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.

 

 

Apart 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.

 

Dosage:

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