Lemon balm (Melissa officinalis) grows really well in my garden, and also in the wild in various locations in New Zealand and other countries. It has a distinctive lemony scent when rubbed, and a plethora of medicinal uses.

Lemon balm was a sacred herb to the ancient Greeks, and widely planted by early beekeepers to keep honeybees happy and well fed with nectar. Its healing properties were increasingly recognised during the Medieval and Renaissance ages, and by the 9th century it was widely planted in monastery gardens. Widespread medicinal uses were described by the Greek and Persian physicians Dioscorides and Avicenna and reiterated by the 17th century English herbalist Nicholas Culpeper, who also described it as ‘an excellent remedy for a cold and moist stomach’, which ‘cheers the heart, refresheth the mind, takes away grief, sorrow and care, instead of which it produces joy and mirth’(1).

Like other members of the lamiaceae (mint) family of plants such as peppermint, basil, rosemary and sage, aerial parts of lemon balm can be a valuable component to the management of nervous dyspepsia and digestive conditions such as bloating and irritable bowel syndrome.  Perhaps more than anything though, its potential applications for nervous system conditions such as anxiety and mood disorders, have been increasingly supported by animal and human clinical studies in recent years.

Administration of a single dose of lemon balm to healthy student volunteers was first reported to improve cognitive performance in a laboratory model of acute stress by British researchers in 2002 (2-6). These and subsequent experiments measured a reduction in the negative effects of stress on mood and improved self ratings of calmness, while not causing any reduction in accuracy whilst undertaking required laboratory tasks. These effects were apparent for up to 6 hours following lemon balm administration.

A pilot trial in which 20 volunteers suffering from mild to moderate anxiety disorders and sleep disturbances took lemon balm for 15 days, found most responded to treatment, with a reduction in anxiety and associated symptoms, and an improvement in sleep(7). While this was an open-label study with no placebo, and clinician contact may have contributed to the symptom improvement observed, it supports further controlled trials with larger patient numbers.

Other clinical studies have expanded our understanding of lemon balm’s relaxant properties. Favourable effects were reported in an Iranian trial in which lemon balm capsules were taken twice daily by young women with premenstrual syndrome over a 3 month period(8). Those who received lemon balm reported a significant reduction in psychosomatic symptoms, anxiety and sleeping disorder, as well as improvements in social functioning difficulties.

Results from two studies involving combinations of lemon balm with other plant extracts, are also of interest. These include a small placebo controlled trial using a combination of lemon balm with the Iranian herb Nepeta menthoides (Ostokhodus) which improved insomnia, depression and anxiety in a group of 67 insomniacs(9). A recent Swiss retrospective study also investigated the effects of a combination product containing lemon balm, valerian, passionflower and butterbur extracts on the prescription pattern of benzodiazepines and other psychoactive drugs in hospitalised psychiatric patients. This found concomitant prescribing of benzodiazepines for anxiety to be lower in patients taking the combination herbal product, although the level of prescribing of hypnotics and antidepressants (including herbal ones), was higher(10).

Anxiety disorders can affect cardiovascular parameters such as the heart rate and blood pressure, and a diagnosis of a cardiovascular medical condition can cause or exacerbate anxiety. Culpeper’s comments and other traditional use information allude to an affinity for the cardiovascular system for lemon balm, and in fact two clinical trials have found favourable outcomes in this regard.

Treatment of a group of 71 volunteers suffering from an abnormal awareness of heartbeat with the equivalent of 5 grams dried lemon balm leaves daily for 14 days, resulted in less frequent and less intense symptoms of heart palpitations (11, 12). Lemon balm treatment also reduced the number of patients with concomitant anxiety and insomnia disorder in this study. Another small trial reported a reduction in symptoms and signs of depression, anxiety, stress and sleep disorder, in a group of patients with chronic but stable angina following an 8 week course of lemon balm treatment(13).

Recent animal studies also provide further interesting data. Adipogenesis and obesity can also accompany chronic stress, and the finding that lemon balm lead to improvements in fasting blood glucose, glucose tolerance, and pancreatic dysfunction in female obese mice, has implications for the potential prevention of visceral obesity and insulin resistance in obese premenopausal women(14).

Another study further evaluated the effects of a hydro-alcoholic extract of lemon balm in a behavioural study in mice(15). Reversal of behaviours reflective of anxiety and helplessness occurred following lemon balm treatment, effects accompanied by enhanced enzymatic antioxidant activities and restoration of serum corticosterone levels previously disrupted by stress.

The mechanism(s) of action of lemon balm’s anxiolytic and possible mood modulating effects, seem to involve the gamma amino butyric acid (GABA) neurotransmission system(16). In vitro studies have reported inhibitory activity against GABA transaminase for lemon balm extracts, an enzyme involved in metabolising this endogenous ‘relaxant’ neurotransmitter.

The collective picture emerging for lemon balm and how it affects our brains and functioning, is that of a uniquely compelling and probably dose-related combination of relaxant as well as cognitive enhancing properties. Possible applications in those with accompanying digestive or cardiovascular conditions or a predisposition to obesity or depression, are also suggested. These attributes together with the various other established and likely health benefits of this easy to grow plant, would seem to make it an ideal daily tonic to help with stress management, in the modern world.


  1. Culpeper, Nicholas. (1653). A Complete Herbal. London, Peter Cole.
  2. Kennedy DO et al,  Pharmacol Biochem Behav. 2002 Jul;72(4):953-64.
  3. Kennedy DO et al. Psychosom Med. Jul-Aug 2004;66(4):607-13
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  5. Rasmussen PL, Phytonews 20, published by Phytomed Medicinal Herbs Ltd, Dec 2004.ISSN 1175-0251.
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  7. Cases J et al, Med J Nutrition Metab. 2011 Dec;4(3):211-218.
  8. Heydari N et al, Int J Adolesc Med Health. 2018 Jan 25;31(3):/j/ijamh.2019.31.issue-3/ijamh-
  9. Ranjbar M et al,egr Med Res. 2018 Dec;7(4):328-332 
  10. Keck et al, Phytother Res. 2020 Jun;34(6):1436-1445.
  11. Alijaniha F et cl, J Ethnopharmacol 2015; 164:378-384.
  12. Rasmussen PL, Phytonews 41, published by Phytomed Medicinal Herbs Ltd, Mar 2017.ISSN 1175-0251.
  13. Haybar H et al, Clin Nutr ESPEN. 2018 Aug;26:47-52.
  14. Lee D et al, J Ethnopharmacol. 2020 May 10;253:112646.
  15. Ghazizadeh J et al, Exp Physiol. 2020 Apr;105(4):707-720
  16. Awad R et al, Can J Physiol Pharmacol. 2007 Sep;85(9):933-42

Calendula – a powerful healing herb

Flowers of the English or Pot Marigold (Calendula officinalis), have long been recommended and used for minor cuts, grazes, and slow healing wounds. However despite this popularity, and it being approved by the European Medicines Agency as a traditional medicinal product(1), clinical trials involving calendula have been few and far between until recently. Now though, results from at least 10 clinical trials involving use of topical dosage forms of calendula for a range of clinical conditions, have been published.

Preventive effects against radiation-induced dermatitis were reported by French oncologists in a study involving 254 breast cancer patients in 2004. Only 41% of patients who received calendula ointment treatment after each radiotherapy session subsequently developed acute dermatitis, compared to 63% of those given topical trolamine treatment. Reduced radiation-induced pain, and less frequent interruption of the radiotherapy treatment regimen, were other positive outcomes associated with calendula ointment application(2,3).

A more recent Australian trial involving 81 women undergoing breast cancer radiotherapy compared topical calendula with the standard sorbolene treatment. The prevalence of radiation-induced dermatitis was 53% in the calendula group and 62% in the sorbolene group. While this difference was not statistically significant, the study was underpowered due to less than half the recruitment target of 178 patients, being achieved(4). Use of a calendula mouthwash has also been reported to reduce the intensity of radiation-induced oropharyngeal mucositis in patients with head and neck cancers undergoing radiotherapy(5).

Other trials have evaluated calendula in the management of venous leg ulcers. The first of these compared twice daily application of calendula ointment with saline solution dressings, in a group of 34 patients over a 3 week period(6). After the third week, the total surface of the ulcers decreased by an average of 41.7% in the calendula group, but only 14.5% in the group treated with saline dressings. In four calendula treated patients, complete wound closure was achieved. 

A Brazilian clinical trial evaluated the effectiveness of a spray application of calendula extract on the healing rate of 38 non-healing diabetic leg ulcers(7). Treatment entailed twice daily application of calendula or standard hospital procedure, consisting of the enzyme collagenase, the antibiotic chloramphenicol, and 1% silver sulfadiazine cream for a period of 30 weeks or until ulcers healed.

