey, jam, and jelly<br />
Coffee/Tea<br />
Coffee and tea, regular and decaffeinated<br />
Energy drinks<br />
Sodas and fruit drinks, including Hi-C, Kool-Aid, lemonade, and cranberry cocktail<br />
Alcohol<br />
Beer, wine, wine coolers, hard liquor, and mixed drinks<br />
a n = 4404; weighted n = 60,274,698. NHANES 2003–2004 and 2005–2006 were combined into one master database, NHANES 2003–2006<br />
b Foods consumed by survey participants were categorized into 30 food groups based on nutrient profiles or culinary use<br />
c Food consumption data were collected using a 216-item qualitative Food Frequency Questionnaire<br />
10
variables. Variables found to be non-significant such as<br />
PIR and use of supplements were dropped from the<br />
model. Because previous studies found differences of serum<br />
25(OH)D concentrations by sex 11, 26 , the present analysis<br />
for the relation between serum 25(OH)D and dietary<br />
patterns was then stratified by sex. Univariate ANOVA was<br />
used to establish if serum 25(OH)D concentrations varied<br />
across dietary patterns for all subjects, boys, and girls in an<br />
unadjusted analysis. Analysis of covariance (ANCOVA)<br />
was utilized to establish if serum 25(OH)D concentrations<br />
varied across dietary patterns after adjusting for various<br />
confounding variables. Multiple comparisons among dietary<br />
patterns for serum 25(OH)D concentrations were made<br />
using independent unpaired t-tests with a Bonferroni<br />
correction. Serum 25(OH)D concentrations were presented<br />
as mean ± standard error (SE). Statistical significance was<br />
set at a = 0.05.<br />
RESULTS<br />
General demographic characteristics of study sample<br />
The sample consisted of 51.5% (n = 2154) boys and 48.5%<br />
(n = 2250) girls. Of the 4404 participants, 62.5% (n =<br />
1293) were NHW, 15.3% (n = 1428) were NHB, and<br />
13.3% (n = 1323) were H/MA. The participants were<br />
distributed across the age categories: 8.4% (n = 399) 2–3<br />
y, 26.4% (n = 924) 4–8 y, 29.9% (n = 1282) 9–13 y, and<br />
35.3% (n = 1799) 14–19 y olds. Of the study population,<br />
34.1% (n = 1133) reported having taken a supplement 30 d<br />
prior to the completing the survey. The majority (61.1%, n<br />
= 2215) of the participants were examined in the summer.<br />
84.8% (n = 3626) were classified as healthy weight and<br />
15.2% (n = 778) as overweight and obese based on the<br />
BMI. The majority (49.9%, n = 1984) reported ≤2 h/d of<br />
television, computer, and video game usage, although 28.5%<br />
(n = 1296) reported between 3 and 4 h/d of usage and<br />
21.6% (n = 1124) reported > 4 h/d of usage.<br />
Dietary patterns<br />
Two major dietary patterns were identified based on the<br />
factor analysis from the 30 predefined food groups (Table<br />
1). Higher positive factor loading scores are interpreted<br />
to contribute most to the factor score, and conversely,<br />
higher negative factor loading scores contribute least to<br />
the factor score. The 1st factor had heavy factor loading<br />
scores for meats, snacks and sweets, condiments, mixed<br />
dishes, pizza, processed meats, refined grains, high fat dairy,<br />
coffee/tea, poultry, starchy vegetables, and fish and other<br />
seafood. Thus, the 1st factor was labeled as the High-Fat-<br />
Low-Vegetable Dietary (HFLVD) pattern. This was the<br />
most dominant dietary food pattern in the population and<br />
explained largest variance in food intake. The 2nd factor had<br />
heavy factor loading scores for all vegetable groups, fruit,<br />
other fats, mixed dishes, fish and other seafood, tomatoes,<br />
and meats. Thus, the 2nd factor was labeled as the Prudent<br />
dietary (PD) pattern. The detailed factor loading matrixes<br />
are listed in Table 2.<br />
11<br />
<strong>ACNEM</strong> <strong>Journal</strong> <strong>Vol</strong> <strong>37</strong> <strong>No</strong> 2 – <strong>June</strong> <strong>2018</strong><br />
Characteristics of study population by dietary pattern<br />
The sample distribution by characteristics of the study<br />
population across tertiles of each dietary pattern is<br />
presented in Table 3. Proportion of persons belonging to<br />
NHW and H/MA race-ethnicities tended to decrease,<br />
while proportion of persons belonging to NHB tended to<br />
increase across the tertiles of HFLVD pattern scores (P <<br />
0.001). Ganji etProportion al. Nutrition <strong>Journal</strong> of children (<strong>2018</strong>) 17:58 in the 14–19 y old age group<br />
tended to increase from tertile 1 (30.1%) to tertile 3 (40.6%)<br />
(P = 0.003), while their proportion tended to decrease from<br />
Table 2 Factor loading matrix for dietary patterns in National<br />
Health and Nutrition Examination Survey (NHANES) 2003-2006 a,b<br />
Category c<br />
Cruciferous & green<br />
vegetables<br />
Factor 1: HFLVD<br />
Pattern d<br />
0.118 0.705<br />
Factor 2: PD<br />
Pattern d<br />
Other vegetables 0.144 0.734<br />
Tomatoes 0.172 0.464<br />
Starchy vegetables 0.514 0.518<br />
Fruit 0.199 0.676<br />
Fruit juice 0.364 0.243<br />
Nuts 0.228 0.409<br />
Legumes 0.085 0.406<br />
Fish & other seafood 0.505 0.479<br />
Meat 0.645 0.457<br />
Poultry 0.519 0.392<br />
Processed Meat 0.580 0.346<br />
Whole grains −0.049 0.448<br />
Refined grains 0.570 0.448<br />
Cereals 0.084 0.347<br />
Eggs 0.279 0.298<br />
Low fat dairy −0.136 0.413<br />
High fat dairy 0.543 0.133<br />
Dairy Alternative/Meal<br />
Replacement<br />
0.203 0.082<br />
Creamed soups 0.163 0.196<br />
Other soups 0.299 0.415<br />
Mixed dishes 0.605 0.523<br />
Pizza 0.604 0.089<br />
Snacks & sweets 0.635 0.338<br />
Butter & Margarine 0.423 0.288<br />
Other fats 0.353 0.525<br />
Condiments 0.632 0.173<br />
Energy drinks 0.513 −0.074<br />
Alcohol 0.120 −0.018<br />
Coffee/Tea 0.523 −0.078<br />
a n = 4404; weighted, n = 60,274,698. Correlation coefficients<br />
b Factor procedure, principal component analysis. Two factors with Eigenvalues<br />
≥1.5 were rotated and extracted. Factors were labeled according to the foods<br />
found to have the highest correlation coefficients within each factor (dietary<br />
pattern). Positive factor scores indicate that those foods are more likely to be<br />
consumed in that dietary pattern. Lower negative scores indicate that those<br />
foods are least likely to be consumed in that dietary pattern<br />
c Food categories were based on consumption data collected from a 216-item<br />
Food Frequency Questionnaire from NHANES 2003–2004 and 2005–2006.<br />
Individual foods were categorized into 30 food groups<br />
d High-Fat-Low-Vegetable Dietary Pattern or Prudent Dietary Pattern<br />
to increase across the tertiles of HFLVD pattern scores<br />
(P < 0.001). Proportion of children in the 14–19 y old<br />
age group tended to increase from tertile 1 (30.1%) to<br />
tended t<br />
(26.8%)<br />
patterns,<br />
category<br />
the high<br />
pattern,<br />
of comb<br />
tended t<br />
the high<br />
while th<br />
(42.7%)<br />
(P < 0.00<br />
Subject<br />
tern (P f<br />
the PD p<br />
have con<br />
group of<br />
< 0.001. S<br />
pattern h<br />
puter, an<br />
group (≤<br />
high-inta<br />
bined us<br />
(P for tre<br />
Relation b<br />
The rela<br />
and dieta<br />
scores ar<br />
gression<br />
fered sig<br />
pattern s<br />
0.012). S<br />
scores ha<br />
pared to<br />
scores (+<br />
spectively<br />
ing varia<br />
the boys<br />
HFLVD o<br />
Girls wit<br />
slightly h<br />
compared<br />
19.9 ± 0.6<br />
The re<br />
and dieta<br />
presented<br />
with high<br />
showed a<br />
concentr<br />
adjusted<br />
scores to<br />
ation wit
Ganji et al. Nutrition <strong>Journal</strong> (<strong>2018</strong>) 17:58 Page 7 of 11<br />
<strong>ACNEM</strong> <strong>Journal</strong> <strong>Vol</strong> <strong>37</strong> <strong>No</strong> 2 – <strong>June</strong> <strong>2018</strong><br />
Table 3 Sample distribution by demographic and health characteristics according to the tertiles of factor scores for dietary patterns:<br />
National Health and Nutrition Examination Survey (NHANES) 2003-2006 a, b<br />
Characteristic HFLVD Pattern Score c (n = 4404) PD Pattern Score c (n = 4404)<br />
Low<br />
( 0.000925)<br />
P for Trend d<br />
Low<br />
(< 0.004175)<br />
Medium (− 0.004175<br />
to 0.001912)<br />
N 1338 1465 1601 1523 1<strong>37</strong>6 1505<br />
Sex<br />
High<br />
(> 0.001912)<br />
Boys, % 48.6 51.8 54.2 0.165 48.7 55.8 50.1 0.098<br />
Girls, % 51.4 48.2 45.8 51.3 44.2 49.9<br />
Race-ethnicity<br />
NHW, % 70.0 62.2 55.2 < 0.001 61.0 66.4 60.0 0.003<br />
NHB, % 7.3 13.9 24.7 18.0 13.2 14.7<br />
Age<br />
H/MA, % 14.3 14.1 11.5 10.9 13.1 15.9<br />
Other, % 8.3 9.8 8.6 10.9 7.3 9.4<br />
P for Trend d<br />
2–3 y, % 9.6 8.9 6.7 0.003 5.3 8.9 11.0 < 0.001<br />
4–8 y, % 25.8 26.6 26.8 18.6 30.0 30.4<br />
9–13 y, % 34.6 29.4 25.8 27.3 30.7 31.8<br />
14–19 y, % 30.1 35.1 40.6 48.8 30.4 26.8<br />
Poverty income ratio e<br />
< 1.0, % 16.7 19.6 28.4 < 0.001 20.4 20.0 24.3 0.001<br />
1.0–2.5, % 33.0 31.9 32.0 32.5 29.8 34.7<br />
≥2.5, % 48.1 44.7 <strong>37</strong>.2 42.3 48.2 39.3<br />
<strong>No</strong>t reported, % 2.1 3.8 2.4 4.8 2.0 1.6<br />
Season of Examination f<br />
Fall/Winter, % 40.2 39.6 36.8 0.693 39.0 36.3 41.4 0.395<br />
Spring/Summer, % 59.8 60.4 63.2 61.0 63.7 58.6<br />
Use of Supplements g<br />
Yes, % 38.4 35.3 28.5 0.003 27.0 36.4 38.9 < 0.001<br />
<strong>No</strong>, % 61.6 64.7 71.5 73.0 63.6 61.1<br />
Body mass index<br />
4 h, % 15.2 22.8 26.9 27.0 20.6 17.3<br />
a n = 4404; weighted n = 60,274,698. NHANES 2003–2004 and 2005–2006 were combined into one master database, NHANES 2003–2006<br />
b Dietary pattern scores were stratified into tertiles (low, medium, and high) based on factor scores for each dietary pattern<br />
c High-Fat-Low-Vegetable Dietary pattern or Prudent Dietary pattern<br />
d Significance determined by Rao-Scott chi-square test<br />
e Ratio of income to the family’s appropriate poverty threshold. A ratio of < 1.0 is characterized as below poverty<br />
f Data collected during May 1–October 31 (spring/summer) and <strong>No</strong>vember 1–April 30 (fall/winter)<br />
g Participants who took supplements 30 days before survey was conducted<br />
h Data collected on the combined hours of television, computer, and video games usage per day<br />
tertile boys and 1 (48.8%) girls, only to tertile girls showed 3 (26.8%) significant (P < 0.001). relation In both with showed pattern a(P significant for trend = positive 0.003) and association the high-intake to serum group<br />
the serum HFLVD 25(OH)D and PD concentrations patterns, the for proportion both dietary of children pattern in 25(OH)D of the PD concentrations pattern (P for (β trend< = 79.8; P 0.001) = 0.035). were more likely<br />
the scores. lowest Girls PIR with category higher tended HFLVD to increase contribution from the scores lowest In to have the consumed adjusted multivariate supplements. regression Subjects in analysis, the low-intake all<br />
tertile showed to the a significant highest tertile negative pattern relation scores. In (β = the − 193; HFLVD P < subjects group of with the higher PD pattern PD contribution had a higher scores BMI (P tofor overall trend <<br />
pattern, 0.001) the andproportion girls withof higher children PDwho contribution viewed ≤2 h scores of diet 0.001. showed Subjects a significant in the high-intake positive relation group of with the HFLVD serum<br />
combined television, computer, and video games tended pattern had higher combined usage of television, computer,<br />
to decrease from the lowest tertile (59.8%) to the highest and video games/d than those in the low-intake group (≤2<br />
tertile (41.6%) pattern scores (P < 0.001), while they h/d) (P for trend < 0.0001). Subjects in the high-intake<br />
tended to increase from the lowest (42.7%) to the highest group of the PD pattern had lower combined usage of<br />
tertile (55.4%) pattern scores (P < 0.001).<br />
television, computer, and video games/d (P for trend <<br />
0.0001).<br />
Subjects in the low-intake group of the HFLVD<br />
12
Ganji et al. Nutrition <strong>Journal</strong> (<strong>2018</strong>) 17:58 Page 8 of 11<br />
<strong>ACNEM</strong> <strong>Journal</strong> <strong>Vol</strong> <strong>37</strong> <strong>No</strong> 2 – <strong>June</strong> <strong>2018</strong><br />
Table 4 Relation of serum 25(OH)D concentrations with dietary pattern scores: National Health and Nutrition Examination Survey<br />
(NHANES) 2003-2006 a,b<br />
HFLVD Pattern Score (n = 4404) c, d<br />
PD Pattern Score (n = 4404) c, d<br />
Unadjusted analysis<br />
All subjects<br />
(n = 4404)<br />
Low<br />
( 0.000925) P- value e Low<br />
(< 0.004175)<br />
Medium (− 0.004175<br />
to 0.001912)<br />
High<br />
(> 0.001912)<br />
ng/mL ng/mL ng/mL ng/mL ng/mL ng/mL<br />
27.3 ± 0.5 26.1 ± 0.6 24.8 ± 0.7 0.003 24.7 ± 0.7 26.8 ± 0.5 26.7 ± 0.6 0.012<br />
Boys (n = 2154) 27.4 ± 0.6 26.8 ± 0.7 25.8 ± 0.8 0.123 25.8 ± 0.7 26.9 ± 0.7 27.3 ± 0.7 0.151<br />
Girls (n = 2250) 27.2 ± 0.7 25.2 ± 0.8 23.6 ± 0.8 0.003 23.6 ± 0.9 26.6 ± 0.6 26.1 ± 0.7 0.005<br />
Adjusted analysis<br />
All subjects 22.1 ± 0.4 22.1 ± 0.3 21.7 ± 0.5 0.594 21.4 ± 0.5 22.1 ± 0.3 22.5 ± 0.4 0.195<br />
(n = 4404) f<br />
Boys (n = 2154) g 22.9 ± 0.5 23.3 ± 0.4 23.1 ± 0.6 0.810 23.0 ± 0.5 22.9 ± 0.4 23.5 ± 0.5 0.<strong>37</strong>0<br />
Girls (n = 2250) g 21.4 ± 0.5 20.9 ± 0.5 20.4 ± 0.7 0.529 19.9 ± 0.6 21.5 ± 0.5 21.5 ± 0.5 0.064<br />
P- value e<br />
a n = 4404; weighted n = 60,274,698. NHANES 2003–2004 and 2005–2006 were combined into one master database, NHANES 2003–2006. Regression analysis of<br />
dietary patterns scores and serum 25(OH)D concentrations<br />
b Dietary pattern scores were stratified into tertiles (low, medium, and high) based on factor scores for each dietary pattern<br />
c Mean ± standard error<br />
d High-Fat-Low-Vegetable Dietary Pattern or Prudent Dietary Pattern<br />
e Significance determined by F-test in analysis of variance for unadjusted analysis and in analysis of covariance for adjusted analysis<br />
f Analysis was adjusted for sex, race-ethnicity, age, season of examination, body mass index, and daily screen viewing. Poverty income ratio, supplement use, and<br />
energy intake were not found significant in this model and therefore those variables dropped<br />
g Analysis was adjusted for race-ethnicity, age, time of examination, body mass index, and daily screen viewing. Poverty income ratio, supplement use, and energy<br />
intake were not found significant in this model and therefore these variables were dropped<br />
children concentrations [27]. Poti (ß et = 79.8; al. [27] P = using 0.035). the NHANES data<br />
derived Western and Prudent dietary patterns. Studies<br />
relating In the vitamin adjusted Dmultivariate intake withregression the vitamin analysis, D status all have subjects<br />
shown with higher conflicting PD contribution results [13, scores 15, 27]. to overall We found diet showed that<br />
subjects a significant with positive high PDrelation patternwith scores serum had25(OH)D significantly (ß =<br />
higher 59.1; serum P = 0.017). 25(OH) Similarly, concentrations when subjects compared were tostratified<br />
those<br />
with into HFLVD boys and pattern girls in scores. the adjusted In contrast, analysis, Polish only vegetarianshowed<br />
children a significant had 2-foldrelation lower with serum serum 25(OH)D 25(OH)D concen-<br />
girls<br />
trations concentrations than infor their both omnivorous pattern scores. counterparts Girls with higher [28].<br />
While HFLVD in this contribution study thosescores who consumed showed a significant the PD pattern negative<br />
were relation not (ß necessarily = − 88.5; vegetarians, P = 0.016) they and girls did have with higher PD<br />
