The
Natural
Therapist
EDITION 36 NO. 4 | SUMMER 2021
ISSN 1031 6965
Summer 2021
The Official Journal of THE AUSTRALIAN NATURAL THERAPISTS ASSOCIATION
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TARGETING OPTIMAL HEALTH
Contents Edition 36 No. 4
|
Summer 2021
10
18
Literature Review Coenzyme Q10 and Hypertension
Deeper Waters of Soul - Leaning in to Trust the Self
ANTA Member, Miriam Cullen, explores
Kaitlin Edin dives deeper into the fascination
the literature around coenzyme Q10 and
with the prescriptive and defining powers of
hypertension.
language within Eastern Medicine.
32
39
44
Important Nutrients During the Pregnancy Transition
Osteogenesis Imperfecta - Research Paper ANTA Member, Bianca Vogel, researches the
Withania and Liver Damage - Should we be worried?
George Thouas provides an overview of the
clinical features, molecular basis, aetiology of
Kerry Bone further explores Withania and its
Traditional Chinese Herbal Formulas - Ping Wei San - Research Update
critical nutrients and supporting evidence
osteogenesis imperfecta.
direct impact on liver damage.
Tony Reid researches the Traditional Chinese
From the Chair 5
Executive Officer Report
ANTA News
6 ANTA News 7 Notable Naturopaths with Ananda Mahony
24
for importance before, during and after
Herbal Formula, Ping Wei San. Tony breaks
pregnancy.
down the botanical features and explains the protocols for gastrointestinal disorders.
The
Natural Therapist
EDITION 36 NUMBER 4 – SUMMER 2021
ISSN 1031 6965
ANTA BRANCH CHAIRPERSONS
The Natural Therapist is published Warren Maginn Isaac Enbom by the Australian Natural Therapists • National Vice-President • Director of ANTA Association (ANTA) for natural • Director of ANTA • National Remedial Therapy Branch Chair therapy practitioners. The opinions • National Nutrition Branch Chair • ANTAB Committee Member and views expressed by the • TGA Chair • ANRANT Committee Member contributors and advertisers are not • Ethics Panel Chair Mark Shoring necessarily the opinions and views • ANTAB Committee Member • Director of ANTA of ANTA. Every effort is taken to • ANRANT Committee Member • National Multi-Modality Branch Chair ensure accuracy and ANTA accepts Shaun Brewster • ANTAB Committee Member no responsibility for omissions, • National Treasurer • ANRANT Committee Member errors or inaccuracies. ANTA relies • Director of ANTA on contributors and advertisers to Tino D’Angelo • National Myotherapy Branch Chair make sure material provided for • Director of ANTA • ANTAB Chair The Natural Therapist complies • National Chinese Herbal Medicine Branch • ANRANT Committee Member with the Australian Consumer Chair • Health Fund Chair Law under the Competition and Ananda Mahony Consumer Act 2010. ANTA accepts Jim Olds • Director of ANTA no responsibility for breaches of • Executive Officer • National Naturopathy Branch Chair • Company Secretary the Australian Consumer Law • Business Plan Chair by contributors or advertisers. Kaitlin Edin • ANRANT Chair Material in The Natural Therapist is • Director of ANTA • National Acupuncture Branch Chair subject to copyright and may not • ANTAB Committee Member be reproduced in any form without • ANRANT Committee Member the permission of ANTA and its contributors. PAGE 4 | SUMMER 2021 | THE NATURAL THERAPIST VOL 36 NO. 4
The
Natural Therapist
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ANTA Executive Welcome Summer 2021
From the Chair As the year draws to a close, I would like to acknowledge those members that have had the year disrupted with the many lockdowns that occurred throughout the country at different times. I am constantly reminded of how our members’ lives and in particular their workplaces have been disrupted for an extended period over the last two years. ANTA National Council and staff would like to offer their thanks and well wishes to all members for the past year and into the Christmas/ New Year break. The respect and admiration we feel for all those affected, our ANTA Members and their colleagues is immense. The professional way they endured the conditions fill us with awe in which they endured the conditions and resilience to be ready to return to business at the first opportunity. The staff at the National Administration Office have provided a high level of understanding and support to all ANTA Members and I thank them sincerely for the professionalism and dedication to the task they have displayed throughout the last couple of years. We have provided services and support along with concessions for those most affected by changing circumstances in your regions. This will continue while we look to the present circumstances and challenges you endure, while we are planning to support and assist with your business location and activity exposure. We want you to be discoverable when you are available and able to continue your practices again. ANTA’s investment for the future includes, but is not limited to, broadening digital services to our Membership to achieve economies of scale and avoid increasing fees when you are already hurting. ANTA’s new website has taken some time to complete and has gone live. The new and visible strategies we have in place will inform and support you while preparing to resume full-time practice.
Cost and Fees to Members
ANTA is also conducting a moratorium on Membership fees. Fees have remained the same
Summer 2021
for over 20 years as a result of sound management and a lean and agile ANTA Administration Team. A slight increase to the lowest tier fees occurred in 2019, however, this tier remains the lowest across professional associations in Australia. Invoices were issued for all non-AHPRA Members in October, with a due date of 31st December 2021. If you are struggling financially, we do offer payment plans. Please contact the National Administration Office on 1800 817 577 to discuss your options.
Continuing Professional Education (CPE) Points
Continuing Professional Education is a globally recognised requirement for maintaining current as a practitioner. CPE needs to be completed by all ANTA Members, each and every year. ANTA Members that are eligible for Private Health Funds, need to ensure that their 20 CPE points are lodged within the ANTA Member Centre before the 31st of December each year. ANTA Members are encouraged to access these resources to either fulfil or complement the compulsory ongoing training that is part of the terms and conditions of their membership with ANTA. Of course, the Private Health Funds audit our Member records regularly to assure we are complying with their respective terms and conditions. Any Members becoming concerned about their CPE status should contact the ANTA office to clarify their membership eligibility.
ANTA Office Closure
The National Administration Office will be closed from Wednesday 22nd of December, 2021 until Monday 10th of January, 2022. ANTA National Council and Staff would like to wish all ANTA Members a happy and safe Christmas break. Regards
Jim Olds
ANTA Fellow ANTA Executive Officer & Company Secretary BHSc MST, BHSc Comp Med, GC Higher Ed, MSC, Dip Nut, Dip RM, Dip TCMRM
THE NATURAL THERAPIST VOL 36 NO. 4 | SUMMER 2021 | PAGE 5
ANTA News Summer 2021
ANTA News
ANTA Office Closure
The ANTA Office will be closed from Wednesday 22nd December, 2021 and will re-open Monday 11th January, 2022. During this time, no emails or calls will be answered. If you need assistance, please send an email to info@anta.com.au and a response will be provided when the office reopens. All ANTA Board of Directors and staff would like to wish all Members and their families a happy and safe Christmas.
Continuing Professional Education due by the 31st December 2021
Continuing Professional Education (CPE) is the upgrading or acquisition of knowledge and skills in the accredited modalities that will aid the practitioner in providing the patient with a high standard of health care. CPE is an important part of providing professional health care services to patients and ensures practitioners regularly update their clinical skills and professional knowledge. ANTA requires members to complete 20 CPE hours annually (January to December). CPE hours need to be lodged within the ANTA Member Centre before the 31st December, 2021. If you have issues trying to sign in to the ANTA Member Centre, please contact the office before the 22nd December, 2021.
Non-AHPRA Members - Membership is due by the 31st December, 2021
For non-AHPRA Members, your membership is due by the 31st December, 2021. Invoices were issued in October 2021, with multiple reminder notices sent. Please check your junk/spam folders within your emails or sign in to your ANTA Member Centre. Open invoices can be found under the ‘My Orders’ tab within the ANTA Member Centre. If you are not practising, we do have non-practising membership options. Please contact the office on 1800 817 577 to discuss your options.
ANTA Membership requirement - Working with Children or Police Check
It is now a requirement for all ANTA Members to provide either a Working with Children Check or Police Check. For members receiving health fund recognition, this is also being implemented by some health funds and your provider numbers may cease if we do not have this information.
Working with Children Check - Is only for those Members who work directly with persons under 18 years of age. Some states do not require this, please check with your state, regardless of whether a parent or guardian is present. Police Check - For anyone who is not providing a Working with Children Check or if your state does not require this check for natural therapists. PAGE 6 | SUMMER 2021 | THE NATURAL THERAPIST VOL 36 NO. 4
Notable Naturopaths with Ananda Mahony
In the first edition of Notable Naturopaths, ANTA Naturopathy Branch Chair, Ananda Mahony will sit down with some notable Naturopaths within the profession. This first interview is with Elizabeth Greenwood, the past President of ANTA. What is your area of interest within your modality?
My chosen modality within Naturopathic medicine would have to be herbal medicine. Having a Masters in Herbal Medicine with a strong pharmacognosy focus means that I explore the herbs from the many angles of botany, manufacturing, quality, plant chemistry and scientific evidence as well as therapeutic application. My main focus is on the traditional use of herbal medicines, specifically western herbal medicine and aromatherapy. As such, I have been interested in medicinal bathing for many years. Traditionally, many herbal medicines were used in a bath method, so I can be found scouring old herbal books for these gems of practice wisdom. I combine this with the known (and yet to be known) benefits of bathing in natural thermal mineral springs. I do call it ‘research’, but it is not an arduous task by any means.
What inspired your interest in this area?
It is very natural for us English folk to find ourselves rejuvenating mentally and physically by submerging ourselves in a vessel of warm water for a period of time. My cultural tendencies, combined with my passion for traditional knowledge, have kept me wondering how I can validate these potentially therapeutic effects. It was in 1995, when I did an assignment for my Aromatherapy Certificate with Salvatore Battaglia, that I looked into my questions of ‘when we add lavender to a bath, how do we know it has physical relaxation effects?’ I discovered the mechanisms of transdermal absorption in a bath compared to other methods and followed the evolving research to minerals, nutrients, herbs and whatever else I could read about. My continued inspiration for this area is to validate traditional practice through modern scientific methods. It is an exciting and pertinent time to being doing this kind of work.
How has bathing impacted your practice / recommendations to patients?
Balneotherapy has added so much to my practice. I can tell you so many case studies where ‘that one bath changed my life’. A person can gain so much from implementing the self-care practice of a bath, but it is so much more than that. To treat with internal medicines is fantastic, but to treat with external and internal at the same time is truly holistic and embodying all resources. This is why in 2002 I started my Balneotherapy range of products that can be used alongside common
Naturopathic practices. ‘Embody’ was well received and we are actually relaunching it based on new ingredients. Since I first designed the Embody range, there has been a huge amount of Balneotherapy research emerge and so it seems practical to provide practitioners easy access to in-home Balneotherapy products to use with clients. The first product to be relaunched soon is Soothe: Yellow for post-exercise recovery and general aches and the formula and more information can be found here www.embodyculture.com.au
What has caught your attention this week?
It is hard to go anywhere without the emotional debates and passions related to the pandemic catching my attention. However, in order to gain some focus, clarity and optimism I have been drawn towards the amazing array of beautiful wildflowers that are brightening up our Spring time. The flowers in Australia are so colourful, vibrant and of such dynamic shapes that they really do distract you from the confusion and remind us of the inevitable and omnipresent cycles of nature. To be sobered by something so beautiful, innocent and reliable is a gift during these times. Adding a few of these wildflowers to a bath, you can create your own version of a personalised flower remedy.
What is upcoming for you?
I have stepped down from my cherished role as National President of ANTA. My decision was based on my acceptance into a Professional Doctorate programme where I am studying Balneotherapy. This is a huge undertaking, and one that I have desired for many years, wishing to formalise my studies in order to give back to my profession and validate our traditions. I look forward to sharing my research and findings as I progress. I am also busy with my mentoring and workshop offerings through Holistic Studio. Here, I have moved some workshops online and my career guidance mentoring, business building and individualised educational support is my primary focus to strengthen our profession through supporting practitioners. I run courses on Iridology, Aromatherapy and Herbal Energetics in order to keep these amazing modalities and approaches visible in our holistic practice. If you would like more information on this please get in touch - www.holisticstudio.com.au
THE NATURAL THERAPIST VOL 36 NO. 4 | SUMMER 2021 | PAGE 7
Professor Kerry Bone is now live on Facebook @profkerrybone Follow for the latest in natural medicine science and research, plus be the first to find out about Kerry’s upcoming activities, events and book launches.