After 12 weeks of treatment, 39% of wounds treated with calendula were completely closed, but none in the standard treatment control group. After 30 weeks treatment, 72% achieved complete wound closure, compared to only 32% in the control group. Average healing times were 12 weeks in the calendula treatment group, versus 25 weeks in the control group. No adverse events were observed during calendula treatment.

While confirmation of these benefits through a trial involving greater patient numbers is needed, these studies suggest a significant acceleration of venous ulcer healing through twice daily application of topical calendula products.

A shortened duration of caesarian wound healing, has also been recently reported by another Iranian trial involving 72 women, through twice daily application of calendula ointment versus the standard hospital post surgical routine(8). Faster wound healing after episiotomy, has also been reported from an Italian trial recently(9). Women who received calendula ointment compared to standard care benefited from a significantly lower pain level starting from day two after episiotomy, as well as improved wound healing in terms of redness and oedema.

Several mechanisms of action are likely to be responsible for these effects of calendula on wound healing or dermatitis prevention. Beneficial effects on granulation tissue and new tissue formation during acute wound healing have been observed in vitro using human immortalised keratinocytes and human dermal fibroblasts(10). A recent review of calendula’s effects on acute wounds which incorporated 7 animal and 7 clinical studies, reported faster resolution of the inflammation phase and increased production of granulation tissue, in acute wounds treated with calendula(11).

Another traditional application of calendula is for the treatment of fungal infections, and findings from another Iranian trial comparing a 7 day treatment of calendula or clotrimazole cream for the treatment of vaginal candidiasis in a group of 150 women aged 18–45 years, are of interest(12). While a higher rate of negative testing for candidiasis was measured at 10-15 days post treatment in the clotrimazole than in the calendula group (74% vs 49% negative tests for candidiasis), when further testing was undertaken at 30-35 days after treatment, calendula treatment was associated with 77% testing negative for candidiasis, versus only 34% in the clotrimazole group. Signs and symptoms were similar in both groups at 10-15 days post treatment, but significantly less in the calendula group, at the later follow-up. Thus vaginal administration of calendula cream was effective in treating vaginal candidiasis, and while the onset of effect was delayed compared to clotrimazole, a greater and longer term effect was seen following calendula treatment(12)

With antibiotic resistance becoming an increasing problem, not to mention the high and rising costs of wound care management associated with aging populations and the impact of diabetes, investigation into plant-based alternative wound treatment agents, is gaining more research attention.

The orange-yellow flowers of calendula have a convincing reputation for helping to enhance wound healing in traditional herbal medicine. Encouragingly, its potential usefulness in wound care management and fungal infections such as candidiasis, is being increasingly validated by a growing number of clinical studies published in recent years.


  1. https://www.ema.europa.eu/en/medicines/herbal/calendulae-flos.
  2. Pommier P et al, J Clin Oncol. 2004 Apr 15;22(8):1447-53.
  3. Rasmussen PL, Calendula for radiotherapy-induced skin damage. Phytonews 20, published by Phytomed Medicinal Herbs Ltd, Dec 2004.ISSN 1175-0251.
  4. Siddiquee S et al, Australas J Dermatol 2020 Sep 23. doi: 10.1111/ajd.13434. Online ahead of print.
  5. Babaee B et al, Daru. 2013 Mar 7;21(1):18.
  6. Duran V et al, Int J Tissue React. 2005;27(3):101-6.
  7. Buzzi M et al, Ostomy/wound Management 2016; 62(3):8-24.
  8. Jahdi F et al, J Family Med Prim Care. Sep-Oct 2018;7(5):893-897.
  9. De Angelis CD et al,  Matern Fetal Neonatal Med. 2020 May 27;1-5. doi: 10.1080/14767058.2020.1770219. Online ahead of print.
  10. Nicolaus C et al, J Ethnopharmacol. 2017 Jan 20;196:94-103.
  11. Givol O et al,Wound Repair Regen 2019 Sep;27(5):548-561.
  12. Saffari E et al, Women Health Nov-Dec 2017;57(10):1145-1160.

Echinacea in the time of a pandemic

While here in New Zealand we are now very fortunate that very low numbers of new Covid-19 cases are being reported, and the wearing of masks and social distancing practices are starting to seem like a distant memory to many people, much of the world is not so lucky. As our days lengthen and thoughts of a forthcoming summer break brighten our days, the virus continues to wreak havoc and cause huge stress and loss of life, in so many other countries.

Over the next few months those lucky enough to be living in New Zealand will hopefully be able to attend concerts, shows, sports events and festivals again, and these will help facilitate some kind of ‘return to normality’ from our spells in lockdown over autumn and winter. However, the coming summer may become a period of relative respite, because pressure will grow to further reopen our borders, and no public health or border protection system is invincible. Therefore as we prepare for or engage with gatherings involving larger numbers of people where the risk of community transmission is greater, ensuring a healthy immunity over the next few months and then as we move into autumn, remains important.

Evidence of efficacy is often a challenging subject to address with phytomedicines, due to the phytochemical diversity of whole plants and the many different extracts and products to evaluate.  Not to mention the difficulties in accessing funding to undertake clinical trials where large patient numbers and/or lengthy treatment interventions are often required to achieve adequate statistical power.

Pandemics have afflicted the human race throughout our entire history, and plant-based medicines have been a cornerstone of how we dealt with these, way before single active chemical interventions (drugs or vaccines) were conceived. The current Covid-19 pandemic is a reminder that drugs are often unable to protect us against everything that the natural world throws at us.

Significant evidence indicates that a dysregulated innate immune response contributes to the clinical presentation of patients with severe Covid-19 infections(1,2).  

Covid-19 pathology

A meta-analysis of 21 studies, found that biomarkers of inflammation, cardiac and muscle injury, liver and kidney function and coagulation measures were significantly elevated in patients with both severe and fatal Covid-19. In particular, interleukins 6 (IL-6) and 10 (IL-10) and serum ferritin were strong discriminators for severe disease(2).

These elevations in inflammatory cytokines have led to the view that an immunity-mediated “cytokine storm,” is primarily responsible for the toxicity and end-organ damage mediated by Covid-19 infections. The combined effect seems to be promotion of granulocyte infiltration into the lungs, resulting in acute lung injury & sometimes death due to primary respiratory failure. An abnormal immune mechanism and upregulationof genes involved in apoptosis, tissue injury & oxidative damage, can also damage organs such as the heart, kidney and liver, and lead to multiple organ exhaustion and shut down, or residual damage to these post infection recovery.

Attenuation of the peak immune response, either with corticosteroids such as dexamethasone or more specifically targeting of interleukin IL-6 or IL-1β to limit damage to other organs during the early immune response, may benefit some patients(3,4). There are risks with such drug therapy however, as early immune hyperactivity may be a reflection of high viral burden and a much-needed protective antibody response, and our understanding of the how this clever coronavirus influences immune mechanisms at different infection stages in different patients, is still lacking.

Echinacea’s immunomodulatory effects:

In western herbal medicine, one of the most highly regarded phytomedicines from both a traditional as well as evidence-based perspective, is the well known Echinacea (Purple coneflower). Two species are generally used, Echinacea purpurea and Echinacea angustifolia.

A principle application claimed for Echinacea-based products over the last 50 years has been as a prophylactic or treatment for colds and influenza. Several clinical trials have shown beneficial effects of Echinacea in this context, although others have had less favourable outcomes, particularly where product quality or doses used have been suboptimal(5). Few adverse events have been reported, and the risk of interactions is low(6).  But what is the evidence that this phytomedicine can help us during the current global Covid-19 pandemic?

A number of natural products including Echinacea have shown in vitro effects against the SARS-CoV-2 coronavirus responsible for Covid-19(7-9), although these are limited to date, and clinical studies are lacking.

Echinacea is frequently portrayed as an ‘immune stimulant’ herb in the popular media and therefore sometimes claimed to be contraindicated in situations where elements of the immune system are ‘overactivated’. This is a gross simplification of the effects of this phytomedicine, as its widespread traditional use for conditions that are largely inflammatory and autoimmune in nature has been largely overlooked, as have anti-inflammatory properties particularly for its constituent alkylamides and high alkylamide-containing products(10-12).

Studies using different types of Echinacea purpurea on murine dendritic cells (immune cells in mice which play important roles in activating and initiating immune responses) found immunostimulatory, immunosuppressive, and/or anti-inflammatory actions can all be produced, with distinctively different outcomes depending on the plant part and extraction method used(13). Furthermore, different actions appear to occur during uninfected and infected states, suggesting that there is much more to Echinacea than a simple immune stimulant action. These include its influences on cytokine secretion.