factor contribution scores for scores many showed similara significant type of foods positive foundassociation<br />
in a<br />
vegetarian (ß = 82.1; diet P = and 0.015) lesserto factor serum scores 25(OH)D for foods concentrations. typical<br />
in an omnivorous diet. However Chan et al. [29] found<br />
no association between serum 25(OH)D and vegetarian<br />
status. DISCUSSION Differences between studies may be due to<br />
differences in subject characteristics and confounding<br />
variables To our used knowledge, in the statistical this the analysis. most comprehensive study<br />
that The investigated highest serumthe concentrations relation between for serum all subjects 25(OH) were<br />
found D concentrations in those with and low-intake dietary patterns HFLVD in children scores or and in<br />
those adolescents with medium- in a nationally and high-intake representative PD pattern sample scores. survey.<br />
InUsing this analysis factor analysis, individuals we derived were scored HFLVD on each and PD pattern, patterns.<br />
therefore Serum 25(OH)D a person’s diet was would significantly be represented lower in HFLVD by a combination<br />
compared of both to PD factors. pattern, Aand highthe factor highest score serum from25(OH)<br />
one<br />
dietary D concentrations pattern doesfor not all necessarily subjects were mean in those a lowwith factor low<br />
score HFLVD from or themedium other dietary and high-intake pattern for PD anpatterns individual. scores.<br />
However, In the multivariate these results adjusted seem toanalysis, suggesta that significant the greatest positive<br />
serum relation 25(OH)D was found concentrations between PD occurred pattern factor in individuals scores and<br />
who serum consumed 25(OH)D a healthier concentrations. type diet When that data had were a higher stratified<br />
by sex, a significant positive relation was observed in girls<br />
who consumed the PD dietary pattern and a significant<br />
negative relation was observed in girls who consumed the<br />
HFLVD dietary pattern.<br />
Dietary patterns derived in this study were similar to<br />
the dietary patterns reported in the literature on US<br />
13
Ganji et al. Nutrition <strong>Journal</strong> (<strong>2018</strong>) 17:58 Page 9 of 11<br />
<strong>ACNEM</strong> <strong>Journal</strong> <strong>Vol</strong> <strong>37</strong> <strong>No</strong> 2 – <strong>June</strong> <strong>2018</strong><br />
Table 5 Relation of serum 25(OH)D concentrations with dietary<br />
pattern scores: National Health and Nutrition Examination<br />
Survey (NHANES) 2003-2006 a,b<br />
β c Standardized β SE for β d P-value e<br />
Unadjusted analysis<br />
HFLVD Pattern Score f<br />
All subjects −135.6 −0.13 32.3 < 0.001<br />
Boys −81.4 −0.08 47.8 0.099<br />
Girls −193.0 −0.19 36.7 < 0.001<br />
PD Pattern Score f<br />
All subjects 57.12 0.06 30.8 0.073<br />
Boys 36.13 0.04 31.8 0.265<br />
Girls 79.75 0.08 36.1 0.035<br />
Adjusted analysis<br />
HFLVD Pattern Score f<br />
All subjects g − 39.1 −0.04 26.6 0.153<br />
Boys h 17.7 0.02 36.3 0.631<br />
Girls h − 88.5 −0.09 34.6 0.016<br />
PD Pattern Score f<br />
All subjects g 59.1 0.06 23.5 0.017<br />
Boys h 35.7 0.03 24.1 0.149<br />
Girls h 82.1 0.08 31.8 0.015<br />
a n = 4404; weighted n = 60,274,698. NHANES 2003–2004 and 2005–2006 were<br />
combined into one master database, NHANES 2001–2006<br />
b Regression analysis using factor scores as continuous variable and dependent<br />
variable, serum 25(OH)D concentrations<br />
c Multivariate regression coefficient<br />
d Standard error for multivariate regression coefficient<br />
e Significance between dietary patterns and serum 25(OH)D in the<br />
regression model<br />
f High-Fat-Low-Vegetable Dietary pattern or Prudent Dietary pattern<br />
g Analysis was adjusted for sex, race-ethnicity, age, season of examination,<br />
body mass index, and daily screen viewing. Poverty income ratio, supplement<br />
use, and energy intake were not found significant in this model, therefore<br />
those variables were dropped from the analysis<br />
h Analysis was adjusted for race-ethnicity, age, season of examination, body<br />
mass index, and daily sun screen viewing. Poverty income ratio, supplement<br />
use, and energy intake were not found significant in this model, therefore<br />
those variables were dropped from the analysis<br />
children emphasis 27 . Poti on vegetables, et al. 27 using fruits, the NHANES and some data emphasis derived on<br />
Western mixed dishes, and Prudent fish, and dietary meats. patterns. The differences Studies relating seen in<br />
vitamin serum D 25(OH)D intake with concentrations the vitamin D may status behave dueshown<br />
to the<br />
conflicting factors other results than 13,15,27 diet; . We because found that whensubjects the analysis with high was<br />
PD adjusted pattern for scores confounding had significantly variables, higher the serum association 25(OH)<br />
concentrations between serumcompared 25(OH)D to those concentrations with HFLVD andpattern<br />
dietary<br />
scores. patterns In contrast, was no longer Polish present. vegetarian This children was seen had in 2-fold other<br />
lower studies serum such25(OH)D that otherconcentrations factors such asthan race, in season, their and<br />
omnivorous sun exposure counterparts were more 28 . significant While in this predictors study those of serum who<br />
consumed 25(OH)D the concentrations PD pattern than were dietary not necessarily intake [30, vegetarians, 31].<br />
they The did higher have higher serumfactor 25(OH)D scores concentrations for many similar intype<br />
those<br />
of who foods adhere found more in a closely vegetarian to adiet PD and pattern lesser may factor be related scores<br />
for to foods certain typical lifestyle in an and omnivorous health-related diet. However factors. Chan In this et<br />
al. study, 29 found weno found association that children between with serum high 25(OH)D PD pattern and<br />
vegetarian scores hadstatus. consumed Differences morebetween supplements studies compared may be due to<br />
to differences in subject characteristics and confounding<br />
variables used in the statistical analysis.<br />
The highest serum concentrations for all subjects were<br />
found in those with low-intake HFLVD scores or in those<br />
with medium- and high-intake PD pattern scores. In this<br />
analysis individuals were scored on each pattern, therefore<br />
a person’s diet would be represented by a combination of<br />
this both with factors. high A HFLVD high factor pattern score scores. from Consumption one dietary pattern of<br />
dietary does not supplements necessarily has mean been a low associated factor score with from anthe<br />
increase<br />
other of dietary serumpattern 25(OH)D for an concentration individual. However, [32]. Children these<br />
who results consumed seem to vitamin suggest Dthat supplements the greatest were serum less 25(OH) likely<br />
toD beconcentrations vitamin D deficient occurred [9]. in Additionally, individuals who it has consumed been a<br />
suggested healthier that type the diet bioavailability that had a higher of vitamin emphasis D on may vegetables, be<br />
lowfruits, in those and who some are emphasis overweight on mixed or obese dishes, because fish, and of excessive<br />
The differences sequestering seen of in vitamin serum D25(OH)D in adiposeconcentrations<br />
tissue [33].<br />
meats.<br />
Gordon may be etdue al. to [12] the found factors that other a higher than diet; BMI because and being when<br />
African the analysis American was adjusted was associated for confounding with decreased variables, serum the<br />
25(OH)D. association Similarly, between we serum found 25(OH)D that subjects concentrations with highand<br />
HFLVD dietary patterns scores was no were longer tend present. to beThis overweight was seen orin<br />
obese other and studies NHB. such Thisthat could other be factors a possible such explanation as race, season, of<br />
theand lower sun serum exposure 25(OH)D were more concentrations significant predictors in those who of serum<br />
adhered 25(OH)D moreconcentrations closely to thethan HFLVD dietary pattern. intake 30,31 Furthermore,<br />
greater indoor activity measured by hours spent<br />
.<br />
watching The higher television, serum 25(OH)D using computers, concentrations or playing those videowho<br />
games adhere hasmore also closely been found to a PD to be pattern a factor may associated be related with to<br />
lower certain 25(OH)D lifestyle concentrations and health-related [9]. In factors. the present In this study,<br />
there we found was athat greater children proportion with high ofPD children pattern who scores had<br />
≤2had h/dconsumed of screenmore viewing supplements time hadcompared higher PDto this pattern with<br />
scores high HFLVD comparedpattern to those scores. with Consumption high HFLVDof dietary pattern<br />
score supplements suggestinghas decreased been associated overall screen with an viewing increase time of serum is<br />
an25(OH)D importantconcentration factor for the 32 . increased Children who serumconsumed<br />
25(OH)D<br />
concentrations vitamin D supplements in those who were adhere less likely to a PD. to be vitamin D<br />
Furthermore, deficient9. Additionally, the relation it has ofbeen serum suggested 25(OH)D that with the<br />
both bioavailability dietary patterns of vitamin remained D may forbe girls low only in those in the who ad-arjusted<br />
overweight analysis. or obese Nanri because et al. [34] of excessive found higher sequestering serumof<br />
25(OH)D vitamin D concentrations in adipose tissue in 33 women . Gordon who et al. had 12 found higher that a<br />
fish/shellfish higher BMI consumption and being African and lower American BMI. was They associated proposed<br />
with the decreased difference serum may25(OH)D. be related to Similarly, body composition we found that<br />
ofsubjects females with compared high HFLVD to males. pattern Becausescores women were generally tend to be<br />
have overweight higher or fatobese massand than NHB. men This and could vitamin be a possible D is<br />
fat-soluble, explanation this of could the lower result serum in higher 25(OH)D amounts concentrations being<br />
stored in those in who the fat adhered tissuemore of females closely to and the lower HFLVD serum pattern.<br />
vitamin Furthermore, D concentrations. greater indoor Thisactivity could measured be a possible by hours explanation<br />
spent watching for why television, in the present using study computers, we have or observed playing video<br />
girls games whohas adhere also been most found closely to be toa the factor HFLVD associated pattern with<br />
have lower significantly 25(OH)D lower concentrations9. serum vitamin In Dthe concentrations.<br />
present study, there<br />
The was a present greater study proportion has several of children strengths who that had included ≤2 h/d of<br />
a screen nationally viewing representative time had higher surveyPD with pattern a large scores sample compared<br />
size to of those children with and high adolescents. HFLVD pattern Because score of asuggesting<br />
wide range<br />
ofdecreased data are overall available screen on viewing demographic time is characteristics,<br />
an important factor<br />
dietary for the information, increased serum and other 25(OH)D health-related concentrations factors, in we those<br />
were who able adhere to adjust to a PD. serum 25(OH)D concentrations for<br />
several known confounding variables. Results in this<br />
study Furthermore, can be the interpreted relation of towards serum 25(OH)D the general with US both<br />
children dietary and patterns adolescents remained population for girls only because in the NHANES adjusted<br />
is analysis. based onNanri a probability et al. 34 found sample higher survey serum design 25(OH)D and is<br />
representative concentrations ofin women the USwho population. had higher fish/shellfish<br />
Because of<br />
cross-sectional consumption and nature lower of BMI. this study, They proposed cause and the effect difference<br />
measurement may be related is not to body possible. composition In addition, of females dietary compared intakes to<br />
ofmales. children Because estimated women by generally a FFQ may have be higher underreported fat mass than<br />
due men to subjects’ and vitamin inability D is fat-soluble, to recall intakes this could accurately result [35]. in higher<br />
amounts being stored in the fat tissue of females and lower<br />
serum vitamin D concentrations. This could be a possible<br />
explanation for why in the present study we have observed<br />
girls who adhere most closely to the HFLVD pattern have<br />
significantly lower serum vitamin D concentrations.<br />
The present study has several strengths that included a<br />
14
<strong>ACNEM</strong> <strong>Journal</strong> <strong>Vol</strong> <strong>37</strong> <strong>No</strong> 2 – <strong>June</strong> <strong>2018</strong><br />
nationally representative survey with a large sample size<br />
of children and adolescents. Because of a wide range of<br />
data are available on demographic characteristics, dietary<br />
information, and other health-related factors, we were<br />
able to adjust serum 25(OH)D concentrations for several<br />
known confounding variables. Results in this study can be<br />
interpreted towards the general US children and adolescents<br />
population because NHANES is based on a probability<br />
sample survey design and is representative of the US<br />
population. Because of cross-sectional nature of this study,<br />
cause and effect measurement is not possible. In addition,<br />
dietary intakes of children estimated by a FFQ may be<br />
underreported due to subjects’ inability to recall intakes<br />
accurately 35 .<br />
The errors in reporting food intakes may be minimal<br />
because the FFQ used in NHANES had been previously<br />
tested and validated by the National Cancer Institute.<br />
CONCLUSION<br />
Overall, serum 25(OH)D concentration was associated<br />
with the PD pattern but not with the HFLVD pattern<br />
in US children and adolescents. When stratified by sex,<br />
the relation between dietary patterns and serum 25(OH)<br />
D was confined to only girls. Although vitamin D status<br />
has improved slightly recently, the hypovitaminosis D is<br />
still evident in US children and adolescents 36 . Because of<br />
hypovitaminosis D is linked to several chronic diseases 3–5 ,<br />
it is prudent to improve the vitamin D status of children<br />
to reduce the future risk for chronic diseases. In public<br />
health perspective, it is important to encourage children,<br />
especially girls who are consuming HFLVD pattern to shift<br />
to healthier diet.<br />
Abbreviations<br />
25(OH)D: 25-hydroxyvitamin D; ANCOVA: Analysis of<br />
Covariance; BMI: Body mass index; FFQ: Food frequency<br />
questionnaire; H/MA: Hispanic/Mexican American;<br />
HFLVD: High Fat-Low-Vegetable Dietary Pattern; MEC:<br />
Mobile Examination Centers; NCHS: National Center for<br />
Health Statistics; NHANES: National Health and Nutrition<br />
Examination Survey; NHB: non-Hispanic black; NHW: non-<br />
Hispanic white; PD: Prudent Dietary Pattern; PIR: Poverty<br />
Income Ratio; SE: Standard error; T2DM: type-2 diabetes<br />
mellitus<br />
Availability of data and materials<br />
The database for the current study are available from the<br />
corresponding author on reasonable request.<br />
Authors’ contributions<br />
All authors substantially contributed to the conception, design,<br />
acquisition of data, analysis, and interpretation of results. VG<br />
and BM wrote the manuscript. WEVF was in charge of data<br />
management and data analysis. All authors reviewed, revised, and<br />
edited the manuscript. All authors read and approved the final<br />
