Introduction
It’s 6 am and you have a long day of work, family obligations, and gym training ahead. Time to start it off right with your usual tea or coffee, right?
Wrong! Well, not entirely. Coffee or tea may help your productivity, but so can ashwagandha, theanine, and GABA. There are reasons these ingredients are skyrocketing in popularity and are included in pre-workouts and nootropic products alike. Those reasons are both scientific and subjective. This article is going to dive deep into the science behind these nootropic ingredients. In general, theanine, ashwagandha and GABA do not have the same effect on the brain or heart as caffeine. Caffeine acts faster and has more effects on alertness, while theanine acts slower and literally increases calm.
Headaches after caffeine withdrawal are real. However, there may be an underlying reason you feel like you NEED that daily dose of java. It may be called productivity insecurity or in some cases it may be called anxiety. It seems we all suffer from some sort of productivity insecurity, but research has found that women tend to experience more anxiety than men. According to the National Institute of Mental Health, 19% of Americans have experienced any kind of anxiety disorder, with 2.7% of those people experiencing generalized anxiety disorder.
In 2019, 301 million people in the world had an anxiety disorder, making them the most common of all mental disorders. We drink caffeine not necessarily because we’re physically addicted, but we’re afraid of errors that might happen if we’re not at maximum alertness. Nootropics can help reverse engineer this productivity-fear cycle by improving sleep, mood, and focus via different pathways than pure central nervous system stimulation. The result is productivity that is essentially “from the ground up” but in reality, it’s from the GABA up.
One of the most common sources of anxiety is caused by financial distress which can cause a negative effect on job performance. The conservation of resources theory predicts that anxiety caused by financial distress decreases employees work quality because anxiety drains individuals’ physical, cognitive, and psychological resources. Other causes of stress are academic workloads, balancing childcare and work responsibilities, relationship problems, and just plain old loneliness. Of course, coffee, energy drinks, and pre-workout may enhance our mood temporarily, but you may want to consider cycling off these stimulants to avoid dependence and side effects. Enter the world of nootropics where side effects are virtually non-existent with the proper doses.
Unveiling Key Ingredients for Mood Enhancement
The Power of Ashwagandha
Withania somnifera, also known as ashwagandha, is a shrub that is grown in India’s drier regions. Its other nicknames include “winter cherry,” and “Indian ginseng.” Ashwagandha has been used in Ayurveda, or ancient Indian medicine, for 3,000+ years. Most of modern science focuses on the roots, but there are several uses for the leaves in Indian folklore, ranging from joint pain to wound care. Speaking of science, this article will only mention human studies of ingredients, not animal or test tube studies.
Withanolides are naturally occurring steroidal lactones considered to be the bioactive part of ashwagandha. To find out which withanolide is strongest, Indian researchers recently performed an analysis of nine batches of the same brand ashwagandha and found that 12-deoxywithastramonolide was the most active isolated compound.
However, they concluded that there may be some synergy with other withanolides and other parts of the plant contribute to the overall effect. What effect is this? The test they used is called an acetylcholinesterase inhibitory assay (AChE), which measures how well a product inhibits, or blocks, the enzyme cholinesterase from breaking down the neurotransmitter acetylcholine. Acetylcholine causes excitation of the sarcolemma of muscle fibers, causing muscle contraction. It also sends signals related to memory and behavior. Ashwagandha is a natural AChe inhibitor which helps preserve acetylcholine and promote stress reduction.
What Does Ashwagandha Do?
Studies suggest that the stress-relieving property of ashwagandha is due to modulation of the HPA axis. The HPA axis is an important hormonal response system which controls stress. This axis ensures that the body quickly responds to nerve-racking moments and returns to a normal state.
Stress/Anxiety
Forty patients diagnosed with generalized anxiety disorder (GAD) and already taking SSRIs as medication participated in a randomized double-blind placebo-controlled trial. The participants took a 1g capsule of ashwagandha daily for 6 weeks and significantly improved their scores on the Hamilton Anxiety Rating Scale (HARS). These results show promise for the herb to be use an adjunctive therapy to SSRIs for GAD.
A 2019 Cureus study had 58 males and females with high perceived stress scores take either 250 mg ashwagandha, 600 mg ashwagandha or a placebo daily for eight weeks. The study found that both ashwagandha groups lowered their stress scores on the Perceived Stress Scale, lowered their mean cortisol levels and improved their HARS scores. The 600mg dose was found to be more effective in the stress and anxiety reduction compared to the 250 mg daily dose. (NutraBio Calm contains 600 mg of this exact type of ashwagandha, which is used in several studies).
