Tag: antibiotics

Medicine Security in Unsettled Times

On By philrasmIn UncategorizedLeave a comment

Medicinal plants in history

Health workforce shortages. Lengthening waiting lists. Hospital cost over-runs. Type 2 Diabetes, the hidden epidemic. Pandemic viruses.  Antibiotic resistance. Aging populations. Increasing meth use. There’s certainly more than a few nightmares for health policy analysts and decision makers to grapple with, when determining how to best allocate government health spending.

Apart from needing food and shelter, being able to resist the many life-threatening and injurious events and diseases that living on Planet Earth entails, has always been essential for our survival as a species. Thus in addition to having food security (access to sufficient healthy and nutritious food), the adequate supply of affordable and efficacious medicines, is a fundamental requirement to ensure good health and survival of human populations.

Humans have traditionally relied largely upon plants and fungi for medicines, and history shows they have served us well. However, despite the development of chemical drugs occurring only just over a hundred years ago, we often fail to acknowledge how the supply chain of medicinal plants, has greatly influenced the course of human history to date.

During the second world war, Cinchona officinalis (Peruvian bark) for instance, from which the valuable antimalarial drug quinine derives, was sourced almost exclusively from Java in Indonesia. However, after the Japanese invasion in 1942 and the capture by Nazis of processing facilities in the Netherlands, allied forces experienced a critical shortage of antimalarial drugs, which subsequently limited their operations in the southwest Pacific. Concerted efforts were therefore made to establish Cinchona cultivation in other locations, and new plantations in south America were developed(1).

Trade in black pepper, cinnamon and many other spices from India, China and south east Asia to Europe, were key contributors to the accumulation of wealth in early ancient cities such as Constantinople, Alexandria, Damascus and Venice.  Europeans fought the Crusades in large part to maintain a portal to the valuable spice trade. The Opium Wars between China, Britain and France in the mid 19th century, arose from China’s attempts to suppress the large European controlled trade of opium to China at that time.

These and many other examples, are reminders about how plants with powerful pharmacological properties have been important to humans. And how our access to them through either trade barriers and/or insufficient local production, can become seriously restricted.

Pandemic lessons

A key realisation that emerged early during the Covid-19 pandemic, was that despite years of well-funded research and development, drugs don’t provide all the answers when treating or preventing disease. A vaccine was developed and distribution commenced in near record time, but this still took many months and had many limitations. Distribution was delayed particularly to poorer countries, and a large percentage of the world’s population resorted as they always have done, to traditional plant medicines instead.

The pandemic also exposed the failure and cluster risks of modern global medicine supply chains. As levels of demand surged, enormous pressures were placed on already stretched supply chains, and widespread supply bottlenecks appeared.  During the Covid-19 lockdown in February 2022, pharmacy and supermarket shelves in Aotearoa NZ were virtually cleared of analgesics as people stockpiled. China’s zero-Covid policy during the pandemic prompted the closures of its many production facilities. India, which obtains most of its active pharmaceutical ingredients (API’s) from China, feared an imminent shortage of these critical raw materials, and thus promptly halted its exports of many medicinal products.  

Since the pandemic, shortages have occurred in supplies of widely used drugs such as the antidepressant fluoxetine, oestradiol patches used for menopause, and paracetamol. Similar shortfalls have happened in many other countries. The forthcoming withdrawal of the U.S. from the World Health Organisation, also doesn’t bode well for future international collaboration or worldwide medicine security.

Antibiotic resistance, is another ticking timebomb already responsible for over a million deaths a year globally, and placing a growing burden on health budgets. Rates of antimicrobial resistance are increasing in Aotearoa New Zealand and globally, including to last-line carbapenem antibiotics usually reserved for severe infections(2). It is a serious problem directly related to their overusage. Resistance to commonly used disinfectants and sanitizing agents, is also of increasing concern(3-5). Reducing their usage through increased utilization of plant derived medicines to help control infection, is a highly recommendable and evidence-based strategy.

Medicine shortfalls

Economic pressures, subsidisation policies and looser regulatory provisions in low-wage countries, have led to vital parts of medicine manufacturing being relocated to Asian countries over the past couple of decades. Historically also, global supplies of medicinal plants have largely derived from countries with low labour costs.