manuscript.<br />
Ethics approval and consent to participate<br />
This study was based on publically available data from the<br />
NCHS. All NHANES protocols were approved by the NCHS<br />
Ethics Review Board prior to data collection.<br />
Competing interests<br />
The authors declare that they have no competing interests.<br />
References<br />
1. Pozzilli P, Manfrini S, Crinò A, Picardi A, Leomanni C,<br />
Cherubini V, et al. Low levels of 25-hydroxyvitamin D3 and<br />
1,25-dihydroxyvitamin D3 in patients with newly diagnosed type<br />
1 diabetes. Horm Metab Res. 2005;<strong>37</strong>:680–3.<br />
2. Munger KL, Levin LI, Hollis BW, Howard NS, Ascherio A.<br />
Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis.<br />
JAMA. 2006;296:2832–8.<br />
3. Reis JP, von Mühlen D, Miller ER 3rd, Michos ED, Appel LJ.<br />
Vitamin D status and cardiometabolic risk factors in the United<br />
States adolescent population. Pediatrics. 2009;124:e<strong>37</strong>1–9.<br />
4. Ganji V, Zhang X, Shaikh N, Tangpricha V. Serum<br />
25-hydroxyvitamin D concentrations are associated with<br />
prevalence of metabolic syndrome and various cardiometabolic risk<br />
factors in US children and adolescents based on assay-adjusted<br />
serum 25-hydroxyvitamin D data from NHANES 2001-2006.<br />
Am J Clin Nutr. 2011;94:225–33.<br />
5. Nunlee-Bland G, Gambhir K, Abrams C, Abdul M, Vahedi<br />
M, Odonkor W. Vitamin D deficiency and insulin resistance in<br />
obese African-American adolescents. J Pediatr Endocrinol Metab.<br />
2011;24:29–33.<br />
6. Ganji V, Milone C, Cody MM, McCarty F, Wang YT. Serum<br />
vitamin D concentrations are related to depression in young<br />
adult US population: the third National Health and nutrition<br />
examination survey. Int Arch Med. 2010;3:29.<br />
7. Sinha A, Avery P, Turner S, Bailey S, Cheetham T. Vitamin D<br />
status in paediatric patients with cancer. Pediatr Blood Cancer.<br />
2011;57:594–8.<br />
8. Holick MF. Vitamin D deficiency. N Engl J Med.<br />
2007;357:266–81.<br />
9. Kumar J, Muntner P, Kaskel FJ, Hailpern SM, Melamed ML.<br />
Prevalence and associations of 25-hydroxyvitamin D deficiency in<br />
US children: NHANES 2001-2004. Pediatrics. 2009;124:e362–<br />
70.<br />
10. Mansbach JM, Ginde AA, Camargo CA Jr. Serum<br />
25-hydroxyvitamin D levels among US children aged 1<br />
to 11 years: do children need more vitamin D? Pediatrics.<br />
2009;124:1404–10.<br />
11. Saintonge S, Bang H, Gerber LM. Implications of a new<br />
definition of vitamin D deficiency in a multiracial us adolescent<br />
population: the National Health and nutrition examination survey<br />
III. Pediatrics. 2009;123:797–803.<br />
12. Gordon CM, DePeter KC, Feldman HA, Grace E, Emans SJ.<br />
Prevalence of vitamin D deficiency among healthy adolescents.<br />
Arch Pediatr Adolesc Med. 2004;158:531–7.<br />
13. Houghton LA, Gray AR, Szymlek-Gay EA, Heath A-LM.<br />
Ferguson EL vitamin D-fortified milk achieves the targeted<br />
15
<strong>ACNEM</strong> <strong>Journal</strong> <strong>Vol</strong> <strong>37</strong> <strong>No</strong> 2 – <strong>June</strong> <strong>2018</strong><br />
serum 25-hydroxyvitamin D concentration without affecting<br />
that of parathyroid hormone in New Zealand toddlers. J Nutr.<br />
2011;141:1840–6.<br />
14. Xu C, Perera RA, Chan YH, Fang VJ, Ng S, Ip DK, et al.<br />
Determinants of serum 25-hydroxyvitamin D in Hong Kong. Br J<br />
Nutr. 2015;114:144–51.<br />
15. Cole CR, Grant FK, Tangpricha V, Swaby-Ellis ED, Smith<br />
JL, Jacques A, et al. 25-hydroxyvitamin D status of healthy,<br />
low-income, minority children in Atlanta. Georgia Pediatrics.<br />
2010;125:633–9.<br />
16. Lehmann B, Meurer M. Vitamin D metabolism. Dermatol Ther.<br />
2010;23:2–12.<br />
17. American Academy of Pediatrics. Ultraviolet light: a hazard<br />
to children. American Academy of Pediatrics. Committee on<br />
Environmental Health. Pediatrics. 1999;104:328–33.<br />
18. Misra M, Pacaud D, Petryk A, Collett-Solberg PF, Kappy<br />
M. Drug and therapeutics Committee of the Lawson Wilkins<br />
Pediatric Endocrine Society. Vitamin D deficiency in children<br />
and its management: review of current knowledge and<br />
recommendations. Pediatrics. 2008;122:398–417.<br />
19. Kerver JM, Yang EJ, Bianchi L, Song WO. Dietary patterns<br />
associated with risk factors for cardiovascular disease in healthy US<br />
adults. Am J Clin Nutr. 2003;78:1103–10.<br />
20. National Center for Health Statistics. National Health and<br />
Nutrition Examination Survey Analytic and Reporting Guidelines<br />
(<strong>2018</strong>) http://www.cdc.gov/nchs/data/nhanes/nhanes_03_04/<br />
nhanes_analytic_guidelines_dec_2005 pdf (accessed April <strong>2018</strong>).<br />
21. National Center for Health Statistics. National Health and<br />
Nutrition Examination Survey- Survey Brochures and Consent<br />
Documents (<strong>2018</strong>) https://wwwn.cdc.gov/nchs/nhanes/<br />
continuousnhanes/documents.aspx?BeginYear=2003 (accessed<br />
April <strong>2018</strong>).<br />
22. National Center for Health Statistics. National Health and<br />
Nutrition Examination Survey Laboratory Protocol 2003–2004<br />
(<strong>2018</strong>) https://wwwn.cdc.gov/nchs/nhanes/continuousnhanes/<br />
labmethods.aspx?BeginYear=2003 (accessed February <strong>2018</strong>).<br />
Ganji et al. Nutrition <strong>Journal</strong> (<strong>2018</strong>) 17:58 Page 10 of 11<br />
23. National Center for Health Statistics. National Health and<br />
Nutrition Examination Survey Laboratory Protocol 2004–2006<br />
(<strong>2018</strong>) https://wwwn.cdc.gov/nchs/nhanes/continuousnhanes/<br />
labmethods.aspx?BeginYear=2005 (accessed February <strong>2018</strong>).<br />
consumption with poor dietary outcomes and obesity among<br />
children: is it the fast food or the remainder of the diet? Am J Clin<br />
Nutr. 2014;99:162–71.<br />
28. Ambroszkiewicz J, Klemarczyk W, Gajewska J, Chełchowska<br />
M, Laskowska-Klita T. Serum concentration of biochemical<br />
bone turnover markers in vegetarian children. Adv Med Sci.<br />
2007;52:279–82.<br />
29. Chan J, Jaceldo-Siegl K, Fraser GE. Serum 25-hydroxyvitamin D<br />
status of vegetarians, partial vegetarians, and nonvegetarians: the<br />
Adventist health Study-2. Am J Clin Nutr. 2009;89:1686S–92S.<br />
30. Rajakumar K, Holick MF, Jeong K, Moore CG, Chen TC,<br />
Olabopo F, et al. Impact of season and diet on vitamin D status of<br />
African American and Caucasian children. Clin Pediatr (Phila).<br />
2011;50:493–502.<br />
31. Hall LM, Kimlin MG, Aronov PA, Hammock BD, Slusser<br />
JR, Woodhouse LR, et al. Vitamin D intake needed to maintain<br />
target serum 25-hydroxyvitamin D concentrations in participants<br />
with low sun exposure and dark skin pigmentation is substantially<br />
higher than current recommendations. J Nutr. 2010;140:542–50.<br />
32. Burgaz A, Akesson A, Oster A, Michaëlsson K, Wolk A.<br />
Associations of diet, supplement use, and ultraviolet B radiation<br />
exposure with vitamin D status in Swedish women during winter.<br />
Am J Clin Nutr. 2007;86:1399–404.<br />
33. Smotkin-Tangorra M, Purushothaman R, Gupta A, Nejati<br />
G, Anhalt H, Ten S. Prevalence of vitamin D insufficiency in<br />
obese children and adolescents. J Pediatr Endocrinol Metab.<br />
2007;20:817–23.<br />
34. Nanri A, Foo LH, Nakamura K, Hori A, Poudel-Tandukar K,<br />
Matsushita Y, et al. Serum 25-hydroxyvitamin D concentrations<br />
and season-specific correlates in Japanese adults. J Epidemiol.<br />
2011;21:346–53.<br />
35. Schaefer EJ, Augustin JL, Schaefer MM, Rasmussen H, Ordovas<br />
JM, Dallal GE, et al. Lack of efficacy of a food-frequency<br />
questionnaire in assessing dietary macronutrient intakes in<br />
subjects consuming diets of known composition. Am J Clin Nutr.<br />
2000;71:746–51.<br />
36. Schleicher RL, Sternberg MR, Lacher DA, Sempos CT, Looker<br />
AC, Durazo-Arvizu RA, et al. The vitamin D status of the<br />
US population from 1988 to 2010 using standardized serum<br />
concentrations of 25-hydroxyvitamin D shows recent modest<br />
increases. Am J Clin Nutr. 2016;104:454–61.<br />
24. National Center for Health Statistics. Analytical <strong>No</strong>te for<br />
25-Hydroxyvitamin D Data Analysis using NHANES III<br />
(1988-1994), NHANES 2001–2006, and NHANES 2007–<br />
2010 (<strong>2018</strong>) https://wwwn.cdc.gov/nchs/nhanes/vitamind/<br />
analyticalnote.aspx?h=/Nchs/Nhanes/2005-2006/VID_D.<br />
htm&t=VID_D%20Doc (accessed April <strong>2018</strong>).<br />
25. Hu FB, Rimm E, Smith-Warner SA, Feskanich D, Stampfer MJ,<br />
Ascherio A, et al. Reproducibility and validity of dietary patterns<br />
assessed with a foodfrequency questionnaire. Am J Clin Nutr.<br />
1999;69:243–9.<br />
26. Ganji V, Zhang X, Tangpricha V. Serum 25-hydroxyvitamin<br />
D concentrations and prevalence estimates of hypovitaminosis<br />
D in the U.S. population based on assay-adjusted data. J Nutr.<br />
2012;142:498–507.<br />
27. Poti JM, Duffey KJ, Popkin BM. The association of fast food<br />
This is an open access article distributed under the terms of the<br />
Creative Commons Attribution License,<br />
(https://creativecommons.org/licenses/by/4.0)<br />
16
Parex<br />
Plus<br />
Meta Zinc<br />
with Vitamin C<br />
Your Partner in Functional Medicine<br />
Your Partner<br />
in Resources<br />
Your Partner in Continued<br />
Professional Education<br />
Technical Data that brings<br />
evidence together in one place.<br />
The latest scientific research and<br />
clinical information to ensure your<br />
practice remains up to date in this<br />
rapidly evolving field.<br />
Questionnaires and patient<br />
resources to help in comprehensive<br />
case taking and lifestyle prescriptions.<br />
Metagenics Clinical Education is offered<br />
via seminar, webinar and podcast so<br />
you can access world-class education,<br />
wherever you are.<br />
Partner With<br />
the Best Products<br />
OmegaCare<br />
MetaPure<br />
EPA/DHA<br />
AdrenoTone<br />
e<br />
Metagenics has the broadest Practitioner only<br />
range of Natural Medicines, manufactured<br />
to the highest standards, providing all the<br />
combinations you will need to tailor specific<br />
solutions for your patients’ needs.<br />
REGISTER NOW<br />
Watch online within 30 days<br />
following the live webinar<br />
THE MICROBIOME:<br />
THE FORGOTTEN GENOME IN<br />
PERSONALISED MEDICINE<br />
Thursday 5 th July, <strong>2018</strong> 6:00 pm<br />
Containing over 100-fold more genes, research is indicating that the microbial<br />
genome is a greater contributor to health and disease than the human genome.<br />
Join us as we introduce this concept and explore the microbiome’s contribution<br />
to not only gut disorders, but also neural, immune and metabolic disorders.<br />
For more information and to register for this webinar visit<br />
www.metagenics.com.au/education/webinars<br />
MET5692 - 05/18<br />
For more information or to become a Metagenics member call 1800 777 648
Delivering tradition<br />
wrapped in science<br />
Coming July <strong>2018</strong><br />
www.bioceuticals.com.au<br />
1300 650 455
<strong>ACNEM</strong> <strong>Journal</strong> <strong>Vol</strong> <strong>37</strong> <strong>No</strong> 2 – <strong>June</strong> <strong>2018</strong><br />
CASE STUDY<br />
ALZHEIMER’S DISEASE<br />
a nutritional and<br />
environmental perspective<br />
Author:<br />
Dr Inanch Mehmet<br />
Abstract: This is a case study on a 78 year old man with<br />
early Alzheimer’s dementia (AD) and mild cognitive<br />
impairment (MCI). He was already seeing a geriatrician and<br />
put on an anticholinesterase inhibitor. He had no dietary<br />
or environmental interventions when he came to see me<br />
and was found to have high cholesterol, high homocysteine.<br />
MTHFR heterozygous c665C and c1286A, a high copper:<br />
zinc ratio, gut dysbiosis and insomnia. The goal was to treat<br />
the patient as an integrative physician and reverse what was<br />
possible using evidence-based practice including reducing<br />
homocysteine and copper and repairing the gut. The patient<br />
had only been receiving treatment for two months and will<br />
need at least 6-12 months to see if interventions have made<br />
a difference. During this time the patient will be monitored<br />
with MMSE and blood tests. The patient was treated with<br />
diet, exercise, lifestyle and supplements in order to reduce<br />
Alzheimer’s progression. Furthermore environmental toxins<br />
and body burden was reduced. Can anything be done about<br />
genetic predisposition to AD or has the horse bolted?<br />
Key Words: Alzheimer’s disease, mild cognitive<br />
impairment, copper toxicity, homocysteine, gut dysbiosis,<br />
MTHFR, insomnia, low zinc, essential fatty acids,<br />
coenzyme q10, methylation, MTHFR, folate, cobalamin,<br />
pyridoxine 5 phosphate, nicotinamide, riboflavin 5<br />
phosphate, DHA, phosphatidylserine, antioxidants,<br />
flavanoids, mixed tocopherols, vitamin C, oxidation,<br />
streptococcus, enterococcus, lactic acid, leaky gut,<br />
lactobacillus, bifidobacterium, vitamin d, curcumin, Ginko<br />
Bilbao, Beta amyloid, acetyl L carnitine, melatonin, 5HTP,<br />
Alpha lipoic acid, olive oil, Mediterranean diet, BPA,<br />
PCPs, organophosphates, phthalates, mercury, aluminium,<br />
APOE4.<br />
INTRODUCTION<br />
Alzheimer’s disease is characterised by memory impairment<br />
and according to the DSM must include at least one of<br />
the following; aphasia, apraxia, agnosia or disturbance in<br />
executive function. It interferes with daily function and<br />
characterised by a gradual onset and continuing decline.<br />
Traditionally western medicine has no effective treatments<br />
for this gut wrenching and costly ailment. 1<br />
AD is driven by two processes: extracellular deposition<br />
of beta amyloid-Aß and intracellular accumulation of tau<br />
protein. Both these compounds are insoluble. Aß is the<br />
main component of senile plaques and tau is the component<br />
of neurofibrillary tangles. Aß deposition is specific for AD<br />
and is thought to be primary. Tau accumulation is also<br />
seen in other degenerative diseases and is thought to be<br />
secondary.<br />
Aß is toxic to neurons. It causes loss of long term<br />
potentiation, damages synapses, and kills neurons.<br />
Moreover, it shows selective neurotoxicity for the<br />
hippocampus and entorhinal cortex (areas that are severely<br />
affected in AD) while sparing cerebellar neurons. This<br />
damage is mediated by free radicals, which are generated<br />
when soluble Aß is complexed with Zn, Cu, and Fe.<br />
Tau aggregates as pairs of filaments that are twisted around<br />
one another (paired helical filaments). These deposits<br />
interfere with cellular functions by displacing organelles.<br />
By distorting the spacing of microtubules, they impair<br />
the axonal transport thus affecting the nutrition of axon<br />
terminals and dendrites.<br />
Genetics accounts for 70 per cent of the risk, and the<br />
most important genetic risk factor is the Apolipoprotein E<br />
(ApoE) genotype. ApoE is a protein that carries cholesterol<br />
in and out of cells. It occurs in three isoforms: ApoE2,<br />
ApoE3, and ApoE4. The gene for ApoE is on chromosome<br />
19. One copy is inherited from each parent. The ApoE4<br />
allele confers a high risk for AD, the rare ApoE2 confers<br />
a low risk, and the most common ApoE3 an intermediate<br />
risk. Persons who are homozygous for the ApoE4 allele<br />
develop AD at a mean age 70. Persons with other ApoE<br />
genotypes develop the disease later or not at all. However,<br />
having an ApoE4 allele does not mean that one will<br />
invariably develop AD. Furthermore, the role of ApoE4<br />
in non-Europeans is not as well established. The ApoE4<br />