Each week I’ll be sharing exclusive content to this page, including segments such as Q&A with Kerry, Practitioner Tips and my favourite segment, Grumpy Old Herbalist.
Key features of Kerry’s Facebook page include: The latest in science and research Kerry answering the questions you’ve always wanted to ask The best of Kerry’s Practitioner Tips Kerry’s monthly segment on correcting herbal injustices Keeping up to date with Kerry’s latest activities and events
• • • • •
Follow @profkerrybone so you don’t miss out!
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Whatever journey you decide to take, and whatever stage of your career you’re at, we’re here so that you don’t have to face challenges alone.
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ANTA Member Article Summer 2021
Miriam Cullen
DipHSc (Nutritional Medicine) BHSc (Naturopathy) ANTA Member
Literature Review - Coenzyme Q10 and Hypertension Introduction
Hypertension refers to persistently high blood pressure in the systemic arteries, expressed as a ratio of systolic and diastolic blood pressure1. The Australian guidelines classifies Grade 1 (mild) hypertension as having a persistent blood pressure of 140-159/90-99mmHg, Grade 2 (moderate) hypertension as 160-179/100-109mmHg and Grade 3 (severe) hypertension as ≥ 180/110mmHg2. Most individuals with hypertension are asymptomatic, however being hypertensive increases their risk of coronary heart disease, heart failure, stroke, myocardial infraction, atrial fibrillation, peripheral artery disease, chronic kidney disease, cognitive impairment and all-cause death and disability1. It poses a huge economic burden, with the estimated loss of productivity-adjusted life years equating to $137.2 billion dollars in gross domestic product over a working lifetime3. Yet 50% of United States adults who are using antihypertensive medications are still not achieving optimal blood pressure goals, and 80% of individuals with hypertension believe that adjunctive complementary and alternative medicine and orthodox therapies are superior than either therapy alone4. Thus, this literature review will appraise the evidence regarding the use of the natural therapeutic, Coenzyme Q10, for the treatment of hypertension.
Hypertension Prevalence
In 2014-2015, it was estimated that there were six million adults who were hypertensive and using antihypertensive medications in Australia, amounting to a staggering 25% of the population2.
Pathophysiology
The pathophysiology of hypertension (HT) is complex and involves multiple systems and biochemical processes1. Firstly, the ReninAngiotensin-Aldesterone system (RAAS) may be compromised as a result of oxidative stress
amounting to renal, cardiac and vascular injury1. Consequently, angiotensin II enhances sodium reabsorption by increasing the sodium-hydrogen exchanger, elevating aldosterone secretion and inducing vasoconstriction on the systemic arterioles5. Sodium homeostasis may also be dysregulated due to increased serum sodium concentration, promoting fluid retention and increasing blood volume and blood pressure (BP)1. A natriuretic peptide deficiency also plays a role, as atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are involved in sodium balance and blood pressure through their vasodilatory action and their ability to increase glomerular filtration rate1.
PAGE 10 | SUMMER 2021 | THE NATURAL THERAPIST VOL 36 NO. 4
ANTA Member Article Summer 2021
Oxidative stress, inflammation and the interruption of nitric oxide production can also cause endothelial dysfunction and the reduction in vascular tone and morphology1. C-reactive protein (CRP), a biomarker of inflammation, is also involved in the pathogenesis of HT through its ability to promote vasoconstriction, endothelial dysfunction, vascular smooth muscle proliferation and arterial stiffness6. Finally, sympathetic nervous system (SNS) activation which increases plasma catecholamines results in vasoconstriction, endothelial dysfunction, vascular smooth muscle proliferation and an increase in arterial stiffness1.
Aetiology
Like the pathophysiology of HT, the aetiology is equally complex and involves a combination of factors including excessive sodium intake, insufficient potassium and magnesium intake, overweight and obesity, alcohol and low physical activity7. Interestingly, obese individuals have also been shown to have a natriuretic peptide
deficiency8. Aging, being male, insulin resistance and psychological stressors are also risk factors for HT9. HT is more common in individuals with lower household incomes, those in regional areas, and Aboriginal and Torres Strait Islander people2. Other intrauterine factors include gestational diabetes and pre-eclampsia1.
Medical Treatment
The gold standard treatments for HT include thiazide diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and dihydropyridine calcium channel blockers4. Unfortunately, many of these medications have undesirable side effects such as renal or cardiac dysfunction, cough and depression are often ineffective7. Nonpharmaceutical interventions include a salt-restricted diet, increasing potassium intake, reducing alcohol intake, increasing physical activity and weight loss1. The National Heart Foundation of Australia recommends that physicians begin hypertensive therapy immediately if a patient has Grade 2 HT,
Table 1: PICO components that formed research questions Population
Intervention
Comparator
Outcomes
Individual with Grade 1 Hypertension or higher
Coenzyme Q10 (uniquinone or ubiquinol) supplementation
Placebo or Conventional medical treatment
- Systolic Blood Pressure - Diastolic Blood Pressure
THE NATURAL THERAPIST VOL 36 NO. 4 | SUMMER 2021 | PAGE 11
ANTA Member Article Summer 2021
Table 2: Selection criteria Inclusion Trial Type
• • • • •
Exclusion
Systematic reviews and meta analysis Randomised Controlled trials Nonrandomised Controlled trials Pilot trials Animal trials
• • • • • • • • •
Prospective Observational Study Research reviews Cross-sectional study Case-control study Longitudinal trials Cell-line studies Case reports and series Ideas, editorials, opinions Open label studies
Language
English
Non-English
Date
2011 and later
Prior to 2011
Population
Individuals with Grade 1 Hypertension or higher
Individuals with optimal blood pressure
Trial Length
≥ 10 days
< 10 days
Sample Size
≥ 10
< 10
Text Access
Full Manuscript Access
Abstract only
Databases
Pubmed: Quality-assured widely accessible biomedical resources12 Cochrane Library: Not-for-profit organisation providing independent systematic reviews13 EBSCOhost - All Databases: Broader search base14
Key Words
Bolean Operators
• • • • • •
Hypertension High Blood Pressure Coenzyme Q10 CoQ10 Ubiquinone Ubiquinol
‘AND’ and ‘OR’ Eg. (Hypertension OR “High Blood Pressure”) AND (Coenzyme Q10 OR CoQ10 OR Ubiquinone OR Ubiquinol)
however the decision to treat at lower BP levels is considered if there is evidence of cardiovascular disease (CVD) risk or endothelial damage2. The target BP for physicians is <140/90mmHg (millimetres of mercury) or lower if tolerated2.
Coenzyme Q10 Background
Coenzyme Q10 (CoQ10) is an endogenous, lipidsoluble compound found in all cell membranes and mitochondria10. It exists as ubiquinol, its reduced form, and ubiquinone, its oxidised form10. It plays a major role in the mitochondrial respiratory chain for energy production, and as a result is found in high concentrations in metabolically active organs such as the heart, kidneys and liver4.
Mechanism of Action
CoQ10 deficiency may be a potential risk factor in HT4. As well as adenosine triphosphate (ATP) production, CoQ10 is involved in vitamin and PAGE 12 | SUMMER 2021 | THE NATURAL THERAPIST VOL 36 NO. 4
antioxidant regeneration11. It demonstrates vasodilatory capabilities by increasing nitric oxide bioavailability, inhibits lipid peroxidation and has a direct protective effect on the endothelium and vascular smooth muscle4,10. It also modulates the effect of angiotensin on sodium retention by decreasing aldosterone10. A deficiency of CoQ10 is associated with greater inflammatory responses through nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) activation which also accounts for CoQ10s anti-inflammatory effects10. The widespread use of statins suppress the synthesis of endogenous CoQ10 and may also be a contributing factor in the pathogenesis of HT 7.
Methodology Research Question
A search strategy was implemented based on the population-intervention-comparison-outcome (PICO) model to answer the clinical question: Can CoQ10 reduce systolic and diastolic blood pressure
ANTA Member Article Summer 2021
in individuals with Grade 1 HT or higher when compared to a placebo or conventional medical treatment?
Selection Criteria
Table 2 outlines the databases, keywords and boolean operators utilised in the literature review search and screening that was conducted on the 5th of July 2021.
Literature Review Results Description of Included Studies
Six full-text manuscripts published after 2011 were included in this literature review. The Appendix which outlines the methodology of each study is available upon request. The studies included three systematic reviews and three randomized control trials (RCTs). Participants included individuals with metabolic diseases, coronary heart disease (CHD), mild and primary HT. Primary outcome measures were systolic blood pressure (SBP) and diastolic blood pressure (DBP).
Results of Systematic Reviews
Tabrizi et al. (2018, pp. 41-50)7 carried out a systematic review and meta-analyses of 17 RCTs (n=684) to summarise the evidence of the effects of CoQ10 supplementation on BP in patients with
metabolic diseases. The review concluded that CoQ10 supplementation reduced SBP significantly, however its effect on DBP was not statistically significant7. Ayers et al. (2018, pp. 1-7)15 also conducted a systematic review examining 10 recent RCTs (n=127) evaluating the role of CoQ10 in the management of CHD. The review contained three RCTs which included SBP and DBP as outcome measures, and concluded that the antihypertensive capability of CoQ10 was unclear15. Ho et al. (2016, p. 1-22)16 published an updated Cochrane meta -nalysis and systematic review with the primary aim to determine the blood pressure-lowering effect of CoQ10 in primary HT. It included two RCTs (n=50) and concluded that there was moderate-quality evidence that CoQ10 did not statistically significantly lower blood pressure16.
Results of Randomised Control Trials
Izadi et al. (2019, pp. 1-10)17 conducted an RCT investigating the effect of 200mg of CoQ10 and/or Vitamin E on cardiometabolic outcomes including SBP and DBP in 77 women with polycystic ovarian syndrome (PCOS) over eight weeks. The study concluded that CoQ10 had a statistically significant effect on SBP (p=0.005); however, the reduction in DBP was not statistically significant (p=0.10). A RCT conducted by Mazza et al. (2018, pp. 992 - 996)18 investigated the efficacy and safety of 30mg of CoQ10 and red yeast rice daily with a Mediterranean diet (MD) versus an MD alone in lowering blood pressure in 104 individuals with metabolic syndrome (MetS) over eight weeks. It was observed that SBP and DBP were significantly lower (p<0.001) in the treatment group when compared to the control group18. The results of a randomised, doubleblind, placebo-controlled 12-week crossover study conducted by Young et al. (2018, pp. 261-270)19 on 30 subjects with MetS and inadequate BP control over 12 weeks were not as conclusive, and somewhat contradictory to the general trends in the results of previous studies. The treatment group received 100mg of CoQ10 twice daily, and when compared to placebo the authors concluded that CoQ10 did not statistically significantly reduce systolic or diastolic 24- ambulatory BP (p=0.12)19. Rather, the results demonstrated a significant reduction in daytime diastolic loads (p=0.007) when compared to placebo19.
THE NATURAL THERAPIST VOL 36 NO. 4 | SUMMER 2021 | PAGE 13
ANTA Member Article Summer 2021
Discussion Limitations
One of the major limitations of three of the studies included was their small (n<100) sample size16,17,19. Generally, these studies were less conclusive about the positive effects of CoQ10 on SBP and DBP. Interestingly, the studies with larger sample sizes such as Tabrizi et al. (2018, p. 41)7 and Mazza et al. (2018, p. 1)18 demonstrated statistically significant decreases in SBP. However, these studies were not without their limitations. Tabrizi et al. (2018, p. 43)7 included studies published over 30 years ago, and Mazza et al. (2018, p. 1)18 utilised a combination nutraceutical in the intervention group, with no blinding or placebo control group. It is difficult to isolate the individual effect of CoQ10 in study designs such as this. Unfortunately, two of the RCTs had relatively short trial lengths of eight weeks17,18. However, the study conducted by Izadi et al. (2019, p. 3)17 was thorough in its exclusion criteria as well as the recording of confounders such as diet and physical activity. Multiple studies attempted to reduce the risk of the white coat effect by taking multiple measurements and averaging the results or by using a 24-hour ambulatory blood pressure monitor, however this is still a confounding phenomenon20,18,19.