Key outcomes when Echinacea is taken by healthy volunteers seem to be increased numbers of circulating white blood cells, monocytes, neutrophils and natural killer (NK) cells, and thus enhancement of the non-specific (innate) immune system. This is thought to improve the body’s ability to maintain immunosurveillance against a variety of potential viral or bacterial pathogens or spontaneous-developing tumours.  Daily administration of Echinacea purpurea root prolonged the life spans of normal mice(14), and Echinacea purpurea had a suppressive effect on spontaneously occurring leukaemia caused by a murine leukaemia virus(15). It has also been reported to have beneficial effects on stress-induced immunosuppression in rodents, by increasing splenocyte proliferation and NK cell activity, while restoring and modulating T lymphocyte subsets and serum cytokine levels(16). These essentially prophylactic effects were largely related to enhancement of immune systems.

Administration of Echinacea during an infection however, is likely to produce somewhat different outcomes, as is shown by various studies(17-19).

Rhinovirus infection in a line of human bronchial epithelial cells was shown to induce or increase the secretion of at least 31 different inflammatory cytokines and chemokines, including the interleukins IL-1β, IL-3, IL-5, IL-6, IL-17, granulocyte-macrophage colony stimulating factor, interferon-gamma (IFN-ﻻ), and tumor necrosis factor (TNF-α).  Echinacea treatment of the infected cells over 48 hours however, reversed this stimulation of inflammatory cytokine and chemokine levels, either partially or completely(17)

Subsequent studies reported that Echinacea purpurea reduced rhinovirus induced secretion of interleukin-6 and interleukin-8 from human bronchial epithelial cells, regardless of whether it was added before or after virus infection(18).

In contrast to the above effects on infected cells, when uninfected cells were treated with Echinacea, cytokine levels were mostly increased, particularly by a root-derived rather than fresh whole plant-derived preparation.

These investigations provide support for an immunomodulatory mode of action for Echinacea, whereby the immune system is enhanced when Echinacea is taken in the absence of infection, but excessive and possibly damaging inflammation during a viral infection may be reduced. This suggests not only a useful prophylactic effect of Echinacea against unwanted viruses, but also a potential usefulness during upper respiratory tract viral infections such as rhinovirus. While much more work needs to be done, these effects could extend also to other highly pathogenic viral infections in which excessive activation of elements of the immune response and a sudden and unregulated increase in the production of pro-inflammatory cytokines, may occur(19,20).

An assessment of human trials involving Echinacea use for up to 4 months, failed to locate any evidence of cytokine storm(21). Furthermore, those which measured changes in cytokine levels in response to Echinacea use, provide results which are largely consistent with a decrease in pro-inflammatory cytokines. While there is currently no research on the therapeutic effects of Echinacea in the management of cytokine storm, this evidence suggests further research is warranted.

Traditional and modern day use experience points to potential benefits and few if any contraindications of daily prophylactic use of Echinacea to further enhance our immunity to contracting infection, beyond advisable public health measures such as social distancing and good hygiene. Additionally, while much is unknown and more research is advocated, this highly regarded phytomedicine could also provide useful anti-inflammatory and immunomodulatory effects as part of the very challenging management of seriously ill patients, where a hyperinflammatory situation seems contributory to worse outcomes.

Secondary bacterial infections:

Secondary or co-existing bacterial infections are a common cause of pneumonia and death in patients with viral infections of the respiratory tract. Viral infections can express bacterial adhesion receptors, and the virus-induced inflammatory response can also disturb the integrity of the physical barrier to bacteria.  The use of prophylactic antibiotics in Covid-19 infected patients has therefore become relatively common. Recent reviews however, suggest the frequency of such secondary bacterial infections may be less than initially thought. These found bacterial co-infection was identified in only 3.5-7% of patients, and secondary bacterial infection in 14% of patients (22,23), While such infections are more common in seriously ill and elderly patients, and antibiotics should of course be used when indicated, not overusing them in an age of increasing antibiotic resistance, is also important. As such, evidence suggesting echinacea may prevent virus-induced bacterial adhesion to cell membranes(24), suggests another potential mechanism of action to improve host resistance against such unwanted secondary infections.

Dietary supplementation with Echinacea purpurea has been reported to improve the final body weight and immune response of non-infected chickens, and reduce the mortality of those infected with E. coli(25)

A recent clinical trial involving 300 children in Eqypt with recurrent tonsillitis, reported fewer tonsillitis attacks and less severe symptoms when Echinacea was taken alongside the antibiotic azithromycin, three times daily for 10 consecutive days every month for 6 consecutive months(26). While the plant part(s) used and phytochemical analysis of the preparation involved was not disclosed in this report, these findings are supported also by the clinical experience of many western medical herbalists, who prescribe concomitant Echinacea in patients receiving antibiotic treatment. Usage of Echinacea as an adjunctive with antibiotics, clearly warrants further clinical trials.

Effects on Stress?

Another unexpected but potentially helpful application of some Echinacea preparations in a stress-invoking pandemic world, is to help alleviate anxiety. Anxiolytic effects have been reported previously for certain Echinacea extracts and products, but clinical evidence has been lacking. However, a recent double blind, placebo controlled trial in which volunteers prone to anxiety took a standardized Echinacea angustifolia root extract twice daily for 7 days, found a decrease of 11 in state anxiety scores after 7 days of Echinacea, compared to only 3 in the placebo group(27).

Echinacea products are being sought after in northern hemisphere countries as second or third waves of the Covid-19 pandemic continue to plague multiple nations.  While clinical studies are sadly lacking and are sorely needed, the many potentially relevant pharmacological properties shown by this highly regarded phytomedicine would seem to go a long way to justify its recent rise in popularity.



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Roots of the European and northern Asian herb Valerian (Valeriana officinalis), are well known for their relaxant and anxiolytic properties, and usefulness in the management of insomnia and mild anxiety. Clinical trials into its effects on insomnia and sleep problems including in menopausal women and patients withdrawing from benzodiazepine drugs, have generally reported favourable findings(1-4).

As with all medicinal plants, a single useful application is a far-fetched concept, and Valerian is no different in this. Apart from being pleasing to some cats in a similar way catnip is, another increasingly supported application for this well known herb, is to help support cognitive function.

Conventional sleeping tablets such as triazolam and zopiclone have detrimental effects on cognitive function(5,6), but comparative studies found valerian to show no such negative effects(1, 7). Next day hangover like symptoms and cognitive deficits are relatively frequent adverse events of all drug-based anti-anxiety or sedative agents, so this itself is a significant valerian advantage. However, evidence that valerian may additionally protect against cognitive decline or enhance cognitive functions in other settings, is of interest.

Early indications of cognitive enhancing effects of valerian particularly in the elderly, came from a Korean study in aged mice published in the journal Exp Gerontology(8). Following 3 weeks of valerian root administration (and valerenic acid), improvements occurred in several behavioural parameters indicative of improved cognitive functions, including exploration of new objects, escape latency, and swimming speeds. These effects were accompanied by enhancement in nerve cell differentiation and neuroblast differentiation, and reduced serum levels of corticosterone, in the valerian versus control treated mice. While an animal study, these findings suggest similar cognitive promoting effects in elderly humans.

Since then, at least two human clinical studies have measured changes in cognitive function following valerian administration. These include a study with 39 patients on haemodialysis whose cognitive status improved after taking valerian 60 minutes before bedtime for one month(9). The prevalence of cognitive disorders in kidney failure patients undergoing haemodialysis is twice as high as the general population, and these are often undiagnosed(10).  Neuroprotective properties, as reported for ethanolic extracts of valerian in animal studies, may be contributory to such benefits(11, 12).

Another study explored cognitive dysfunction in 61 patients aged between 30 and 70 years, scheduled for elective coronary artery bypass surgery(13). Patients received either valerian or placebo capsules twice daily for 8 weeks following surgery. Cognitive brain function was evaluated prior to surgery and at 10-day and 2-months following, using the Mini Mental State Examination (MMSE) test. In the valerian treated patient group the mean MMSE score decreased from 27.03 ± 2.02 in the preoperative period to 26.52 ± 1.82 at the 10th day, and then increased to 27.45 ± 1.36 at the 60th day. Conversely in the placebo group, scores reduced from 27.37 ± 1.87 in the preoperative period to 24 ± 1.91 at the 10th day, and rose only slightly to 24.83 ± 1.66 at the 60th day. With post-operative cognitive decline now recognised as a negative outcome in many patients undergoing this increasingly common surgical procedure(14), the finding that valerian may prevent this, has implications for coronary artery bypass as well as potentially other forms of surgery.