Most of the world’s pharmaceutical production, and around 30% of the production of plants for medicines, now takes place in China and India.  The high concentration of drug manufacturing steps in a small number of sites, often concentrated in the same geographical area, makes a supply chain vulnerable(6). Modern supply chain concepts such as just-in-time delivery, mean fewer reserves are maintained throughout the value chain.

The rapidly increasing frequency of so-called extreme weather events, reduced biodiversity, global warming and climate change, will also cause further threats to trade and supply chain security. These and other human factors are having increasingly serious impacts not only on food production and supplies, but also on the health and habitats of medicinal plants, and our ability to access them.

Geopolitical events, including wars or the introduction of trade tariffs, can also impact suddenly and significantly on our ability to access medicines which are manufactured or sourced from far away. With an increasingly unsettled international situation and tensions currently in a number of areas of the world, supply chain risks and strategies to mitigate these, should be high on a government’s agenda.

Medicine supplies – a government priority

Governments around the world have been considering and implementing additional measures to better secure medicine supply for their populations in the future. For a multitude of reasons, the inclusion of phytomedicines and their raw materials in these programmes, is essential.

Much was learned about the phytochemistry and potential medicinal properties of plants native to Aotearoa New Zealand during world war 2, when the government funded research in anticipation of a Japanese naval blockade limiting our imported medicine supply chain.

Cuba shifted to a more traditional and plant medicine based healthcare system following the introduction of a U.S. embargo in 1961. It now has some of the best health outcomes in the world, and its population’s average life expectancy is the same as that in the U.S. This has been achieved through an emphasis on prevention and education, universal coverage and access to treatment, within a highly proactive and well resourced primary healthcare system. Cuba’s spending per capita on health, is only a fraction of that allocated in the U.S., and less than half that spent in Aotearoa New Zealand (7).

Need for a Natural Health Agency

Healthy plant based foods and efficacious phytomedicines are powerful tools when building resilience to geopolitical or natural events which disrupt medicine supplies, and contribute greatly to better medicine security.

Aotearoa New Zealand is one of the best food and beverage producing countries in the world, with an ability to grow a wide range of foods and medicinal plants. From blueberries to kiwifruit, green tea to ginkgo, ginseng to saffron, numerous plants seem to have special characteristics and world leading levels of active phytochemicals, when grown here.

This capability together with a hard working and adaptable farming community, smart scientists and an innovative culture, provides the key criteria needed to further establish and promote a robust and export driven natural health product industry here. This could become a major contributor to our economy, as a sustainable, value added and profitable industry well aligned with our intrinsic and unique strengths as a country, and employ and retain both highly skilled and less skilled workforces. A scaled up commercial medicinal plant cultivation and processing industry would also help to mitigate risks from being over dependent on dairy and meat exports, and enable more self-sufficiency and medicine security, at the same time.

A New Zealand Space Agency was established in 2016, to be the lead government agency for space policy, regulation and sector development. This supports the ventures of companies such as Rocket Lab and Elon Musk’s SpaceX, and a NZ Space and Advanced Aviation Strategy 2024 to 2030 sets out the steps being taken to catalyse the sector’s growth.

In its current efforts to improve economic and wellbeing outcomes for Aotearoa New Zealand, it would be refreshing to see the government also implement the establishment of a Natural Health Agency. This could develop much needed new regulations for the sector, facilitate more research and development to support its growth, and improve patient access to evidence-based plant medicine treatments within primary health care. Expenditure on imported drug medicines would be reduced, and rural communities and our environment benefit through establishing new medicinal plant crops and related processing ventures.  

The natural health products sector is a complex but highly promising one for Aotearoa New Zealand, and a strategic, well integrated and coordinated bipartisan programme resourced over several years and insulated from our three year election cycles, would be an excellent use of limited government funds, in these changing times.

And it should lead to more resilience and medicine security, when the next pandemic or serious geopolitical event pulls the carpet out from our currently largely imported medicine supply chain.