allele is also a risk factor for hypercholesterolemia. High<br />
cholesterol levels during mid-life increase the risk of AD<br />
and lowering lipids lowers this risk.<br />
19
<strong>ACNEM</strong> <strong>Journal</strong> <strong>Vol</strong> <strong>37</strong> <strong>No</strong> 2 – <strong>June</strong> <strong>2018</strong><br />
The role of the environment, diet, and general state of<br />
health in AD is being actively explored. Chronic cellular<br />
damage from free radicals, excitotoxicity, nonenzymatic<br />
glycation of proteins, and other factors contributes to the<br />
loss of neurons and synapses that is associated with old age<br />
and aggravates the pathology of AD.<br />
Neuroinflammation is an important factor involved in the<br />
pathogenesis of AD. Acute-phase proteins are elevated in<br />
serum and deposited in SPs; microglial cells accumulate<br />
around SPs; and complement components are present in<br />
SPs. APP is an acute phase protein which is released in<br />
brain tissue following trauma and other insults. The effects<br />
of neuroinflammation are mediated by activated microglial<br />
cells which are a source of cytokines and a potent generator<br />
of free radicals. Advanced molecular studies have revealed<br />
multiple aberrations in the microglial immune response in<br />
AD. These aberrations are triggered by Aß and tau but,<br />
in turn, cause brain damage and accelerate Aß and tau<br />
deposition.<br />
Free radicals and Oxidative stress, compounding with<br />
advancing age, causes mitochondrial DNA mutations,<br />
mitochondrial dysfunction and more oxidative stress.<br />
This process is accelerated in AD by the action of Aß<br />
(a mitochondrial poison and free radical generator) and<br />
activated microglia, also a source of free radicals.<br />
Type 2 diabetes is a risk factor for AD. AD patients have<br />
low levels of insulin and insulin resistance in the brain.<br />
These changes impair energy metabolism in neurons and<br />
adversely effect signalling pathways dependent on insulin<br />
and its receptors. Furthermore, nonenzymatic glycation<br />
of proteins produces neurotoxic derivatives that aggravate<br />
oxidative damage.<br />
Traumatic brain injury is another risk factor. Dementia and<br />
parkinsonism develop sometimes in boxers, football players<br />
and other individuals who have had repeated cerebral<br />
concussions. The brain shows mainly NFTs. Diffuse and<br />
less frequently neuritic plaques are seen inconstantly.<br />
Increased levels of homocysteine (also a risk factor for<br />
stroke) and decreased dietary folate potentiate these<br />
neurotoxic effects. Homocysteine increases with advancing<br />
age and is elevated in persons with polymorphisms of<br />
5,10-methylenetetrahydrofolate reductase (MTHFR), an<br />
important enzyme involved in folate metabolism. Such<br />
polymorphisms are very common. Elevated homocysteine<br />
and decreased folate are associated with increased free<br />
radicals, cytosolic calcium, glutamate excitotoxicity,<br />
apoptosis, and decreased levels of ATP.<br />
Alzheimer’s Disease International predicts Alzheimer’s rates<br />
will triple worldwide by 2050. The Alzheimer’s Association<br />
predicts long-term care costs start at $41 000 per year.<br />
However, Alzheimer’s disease isn’t a natural part of aging<br />
and by staying active and moving plant-based foods to the<br />
centre of our plates, we have a fair shot at rewriting our<br />
genetic code.<br />
The case below demonstrates a multi-faceted individualised<br />
evidence-based approach to Alzheimer’s disease. It<br />
illustrates many variables involved in the treatment of AD<br />
and highlights how important the patient is when it comes<br />
to empowering them, or their carers, to take control of their<br />
health, environment and lifestyle and in effect become the<br />
ultimate patient for their own sake before it’s too late.<br />
CASE PRESENTATION<br />
Mr S.N. is a 78 year old man with early Alzheimer’s<br />
dementia. He has been under the care of a geriatrician<br />
for the last few years and has been taking Aricept 10 mg.<br />
According to the geriatrician report there were no reversible<br />
causes of his dementia found including head trauma, drug<br />
toxicity, metabolic disturbances, hydrocephalus, mass<br />
lesions, infectious processes, collagen vascular diseases,<br />
endocrine disorders, COPD, Heart failure, liver disease or<br />
sleep apnoea. There was no family history of Alzheimer’s.<br />
Past medical history also includes benign prostatic<br />
hypertrophy, vitamin d deficiency, hypercholesterolemia ,<br />
herniotomy, cataract surgery, Left ankle fracture surgery.<br />
Current medications included Aricept 10mg daily. Duodart<br />
500mcg-400mcg 1 nocte. He was also taking a supplement<br />
from bioceuticals called advacal forte twice a day with a<br />
total per dose of elemental Calcium 334mg,phosphorus<br />
88.3mg,vitamin D3 333IU, vitamin K2 30mcg, Magnesium<br />
58mg, Zinc 3.2mg Manganese 1mg Copper 200mcg Silicon<br />
7.26mg Boron 1mg. He was also taking some fish oils and<br />
Blackmore’s magnesium.<br />
Nutritional assessment was performed and his diet was<br />
inorganic and high in gluten, dairy, refined carbohydrates,<br />
artificial colours, flavours and preservatives. He would eat<br />
take away 2x/week. He would drink coffee 2x/day. He<br />
would have one alcohol drink once a week and is a nonsmoker.<br />
He is now retired but his occupational history was as a<br />
form worker in the building industry. He denied any current<br />
high stress levels. He says he walks 50 minutes a day and<br />
gets morning sun while exercising. He did not undertake<br />
any other forms of relaxation or hobbies. There was no<br />
significant travel history.<br />
Significant findings on systems review included<br />
constipation, dental periodontitis, and cravings of sugar,<br />
dairy and gluten (namely bread).<br />
He denied any fatigue, depression or anxiety. He had good<br />
sleep (except for nocturia) and good dream recall.<br />
He complained of chronic sinus congestion and occasional<br />
musculoskeletal cramps. He had some watery eyes and itchy<br />
ears.<br />
MMSE; 24/30 indicating mild cognitive impairment.<br />
20
<strong>ACNEM</strong> <strong>Journal</strong> <strong>Vol</strong> <strong>37</strong> <strong>No</strong> 2 – <strong>June</strong> <strong>2018</strong><br />
Examination revealed an endomorphic body type. Happy<br />
affect and normal gait. He had some nasolabial redness and<br />
flakiness. His hair was thinning. He had crimson crescents<br />
in his pharynx and a coated strawberry tipped and creviced<br />
tongue. His hands showed collapsed finger pulps and<br />
small muscle wasting. His nails were bitten and brittle and<br />
showed vertical grooves and white spots. His skin was dry.<br />
His abdomen was soft and non tender .His central nervous<br />
system revealed no further abnormality.<br />
PATHOLOGY, INVESTIGATIONS AND RESULTS<br />
CT sinuses showed complete opacification right maxillary<br />
antrum, rhinitis and sphenoidal encroachment on the<br />
nasopharyngeal airway.<br />
CT chest shows stable lymph nodes in the mediastinum<br />
and degenerative changes in the thoracic spine. Lymph<br />
nodes being followed up 6-12 monthly with CT by his GP.<br />
FBC showed platelets 146 x10^9/L(low), lymphocytes 1.1<br />
x10^9/L (low normal), basophils 0.0 x10^9/L MCV 91 fL<br />
Sodium/potassium ratio 30.8mmol/L,<br />
Urea 7.4 mmol/L, Creatinine 83 umol/L urea/creatinine 89<br />
umol/L<br />
Cholesterol 6.1mmol/L (high) Triglyceride 1.1mmol/L<br />
Ca/PO4 2.28 mmol/L Corrected ca 2.26, PO4 0.99<br />
TSH 1.30 mIU/L<br />
Fasting glucose 4.9 mmol/L, Insulin 4mU/L<br />
Iron 15.9 umol/L, Transferrin 2.0 g/L (low normal),<br />
Ferritin 103 ug/L<br />
Vitamin D 78 nmol/L<br />
Homocysteine 12.3 umol/L (high normal)<br />
Active B12 >128 pmol/L. <strong>No</strong>te on 12/11/16 B12 was 9<br />
and has been replaced with imtramuscular injections.<br />
Serum folate 25 nmol/L<br />
ANA not detected<br />
MTHFR c665cT and 1286ac both heterozygous<br />
Plasma zinc 9.2 umol/L(low normal)<br />
Se Copper 15 umol/L<br />
Copper/zinc; 1.63 umol/L<br />
Histamine 0.5 umol/L<br />
A dexa scan was performed and was osteopenic T score 1.8<br />
Z score 2.5<br />
A bioscreen was also ordered and revealed a high<br />
aerobe: anaerobe ratio with an overgrowth of e.coli,<br />
streptococcus, staphylococcus and enterococcus. He also<br />
had an overgrowth of lactobacillus, and undergrowth of<br />
bifidobacterium and eubacterium.<br />
FINAL DIAGNOSIS<br />
Early Alzheimer’s dementia with memory loss and cognitive<br />
decline with some disturbance in executive function.<br />
High copper:zinc ratio. High Homocysteine. MTHFR<br />
heterozygous.<br />
TREATMENT AND MANAGEMENT<br />
Mr S.N. was advised to reduce his body burden. This<br />
included eating an organic diet with no artificial colours,<br />
flavours or preservatives.<br />
He was advised to avoid any PCBs and BPAs i.e. plastic<br />
containers and canned foods. He was advised to avoid<br />
paints, solvents, sealants and pesticides.<br />
He did not eat any fish and was advised to eat wild caught<br />
fish (salmon size or smaller), organic or free range meat,<br />
chicken and eggs and fruit and vegetables (two and five<br />
serves/day respectively).<br />
Other dietary considerations included drinking only filtered<br />
water, cooking with stainless steel, avoiding aluminium and<br />
Teflon frying pans, avoiding hydrogenated vegetable oils<br />
and using olive oil for cooking, using more natural chemical<br />
free options with perfumes, antiperspirants, detergents,<br />
sunscreens and washing powders.<br />
He was put on a low stress diet i.e. avoid sugar, gluten, dairy,<br />
take away foods, and advised to eat more low stress foods<br />
i.e. nutrient rich, low GI, high antioxidant fruits, vegetables,<br />
salads, legumes, nuts and seeds. Gluten free grains i.e. corn,<br />
rice, millet and quinoa were advised. He was advised to<br />
include more essential fatty acids in his diet and flavanoids.<br />
With regards to his gut he was advised to increase his<br />
intake of fructo-oligosaccharide (FOS) and actually put<br />
on an FOS supplement (1/2-2 tablespoons/day) to reduce<br />
E.Coli and promote bifidobacteria growth.<br />
He was also put on a supplement containing Glutamine,<br />
zinc, vitamin A, vitamin D3, boswellia, aloe vera and<br />
arabinogalactan for leaky gut and bifidobacteria promotion.<br />
He was prescribed amoxicillin 500mg bd for two weeks to<br />
suppress enterococcus, streptococcus and lactobacillus .<br />
All lactobacillus and lactic acid producing probiotics were<br />
ceased . A bifidobacterium probiotic was started (5 billion<br />
bd between antibiotic doses for one month).<br />
Arginine was also started to promote eubacterium species.<br />
He was started on some antioxidants including vitamin c<br />
2gm, mixed tocopherols 400mg, coq10 300mg, l-carnitine<br />
2gm, R-alpha lipoic acid 600mg as total daily elemental<br />
doses.<br />
21
<strong>ACNEM</strong> <strong>Journal</strong> <strong>Vol</strong> <strong>37</strong> <strong>No</strong> 2 – <strong>June</strong> <strong>2018</strong><br />
He was also put on curcumin 350mg bd, and another<br />
formula containing; Omega 3; 2.3 gm, EPA 253 mg,<br />
DHA 1gm, lecithin 1.5gm, phosphatydil choline 520mg,<br />
phosphatydil serine 150mg, tocotrienols 80mg and vitamin<br />
D3 500iu.<br />
He was put on melatonin 1gm nocte + 5HTP 100mg<br />
nocte to help with sleep.<br />
To reduce copper and homocysteine and improve zinc,<br />
further compounded nutritional supplements given included<br />
riboflavin-5- phosphate 100mg , nicotinamide 100mg, P5P<br />
50mg, methylcobalamin 1000mcg, methyl folate 1000mcg,<br />
zinc(as picolinate) 40mg, chromium 400mcg, magnesium<br />
(as glycinate) 400mg, molybdenum 100mcg, selenium<br />
100mcg and manganese 15mg. All elemental doses.<br />
He could continue his Ginko Biloba.<br />
It was recommended he continue physical exercise and also<br />
play some brain games.<br />
Future considerations include APOE testing and heavy<br />
metals testing post chelation. This patient has some<br />
financial concerns so this testing was not performed at this<br />
time.<br />
METHODS TO MONITOR OUTCOMES<br />
FBC<br />
Cholesterol triglyceride HDL levels<br />
serum B12 folate levels<br />
Homocysteine<br />
Serum copper plasma zinc<br />
Bioscreen<br />
MMSE<br />
<strong>No</strong>te; acetyl l-carnitine although usually well tolerated but<br />
can cause nausea, vomiting, depression, mania, confusion,<br />
and aggression in AD patients.<br />
DISCUSSION<br />
The most important questions in Mr S.N.’s case is why<br />
did he develop Alzheimer’s disease, how can we prevent it<br />
progressing and can we reverse it?<br />
According to his geriatrician he has Alzheimer’s however on<br />
examination he seems to be functioning well and continues<br />
to drive. Does he have mild cognitive impairment or age<br />
related memory impairment? Studies show a probable<br />
increase to Alzheimer’s at 10-15 per cent/year anyway and<br />
the treatment principles remain the same. 2<br />
Mr S.N.’s risk factors include his age (2% aged 75-79), low<br />
educational attainment 3 , hyperlipidaemia 4 and an elevated<br />
homocysteine level 5 .<br />
He was supplemented with folate, B6 and B12 and it<br />
is noteworthy that these are essential cofactors for the<br />
methylation of homocysteine. In one study of older<br />
individuals with elevated homocysteine levels and cognitive<br />
decline the supplementation of these three vitamins<br />
maintained memory performance and reduced the rate of<br />
brain atrophy. He was also advised to have a high plant<br />
based diet which is rich in B vitamins. 6<br />
He is also MTHFR heterozygous further justifying<br />
supplementation with B2, methylfolate, methylcobalamin<br />
and B6 7 . He lacks any basophils which can also indicate B3,<br />
folate and B12 deficiency. 8<br />
His platelets reflect likely an essential fatty acid imbalance<br />
and his diet lacks omega 3’s. One study showed deficiency<br />
in docosahexaenoic acid (DHA), a brain-essential omega-3<br />
fatty acid, is associated with cognitive decline. 9 In human<br />
neuronal cells DHA attenuates amyloid beta secretion<br />
which is accompanied by the formation of NPD1 which<br />
promotes brain cell survival by inducing neuroprotective<br />
gene expression. Hence he was supplemented with DHA.<br />
This supplement also contained phosphatydilserine.<br />
Phosphatidylserine (PS) is a key constituent of brain and<br />
nerve cell membranes and may help to improve memory<br />
in people with age-related cognitive decline. A doubleblind,<br />
placebo controlled study using 494 patients, over<br />
the age of 65, examined the benefits of 300 mg of PS<br />
on men and women with moderate to severe age-related<br />
cognitive decline. Significant improvements in behaviour<br />
and cognitive performance, including memory recall, were<br />
distinguished in the PS group, compared to placebo. 10<br />
He has a high copper: zinc ratio and this is a risk factor<br />
and should be rectified 11 . Excess copper, causes neuronal<br />
toxicity. Also zinc deficiency, causes neuronal damage.<br />
Brewer et al presents evidence that Alzheimer's disease<br />
(AD) has become an epidemic in developed, but not<br />
undeveloped, countries and that the epidemic is a new<br />
disease phenomenon, beginning in the early-1900s and<br />
exploding in the last 50 years. This leads to the conclusion<br />
that something in the developed environment is a major<br />
risk factor for AD. They hypothesized that the factor is<br />