Implications for Clinical Practice
The six studies included in this literature review demonstrate great statistical heterogeneity as a result of broad clinical and methodological diversity. Thus, the clinically relevant impact of CoQ10 on BP is unclear, and it should be not be employed a primary treatment for those with HT, however it may be a beneficial adjunctive therapy. Overall, there was great variation in population demographics. The systematic review conducted by Tabrizi et al. (2018, p. 43)7 included individuals from nine different countries, four of those being Australians aged between 25 and 79 years old. However, the RCT conducted by Izadi et al. (2019, p. 2)17 only included women with PCOS aged between 20-40 years old, limiting the clinical generalisability of the results to the wider population. Furthermore, 90% of participants in the Young et al. (2012, p. 262)19 study were of caucasian descent, also limiting clinical generalisability.
ubiquinone). Although the primary therapeutic dosage range and form of CoQ10 is not known, there were no adverse effects reported in any of the included studies, attesting to the safety of this nutraceutical in clinical practice. Multiple studies also demonstrated no clinically relevant laboratory changes in safety parameters18,19. Finally, the extremely low or non-existent dropout rates also attest to the high tolerability of this treatment. Nevertheless, caution is required when co-prescribing with warfarin or fenofibrate due to potential interactions15,19. As the trial length of the majority of the included studies were at least 12 weeks, it is advised that practitioners supplement with CoQ10 for this period of time to increase their likelihood of a positive response. The reported change in SBP in the included studies ranged from -4mmHg to -12.2mmHg. The reported change in DBP overall was less remarkable. Thus, the clinical use of CoQ10 for HT may be relevant in individuals who are borderline hypertensive and only require slight BP reductions or those with isolated systolic HT with limited CVD risk factors2.
Conclusion
This review suggests that CoQ10 is a promising adjunctive antihypertensive treatment for patients with borderline, Grade 1 HT or isolated systolic HT. These findings are consistent with recent studies which remain inconclusive regarding the broader clinical relevance and optimum dose of CoQ10 supplementation in HT. Further RCT’s with larger sample sizes and longer trial lengths are necessary to solidify the role of CoQ10 in the management of HT. These studies should also include multiple treatment arms in order to ascertain the therapeutic effect of a variety of dosages CoQ10, as well as whether the reduced or oxidised form is more advantageous.
There was also great variety in dosage ranges used, from 30mg in the Mazza et al. (2018, p. 4)18 RCT, to 900mg in the Tabrizi et al. (2018, p. 43)7 systematic review. In addition, the authors did not specify which forms of CoQ10 were utilised (ubiquinol or PAGE 14 | SUMMER 2021 | THE NATURAL THERAPIST VOL 36 NO. 4
For references log into your ANTA Member Centre > The Natural Therapist > Journal Articles
ANTA Member Article Summer 2021
Kaitlin Edin
Acupuncturist | Eastern Herbal Medicine Chinese Medicine Practitioner National Acupuncture Branch Chair - ANTA
Deeper Waters of Soul Leaning in to Trust the Self In 2009 I published a peer-reviewed paper in a Chinese medicine journal entitled Integrative Medicine: Combining the Practice of Orthodox & Alternative Medicine – Inclusive of ‘Other’ or just another path to Exclusivity? 1 . While the main themes of that article were about exploring the cooption of ‘alternative’ or traditional medical models into the mainstream orthodoxy, my fascination was with the prescriptive and defining powers of language and the narrative frames and themes we use to communicate our values. On the cusp of graduation and with the intensity of a new recruit, I was interested in the way that language defined, created or limited the power and agency of my profession. My article focused on the external language of definitions and placement. It was about how we position ourselves through language in a landscape
of a dominant cultural paradigm of Western and conventional medicine. It is a landscape that can be hostile to the ‘otherness’ of our shape as Eastern and therefore alternative medicine, but it will also be tolerant of that otherness, as long as it is diminutive and doesn’t threaten the hegemony and agency of the ‘real medicine’. In other words, know your place and the birds of prey, those hegemonies of culture, will make a claim on the ‘things that work’. To some extent, Chinese/Eastern medicine is underpinned, fortified and anchored by Western scientific models because Western science finds the modalities we use (herbal medicines, acupuncture, moxa, gua sha and cupping) to have value and significant effects above and beyond placebo (ignoring that placebo in clinical practice may represent the acceptance of any intervention with the body). This means that the
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ANTA Member Article Summer 2021
truth of what we do is properly justified. It is a valuable embrace, but it is not a defining one. That Eastern perspectives, modalities and knowledge are to a very large degree rationalised with the Western scientific frame means that the bones of the Eastern medical corpus have integrity. As a system and medical paradigm, it bears more than one way of looking, more than one approach, and this strengthens rather than weakens our authenticity. But it also places great strain on the understanding of the medicine by those who practise it without self-awareness and without some literacy in difference. When I was first coming to grips with the language and terminology of Chinese medicine, I nearly tore my hair out. My sense of precision insisted that it was nonsense to have multiple words for spleen qi when one would do. Such was the inherited dogma I didn’t even know I possessed. Fellow students were kinder about it, and kind to me too. My gratitude for their forbearance should be noted here; they know who they are. But for my own sake, I learnt to hone that need for precision into my acupuncture and palpatory skills, so at least my Western mind and scientific training wasn’t wholly a meanness without application.
no longer the precision of the path’s unblurring lines I am seeking; rather, the precision of understanding what the lines and the spaces between them mean. As I have learnt to trust my own perspective and perceptions, that beautiful place where the Yi, Shen and Jing fold into each other, I am rewarded with the rich interweaving of an embodied knowledge. I have gleaned enough across each of the tiers of existence – mind, body, soul – to be able to trust in the informed and intuitive place within me. And this enables me to not only enjoy the variety of interpretations, but to seek it out against the dogma and prescriptive narratives which abound.
During my university studies, the many and varied ways perception was rendered in those endless textbooks was due, in part, to reading the medicine in translation. Each translator will have a different word to mean a similar thing; each lineage will prefer or monopolise terminology. But it is also, I suppose, the nature of the transformation that pictographic characters are being rendered into a very linear language. After many years, I now understand, ruefully, that it’s a bit like being asked to describe the Mona Lisa. Is it an upturning of the lips, a smile, or a smirk? Translation reminds us that there is almost infinite variety in interpretation. And interpretation is fundamental to our experience of reality. My insistence on linguistic precision was about getting things right, to ensure a level of control over ‘my reality’. It was hardly surprising; this is what a novice does. I was like a small child wandering into an unknown and ambivalent landscape. I needed precision and discernment to ensure I pocketed the nutritive rather than the ersatz, toxic fruit, and to keep to the Camino rather than get side-tracked into dead ends. As with all journeys, I have learnt that I need to reshape my requirement for precision. It is
However, in 2009, as a newly minted Acupuncture and Chinese Herbal medicine practitioner, I was struggling with the articulation of a medical paradigm, and failing with the language I had been given by my university education around Chinese medicine. I was concentrating too hard on the externals and the identifiers. Was I alternative, complementary or allied? How would I navigate the national identity embedded within the medicine? Could I practise Chinese medicine when I wasn’t Chinese? It was conceptually problematic, and like so many beginners, I focused on the yang or external aspect of the dilemma. This distraction meant that I missed the greater conversation for quite a long THE NATURAL THERAPIST VOL 36 NO. 4 | SUMMER 2021 | PAGE 19
ANTA Member Article Summer 2021
time. It may be a truism for those who have arrived at mastery, but the deeper, greater and more fulfilling conversation is within the medicine itself. Every journeyman and woman has glimpsed the insights of the embodied yin aspect. They know that it is the internal cultivation, the soul and spirits dialogue, that holds the abiding and soul-shaking treasure. There is a reason, a very deep and embedded reason, why the medical language of Eastern diagnosis is expressed in poetry and underpinned by the spirit of Daoist thought and practice. David Whyte claims that poetry is the language against which we have no defence, and as a very successful modern poet, he would know2. He speaks from a tradition inherited from the Celts, who honoured the power of words in blessings and curses. For the Celts, language was as material and foundational as wood, bedrock, water and steel. They asserted, too, perhaps because they were so fully cognizant of language as a twist tie, that the physical body is held in and by the soul. The soul is not a seed-like thing or abstract concept within us, but it is the enigmatic and auric holding around the physical self3. When we perceive the soul this way, we begin to appreciate that the soul deflects, absorbs and responds to caress or injury before the physical body has even been broached.
of the soul, were not so different to the Celts. They knew that to speak of all that the human heartmind-body contains, as well as the context, space and environment that holds it, needs language that is expansive enough. In other words, generous and spacious, symbolic, metaphorical, nuanced and precise, especially when we are speaking to one, or the many, in need of care. It is a source of continuing frustration and disappointment to me that the language of symbolism and metaphor, the figurative and poetic of classical medicine, has been stripped out of undergraduate and postgraduate studies in the interests of Western science and transactional language. Or worse, rendered literal in the smallhearted meanness of transactional minds. Such is the malaise of modern educational institutions everywhere. Perhaps it is part of how modernity distracts and fatigues us and our imagination through being so prescriptive with the formula, so controlling of the dreamers and their dreams. It is because the cosmology, the yin aspect of the art, philosophy, humour and relational messiness of the medicine, has been seen as disposable, unclean and somehow less than the bright clear yang of the technical, observational, muscular and scientific. Kierkegaard puts it this way: there is a compulsion to completely absorb oneself in either the finite or the infinite, for in doing so one abandons the responsibility of being a self. To lose oneself in the finite is to live a life imprisoned in what one perceives as being an inescapable environment… To lose oneself in the infinite is to live as though life is nothing but a series of endless experiments… To be a self requires that one balances those opposing tensions4. There is no either/or.
Interestingly, within Chinese medicine, the soul is said to be held in the Liver, the organ system with its sphere of influence (from the meridian to the organ) that symbolises our sense of vision. It masters the doing and organisation of things and is happiest and healthiest when unfettered, for it governs the free flow of qi, the interchange and absorption of information (externally environmental and internally emotional). The ancient shamans of all directions, those honoured translators of the etheric and the holders PAGE 20 | SUMMER 2021 | THE NATURAL THERAPIST VOL 36 NO. 4
ANTA Member Article Summer 2021
And as we know from our very first lessons, the yin and yang are complementarities, they define each other. They provide in their own way the space for the other to exist. This is an articulation of existence. Yin and Yang can only embrace and define the other, with and by its own inherent qualities. How, then, do we practise only within the light and busyness of the yang, without deeply knowing the rich yin of expansive darkness that represents containment, absorption, reflection? The night brings a liberation that the day does not. In the dark, the horizon is less visible, less obvious, less determining of the path and its placement. What land do we inhabit as seekers, pilgrims, practitioners, and how do we connect when we have been disenfranchised from the language of our chosen profession, the calling of the healer’s inheritance?
The ability to be discerning with the energies of our spirit and our life force best comes through the lens of kindness and our own seated awareness, rather than the mean shallows of tradition. I urge you to find the richness and spiritual depth in the medicine, even when long clinical days wear you down. If you are burning out or have already done so, then let me assure you that now, more than ever, is the time to reconnect to the deeper waters of the soul. It is there that you will find the true reason for your fatigue, as well as the imaginative seeds that will rekindle your fire and love. Let us not allow these days of fear and fright and viral contagion to blind us to the real infection and virulence of the distrust we have of our own self and of each other. Blessèd be the space between us.
There are many ways forward; it is the nature of health that we have diversity. This is true for the bacteria in our gut as much as it is for our many ways of practising the philosophies and techniques. Be in conversation with all parts and lean into those parts that seem unlike you or cause discomfort. The exiled hold great wisdom. Where is the art of our craft if we only employ the technical? The back of this medicine is broad; do not be corralled into specialities. Make your speciality the medicine. It produces far more than you can ever keep up your sleeve. And let go of always wanting to have or be the answer.
For references log into your ANTA Member Centre > The Natural Therapist > Journal Articles
THE NATURAL THERAPIST VOL 36 NO. 4 | SUMMER 2021 | PAGE 21
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ANTA Member Article Summer 2021
George Thouas, PhD
Head of R&D, Max Biocare Pty Ltd
Important Nutrients During the Pregnancy Transition Introduction
Whether during lockdowns or the winter months, spending more time indoors usually means that couples are focusing more on their reproductive health. While we may think we have adequate nutrition, it pays to take a closer look at this aspect of health. Balanced nutrition is very important for baseline reproductive health because it is sensitive to even mild or moderate nutrient deficiencies. Although food intake may be adequate, it may not necessarily be of suitable nutrient density. During pregnancy, the baseline is raised and imposes an increased level of nutritional demand on women as their bodies adapt to the additional intakes of their little passengers. Lessons learned from food fortification projects around the world have provided valuable insights into which nutrients are essential in preventing deficiencies that may lead to growth deficits and other health complications, during pregnancy or later in childhood. However, all vitamins could be thought of as essential for this purpose. This article provides an overview of some of the more critical nutrients and supporting evidence for their importance before, during and after pregnancy.