According to a Medicine (Baltimore) study, 240 mg daily of ashwagandha can decrease anxiety levels by 17% more than a placebo as measured by the HARS. In this study, people took the ashwagandha daily for 60 days and had statistically significant lower anxiety and cortisol levels. The subjects also improved their scores on the Depression, Anxiety, Stress Scale (DASS-21).
In a 2021 Evidence Based Complementary and Alternative Medicine Study, 125 participants took a sustained release 300 mg ashwagandha pill once daily for 90 days and saw their perceived stress scores and cortisol levels significantly decrease. They also reported significant increases in the Oxford Happiness Questionnaire and a recall memory test.
Researchers out of Jacksonville University recently examined the effects of 225 mg daily ashwagandha, 400 mg daily ashwagandha, or a placebo on cognitive function and stress in 57 healthy adults over the course of 30 days. The subjects that took the 400 mg dose saw a statistically significant decrease in reaction time (which is an improvement) and a reduction in cortisol levels. Interestingly, the 225 mg group saw a statistically significant decrease in cortisol compared to the 400 mg group.
For human trials on anxiety/stress conducted prior to 2015, visit the following systematic review.
Memory
According to the Journal of Dietary Supplements, a 600 mg daily dose of ashwagandha can improve immediate and general memory, executive function, attention, and information processing speed in people with mild cognitive impairment (MCI). MCI involves mild subjective complaints of memory loss without any medical explanation. The subjects saw these cognitive benefits after 8 weeks of supplementation.
Male Infertility
Normozoospermic infertile men are unable to fertilize a woman despite sperm concentration in the range considered normal. This is called unexplained infertility. A 2011 study compared 60 of these men (some of which smoked or had high stress levels) to 60 men with fertile sperm. All men were given 5g of Ashwagandha daily for three months. As a result, the levels of luteinizing hormone, testosterone and antioxidants increased while stress and serum cortisol levels decreased.
According to the authors, stress leads to low testosterone levels due to a reduction in the LH pulse frequency. Ashwagandha reduces stress, which in turn improves fertility by modulating the hypothalamic, pituitary, gonadal axis. Indeed, 14% of the infertile men had gotten their partners pregnant at 3 months follow up.
Testosterone Levels
In a 2022 Health Science Reports study, 50 males with low sexual drive took 600mg ashwagandha or placebo daily for 8 weeks. The ashwagandha group saw their serum testosterone levels increase by an average of 72 ng/dl while the placebo group only increased by 5 ng/dl. That’s a 17% increase for the ashwagandha group versus a 2% increase for the placebo group.
Coincidentally, a 2013 study on ashwagandha and hormones also saw a 17% increase in testosterone compared to baseline levels, but these guys took 675 mg per day for 90 days. This was an average of 100 ng/dl increase from the baseline by taking the ashwagandha.
According to the Journal of International Society of Sports Nutrition, ashwagandha may improve muscle strength and size in beginners more so than those taking a placebo. After 8 weeks of resistance training and taking 600mg ashwagandha daily, the treatment group saw significantly bigger upper body muscles and the bench press and leg extension strength compared to the placebo group. Testosterone also increased significantly more in the ashwagandha group (96 ng/dl average increase vs 18 ng/dl average increase for placebo).
Sleep
A recent randomized controlled trial (RCT) examined the effects of 600mg ashwagandha or a placebo taken daily for 8 weeks on sleep quality of healthy subjects and those having insomnia. Sleep parameters such as Sleep Onset Latency (SOL), Total Sleep Time (TST), Wake After Sleep Onset (WASO), Total time in bed (TIB) and Sleep efficiency (SE) were assessed. In both the healthy and insomnia subjects, there was significant improvement in sleep parameters compared to the placebo group. These improvements were greater in the insomnia patients.
In one study of college students, 700 mg of ashwagandha or placebo was administered daily for 30 days to assess its effect on stress, energy, and sleep. Using daily check-ins and focus groups, the researchers concluded that the students improved perceived well-being through supporting sustained energy, heightened mental clarity, and enhanced sleep quality.
According to a recent RCT published in Sleep Medicine, 120 mg of standardized ashwagandha (Shoden) taken once daily for 6 weeks can improve sleep quality in healthy adults. The subjects saw significant improvements in sleep efficiency, hours and latency which is the amount of time it takes to fall asleep.
Ashwagandha has also been found to be safe and effective for improving sleep quality in elderly adults (Ages 65-80), says Indian researchers. In a12-week study, participants were assigned to take either 600 mg of ashwagandha or a placebo daily and were surveyed on their sleep and quality of life. The ashwagandha group saw significant increases in sleep quality and mental alertness while rising.
For more information on ashwagandha and sleep, check out this review.
