Safety fears as supplement sales soar along with Covid cases

Sales of natural health supplements have soared in the time of Covid, but some can cause life-threatening reactions. Experts say they should be treated with the same caution as pharmaceuticals. Naomi Arnold reports.

In February 2016, Heather Burgher bought a box of Good Health Viralex Attack from a pharmacist. Flu was going around, she had a bit of a sore throat, and the box promised "rapid immune defence" and a "natural, fast acting formula to fight ills and chills", thanks to olive leaf and high-strength Andrographis paniculata. She took two of the pills in her Oamaru home before bed.

It was fast-acting, all right. Within about 20 minutes, Burgher felt a sharp pain in her heart and down her left arm, and pressure began to grip her chest. She thought she was having a heart attack. Then her hands began to swell, welts appeared, and her whole body started to tingle and itch. She realised it wasn't her heart. It was some sort of allergic reaction. Her blood pressure was crashing, she was struggling to draw in air, and she had the sensation that her organs were swelling, as though they were growing too big for her skin.

Thankfully, her daughter Candice was with her, and Burgher lived only about three minutes from Oamaru Hospital. They grabbed the box of Viralex as they left. By the time they got to the hospital, Burgher's vision was blurring and she was losing all feeling in her body. As she tried to get into a wheelchair, she collapsed.

Her memory of those moments is still vivid. She remembers a doctor giving orders and heard someone say, "Her veins are collapsing, blood pressure falling." She recalls convulsing and shaking on a bed, unable to talk or move her body. She saw Candice in distress and watched her put her head in her hands as medical staff told her they were about to do a tracheotomy to assist Burgher's breathing. She heard them say the helicopter would be there at 11.23pm. She saw a porter look at her, and she felt he was acknowledging she was about to die.

But the medical team stabilised her, and she was airlifted to Dunedin Hospital's intensive care unit, where she spent two days recovering. Shocked by her near death and wanting to warn others, she spoke about her experience to the media, and word got around quickly. She received calls from two other women who said they'd also had allergic reactions to Viralex.

She contacted Good Health and spoke to one of their naturopaths, who Burgher says told her she knew of three others, including a lab worker, who'd also had reactions to the pills. Burgher approached health stores, but they were reluctant to talk about it. She wrote twice to the Ministry of Health and tried calling a few times as well, but it said Viralex was classified as a food supplement, and therefore had nothing to do with the Ministry of Health.

"It was, 'there's no regulation' and that was the end of it," she says. "I think a lot of people aren't really aware of what herbal medication can do.

"I suppose we all think, 'Let's go the natural way', and I guess with Covid now, people will be looking for options and thinking we need to have an immune boost to look after ourselves."

Burgher had bought and used the Viralex pills before, with no ill effects, and believes it was the higher strength of the andrographis in the product she took that triggered her reaction. Good Health recalled the product not long after, and no longer uses A. paniculata in its formulations. A Good Health naturopath, who did not want to use her name, told RNZ the company takes reactions seriously, and Burgher's was the most serious reaction they'd ever had.

"Through extensive investigation it was discovered that she had reacted to the andrographis extract in that product at the time," she says. "So that was certainly something that Good Health had to look at straight away. It was dealt with immediately; we then removed andrographis as an ingredient in our formula, and we replaced it with a different herb, a safer herb called Astragalus membranicus."

She says they haven't received any reports of adverse reactions to Viralex since.

In March 2017, Medsafe listed A. paniculata as posing a potential risk for serious allergic reactions, such as anaphylaxis, rashes, and trouble breathing, after the Centre for Adverse Reactions Monitoring (CARM) noted a number of cases in New Zealand. The World Health Organisation's (WHO) global Individual Case Safety Report database (VigiBase) contains 344 reports related to it. Between December 2002 and April 2014, the Therapeutic Goods Administration in Australia received 43 reports of anaphylaxis and 78 reports of other allergic-type reactions associated with products that contain it, too.

Yet it not only remains a very common ingredient, but like all natural health supplements it doesn't have to be regulated as a medicine, so doesn't have to carry any proof of its claims or any warnings about its use.

Aside from anaphylaxis, liver injury from natural health supplements is an under-recognised yet growing problem, several research papers say. A study from the United States' Drug Induced Liver Injury Network (DILIN) has found the proportion of liver injuries caused by herbal and dietary supplements has increased from 7 percent in 2004-05 to 20 percent in 2013-14, which the authors attribute to more people taking them. People with liver injury from herbal and dietary supplements also have a higher liver transplant rate (56 percent versus 32 percent) and a lower rate of survival (17 percent vs 34 percent) compared to injury from other drugs.

