Hungry no more
New Zealand plant scientists have developed a new pill to control appetite that could revolutionise the weight-loss market when it’s released today. Donna Chisholm reports.
Fast refers to the mainly caffeine-based supplements that speed up your metabolism to burn fat, fillers are fibre-based products that swell in the stomach to make you feel fuller, and “farts” are laxatives. Add to these the ubiquitous garcinia cambogia, a citrus-rind extract which, if it works at all, is meant to do so by stimulating the release of serotonin to lift mood and suppress appetite. Perhaps that’s a fourth “f” – the feel-good factor.
Weight-loss treatment is a field that’s littered with failure, as most studies show supplements make almost no measurable difference. But Kiwi scientists at Plant & Food Research and a natural products company, Lifestream, have now teamed up to market a bitter extract of hops that they believe will be a game-changer in the market.
Calocurb, the brand name for the trademarked extract the scientists called Amarasate, is the first supplement in the world that acts by triggering the release of satiety hormones in the gut that signal the brain to tell us to stop eating, a process research leader Dr John Ingram, scientist Dr Ed Walker and the team have labelled the “bitter brake”. It’s an evolutionary defence mechanism – traditionally, bitter foods are potentially harmful, while sweeter ones are safe.
“We’re very excited,” says Ingram. “It’s been a long road.”
The weight management market for slimming products in New Zealand is worth around $50 million a year, but meal replacement shakes dominate sales. Worldwide, the market is estimated to top $300 billion.
Amarasate was developed in a six-year research project, funded in part by $20 million from the Ministry of Business, Innovation and Employment and investment from food companies, to investigate and target satiety mechanisms in various levels of the gastrointestinal tract.
Ingram’s team tested 900 extracts – 10 of which were from hops – on enteroendocrine cells in the lab. The cells sense and “taste” food as it passes through the gut, sending hormonal signals to tell the brain what we’re eating. When a bitter compound attaches to the bitter taste receptors in the enteroendocrine cell, it sparks a cascade within the cell that releases calcium, and the calcium triggers the cell to release satiety hormones.
He says the extract that’s now being marketed significantly outperformed the others in initial screening tests in 2013. “We got to the secondary screen, using a lot of different doses, and the really potent ones worked at lower and lower doses. That’s where it started to shine – you knew it wouldn’t take that much to achieve the effect.”
At that stage, the team remained cautious because the success rate of products identified in cell-based screening is “incredibly low” when they’re used clinically. One of the first challenges was to put the extract in capsule form so it could be delivered past the stomach to the duodenum, where the satiety hormones are released. An American company with technology that forms part of the product’s trademark produced the first capsules that same year.
“The real eureka moment came when I tried the capsule for the first time in late 2013,” says Ingram. “I can still recall the excitement when the satiety effect kicked in. You seem to lose interest in food. You lose the hunger drive. You can still eat food, but you don’t feel like it. I thought, ‘We’ve cracked it!’ Those rare moments are incredibly special.”
The product is being marketed on the strength of one double-blind, randomised clinical study in 19 lean men, published in 2016, which showed the extract reduced consumption by an average of one megajoule – 238 calories – when taken an hour before the meal.
When the results of that study came in, says Ingram, “we were ecstatic… over the moon. This is a very potent effect. To get a megajoule reduction in intake for these sorts of studies is quite spectacular.” The feeling of satiety lasts for three hours or more.
Two more studies are about to begin – one looking at the effect of the extract in overweight and obese women, the other in overweight and obese men. When the supplement goes to market through the Calocurb website today, it can’t legally be promoted for “weight loss” because our law forbids that claim being made about a natural product, even if subsequent research finds study participants do lose weight.
That doesn’t faze Lifestream chief executive Sarah Kennedy, a former vet and animal nutritionist, who was for 11 years the CEO at Vitaco, the country’s biggest supplier of branded vitamins and supplements. She’s brought in PR guru Deborah Pead to help launch the new product using the same approach – news stories and “a mix of paid and unpaid digital influencers” – that Pead used to great effect for the birth of My Food Bag in 2013. This time, Pead has skin in the game as an investor in Lifestream. Both are careful to stress that Calocurb is not a magic pill but a “helper”. Pead describes most weight-loss supplements as “hope in a bottle”.
