Big brain boost? What science says about the power of nootropics to enhance our minds

The comedian and actor Hannah Gadsby quipped in her hit show Nanette that she identified as [pause for dramatic effect] “tired”. In a monologue that resonated with many hard truths, that one particularly struck home for me.

The common refrain is so many of us are exhausted, have trouble sleeping, can’t concentrate, and can’t seem to get even simple tasks done without a baffling amount of procrastination.

It’s hardly surprising therefore that a large and lucrative market has sprung up dealing in so-called “natural” brain boosters, or nootropics; over-the-counter supplements, drinks and other products claiming to improve brain health and cognitive performance, sharpen memory, reduce tiredness, lift mood, and even slow age-related neurodegeneration. Already valued at US$2.2bn globally, by some estimates, the market is forecast to grow to US$4.4bn by 2032.

The list of brain-boosting ingredients in these products, ranging from drinks to cookies, spans the familiar, such as caffeine, to the less well-known; products such as ayahuasca, ashwagandha, bacopa and L-theanine. Some are newly discovered, others have been used in traditional medicines for possibly thousands of years.

But, as with so many over-the-counter products, there’s a big question mark over whether any have adequate scientific evidence to back their claims.

Related: People who use ‘smart drugs’ worse at complex tasks, study finds

The short answer, according to Prof Kaarin Anstey, director of the UNSW Ageing Futures Institute, is that they don’t. “There’s been a lot of work done on supplements and the conclusion is that it’s not worth investing in supplements,” Anstey says.

That doesn’t mean that nootropic chemicals and compounds found in foods or drinks don’t have effects on the brain and central nervous system, as anyone who’s ever had too much coffee or taken a guarana-based energy drink to try to pull an all-night work marathon can attest. There is growing evidence that some plant-derived compounds do affect the brain in a variety of ways. Researchers are looking more closely 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 a healthy brain with supplements, the gap between what scientific evidence hints at and what companies claim is particularly wide.

To get a ‘natural’ brain boosting product listed on the Australian Register of Therapeutic Goods, manufacturers only have to show 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 are within the range of ‘low-level indications’ set by the Therapeutic Goods Administration. This applies to claims such as helping mind relaxation, enhancing brain health, increasing cognitive performance and reducing cognitive fatigue.

Companies don’t actually have to provide evidence that the product does what they claim it does. This is a far cry from the more stringent requirements for registered and prescription medicines, which are required to provide detailed clinical evidence of their effectiveness and safety before they get 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 what she calls ‘nutritional psychiatry’, looking for plant-based compounds that have any kind of psychoactive effect and exploring the mechanisms of that effect.

That lack of information extends to understanding the full neurological effects of nootropics. “It’s a psychoactive substance, yet the regulations around these substances are so much more relaxed, and we have such little idea about what the impacts on the brain might be.”

Green also worries that many of these products are marketed to people in their late teens and early adulthood. “This is a period of time where the brain undergoes its final maturation,” Green says. Using any neuroactive products, whether licit or illicit, during this period of time, she says, could “shift the neurodevelopmental trajectory” in such a way that may lead to illnesses further down the track.

‘Nature might have some better answers’

But the prospect of discovering new compounds that could alter brain development, chemistry and function is a tantalising one, especially with dementia 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 out of ten Australians have experienced mental health issues at some point in their lives, and 18% of Australians took a prescribed mental health medication in 2021-22.

It’s what motivated Green’s interest in the field. She started her career studying conventional psychopharmacological therapies, such as prescription anti-psychotic and antidepressant medications, but soon felt this field of medicine had hit something of a roadblock. “We haven’t made much progress since basically the fifties,” she argues. “So I started to think, perhaps the traditional kind of white powder is not the way to go about it, and that nature might have some better answers for us.”

One of her recent studies reported on the levels of neuroprotective compounds – in particular, ones that reduce oxidative stress, which is linked to inflammation, – in foods including queen garnet plum, clove, 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 boost these cells after they experienced oxidative stress, or neutralise the substances that caused the oxidative stress.

At the Queensland Brain Institute, neurophysiologist Professor Frédéric Meunier is investigating the nootropic activity of the Lion’s Mane mushroom – Hericium erinaceus. Even in the fantastical world of the mycological, Lion’s Mane is a weird one – it looks a bit like a pale hairy brain.

Meunier and colleagues have been treating cells from the hippocampus – the region of the brain associated with memory – with various compounds isolated from the mushroom, as well as feeding mice varying concentrations of the mushroom.

Mice fed extracts of the mushroom were more inquisitive and performed better on memory tests. But mice studies do not predict human results, and even so the study’s findings are a long way from developing something that boosts cognition or memory, or staves off their age-related loss. However, Meunier is hoping to establish a research centre specifically focused on healthy brain ageing, with a view to identifying and trialling compounds that improve cognitive retention, strengthening the brain against the declines of age.

One challenge with studying the possible benefits of nootropics is that even if they do have a clinical effect, it’s likely to be small, says Prof Nenad Naumovski, a researcher in human nutrition at the University of Canberra.

“With these types of products, it’s very difficult to look into the very large physiological changes, like what you would expect to see with medications,” Naumovski says.

Instead, researchers are looking for hints in the brain chemistry of smaller benefits that might build up over time, such as an increase in antioxidant levels that some think could lower 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’s an amino acid – the substances most commonly known as the building blocks for proteins – and it’s found in particularly high levels in green tea, which also contains caffeine, albeit at lower levels than in coffee.

L-theanine, particularly in combination with caffeine, is one of the more studied natural nootropics. Studies suggest it can improve attention, memory and distraction levels.

“Once it has been consumed, once it passes the blood-brain barrier, it stimulates the production of alpha waves in the brain, and that is also associated with that feeling of alertness, but a calmness,” Naumovski says. The combination of L-theanine and caffeine in green tea seems to be key, he says, as the L-theanine interacts with the caffeine to lower the effect it has on heart rate but without reducing the caffeine ‘kick’. Naumovski and colleagues are also now investigating whether L-theanine in green tea can have benefits for sleep and are recruiting participants for a clinical trial called THESleep Project in Canberra.

Supplements v balanced diet

Perhaps the strongest evidence for the power and effectiveness of plant-based nootropics is when they’re consumed in their original form – fresh fruit and vegetables, for example – as part of a balanced healthy diet, Anstey says. “There’s lots of nutrients in fruit and vegetables that are neuroprotective,” she says, and they also have positive effects on almost every other aspect of healthl.

Like so many quests for a medical magical bullet that will solve complex problems, like mental exhaustion or dementia, the answerusually lies in simply following a healthy diet.

Green’s own research on natural nootropics has had an effect on her dietary habits. She tries to include as many purple foods in her family’s diet, but also focuses on getting lots of different coloured plant foods on to the plate.

“It’s about modifying the trajectory,” Anstey says. “A healthy diet can slow down some of those processes or stop them starting.”