inorganic copper, leached from the copper plumbing, the use<br />
of which coincides with the AD epidemic. They present a<br />
web of evidence supporting this hypothesis. Regarding zinc,<br />
they have shown that patients with AD are zinc deficient<br />
when compared with age-matched controls. Zinc has critical<br />
functions in the brain, and lack of zinc can cause neuronal<br />
death. A non-blinded study about 20 years ago showed<br />
considerable improvement in AD with zinc therapy, and a<br />
mouse AD model study also showed significant cognitive<br />
benefit from zinc supplementation. In a small blinded study<br />
they carried out, analysis revealed that six months of zinc<br />
therapy resulted in significant benefit relative to placebo<br />
controls in cognition. These two factors may be linked in<br />
that zinc therapy significantly reduced free copper levels.<br />
Thus, zinc may act by lowering copper toxicity or by direct<br />
benefit on neuronal health, or both. 12 Mr S N was placed<br />
on zinc, molybdenum, manganese, vitamin c, chromium and<br />
magnesium to reduce copper. He was also advised to drink<br />
filtered water only and avoid any copper in his vitamins.<br />
22
<strong>ACNEM</strong> <strong>Journal</strong> <strong>Vol</strong> <strong>37</strong> <strong>No</strong> 2 – <strong>June</strong> <strong>2018</strong><br />
He eats a highly processed diet which lacks antioxidants 13<br />
and flavanoids 14 .<br />
In a cross-sectional study of 2031 patients aged 70-74 the<br />
consumption of 10g/day of chocolate and 75ml/d of red<br />
wine resulted in superior cognitive performance. Hence he<br />
was educated on flavanoids and advised to incorporate them<br />
into his daily dietary routine. 14<br />
Antioxidants protect neurons from free radical and<br />
reactive oxygen damage. 15 Vitamin E and C in particular<br />
protected against dementia and was associated with reduced<br />
Alzheimer’s prevalence ( OR 0.22). 16 He was supplemented<br />
with both (mixed tocopherols) and there may be merit in<br />
this preventing further decline in cognition.<br />
A RCT of 613 patients with mild to moderate AD over<br />
five years showed on 2000iu/day of alpha tocopherol there<br />
was a 19 per cent delay in clinical progression compared<br />
with placebo. 17 He was also advised to get more of these<br />
vitamins in his diet, ie seeds, nuts, green leafy vegetables,<br />
some fruits and whole grains as dietary sources were more<br />
protective. 18<br />
With regard to his Bioscreen data increased distribution of<br />
lactic acid bacteria (Streptococcus, Enterococcus sp.) may<br />
lower the colonic pH 19 and has been reported to modify<br />
faecal microbial metabolism particularly the Bacteroides and<br />
Bifidobacterium spp, resulting in a decreased production<br />
of volatile fatty acids 20 , and also alter intestinal epithelial<br />
barrier function increasing passive intestinal permeability<br />
to small and large molecules. Although this consideration<br />
requires further study he was still treated for leaky gut.<br />
High colonization of faecal lactic acid bacteria<br />
(Streptococcus, Enterococcus sp.) significantly and<br />
positively correlate with cognitive dysfunctions<br />
(nervousness, memory loss, forgetfulness, confusion, mind<br />
going blank) 21,22,23,24 and sleep patterns.<br />
Also he had high levels of Lactobacillus spp. in the<br />
anaerobic microbial flora. Metabolic acidosis and<br />
neurological dysfunction (depressed conscious state,<br />
confusion, aggressive behaviour, slurred speech and ataxia)<br />
have been reported in patients with increased level of<br />
lactobacilli in the anaerobic faecal flora 25 .<br />
FOS was started to reduce E.Coli and promote<br />
bifidobacteria growth. 26<br />
Hence it is imperative to treat his gut dysbiosis.<br />
Mr S.N. has a very good vitamin D level however I<br />
maintained him on about 3500 iu /day. This is because a<br />
studies suggest that lower vitamin D concentrations are<br />
associated with poorer cognitive function and a higher risk<br />
of AD. 27 Vitamin D insufficiency may be a modifiable<br />
risk factor for dementia as the role of vitamin D in brain<br />
function is becoming clearer. At the molecular level, the<br />
brain has the ability to synthesize the active form of<br />
vitamin D (1,25-dihydroxyvitamin D) with predominance<br />
in the hypothalamus and the substantia nigra. Vitamin D<br />
regulates genes allowing cells to synthesize relevant products<br />
in response to routine signals. Vitamin D contributes to<br />
neuroprotection by modulating the production of nerve<br />
growth factor (NGF), neurotrophin 3, glial cell derived<br />
neurotrophic factor (GDNF), nitric oxide synthase (iNOS),<br />
and choline acetyl transferase.<br />
Curcumin has many modes of action in AD including<br />
antioxidant effects, metal chelation, actions on glial cells<br />
including decreased proliferation of neuroglial cells<br />
and increased oligodendrocyte activity. It also has anti<br />
inflammatory effects and reduces beta amyloid plaques. 28<br />
Research indicates the prevalence of AD among adults aged<br />
70-79 years in India is 4.4 times less than that of adults<br />
aged 70-79 years in the United States most likely due to<br />
high curcumin consumption. 29 I maintained Mr S N on<br />
350mg bd.<br />
Mr S N was already on Ginko Biloba and he was urged to<br />
keep taking this. Studies show it protects against neuronal<br />
damage and improves blood viscosity. Various in vivo<br />
and in vitro preclinical studies support the notion that<br />
Ginkgo biloba extract may be effective in the treatment<br />
and prevention of AD. Anti-oxidation, anti-apoptosis, antiinflammation,<br />
protection against mitochondrial dysfunction,<br />
amyloidogenesis and Aβ aggregation, ion homeostasis,<br />
modulation of phosphorylation of tau protein and even<br />
induction of growth factors are possible mechanisms of<br />
action. 30<br />
Coq10 improves nerve and glial cell energy metabolism<br />
however there are no RCT’s. 31 He was supplemented with<br />
300mg/d.<br />
L-carnitine is a scavenger of free radicals in the<br />
mitochondria, a cell membrane stabiliser and stimulates<br />
nerve growth factor. 32 It improves fatigue and physical<br />
and mental function in the elderly and improves both the<br />
cognitive status and physical functions. 33<br />
Melatonin is shown to decline in AD patients resulting<br />
in circadian disorganization and decreased sleep and<br />
cognitive dysfunction. Melatonin also has antioxidant,<br />
antiamyloidogenic and mitochondrial effects indicating its<br />
potentiality to interfere with the onset of the disease. This<br />
is of particularly importance in mild cognitive impairment<br />
(MCI) hence supplementation has a definite add on role.<br />
Melatonin replacement has been shown to be effective in<br />
treating sundowning and other sleep wake disorders in AD<br />
patients. 34<br />
There is not much data on 5HTP however as a precursor<br />
to serotonin and melatonin it also aids in sleep.<br />
Alpha lipoic acid is an antioxidant that has positive<br />
effects on glucose metabolism, oxidative stress and energy<br />
depletion which are characteristic of AD. In one small study<br />
600mg/day was given to nine patients with AD who were<br />
also receiving standard treatment with acetylcholinesterase<br />
inhibitors over about a year. Results showed stabilisation<br />
of cognitive function measured by MMSE and ADAScog.<br />
Alpha-lipoic acid might be a successful 'neuroprotective'<br />
therapy option for AD and related dementias. 35<br />
Oleocanthal, a phenolic component of extra-virgin olive<br />
oil, has been recently linked to reduced risk of Alzheimer's<br />
23
<strong>ACNEM</strong> <strong>Journal</strong> <strong>Vol</strong> <strong>37</strong> <strong>No</strong> 2 – <strong>June</strong> <strong>2018</strong><br />
disease (AD). The mechanism in in vitro and in vivo studies<br />
is the clearance of B amyloid at the blood brain barrier. 36 .<br />
1 litre of extra virgin olive oil /week resulted in better<br />
cognition. <strong>37</strong> Published studies suggest that greater adherence<br />
to Mediterranean diet is associated with slower cognitive<br />
decline and lower risk of developing Alzheimer’s disease. 38<br />
So Mr S.N. was advised a diet high in olive oil, omega 3<br />
from fish, low in saturated fat, high in plant phenols, high<br />
vegetable and moderate fruit to improve oxidation and<br />
inflammation and switch on nitric oxide and change gene<br />
expression.<br />
Mr S N was also advised to continue to remain active. In<br />
one study 12 weeks of moderate exercise improved neural<br />
efficiency in mild cognitive impairment as measured by<br />
functional MRI. 39<br />
In terms of general body burden BPAs, PCBs, pesticides,<br />
phthalates, mercury, aluminium, lead, and cadmium should<br />
all be avoided. 40,41,42,43,44<br />
If he fails to improve it is worth while doing a postchelation<br />
heavy metals challenge urine test and considering<br />
chelation or detoxification if he has high heavy metals.<br />
Aluminium and mercury have been demonstrated in the<br />
brains of AD patients. 40,44 In areas of high aluminium<br />
water contamination there is a higher prevalence of AD 44 .<br />
Significant memory deficits were found in 32 out of 40<br />
studies on individuals exposed to inorganic mercury. 44<br />
We know mercury interferes with polymerization of<br />
microtubules, increases secretion of Abeta proteins,<br />
promotes hyperphosphorylation of tau protein, changes<br />
mitochondrial structure, interferes with cell-maturation,<br />
DNA repair, glutathione level and linkage and structure of<br />
microtubules. 44<br />
ApoE4 is the major genetic risk factor for Alzheimer‘s .How<br />
apoE4 influences AD onset and progression has yet to be<br />
proven. It has probable effects on Abeta aggregation and<br />
clearance which plays a major role in AD pathogenesis. It<br />
possibly modulates tau phosphorylation, as well as plays a<br />
role in synaptic plasticity and neuroinflammation. 45<br />
Is it worthwhile testing APO-E in this patient and will it<br />
make a difference to the treatment outcome? In one study<br />
MCI subjects carrying the APOE 4 allele showed distinct<br />
cognitive and imaging profiles, which appeared to resemble<br />
those of early Alzheimer patients. APOE4 genotype<br />
was associated with greater impairments in memory and<br />
functional activities as well as hippocampal atrophy. 46 So if<br />
he was APOE4 positive he would have a worse prognosis<br />
but what can we do about it that is different to what we are<br />
already doing?<br />
In another study B-amyloid was measured in the CSF<br />
of those with MCI and APOE4 and found to be higher<br />
in those on a high saturated fat /high GI diet compared<br />
to those on a low saturated fat/ low GI diet .When the<br />
diet changed to a low one the levels went down. 47 If the<br />
patient can afford the test he should do one to confirm<br />
his prognosis. In any case he has to stay on a healthy diet.<br />
APOE4 testing may be more useful in the asymptomatic<br />
patient who is considering making lifestyle changes to avoid<br />
dementia and many other cardiovascular morbidities and<br />
mortalities.<br />
CONCLUSION<br />
There are many factors that contribute to Alzheimer’s<br />
disease and multiple modalities which need to be addressed<br />
and rectified to effectively treat Alzheimer’s in order to<br />
prevent it progressing. At the very least one should follow<br />
the lifestyle recommendations of the ‘physicians committee<br />
for responsible medicine’. This includes eating plant-based<br />
foods predominantly, ie vegetables, legumes (beans, peas,<br />
and lentils), fruits, and whole grains should replace meats<br />
and dairy products as primary staples of the diet. Further to<br />
this consume 15mg of vitamin E daily through seeds, nuts,<br />
green leafy vegetables, and whole grains. Avoid trans and<br />
saturated fats. Take a B12 supplement. Avoid vitamins with<br />
iron and copper. Avoid aluminium, eg in cookware, antacids<br />
and baking powder. Exercise aerobically for 120 minutes/<br />
week. An addition to this diet would be to include olive oil<br />
like the Mediterranean one and include lots of flavanoids.<br />
Also vitamin D is very important so advise the patient to<br />
get 30 minutes of morning sun every day. 48<br />
Without the necessary lifestyle changes supplements will<br />
not make a difference however they can get the patient<br />
cognitively stable more quickly with the right lifestyle.<br />
Ultimately the patient is in control of their own health.<br />
From a physicians point of view control all the risk factors<br />
you can including reducing homocysteine, cholesterol and<br />
copper. Manage the gut and detoxify any heavy metals.<br />
References<br />
1. Tricco AC, et al. Efficacy and safety of cognitive enhancers for<br />
patients with mild cognitive impairment: a systematic review and<br />
meta-analysis. CMAJ. 2013:185(16):1393-401.<br />
2. Grundman MR, et al. Mild Cognitive Impairment Can Be<br />
Distinguished From Alzheimer Disease and <strong>No</strong>rmal Aging for<br />
Clinical Trials. Arch Neurol 2004:61(1): 59-66.<br />
3. Farfel J, Nitrini R, et al. Very low levels of education and<br />
cognitive reserve: a clinicopathologic study. Neurology<br />
2013;81(7): 650-7.<br />
4. Tan ZS, Seshadri S, Beiser A, et al. Plasma total cholesterol level<br />
as a risk factor for Alzheimer disease: The Framingham Study.<br />
Ann Intern Med. 2002;1<strong>37</strong>:149–155.<br />
5. Seshadri S, Beiser A; Selhub J, Jacques PF, Rosenberg<br />
IH, D'Agostino RB, Wilson PFW, and Wolf PA. Plasma<br />
Homocysteine as a Risk Factor for Dementia and Alzheimer's<br />
Disease. Engl J Med 2002(February 14);346:476-483.<br />
6. de Jager C, Oulhaj A, et al. Cognitive and clinical outcomes of<br />
lowering homocysteine-lowering B-vitamin treatment in mild<br />
cognitive impairment: A randomized controlled trial. Int J<br />
Geriatr Psychiatry. 2012;27: 592-600.<br />
7. Ramos M, Allen L, et al. Low folate status is associated with<br />
impaired cognitive function and dementia in the Sacramento<br />
24
<strong>ACNEM</strong> <strong>Journal</strong> <strong>Vol</strong> <strong>37</strong> <strong>No</strong> 2 – <strong>June</strong> <strong>2018</strong><br />
Area Latino Study on Aging. Am J Clin Nutr. 2005; 82(6)<br />
1346-1352 82(6): 1346-1352.<br />
8. Hooshmand B, Solomon A, et al.. Associations between serum<br />
homocysteine, holotranscobalamin, folate and cognition in the<br />
elderly: a longitudinal study. J Intern Med. 2012;271(12): 204-<br />
12.<br />
9. Lukiw WJ, Cui J, Marcheselli VL, Bodker M, Botkjaer A,<br />
Gotlinger K, Serhan CN, Bazan NG. Alzheimer's disease:<br />
a case control study. A role for docosahexaenoic acid derived<br />
neuroprotectin D1 in neural cell survival and Alzheimer disease.<br />
Br J Nutr. 2003;(89):483–489.<br />
10. Cenacchi T, et al. Cognitive decline in the elderly: a doubleblind,<br />
placebo-controlled multicenter study on efficacy<br />
of phosphatidylserine administration. Aging (Milano).<br />
1993;5(2):123-33.<br />
11. Brewer G. The risks of copper toxicity contributing to cognitive<br />
decline in the aging population and Alzheimer's disease. J Am<br />
Coll Nutr. 2009;28: 238-242.<br />
12. Brewer GJ. Copper excess, zinc deficiency, and cognition loss in<br />
Alzheimer's disease. Biofactors. 2012 (Mar-Apr);38(2):107-13.<br />
13. Devore E, Goldstein F, et al. Dietary antioxidants and long-term<br />
risk of dementia. Arch Neurol. 2010;67: 819-825.<br />