References:

  1. Shanks GD. Historical Review: Problematic Malaria Prophylaxis with Quinine. Am J Trop Med Hyg. 2016 Aug 3;95(2):269-72. doi: 10.4269/ajtmh.16-0138.
  2. Ministry of Health , Manatū Hauora. Growing risk of antimicrobial resistance infection in New Zealand, 18 Nov 2024. https://www.health.govt.nz/news/growing-risk-of-antimicrobial-resistance-infection-in-new-zealand#:~:text=’Resistant%20strains%20of%20bacteria%20and
  3. Van den Poel B, Saegeman V, Schuermans A. Increasing usage of chlorhexidine in health care settings: blessing or curse? A narrative review of the risk of chlorhexidine resistance and the implications for infection prevention and control. Eur J Clin Microbiol Infect Dis. 2022 Mar;41(3):349-362.
  4. Kampf G. Acquired resistance to chlorhexidine – is it time to establish an ‘antiseptic stewardship’ initiative? J Hosp Infect. 2016 Nov;94(3):213-227. 
  5. Fernandes ÂR, Rodrigues AG, Cobrado L. Effect of prolonged exposure to disinfectants in the antimicrobial resistance profile of relevant micro-organisms: a systematic review. J Hosp Infect. 2024 Sep;151:45-59. 
  6. OECD Health Policy Studies. Securing Medical Supply Chains in a Post-Pandemic World. OECD Health Policy Studies, OECD Publishing, Paris. ISSN 2024-319X (online)
  7. M, Sarvestani MA. A Review on the Approach to Herbal Medicine in Cuban Healthcare System. Hispanic Health Care International. 2024;0(0). doi:10.1177/15404153241291747
  8. https://herbblurb.com/2019/06/21/why-new-zealand-grown-herbs-are-best/

Cinchona seedlings growing in Washington DC, USA, in November 1943 taken from Mindanao in the Philippines to re-establish quinine production in the Americas.

US Army Photograph, now in the public domain.

Herbs and Cancer

On By HerbBlurbIn Antibiotic Resistance, cancer, Environment, Herbal MedicineLeave a comment

A diagnosis of cancer is a highly stressful experience and increasingly, a common reason for people to consult a medical herbalist. With ongoing environmental exposures to carcinogenic agents, genetic predispositions and aging populations, this is likely to continue in coming decades.

Pharmaceutical company expenditure on research into new cancer drugs far outweighs that spent on developing new antibiotics or antidepressants, and advances in diagnosis, surgery, chemotherapy, radiotherapy and other cancer treatments, continue to be made. These can be expensive however, and waiting lists unacceptably long, in an increasingly stressed healthcare system. Also, conventional medicine is not always effective in the treatment of cancer and in many patients, its adverse effects and a relatively poor risk versus benefit rationale, are reasons for exploring herbal and other natural treatments.

Consequently, there is a huge amount of material on the subject available online, in magazines and books, including websites offering cancer cures through expensive clinic programmes, or ‘ready to take’ products that are heavily marketed. Soon after informing friends, colleagues and family, newly diagnosed patients tend to be inundated with suggestions and recommendations to take a wide range of ‘herbal remedies’, ‘dietary supplements’, ‘superfoods’ and other ‘alternative treatments’, several promising a cure, and strongly advocating against conventional treatments.  Care should be taken with all of these.

It’s fairly well known that a large percentage of chemotherapeutic drugs for cancer and leukaemia treatment are molecules identified and isolated from plants or their synthetic equivalents or close derivatives. Research on herbs has led to the development of anti-cancer drugs such as vincristine, vinblastine, paclitaxel, docetaxel, etoposide, teniposide and more.

These are however, strong and individual chemicals found in or derived from plants, they are not the plants themselves. It is inappropriate to extrapolate from the anticancer effects of large doses of these drugs (often given by injection rather than orally), and to claim that a plant extract from which chemotherapy drugs have been developed will also exhibit significant anticancer properties. Also, successful traditional uses of most of these plants for the treatment (as opposed to prevention) of cancer in humans is in fact poorly established. Finally, the likelihood of something that kills cancer cells in vitro (in laboratory cultures) doing the same thing when taken orally by human patients, is actually pretty low, just as the diabetes drug insulin is poorly absorbed when taken orally, and needs to be administered by injection.

Of more relevance from a scientific evidence-based perspective, are herbs and natural products that show useful outcomes (efficacy) when used in studies involving rats and mice (rodents). We now know that the mouse and human genomes are approximately 85% identical, meaning that if something works in mice, it has a reasonable chance of also working in humans. A 2005 Canadian study that found daily oral ingestion of Echinacea purpurea root from the age of 6 weeks until death from natural causes (‘old age’) reduced the incidence of spontaneous tumours and prolonged the life expectancy of mice, is therefore highly relevant(1, 2). This type of study should be given more prominence than claims that oral administration of Madagascar periwinkle (Catharanthus roseus, the source of the anti-cancer drugs vincristine and vinblastine), can help fight cancer.