Keywords: omega 3, DHA, folate, folic, acid, iron, iodine, vitamin D3, preconception, pregnancy, post-partum, newborn, micronutrients PAGE 24 | SUMMER 2021 | THE NATURAL THERAPIST VOL 36 NO. 4
ANTA Member Article Summer 2021
Omega-3 Fatty Acids
Long chain (>C20) polyunsaturated fatty acids (PUFAs) of the omega-3 class including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and docosapentaenoic acid (DPA) are normally found in foods such as marine sources and eggs, but are rarely found in plants. The inability of humans to manufacture omega-3’s efficiently is the main basis from their dietary supplementation, especially during times of increased demand, such as pregnancy. DHA is perhaps the most critical omega-3 in prenatal life. It rapidly accumulates in the fetal brain during the last trimester to support neurogenesis1 and continues to increase as it supports synaptogenesis up to 2 years. Supplementation of omega-3’s, including DHA, during pregnancy has been shown to significantly improve childhood learning, behaviour, motor control and visual acuity2,3,4,5,6 and reduces the prevalence of allergies, asthma and respiratory infections7,8,9. A 2016 meta-analysis found that omega-3 PUFA supplementation reduced the risk of prematurity and early permature birth, thereby normalising birth weight and gestational age at delivery10. Revised international guidelines on omega-3 use during pregnancy recommend at least 300mg/d of DHA11 combined along with EPA, to support the transfer of both forms across the placenta12. While the Australian Natural Health and Medical Research Council (NHRMC) guidelines recommend up to 500mg/d of omega-3 fatty acids, which includes DHA and EPA13. There are additional studies to support the use of omega-3 during the pre-conception and postpartum periods as well. From pre-conception, higher DHA levels have been positively correlated with improvements in embryo morphology14, clinical pregnancy and live birth outcomes15 in women undergoing infertility treatment. While after birth, breast milk levels of DHA reflect the mother’s own status, with higher levels reported in nationalities
with higher habitual seafood consumption16. A study conducted in The Netherlands reported that at 12 years of age, children fed with breast milk containing a high concentration omgea-3 (as infants) exhibited lower blood pressure, compared to those not breastfed at all17. The benefits also extended to mums, with higher DHA status in mums and greater consumption of omega-3 shown to assist with postpartum depression symptoms18,19, which can be associated with prematurity20,21,22. A recent epidemiological study of over 90,000 Japanese mothers found that those with higher omega-3 intake reported a significant reduction in child abuse, including hitting (↓30%), shaking the baby (↓13% at 1 month, ↓30% at 6 months) and neglect (↓12%)23.
Folate (Vitamin B9)
The importance of folate during preconception and pregnancy relates to its role in regulating purine and pyrimidine synthesis for DNA production in rapidly dividing cells. Folate is also part of the methyl cycle that controls gene activation. The most notable examples of the importance of folate are in the differentiation of (i) the maternal erthrocyte pool as blood volume expands, and (ii) of the foetal central nervous and cardiovascular systems. Folate, iron and B12 deficiencies are linked to different forms of anemia, while folate deficiency is linked to neural tube defects (NTDs), cardiac malformations and general growth delays24. The relationship to NTDs was first reported by Smithells and coworkers (1980)25, where in unsupplemented mothers, the rate of NTD’s was 5%, but in mothers who took multivitamin containing 360µg/day of folic acid, the rate was only 0.6% (a more than 5-fold reduction). Since then, a series of meta-analyses has determined that 400µg/day of dietary folic acid used at least one month prior to conception, and through the first trimester, is effective at reducing the incidence and recurrence of NTD’s26,27, as well as reducing the risk of pregnancy terminations due to developmental anomalies by 30%. In a meta-analysis of 17 clinical trials, the same level of folate included as part of a multiple micronutrient (MMN) supplements for
THE NATURAL THERAPIST VOL 36 NO. 4 | SUMMER 2021 | PAGE 25
ANTA Member Article Summer 2021
pregnant women28, also resulted in reduction in the risk of newborns with low birthweight (12%) and being small size for gestational age (8%). While folic acid is still the only form of folate with evidence for NTD prevention, other forms of folate have become available for supplementation, including folinic acid and 5-methylfolate. As opposed to four enzyme steps for the conversion of folic acid and dietary folates into the bioactive form, folinic acid only requires two steps, while 5-methylfolate only requires one step. In any case, supplemental levels should remain in line with recommended nutrient intakes to prevent the emerging problem of unmetabolized folates in the bloodstream29.
Iron
through breast milk, especially in the first year. Depending on the iron status of women, different iron levels and forms are perscribed. The most common form with the highest available iron level is the mineral salt, iron sulfate. Other forms have also become available, owing to reports of digestive side effects of mineral iron (e.g. constipation, diarrhea, dark stools, metallic taste) including amino acid chelates, lactoferrin and heme iron. Iron chelates, such as bisglycinate chelate, have been used successfully during pregnancy, and show favorable digestion tolerance and absorption profiles compared to other forms33,34,35. Whichever iron forms and formats are used, it is always advisable to gauge the iron status of the patient before any recommendations are made, to avoid iron overload.
Vitamin D
Iron is typically available from meats and animal products as heme iron, and while it can be found in some leafy vegetables as non-heme iron, they would need to be consumed in very large quantities to have any real impact on iron stores. Additionally, phytates from plant matter can bind to and deplete iron before it is absorbed across the gut, so iron supplementation may be advisable for vegan/ vegetarian women to prevent iron deficiency, depending on their iron status. As described above, iron is critical for erythrocyte (red blood cell) formation because it forms part of the structure of hemoglobin. About 80% of circulating iron is bound up in erythrocyte hemoglobin. Iron is also a cofactor in enzyme steps that convert macronutrients into energy. Iron requirements increase by 50% during pregnancy, hence iron deficiency is the most common nutrient deficiency and cause of anemia worldwide, affecting up to half of pregnant women. Iron deficiency has been linked to neurological damage30,31, intrauterine growth retardation, prematurity, low birth-weight and an increased risk of infant mortality in developing countries32. Iron deficiency also extends beyond birth, as depleted pools in the newborn may persist during the first year, while depleted mothers continue to lose iron
Vitamin D, like iron, requires a gradual building-up of stores over time. Its main role is in the promotion of intestinal transport of calcium and divalent minerals. Calcium demands for pregnancy and breastfeeding are higher than for non-pregnant women to maintain maternal bone mineral reserves during fetal and newborn skeletal and muscular development. Vitamin D also plays other independent roles, as a molecular precursor for immune mediators and antibiotic proteins, in the pathogenesis of pre-eclampsia36, for preventing newborn/infant neurocognitive deficits37,38, and even as a growth factor. Vitamin D supplementation, typically as vitamin D3 (colecalciferol) during pregnancy has been shown to reduce the risk of maternal kidney dysfunction, pre-term delivery and low birthweight39,40. Post-partum improvements in maternal spinal and femoral bone density have also been reported41. An emerging trend has been the increased risk of gestational diabetes mellitus (GDM) in association with viatmin D deficiency42. If left untreated, this condition can predispose women to pre-eclampsia,
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ANTA Member Article Summer 2021
vaginal infections and a greater need for caesarean sections. A remarkable finding from a small Iranian trial of vitamin D3 supplementation in 80 pregnant women who were indicated for GDM, was a 3-fold decrease in the subsequent incidence of the condition (control, 34.8% vs test, 11.4%; p<0.01), which was inversely related to a 3-fold increase in the response to glucose challenge tests (control, 10.9 vs test, 35.9%; p<0.005)43. Vitamin D supplementation for as little as six weeks in another study of women with a similar cultural background showed a 60% reduction in hospitalisation rate and caesarean section procedures, as well as an absence of macrosomia, compared to 13% incidence in control group newborns44.
all stages of the reproductive life cycle in western countries50,51.
Iodine
The reproductive system, particularly egg (oocyte) formation, is highly sensitive to free radical damage, so antioxidant defense has adapted to protect these delicate processes. The main antioxidant vitamins include vitamins C, E and carotenoids, which are found in fruits, vegetables, seeds, nuts and eggs. Vitamin C is a cofactor for many important metabolic reactions and has potent antioxidant boosting properties. Early on, it protects the maturing oocyte with the antral follicle. Later, it is required for making collagen, which is used to make bones flexible when combined with the hardness of hydroxyapatite. Vitamin C is also required for absorption of iron in the intestine. Vitamin E is best recognised for its potent antioxidant properties which specifically target lipid peroxides, to protect cell membranes from free radical damage. Organs such as the lungs, eyes, brain, skin, liver and gut accumulate vitamin E to protect the exposed cell membranes from different forms of attacks, including light damage, microbial damage and metabolic toxicity. Vitamins C and E, along with B3, B12 and zinc, were found to be lower in women with a history of three or more miscarriages, compared to controls52.
Iodine is often overlooked, but it plays a critical role in regulating basal metabolic activity through its concentration in the thyroid gland for thyroid hormone production. The implementation of government programs for iodisation of foods, such as salt and bread, has contributed greatly to lowering the rate of fetal brain and growth abnormalities related to iodine deficiency and thyroid problems in developing countries. Dietary supplementation with iodine from the second trimester has been definitively shown to prevent growth retardation and neurological deficits in newborns45,46. A 2021 meta-analysis of eight studies, selected from a total of 136, has confirmed that idoine supplementation during pregnancy for mild deficiency supported improvements in psychomotor impairments in children up to 18 months of age47. The World Health Organisation recommends supplementation at least 150mcg/d to ensure an adequate supply of iodine during pregnancy48,49. These requirements are slightly elevated for breastfeeding mothers, based on indications that maternal iodine supports newborn brain and thyroid function via the modification of levels in breast milk. Despite this, and an incidence of goiter in females that is almost double that of males, it is surprising that iodine has for decades been overlooked for
Antioxidant Vitamins
Zinc
I often joke about the fact that its not a question of what zinc does, but rather, what it doesn’t do. Which isn’t much! Zinc participates in a wide range THE NATURAL THERAPIST VOL 36 NO. 4 | SUMMER 2021 | PAGE 27
ANTA Member Article Summer 2021
of biochemical pathways as an enzyme cofactor for metabolism, antioxidant defense, the immune system and wound repair, and is essential at all stages of the reproductive cycle. The zinc-dependent DNA binding protein, zinc finger x-chromosomal protein (ZFX), is expressed in very early embryos59 where it controls gene activation during the first few cell divisions. Later on, matrix-metalloproteases (also zinc-dependent) regulate binding and digestion of the endometrium by the blastocyst. More widely, zinc-dependent collagenases (MMPs) regulate a range of tissue remodeling events, such as during implantation, angiogenesis and placental formation, with potential involvements in specific gestational complications60. Zinc supplementation during pregnancy has been shown to reduce the risk of stillbirth and other complications61, including lowering the risk of preterm delivery and reduced cranial circumference62,63. Supplementation of pregnant women with zinc in combination with magnesium, calcium, and Vitamin D3 was shown to positively influence newborn size, trace mineral status and maternal blood pressure, for women at risk of preeclampsia64. Zinc supplementation has also been used to successfully counteract deficiencies observed in women undergoing assisted conception65. Interestingly, a case-control study reports that preconception zinc intake has a similar benefit to folate, in being able to prospectively reduce the risk of neurological defects in early pregnancy66.
the most concern clinically has been the association of low folate (B9) and B12 status with anemia in women55, which is why iron and folate are frequently supplemented together. In one study, 60% of women with morning sickness were deficient in vitamins B1, B2 and B6, and showed signs of dehydration56. Elsewhere, B6 supplementation from 10mcg/d has been demonstrated to support morning sickness during pregnancy57, and may be protective against cardiovascular system malformations in the fetus58. Others like biotin deficiency are less well described but may be more common than previously thought. In one pilot study of 10 women, 80% of pregnant women had lower levels of the biotindependent enzyme, propionyl-CoA carboxylase (PCC) throughout pregnancy, and mild biotin deficiency has been linked to fetal developmental abnormalities in non-human studies55.