Valerian is also used traditionally for digestive or menstrual cramps, and for nervous headaches(15, 16). Prior to the development of early tranquilliser drugs such as barbiturates, or when these weren’t accessible, it was also a valued intervention in the management of some forms of pain.

Support for these historical applications has emerged recently from results of a clinical trial in Iran which investigated the effects of valerian on tension headaches. These present as dull pain, tightness, or pressure around the forehead or back of the head and neck, and are the most common type of headache.

The study included 88 participants with tension-type headache, randomly assigned to take valerian or placebo capsules twice daily after dinner for a month. After this one month treatment, valerian was associated with a significant reduction in the negative impacts of headaches on daily living and disability, and a reduction in the severity score, relative to the placebo group(17).

Finally, as anti-anxiety and sedative drugs can impart clinical improvement in some patients with depression, and potential antidepressant activity has been implicated for valerian in an animal model of depression associated with chronic stress(18, 19), beneficial applications in some patients with depression, are possible. Depression can also be accompanied by cognitive disturbances and a compromised memory. As such, herbs such as ginkgo and valerian for which benefits on associated cognitive function have been shown, may offer additional effects beyond those of antidepressant herbs and drugs, in the management of patients with depressive illness.


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  19. Kandilarov IK et al, Folia Med (Plovdiv) 2018; 60(1):110-116.

Ligustrum lucidum – synergistic effects with other herbs and drugs in the management of cancer, bone marrow suppression, and depression?

I’ve written previously about the many medicinal properties of the dark red fruits of Ligustrum lucidum (Glossy Privet), the most invasive tree in New Zealand(1, 2). These include prophylactic effects against osteoporosis, beneficial effects on bone growth and strength, protection actions against liver toxins, and possible applications for one of our biggest and growing health burdens, diabetes mellitus.

During the March to June New Zealand Covid-19 Lockdown, I became more attentive to my local environment, and being a herbalist, plants featured prominently in this. Plants in our individual immediate environments can be useful as a source of food, recreation, exercise, de-stressing, and other survival related concerns, including as medicines.

It is however, a sad reflection on the current human disconnect from our local environment, that while this tree offers an evidence-based and readily available partial solution to common health problems experienced by thousands of New Zealanders, hardly anyone seems to know about this, or consider utilising this plant for something useful. Just as we viewed Mānuka many years ago, when it was cursed as an unwanted scrubweed by farmers, until its numerous medicinal properties became recognised again.

Ligustrum fruits are also used as an adjunct in cancer therapy(3). Inhibitory effects against benzopyrene and aflatoxin induced cancer(3, 4), potential applications in the treatment of liver(5) and brain(6) cancer, and enhanced sensitivity of human colorectal carcinoma cells to the chemotherapy drug doxorubicin(7), have been reported.

During chemotherapy treatment of cancer patients, a common and serious adverse event is myelosuppression, damage to the bone marrow resulting in decreased production of blood cells (haematopoiesis), and lowered immunity.

Ginseng (Panax ginseng) has been reported to ameliorate myelosuppression produced by the chemotherapy drug 5-flurouracil(8). Recent research now suggests that Ligustrum also may help with the clinical management of this condition, and that a combination of Ligustrum with Panax ginseng, even more so(9).

Mice who developed myelosuppression following administration of the chemotherapy drug cyclophosphamide, were given aqueous extracts of either Panax ginseng, Ligustrum lucidum, or a combination of these two herbs. Both ginseng and Ligustrum each individually increased levels and activity of several different haemotopoietic factors including peripheral blood cells, bone marrow cells and colony-forming unit-granulocyte macrophages, and upregulated cytokines involved in haematopoiesis. These protective effects against bone marrow suppression were even greater though, when a combination of Ginseng and Ligustrum was used.

Combining Ligustrum with Ginseng and using as an adjunctive treatment during chemotherapy treatment, may therefore help manage the negative effects on bone marrow thus enabling an optimal chemotherapy regimen to be implemented. Preventative effects against chemotherapy-induced myelosuppression have also been reported for a combination of Ligustrum with Eleutherococcus senticosus(10).

Other recent research on Ligustrum suggests it may also combine well with the highly regarded medicinal fungus Cordyceps(11). The Cordyceps genus are a type of fungi requiring an insect or insect larvae as host. Cordyceps has been used in TCM for over 300 years to treat a diverse range of conditions, including respiratory, kidney, liver and cardiovascular diseases, low libido, impotence, hyperlipidaemia, hyperglycaemia, fatigue, convalescence, and to promote energy(12).  Cordyceps is also gaining interest as a potential anti-cancer agent(13, 14), including as an inhibitor of metastases (secondary cancers), and as an adjunct during chemotherapy and radiotherapy(15, 16).

Unlike the closely related Cordyceps sinensis, a species restricted to a specific zone and insect host which has been overharvested in the wild and now endangered, Cordyceps militaris is cultivated on a range of host insects, and still contains significant levels of a key active compound cordycepin (3-deoxyadenosine). However, upon entering the body cordycepin is quickly metabolized into an inactive metabolite 3′-deoxyinosine, by the enzyme adenosine deaminase which is widely distributed in mammalian blood and tissues, thus limiting its activity when administered alone.

However, researchers in Shanghai have recently shown that oleanolic acid and ursolic acid, key triterpenoid constituents extracted from Ligustrum lucidum fruits, act as potent adenosine deaminase inhibitors. This suggests combining cordycepin or Cordyceps with Ligustrum, may be another useful combination in clinical practice(11).

Finally, potential applications of Ligustrum lucidum in the management of some types of depression, have recently been revealed(17).

Depression sometimes develops as a result of a head injury or in neurodegenerative disorders such as Parkinson’s disease or dementia, with central nervous system inflammation (neuroinflammation) being a common underlying factor. Recent clinical and preclinical evidence also suggests that this inflammation in nerve tissues may be a key factor involved in the onset of major depression(18).

Phenol glycosides from Ligustrum lucidum were evaluated for their effects on neuroinflammation and depressive-like behavior in mice. Mice received the Ligustrum derived extract for two weeks prior to treatment with lipopolysaccharide (LPS), which induced an inflammatory reaction. Ligustrum phenol glycoside pre-treatment ameliorated LPS-induced depressive-like behaviors, effects associated with reduced neuroinflammation of the hypothalamus, less activation of microglia (a type of brain cell) and inflammatory cytokine production, and improvement in vitamin D metabolism.

Like hundreds of other clever plants, Ligustrum lucidum has become so well colonised in New Zealand it is classed as a ‘noxious’ weed. The dark purple brown berries that appear in autumn make a wonderful healthy feast for our large bird population who excrete the seeds far and wide. And like lots of introduced plants endemic in our environment (weeds), it provides a readily accessible, free or cheap source of plant medicine with many potential benefits.

The above research on this plant is just some of that published this year to date. Perhaps assigning ‘shovel ready’ unemployed Kiwis to harvest the berries at the same time as culling numbers of this tree and undertaking further research towards processing these into natural medicines, might improve human and animal health, reduce medical care costs and prevent chronic debilitating illnesses. This would make sense in the Covid-19 plighted economy we are now living in.



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  2. Rasmussen PL, https://herbblurb.com/2019/01/24/honeysuckle-and-other-useful-weeds-surrounding-us/
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New Zealand Horseradish – a winter tonic for lungs and immunity and more

Aside from being a condiment to various foods, horseradish (Armoracia rusticana) root has been traditionally used for coughs and colds for centuries in Europe and parts of Asia. Making a syrup from the distinctively pungent large roots of this plant which grew vigorously at my allotments when I was a herbal student in the UK many years ago, was one of my first experiences with manufacturing a herbal cough medicine, and it is great to now have access to this wonderful herb, grown here in New Zealand.

The source of its pungency and warming aromatic properties, are phytochemicals known as glucosinolates (so-called ‘mustard oil glycosides’) which break down to release volatile and highly bioactive compounds known as isothiocyanates. These act as natural expectorants to encourage mucus elimination, as well as having warming and invigorating actions that can improve the body’s natural defences against unwanted bugs.

Horseradish and its isothiocyanates have been subject to a fair amount of research in recent years, findings from which provide further support for both its traditional as well as potential new applications.