The best contribution that most herbs make is in fact related to their preventive effects against human cancers, just as a diet rich in vegetables and low in or excluding red meat is now well established to do the same. Well-known herbs and spices such as ginger, garlic, turmeric, rosemary, nasturtium and watercress, are just some for which compelling evidence now exists as to their prophylactic properties. Incorporating these and many others into the diet or taking as a tonic on a regular basis, is likely to help reduce the likelihood of developing many different types of cancer.

When it comes to management of patients with a cancer diagnosis, one of the most promising contributions that herbs can make, is as adjunctive treatments to be taken alongside the anti-cancer drugs and other conventional interventions that modern medicine now has available. Evidence from a large number of animal studies and a growing number of human clinical trials, now strongly supports this approach, key outcomes being to help increase the chances of achieving remission, and/or reduce the likelihood of treatment-related adverse effects such as infertility and fatigue. Sadly, however, most of my cancer patients don’t come to see me until either after they have undergone chemotherapy, or where it is no longer an option, and a small number firmly opt against conventional treatment. This is perfectly their right and completely understandable, but may not have been their decision if they had been informed of the valuable contribution an individualised concurrent herbal treatment regimen can sometimes make.

It is in fact a reflection of the widespread lack of acknowledgement and appropriate regulation of highly trained medical herbalists, that most people’s view of virtually all herbs and herbal products, is that they are only things to be sourced from ‘over the counter’ (OTC) or internet outlets. This is a far cry from their view of drugs, where when suffering from most debilitating or serious conditions, the prescribing expertise of a medical practitioner or specialist such as an oncologist, is sought prior to embarking upon drug treatments.

While proactive selfcare should be actively encouraged as the best preventive approach to cancer and other illnesses. However, once cancer is diagnosed, while herbs are rarely a magic cure, seeking the best professional advice rather than relying on google apps or recommendations from those not trained in herbal medicine, is highly recommendable.

 

Refs:

 

  1. Brousseau M, Miller Enhancement of natural killer cells and increased survival of aging mice fed daily Echinacea root extract from youth. Biogerontology. 2005;6(3):157-63.

 

  1. Miller Echinacea: a miracle herb against aging and cancer? Evidence in vivo in mice.

Evid Based Complement Alternat Med. 2005 Sep;2(3):309-14.

 

 

Antibiotics and their effects on Plants

On By HerbBlurbIn Antibiotic Resistance, Antimicrobial chemicals, Environment, Herbal Medicine, PesticidesLeave a comment

Soil bacteria and fungi are a rich source of natural antibiotics, but the prevalence of human-made antibiotics and antibiotic resistance genes in soils, is an emerging concern. Antibiotics are widely used to promote livestock growth in modern non-organic agriculture, with poultry, cattle and pigs, being regularly treated with these antibacterial drugs. Millions of kilograms of antibiotics are released into the environment annually, much in the excrement of grazing animals, or through application of manure to agricultural fields(1). Discharge of human waste into waterways and the use of contaminated irrigation water or sewerage sludge to fertilise crops in many countries, is also a contributory cause. As a result, a higher level of antibiotic resistance is now apparent in conventional agricultural versus natural forest soils(2).

Soil and water-containing antibiotics constitute a potential route of human exposure to antibiotic resistance genes through their uptake by plants(3-8).  Uptake by plants can also have other effects, such as the accumulation of nitrofuran-type antibiotics in the edible parts of spring onions, and the subsequent metabolism of these into genotoxic and potentially carcinogenic hydrazine-containing metabolites(9).

The other consideration is the effects these human-made antibiotics have on the soil or plants themselves.  With human and animal health being intrinsically connected to that of plants and soil, and increasing research showing the many symbiotic and complex relationships between living organisms and their environment, effects of human-made antibiotics on plant health, should also be considered.

The high level of contamination with antibiotic residues and transferable resistance genes in pig manure applied to soil, has been shown to change the antibiotic resistant gene reservoir of the plant microbiome(10).  Carrots and lettuce can uptake amoxicillin and tetracycline(4), and tetracycline residues have toxic effects on both root and stems of germinating lettuce seedlings(11).  Oxytetracycline residues from cattle manure have also been shown to affect the diversity and type of nitrogen-fixing soil bacteria communities(12).