Kennedy says when Plant & Food’s commercial development manager Brendan Vercoe approached her more than 18 months ago about Calocurb, she was struck by the findings from the trial in the lean men. “To get a natural product that’s gone through a double blind clinical trial and gets that sort of result really impressed me.
“It’s quite hard to get a clinical trial of a natural product that shows a definitive result like that over a short period, because they are low potency and you take them for a long time. What entranced me is the weight loss market has been absolutely flat, with nothing new in six years, since garcinia cambogia came along.”
She believes it’s important to keep the business New Zealand-based. “A huge part of this is to show the world we can create world-leading science in New Zealand, commercialise it, and bring that benefit back.”
Private equity partners have raised $3 million to get the product off the ground. It will be sold online and initially available only to buyers in New Zealand, then Australia and later China. Kennedy says 65% of weight management products in the US are sold online. “It’s a bit like sex toys. People don’t like walking into a shop and buying them.”
She predicts product sales could top $15 million in the first year, before climbing to as much as $100 million within four years, and the deal includes a guaranteed 3% royalty payment to Plant & Food in perpetuity. A 45-capsule bottle will sell for $59.95. The company’s business plan was validated through the Global Access Programme at the University of California, Los Angeles.
Kennedy uses the capsules when she’s travelling, when meal times can be unpredictable and food quality variable. Side effects appear to be few. “Some guys who’ve used it thought they got a tiny amount of reflux, but they love it because it tastes like when you burp beer. You can get a small laxative effect, but it’s a softening of the stool, not diarrhoea.”
She and Ingram are mindful of the potential for misuse of Calocurb by young people with eating disorders. The label recommends it shouldn’t be used by those under 18. “We’re promoting it to support adults in weight management goals,” she says, “with an emphasis on health and nutrition instead of the outdated understanding of dieting.”
The company aims to provide social media advice by a psychologist discussing body image and “the hard truths” of self-esteem, diet-pill abuse and signs of eating disorders. “We won’t be mass-marketing the product. We’ll be very focused on our key demographic of 35-54-year-olds.”
Lifestream’s medical ambassador, Auckland obstetrician and gynaecologist Emma Parry, says the bitter brake mechanism makes scientific sense, and even though Calocurb has only one clinical trial to back it so far, “there are many things touted out there as helping with weight management without any science behind them. This is early science and in an ideal world you’d have more studies. If it was a medicine, it would go through a very different process. But as a health professional, I love the fact it’s a natural product, it’s got research behind it and it supports people in not eating so much food. Portion size and portion control are among the major causes of our obesity problem, so it gives people an opportunity to take back a little control.”
Parry says though she’s no expert in weight management, her understanding is that bariatric surgery is the only treatment proven to work. “So if there’s an option that’s not so extreme, I’d support that.”
Kennedy’s GP, who didn’t want to be named, tried the extract for a few days before Christmas and told North & South she thought it did lessen her appetite. “I didn’t feel like a meal at all, so I either didn’t have one or I ate less.”
She says she’d recommend it to patients as part of a conversation about weight-control advice but it may be particularly helpful for those having trouble with portion size, or managing the 5:2 diet, which involves fasting days. “It’s exciting – and because it’s New Zealand-based, it’s even more exciting.”
Plant & Food, which developed the hop variety in the 1980s for beer bittering, won’t name it for commercial reasons, but New Zealand Hops chief executive Doug Donelan says it’s a popular type grown in Nelson and used in a number of mainstream premium lager-style beers. “It’s quite high in what’s known as alpha acids – the potential it has for efficient bitterness.”