Antimicrobial actions are prominent features of horseradish extracts. Significant antibacterial activity has been shown against a wide range of pathogenic microbes, including bacteria responsible for chest, skin, oral and urinary tract infections(1-6). Isothiocyanates derived from horseradish also exhibit a non-selective antimicrobial activity against several bacterial strains including resistant forms of Haemophilus influenza and E. coli, and yeasts such as Candida albicans(2, 4, 7).  The principle isothiocyanate allyl isothiocyanate has synergistic antifungal activity with the drug fluconazole against Candida biofilms(8).

Clinical studies using a combination of horseradish root with nasturtium herb have found it to have comparable efficacy to antibiotics in the treatment of acute sinusitis and acute bronchitis(1). A combination of horseradish with green tea and other herbs has also been reported to have greater efficacy than oseltamivir in preventing H3N2 avian influenza viral transmission(9), suggesting potential antiviral actions.

An excessive host inflammatory response in the lungs is increasingly linked to an unfavourable prognosis when highly pathogenic bacterial or viral infections take hold in the respiratory tract. As such, the anti-inflammatory properties of horseradish and its affinity for the lungs, are probably useful. Diverse anti-inflammatory effects including reduced nitric oxide, tumor necrosis factor-α and interleukin-6 release, and COX-2 expression, have been reported(10-14). Apart from being anti-inflammatory(15), allyl isothiocyanate induces the expression of multidrug resistance-associated protein 1 (MRP1), which plays a protective role against oxidative stress, lung inflammation and progression of chronic obstructive pulmonary disease (COPD)(16).

Other horseradish phytochemicals have also been associated with anti-inflammatory activities in human immune cells. These include inhibition of the cyclooxygenase (COX-2) enzyme, as well as lipoxygenase pathways (PGE2 synthesis and leukotriene LTB4 release)(10, 14). Anti-inflammatory and potential neuroprotective effects, have also been reported recently for hydantoin and thiohydantoin constituents of horseradish(17).

Like many medicinal plants, horseradish is a powerful antioxidant, and recent research suggests a link between its antimicrobial activities, and antioxidant properties(12). An Italian study found fumigation with allyl isothiocyanate to enhance the Vitamin C, polyphenol and flavonoid content of kiwifruit after 120 days of storage, thus improving its antioxidant and potential health benefits(18).

Protection against DNA damage and cell death from oxidative stress, and inhibition of the COX-1 enzyme may also contribute to the reputation of horseradish to protect against various cancers. Isothiocyanates such as allyl isothiocyanate derived from horseradish and other plants such as brasiccas and nasturtium have been increasingly investigated for their anticancer properties in recent years(10, 19, 20, 21). Horseradish flavonoid constituents such as kaempferol and quercetin also seem to help prevent cellular mutations that can lead to cancer(22).

The use of horseradish as a condiment to help digest rich food has been given a tick of approval by Serbian and Austrian research showing powerful spasmolytic (muscle relaxant) effects on the bowel for its isothiocyanates(4, 23). Potential benefits in the management of diabetes type 2 have also been implicated by recent reports that it is a strong inhibitor of the enzyme α-glucosidase, which breaks complex carbohydrates down to glucose(24).

New Zealand grown horseradish is an ideal herb to include in a winter immune tonic, as well as a regular tonic for those who through lifestyle or occupational exposure to various carcinogens, may be at risk of COPD or various cancers. Its affinity for lung conditions in particular, make it a valuable herb to enhance immunity and optimise lung health, during 2020.



  1. Goos KH et al, Arzneimittelforschung 2006; 56(3):249-257.
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  8. Raut JS et al, J Microbiol Biotechnol. 2017 Apr 28;27(4):685-693
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  13. Marzocco S et al, Food Funct. 2015 Dec;6(12):3778-88
  14. Herz C et al, Evid Based Complement Alternat Med 2017. 2017:1950692
  15. Subedi L et al, Int J Mol Sci. 2017 Jul 3;18(7):1423.
  16. Wang S et al, Oxid Med Cell Longev. 2015;2015:903782.
  17. Lee TH et al, J Nat Prod. 2019 Nov 22;82(11):3020-3024.
  18. Ugolini L et al, J Food Sci Technol. 2017 Mar;54(3):751-760
  19. Zhang Y et al, Mol Nutr Food Res. 2010 Jan;54(1):127-35.
  20. Gerhauser C. Curr Opin Clin Nutr Metab Care. 2013 Jul;16(4):405-10
  21. Novio S et al, Molecules. 2016 May 12;21(5):626.
  22. Gafricova M et al, Molecules 2014 Mar 14;19(3):3160-72.
  23. Donnerer J, Liebmann I. Pharmacology. 2017;99(1-2):79-83.
  24. Javaid A et al, Comb Chem High Throughput Screen. 2020 May 26 (epub ahead of print)



Almost all of New Zealand’s economy is based upon plants, and how prolifically they grow here. Even after much of the native bush was felled to make way for sheep, cows and pine trees, it’s the grass and plants that replaced this, that feed milk or meat producing animals. Agricultural products continue to make up a huge percentage of our exports and GDP contribution, even more so now that Covid-19 has seen plummeting earnings from industries such as tourism and foreign student education provision.

The success of NZ’s Food and Beverage industries derives not only from our reputation for producing high quality products, but also establishment of and maintenance of world class regulations. Nobody in Shanghai or Tokyo or New York wants to buy NZ organic milk from grass fed cows, unless they are sure that what they are paying a premium for, is exactly as stated on the label, and that it is safe. Regulations are there to make sure expected quality parameters are upheld, ensure safety, and in many industry sectors, help facilitate exports.

As with quality food and beverage products, herbal medicines are growing in popularity and global demand, and the current Covid 19 pandemic has reminded us that drugs are not always a solution to rely upon to save us from nature’s dominance over our plight.

Demand for various herbal medicines has long surpassed the point where demand exceeds supply. As with the global food supply chain, changing consumer preferences and climate change stressors, are also contributing to this supply shortfall.

As I’ve written previously, this provides huge opportunities for New Zealand. We have a rich diversity of natural resources, fertile soils, great farmers, and an enviable track record of research and development in biological and agricultural sciences, and pharmaceutical company development.

Why then have successive governments since the last Labour one, not taken the need to regulate and enable the absolutely huge growth potential of a local natural health product industry seriously?

The recent decision by the Ministry of Health to reclassify ‘Artemisia annua extract’ as a prescription only medicine, is symptomatic of these serious regulatory deficits for natural health products.

On 18 May the Ministry of Health issued a Gazette notice to reclassify ‘Artemisia annua extract’ as a Prescription-Only Medicine, following receipt by the New Zealand Pharmacovigilance Centre of 29 reports of hepatic adverse reactions occurring in patients taking two specific products purchased ‘over-the-counter’, and made in NZ from a supercritical CO2 extract of Artemisia annua in grapeseed oil.

What this effectively means, is that all Artemisia annua containing products in addition to those containing the particular extract involved in these adverse event reports, have now become ‘prescription only’. In other words, medical herbalists and naturopaths, most of whom have undertaken at least 3 years study to obtain a degree qualification in natural medicine, are no longer able to treat patients with traditional and GMP manufactured preparations of this herb. But somehow, doctors and other registered medical practitioners who have had no training at all in herbal or natural medicine, are suddenly deemed adequately qualified to prescribe ‘Artemisia annua extract’.

In fact no other regulator in the world has restricted access to all ‘Artemisia annua extracts’, because evidence implicating the herb Artemisia annua itself in liver adverse events, is basically zilch. There is a lack of adverse event reports involving Artemisia annua-containing products reported to pharmacovigilance agencies in other countries, and no previous association of Artemisia annua with liver adverse events exists in its extensive scientific literature.

Such a cluster of cases in New Zealand only, all apart from 1 relating to one particular product manufactured and sold direct to consumers as a ‘dietary supplement’, reeks of a product quality problem. The supercritical CO2 extract used, is also very different to more traditionally used forms of Artemisia annua. As is low alcohol beer from Schnapps.


Why then has the NZ regulator taken this course of action?

Lack of any definition of a ‘natural health product’ in any New Zealand legislation, should raise a large red flag, in terms of how ridiculously outdated our regulations for natural health products are. This is the case despite the NZ Natural Health Products Industry trying for more than 20 years to get successive governments to introduce regulations to replace the completely outdated 1981 Medicines Act, and inadequate Dietary Supplements Regulations.

In 2003, the NZ and Australian governments signed a treaty to establish a joint scheme for the regulation of Therapeutic Products (ANZTPA), which would have included regulations also for natural health products. These are known as and regulated as ‘complementary medicines’, by the Australian regulator, the TGA.