"These things should be taken seriously," Good Health's naturopath says. "I always encourage people to be checking natural supplements that they are wanting to use alongside any prescription medications [with] their health professional.

"Part of my job is to inform them to be careful. I have a general rule of thumb too, where we say to them, even if it's just a simple everyday multi, to please wait two hours if they are taking any prescription medications. So I'm very, very careful."

But consumers often aren't, because of the widespread perception that natural means safe. How many people, browsing a natural health website or store shelf for something that might help them feel better, would book a consultation with their GP to check a product before adding it to their cart? If you're feeling a bit fluey, you can simply buy one or two or 10 products online and take them all, with no medical oversight as to what else you might be taking and how they might interact with any prescription medication or health conditions.

A search of New Zealand shopping website Health Post, for example, turns up nine products containing A. paniculata and only one has a warning that echoes Medsafe's. Life Pharmacy offers four products containing it. None of its listings contain any warnings for the buyer.

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The phrase "natural health supplements" covers a vast spectrum of products, ranging from the vitamins, minerals and oils you'd find in food (such as fish oil, magnesium and zinc), to the herbs and other natural substances that have been used for centuries across different cultures and are the ancestors of modern medicine. Natural health supplements fall under what's called complementary and alternative medicine (CAM), which describes the products as well as practices used alongside or instead of conventional medicine.

One of the most common arguments in favour of natural health supplements is that conventional, prescribed medicines and vaccines are more likely to hurt more people. That's true; conventional medicines make up most of the reactions reported to CARM, partly because they are far more widely taken (more than 365 million funded paracetamol tablets are dispensed each year, for example; that doesn't include supermarket sales. And that drug is responsible for most of the calls made to Dunedin's National Poisons Centre). While Andrographis paniculata, which sent Heather Burgher into anaphylaxis, has 344 records in the WHO database, the world's most-prescribed anti-inflammatory, diclofenac, has 148,704. Since 1992, just 582 suspected adverse reactions to CAM have been reported to Medsafe.

There have been two reported deaths in relation to an adverse reaction to CAM between 2012 and 2020, Medsafe data shows. A list of more than 100 CAM reactions from January 2018 to December 2020, released to RNZ under the Official Information Act, reveals more anaphylaxis, as well as vision problems, jaundice, convulsions, rectal bleeding, swelling, vomiting, nephritis, abortion, impaired liver function, renal failure, liver failure, cardiac arrest and sudden death. Many people were taking multiple supplements, along with pharmaceutical medication - one was taking seven products at once.

A systemic review of adverse reaction reporting in 2006 estimated just 6 percent of all adverse reactions are reported at all. An article in a Medsafe journal suggests CAM underreporting could be because reactions aren't well-recognised by consumers and healthcare professionals; that there is a lack of awareness that adverse reactions to CAM can be reported to CARM; there's uncertainty about what can be reported; there can be an assumption that 'natural' means safe; and there can be a lack of discussion between patients and healthcare professionals about their use.

Reports of suspected adverse reactions to CAM are rare compared to vaccines and medications. But RNZ gathered published Medsafe data over 10 years and found that on average, when people do experience reactions to CAM, 28.5 percent of those are considered "serious". A "serious" reaction, according to international criteria, is one that results in death, is life-threatening, causes or prolongs hospitalisation, results in persistent or significant disability or incapacity, or is otherwise "a medically important event".

The proportions of serious reactions to CAM and to pharmaceutical medicines are similar; on average, 34.2 percent of medicine reactions are serious. Both are in stark contrast to serious reactions to vaccines, of which only 3.7 percent of reactions are serious.

The figures suggest that although reactions to CAM may be either happening less frequently or are reported less frequently, the reactions can be just as dangerous as those to pharmaceuticals.

New Zealand Medical Association chair and GP Alistair Humphrey wants the adverse effects of CAM to be well-researched before they are sold to a customer.

"There are many cases when problems can arise from liver toxicity, down to allergic reactions [which] are relatively common, because often a natural product has a mix of substances in there," he says. "And they're not necessarily addressed properly by the people selling the products."

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Natural health products are big business and a boon for New Zealand's economy. In 2019, industry body Natural Health Products NZ estimated the wider New Zealand supplement industry contributed $2.3 billion to the economy annually, up 64 percent from 2014, and had a five-year compound annual growth rate of 10 percent.