14. Nurk E, Refsum H, Drevon CA, Tell GS, Nygaard HA,<br />
Engedal K, Smith AD. Intake of flavanoid-rich wine, tea, and<br />
chocolate by elderly men and women is associated with better<br />
cognitive test performance. J Nutr. 2009 Jan;139(1):120-7.<br />
15. Esposito E, Rotilio D, Di Matteo V, Di Giulio C, Cacchio<br />
M, Algeri S. A review of specific dietary antioxidants and the<br />
effects on biochemical mechanisms related to neurodegenerative<br />
processes. Neurobiology of Aging. 2002;(23)719–735<br />
16. Zandi PP1, Anthony JC, Khachaturian AS, Stone SV,<br />
Gustafson D, Tschanz JT, <strong>No</strong>rton MC, Welsh-Bohmer KA,<br />
Breitner JC; Cache County Study Group.Reduced risk of<br />
Alzheimer disease in users of antioxidant vitamin supplements:<br />
the Cache County Study. Arch Neurol. 2004 Jan;61(1):82-8.<br />
17. Dysken M, Sano M et al. Effect of vitamin E and memantine<br />
on functional decline in Alzheimer disease: the TEAM-AD VA<br />
cooperative randomized trial. JAMA. 2014;311(1): 33-44.<br />
18. Morris MC, Evans DA, Tangney CC, Bienias JL, Wilson RS,<br />
Aggarwal NT and Scherr, PA. Relation of the tocopherol forms<br />
to incident Alzheimer disease and cognitive change. Am J Clin<br />
Nutr. 2005;(81): 508–514.<br />
19. van der Wiel¬Korstanje JA, Winkler KC. The faecal flora in<br />
ulcerative colitis. J Med Microbiol. 1975;8:491¬501.<br />
20. Edwards CA, Duerden BI, Read NW. The effects of pH on<br />
colonic bacteria grown in continuous culture. <strong>Journal</strong> of Medical<br />
Microbiology. 1985;19(2):169-¬80.<br />
21. Caldarini MI, Pons S, D'Agostino D, et al. Abnormal fecal<br />
flora in a patient with short bowel syndrome. An in vitro study<br />
on effect of pH on D-¬lactic acid production. Dig Dis Sci.<br />
1996;41:1649-¬1652<br />
22. Hove H, Mortensen PB. Colonic lactate metabolism and<br />
D-¬lactic acidosis. Dig Dis Sci 1995;40.<br />
23. Shah M, Beuerlein M, Danayan K. An approach to the patient<br />
with a life-¬threatening acid-¬base disturbance: the acidemias.<br />
University of Toronto Medical <strong>Journal</strong>. 2001;78:122-¬28.<br />
24. Uribarri J, Oh MS, Carroll HJ. D-¬lactic acidosis. A review of<br />
clinical presentation, biochemical features, and pathophysiologic<br />
mechanisms. Medicine (Baltimore) 30 1998;77:73-¬82.<br />
25. Haan E, Brown G, Bankier A, Mitchell D, Hunt S, Blakey<br />
J, Barnes G. Severe illness caused by the products of bacterial<br />
metabolism in a child with a short gut. European <strong>Journal</strong> of<br />
Pediatrics. 1985;144(1):63-¬5.<br />
26. Wang X, Gibson GR. Effects of the in vitro fermentation of<br />
oligofructose and inulin by bacteria growing in the human large<br />
intestine. <strong>Journal</strong> of Applied Bacteriology 1993;75:<strong>37</strong>3-¬80.<br />
27. Balion C, et al. "Vitamin D, cognition, and dementia: A<br />
systematic review and meta-analysis." Neurology, 2012; 79(13):<br />
1397-1405<br />
28. Mishra S and Palanivelu K. The effect of curcumin (turmeric)<br />
on Alzheimer's disease: An overview Ann Indian Acad Neurol.<br />
2008 Jan-Mar; 11(1): 13–19.<br />
29. Pandav R, Belle SH, DeKosky ST. Apolipoprotein E<br />
polymorphism and Alzheimer's disease: The Indo-US crossnational<br />
dementia study. Arch Neurol. 2000;57:824–30.<br />
30. Shi C, Liu J, Wu F and Yew DT.. Ginkgo biloba Extract<br />
in Alzheimer’s Disease: From Action Mechanisms to Medical<br />
Practice. Int J Mol Sci. 2010 Jan; 11(1): 107–123.<br />
31. Young AJ, et al. Coenzyme Q10: A Promising Treatment for<br />
Alzheimer’s Disease? Abstr AcademyHealth Meet. 2004; 21:<br />
abstract no. 1715.<br />
32. Ott BR, Owens NJ Complementary and alternative<br />
medicines for Alzheimer's disease. J Geriatr Psychiatry Neurol.<br />
1998;11:163-173<br />
33. Malaguarnera M1, Gargante MP, Cristaldi E, Colonna V,<br />
Messano M, Koverech A, Neri S, Vacante M, Cammalleri<br />
L, Motta M. Acetyl L-carnitine (ALC) treatment in elderly<br />
patients with fatigue. Arch Gerontol Geriatr. 2008 Mar-<br />
Apr;46(2):181-90.<br />
34. Cardinali DP, Furio AM, and Brusco LI...Clinical Aspects of<br />
Melatonin Intervention in Alzheimer’s Disease Progression .<br />
Curr Neuropharmacol. 2010 Sep; 8(3): 218–227.<br />
35. Hager K1, Marahrens A, Kenklies M, Riederer P, Münch<br />
G. Alpha-lipoic acid as a new treatment option for Alzheimer<br />
[corrected] type dementia. Arch Gerontol Geriatr. 2001<br />
Jun;32(3):275-82.<br />
36. Abuznait AH1, Qosa H, Busnena BA, El Sayed KA,<br />
Kaddoumi A.Olive-oil-derived oleocanthal enhances β-amyloid<br />
clearance as a potential neuroprotective mechanism against<br />
Alzheimer's disease: in vitro and in vivo studies. ACS Chem<br />
Neurosci. 2013 Jun 19;4(6):973-82.<br />
<strong>37</strong>. Martínez-Lapiscina EH1, Clavero P, Toledo E, San Julián<br />
B, Sanchez-Tainta A, Corella D, Lamuela-Raventós RM,<br />
Martínez JA, Martínez-Gonzalez MÁ. Virgin olive oil<br />
supplementation and long-term cognition: the PREDIMED-<br />
NAVARRA randomized, trial. J Nutr Health Aging.<br />
2013;17(6):544-52.<br />
38. Lourida, I, Soni M, et al. (2013). Mediterranean diet, cognitive<br />
function, and dementia: a systematic review. Epidemiology<br />
24(4): 479-89.<br />
25
<strong>ACNEM</strong> <strong>Journal</strong> <strong>Vol</strong> <strong>37</strong> <strong>No</strong> 2 – <strong>June</strong> <strong>2018</strong><br />
39. Smith JC, Nielson KA, Antuono P, Lyons JA, Hanson RJ, Butts<br />
AM, Hantke NC, Verber MD. Semantic memory functional<br />
MRI and cognitive function after exercise intervention in mild<br />
cognitive impairment. J Alzheimer’s Dis. 2013;<strong>37</strong>(1):197-215<br />
40. Crapper, D, Krishnan, S, et al. Aluminum, neurofibrillary<br />
degeneration and Alzheimer's disease. Brain (1976);99: 67-80.<br />
41. Crinnion, W. Polychlorinated biphenyls: persistent pollutants<br />
with immunological, neurological, and endocrinological<br />
consequences. Altern Med Rev. 2013;16(1): 5-13.<br />
42. Kawahara, M and Kato-Negishi M. Link between aluminum<br />
and the pathogenesis of Alzheimer's disease: The integration of<br />
aluminum and amyloid cascade hypotheses. Int. J Alzheimer's<br />
Dis March. 2011;8: 276393.<br />
357–<strong>37</strong>4.<br />
45. Kim J, Basak J, et al. (2009). The role of apolipoprotein E in<br />
Alzheimer's disease. Neuron 63(3): 287-303.<br />
46. Farlow M, He Y, et al. (2004). Impact of APOE in mild<br />
cognitive impairment. Neurology 63(10): 1898-901<br />
47. Hanson, A, Bayer-Carter J, et al.. "Effect of Apolipoprotein<br />
E Genotype and Diet on Apolipoprotein E Lipidation and<br />
Amyloid Peptides Randomized Clinical Trial." JAMA Neurol.<br />
2013;70(8): 972-80.<br />
48. Physicians Committee for Responsible Medicine. Dietary<br />
Guidelines for Alzheimer’s Prevention. International Conference<br />
on Nutrition and the Brain, 2013. Washington.<br />
43. Rondeau V, Jacqmin-Gadda H, et al. Aluminum and silica in<br />
drinking water and the risk of Alzheimer's disease or cognitive<br />
decline: Findings from 15-year follow up of the PAQUID cohort.<br />
Am J Epidemiol. 2009;169: 489-496.<br />
44. Muttera J, Curthb A, et al. Does Inorganic Mercury Play a Role<br />
in Alzheimer’s Disease? A Systematic Review and an Integrated<br />
Molecular Mechanism. <strong>Journal</strong> of Alzheimer’s Disease. 2010;22:<br />
OPTIMISE YOUR<br />
CLINICAL SUCCESS<br />
By Using Products of the Highest Quality and Efficacy<br />
HYPO-ALLERGENIC<br />
FULL<br />
TRANSPARENCY<br />
LABEL<br />
Vegan<br />
Friendly<br />
NO<br />
HARSH<br />
ADDITIVES<br />
ALL RESEARCH NUTRITION PRODUCTS CONTAIN<br />
NO SOY NO YEAST NO DAIRY NO EGG NO GLUTEN NO SUGAR<br />
www.prac.researchnutrition.com.au<br />
PH 1800 110 158 | support@researchnutrition.com.au<br />
26
Injectable Nutrients<br />
Manufactured to the world’s highest standard,<br />
the European PIC/S Code of GMP.<br />
With over 40 years of sterile manufacturing experience,<br />
Biological Therapies produces the highest quality products<br />
that meet your safety & effi cacy requirements.<br />
PBS Information: These products are not listed on the PBS.<br />
Biological Therapies<br />
Suite 5, 20-30 Malcolm Road, Braeside VIC 3195<br />
Tel +61 3 9587 3948 • Fax +61 3 9587 1720 • Toll Free 1800 063 948<br />
info@biol.com.au • biologicaltherapies.com.au<br />
ABN: 99 006 897 856<br />
Version ID: <strong>ACNEM</strong>_<strong>Journal</strong>_Ad_A4_Mar_<strong>2018</strong>
<strong>ACNEM</strong> <strong>Journal</strong> <strong>Vol</strong> <strong>37</strong> <strong>No</strong> 2 – <strong>June</strong> <strong>2018</strong><br />
COMMENTARY<br />
Re-integrating Medicine<br />
Part 2: Reclaiming Science<br />
Author:<br />
John Smartt<br />
If you are an integrative practitioner, unfortunately some of your<br />
colleagues probably think that you’re “unscientific”. They may<br />
also believe that, because of this, what you do is fundamentally<br />
unsafe for patients.<br />
If you are like all of the integrative doctors I know, you would<br />
prefer not to engage in an argument about this. You probably<br />
became interested in this field because mainstream medicine<br />
didn’t provide the answers you were looking for to treat:<br />
yourself, a family member, or a number of your patients; people<br />
who had complex and chronic conditions. You realised how<br />
narrow your university and hospital-based education was, and<br />
that it had more to do with short-term emergency medicine<br />
than ongoing health-related quality of life, and you decided to<br />
broaden your knowledge. You probably did this because you<br />
would rather help patients than gain status among your peers.<br />
You may prefer to stay below the radar, doing what you do for<br />
your patients without having to engage in a rear-guard action<br />
with your profession or its regulators.<br />
Sometimes, unfortunately, you have no choice; and, even if you<br />
seek to avoid controversy, there is always the underlying concern<br />
that it will come and find you. So, at the risk of haranguing the<br />
converted, I wanted to provide an alternative perspective.<br />
Claiming that integrative medicine is “unscientific” shows, I<br />
believe, a complete misunderstanding of: (1) the nature of<br />
science; (2) the way that science progresses; (3) the importance<br />
of sample size in clinical trials; (4) how thin the evidence base<br />
really is for a lot of established medical practice; and (5) the<br />
nature of integrative medicine.<br />
1) Misunderstanding about the nature of science<br />
Science is a cyclical process of continual learning. It starts with<br />
open-minded curiosity, followed by hypothesis formation,<br />
followed by testing of the hypothesis, followed by dissemination<br />
and discussion of the findings, which typically raises more<br />
questions, which provoke further open-minded curiosity. It’s an<br />
ongoing exploration: which is why most journal articles contain<br />
the phrase “more research is needed”. The word “science” cannot<br />
be appropriately used to stifle debate or experimentation. It<br />
should never be used as the basis of dogmatic, entrenched<br />
positions. Science simply isn’t like that. Science tells us that<br />
our understanding is never complete; there is always more to<br />
learn. (This is particularly true when we study human health;<br />
the more we learn, the more we realise how little we know.)<br />
It is really quite sad when people take one part of the cycle –<br />
the publication of findings – and treat that as the totality of<br />
science. To call integrative medicine “unscientific” because it<br />
tends to push the boundaries and look for new solutions fails to<br />
appreciate that actually makes it scientific.<br />
By challenging and testing received wisdom, science has always<br />
stood against unquestioning dogma. It’s unfortunate when<br />
the word “science” is used to support dogmatically entrenched<br />
positions about medicine and human health. When the<br />
following phrases are used, it should put us on high alert that<br />
someone may be trying to disguise their own dogma as science:<br />
• "…science has proven/established…” (implying that no new<br />
evidence or understanding could possibly come along);<br />
• “…there is no evidence that…” (implying that the speaker<br />
is across the more than 100,000 new medical articles<br />
published every month); and<br />
• “…scientific fact…” (implying that everything which can be<br />
known about something is already known about it).<br />
2) Misunderstanding the way that science progresses<br />
There is a wonderful book by Thomas Kuhn, called “The<br />
Structure of Scientific Revolutions”1. It should be required<br />
reading as part of all university-based science courses. In this<br />
book, Kuhn demonstrates that, historically, “normal science”<br />
proceeds incrementally - based on the broad frameworks that<br />
people were initially taught. Those with established expertise<br />
are happy to accept its findings. But paradigm-busting<br />
breakthroughs are usually resisted; particularly by those most<br />
entrenched in existing paradigms.<br />
Integrative/functional medicine is paradigm-busting. It involves<br />
moving from a number of accepted medical approaches (whose<br />
power lays in the fact that they are normally invisible). These<br />
paradigms include the ideas that:<br />
• everything in the body acts in isolation, and a condition<br />
appearing in an organ or system can be resolved completely<br />
by only attending only to that to that organ or system;<br />
• the person in front of you will be representative of others<br />
with the same named condition, so that the treatment that<br />
works for others will work for them without the clinician<br />
having to reason things out for themselves;<br />
28
<strong>ACNEM</strong> <strong>Journal</strong> <strong>Vol</strong> <strong>37</strong> <strong>No</strong> 2 – <strong>June</strong> <strong>2018</strong><br />
• because underlying causes are complex, there is no need to<br />
look for them;<br />
• the patient has the disease, the doctor has the cure, and the<br />
patient’s own self-healing mechanisms don’t really come<br />
into it; and<br />
• all medical truth comes from either drug companies or<br />
equipment manufacturers (or those they fund) and it isn’t<br />
worth looking elsewhere for it because nothing else will be<br />
helpful.<br />
Integrative medicine challenges all of those paradigms, which<br />
isn’t surprising; they are all illogical. But when you challenge<br />
paradigms, you almost inevitably provoke a backlash, and<br />
particularly when you challenge existing power structures and/<br />
or economic interests. There is typically a period of turmoil<br />
while different worldviews compete, before one (which was<br />
initially held by a small minority) finally comes to dominate. It<br />
has always been so.<br />
The fact that you follow a minority opinion does not, in any<br />
sense, indicate that you are wrong, or even likely to be so.<br />
History is, in fact, on your side.<br />
3) Misunderstanding of the importance of sample-size in<br />
clinical trials<br />
There is a common and completely erroneous belief that large<br />
trials are going to provide more important results than small<br />
ones. What actually happens is that (as a generalization)<br />
the smaller the effect size, the larger the trial that is needed<br />
to demonstrate statistical significance. Here is a thoughtexperiment<br />
to illustrate this.<br />
Suppose that you had a technique for flipping a coin, so that<br />
you could influence the way it would fall. In order to prove that<br />
your technique worked, you would have to flip it a number of<br />
times. But how many?<br />
If you flip it once and get heads, no one is likely to be<br />