Take Home
To sum up, specific nutrients play specific roles in reproductive health, at all stages. However, it is often difficult to pinpoint which of these are deficient, and further evaluation by a healthcare provider may be warranted. Many micronutrients take time to build up in female tissue stores, therefore it is important to plan ahead. The ultimate take home from all this would be a normal, healthy child!
B-Complex Vitamins
B-Complex Vitamins are required on a daily basis, because they are water soluble and readily lost from the system. The two main roles for B-complex vitamins are (i) energy production (B1, B2, B3, B5, B7) and (ii) control of deoxyribonucleic acid (DNA) production and cell division (B1, B2, B6, B12). These processes are critical drivers of development, as seen with specific deficiencies, such as B1 deficiency-(beri beri) neuropathy53. Dehydration or acute illness can lead to B-vitamin wash-out and depletion of stores. B-vitamins also have the tendency to be deficient during pregnancy, because of their increased transport requirements across the placenta54. Of PAGE 28 | SUMMER 2021 | THE NATURAL THERAPIST VOL 36 NO. 4
For references log into your ANTA Member Centre > The Natural Therapist > Journal Articles
THE NATURAL THERAPIST VOL 36 NO. 4 | SUMMER 2021 | PAGE 29
Plasmalogens A key glycerophospholipid found in healthy brain cells
Plasmalogens are critically involved in the physiological and structural aspects of brain health and by acting as antioxidants, which protect neural membranes against oxidative stress. Plasmalogens naturally decline with ageing and are reduced in people aged 65 years and over by 40%. Figure 1: Plasmalogens are reduced by 40% in people aged 65 years and over 300
% of total phospholipids
240 180 120 60
Plasmalogens are a naturally occurring glycerophospholipid that comprise approximately 20% of the total phospholipids found in cell membranes. In the brain, plasmolagens constitute up to 50% of total phospholipids.
0
Age: 23.5 +/- 3.6
Age: 65.5 +/- 12.0
Serum Plasmalogen Level (µM)
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BioMedica Nutraceuticals P 1300 884 702 | www.biomedica.com.au PAGE 30 | SUMMER 2021 | THE NATURAL THERAPIST VOL 36 NO. 4
ANTA Member Article Summer 2021
Bianca Vogel
BHSc (Naturopathy) MSc (Diagnostic Genomics) ANTA Member
Osteogenesis Imperfecta Research Paper Introduction
Osteogenesis imperfecta is a heterogeneous, inherited disorder of collagen tissue and bone matrix formation and regulation. In recent years, many genes have been tied to the pathogenesis of Osteogenesis imperfecta resulting in many forms of the disorder. Despite its many forms it is characterised by alterations in bone mineral density, strength and formation. This report has been conducted to enhance the understanding between the relationship of collagen, bone matrix and the pathogenesis of Osteogenesis imperfecta, particularly focusing on the more commonly seen genes known to cause this disorder - Collagen type 1, alpha 1 and Collagen type 1, alpha 2.
Clinical Features
Osteogenesis imperfecta (OI) is known as the most commonly occurring genetic skeletal disorder, with its incidence ranging between ~1:15,000 ~1:20,0001. There are numerous genes associated with the pathogenesis of OI, amongst these genes, over 1500 variants have been identified2. This significant heterogeneity is associated with the variety of phenotypical presentations seen in the disorder. Despite this variety amongst sufferers of the disorder, the characterising features of OI include reductions in bone mineral density (BMD), poor bone strength, regular fractures of the bone and progression to bone deformity (BD)3. Other commonly described signs and symptoms of OI include short stature, progressive hearing loss, blue sclerae, brittle and opalescent teeth, joint laxity, weak muscle tone, kyphosis, scoliosis, basilar
impression, deformities of the chest wall, easy bruising, progressive impairment of pulmonary function and dentinogenesis imperfecta2. Radiographic results will show signs of long, bowed bones, gracilis ribs, thin thoracic apex and compression of the vertabra, osteopenia and poorly tubularised, narrow, long bones. Additionally, in OI, increases in osteocyte lacunae, vascular porosity and bone matrix mineralisation occur4. Consequentially, this results in trabecular bone with lowered trabecular number, connectivity, thickness and volumetric bone mass. As well as decreases in cortical thickness, reduced mechanical anisotropy and enhanced pore percentage in cortical bone4.
Diagnostic Criteria
Originally, OI was classified using the diagnostic criteria by Sillence. This categorised OI in to four
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ANTA Member Article Summer 2021
types based on phenotypic features. Traditionally, these four criteria included types 1, 2, 3 and 4, also known as the mild, lethal, survivable but severe and moderate types, respectively3. After this criteria was created OI knowledge increased considerably, to account for this the Nosology Group of International Skeletal Dysplasia Society introduced type 5 to the criteria in 20152 (see Table 1).
Table 1: Nosology Group of International Skeletal Dysplasia Society Osteogenesis Imperfecta Classification2 Osteogenesis imperfecta Type
Inheritance
Features
1
Autosomal dominant
Non-deforming form • Osseous fragility • Pre-senile hearing loss • Blue sclerae
2
Autosomal dominant, Autosomal recessive
Perinatal lethal form • Extremely severe osseous fragility
3
Autosomal dominant, Autosomal recessive
Progressively deforming form • Moderate to severe osseous fragility
4
Autosomal dominant, Autosomal recessive
Moderate form • Generally normal sclerae
5
Autosomal dominant, Autosomal recessive
Calcification of the interosseous membrane and/ or hypertrophic callus
This form of classification relies on phenotype as the rule for diagnosis. However, due to OI molecular factors not being considered in the Sillence-based criteria, a severity grading scale (See Table 2) has been formulated by Van Dijk and Sillence for clinical use. Through the grading scale, clinical and historical data, skeletal condition with fracture incidence and timing, bone densitometry, mobility and ambulatory level are considered. This scale allows clinicians guidance on disease progression trajectories and possible treatment options2.
Osteogenesis Imperfecta Molecular Basis
Bone tissue consists of 30% collagenous matrix and 60% of a mineral component located amongst collagen fibres. The proportion of bone tissue reliant on collagen explains the severe consequences seen in bone architecture and matrices in OI patients. The general perception is that ~90% of OI cases are due to variants in the Collagen type 1, alpha 1 (COL1A1) and Collagen type 1, alpha 2 (COL1A2) genes1. Studies
of different ethnicities show ranges of COL1A1 and COL1A2 aetiological responsibility between 58-96%5. Both of these genes are important encoders of Collagen type 1 (Col1). Despite COL1A1 and COL1A2 being predominantly causative in OI, there are many other genes that can cause the disorder. These genes do not encode collagen, rather they are involved in the processing, post-translational modifications and crosslinking of Col1, as well as the differentiation and functioning of osteoblasts. Dependent on the variant nature and location, as well as the function the gene exhibits, each error can result in mild to severe forms of OI. Each gene correlates with different presentations of OI and are therefore given their own genetic classifications, from type I to type XX6 (see Table 3).
Collagen Structure, Production and Function
The collagen proteins are the most abundant proteins in the extracellular matrix (ECM) in humans. Collagens provide a range of functions to the body, aside from their structural support in the ECM, they also are involved in the enmeshment, storage and delivery of cytokines and growth factors. This function explains their integral relationship to wound healing, repair of tissues and development of organs. The fibril-forming collagens (including Col1) are distributed amongst the bone, ligaments, tendon, cornea and dermis, here they play a role in fascia and tendon tensile stiffness, and in bone load bearing, torsional stiffness and tensile strength. The fibrilforming collagens are the most abundant family of collagens, accounting for ~90% of total collagen in the body. This family of collagens form over 90% of bone mass and are the major collagen seen in tendons, skin, cornea, ligaments and interstitial connective tissues26. These collagens are secreted mainly by the dermal fibroblasts, tenocytes and osteoblasts10. The genes COL1A1 and COL1A2 encode the collagen pro-α2 chains, respectively, which go on to form type 1 procollagen and eventually, Col1. The fibril-forming collagens are characterised by their structural domains with repetitions of Gly-X-Y triplets. As the Gly-X-Y suggests, glycine residue is a structural prerequisite for the assembly into the triple helical formation of collagen and is seen at every third helical residue1. Regularly, we see proline and hydroxyproline occupying the X and Y positions. As two collagen pro-α1 and one collagen pro-α2 protein chains assemble around a central axis, the residues of glycine line up in the centre, forming a triple helix. Disulphide bonds then congregate at the C-terminus end. Following this, bulkier side chains of other amino acids form the outer sides of the molecule26. The three pro-α chains then fold THE NATURAL THERAPIST VOL 36 NO. 4 | SUMMER 2021 | PAGE 33
ANTA Member Article Summer 2021
Table 2: Van Dijk and Sillence Osteogenesis Imperfecta Severity Grading Scale2 Intrauterine Growth velocity (ultrasound at 20 and height weeks of pregnancy)
Intrinsic bone deformations
Annualised prepubertal fracture rate
Locomotion status
Mild Osteogenesis imperfecta
• No fracture • No long bone deformities
Normal or near normal
None
≤1
Ambulant
Moderate Osteogenesis imperfecta
• Rare fetal long bone fracture or bowing
Decreased
Anterior femoral and tibial bowing
>1
Ambulant
Severe Osteogenesis imperfecta
• Long bones shortening • Long bone fracture and bowing • Rib fracture
Severely decreased
Long bone and spine progressive deformity
>3
Wheel-chair dependent
Extremely severe Osteogenesis imperfecta
• Long bone shortening • Long bone fracture and bowing • Rib fracture • ↓ Mineralisation
Multiple long bone fractures at birth, all vertebrae are crushed, small thorax, respiratory distress Perinatally lethal course
in a zipper-like fashion, this forms the triple helix shape all within the endoplasmic reticulum (ER) (see Figure 1)4. As the zipper-like folding occurs, it runs from the C-terminus to the N-terminus ends of the molecule. During this, a hydroxy group attaches to particular prolines and lysines, creating hydroxyproline and hydroxylysine. To finalise the formation of the procollagen, it is excreted by an osteoblast into the ECM space. The formation of this triple helix structure is relatively simple, however in order to make type 1 collagen, the biosynthesis of type 1 procollagen must occur, this is incredibly complex. Several steps are involved which require a series of proteins for procollagen post-translational modifications, folding, transport, secretion and quality control10. Essentially, conversion into collagen beings via cleaving the pro-peptides of the molecule4. Once collagen is formed, a series of steps ensue to produce Col1.
COL1A1 and COL1A2 Correlation to Osteogenesis Imperfecta
As previously mentioned, COL1A1 and COL1A2 encode the collagen pro-α1 and collagen pro-α2 chains, respectively. Patients with OI tend to have variants in different locations along the COL1A1/ COL1A2 genes. The severity of OI can be determined somewhat by the nature of a variant, as well as its proximity to the C-terminus of the collagen protein4.
COL1A1 variants tend to be more frequent than COL1A2 variants, although both occur frequently.
