Herbs and Cancer

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.

 

 

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Antimicrobial Endophytes in Echinacea, Olive and Manuka

While plants are being extensively explored for new therapeutic properties and pharmacological activities, the communities of live fungi and bacteria known as endophytes that live between living plant cells, are also now being regarded as having many useful potential medicinal applications. Ironically, in recent years it is these microorganisms associated with plants rather than plants themselves, which seem to be receive much research interest.

Endophytes are microorganisms that live within a plant for at least part of their life cycles, without causing apparent disease or infections in the plant. Different endophytes seem to have affinities for particular plants, with which they have distinctive and cherished but complex interactions while each of them grows. They are for instance known to sometimes enhance host growth and nutrient gain, improve the plant’s ability to tolerate various types of stressors, and enhance the its resistance to insects and pests. The rrelationships that these bacteria and fungal communities have with their host plant varies from symbiotic to parasitic, to bordering on pathogenic.
Some very unusual and valuable bioactive substances are sometimes produced by these endophytes, such as alkaloids, phenolic acids, quinones, steroids, saponins, tannins, and terpenoids, and these are increasingly being recognized as sources of novel compounds which may help to maintain or solve not only the plant’s health challenges, but can also have applications in human and animal health problems.
Over the past few decades, some highly medicinal compounds produced by endophytic microbes lead to novel drug development. These include Taxol (paclitaxol), a complex diterpene alkaloid produced by the endophyte Metarhizium anisopliae found in the bark of the Pacific Yew (Taxus brevifolia) tree, and one of the most promising anticancer agents ever developed. Also streptomycin, an antibiotic produced from the bacterial endophyte Streptomyces.

Other endophytes possess antibacterial activities which may be useful in treating various infections, and in a world where antibiotic resistance is becoming a major public health threat, these are obviously of great interest. Exploring and bioprospecting these for potential antimicrobial compounds may well yield valuable new natural products or drugs to help in the fight against resistant organisms(1,2,3,4).

It now seems that bacterial communities colonizing Echinacea purpurea contribute to its well-known immune enhancing activity(5). American researchers have reported that Echinacea’s stimulating activity on monocytes (a type of white blood cell involved in engulfing and destroying harmful microbes), could be solely if not partially accounted for by the activities and prevalence of Proteobacteria, a family of bacteria found in the bacterial community associated with this medicinal plant.
A screen of 151 different endophytic bacteria isolated from three different compartments of Echinacea purpurea, revealed that several bacteria isolated from the roots are strong inhibitors of Burkholderia cepacia complex bacteria, a serious threat particularly in immune-compromised cystic fibrosis patients(6). One of these bacterial strains also showed antimicrobial effects against Acinetobacter baumannii, a pathogenic bacteria mainly associated with hospital-acquired infections, and Klebsiella pneumoniae, also increasingly incriminated in hospital infections(7). Interestingly, the type of bacteria and their antimicrobial effects varied considerably, according to which part of the plant (root, stem, leaves etc) they were associated with. This has resemblances to different plant parts of Echinacea having different phytochemical and thus pharmacological activities, such as Echinacea roots being richest in alkylamides and thus anti-inflammatory activities.

Endophytic fungi including Penicillium commune and Penicillium canescens (related to the Penicillium notatum mould from which the first antibiotic penicillin originated), have also been isolated from the leaves of olive (Olea europaea) trees, and several of these have also shown antibacterial as well as antifungal activities in recent work(8).

Finally, a rich endophyte community has recently been identified by Lincoln University researchers for the New Zealand native plant Manuka (Leptospermum scoparium). A total of 192 culturable bacteria were recovered from leaves, stems and roots, including some showing activity against the bacterial pathogen, Pseudomonas syringae pv. actinidiae(9), otherwise known by Kiwifruit growers as Psa. With Psa being a serious risk to the health of the Kiwifruit vine, it could be that these endophytic bacteria found within Manuka will make a useful contribution to ensuring the future health of the Kiwifruit industry.
While very few of all of the world’s plants have had their complete complement of endophytes studied, these are just three well established medicinal plants from which some highly active cohabitating bacteria and fungi have been sourced. Undoubtedly this area of research will receive much more attention due to growing concerns about antibiotic resistance, as there would seem to be a huge opportunity to find new and interesting endophytes among the wealth of different plants growing not only in soil, but also in waterways and oceans.
Refs:
1. Alvin A et al, Microbiol Res 2014; 169(7-8)L483-495.
2. Martinez-Klimova E et al, Biochem Pharmacol 2016; Oct 27.
3. Kealey C et al, Biotechnol Lett 2017; Mar 8 (epub ahead of print)
4. Tanwar A et al, Microbiol Path 2016;101:76-82
5. Haron MH et al, Planta Med 2016; 82(14):1258-1265.
6. Chiellini C et al, Microbiol Res 2017; 196:34-43.
7. Presta L et al, Res Microbiol 2017; 168(3):293-305.
8. Malhadas C et al, World J Microbiol Biotechnol 2017; 33(3):46.
9. Wicaksono WA et al, PLoS One 2016; 11(9):e0163717.