The Covid-19 pandemic has been good for business too. In the US, sales of supplements were 16.7 percent higher than a year ago in the four weeks to 11 July, having risen as much as 51.2 percent in March as Covid-19 continued its spread.

Data from Nielsen shows that in New Zealand, total sales of health supplements in supermarkets alone were worth approximately $130 million for the year to 12 September 2021, growing 2.4 percent compared to the same period last year. In the year before, health supplements saw a 10 percent increase in dollar sales for the year to September 13, 2020.

Yet University of Canterbury toxicology professor Ian Shaw says the evidence for natural health supplements working is "scant, to say the least".

So who uses them? A piece of 2017 research by University of Canterbury masters student Peter Harris found 80 percent of New Zealanders have used a CAM product. The Ministry of Health last gathered data on supplement use in 2008/9 in the New Zealand Adult Nutrition Survey. It found nearly 50 percent of New Zealanders aged over 15 had used supplements in the past year, although the proportion was higher for women (53 percent) than for men (41.9 percent).

Other research, including a 2011 New Zealand study, found 47 percent of men over 40 use at least one supplement and 30 percent of users took more than two, with a median spend of $20 a month.

CAM use is extensive in the elderly, but, like in other age brackets, this isn't necessarily monitored by GPs. One German study of 400 over-70s found nearly two out of three used at least one. But only a fifth had been asked about their CAM use by their GP, and more than half of the respondents couldn't assess whether their preparations would have side effects. Only 5 percent were aware of potentially harmful drug interactions, such as those that can happen when taking Ginkgo biloba or St John's Wort.

Similarly, in an Australian study of older rural people, more than three-quarters had used at least one CAM product in the past 12 months, but nearly half hadn't discussed it with their doctor.

In fact, international research has shown more than 40 percent of people don't discuss their CAM with their doctor, which is also reflected in a New Zealand study of cancer patients, where more than half had not discussed their CAM use with their oncologist. Patients may feel their turmeric pills or health tonic are natural and therefore can't do any harm, so fail to mention them-or even remember taking them-at their consult.

That means doctors prescribing conventional medication might not know how patients are mixing them with supplements. So CAM is usually taken outside of medical supervision.

Alistair Humphrey says he thinks this lack of discussion may come down to a "slight sense of embarrassment" for patients.

"It is in part the fault of us as doctors; we may come across rather too strongly against natural products, may dismiss them too readily, because they've not been tested," he says.

"And I think people realise that. So they don't necessarily want to tell their doctor that they're taking something that their doctor hasn't prescribed.

"However, I think most, certainly most good GPs will have a relationship with their patients such that when they actually specifically ask about other products, like natural products somebody might be taking and then their patients will often let them know. But certainly in the first instance, I know people are very reluctant to say why they've gone for an alternative.

"As GPs, we are well aware that people will try all sorts of things with various conditions. I think it's important for both the general public and doctors to understand that this is going to happen, and that we need to be open and honest about it with each other. Doctors should not condemn [natural products] too strongly; they need to understand them."

Natural health practitioners can easily explain any ill effects such as rashes, fatigue, diarrhoea and headaches as the body "detoxing". On its website, one New Zealand company openly attributes these sorts of reactions to the "Herxhiemer effect", totally misappropriating the name of a life-threatening reaction to antibiotics as a "healing effect".

In his PhD thesis on complementary and alternative medicine regulation in New Zealand, Peter Harris wrote there is a "pervasive, Antipodean… laissez-faire attitude towards CAM products, [an assumption] that they are regulated somehow, because that is just the way things are: foods are regulated, medicines are regulated, so CAM products must be too."

Public belief in their effect, he says, ranges from the "naïve-'they might do something but at least they will not harm me'-to the actively illogical: 'natural so must be safe'". He wants a three-tier system for CAM with a blacklist for prohibited ingredients and proposed a draft bill.

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Vitamins and minerals are one of the most popular pills people pop, and Shaw says the risk of taking those (other than vitamin D) is "incredibly low". Indeed, the University of Canterbury Mental Health and Nutrition Research Lab, led by clinical psychology professor Dr Julia Rucklidge, has run many studies into vitamins and minerals formulated to improve mental health. They show clinically-sound positive effects. But they are results achieved in consultation with the patient's doctor and manufacturers, and Rucklidge warns they can't be replicated by taking a self-prescribed mix of supermarket or health shop multivitamins or herbal extracts.