Cardiorespiratory endurance
A meta-analysis of four studies in the journal Nutrients examined the effect of ashwagandha on VO2 max, or the maximum of oxygen you can uptake during exercise. Higher VO2max levels are associated with better cardiovascular/aerobic endurance. The authors concluded that “Ashwagandha supplementation might improve the VO2max in athletes and non-athlete. The analyzed studies used oral administration of Ashwagandha which varied between 2 and 12 weeks with intakes between 300 to 1000 mg/day.”
Discovering L-Theanine
Theanine is a non-protein amino acid discovered in the leaves of green tea (Camellia sinensis) in 1949. The most abundant amino acid in green tea, theanine is responsible for the strong smell and linked to the umami taste. Also called gamma-glutamylethlamide, theanine has also been studied for its stress reduction, calming, and focus-inducing effects. The conditionally essential amino acid glutamine is a core part of its structure, and theanine gets hydrolyzed into glutamic acid after digestion. Green tea also contains caffeine and catechins, of which epigallocatechin gallate (EGCG) is the most abundant.
Theanine and caffeine seem to be linked in the literature, with studies looking at the effect of theanine alone, caffeine alone or caffeine and theanine combined. Studies look at both subjective and objective markers, with the objective ones often being quite complex/specific mental tasks. In general, caffeine takes about 30 minutes to reach peak effects whereas theanine takes about 50 minutes. Let’s look at the benefits of theanine, a popular soothing ingredient.
What Does Theanine Do?
Stress/Anxiety
Twenty healthy Japanese pharmacy school students participated as subjects in a theanine study during their clinical rotations. The students were given 400 mg of theanine or a placebo daily for 17 days. The researchers assessed the physiological stress response by measuring salivary amylase (sAA), as this enzyme is increased rapidly in response to physiological and psychological stress. Subjective stress was analyzed using visual analog scales (VAS 1-10) anxiety was assessed using the state-trait anxiety inventory (STAI), and sleeping hours were also recorded. The results showed that morning sAA levels were significantly lower in the theanine group vs the placebo group and theanine significantly decreased subjective stress. Hours slept were significantly higher in the low sAA group compared to the high sAA group.
Ingestion of 200 mg theanine alone can reduce blood pressure in a high response group and decrease subjective stress (as measured by Profile of Mood State) after the performance of mental tasks, according to a 2012 study. The high response group consisted of “participants whose blood pressure increased more than average by a performance of a mental task after placebo intake.”
Theanine supplementation was found to have multiple beneficial effects of the symptoms of major depressive disorder in patients. In an 8-week study, patients with depression took 250mg daily along with their standard medication and saw a decrease in subjective scores in depression and anxiety scales. The subjects also saw improved sleep quality and cognitive enhancements. This was an open-label study meaning it was not blinded and subjects knew they were taking theanine.
Cognition/Focus
An RCT in Pharmacology examined the effects of theanine, caffeine, or theanine and caffeine on sustained attention. Subjects in this study performed the Sustained Attention to Response Task (SART) over a two-hour session on each of four days, on which they were administered caffeine (50 mg), theanine (100 mg) the combination, or placebo. Caffeine decreased omission errors by 50% while theanine decreased these errors by 30% compared to placebo. Caffeine decreased commission errors by 30% compared to 23% reduction by taking the theanine.
Sensorimotor gating is the ability of the brain to filter or “gate” unnecessary/irrelevant information when exposed to several stimuli in the environment. An example of this would be focusing on one conversation in the gym during a loud music and other people talking. According to a 2014 study, doses of 200mg or 400mg of theanine can significantly increase sensorimotor gating as measured by prepulse inhibition in healthy adults.
In a Nutrition Research study, researchers used magnetic resonance imaging (MRI) during visual color discrimination tasks to assess the effects of 200mg theanine, 160mg caffeine, and a combination of both on attention. Theanine alone resulted in an increased ability to ignore distractor colors and focus on the target colors, compared to placebo. Researchers also suggested that “l-theanine and caffeine seem to have a synergistic action in decreasing mind wandering.”
Immune System
The combination of 700mg of the amino acid cysteine and 280 mg theanine taken daily resulted in significantly lower incidences of the common cold compared to placebo, in a 2010 study. Significant reductions in fever and chills and a decreasing trend in runny nose, sore throat, and joint pain were found during this 35-day study.
The Role of Gaba in Relaxation
Natural killer cells (NK) are white blood cells that fight infection, specifically destroying pathogens without prior exposure to them. During periods of intense training, immune suppression occurs. According to a Journal of Strength & Conditioning Research study, NKs were not affected with 3 days of resistance per week but started to decrease when participants trained 6 times per week. Supplementation with 700mg cystine and 280mg theanine restored lost NKs during the increased training load week, indicating a positive immune response. A separate study examined the immune effects of cystine and theanine on endurance athletes which also found recovery benefits.