convinced. You had a 50% chance of getting that. But if you flip<br />
it five times and get heads, you only have 1 chance in 32 of that<br />
happening by chance. That is, less than 5%, giving you a P value,<br />
in statistical terms, of 0.05. There is only 1 chance in 1,024<br />
of flipping it 10 times in a row and getting heads; a P value<br />
of 0.001. If you do that, everyone will be convinced that your<br />
technique works. So a small sample size (in this case, n=10) can<br />
deliver very convincing results, intuitively and statistically.<br />
This only applies, though, if your technique works every<br />
single time. <strong>No</strong>w imagine that your technique only works<br />
approximately one time in every ten. If you flip the coin ten<br />
times, and you get heads on 6 of those occasions, no one will<br />
be very convinced. But if you flip it 10,000 times and get heads<br />
on 6,000 of them, you can probably prove statistically that it<br />
is effective. In fact, if you don’t mind confusing absolute and<br />
relative risk (which so many don’t), you can say that, as your<br />
technique gave you 6,000 heads and only 4,000 tails, it improves<br />
your chance of getting heads by 50%; and you have a very large<br />
trial to prove it!<br />
A 2007 review by Bero et al looked at 192 trials into statins.<br />
It found that the larger the sample size, the more likely it was<br />
to find in favour of the statin. That shouldn’t be interpreted as<br />
meaning that better trials produced more favourable results;<br />
that wasn’t the case at all. The same review found that funding<br />
from the test drug company was associated with results and<br />
conclusions that favoured the test drug when controlling for<br />
other factors, while studies with adequate blinding were less<br />
likely to report statistically significant results favouring the test<br />
drug 2 .<br />
Once someone has gone to the trouble and expense of designing<br />
a new drug and setting up a trial for it, it is relatively easy and<br />
inexpensive to add more participants to it. Just because that has<br />
happened, it shouldn’t automatically convince anyone that the<br />
results are likely to be more important than any other, smaller<br />
study; possibly quite the reverse. The important issues are the<br />
design of the study, the appropriateness of subject-selection, the<br />
appropriateness of the statistics, the size of the effect and the<br />
likelihood that the effect was obtained by random chance.<br />
4) Misunderstanding of the amount of evidence supporting<br />
mainstream medicine<br />
There is much less good evidence for accepted medical<br />
interventions than you may believe. That isn’t just my opinion;<br />
it’s the opinion of editors of some of the best-respected medical<br />
journals.<br />
This, from Richard Horton, the editor of The Lancet: “Much<br />
of the scientific literature, perhaps half, may simply be untrue.” 3<br />
And this, from Marcia Engell, former editor of the New<br />
England <strong>Journal</strong> of Medicine: “It is simply no longer possible to<br />
believe much of the clinical research that is published, or to rely<br />
on the judgment of trusted physicians or authoritative medical<br />
guidelines. I take no pleasure in this conclusion, which I reached<br />
slowly and reluctantly over my two decades as an editor of The<br />
New England <strong>Journal</strong> of Medicine……Most of the big drug<br />
companies have settled charges of fraud, off-label marketing,<br />
and other offences. TAP Pharmaceuticals, for example, in 2001<br />
pleaded guilty and agreed to pay $875 million to settle criminal<br />
and civil charges brought under the federal False Claims Act<br />
over its fraudulent marketing of Lupron, a drug used for<br />
treatment of prostate cancer. In addition to GlaxoSmithKline,<br />
Pfizer, and TAP, other companies that have settled charges<br />
of fraud include Merck, Eli Lilly, and Abbott. The costs,<br />
while enormous in some cases, are still dwarfed by the profits<br />
generated by these illegal activities, and are therefore not much<br />
of a deterrent.” 4<br />
The British House of Commons Public Accounts Committee<br />
noted late in 2013 that drug companies, despite much negative<br />
publicity around the practice, were still only publishing around<br />
50% of the results of clinical trials which they funded 5 .<br />
In 2017 the British Medical <strong>Journal</strong> published a study on<br />
payments from pharmaceutical and medical-equipment<br />
manufacturers to US medical-journal editors. Of 713 editors,<br />
it found that 50.6% received some form of financial payments<br />
from these sources in 2014. 6<br />
At the present time, there is simply too much money available<br />
in pharmaceuticals and medical equipment, and the legislative<br />
oversight is too inadequate, to enable us to trust much of the<br />
“scientific” support for mainstream medicine.<br />
29
<strong>ACNEM</strong> <strong>Journal</strong> <strong>Vol</strong> <strong>37</strong> <strong>No</strong> 2 – <strong>June</strong> <strong>2018</strong><br />
5) Misunderstanding integrative medicine<br />
In my experience, at least, presentations about integrative<br />
medicine are normally based on a large number of studies,<br />
whereas mainstream presentations tend to be based on one<br />
or two; possibly ones that haven’t even been completed or<br />
peer reviewed. Usually ones that someone stands to make<br />
a lot of money from. Of course, that could be a widely offtarget<br />
generalisation. You will know whether it is or not, from<br />
your own experience. But quite apart from this, integrative<br />
medicine is fundamentally scientific by it’s nature, in a way that<br />
mainstream medicine is not.<br />
If you start with an open mind about your patients and the<br />
conditions they bring to you, you are being scientific. If you are<br />
curious about underlying causes, rather than just leaping in to<br />
apply a treatment-of-choice to the first thing that presents, you<br />
are being scientific. If you form a hypothesis and test it, you are<br />
being scientific. If you are willing to push the boundaries and<br />
look outside the tried-and-trusted, you are being scientific. If<br />
you discuss the results of tests and of responses to treatment<br />
with your patient and your peers, you are being scientific. If you<br />
are open to have been found wrong, and you are willing to keep<br />
digging, you are being scientific. If you keep trying to find ways<br />
to help your patients to be more healthy, more quickly, you are<br />
being scientific.<br />
Taking this sort of approach to treatment is, I believe, the most<br />
scientific approach to medicine, whereas only being willing to<br />
accept the received findings from drug companies, equipment<br />
manufacturers and those whom they pay, is dogmatism. And<br />
dogmatism has always been the enemy of science.<br />
On patient safety<br />
If you are going to be truly scientific, you need to be willing<br />
to experiment on your patients. That statement may sound<br />
frightening, but, leaving science out of it, if you are seeing<br />
patients who badly need help, and who haven’t been helped<br />
by any of the standard treatments on offer, you need to be<br />
willing to try something different. If you truly want to practice<br />
individualised medicine, and you recognise that no studies<br />
have been done on the complex individual in front of you, then<br />
you are going to have to experiment. You aren’t alone, though;<br />
across all medicine, it is estimated that 50% of prescriptions<br />
are “off-label” (prescribed for purposes for which they have not<br />
had research-based regulatory approval) 7 . If you are dealing<br />
with patients who are already prescribed multiple drugs, you<br />
can guarantee that no research study has been done on the<br />
combined effects of all of the drugs that they are on.<br />
While you may be accused by your mainstream colleagues of<br />
being unsafe by experimenting on patients, it is important to<br />
remember that, in terms of patient safety, mainstream medicine<br />
lives in a very fragile glass house, and that it shouldn’t throw<br />
stones at anybody. In one classic study, it was found that 36% of<br />
patients in the hospital under review suffered from an iatrogenic<br />
illness. In 9% of these cases it was considered major, and in<br />
2% it was believed to contribute to the patient’s death. This<br />
study also found that exposure to pharmaceutical drugs was a<br />
particularly important factor in this outcome 8 .<br />
However, mainstream medicine shouldn’t function as the<br />
benchmark for patient safety; partly because it is more focused<br />
on acute and life-threatening conditions, and partly because<br />
treating individuals solely as members of a category, and then<br />
applying a treatment of choice for that category without<br />
considering individual issues, is inherently unsafe. We would all<br />
hope and expect that integrative medicine could do a lot better<br />
than that. (There is another factor in safety, as well; a more<br />
self-interested one for the integrative doctor. If what you do<br />
is consistent with mainstream practice, that fact may give you<br />
some legal protection if things go badly. If you take a different<br />
path, you are more exposed.)<br />
So here are some random thoughts about how to make sure<br />
what you do is as safe as it can be, while being even more<br />
scientific:<br />
1. Test thoroughly before you prescribe (even “safe” things like<br />
herbals and supplements). It may frustrate your patients, it<br />
may seem expensive, and it may seem to delay results. More<br />
often, though, there is a hare-and-tortoise effect; when you<br />
get it right before you prescribe, you are more likely to get a<br />
quick result while ultimately costing the patient less.<br />
2. Keep an open mind about what you are seeing; there is<br />
always more to the picture than you will ever understand.<br />
Avoid absolutes: both in your advertising, and in your<br />
communication with patients.<br />
3. Balance your open-mindedness with cynicism. Or, in other<br />
words, balance your open-mindedness with more openmindedness.<br />
Don’t automatically believe what you hear or<br />
read about – from any source – without checking it for<br />
yourself.<br />
4. Communicate honestly to patients, about the level of<br />
evidence for what you are offering, how widely accepted it<br />
is (or isn’t) and, of course, any risks involved. Involve them<br />
in your decisions about their health. If they have been to<br />
a lot of practitioners and know a great deal about their<br />
condition, they will probably appreciate this response. If<br />
they are new to the complex-condition-merry-go-round,<br />
they will probably want you to sound confident and<br />
reassuring. Try to avoid doing so; it’s asking for trouble<br />
in the long-term. Educate them enough so that you can<br />
genuinely make joint decisions with them.<br />
5. Create an environment where patients feel safe to talk to<br />
you about the results of their treatment, and particularly<br />
of any adverse effects, or lack of effects, that they are<br />
experiencing.<br />
6. Always remember that your interest is the whole health<br />
of the patient, over both the short- and long-terms. With<br />
that in mind, be particularly careful prescribing anything<br />
for a long time (or just telling them to take something,<br />
and not telling them when to stop). Most vitamin and<br />
mineral supplements, for example, will begin to replace<br />
other vitamins and minerals if they are taken for long<br />
enough. This can become life-threatening. (Thankfully<br />
the tendency to automatically prescribe long-term calcium<br />
for osteoporosis is dying out in the face of the evidence;<br />
but things like long-term magnesium are still routinely<br />
prescribed.) Also be particularly careful prescribing<br />
30
<strong>ACNEM</strong> <strong>Journal</strong> <strong>Vol</strong> <strong>37</strong> <strong>No</strong> 2 – <strong>June</strong> <strong>2018</strong><br />
hormones. Endocrine interactions form an exceptionally<br />
complex web, and it is virtually impossible to understand<br />
the flow-on effects of any hormone supplement on any<br />
individual. There is probably no hormone that doesn’t, by<br />
indirect means, affect most other hormones. And each of<br />
those hormones has a great number of different effects.<br />
7. Keep your diagnosis complex and your treatment as<br />
simple as possible. It is as impossible to understand the<br />
combined effects of multiple bioactive supplements as it is<br />
to understand the effects of poly pharmacy.<br />
8. If you find that your prescribing habits are being<br />
influenced by the fact that you make a percentage from the<br />
supplements you sell, then stop. You are on a very slippery<br />
slope that may not end well for anyone.<br />
Conclusion<br />
Integrative medicine is at the forefront of science, and at the<br />
forefront of patient care in a world where complex, chronic<br />
and challenging conditions are on the rise. We can probably all<br />
benefit from being more scientific; but integrative medicine is<br />
much closer to it than most of what happens in the mainstream.<br />
If you have the misfortune to be dragged into debates or<br />
complaints about what you do, you should know that science is<br />
on your side, and you are on the side of science.<br />
About the author:<br />
John Smartt has a background in ‘organisation development’, which<br />
involves helping organisations to change their corporate cultures<br />
(including thinking through their underlying assumptions). At the age<br />
of 39 he added an additional career, and spent five years studying to<br />
become an osteopath. He has now been practicing for 16 years.<br />
References<br />
1. Kuhn, T. The Structure of Scientific Revolutions, The<br />
University of Chicago Press, Chicago; 1962<br />
2. Bero L, Oostvogel F, Bacchetti P, Lee K. Factors associated<br />
with findings of published trials of drug-drug comparisons: why<br />
some statins appear more efficacious than others. PLoS Med<br />
Jun; 2007 4(6):e184 http://journals.plos.org/plosmedicine/<br />
article?id=10.1<strong>37</strong>1/journal.pmed.0040184<br />
3. Horton, R. What is Medicine’s 5 Sigma? The Lancet, 2015<br />
(11 April);385,(9976), p1380,<br />
4. http://www.nybooks.com/articles/2009/01/15/drugcompanies-doctorsa-story-of-corruption/<br />
5. Tovey, D. "Why the Public Accounts Committee Report on<br />
Tamiflu Is Important for Us All", Huffington Post, 2014: 3<br />
January.<br />
6. Liu JJ, Bell CM, Matelski JJ, Detsky AS, Cram P. Payments<br />
by US pharmaceutical and medical device manufacturers to<br />
US medical journal editors: retrospective observational study.<br />
BMJ. 2017 (Oct 26);359:j4619 http://www.ncbi.nlm.nih.<br />
gov/pubmed<br />
7. http://www.nybooks.com/articles/2009/01/15/drugcompanies-doctorsa-story-of-corruption/<br />
8. Steel K, Gertman PM, Crescenzi C, Anderson J. Iatrogenic<br />
illness on a general medical service at a university hospital Qual<br />
Saf Health Care 2004;13:76–81<br />
SYMPOSIUM<br />
Practitioner Perspectives<br />
& Clinical Insights into<br />
Environmental Toxicity<br />
& Detoxification<br />
Brisbane<br />
Saturday 27 + Sunday 28<br />
October <strong>2018</strong><br />
Join us as leading Australian and<br />
International experts discuss their<br />
perspectives around environmental<br />
toxicity and how to maximise the<br />
body’s own detoxification capabilities.<br />
We hope to see you there.<br />
Investment<br />