Figure 1: Structure of Collagen27
The dominant variations to COL1A1 and COL1A2 are haploinsufficiency variants and helical glycine variants. Haploinsufficiency variants result in quantitative defects, meaning the synthesis of Col1 will be normal, but only half the amount will be produced. Despite only half of the usual Col1 being produced, a normal level of the lysyl hydroxylating enzymes are produced, resulting in an enhanced enzyme to collagen ration. This imbalanced ratio leads to heightened hydroxylation and glycosylation levels. These defects are associated with the milder forms of OI. Regularly seen variants here will be heterozygous null variants in COL1A1 alleles28. Helical glycine variants effect the synthesis of Col1 causing qualitative defects. The most common variants associated with qualitative defects are
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ANTA Member Article Summer 2021
Table 3: Genes Involved in Osteogenesis Imperfecta Aetiology Gene
Inheritance
Protein Encoded
Protein Primary Function in Relation to Osteogenesis Imperfecta
Osteogenesis Imperfecta Genetic Classification
Disruption of Collagen Structure and Synthesis
COL1A1
Autosomal dominant
Collagen pro-α1 chain
Explained below
Types I, II, III, IV7
COL1A2
Autosomal dominant
Collagen pro-α2 chain
Explained below
Types II, III, IV8
Impaired Bone Mineralisation
IFITM5
Autosomal dominant
Interferon-induced transmembrane protein 59
Appears to have a crucial role in bone mineralisation10
Type V9
SERPINF1
Autosomal recessive
Pigment epitheliumderived factor11
An anti-angiogenic factor whose effect on the receptor activator of nuclear factor-κβ ligand pathway increases osteoclast activity10
Type VI11
Abnormal Post-Translational Modifications of Collagen
CRTAP
Autosomal recessive
Cartilage-associated protein12
Appears involved in the formation of the triple helix procession from the C-terminal to amino-terminal end of Col110
Type VII12
P3H1
Autosomal recessive
Proylyl 3-hydroxylase 113
Hydroxylates specific prolines in the X position of Gly-X-Y chain10
Type VII13
PPIB
Autosomal recessive
Peptidyl-prolyl cis-trans isomerase B14
Appears involved in the formation of the triple helix procession from the C-terminal to amino-terminal end of Col110
Type IX14
Reduced Collagen Cross-Linking and Processing
SERPINH1
Autosomal recessive
Serpin H115
Stabilises the newly formed Col1 triple helices Allows for binding sites along the helical portion of Col1 to assist the shuttling of folded collagen in to the cis golgi10
Type X15
FKBP10
Autosomal recessive
Peptidyl-prolyl cis-trans isomerase FKBP1016
Appears involved in the formation of the triple helix procession from the C-terminal to amino-terminal end of Col110
Type XI16
SP7
Autosomal recessive
Transcription factor SP717
Essential in the formation of bone10
Type XII17
Alterations to Osteoblast Function and Differentiation
BMP1
Autosomal recessive
Bone morphogenetic protein 118
Assists in the cleavage of the pro-peptides of procollagen in to mature Col110
Type XIII18
TMEM38B
Autosomal recessive
Trimeric intracellular cation channel type B19
A cation-specific, monovalent channel necessary for intracellular calcium flux, as well as cell differentiation10
Type XIV19
WNT1
Autosomal recessive or Autosomal dominant
Proto-oncogene Wnt 120
Through interactions with the receptor Frizzled and its co-receptor lowdensity lipoprotein receptor-related protein 5/6, this protein activates bone formation10
Type XV20
CREB3L1
Autosomal recessive
Cyclic AMP-responsive element-binding protein 3-like protein 121
An ER stress transducer important in the regulation of gene transcription, particularly those involved in maturation, developmental processes and differentiation10
Type XVI21
SPARC
Autosomal recessive
Sparc
Protein of the matrix that can elicit changes to cell shape, halt cell-cycle progression and enhance the synthesis of ECM
Type XVII22
TENT5A
Autosomal recessive
Terminal nucleotidyltransferase 5A
A nucleotidyltransferase that appears to act as a poly(A) RNA polymerase, with associations to height, BMI, and white blood cell regulatory functions
Type XVIII23
MBTPS2
X-linked recessive
Membrane-bound Found in the Golgi membrane, essential for the cleaving of regulatory transcription factor site 2 proteins transported from the ER during stress or sterol metabolite protease24 deficiency10
Type XIX24
MESD
Autosomal recessive
LRP chaperone MESD
Type XX25
A chaperone found in the ER that transports Lrp5 and Lrp6, in conjunction with Frizzled. This is also a co-receptor for Wnt signal transduction
THE NATURAL THERAPIST VOL 36 NO. 4 | SUMMER 2021 | PAGE 35
ANTA Member Article Summer 2021
single-nucleotide substitutions, where glycine is substituted with a heavier residue. Dependent on the replacement amino acid, the phenotypes seen in this variant will be different each time. It has been documented that single-nucleotide changes in the pro-α1 chains are more severe than those in the pro-α2 chains6. Splice site variants causing exon skipping and a change in Gly-X-Y chain alignment and successive Col1 secretion and folding. Variants that cause disruption to the procollagen c-propeptide domain also can cause qualitative defects. Additionally, deletions and duplications in one or two Gly-X-Y chain triplets can cause qualitative defects. Structural irregularities are often seen in type I and type II OI and are associated with mild to severe forms29. The severity seen in structural variants is due to a number of reasons. One reason is that the structurally unfolded pro-α1 chains can confine in the ER for a prolonged period of time, resulting in long-term exposure to posttranslational-modifying enzymes and a prevasive modification to the collagen chains. Overly modified collagen molecules can assemble into abnormal fibrils, leading to an abnormal ECM - this is one of the key issues correlated with OI bone fragility. Additionally, another reason to the severity is that the structurally incorrect Col1 becomes partially retained in the ER, causing stress to the organelles which can result in apoptosis, autophagy and impaired osteoblast differentiation, further exacerbating ECM disruption and reducing collagen synthesis and subsequent bone mass10.
helix structure30. Certain gap regions with specific and highly important fuctions suggest that location, although not linear in presentation, can be important in disease progression as well28. A combination of the location of variants along the chain, the nature of the substituting amino acids and the chains in which the substitutions occur all contribute to the phenotypic outcome10. To add to this, the ranging penetrance seen in OI means even patients with the same glycine substitutions can show different phenotypes28.
With any substitution of glycine resulting in a structural defect, the severity of that defect will be dependent on the position of the amino acid substitution. For example, substitutions that occur in the C-terminal result in severe phenotypes, and N-terminal substitutions tend to be much milder. In addition to this, if a residue with a large lateral chain or a residue that is charged is substituted, this will yield a severe phenotype regardless of location, due to their highly disruptive consequences on the triple
Errors in the genes associated with collagen and bone matrices can be both detrimental and inordinately diverse. OI is a disorder of characterizable heterogeneity caused not only by genetic variants, but by the nature and location of each variant in relation to the gene that they impact.
Discussion
The heterogeneity in OI is significant, as are the levels of expression and penetrance. This disorder displays a wide range of both genotypes and phenotypes. This report highlights collagen’s integral role in OI pathogenesis, and specifically the importance of its structure and quantity in the functioning of the human body. Through researching into the effect that variant location and nature can have on the pathogenesis of OI, it has been noted that even patients with the same genotypes can experience different phenotypes. Looking forward, more clarity in regards to location of variants, and their association to collagen structure and quality will be beneficial for the genetic counselling of future OI patients. This clarity will also be beneficial for clinicians in building treatment plans based on genotypic profiles.
Conclusion
PAGE 36 | SUMMER 2021 | THE NATURAL THERAPIST VOL 36 NO. 4
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THE NATURAL THERAPIST VOL 36 NO. 4 | SUMMER 2021 | PAGE 37
“
Lactobacillus crispatus & vaginal microbiome stability By Benjamin Makeham, Manager of Science and Research at ACTIVATED PROBIOTICS
A healthy vaginal microbiome
The benefits of Lactobacillus crispatus
A healthy vaginal microbiome (VMB) is characterised by low diversity of microorganisms and Lactobacilli dominance. Lactobacilli are necessary for the production of lactic acid to help maintain optimal vaginal pH (3.5-4.5) and deter the growth of pathogenic microorganisms. Lactobacilli bacteria also help to protect against vaginal infections by producing other antimicrobial metabolites such as hydrogen peroxide, competing for nutrients and adhesion sites, and promoting a healthy vaginal mucosal barrier (1).
In the VMB, L. crispatus produces the highest amount of lactic acid compared to other Lactobacilli species, and is one of the most important producers of hydrogen peroxide and other antimicrobial substances such as bacteriocins (2, 4). In this way, L. crispatus helps to create a vaginal environment that is inhospitable to the growth of pathogenic bacteria.
Vaginal dysbiosis For many women, the most evident examples of vaginal dysbiosis are bacterial vaginosis and vulvovaginal candidiasis (vaginal thrush). These common vulvovaginal infections (VVIs) are caused by disruptions to the VMB, and can have a significant impact on quality of life and increase the risk of pregnancy-related complications and sexually transmitted infections (1, 2). Conventional antimicrobial treatments often provide short-term relief, however due to their inability to address underlying VMB dysbiosis and Lactobacilli deficiency, long-term recurrent infections are a significant clinical problem (3).
Community state types of the VMB Across different women, there are five recognised vaginal microbial community state types (CSTs), with four dominated by a specific Lactobacilli species, including Lactobacillus crispatus (CST-I), L. gasseri (CST-II), L. iners (CST-III) and L. jensenii (CST-V), and one characterised by a greater diversity of non-Lactobacilli microorganisms (CST-IV). Compared to other community subtypes, L. crispatus dominance is the only subtybe consistently linked with good vaginal health, vaginal microbiome stability and a lower risk of developing VVIs (1).
L. crispatus is also associated with an increased abundance of mannitol in the vagina, helping to enhance the mucous layer and improve the tonicity of the epithelium (5). It has also been shown to accelerate wound healing in vaginal epithelial cells (6). These effects on the vaginal epithelium supports the maintenance of a healthy VMB and creates a strong physical defence barrier that inhibits penetration of pathogens (7). Furthermore, L. crispatus promotes an anti-inflammatory vaginal immune profile that promotes good vaginal health and optimises the local immune response to pathogens (1). Collectively, the actions of L. crispatus help to inhibit pathogenic overgrowth, reduce the risk of VVIs and maintain a stable vaginal microbiome. For example there is an inverse association between levels of L. crispatus and the main bacterium
associated with BV, Gardnerella vaginalis, and the presence of L. crispatus is associated with diminished virulence of C. albicans (1, 8). Interestingly, L. crispatus also prevents the growth of non-native intestinal pathogens and those associated with urinary tract infections and aerobic vaginitis such as S. aureus, Klebsiella spp., E. faecalis and E. coli (1).
Biome Her Probiotic Activated Probiotics’ Biome Her Probiotic was specifically formulated to help maintain a healthy vaginal microbiome, combining a unique strain of Lactobacillus crispatus (LCR01) with two-clinically trialled probiotic strains shown to reduce the recurrence of vulvovaginal candidiasis: Lactobacillus acidophilus LA02 and Lactobacillus fermentum LF10 (3). With the inclusion of Lactobacillus crispatus LCR01, Biome Her Probiotic is the first practitioner-only probiotic product to include a member of the native vaginal species consistently linked to vaginal microbiome stability and protective effects against vaginal dysbiosis (1, 8).