Gamma-aminobutyric acid (GABA) is a naturally occurring amino acid produced in the brain. It’s one of the inhibitory neurotransmitters found in foods in low levels and in higher levels in fermented foods. Inhibitory neurotransmitters inhibit, or block, the overexcitation of nerves. Proper central nervous system function depends on the balance between excitatory and inhibitory neurotransmitter systems. The excitatory system is regulated by glutamate while the inhibitor system is regulated by GABA. Additionally, low levels of GABA are associated with depression. With that said, there seems to be diminishing returns in regard to GABA, where too much causes
GABA is not to be confused with gabapentin, which is an anticonvulsant medication prescribed for conditions such as epilepsy, Parkinson’s disease and even depression. With that said, GABA supplementation has been studied, just not extensively. Magnetic resonance spectroscopy (MRS), a technique for analyzing the chemicals in the brain, has been utilized to measure GABA levels in humans. However, as of this writing this technology has not been used directly after oral GABA supplementation. Here’s what we do know about GABA supplementation and levels.
What Does GABA Do?
Attention
A 2018 Brain and Cognition study found that 800mg of GABA supplementation increased performance in an attention task, including decreased errors. The researchers commented that there is speculation as to whether or not GABA crosses the blood brain barrier, but that “GABA intake might help to distribute limited attentional resources more efficiently, and can specifically improve the identification and ordering of visual events that occur in close temporal succession.”
Mood
Russian researchers used MRS to measure GABA levels in both healthy people and people at ultra high risk for schizophrenia. The high risk group were not diagnosed with schizophrenia but with other mental health disorders such as affective disorder or decompensated personality disorder. Compared to the healthy people, those at risk of schizophrenia had a statistically significant 25% lower GABA concentration in the left AC cortex.
Japanese researchers conducted interesting experiments back in 2006 on the effect of GABA and theanine on anxiety and stress. In the first part, they measured brain wave activity after ingestion of 100 mg GABA, 200 mg theanine or distilled water and found that GABA significantly increased alpha brain wave activity and decreased beta wave activity. Alpha brain waves are present during calm, relaxed states whereas beta waves occur during stressful situations or where high levels of concentration are necessary.
The second part of the study divided participants into two groups: GABA and placebo and measured participants’ levels of immunoglobulin A (IgA) in their saliva, since high levels of this biomarker are linked to more relaxation. The participants had a history of acrophobia (fear of heights) and were instructed to walk across Japan’s longest bridge, having their saliva collected along the way. The GABA group showed significantly higher levels at the bridge’s middle and end compared to the placebo.
Embracing Natural Mood Enhancers
Trying to improve mood using natural remedies rather than pharmacological ones is nothing new. Yet we see ingredients like matcha, ashwagandha, and GABA surge in popularity. Behind every trendy and buzzword, there seems to be some evidence whether it be anecdotal, empirical or both. In simpler terms, it’s supply and demand. Wanting a “quick cure” is out and searching for a whole food remedy is in. Foodies jump on the supplement bandwagon once they find out the real benefits of the latest nutrition fad.
While you might be ordering matcha tea because it’s trendy, you really should know that matcha has more theanine and caffeine than green tea. Matcha is the powdered form of green tea leaves that are harvested in shaded conditions for weeks. This shading increases its theanine content, enhancing its long, sustained relaxation effect.
As for ashwagandha, farmers are just scratching the surface on how to harvest it efficiently. Organic manure and microbial consortium (essentially probiotics for the soil) have been shown to increase the bioactivity and yield of ashwagandha. In the field of mood enhancement, novel drugs targeting both the glutamate and GABA systems are in the pipeline, researchers continue to search for the perfect balance between relaxation and excitement.
Overall, NutraBio Calm is a simple formula that can be used in conjunction with other nootropics, or as a replacement/addition to caffeine. Don’t underestimate the ingredients’ effects on relaxation and on “tunnel vision” which we now know is called sensorimotor gating.
By: Mark Barroso, MS, LAT, ATC, CSCS
These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.
At NutraBio, we believe in the power of purity for peak performance and wellness. Every supplement we offer is third-party tested and made in our own USA manufacturing facility, ensuring unparalleled quality control from beginning to end. With NutraBio, you're guaranteed fully dosed, fully transparent ingredients for the best results—because what you put in your body matters. Our commitment to E.T.H.I.Cs—Efficacy, Transparency, Honesty, Innovation, and Commitment—drives us to be your trusted partner on your health and performance journey.