Why Herbs Should Be the First Choice of Treatment for Acute Anxiety

Anxiety can manifest in a wide range of ways. Apart from the internal emotional fearfulness, symptoms can include irritability, agitation, muscle tension, palpitations, sweating, insomnia, breathlessness, poor concentration, reduced socialisation and ability to undertake everyday activities. It is the most prevalent mental health disorder affecting children and adults, but many more people are dealing with problematic anxiety symptoms without any diagnosis.

In our increasingly changing world, where our daily exposure to stressful stimuli and life challenges can produce a rising barometer of worries, anxiety is often a major impediment to leading a fulfilling and happy life. Like most other health woes, humans have long pursued various practices to help overcome anxiety, the most popular of which is alcohol. Then there are drug medications, which have long been used to relieve anxiety, and remain widely prescribed.

Barbiturates were the first of these, sedative and anticonvulsant drugs which became popular particularly with sleep-deprived young mothers in the middle of last century, but which lead to the overdose deaths of thousands of people, including Elvis Presley and Marilyn Monroe. The next day ‘hangover effect’ from barbiturates was also always a problem, and development of a new chemical group of anxiolytic (anti-anxiety) and sedative drugs known as the benzodiazepines, lead to these superceding the barbiturates for the treatment of anxiety and insomnia. Benzodiazepines seem to act predominantly through stimulating GABA (gamma amino butyric acid) receptors in the central nervous system, and the commercialisation of Valium® (diazepam) by Roche in 1963 marked the start of a period during which this and other benzodiazepine drugs such as lorazepam, alprazolam and clonazepam began to be widely prescribed by GP’s and psychiatrists for anxiety and sleep difficulties. Between 1969 and 1982 Valium® was the most prescribed drug in the U.S., during which time Roche’s share price soared.

While safer than barbiturates, and effective as a ‘quick fix’ for anxious feelings or insomnia, safety concerns for benzodiazepines soon emerged. Feelings of fatigue, or a hangover the following day when taken as sleeping tablets, and a wide range of other side effects are all too common experiences. Most significant of these is the development of tolerance when they are used for more than a short period of time. As anyone who has been through it will testify, withdrawing from long term benzodiazepine use is a hugely stressful, unpleasant and often very protracted experience.

Feelings of depression can both contribute to or arise from excessive anxiety, and it is not uncommon for feelings of low mood and a low tolerance to stress, to be experienced together with anxiety. Apart from GABA, neurotransmitters such as serotonin, adrenaline and dopamine are intrinsically involved in influencing our emotions and mood, interacting together in complex ways that scientists still have little understanding of. It is therefore not surprising that many SSRI’s (selective serotonin reuptake inhibitor) drugs, used primarily as antidepressants, can have an anxiolytic effect in some people, and in many countries, these are often prescribed instead of or together with benzodiazepines, for anxiety conditions.

While sometimes effective as anxiolytics and less likely to produce adverse effects than most older generation tricyclic antidepressants, some find that SSRI’s can cause or increase anxiety feelings, or experience any one or more of a wide range of unpleasant side effects including insomnia, weight gain, emotional numbing or sexual dysfunction.

Another class of non-benzodiazepine sleeping tablets, the so-called  ‘Z-drugs’ such as zopiclone and zolpidem, have become popular in recent years, and while initially thought to be less habit-forming than benzodiazepines, they can also be very difficult to withdraw from after more than short-term use.

A large number of herbs have been traditionally used for nervous conditions and their anxiolytic effects, several of which have been shown in clinical trials to be beneficial as anxiety treatments. These include Chamomile, Skullcap, Passionflower, Valerian, Kava, Lemon balm and Withania.  Despite the number of well-designed trials undertaken to date being relatively low, and results sometimes variable depending on the particular herbal product(s) and dosages used, results are encouraging and in all cases show a better safety profile than for comparable anxiolytic drugs.

Of these, Kava (Piper methysticum), is the most studied, and is a non-addictive anxiolytic with great potential to treat anxiety. Its effectiveness in treating anxiety has been affirmed through several clinical trials and meta-analysis(1-3). While case reports of liver toxicity associated with kava usage lead to its restriction in some countries at the end of last century, use of the wrong plant part as raw material, or use in combination with alcohol or various drugs, were likely contributory factors. Also the frequency of such adverse events reports was substantially less than that for paracetamol, a commonly used analgesic.

Aerial parts of the herb Passionflower (Passiflora incarnata), have also been taken for anxiety for many centuries, and in a trial involving 36 outpatients with generalized anxiety disorder, it was as effective as the benzodiazepine drug oxazepam, but unlike oxazepam caused no impairment of job performance(4).