Still, many natural health supplements are not simply daily multivitamins that might not do any good but won't do any harm; they're unregulated, high-potency, pharmacologically-active doses with unknown effects when taken alone, combined, or mixed with pharmaceuticals. People would never eat a daily serving of astringent, bitter olive leaves to get 500mg of olive phenolics, an active ingredient that has no recommended daily intake. But they can take that much in a capsule along with the rest of the supplement regime lined up in their kitchens.

Shaw recalls advising on the case of a 67-year-old woman, "usually a calm, considerate person", who became tearful, angry, easily annoyed, negative, reactive, and lacking in control after taking a supplement containing horseradish root, eyebright, and olive leaf extract; a pharmacist had advised taking it for hayfever and sinus relief.

But the woman was already taking 500mg/day of olive leaf extract in a different formulation and had done so for the past two years without incident. A small increase via the new supplement caused the toxic effects. Her symptoms disappeared when she stopped the hayfever treatment.

Shaw says that case is a good example of why we should require dietary supplements to undergo toxicity and efficacy testing before they are approved for marketing, if they're to be used for a medical purpose.

Instead, he says, we see woolly claims that use words like "supports" and "aids" or "reported to be helpful for". A claim that a product reduces inflammation, for example, may be backed up by a legitimate piece of research-but the research itself could be only tangentially related to reducing a marker of inflammation in a lab setting, and have nothing to do with treating a chronic disease in a human body.

Another big issue is that dietary supplements can be mislabelled. A 2019 DILIN study checked the contents of herbal and dietary supplements collected from patients. Of 272 products, the chemical contents of half of them didn't match their label. The worst offenders were appearance enhancement, sexual performance and weight loss products.

Undeclared prescription medicines have been found in complementary medicines in New Zealand, including those used for slimming and erectile dysfunction. In 2011, Ayurvedic products supplied by an Auckland practitioner were found to have dangerously high levels of lead, and one person was hospitalised.

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But while sales of natural health supplements are rising in the time of Covid, the laws around CAM are a legislative mess, and people on all sides of the industry have voiced their frustrations.

Most other OECD countries have regulatory regimes governing supplements' safe marketing, sale and use. New Zealand doesn't. Here, supplements fall under the Food Act and Dietary Supplements Regulations, with the Advertising Standards Authority and Fair Trading Act theoretically protecting New Zealanders from misleading claims about health products.

In a cabinet paper, former Health Minister David Clark described the system like this: "The regulation that is in place is poorly suited to the products, there is widespread noncompliance, and widespread non-enforcement."

In response to questions put by RNZ, a Ministry of Health spokesman says the Ministry of Health and Ministry of Primary Industries are "continuing work on options to regulate natural health products", work that has been delayed by the Covid-19 response.

For now, we are stuck without a comprehensive regulatory regime, even though the industry and health practitioners have been calling for one for decades.

Natural Health Products New Zealand refused RNZ's interview request, but chair Lorraine Moser said in a written statement that the Ministry of Health and Ministry for Primary Industries are responsible for ensuring there are fit for purpose regulations for natural health and supplementary products.

"This includes the reporting, analysing and implementing preventative and corrective actions for any reported potential adverse reactions," Moser says.

"Protecting people's health and well-being is our top priority and to this end all of our members agree to abide by our Code of Conduct. Furthermore, we always encourage consumers to consult with a health professional before taking any natural health product and to follow the usage instructions."

Moser says that although consumers are protected by product-specific regulations and consumer law, "regulatory reform for New Zealand's natural health products sector is long overdue".

"This country's regulations are extremely out of date and are no longer fit for purpose despite Natural Health Products NZ having worked with every government in the last two decades to advocate for them to be modernised.

"As a result, export and local trade is being held back and we are missing out on opportunities that could aid the economic recovery from COVID19.

"As a $2.3 billion dollar per annum industry, the natural health products sector could be making a much larger contribution to the economy, but outdated rules force us to compete with one hand tied behind our back and puts us at a major disadvantage to competitor countries with modern regulations."

Toxicology and health experts say we need a new system that ensures manufacturers have greater accountability, and it should make natural health products subject to the same evidence-based scientific testing as other therapeutic products.

In a submission on the extension of the Food Act, the New Zealand Medical Association former chair Kate Baddock said the organisation's view was that natural health products "should fall under the regulatory scheme for all therapeutic products, such as is the case in Australia".