A recent European study has shown that even small amounts of antibiotics can have a range of potentially negative effects on plant traits(13). The comprehensive study examined the effects of three antibiotics (penicillin, tetracycline and sulfadiazine), on germination and growth of four plant species. These included two cultivated species (rapeseed, Brassica napus and common wheat, Tricicum aestivum), and two non-crop (herb) species (Shepherd’s purse, Capsella bursa-pastoria and Common Windgrass, Apera spicaventi). In farmland fertilised with manure containing antibiotic concentrations as typically found in agricultural soils, various effects on the plants were observed.

Main effects were delayed germination or reduced plant biomass. These effects varied markedly depending on the plant species concerned, but were most pronounced in the two herb species, particularly by penicillin and sulfadiazine. This suggests that different antibiotics could potentially affect the prevalence and types of species, and the diversity of natural plant communities near agricultural fields. Furthermore, these species-specific responses may not only alter the competitive abilities and makeup of the plant community, but also have secondary effects on other species such as pollinating and herbivorous insects(13).

Petrochemical residues and the use of non-organic agricultural pesticides and insecticides, are also starting to come under the spotlight as likely contributors to multi-drug antibiotic resistance among soil bacteria. A recent Chinese study has demonstrated that petrochemical residue -polluted soils were more than 15 times more likely than less-contaminated ones, to contain antibiotic resistance genes. This strong association of soil pollution with polycyclic aromatic hydrocarbons, suggests these may also be contributing to the growing amounts of antibiotic resistant genes in human-impacted environments(14).

In non-organic agriculture, soil bacteria can be continuously exposed to synthetic pesticides at sub-lethal concentrations, and a recent Indian study has found that insecticide-contaminated soil may have contributed to development of resistance to a range of different antibiotics, by several Bacillus species(15).

Silver nanoparticles are also now widely used in antibacterial products, and these inevitably discharge into aquatic environments and have been shown to affect the nitrogen cycle in phytoplankton and aquatic plant life(16).

Antimicrobial chemicals such as triclosan and triclocarban, which are used in some liquid soaps and toothpastes, can take a long time to break down in the environment and have been shown to have detrimental effects on aquatic organisms, and potentially contribute to antimicrobial resistance(17-19).

Soil and plant health are pivotal to the health of the planet and all its living organisms, and antibiotic drugs have saved many millions of lives. However, the widespread use of antibiotics in non-organic agricultural production systems particularly those involving animals, should be curtailed.

Refs:

  1. Popova IE et al, J Environ Sci Health B 2017; 52(5):298-305.
  2. Popowska M et al, Antimicrob Agents Chemother 2012; 56(3):1434-1443.
  3. Grote M. et al, Landbauforschung Volkenrode 2007; 57: 25-32.
  4. Azanu D et al, Chemosphere 2016; 157:107-114.
  5. Rahube TO et al, Can J Microbiol 2016; 62(7):600-7.
  6. Pan M et al, J Agric Food Chem 2014; 62:11062-11069.
  7. Kang DH et al, J AGric Food Chem 2013; 61:9992-10001.
  8. Kumar K et al, J Environment Qual 2005; 32:2082-2085.
  9. Wang Y et al, J Agric Food Chem 2017; 65(21):4255-4261.
  10. Wolters B et al, Appl Microbiol Biotechnol 2016; 100(21):9343-9353.
  11. Pino MR et al, Environ Sci Pollut Res Int 2016; 23(22):22530-22541.
  12. Sun J et al, Bioresour Technol 2016; 801-807, epub May 21.
  13. Minden V et al, AoB Plants 2017; 9(2):plx020.
  14. Chen B et al, Environ Pollut 2017; 220(Pt B):1005-1013.
  15. Rangasamy K et al, Microb Pathog 2017; 103:153-165.
  16. Jiang HS et al, Environ Pollut 2017; 223:395-402.
  17. Falisse E et al, Aquat Toxicol 2017; 189:97-107.
  18. McNamara PJ, Levy SB. Antimicrob Agents Chemother 2016; 60(12):7015-7016.
  19. Tremblay Louis, Environmental toxicologist, Cawthron Institute, Nelson, New Zealand Herald, 23 June 2017.