Benefits of Lactobacillus crispatus dominance Increased lactic acid production Reduced risk of vulvovaginal infections Improved vaginal epithelial cell health ACTIVATEDPROBIOTICS.COM.AU
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ANTA Member Article Summer 2021
Kerry Bone
Founder and Director of Research at MediHerb Principal of Australian College of Phytotherapy Adjunct Professor of New York Chiropractic College
Withania and Liver Damage Should We be Worried? With the increasing use and scrutiny of medicinal plants comes the increased possibility of finding rare, unexpected adverse reactions. However, it is important that such reports are carefully analysed and backed up by other studies before definitive conclusions are formed. Recently, five cases have emerged connecting idiosyncratic drug-induced liver injury (DILI) to the use of Withania1. I mentioned these in a previous article in The Natural Therapist, but would now like to take the opportunity to examine them in detail. In all reported cases the damage was reversible with discontinuation of the herb and resulted in no permanent liver injury. The report has been criticised for its incompleteness and a lack of plausibility2. Liver toxicity related to drugs and plants is divided into two varieties, based on the presumed mechanism of action of the intervention: intrinsic and idiosyncratic. The intrinsic (direct or predictable) type is dose-related and occurs after short exposure (hours to days) to the herb or drug, which is known
to be toxic to the liver at a given threshold dose. By contrast, the idiosyncratic (indirect or unpredictable) variety of DILI is determined by the interaction of often unknown environmental and host factors with the treatment. As a consequence, idiosyncratic DILI is rare, has a longer latency period (from a few days to several months), and is not dose-related. The immune system is typically involved in driving the observed liver damage in idiosyncratic DILI3. How widespread is idiosyncratic DILI from herbal therapy? A recent analysis suggests it might be more of a problem in the East4, despite several attempts to use it as an issue to discredit herbal therapy in the West, including from Australia5. The analysis in fact revealed that prescribed drugs are still the main problem for DILI. It found 12 studies that showed the distribution of drugs implicated in DILI in the East, with a total of 33,294 patients, and 16 in the West with a total of 26,069 DILI cases. In the East, the most common agents by class were anti-tuberculosis drugs (26.6%), herbal and alternative medications THE NATURAL THERAPIST VOL 36 NO. 4 | SUMMER 2021 | PAGE 39
ANTA Member Article Summer 2021
(25.3%), and antibiotics (15.7%), while in the West, antibiotics (34.9%), cardiovascular agents (17.3%), and non-steroidal anti-inflammatory drugs (12.5%) were the commonest, with herbs and supplements at 5.6%. For individual agents, the most common agents in the East were isoniazid-rifampicinpyrazinamide (25.4%), phenytoin (3.5%), and cephalosporin (2.9%) while in the West, amoxicillinpotassium clavulanate combination (11.3%), nimesulide (6.3%), and ibuprofen (6.1%) were the commonest. The high prevalence of DILI from herbal and alternative medications in the East could mainly reflect quality issues, as medicines there might be adulterated with conventional drugs6. Regarding the report from Iceland, it described five cases of liver injury that the authors attributed to Withania-containing supplements; three were collected during 2017-2018 from Iceland, and another two from the Drug-Induced Liver Injury Network (DILIN) in 2016 (presumably from other countries)7. Among the five patients, three were males and the mean age was 43 years (age range 21 to 62). All patients developed jaundice and symptoms such as nausea, lethargy, pruritus and abdominal discomfort after a latency period of 2 to 12 weeks after beginning Withania. The liver injury was cholestatic or mixed. Pruritus and hyperbilirubinaemia were prolonged (5 to 20 weeks), but no patient developed hepatic failure. Liver tests normalised within one to five months in four patients and one case was lost to followup. One biopsy was performed, showing acute cholestatic hepatitis. Chemical analysis by the authors ‘confirmed’ Withania in available supplements; no other toxic compounds were identified. No patient was taking potentially hepatotoxic prescription medications, although four were consuming additional supplements, and in one case, Rhodiola was deemed
to be a possible ‘causative agent’ along with Withania. The role of Withania in causing liver injury was judged as definite in one case, highly likely in two, probable in one and only possible in one. Viral markers for acute hepatitis A, B and C as well as cytomegalovirus IgM were negative in all patients. However, hepatitis C virus (HCV) ribonucleic acid (RNA) polymerase chain reaction (PCR) was performed in only one case (and was negative) and hepatitis E virus (HEV) testing was not undertaken. Liver injury was moderate, for example the mean peak alanine transaminase (ALT) recorded in the five cases was 361U/L, and for aspartate transaminase (AST) this mean was 240U/L. All three Iceland cases were from the same product (manufactured in the US) and one DILIN case was also linked to a different US product. I purchased and initiated an analysis of the US product implicated in the three Iceland cases. According to the relevant USP (United States Pharmacopeia) method, the product was found to contain a high percentage of Withania leaf, despite the label claiming only root as the plant part. Perhaps this issue (contamination with Withania leaf) was the cause of the idiosyncratic DILI (assuming there is a link with the product, which is still uncertain). Furthermore, this US product was the only ‘definite’ case, as rated by the authors (see above). At this stage it is important to be alert for a similar potential reaction in patients, but there is no cause for alarm, especially if high quality Withania products are used with a confirmed absence of leaf. Ironically, there are laboratory experiments demonstrating Withania root protects against liver damage8.
PAGE 40 | SUMMER 2021 | THE NATURAL THERAPIST VOL 36 NO. 4
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ANTA Member Article Summer 2021
Tony Reid
M.Ac (Acupuncture) M.TCM (Traditional Chinese Medicine)
Traditional Chinese Herbal Formulas Ping Wei San - Research Update Introduction
The traditional Chinese herbal formula, Ping Wei San (‘Calm the Stomach Powder’), has been used in China for over 1,000 years for gastro-intestinal disorders. It has recently been the focus of animal and human studies, which, in addition to elucidating possible mechanisms of action, also support its efficacy in the treatment of various inflammatory and motility disorders of the gastrointestinal tract. This paper aims to summarise the results of these studies, correlate them with traditional theories and provide practical examples of this formula’s clinical applications.
Classical Sources and Traditional Applications
Ping Wei San (PWS), a.k.a. Magnolia & Ginger Combination, was first recorded in the Formulary of the Tai Ping Welfare Dispensary Bureau (ta ping hui min he ji ju fang), a compilation of effective formulas that were used in the public dispensaries of the Song Dynastic period (960-1279 CE). The implied meaning of the formula name is to balance and harmonize the Stomach and Intestines, by restoring the normal descending movement of the Stomach Qi, through which the contents of the stomach and intestines are moved in an aboral direction. The actions of the formula are to dry Damp, promote the Spleen’s transporting function, and to promote normal Qi
movement in the Stomach and Intestines1. The formula is a simple combination of four herbs, to be administered with a variable amount of Chinese dates and ginger, according to the discretion of the prescribing physician. Originally prepared as a powder, PWS was taken as a draft in doses of 6-9g and washed down with a weak decoction of dates and ginger to make it more palatable and prevent immediate regurgitation2. It is available in prepared form, often without the dates and ginger as their actions may be covered, respectively, by pre-preparation of Glycyrrhiza root
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with honey and pre-preparation of Magnolia bark with ginger juice. Ingredient
Traditional Chinese Medicine Actions
Atractylodes lancea, rhizome (dry fried)
Dries Damp and promotes the Spleen’s transporting function
Magnolia officinalis, stem bark (ginger fried)
Dries Damp and redirects the Qi downwards
Citrus reticulata, fruit peel
Redirects the Qi downwards and dried Damp
Glycyrrhiza uralensis, root (honey fried)
Harmonizes the Stomach and strengthens the Spleen, harmonises the formula
gastritis, chronic colitis, irritable bowel syndrome and diarrhea in infants. In addition, it may also be used as the basis for prescriptions in the treatment of amenorrhea, premenstrual syndrome, cervicitis, eczema pertussis, erectile dysfunction and halitosis3.
Botanical Features, Phytochemistry and Pharmacological Actions of the Ingredients Atractylodes lancea, rhizome (cang zhu)
The formula’s principal herb is the rhizome of Atractylodes lancea (‘grey/black Atractylodes’), which dispels Damp and promotes movement of the Spleen Qi. The deputy herb is Magnolia officinalis bark, which reinforces the principal herb’s actions to disperse stagnant Qi, promote normal Qi movement and resolve Damp. The assistant is Citrus reticulata peel, which mainly acts to normalise (‘harmonise’) the Stomach Qi, while secondarily drying Damp. The envoy, which helps focus the formula’s actions on the Spleen-Stomach is prepared Glycyrrhiza uralensis root. It also acts to ‘harmonise’ the formula so that the harsh dispelling nature of the other ingredients do not further upset the Stomach1. The disorders that may be treated by this formula are characterised by Qi stagnation within the organs of digestion - the Spleen, Stomach and Intestines. The key clinical features are distention and a sense of fullness in the epigastrium, belching, reflux, nausea or vomiting. This equates with functional dyspepsia in Western medicine, which is regarded primarily as a motility disorder. However, Traditional Chinese Medicine (TCM) physicians also look to the underlying causes, and are not content to regard such a condition as merely ‘functional’. The important clinical signs are a thick, ‘greasy’ coating on the tongue, fatigue with a heavy sensation in the limbs, increased desire to sleep, loose stools, swollen tongue, and possibly also a slippery pulse. These are all signs of retained Damp, which is the underlying cause of the presenting symptoms. Lifestyle factors such as overconsumption of Cold-natured and raw foods as well as overeating and insufficient exercise are common causes for this type of retained Damp1.
Atractylodes lancea is a dioecious, perennial herb of the Compositae (Asteraceae) family. It is found on hill or mountain slopes at altitudes between 7002500m. The herb has been cultivated for over 700 years, the best quality rhizomes coming from the mountainous regions of Jiangsu. The rhizomes are harvested in the spring and autumn, dried in the sun and then sliced. As a medicine it is generally used in pre-prepared form - stemed and dry-fried, with or without adjuvant. It is traditionally used in the treatment of a variety of conditions, including gastrointestinal disorders, common cold, influenza, rheumatic disorders and night blindness4,5,6,7. Atractylodes lancea rhizome (ALR) contains over 230 potentially active compounds, including terpenoids, terpenoid glycosides, alkynes, alkyne glycosides, aromatic glycosides, acyl sugar compounds, lignans, phenolic acids and pyrazines. Studies on rats, mice and cell cultures have shown that extracts of ALR have the following actions5,7: • Improves gastro-intestinal function: Delays gastric emptying and stimulates small intestinal motility in a dose dependent manner; promotes healing of gastric mucosal ulceration by reducing inflammatory mediators such as TNF-α, PGE2, IL-8 and IL-6 and increasing factors TFF2 and EFGE to assist repair (in rat model) • Immunomodulatory actions: Induction of granulocytes, macrophages and T-cells in the intestinal immune system (in cell cultures) • Anti-tumour actions: Specifically against
In China, physicians use this formula as the basis for treating a variety of gastrointestinal conditions, including peptic ulcer, chronic THE NATURAL THERAPIST VOL 36 NO. 4 | SUMMER 2021 | PAGE 45
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cholangiocarcinoma. Also against bladder cancer, melanoma, and lukemia (in vitro and in vivo animal studies) • Anti-inflammatory actions: Through downregulating various inflammatory pathways, e.g. 5-LOX and COX-1, NO, prostaglandin E2 (in rats, mice and cell lines) • Antibacterial activity: Inhibitory effect on various fungi and bacteria, including a strong action against candida albicans • Actions on the nervous system: Isolated components have demonstrated actions on the central nervous system and nerve tissue • Cardiovascular: Anti-platelet action, therefore caution is advised in patients with coagulation disorders • Antipyretic: At very high doses, i.e. above 5gm/kg body mass (in rat model) • Hypoglycemic and hypolipemic: In mouse model of obesity
Magnolia officinalis, bark (hou po)
Magnolia is a deciduous tree of the Magnoliaciae family, that grows to around 20m in height. It grows in warm and humid areas throughout China, on mountains or in valleys at heights of 300-1500m. It belongs to an ancient family of plants that have been on the planet for at least 95 million years, predating the appearance of bees. Therefore, it relies on beetles for pollination. The bark and flowers have been used in traditional medicine for over 2,500 years but have only been cultivated fairly recently due to the declining wild population. The best quality comes from Sichuan and is named chuan hou po. Harvested in late spring and early winter, the bark is stripped from the stems, boiled for a short time and then stored in a damp environment to ‘sweat’ until the inner surface becomes purple-brown or deep brown. It is then steamed, rolled into a tubular shape and cut. The cut product is generally processed with ginger juice. It is used traditionally in formulas that treat various digestive, respiratory and emotionbased disorders8,9,10.
Magnolia bark contains over 200 potential active components. These include lignans, phenylethanoid glycosides, phenolic glycosides, alkaloids, steroids, and volatile oils. Studies on rodents and cell cultures have demonstrated a wide range of pharmacological activities, summarised below8,9: • Gastrointestinal: Antispasmodic action on smooth muscle in the gastrointestinal tract (GIT), promotes GIT motility with increased gastric emptying and intestinal transit rates (in mouse and rat models) • Cadiovascular: Cardioprotective against lipid peroxidation, ischemia and reperfusion induced ventricular arrhythmias as well as reducing size of infarcts; reduces atherosclerotic plaque formation; anti-platelet activity (in rat models) • Cerebrovascular: Protection against cerebral ischemia-reperfusion injury (in rat models) • Anti-asthma: Antispasmodic action on respiratory smooth muscle and suppression of lymphocyte mediated allergic reaction • Anti-diabetes: Reduces body fat accumulation, insulin resistance and adipose inflammation. Also inhibits formation of advanced glycation end products (AGE’s) to prevent complications of diabetes (in rat and mouse models) • Mood disorders: Anxiolytic and antidepressant effects (in rate and mouse models) • Anti-Alzheimer’s: Prevention of memory loss and genesis of amyloid plaque (in rat and mouse models) • Anti-Parkinson’s disease (PD): Prevented development of PD (in mouse model) • Antibacterial: Broad spectrum anti-bacterial action, particularly against Gram-positive species, such as Staphylococcus aureus. It acts on several different targets and pathways, making the development of resistance unlikely • Anti-tumour: Acts on several signalling pathways that control cell metabolism, growth and proliferation to modulate cancer initiation and progression and also to induce apoptosis of tumour cells (specifically cancers of the breast, cervix, prostate, bladder, lung, colon, rectum, pancreas, glial cells, stomach, thyroid and skin) • Anti-inflammatory: Strong effects on reducing the production of pro-inflammatory mediators • Anti-oxidative: Components of magnolia bark have effects that are 1,000 times greater than the antioxidant effect of alpha tocopherol. These actions most likely underlie the cerebro-protective and cardioprotective effects.