"We believe that natural health products must also be subject to evidence-based scientific testing," she said. "This includes ensuring an adequate assessment of safety, with specific consideration given to post marketing surveillance and adverse reaction monitoring".

Shaw believes we need toxicological evaluation of dietary supplements before they're allowed to be sold. Europe, for example, requires companies to submit an assessment of recommended daily intakes, potential risks and side effects.

"I don't mean the $20 million full toxicity studies, but an assessment of the toxicity based on the literature that's out there, or toxicological opinion, or it could well require some testing to give an idea of what sort of level of toxicity that we're talking about."

"It's a big business, but they're making a lot of money because they don't need to do the toxicity testing to make sure their products are safe," he says.

There has been "a quite definite move from the dietary supplement companies to push very close to the line and making medicinal claims for their products," he says.

"They will employ lawyers to look very closely at the regulation so that they can make a statement that isn't tantamount to a medicinal claim but is so close to it, that it makes their materials look like medicines".

He says he has no problem with that, providing, if there is a medical claim, that the risk has also been assessed.

"Because if there's a medicinal claim, that's a benefit and we've got to assess that benefit against the risk, which is what you do for a medicine," he says. "It's unfair if you have dietary supplements, which are sailing very close to the wind but don't have to do any of the toxicity testing."

We can all be led astray by marketing, and Shaw also worries about the creeping medicalisation of supplements over the past decade.

Shaw and Peter Harris' research has found that products have been made to look more like medicines, and that consumers trust them more when this is done. Their study asked 200 people what they thought of different packaging, asking if the product was a medicine, and if the product would make them feel better. Plain white packaging or simple labels with words such as "XXX is thought to treat the symptoms of the common cold" was regarded at the medicine end of the spectrum.

"This survey definitely showed that people thought the simple, more medicinal-like packaging meant it was a medicine; [it] was categorical."

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Victoria University of Wellington adjunct professor Shaun Holt holds pharmacy and medical degrees, is the founder of natural therapeutic company HoneyLab, and has written eight books on how useful complementary therapies can be.

But he's campaigned strongly against some dubious therapies-like an ingestible bleach 'cure' for cancer, infamously promoted by Colin Meads-and those for which there is a lack of evidence, such as taking high doses of vitamin C.

"I actively oppose people who are promoting anti-scientific things," he says.

He splits the harm that CAM can cause into six different categories. First on his list is a substance like amygdalin, aka Laetrile, a bitter substance found in some fruit pits such as apricots, peaches and plums which can contain naturally low levels of cyanide and can be fatal.

Second is people delaying treatment in favour of natural therapies - Apple founder Steve Jobs famously delayed pancreatic cancer surgery for nine months in favour of an alternative therapy and died seven years later.

"The actual treatments don't harm them, but the fact that they haven't sought medical help, which could help, is harmful," Holt says. "I've met some very, very intelligent people using some very, very crazy therapies."

The third of his six categories is bad advice from unqualified practitioners. "For example, the vast majority of the alternative practitioners I've debated with are anti-vaccination," he says.

The fourth is psychological harm from false hope about cures; the fifth, financial harm.

"That can be just wasting $30 on a bottle of supplements that aren't going to help you one iota to people who go to, say, a Mexican cancer clinic and spend a million dollars on treatment that's not going to help them."

Finally, a lot of the alternative medicine field is simply anti-scientific, he says. "It's based on touchy-feely stories and anecdotes and not hard science."

He says the term 'alternative medicine' can be misleading; in fact, there's only medicine that works and medicine that doesn't.

"I think like anything you're going to treat yourself with, you should be well educated, you should take advice from your doctor," he says. "If something's too good to be true, or sounds like it, it probably is.

"And you've got to be careful. There are dangerous things out there. But there are also some really useful things out there as well".

A common fallacy he sees often in natural health is that if a small amount of something is good for you, "a really massive amount must be really good for you".

"That's not usually how nature works. Anything that can have a positive effect can have a negative effect as well."

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Five years on from her reaction to Andrographis paniculata, Heather Burgher still has an enlarged liver. She always carries an Epi-Pen and wears a MedicAlert bracelet, because the anaphylactic reaction she had makes it more likely she'll suffer another in the future.

She will never take a supplement again.

"It's frightening," she says. "There really needs to be a warning for people. I would hate someone else to go through this."

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