Biohacking routines: Nootropic manufacturers explore dopamine modulation and gut-brain axis

11 Mar 2024 --- In light of a growing mindset that good health is associated with mental well-being, nootropics and nutraceuticals are on an upward trajectory. Nutrition Insight catches up with ADM, OmniActive Health Technologies and PharmaLinea in this second installation about the trend, in which we learn that this segment is now only second in value to fitness, with around 49% of consumers using cognition as a measure of health. 

ADM’s Paula Limena, vice president of global marketing, health and wellness, says, “additional research shows that 66% of global consumers state they would like to address their cognitive and mental well-being using supplements, pointing to the growing popularity of supplement offerings with cognitive health support.” 

These dietary supplements may include caffeine, l-theanine, l-carnitine or creatine, which aim to support factors relevant to cognitive health. Consumers are looking to improve their cognitive health and brain performance by optimizing their moods, stress levels and quality of sleep, which should enhance mental clarity and focus throughout the day. 

“Health-conscious consumers are connecting the dots between their diets, gut health and overall well-being, which is prompting these consumers to look at dietary supplement offerings that include gut microbiome modulators, including prebiotics, probiotics and postbiotics,” says Limena. 

Modulating dopamine
According to OmniActive Health Technologies, the most widely used and clinically studied nootropic is caffeine — natural or synthetic. Caffeine from botanical sources is highly sought-after for mental focus and fatigue reduction. The company’s Xtenergy formulation, from Coffea robusta, releases caffeine in a sustained pattern with “no spikes and crashes.”Routines to optimize sleep and metabolism have become regular practice for young professionals. 

“There is also a growing trend for plant-based nootropics that can deliver the benefits of caffeine, but are not caffeine. For these consumers, enXtra, our caffeine-free product, is ideally positioned as a plant-derived nootropic based on how it works and its supporting clinical evidence,” says Sara Zoet, director of branding and activation marketing at OmniActive Health Technologies.

enXtra is made from Alpinia galanga, a plant used in ethnomedical practices by tribes of Northeast India, Thailand and the greater Asia region. The plant has been studied for its nootropic benefits based on its ability to modulate neurotransmitter levels, oxidative stress and neuronal cell integrity. 

“Specifically in the context of enXtra, our mechanism of action points to its role in modulating levels of monoamine oxidase, dopamine and acetylcholine (through acetylcholinesterase) to influence cognitive outcomes, such as alertness, focus and attention,” Zoet notes.

OmniActive formulated its caffeine-based Xtenergy to release caffeine over six to eight hours, which limits the “caffeine-crash” slump, which may include fatigue and tiredness. It circumvents rapid increases in blood caffeine levels, which cause jitters.

“Xtenergy can still deliver on its benefits of a caffeine-based nootropic — mechanistically, it still works as caffeine with respect to alertness — but without the limitations associated with caffeine.” 

Biohacking routines and sleep support
Nootropics can offer different dimensions of cognitive support. For example, it can boost focus in sports performance, improve age-related mental decline, or improve the gut-brain axis to support quality sleep, enhancing cognitive well-being. 

“Similar to mental health being increasingly perceived as imperative for or even synonymous with general health, so has cognitive performance become an equally important counterpart to physical or sports performance,” says Matevž Ambrožič, marketing and PR director at PharmaLinea. 

“The drive among young professionals to do more is fueling biohacking routines with optimized sleep, sugar metabolism and supplementation for the ultimate goal of cognitive performance. Much of it is driven by influencers on podcasts and social media. On the other hand, there is an aging population that is also contributing to nootropic demand to counter cognitive decline. The drivers are multiple, and the market is blooming.” Caffeine from botanical sources is becoming more popular.

According to ADM, sleep support stands out, with research showing a link between sleep, gut health and the microbiome. About 70% of consumers are interested in food, drink and supplement products that help improve sleeping patterns. 

