20 smart extracts for smarter supplements

[For your complete formulation and marketing toolbox on all things related to cognitive supplements, download the free October issue of the Natural Products Insider digital magazine here.]

The brain bone is connected to the hip bone—and just about everything else in the body. So when thinking about antioxidant-rich botanicals that are good for health, chances are they’re probably good for the brain, too. Luckily, the past 20 years have yielded an incredible amount of data to develop botanical-based supplements that are good for the noggin. 

In just the past year or two, dozens of well-designed clinical trials have been performed on brain botanicals. While some of these ingredients might be predictable, others—like pygmy smartweed and king’s salad—are a bit unusual. 

Anyone trying to prevent cognitive decline as they age should be encouraged by research being done around the world. The following summary hits just a sampling of these trials. 

In a 2023 study of 323 older adults with mild cognitive impairment, an extract from lemon balm (Melissa officinalis) significantly improved clinical dementia scores versus placebo. This suggests that lemon balm extract may help prevent cognitive decline. 

A 2021 study found that sesame oil cake extract improved verbal memory and plasma beta amyloid in older adults with memory impairment. Sesame contains lignins and other antioxidants, such as sesamin, with an interesting bit of supporting evidence for anti-aging, vascular and brain health. 

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Spermidine is an endogenous polyamine that synchronizes many biological processes and is considered a potential longevity factor, like rapamycin. It’s found in cheese, mushrooms and whole grains, albeit in small amounts. A 2022 study found that daily consumption of a wheat germ extract containing 0.9 mg spermidine did not modify memory or biomarkers. However, this dosage may be too small to affect cognition. Supplementing with higher doses of spermidine in clinical trials may have the potential to reverse memory deficit in people who are at risk of cognitive decline. 

Berries are also a big focus of cognitive research these days. While much research is mainly concentrating on blueberries and other anthocyanin-rich berries, some traditional berries are showing up in clinical research. One recent study in 312 healthy people found an anthocyanin-rich mulberry milk product (Memberry) improved working memory and suppressed enzymes associated with brain function, including acetylcholinesterase and monoamine oxidase (MAO). 

Ulam raja, or king’s salad (Cosmos caudatus) is an antioxidant-rich green vegetable traditionally consumed in Central America and Southeast Asia, including Malaysia. A 2021 study found that supplementing with 250 mg Cosmos for 12 weeks improved mood disturbance and mental capacity in older adults with mild cognitive impairment. 

Evidence also supports another traditional Malay herb, a phenolic-rich plant called smartweed. In one study, 250 mg pygmy smartweed (Persicaria minor) as Biokesum improved visual memory, mood and brain-derived neurotrophic factor (BDNF) after six months in older adults with mild cognitive impairment. 

Outside of the research that helps people of a certain age, interest is renewing in plant-derived ingredients that support a healthy mood state and sleep patterns for all ages—and without the downsides of stimulants or sedatives. One recent study looked at the effect of a multiherb extract (Euphytose) containing hawthorn berry and ballota (Grecian horehound) for 14 days. This study in healthy people found reduced subjective anxiety versus placebo, along with lowered salivary amylase, a marker of stress that mimics cortisol. 

A number of studies have focused on beneficial combinations of plant extracts for stress and mood. A 2022 study found that a combination of green tea and Rhodiola rosea combined with magnesium and B vitamins improved EEG theta state, and reduced stress and anxiety ratings in 100 healthy adults with moderate stress. 

In another recent study, the combination of beetroot, ginseng and sage in a beverage in healthy adults was synergistically enhanced by apple and coffee berry extracts for improvements in energy ratings and hemodynamic response. 

[For your complete formulation and marketing toolbox on all things related to cognitive supplements, download the free May issue of the Natural Products Insider digital magazine here.]

While the attributes of corn have been extensively studied, research on other parts of the plant that are not typically eaten show promise. A standardized extract from corn leaf (as UP165) was evaluated for its effect on sleep quality in a small randomized controlled trial. Improvements in sleep quality, deep sleep time and improved mood state were observed versus placebo. 

Bacopa monnieri has been studied for its improvement of higher-order cognitive processes like memory and executive function. Recent studies suggest further potential on some of the more elusive emotional and sleep endpoints. A 2022 study in Australia found a Bacopa monnieri extract (CDRI 08) improved cognitive flexibility and interpersonal problems in children with ADHD compared to a placebo. This study adds to the oeuvre of well-designed research supporting bacopa for the brain. 

One of my favorite herbs to use for mental energy and alertness without the crash of caffeine is the spicy root known as galanga (Alpinia galanga), a cousin of ginger and turmeric. A study in healthy adults found improvements in both alertness and calmness with galanga extract (EnXtra) compared to placebo. Notably, no increase of sleep disturbance was found, a benefit that may distinguish galanga from caffeine. 

Lotus seeds are rich in phytonutrients, polyphenols, alkaloids and enzymes like superoxide dismutase—that’s maybe partly why it’s been used as food and medicine for 7,000 years. Recent research suggests treatment with a standardized water extract of lotus (Nelumbinis semen) seeds improved stress and depression ratings in people with mood issues. 

Another 2022 study found that spirulina extract alleviated Alzheimer’s disease symptoms in people with dementia. This is the first study to show the cognitive impact of spirulina, which is known more for its immune-enhancing properties. This may partially explain the connection between brain health and immune health, as brain dysfunction is becoming increasingly linked to immune disorders. 

Echinacea is also known for its immune-enhancing properties, but recent work suggests its influence on cognitive function as well. In a recent study, Echinacea angustifolia extract EP107 at 40 or 80 mg led to improvements in emotional well-being in adults with mild to moderate anxiety. 

While it’s not approved for supplements, a lot of promise is held for psilocybin, from Psilocybe cubensis. Among several studies, one study looking at a single dose of 10-25 mg in 233 adults with treatment-resistant depression was associated with lower severity of depression and anxiety, as well as an improved quality of life. Further research is needed to determine the best sources and doses and the right controls and setting for psilocybin research. 

Research doesn’t just cover the botanicals that can be swallowed—those that can be inhaled have been used in trials as well. In fact, a number of studies have demonstrated the cognitive benefit of essential oil aromatherapy. Most recently, a 2022 study in older adults found that lavender or chamomile oil significantly improved ratings of stress, depression and anxiety within a month. 

These days, supplementing with these herbs as part of the “king’s salad bar” may be our lotus of enlightenment on the natural path toward improved brain function and longevity. 

Blake Ebersole has led several botanical quality initiatives and formed collaborations with dozens of universities and research centers. As president of NaturPro Scientific, Ebersole established quality compliance and product development services for supplements and ingredients such as ID Verified. Follow him on Twitter at @NaturalBlake. 

[For your complete formulation and marketing toolbox on all things related to cognitive supplements, download the free October issue of the Natural Products Insider digital magazine here.]