Government officials, industry representatives, academics and lawyers from both countries then spent 11 years consulting, developing and preparing these regulations for implementation, but opposition from the National, NZ First and Green Parties, and a Labour government majority of 1 at the time, lead to this legislation only passing its first reading in the house, and then being canned by the new National government in 2014.

National and the Greens then spent some years developing a new NZ-only draft Bill, the Natural Health and Supplementary Products Bill. This proposed a much lighter regulatory agency than ANZTPA, but as with ANZTPA, involved a large amount of work and consultation by government officials, industry representatives and academics, who evaluated and prepared a list of several thousand permitted ingredients able to be included in natural health products without any need to apply for a Medicines licence. However, National dragged their heels on this despite being in power for 3 terms of government and the Bill was never passed, even though it was supported by National, the Greens, Labour and NZ First, with only the ACT party opposing it.

Upon coming to power in 2017, the current Labour-NZ First coalition government removed the Natural Health Products Bill from the order paper while it was awaiting its third reading, soon after talks with its coalition partner NZ First.

Various communications and workshops with industry have since taken place, with the apparent objective of reinventing the wheel and finding out how to appropriately regulate natural health products and draft a new Bill, although no timeline for this has been provided. The recent extension of the ‘Dietary Supplement Regulations’ (under which most natural health products are currently ‘regulated’) to 2026, suggests that the government still has no sense of urgency about the need for a drastically different regulatory environment.

Meanwhile this regulatory void means committed New Zealand companies trying to build export markets for locally produced natural health products are struggling to assure customers in offshore markets of their product quality and safety parameters. To make it even harder for them, for several years we’ve had a situation where many products are being imported and sold into New Zealand with illegal label statements and therapeutic claims, but nothing is being done to stop these imported brands competing with more law abiding local companies.

Industry and Ministry of Health officials share some of the responsibility for this debacle, and it is time we stopped pretending that these products are all ‘dietary supplements’. Plant medicines are true medicines, and when good quality products are taken in optimal doses, they can be as effective as drugs for many health conditions. The Australian view of natural health products as ‘complementary medicines’, is much more appropriate, their regulatory system acknowledges their ability to sometimes have therapeutic effects, and also permits such claims to be made on their packaging, where scientific or traditional evidence exists. It also recognises that natural health practitioners after training at least 3 years to obtain degree level qualifications, have particular skills that enable them to use certain forms of herbal medicines that may not necessarily be appropriate or safe as ingredients in ‘over the counter’ products.

The dairy, beef, wine, kiwifruit and so many other vibrant export industries have all been established not only through being lucky enough to have perfect growing conditions here, but also a regulatory system in place that fulfils the needs of any premium quality and premium priced product, to be sold into offshore markets.

Natural health products are challenging to regulate appropriately, but isn’t everything? It’s time for elements of the industry to stop pretending all products are ‘dietary supplements’ rather than medicines, and for New Zealand politicians from all parties to stop messing around with the Natural Health Product Industry like a game of political football, before the next 3 year election cycle.

The long game as we reflect on the post-Covid world, has to seriously leverage New Zealand’s many unique strengths and quality attributes, to create a sustainable portfolio of industries which can boost export revenue, have high margins, look after the environment, and respect the principles of Kaitiakitanga. The local Natural Health Products industry tick all these boxes, but is now in urgent need of world class regulations to support its export lead growth.



Ginkgo – much more than a herb for cognition – part 2.

Ginkgo istock3Apart from possible benefits in the management of conditions such as dementia, stroke, diabetic neuropathies, macular degeneration and glaucoma, the cardioprotective and neuroprotective properties of ginkgo suggest potential applications in other situations in which there is exposure to various drugs or substances with a risk of adverse events.

Adjunct with neurotoxic drugs

Concomitant use of ginkgo may be useful when taking or exposed to other drugs or chemical toxins(1, 2). Animal studies have reported protective actions of ginkgo against ototoxicity (inner ear and auditory nerve damage) from the antibiotic drug gentamycin(3), kidney (nephro) toxicity, liver (hepato) toxicity and genotoxicity from the herbicide glyphosate(4), and nerve damage from the herbicide paraquat(1).

These studies suggest that patients being prescribed gentamycin or other aminoglycoside antibiotics which have a risk of causing hearing or kidney damage, or people regularly using or exposed to herbicides such as glyphosate or paraquat, may benefit from taking ginkgo at the same time.


Supporting liver function:

Ginkgo leaf is a very bitter herb, and some would say that it is therefore hardly surprising that it is a useful agent for liver conditions. In fact there are now numerous studies showing it has protective actions on the liver.

These hepatoprotective effects have been reported in rodent studies against a wide range of liver toxins. They include alcohol, paracetamol, rifampicin & other chemicals(5-11). Improvements have been shown to occur in several liver abnormalities including malondialdehyde levels, glutathione levels, superoxide dismutase, elevated liver enzymes (LFT’s), and histological damage.

Hepatoprotective effects similar to those of silymarin were reported in a 2011 study involving treatment of rats with silymarin or ginkgo for a week prior, or 4 weeks post administration of nitrosodiethylamine, a known liver carcinogen(12). Other rodent studies have revealed potential antitumour effects against liver cancer for ginkgo(13, 14).

These studies suggest ginkgo could be a useful adjunct to take during treatment with the common analgesic paracetamol, as well as other drugs sometimes associated with liver adverse events, such as azathioprine, isoniazid, statins, ketoconazole and nitrofurantoin.

 Ginkgo when given in larger than usual doses to rats, has protective actions against both acute and chronic alcohol-induced liver damage, effects associated with its antioxidant actions, and improvement in hepatic microcirculation(15-18). Those whose alcohol intake is excessive, may do well to consider taking ginkgo to help ameliorate some of its negative effects on the liver.

Adjunct with chemotherapy:

Adverse events to chemotherapy are common, and use of cytotoxic drugs such as doxorubicin and cisplatin can lead to infertility, kidney damage (nephrotoxicity) and damage to the heart (cardiotoxicity) in some cancer patients.

Pre-treatment or concomitant treatment with large doses of oral or intraperitoneal ginkgo in rats has been shown to help protect against chemotherapy-induced adverse effects on other organs. These include protection against cisplatin-induced peripheral neuropathy(19), protection against cisplatin and doxorubicin cardiotoxicity, and cisplatin nephrotoxicity and ototoxicity(20-25).

Other studies have reported protective effects for ginkgo against the damaging effects of doxorubicin & cisplatin on testicular function in male rats(26, 27), and against against oxidative and genotoxic damage in patients with differentiated thyroid cancer during 90 day radio-iodine treatment(28). These results suggest possible benefits of ginkgo if taken during chemotherapy or radiotherapy treatment, by patients wanting to have children in the future.

While few human clinical trials have investigated these promising findings from animal studies, a Chinese clinical trial has reported a lower incidence of ECG abnormalities and cardiotoxicity in 60 breast cancer patients being treated with doxorubicin, when ginkgo was prescribed concurrently(29). Adjunctive Ginkgo also slightly improved overall survival in a small trial involving 27 patients with advanced hepatocellular cancer, compared to previous sorafenib monotherapy(30).

Adjunct with antipsychotics:

The response of schizophrenia patients to antipsychotic drug medications is often less than ideal, and the frequency of adverse events to these associated with low levels of compliance. Findings from a Chinese clinical trial involving 12 weeks of ginkgo and haloperidol or placebo and haloperidol administration in a group 109 schizophrenia patients and previously treated with antipsychotic medications for at least 6 months, are therefore of interest(31).

At the end of the 12 week study, 57% of the ginkgo treated group were rated as responders, versus only 38% of the haloperidol only treatment group, which in itself is highly significant. Additionally however, a lower incidence of extrapyramidal side effects, a major problem with haloperidol and other older generation antipsychotic drugs, was also seen in the ginkgo-treated group(31, 32).

Improvement in some schizophrenia symptom scores was also reported in a subsequent study involving adjunctive ginkgo treatment in patients taking olanzapine, a newer generation antipsychotic drug(33).

Potential applications of ginkgo in the management of other psychiatric conditions including depression and ADHD, have also been suggested(34, 35), though further clinical studies are needed.



A concern is the use of relatively large doses in most animal studies, yet those used in human clinical studies are often much lower, and sometimes probably less than what they should have been. Also given that most neurodegenerative conditions such as dementia, diabetic neuropathies, glaucoma and macular degeneration are slow to develop but tend to be progressive, unless clinical trials involve large participant numbers and continue for a long period of time, their ability to statistically detect clinically significant outcomes , is limited.

Despite these challenges and the cost of long term clinical trials, given the hugely debilitating nature of all of these conditions, and their large burden on both patients and the health care system, further trials to validate promising findings from in vitro and animal studies, and determine optimal dosage and treatment protocols in humans are needed.