Early Bird * $495.00 AUD (incl. GST)<br />
Full Fee $595.00 AUD (incl. GST)<br />
Student 20% discount<br />
*Early bird registrations close Tuesday 31st July <strong>2018</strong><br />
Register Online Today!<br />
Go to: myintegria.com/events-webinars<br />
For other enquiries, please<br />
contact Integria Healthcare<br />
E: seminars@integria.com<br />
P: 1300 654 336 (Option 3)<br />
Presenters: Dr Joseph Pizzorno, Leah Hechtman, Dr Walter J Crinnion, Tabitha McIntosh, Professor Kerry Bone<br />
31
<strong>ACNEM</strong> <strong>Journal</strong> <strong>Vol</strong> <strong>37</strong> <strong>No</strong> 2 – <strong>June</strong> <strong>2018</strong><br />
College News<br />
<strong>ACNEM</strong> Annual Conference<br />
The <strong>2018</strong> conference has come and gone and there<br />
is no doubt from the feedback received that it was an<br />
overwhelming success. A big thank you to all those delegates<br />
who gave up their weekend to come and listen to a range of<br />
presentations from our expert line up of speakers.<br />
The theme of the conference was HEALTH FOR LIFE<br />
| Mastering the Integrated Approach and was held at<br />
the Pullman Melbourne on the Park in East Melbourne.<br />
The total number of attendees was 344. Delegates<br />
included general practitioners, other medical practitioners,<br />
naturopaths, nutritionists/dieticians, pharmacists, nurses<br />
and students from Australia, New Zealand and Singapore.<br />
In the opening session, Dr Robert Roundtree from the<br />
USA gave a presentation entitled: ‘Good Health Begins in<br />
the GIT: Emerging Science behind the Maxim’. Professor<br />
Joseph Proietto then covered; ‘Weight Gain Over a<br />
Lifetime – addressing risk factors, triggers and perpetuating<br />
factors and the role of hunger, cravings and individual<br />
biology. Presentations were then featured under the<br />
headings of Metabolism: New Frontiers, Gut and Immune<br />
Connections: Latest Perspectives, Healthy Ageing: The<br />
Modern Approach and Clinical Tools and Practice.<br />
from the <strong>ACNEM</strong> Board, with a Distinguished<br />
Academic Service Award. The full citation is included<br />
elsewhere in the <strong>Journal</strong>.<br />
• The inaugural Ian Brighthope Oration given by<br />
Associate Professor Ross Grant. The oration was<br />
entitled ‘Oxidative stress in ageing’.<br />
• An opportunity for our student members to<br />
participate in an informal meeting to facilitate<br />
on-going support for our student members.<br />
The conference committee of: Dr Christabelle Yeoh, Dr<br />
Kamal Karl, Dr Kim Hayes, Dr Braham Rabinov, Rachel<br />
Arthur, Dr Keren Witcombe (2017) and Dr Ron Ehrlich<br />
(<strong>2018</strong>) all did an outstanding job of bringing a program<br />
together that focussed on both latest research and practical<br />
applications. The committee is now busy researching and<br />
planning for 2019.<br />
<strong>ACNEM</strong> is indebted to its sponsors – Metagenics,<br />
BioCeuticals, Eagle – Integria, MediHerb – Integria,<br />
Spectrumceuticals, L-Nutra, AIMN, Australian Clinical<br />
Labs, bwellness (BioPractica), BioConcepts, Biological<br />
Therapies, BioMedica, Cell-Logic, Cobram Estate,<br />
Endeavour College of Natural Health, Enterosoz<br />
Australia, FXMed, Natural Chemist Integrative Pharmacy,<br />
NutriPATH, Nutrisearch, NutritionCare, Research<br />
Nutrition, vital.ly and Your Solution Compounding<br />
Pharmacy. Without their support and commitment, a<br />
conference such as this would not be able to be run. We<br />
also acknowledge Lindt and Golden Grind for kindly<br />
donating chocolate and turmeric latte mix as gift sponsors.<br />
The date for 2019 has been locked in and the conference<br />
will be held on 25 and 26 May 2019 - we look forward to<br />
seeing you in 2019.<br />
Thank you to all presenters: Dr Sebastian Brandhorst, Dr<br />
Sreekumar Appukuttannair, Dr Lenny Da Costa, Professor<br />
Emeritus John Tagg, Dr Emma Halmos, Professor Charles<br />
Mackay, Michael Thomsen, Assoc Prof Ross Grant,<br />
Professor David Cameron-Smith, Dr Denise Furness,<br />
Rachel Arthur, Nathan Rose, Warren Maginn, Nicole<br />
Bijlsma and Dr Kenneth Winkel.<br />
Highlights of the conference included:<br />
• The awarding of Dr Debbie Fewtrell, recently retired<br />
33
<strong>ACNEM</strong> <strong>Journal</strong> <strong>Vol</strong> <strong>37</strong> <strong>No</strong> 2 – <strong>June</strong> <strong>2018</strong><br />
Medicinal Cannabis Education – Practitioners<br />
course and Public Event.<br />
<strong>ACNEM</strong> was very pleased to be involved in a three-way<br />
collaboration with the National Institute of Integrative<br />
Medicine (NIIM) and the NICM Health Research Institute<br />
(NICM, Western Sydney University) who all joined<br />
forces under a consortium entitled: ‘Medicinal Cannabis<br />
Education’ (MCE) to deliver Australia’s first two-day,<br />
RACGP-accredited, medicinal cannabis course for heathcare<br />
practitioners.<br />
The course featured US medicinal cannabis expert, Dr Jeffrey<br />
Hergenrather MD, Adjunct Professor John Skerritt, Deputy<br />
Secretary of the Therapeutic Goods Administration’s (TGA)<br />
Health Products Regulation Group and a host of Australian<br />
doctors and academics, and covered the science, regulations,<br />
safe prescribing, and evidence of its effectiveness in treating<br />
many illnesses. <strong>ACNEM</strong>’s President, Dr Christabelle Yeoh<br />
was one of the facilitators for the course. Professor Ian<br />
Brighthope was a key contributor to the development of the<br />
course as well as a presenter.<br />
A public event at the Malvern Town Hall followed the<br />
practitioner education course on the evening of Monday 21<br />
May. This event attracted 150 members of the public and<br />
featured presentations from ‘Amazon John’ Easterling, Dr<br />
Jeffrey Hergenrather, Ms Carol Ireland, CEO of Epilepsy<br />
Action Australia as well as a presentation by a young<br />
Brisbane man Lindsay Carter who suffers from a brain<br />
tumour and epilepsy, and his mother Lanai, who spoke<br />
about Lindsay’s illness and his difficult battle to get access to<br />
medicinal cannabis in Australia.<br />
Medicinal Cannabis Education will be running its next<br />
practitioner training course in Sydney in September <strong>2018</strong>.<br />
Upcoming <strong>ACNEM</strong> training courses<br />
<strong>ACNEM</strong> is very pleased to be heading to Wellington on<br />
28 and 29 July this year to run both its two-day primary<br />
course as well as an Integrative Cancer Care module. The<br />
InterContinental Wellington hotel will be a fantastic venue<br />
for you to join us for these two courses.<br />
The course, held in Melbourne, was opened by Mr Tim<br />
Wilson, Federal MP and US-based, ‘Amazon John’ Easterling,<br />
who has been involved in the medicinal cannabis and<br />
herbal medicine industries for over 20 years. Attended by<br />
55 practitioners, mostly doctors, plus a small number of<br />
pharmacists and other allied healthcare practitioners, the<br />
course received overwhelmingly positive feedback.<br />
The MCE course addressed a critical need to provide GP<br />
education about medicinal cannabis in Australia, and helps<br />
prepare doctors to apply to become authorised prescribers of<br />
medicinal cannabis under the TGA’s Authorised Prescriber<br />
Scheme. Under this scheme, doctors may apply to a human<br />
research ethics committee (HREC) then, if approved, apply<br />
to the TGA for final approval. The Authorised Prescriber<br />
Scheme allows doctors to apply to treat patients with specific<br />
conditions, whereas the alternative Special Access Scheme<br />
allows doctors to apply on a case-by-case basis only. Doctors<br />
still need to satisfy their state health department regulations.<br />
The Integrative Cancer Care module will explore the<br />
speciality area of integrative oncology, showcasing a variety of<br />
therapeutic tools and techniques and features all new content.<br />
We have a range of experienced presenters who will share<br />
their working clinical knowledge of hyperbaric oxygen use<br />
and hyperthermic treatments, as well as bringing you up to<br />
date on the latest research and use of intravenous vitamin C<br />
in this field.<br />
The training will include sessions on how to apply ketogenic<br />
diets in clinical practice and how this can benefit your<br />
patients, as well as how all of these tools and techniques can<br />
be used with other cancer treatments such as chemotherapy<br />
and radiation.<br />
You will also hear about the metabolic theory of cancer,<br />
34
<strong>ACNEM</strong> <strong>Journal</strong> <strong>Vol</strong> <strong>37</strong> <strong>No</strong> 2 – <strong>June</strong> <strong>2018</strong><br />
immune modulating nutraceuticals, environmental and<br />
lifestyle factors and integrative oncology practice. Bring your<br />
tricky case questions and build your network with likeminded<br />
practitioners.<br />
The ‘Integrative Cancer Care’ activity has been endorsed by<br />
The Royal New Zealand College of General Practitioners<br />
(RNZCGP) and has been approved for up to six CME<br />
credits (per session) for the General Practice Educational<br />
Programme (GPEP) and Continuing Professional<br />
Development (CPD) purposes.<br />
The Primary Modules in NEM, designed for GPs,<br />
registrars and other graduate healthcare professionals,<br />
are <strong>ACNEM</strong>’s foundational training in post graduate<br />
Nutritional and Environmental Medicine. These modules<br />
provide an introduction and overview of NEM within<br />
primary care. Each major biological system is explored<br />
covering the key nutritional, environmental and biochemical<br />
factors affecting health and disease. Through case studies<br />
delegates will gain practical tools to aid integration into<br />
daily practice. The Primary Modules enable practitioners to<br />
begin practising NEM confidently and safely.<br />
The ‘Primary Modules in Nutritional and Environmental<br />
Medicine’ activities have been endorsed by The Royal New<br />
Zealand College of General Practitioners (RNZCGP)<br />
and have been approved for up to 12 CME credits (per<br />
session) for the General Practice Educational Programme<br />
(GPEP) and Continuing Professional Development (CPD)<br />
purposes.<br />
We hope to see you in Wellington.<br />
New <strong>ACNEM</strong> Fellow<br />
We are very pleased to congratulate Dr Matthew Strack on<br />
obtaining Fellowship of <strong>ACNEM</strong>. Dr Strack was awarded<br />
his Fellowship during <strong>ACNEM</strong>’s recent Annual Conference<br />
and on behalf of the <strong>ACNEM</strong> Board we congratulate him<br />
on this achievement.<br />
FINDING BALANCE WITH HORMONES<br />
FULL DAY WORKSHOP<br />
AN IN-DEPTH LOOK AT THE HPA AXIS, THE HPO AXIS AND THE HPG AXIS<br />
PRESENTED BY<br />
WORLD EXPERT<br />
IN HORMONES,<br />
DR. CARRIE<br />
JONES, ND, MPH<br />
Methylation<br />
Summit pre-event<br />
THURSDAY 9 TH<br />
AUGUST <strong>2018</strong><br />
THE CONCOURSE<br />
409 Victoria Ave, Chatswood<br />
NSW 2067<br />
ONLY $<strong>37</strong>9<br />
Includes healthy lunch & snacks<br />
BONUS<br />
All Attendees get<br />
a FREE DUTCH<br />
Complete Test!<br />
(VALUE $<strong>37</strong>9)<br />
PROUDLY BROUGHT TO YOU BY<br />
DON’T MISS THIS OPPORTUNITY TO<br />
DISCUSS HORMONES WITH THE EXPERT!<br />
35<br />
Visit prac.researchnutrition.com.au to register
<strong>ACNEM</strong> <strong>Journal</strong> <strong>Vol</strong> <strong>37</strong> <strong>No</strong> 2 – <strong>June</strong> <strong>2018</strong><br />
Awards and Recognition<br />
Dr Debbie Fewtrell<br />
Recipient of the <strong>ACNEM</strong> Distinguished Academic<br />
Service Award<br />
The President, Dr Christablle Yeoh read the following<br />
citation out in presenting Dr Debbie Fewtrell with<br />
the Distinguished Academic Service Award of The<br />
Australasian College of Nutritional and Environmental<br />
Medicine (<strong>ACNEM</strong>) in recognition of her significant<br />
contribution to the work of <strong>ACNEM</strong>. The presentation<br />
was made during <strong>ACNEM</strong>’s <strong>2018</strong> Annual Conference.<br />
Debbie is a general practitioner based in New Zealand<br />
and has a strong focus to inspire and educate parents and<br />
professionals in Australasia to use integrative biomedical<br />
approaches to improve the health and neurological function<br />
of children.<br />
Debbie holds Fellowship of the New Zealand College of<br />
General Practitioners as well as a diploma of obstetrics.<br />
She has also completed physican training in Pfeiffer/Walsh<br />
protocols as well as DAN – Defeat Autism <strong>No</strong>w.<br />
Debbie commenced her <strong>ACNEM</strong> journey over 20 years<br />
ago and has participated in many <strong>ACNEM</strong> training<br />
courses culminating in Fellowship.<br />
Debbie has supported the work of <strong>ACNEM</strong> over many<br />
years and has served on the <strong>ACNEM</strong> Board holding<br />
positions of Vice President, Secretary and as a General<br />
Board Member. Debbie has also been involved with<br />
many committees and has been instrumental in providing<br />
academic input into <strong>ACNEM</strong>’s education. Specificially she<br />
has been both the chair and a member of the Education<br />
and Training Committee. Debbie has also lectured many<br />
times over the years for <strong>ACNEM</strong> – starting in 2006<br />
and has been tireless in her enthusiasm for teaching<br />
fellow colleagues and trainees in the nutritional and<br />
environmental aspects of child health.<br />
Debbie was the driving force and main contributor to<br />
the revised and expanded nutrition medicine curriculum<br />
for the RNZCGP curriculum review in 2012, and a key<br />
contributor to the development of a generic nutritional<br />
medicine seminar for GP trainees which Debbie delivered<br />
with other <strong>ACNEM</strong> Fellows in some of the regional<br />
training programs.<br />
Debbie was also on the New Zeland Guidelines Group<br />
expert panel funded by the Ministries of Health and<br />
Education for eightyears until 2017. This panel was tasked<br />
to systematically review current literature to ensure the<br />
NZ Autism Spectrum Disorder Guidelines professionals<br />
and families were up-to-date and relevant. Debbie was<br />
the driving force in the research and development of<br />
the new additional supplement to the NZ guideline:<br />
‘Gastrointestinal problems in young people in ASD’ which<br />
created new recommendations that firstly GI problems<br />
are more common in children with ASD compared to<br />
their peers . Secondly that GI problems can present with<br />
atypical behaviours in ASD, eg irritability, aggression,<br />
anxiety which warranted thorough GI assessment.This was<br />
a paradigm shift for most mainstream practitioners.<br />
Debbie is also passionate about mentoring and supporting<br />
medical students to pursue training in nutritional and<br />
environmental health and has facilitated a number of<br />
interest groups at medical schools in both New Zealand<br />
and Australia. She continues to be involved in this area<br />
and is always looking to help and support medical students<br />
in this poorly supported, but very important field of<br />
medicine.<br />
Over many years Debbie has shown a deep commitment<br />
to the work of <strong>ACNEM</strong> and it is with great pleasure that I<br />
present Debbie Fewtrell with the <strong>ACNEM</strong> Distinguished<br />
Academic Service Award in recognition of her support and<br />
contribution to <strong>ACNEM</strong>’s education.<br />
36
Change language