Donelan, who’s been involved in the research project since its inception, says New Zealand Hops will be closely watching sales forecasts for the new product and matching production to demand. “We’re quite excited because for us to have a product for hops outside beer gives us a broader customer base and helps to de-risk the business. If it hits the levels they hope, it’ll create jobs, and the facility and growing areas will be expanded to meet the demand.”
If the product gets a lot of traction, says Donelan, the plant could become the single largest hop variety grown in New Zealand and an important earner. Annual revenue from all 18 hop varieties is about $30 million per annum. It takes 3.75 tonnes of dried hops – 5800 plants – to produce one tonne of the extract.
Like Ingram, he’s tried the product. “It works. It makes you feel like you’ve eaten – you don’t feel as hungry. I like to drink beer, so if I wanted to lose some weight, I could in fact not drink beer. But I prefer not to stop drinking beer.”
Ingram stresses that like any weight management product, the extract can’t work alone – it has to be used as part of an energy-restricted diet and increased exercise. But he says in his research career, the development of Amarasate is his team’s biggest achievement to date. “We are all driven to improve people’s health, and this is probably the most impactful thing we’ve ever done.”
The skinny on popular, recent weight-loss drugs.
In 1998, there was only one name on dieters’ lips – Xenical, the new weight-loss drug that looked for a time as if it could be the magic bullet that might halt the obesity epidemic.
In New Zealand, where Xenical wasn’t publicly funded but direct-to-consumer advertising of prescription drugs is allowed, pharmaceutical company Roche embarked on a $2 million television ad campaign. It was an instant success, with the company’s pharmaceutical business manager telling North & South in 2003, “We couldn’t get around the GPs fast enough. They were crying out to see us.”
The product worked by stopping enzymes in the gut from breaking down and absorbing dietary fat, meaning 30-40% would pass through the digestive system. But Xenical’s sales hit their peak within a year or two of the drug’s release and prescription numbers were soon in decline, with increasing concerns over unpleasant side effects – flatulence, an oily discharge and sometimes an inability to control bowel movements – and efficacy.
Xenical was re-classified as a pharmacist-only medicine in 2005, and a doctor’s prescription was no longer required. Nor, apparently, were many sought. Today, 20 years after the fireworks surrounding its launch, it’s faded almost completely from public consciousness.
Roche sold Xenical to German pharmaceutical company Cheplapharm last year. Some of the company’s products, including Xenical, are managed here by Pharmaco, whose head of marketing Chris Ivers told North & South that Xenical was a “very old” product that’s not actively marketed. Pharmaco has no data on current sales.
In 2016, Boston-based health news website Stat reported that internationally, sales of anti-obesity drugs were “flat” and “flailing”, with new products launched in the United States, such as Contrave and Belviq, failing to meet multi-billion dollar sales expectations.
“There is a place for weight-loss drugs… but it is a small place,” American physician David Katz, a world-renowned authority on nutrition, wrote in Britain’s Pharmaceutical Journal. “The history of weight-loss drugs is a litany of disappointments, large and small. From a population health perspective, drugs for weight loss are not merely the wrong answer, they are the wrong answer to the wrong question. The question weight-loss drugs ostensibly answer is: What are some effective ways to facilitate weight loss? When correct answers may include serious illness, eating disorders, or even cocaine use, you are well into the realm of bad questions.”
He wrote that a better question was to ask about the best ways of achieving “sustainable” weight loss. “Unless ‘sustainable’ is constrained within a span of 24 months or thereabouts, no weight loss drug has ever proven to be an answer to this question.”
One of the few drugs available here for weight loss is Duromine, which is said to suppress appetite, but it’s also been linked to drug abuse; in Australia, it’s been nicknamed “legal speed”, and its side effects include increased blood pressure and heart rate, depression, nervousness, dizziness, vomiting and diarrhoea. It’s not Pharmac-funded.
The anti-depressant Fluoxetine and pre-diabetes treatment Metformin are also sometimes prescribed for weight loss, but results are mixed.
Donna Chisholm is North & South’s editor-at-large. This article was published in the April 2018 issue.