“Our ongoing research offers supporting evidence on the gut-brain axis, with recent studies demonstrating the use of probiotic supplementation to help support low mood. The University of Oxford, UK, conducted a study that found changes in psychological processing and measurements of low mood following the use of a 14-strain probiotic supplement,” Limena notes. 

“A study conducted by the Institute of Psychiatry, Psychology and Neuroscience at King’s College London, UK, and led by ADM’s Dr. Viktoriya Nikolova looked at the consumption of the 14-strain probiotic supplement, finding significantly meaningful improvements in mood compared to the placebo group.”

ADM has also developed a mood and stress formulation, which includes ES1 (Bifidobacterium longum CECT7347) and BPL15 (Lactobacillus rhamnosus CECT8361), for which it is currently conducting a human clinical trial. The formulation causes a significant reduction in the response time to octanol stimulus and a reduction in anxiety.

Bounce back with botanicals
Botanical extracts are helpful for cognitive health supplementation. Chamomile, for instance, evokes a sense of relaxation. ADM uses proprietary extraction technology to formulate with ingredients such as guarana, green tea and yerba mate to produce natural sources of caffeine.

“Our WKUP formulation brings together our guarana, green tea extracts and functional carob extract. WKUP may perform comparably to caffeine, without common concerns, such as increased heart rate and temporary impact on blood pressure,” explains Limena.

Green rooibos is becoming popular in the US botanical space, where consumers associate it with mood and stress support, fatigue reduction and sleep quality. ADM is examining the effects of the extract on stress and anxiety in collaboration with the University of Canberra, Australia.

“As product labels are progressively scrutinized, supplements, especially those that support sleep and stress, have witnessed a call for a ‘return to nature’ over the past few years. This includes a push toward ingredients derived from natural sources like herbs and botanical extracts,” notes Limena.

“Consumers want these ingredients — and the associated attributes to cognitive health in convenient, delicious formats. This has spurred the convergence of foods, beverages and dietary supplements, accelerating the movement toward chewable gummy offerings. Stick packs are also on the rise, with the convenience of adding them to one’s daily water.”The regulatory landscape for nootropics and nutraceuticals means that these products have to be supported by scientific evidence.

ADM’s fast melt concept — comprising botanical extracts, vitamins, minerals and probiotics with natural fruit flavors — such as blood orange is an ideal on-the-go option.

Supported by clinical evidence
Consumers are reaching for supplements, functional foods and ready-to-drink formulations that cater to their personal wellness goals and fill nutrition gaps in their diet. OmniActive’s clinical studies are designed with the consumer’s needs in mind and provide assurance that the supporting claims meet regulatory requirements.

“Our clinical data supports the relevance of Xtenergy as a nootropic given its ability to increase and sustain a feeling of alertness and overall positive mood, which coincides with the sustained release profile of Xtenergy,” says Deshanie Rai, vice president of global science, regulatory and advocacy at OmniActive Health Technologies.

“We have several clinical studies supporting the nootropic benefits of enXtra, including a quick increase in mental alertness as soon as 60 minutes after supplementation, which is sustained up to five hours. It helps support focus and attention and reduces feelings of fatigue when consumed acutely as a single dose and with daily supplementation.” 

Nootropics act through various mechanisms of action, including changing the brain’s electrical activity, the activity of neurotransmitters, the decrease of oxidative stress, and the inhibition of specific enzymes necessary for the brain’s functioning.

Maja Orešnik, science and research director at PharmaLinea, says: “The majority of the adult population is used to drinking caffeinated drinks to help them with their day-to-day functioning, focus and energy levels.” 

“Similar or better benefits, with a lower amount of side effects or habituation, can also be expected from other nootropics. Interesting areas one can address with these ingredients are e-gaming and sports, where a lot of focus is needed to achieve good results.”

“In the past, cognitive health products targeted older adults. With the rise of nootropics, the positioning widened. Popular delivery formats resemble the usage — if a direct effect is expected — then direct sticks or shots might be a good choice.” 

By Inga de Jong