And finally:

New Zealand is an excellent country for growing ginkgo, and locally harvested ginkgo leaves have been shown to contain high levels of ginkgo flavone glycosides and terpene lactones.

While it is sometimes claimed that ginkgolic acid, a minor component of ginkgo leaves, is associated with allergic reactions, the evidence basis for this is unconvincing. In fact research is increasingly showing that this compound probably contributes to ginkgo’s cognitive benefits(36), and exhibits a wide range of other useful pharmacological properties. These include anti-diabetic(37), anti-fibrotic(38) and potential anticancer properties, including against pancreatic (39), liver, colon and gastric cancers (40-42).



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ginkgo photo

Ginkgo – much more than a herb for cognition (part 1).

Extracts made from leaves of the ginkgo tree (Ginkgo biloba) are a widely used herbal medicine, mostly due to a reputation to help support cognitive functions in both healthy young(1,2) and middle-aged(3,4) people. However, numerous other potential applications exist for the bitter leaves of this beautiful tree, which has actions as a strong antioxidant and microcirculatory enhancer(5).


More than 400 of the 4000 papers on ginkgo published in the peer-reviewed scientific literature, relate to protective effects against nerve damage or degeneration, in in vitro and animal studies. These include reduced neurodegeneration and oedema in animal models of brain ischaemia(6-8), implicating potential applications of ginkgo to help prevent or reduce ischaemia-induced damage in stroke prone patients(9).

Clinical studies in humans show improved neurological and cognitive outcomes when ginkgo is taken in the immediate period following a stroke(10-12), without increasing the incidence of vascular events. The largest of these was a Chinese multicentre study where 450mg ginkgo extract was given daily together with 100mg aspirin for a 6 month period, in 348 post-stroke patients(11). While these results are promising, further trials involving greater patient numbers and longer treatment durations, are needed.

Parkinson’s disease is a neurodegenerative disorder characterized by the loss of dopaminergic neurons and is associated with oxidative stress, neuroinflammation and apoptosis. Studies in animal models of Parkinsons disease have implicated beneficial actions of ginkgo or its constituents(13-18). These include a reduction in elevated oxidative stress markers and inflammatory cytokines, reduced locomotion impairment(13), clearance of the alpha-synuclein (α-syn) protein by ginkgolic acid(17), and regulation of brain copper levels(19).

Two small trials involving a daily dosage of 240mg extract have investigated ginkgo’s effects on patients with multiple sclerosis, but with mixed results(20, 21).

Potential applications exist also for ginkgo to help protect against neurodegenerative retinal diseases such as macular degeneration or glaucoma, and diabetes.

Glaucoma is primarily a condition of raised intraocular pressure, but even successful intraocular pressure reduction does not stop the progression of glaucoma in all patients. As vascular dysregulation, reduced microcirculation, oxidative stress and inflammation are contributory to its development, ginkgo has relevant pharmacological actions that may be useful(22-25).

Ginkgo pretreatment and early post-treatment has been shown to protect retinal ganglion cells from damage in a rat model of chronic glaucoma(26). Few clinical trials have taken place apart from a Korean trial involving 99 patients given ginkgo for 2 years, which reported improved visual function in some patients with normal tension glaucoma(27). Given the limited treatment options for this increasingly common condition, the use of ginkgo as an adjuvant or preventive therapy should be further explored(24).

Similar potential benefits would seem to exist for age-related macular degeneration (AMD), the leading cause of irreversible blindness in adults over 50 years of age. Two trials involving a total of 119 people have reported some positive effects of ginkgo on vision in AMD patients, for doses of 160mg or 240mg per day taken over a 6 month period(28). A Russian trial involving 240mg ginkgo extract together with lutein, zeaxanthin, vitamins C, E, A and B2, rutin, zinc, selenium and bilberry in diabetic patients with initial stages of diabetic retinopathy or combined diabetic retinopathy and AMD, also found evidence of both preventive and treatment benefits(29). Again however, larger trials and for longer treatment periods, are needed.

Potential benefits in diabetes:

Type 2 Diabetes mellitus is one of the major diseases of the 21st century, and is putting an increasing burden on health care budgets. While dietary education and interventions and exercise can assist, and oral hypoglycaemic drugs or insulin are often prescribed, other interventions to reduce drug medication needs and/or improve patient outcomes can have huge benefits.

Diabetes is primarily a condition of poor blood glucose control, but vascular dysfunction often develops and long term outcomes can include development of conditions such as retinal neuropathy and blindness, peripheral vascular disease leading to leg ulcers, and glomerulonephritis leading to deterioration in kidney function.

Various studies in animals suggest a possible role for ginkgo in protecting against such neuropathies. One in diabetic rats found that 4 weeks treatment with ginkgo and magnetised water protected type 2 diabetic rat kidneys from nephrotoxic damages, effects associated with reduced hyperlipidemia, uraemia, oxidative stress, and renal dysfunction(30). Another found ginkgo pretreatment improved neurological scores, and reduced cerebral infarct volume and acute cerebral ischemia‑reperfusion injury in diabetic rats(31). Improvement in cognitive function has been reported in elderly diabetic mice(32), as has reduced plaque lipid deposition and aorta atherosclerosis, and reduced expressions of cytokines and other inflammatory markers (33). Doses used in these animal studies, however, were generally significantly higher than those normally recommended in humans.

Few clinical trials have been undertaken to date and patient numbers were relatively small. Various trials involving a combined treatment of diabetic patients with a particular combination of various Chinese herbs and ginkgo reported improved outcomes, although the contribution of the relatively low dose of 24mg ginkgo extract used in these studies is unknown(34-36).

Another trial found an improved response through adding ginkgo to the oral hypoglycaemic drug metformin for 90 days(37). Blood levels of fasting glucose, insulin, and HbA1c (glycated haemoglobin), whose elevation is linked to risks of diabetic complications, showed a greater reduction in the combined ginkgo-metformin treatment group, than with metformin treatment alone.

Ginkgo would seem to offer various relevant potential benefits in the prevention and management also of Metabolic syndrome(38). This is an insidious cluster of conditions including high blood pressure, diabetes, obesity and high blood lipids, and associated with an increased risk of cardiovascular disease events. Given the increasing prevalence of Metabolic syndrome including in up to a third of American adults, herbal agents such as ginkgo with diverse but relevant pharmacological actions, should receive greater attention.



  1. Kennedy DO et al, Psychopharmacology (Berl) 2000 Sep;151(4):416-23.
  2. Kennedy DO et al, Physiol Behav 2002 Apr 15;75(5):739-51
  3. Kaschel R et al, Phytomedicine 2011 Nov 15;18(14):1202-7
  4. Cieza A et al, Arch Med Res. Sep-Oct 2003;34(5):373-81.
  5. Wu Y et al, Phytomedicine. 2008;15:164–9.
  6. Saleem S et al, Stroke. 2008 Dec;39(12):3389-96.
  7. Lang D et al, Brain Res 2011 Nov 24;1425:155-63
  8. Tulsulkar J et al, Transl Stroke Res. 2016 Apr;7(2):120-31.
  9. Mdzinarishvili A et al, J Pharm Pharm Sci 2012;15(1):94-102).
  10. Oskouei DS et al, J Stroke Cerebrovasc Dis. 2013 Nov;22(8):e557-63.
  11. Li S et al, Stroke Vasc Neurol. 2017 Dec 18;2(4):189-197.
  12. Ji H et al, Medicine (Baltimore). 2020 Jan;99(2):e18568
  13. Rojas P et al, Nutrition. Nov-Dec 2012;28(11-12):1081-8.
  14. El-Ghazaly MA et al, Toxicol Ind Health. 2015 Dec;31(12):1128-43
  15. Wang YQ et al, Free Radic Res. 2015;49(9):1069-80
  16. Kuang S et al, Can J Neurol Sci. 2018 Mar;45(2):182-187
  17. Vijayakumaran S et al, Mol Cell Neurosci. 2019 Dec;101:103416.
  18. Mohammed N et al, Curr Pharm Biotechnol. 2020 Mar 20.
  19. Rojas P et al, Nutrition. 2009 Apr;25(4):482-5
  20. Johnson SK et al, Explore (NY). 2006 Jan;2(1):19-24
  21. Lovera JF et al, Neurology. 2012 Sep 18;79(12):1278-84
  22. Doozandeh A et al, J Ophthalmic Vis Res. Apr-Jun 2016;11(2):209-20.
  23. Martinez-Solis I et al, Planta Med. 2019 Nov;85(17):1292-1303.
  24. Cybulska-Heinrich AK et al, Mol Vis. 2012;18:390-402.
  25. Bungau S et al, Oxid Med Cell Longev. 2019 Feb 12;2019:9783429.
  26. Hirooka K et al, Curr Eye Res. 2004;28:153–7
  27. Shim SH et al, J Med Food. 2012 Sep;15(9):818-23
  28. Evans JR. Cochrane Database Syst Rev. 2013 Jan 31;2013(1):CD001775.
  29. Moshetova LK et al, Vestn Oftalmol May-Jun 2015;131(3):34-44
  30. Zayed AE et al, Oxid Med Cell Longev. 2018 Jun 11;2018:1785614.
  31. Yan M et al, Mol Med Rep. 2020 Apr;21(4):1809-1818
  32. Guan ZF et al, Metab Brain Dis 2018 33(6):1887-1897.
  33. Tian J et al, Oxid Med Cell Longev. 2019 Mar 18;2019:8134678.
  34. An XF et al, Zhongguo Zhong Xi Jie He Za Zhi. 2016; 36(6):674-677.
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  38. Eisvand F et al, Phytother Res. 2020 Feb 25.

