Comedian and actor Hannah Gadsby joked in her hit show Nanette with which she identified [pause for dramatic effect] “tired”. In a monologue that resonated with many hard truths, that one in particular stood out to me.
The common refrain is that many of us are exhausted, have trouble sleeping, can’t concentrate, and can’t complete even simple tasks without a mind-boggling amount of procrastination.
It is therefore not surprising that a large and lucrative market has emerged dealing in so-called “natural” brain boosters, or nootropics; over-the-counter supplements, drinks, and other products that claim to improve brain health and cognitive performance, sharpen memory, reduce fatigue, improve mood, and even slow age-related neurodegeneration. The market is already valued at $2.2 billion globally by some estimates and is expected to grow to $4.4 billion by 2032.
The list of brain-boosting ingredients in these products, ranging from drinks to cookies, includes the well-known, like caffeine, to the lesser-known; products such as ayahuasca, ashwagandha, bacopa and L-theanine. Some are newly discovered, others have been used in traditional medicine for thousands of years.
But, as with many over-the-counter products, there is a big question mark as to whether there is enough scientific evidence to back up their claims.
Related: People who use ‘smart drugs’ are worse at complex tasks, research shows
The short answer, according to Prof. Kaarin Anstey, director of the UNSW Aging Futures Institute, is that this is not the case. “A lot of work has been done in the field of supplements and the conclusion is that it is not worth investing in supplements,” says Anstey.
That doesn’t mean that nootropic chemicals and compounds found in foods or drinks don’t have an effect on the brain and central nervous system, as anyone who has ever drank too much coffee or drank a guarana-based energy drink to try it all out to get out of the closet. -night work marathon can testify to this. There is growing evidence that some plant compounds affect the brain in different ways. Researchers are taking a closer look at these mechanisms in the hope that it could lead to better prevention or treatment of age-related neurodegeneration and diseases such as dementia. However, when it comes to improving brain health with supplements, the gap between what scientific evidence indicates and what companies claim is extremely wide.
I actually avoid taking supplements because I’m so aware of the lack of information.
For a ‘natural’ brain-boosting product to be listed on the Australian Register of Therapeutic Goods, manufacturers only need to demonstrate that the ingredients in their products are all permitted in Australia; that they are manufactured according to the principles of good manufacturing practice; and that the health claims made fall within the range of “low indications” established by the Therapeutic Goods Administration. This applies to claims such as helping the mind relax, improving brain health, improving cognitive performance and reducing cognitive fatigue.
Companies don’t actually have to prove that the product does what they claim it does. This is a far cry from the stricter requirements for registered and prescription drugs, which must provide detailed clinical evidence of their effectiveness and safety before being approved.
“I actually avoid taking supplements because I’m so aware of the lack of information,” says neuropharmacologist Dr Katrina Green from the University of Wollongong. Her research focus is on what she calls ‘nutritional psychiatry’, looking for plant compounds that have some form of psychoactive effect and investigating the mechanisms of that effect.
That lack of information extends to understanding the full neurological effects of nootropics. “It is a psychoactive substance, but the regulations surrounding these substances are so much more flexible and we have so little idea what the consequences for the brain may be.”
Green also worries that many of these products are marketed to people in their late teens and early adulthood. “This is a period when the brain is undergoing its final maturation,” says Green. Using neuroactive products, both legal and illegal, during this time, she says, could shift the neurodevelopmental trajectory in a way that could lead to disease later on.
‘Nature may have better answers’
But the prospect of discovering new compounds that could alter brain development, chemistry and function is tantalizing, especially as dementia is now the leading cause of death in women and on track to be the same in men. Despite decades of research, there are still no effective treatments, let alone cures, for dementia.
Mental illness is also a modern epidemic – more than four in 10 Australians have experienced mental health problems at some point in their lives, and 18% of Australians took prescription mental health medications in 2021-2022.
It’s what motivated Green’s interest in the field. She began her career studying conventional psychopharmacological therapies, such as prescription antipsychotics and antidepressants, but soon felt that this field had hit a roadblock. “We haven’t made much progress since the 1950s,” she argues. “So I started thinking, maybe the traditional kind of white powder isn’t the way to go about this, and maybe nature has better answers for us.”
One of her recent studies reported on the levels of neuroprotective compounds – specifically compounds that reduce oxidative stress, which is linked to inflammation – in foods such as pomegranate, cloves, elderberry, lemon balm and sage. This study suggested that many of these foods either reduce the negative effects of oxidative stress on SH-Sy5Y nerve cells, help stimulate these cells after they experience oxidative stress, or neutralize the substances that caused the oxidative stress.
At the Queensland Brain Institute, neurophysiologist Professor Frédéric Meunier investigates the nootropic activity of the Lion’s Mane mushroom – Hericium erinaceus. Even in the fantastic world of mycology, Lion’s Mane is a strange world: it looks a bit like a pale, hairy brain.
Meunier and colleagues treated cells from the hippocampus – the area of the brain associated with memory – with various compounds isolated from the mushroom, and fed mice different concentrations of the mushroom.
Mice given extracts of the mushroom were more curious and performed better on memory tests. But studies in mice don’t predict human outcomes, and yet the research findings are still a long way from developing anything that improves cognition or memory, or staves off age-related loss. However, Meunier hopes to establish a research center specifically focused on healthy brain aging, with an eye to identifying and testing compounds that improve cognitive retention and strengthen the brain against aging.
One challenge in studying the potential benefits of nootropics is that even if they have a clinical effect, it is likely to be small, says Prof. Nenad Naumovski, a human nutrition researcher at the University of Canberra.
“With these types of products it is very difficult to look at the very large physiological changes that you would expect with drugs,” says Naumovski.
Instead, researchers are looking for clues in brain chemistry of smaller benefits that can build up over time, such as an increase in antioxidant levels that some think could reduce the brain inflammation associated with so many neurodegenerative diseases, including dementia and multiple sclerosis.
One compound that is emerging as an interesting candidate is L-theanine. It is an amino acid – the substances best known as the building blocks for proteins – and is found in particularly high concentrations in green tea, which also contains caffeine, albeit in lower concentrations than in coffee.
L-theanine, especially when combined with caffeine, is one of the more studied natural nootropics. Studies suggest it can improve attention, memory, and distraction levels.
“Once it’s consumed, once it crosses the blood-brain barrier, it stimulates the production of alpha waves in the brain, and that’s also associated with that feeling of alertness, but with calmness,” says Naumovski. The combination of L-theanine and caffeine in green tea appears to be crucial, he says, because L-theanine works with the caffeine to reduce its effect on heart rate, but without reducing the ‘kick’ of caffeine. Naumovski and colleagues are now also investigating whether L-theanine in green tea may have benefits for sleep and are recruiting participants for a clinical trial called THESleep Project in Canberra.
Supplements versus balanced diet
Perhaps the strongest evidence for the power and effectiveness of plant-based nootropics is when they are consumed in their original form — for example, fresh fruits and vegetables — as part of a balanced, healthy diet, says Anstey. “There are many nutrients in fruits and vegetables that are neuroprotective,” she says, and they also have positive effects on almost every other aspect of health.
As with many searches for a medical magic bullet that will solve complex problems such as mental exhaustion or dementia, the answer usually lies in simply following a healthy diet.
Green’s own research into natural nootropics has had an effect on her dietary habits. She tries to incorporate as many purple foods into her family’s diet as possible, but also focuses on putting lots of different colored plant foods on the plate.
“It’s about adjusting the trajectory,” says Anstey. “A healthy diet can slow or stop some of these processes.”