Citrus reticulata, fruit peel (chen pi)
Citrus peel (CP) is the pericarp of the ripe fruit of PAGE 46 | SUMMER 2021 | THE NATURAL THERAPIST VOL 36 NO. 4
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Citrus reticulata, Blanco, an evergreen of the family Rutaceae. The fruits are cultivated only for the peel, which is used in cooking, beverages and traditional medicine. The ripe fruits are collected in late autumn and early winter, the pericarp removed, cleaned and dried in the sun. The dried pericarps are moistened before being cut. Medicinal quality CP is aged for at least one year. The main medicinal uses are in digestive and respiratory disorders, such as indigestion with adbominal bloating, and respiratory conditions characterised by a productive cough and clear or white frothy sputum11,12. CP contains over 140 potentially active compounds, principally volatile oils, flavonoids and alkaloids as well as small amounts of vitamins and minerals. Ageing allows for the development of increased amounts of flavonoids, as well as changes in the composition of the volatile oils. Studies on animals and tissue cultures have shown to following effects12: • Gastric ulcers: Promotes healing of gastric ulcers, protects gastric endothelium from damage by ethanol (in rat models) • Gastrointestinal: Promotes gastro-intestinal motility (in rate and mouse models) • Use in chronic obstructive pulmonary disease (COPD): Prevents development of pulmonary fibrosis and thickened mucous (in rat and isolated mouse tissue models) • Anti-asthmatic: Antispasmodic action on tracheal smooth muscle (in isolated tissue from guinea pig), prevention of inflammatory cell infiltration and mucous secretion (in mouse model), decreases subepithelial fibrosis and smooth muscle hypertrophy to ameliorate structural remodelling of airways; reduces lung atelectasis (in mouse model) • Lipid metabolism: Anti-hyperlipidemic; antihypercholesterolemic, prevents hepatic steatosis by inhibiting hepatic fatty acid biosynthesis and increasing fatty acid oxidation (in mouse and rat models) • Antithrombotic: Inhibits platelet aggregation induced by collagen, arachidonic acid, adenosine diphosphate and thrombin (in mouse model) • Anti-atherosclerotic: Protection against age related atherosclerosis; stabilises aortic plaque and inhibits vascular inflammation (in cell cultures and in rabbit model) • Myocardial protection: Reduces the size of myocardial infarcts, protects against the effects of myocardial ischemia and reperfusion • Hepatoprotective: Protection against acute injury to hepatocytes by various toxins, including protection against hypercholesterolemia induced
liver injury (in mouse and rat models) • Anti-tumour: Inhibition of tumour cell proliferation and increased apoptosis of tumour cells (in cell cultures); almost complete reversal of nicotine-related damage to lung tissue (in rat model) • Anti-inflammatory: Reduces secretion of proinflammatory cytokines, e.g. NO, TNF-alpha, IL-1beta, and IL-6 (in cell cultures) • Anti-oxidative: Strong actions through various pathways, e.g. DPPH scavenging, hydroxyl radical scavenging, superoxide anion radical scavenging, hydrogen peroxide scavenging, and ferrous ion chelating (chemical tests) • Neuroprotective: Protection against cerebral ischemia-reperfusion injury; prevention of changes seen in dementia; ameliorates the effects of chronic mild unpredictable stress (in mouse and rat models)
Glycyrrhiza uralensis, root (zhi gan cao)
Glycyrrhiza is an herbaceous perennial of the Fabaceae (Leguminosae) family, growing to a height of 1-2m and is widely distributed in Siberia, Mongolia, China and Japan. The roots have a long history of use in food, medicine and more recently in skin care products13,14. In Chinese medicine, it is most frequently used at low dosage in formulas to moderate and harmonise the actions of the other herbs. It may also be used as a tonic for the Spleen and to boost the Qi in general, alleviate coughing by moistening the Lung, alleviate muscle spasm when combined with Paeonia root, also in the treatment of skin lesions, laryngeal inflammation, and as an antidote to various toxic substances15. It contains many different classes of compounds with biological activity, principally triterpene saponins and flavonoids; over 400 of these have been isolated to date. Studies on animals and cell cultures have
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shown that Glycyrrhiza root has the following actions13,15: • Anti-inflammatory: Suppression of proinflammatory cytokines and their receptors, actions on nuclear transcription factors, and removal of reactive oxygen species • Antioxidant: DPPH scavenging, reduces production of superoxide radicals, and reduces the activity of inducible nitrous oxide synthase (iNOS) • Immunoregulatory: Enhances protective immune responses and down-regulates potentially selfdestructive activities of the immune system • Antimicrobial: Against Staph. Aureus, Strep. mutans, P. gingivalius, Candida albicans, E. coli, Helicobacter pylori, amongst others • Antiviral: Against Hepatitis A & C viruses, HIV-1, SARS-related coronaviruses, respiratory syncytial virus, vaccinia virus and others • Anti-ulcer: Enhances mucosal healing in rat model of aspirin induced gastric ulceration • Anti-tumour: Inhibits proliferation of tumour cells and angiogenesis (in human breast, lung, prostate and oral squamous cell carcinoma cell lines) • Hepatoprotective: Protect against liver injury by carbon tetrachloride and other toxins in animal models • Mood and memory: Anti-depressant-like activity in stressed mouse and rat models. Improves learning and memory in rat and mouse models • Blood lipids: Reduces total cholesterol and LDL cholesterol, while also increasing the HDL-C (in animal and human studies)
Zingiber officinale, rhizome (sheng jiang)
Ginger is flowering herbaceous perennial of the Zingiberaceae family. The rhizome has a very long history of use, both culinary and medicinal throughout Asia. To date over 100 active and potentially active components have been isolated from the rhizome. These are primarily phenolic compounds and terpenes. The former includes gingerols, shogaols, paradols, zingerone and quercetin while the latter class includes β-bisabolene, α-curcumene, and zingiberene. Heating and drying alter the chemical composition, producing an increased amount of zingerone and shogaols, which changes the flavour profile17,18. In TCM, fresh raw ginger rhizome is used as a diaphoretic; the dry fried or baked fresh rhizome as a stomachic;
the dried rhizome as used in various internal disorders due to pathogenic Cold; and the charred dried rhizome as a styptic19. Studies on humans have confirmed many of the herb’s traditional actions18. • Anti-emetic: Useful in nausea and vomiting due to pregnancy, chemotherapy, and post-operative, and possibly also motion sickness • Enhances digestion: Improves gastric emptying and motility • Analgesic: Effective in relieving primary dysmenorrhea • Anti-inflammatory: In osteoarthritis with reduction of pro-inflammatory cytokines and perception of pain • Metabolic improvement: Positive effects on biochemical parameters in type 2 diabetes and obesity, reduces the risk factors for metabolic syndrome • Respiratory function: Alleviation of acute respiratory distress syndrome and symptoms of asthma
Ping Wei San: Empirical Research
In studies on rodents, tissue cultures, and humans, PWS has been shown to have the following therapeutic actions: • Alleviates the symptoms of chronic colitis, including ulcerative colitis by improving gut microbiota composition, (note: the following findings may either be due to the improved state of the microbiota or due to a direct effect of the herbal formula) as well as reducing neutrophil infiltration into the inflamed colonic mucosa, reducing pro-inflammatory cytokines such as IL-17A and IFN-γ, improving the expression of occludin activity to restore tight junctions between the colonic epithelial cells, reducing lipopolysaccharide production by the microbiota (in mouse model)20 • Potentiation of pacemaker activity of the Interstitial Cells of Cajal in the small intestine, which stimulates gastrointestinal motility (in mouse and tissue cultures)21 • Reduces disease activity in ulcerative colitis, by direct anti-inflammatory actions as well as actions on the intestinal microbiota (in mouse and tissue cultures)22,23 • Improves survival in cancer patients (in humans)24
Protocols for Gastro-Intestinal Disorders
The following protocols deal with the clinical use of PWS in biomedically defined functional dyspepsia, gastro-oesophageal reflux disorder, irritable bowel syndrome and chronic diarrhea. All of these disorders may be due to underlying small intestinal bacteria overgrowth (SIBO), the main diagnosis of which is
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made on assessment of risk factors (dietary habits, age, body shape, etc.), as well as clinical features (bloating, abdominal distention and discomfort, flatulence, loose stools or diarrhea, fatigue, generalised aches and pains, brain fog). Therefore, a separate protocol for SIBO is included below.
pain that is alleviated by warmth and pressure, intolerance of the cold, cold extremities, fatigue, poor appetite, muscular weakness: Ping Wei San (Magnolia & Ginger Combination) + Fu Zi Li Zhong Wan (Ginseng & Ginger Formula).
Functional dyspepsia - protocol 1 Main symptom - Epigastric discomfort after eating: Ping Wei San (Magnolia & Ginger Combination) + Shen Ling Bai Zhu San (Ginseng & Atractylodes Formula).
• Cold-Damp: Heavy sensation of the head and body, loose or irregular stools (sometimes loose, sometimes dry and sometimes initially dry then loose), increased bowel sounds, poor appetite, nausea, excessive vaginal discharge, pale tongue with a thick white coat. Ping Wei San (Magnolia & Ginger Combination) Plus Chai Hu Shu Gan Tang (Bupleurum & Cyperus Combination) a.k.a. Qi Mover Formula.
Small Intestinal Bacterial Overgrowth (SIBO)
Functional dyspepsia - protocol 2 Main symptom - Feels full after eating very little: Ping Wei San (Magnolia & Ginger Combination) + Jian Pi Wan (Ginseng & Citrus Formula). Functional dyspepsia - protocol 3 Main symptom - Acute epigastric pain and distention after eating: Ping Wei San (Magnolia & Ginger Combination) + Huo Xiang Zheng Qi Wan (Agastache Formula). Irritable Bowel Syndrome - protocol 1 Main symptom - Spleen deficiency pattern, with fatigue, epigastric and abdominal bloating, loose stools, worse with stress or emotional strain: Ping Wei San (Magnolia & Ginger Combination) + Irritable Bowel Formula. Irritable Bowel Syndrome - protocol 2 Main symptom - Liver-Gallbladder Damp-Heat pattern, with sense of abdominal distention, flatulence, nausea, malodorous stools, possibly steatorrhea: Ping Wei San (Magnolia & Ginger Combination) + Yin Chen Hao Wan (Artemisia & Rhubarb Combination). Gastritis (chronic) Main symptom - With sense of epigastric distention: Ping Wei San (Magnolia & Ginger Combination) + Xiang Sha Liu Jun Zi Wan (Saussurea and Cardamon Formula) a.k.a. Digestive Tonic Formula. Reflux or reflux oesophagitis Main symptom - Reflux of gastric contents, possibly also with persistent retrosternal pain that is worse when swallowing (i.e. oesophagitis): Ping Wei San (Magnolia & Ginger Combination) + Wen Dan Tang (Bamboo & Hoelen Formula), a.k.a. Clear the Phlegm Formula. Chronic diarrhea Main symptom - Spleen Yang deficiency pattern (Spleen Cold deficiency pattern), with dull abdominal
• Damp and Heat: Reflux, increased appetite, irritability, dry mouth, malodorous stools, dark coloured urine, red tongue with a yellow coat, possibly also small stones or sludge in the gallbladder. Yin Chen Hao Wan - Jia Wei (Artemisia & Rhubarb Combination) Plus Chai Hu Shu Gan Tang (Bupleurum & Cyperus Combination) a.k.a. Qi Mover Formula. • Food stagnation: Malodorous belching, absence of hunger sensations despite not having eaten for 4 hours or more, worsening of symptoms after eating, improvement of symptoms after passing flatus or stools, irregular (in terms of timing) bowel motions. Bao He Wan (Citrus & Crataegus) a.k.a. Digest-Aid Formula Plus Ping Wei San (Magnolia & Ginger Combination) Note: Continue for 2-3 months until appetite returns to normal (feels hungry again 4-5 hours after eating). • Spleen Qi deficiency: Fatigue, muscular weakness, poor appetite, craving for sweets, loose stools, brain fog, pale tongue with a thick white coat, weak-slippery or weak-soft pulse. Xiang Sha Liu Jun Zi Wan (Saussurea & Cardamon Formula) a.k.a. Digestive Tonic Formula Plus Ping Wei San (Magnolia & Ginger Combination) Note: Course of treatment 2-4 months. For references log into your ANTA Member Centre > The Natural Therapist > Journal Articles
THE NATURAL THERAPIST VOL 36 NO. 4 | SUMMER 2021 | PAGE 49
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