Covid -19: An Opportunity for the New Zealand economy

The Covid-19 pandemic is having and will continue to have a huge impact on the economic wellness of all countries. While effects are far-reaching and multiple industries will be impacted, two of New Zealand’s largest sources of employment and export earnings, have been hard hit by this clever virus, resulting in a sudden increase in financial stress and unemployment. The two industries being tourism and forestry.

With border restrictions and consequently less overseas visitors likely to continue for the foreseeable future, and in the global economic slowdown causing reduced demand for forestry products, the hit on these sectors of our economy from Covid-19 will be harsh. This will be particularly so for people living in New Zealand’s rural regions and small towns, where businesses based around tourism and forestry are often the foundation of the local economy. A re-evaluation of New Zealand’s competitive advantages and emerging opportunities to provide alternative sources of employment and exports in the ‘post Covid-19 world’, is therefore a priority for both the New Zealand government, and many businesses.


New Zealand’s Strategic Advantages:

The diversity and scale of our natural and rural landscapes and environment, is a key strength. This is not only appealing to tourists, but provides an ideal environment to grow a wide range of different plant types in different geographical regions. We already produce more food than is required for the local population, and export many products derived from plants and trees. Exports of wine, kiwifruit, avocados, apples, berries and other fruits, nuts and cereals, have all risen substantially over the past five years. The future of food will be more based upon plants and less on animal products, than it is now.

Another strategic advantage New Zealand has, is being a relatively small country with a low population density, and with a track record of adapting quickly to global economic changes and shifting market trends. This we have had to do several times in our past, each with good long term outcomes. Examples include the assignment of thousands of unemployed men to tree planting and further establishing a forestry industry during the Great Depression in the 1930’s, the shift to new markets after being too dependent on Britain for exports when that country joined the EU in 1973, and the early decisions by Air New Zealand to develop new and emerging markets and invest into more fuel-efficient planes, at a time when most airlines were becoming increasingly under stress early this century.

With Covid-19 being the latest global stressor to our economy, as well as future impacts of climate change and increasingly frequent droughts and floods, a fresh and forward thinking approach to rejuvenating regional and rural economies, is called for. In fact the non-native based forestry industry and elements of our tourism industry had already grown to the point of being unsustainable and having increasingly negative environmental and sociological impacts for some time. Some re-setting of their scale and our dependency on them was needed even before Covid-19. Nature has been protesting about the mounting negative impacts from carbon thirsty human activities for some time now, and there is a need to moderate our excessively animal based farming model for the wellness of both the planet and future generations.


Phytomedicines: The Big Opportunity

Many of our existing food and beverage products have health enhancing properties, but are just the tip of the iceberg in our potential to grow and add value to, a much wider range of plant-derived herbal or phyto (‘plant’) medicines.

Global demand for herbal medicines and their raw materials has been rising for many years due to a multitude of powerful market drivers, and Covid-19 has spurred this even more. This includes demand for products aimed at supporting immunity and stress, but also a wide range of other health and wellness applications.

Aging populations, increasing costs of new drugs and hospital care, and the associated budgetary constraints by government health agencies, are also catalysing increased interest in natural health products. Finally, the increasing evidence for the effectiveness of various phytomedicine interventions for a wide range of health conditions, supported by traditional use as well as modern science.

Covid-19 has dealt us a sudden reminder that drugs don’t always provide all the answers, and the void of antiviral drugs or vaccines to prevent or treat this virus, should be a wakeup call to us all. And then there’s that other closely related and worsening nightmare of antibiotic resistance, which already contributes to more than 700,000 deaths each year(1, 2), telling us again, that fresh approaches are called for in managing and preventing infectious diseases in humans.

New Zealand is currently one of the best placed countries in the world to build a rich natural health product industry that could make a much bigger contribution to our future exports and GDP. Apart from our natural resources, fertile soils and hard-working farmers, we have an enviable track record of research and development in biological and agricultural sciences, and pharmaceutical company development. Many intelligent people who work within universities, crown research institutes, private laboratories and as R&D providers have contributed to building and supporting a range of companies making products from plants that are competitive and premium quality, and in demand from overseas markets. As with other crops such as avocados, fruit and nuts, returns per hectare from growing medicinal plants are relatively high, although initial establishment costs such as growing systems and processing facilities can be significant, and benefit from economies of scale.

Growing ginseng in New Zealand pine forests has been shown to produce a premium quality (high ginsenoside-containing) and potentially very lucrative crop(3, 4). Rising demand for medicinal mushrooms through research supporting their usefulness in conditions such as cancer, immune conditions, viruses and lung inflammation(5), suggests research into some of the diverse introduced and native fungal species we see growing in our native and planted forests, would also be worthwhile.

While some early commercial operations into growing crops such as ginseng, green tea, ginkgo, saffron and mānuka as sources of medicines has revealed many challenges, others focussed on these and other medicinal plant species, have succeeded, and demand is now often outstripping supply. Further opportunities exist with cultivating high quality and sustainably grown phytomedicines such as saffron, rhodiola, false unicorn root and golden seal, all of which demand high prices due to being endangered in the wild yet highly sought after for their medicinal properties.


A Call to Action:

Covid-19 has jolted the world, and caused a sudden shift in the way we used to do things, and how the future will look. Like other countries, New Zealand needs to respond to this as a matter of some urgency, by identifying and pursuing new opportunities that have become even more apparent since this virus jumped into humans.

Businesses themselves will of course continue to develop innovative products and pursue emerging export market opportunities. However, support from government to enable more research and the development of increased local raw material production would both help facilitate increased exports by this fast growing and healthy industry. This would also help regenerate rural economies, and provide new sources of employment to those severely impacted by Covid-19.

A working group of industry, science, Māori, farming and government representatives should be formed to further explore options, and some of the regional development and other government funds that are being allocated to support business development and employment initiatives during the Covid-19 pandemic, could perhaps be allocated to this. An action plan to support new initiatives to help New Zealand leverage some of these large opportunities, could include the following:

  1. Investment in research into phytomedicines as well as that involving drugs, for Covid-19 and as antibiotic alternatives or adjuncts.
  2. A stocktake and comprehensive survey of various weeds, native plants and fungi that could be propagated and harvested as a secondary income earner for the forestry industry.
  3. Research into medicinal plants including field trials on selected species, to learn more about their agronomy, optimal growing conditions and geographical locations, and quality plus commercialisation considerations.
  4. Research into the phytochemistry, pharmacology and agronomy of New Zealand native plants and fungi, and an integrated approach to enable these being able to make a greater contribution to the future health care of both local communities, as well as wellness needs of our future generations and tamariki.
  5. Support for private sector businesses engaged in researching and establishing export markets for innovative, value added natural health products made from locally grown raw materials.
  6. Funding for clinical trials into phytomedicines that have the potential to be both grown in New Zealand, and make a valuable pharmaco-economic contribution to future health care treatments.


Finally, in writing this I’ve been taken back to remembering one of the children’s books I used to read to my son a few years ago,Dinosaurs (and all that rubbish)” by Michael Foreman. The book describes how the dinosaurs have taken over the Earth, after it not being treated kindly by humans, and one piece of it reads:

“As the rubbish was cleared

Green shoots appeared,

Bursting through cracks

And climbing over old forgotten walls.

Telegraph poles and iron pylons

Vanished beneath trailing blossoms,

And a fresh new forest

Of flowers and trees spread

Like a smile around the world”.



Phil Rasmussen

28 April 2020



withania seedlings 2016



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