Roots of the herb Withania (Withania somnifera, Ashwagandha), have a subtle but powerful nervous system and adrenal tonic action, which insulates the nervous system from stress, and enables the adrenal glands to be better prepared to respond appropriately to stressful stimuli. A large number of scientific papers now support its applications for stress-associated anxiety conditions, including several recent human clinical trials(5,6).

While further studies involving greater participant numbers and longer term treatment are needed to identify optimal dosages and phytochemical makeup of the treatments involved, the fact that most herbal anxiolytic agents are safe and have the same or only a slightly higher incidence of adverse effects to placebo, is clear. It is therefore logical that before reverting to drug medications, more likely to produce unwanted adverse effects and in some cases long term dependency, herbal anxiolytics should be tried, in anxiety conditions.

Refs:

  1. Sarris J, Aust NZ J Psychiatry 2011; 45(1):27-35.
  2. Sarris J, J Clin Psychopharmacol 2013; 33(5):643-648.
  3. Savage K et al, Trials 2015; 16:493.
  4. Akhondzadeh S et al, J Clin Pharm Ther 2001; 26(5):363-367.
  5. Chandrasekhar K et al, Indian J Psychol Med 2012; 34(3):255-262.
  6. Pratte MA et al, J Altern Complement Med 2014; 20(12):901-908

Manuka & More

I recently attended a very interesting Hui (Gathering) in Ruatoria and Te Araroa on New Zealand’s East Coast, entitled ‘Manuka and More’.  Around 15 researchers from Crown Research Institutes and industry representatives including myself gave talks on subjects related to the NZ native tree Manuka (Leptospermum scoparium), which grows prolifically around the coast, and provides nectar for honeybees which produce manuka honey.  Manuka honey is being increasingly recognised as a highly active natural product with benefits as an antimicrobial and wound healer, and global demand for it has soared in recent years. Similarly the volatile oil of manuka has antimicrobial and anti-inflammatory properties, and is increasingly sought after.

manuka-4
Studies into what makes manuka honey so special, and characterisation of its many different chemotypes and genotypes, has been a focus of much research in the past decade. To the East Coast locals, manuka was once regarded mainly as a scrub plant and nuisance that was cleared to make way for pastural farming of sheep and cattle, but with honey prices continuing to rise and there being little money now in wool, manuka is being allowed to re-establish itself in many areas. Additionally, a lot of effort is now going into planting nursery-raised seedlings bred from chemotypes thought to produce optimal quality and yields of honey and oil.

With the plantation model being in its relative infancy, research into the potential effects of planted manuka on the local pre-existing chemotypes, and whether the yield of honey or oil will in fact be as high as hoped from these cultivated plants, is an area for ongoing investigation.

A growing number of local East coast people and Maori-controlled enterprises are now getting into the honey producing business, and the number of hives in NZ has nearly doubled from around 350,000 to 700,000 over the past 5 years. The sustainability of this level of honey production is another area requiring research, particularly as bees only feed off manuka (and kanuka) nectar for around 6 weeks each season. Monitoring their activities and ensuring they have sufficient food for the remaining 46 weeks of the year, is important.

Of the various flowering plants NZ honey bees feed off, Willow trees (Salix species), are an important source of pollen and protein for bees to feed their brood in the spring time, thus helping them to expand their population and gain maximum strength before the start of the honey flow season. Around the East coast a large number of willows grow particularly along waterways and on erosion prone areas. While the biggest problems for young willows are grazing animals and pests such as possums, rabbits and hares, an emerging pest is also the giant willow aphid which first appeared in NZ in 2013. Apart from infesting willow trees, this can boost the populations of wasps that attack honey bees.

smaller-leptospermum-scoparium-flower-manuka-flower-julyWhile not pleasing to all, other flowering plants such as the invasive introduced gorse (Ulex europaeus), presently plays an important role as a food source for bees in some areas. However, we should be planting other native species such as Hoheria (Hoheria populnea),  Whauwhaupaku or Five Finger (Pseudopanax arboreus) and many others, to provide pollen and nectar as a replacement for that from this imported thorny plant.

Other research presented at the Hui related to the role that mycorrhizal fungi, which grow on the roots of most plants, may have in ensuring the health of the manuka shrub. Most plants co-exist with these fungi, which help them better absorb nutrients from the surrounding soil, and can also help with disease prevention. Also monitoring for potential disease or infestation threats to Manuka such as Myrtle rust, a serious fungal disease not present in New Zealand, but which can affect other plants in the myrtle (Myrtaceae) family.

Recent studies suggesting that manuka seems to be useful at soaking up excremental pollution, and thus may be an ideal tree to plant alongside waterways polluted by effluent runoff from our overly intensive dairy industry, point to yet another exciting development in our understanding about this amazing native plant.

Overall, the range and quality of the diverse areas of research being undertaken, was most encouraging. This combined with the hands-on experience and traditional knowledge of the local Ngati Porou people who are increasingly finding meaningful employment opportunities from manuka-based businesses, gives great encouragement to the future social, economic and environmental wellbeing, of this beautiful area of New Zealand.