L-theanine for anxiety: Genetics and nature’s chill pill

A popular supplement for anxiety, l-theanine from green tea is often promoted as a miracle solution for mood and sleep.

This article examines the research and clinical trials on l-theanine, explaining how it works and the likely effects of supplementation.

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What is l-theanine?

L-theanine is an amino acid with a similar chemical structure to glutamate, which is a neurotransmitter. It is found in green tea and mushrooms, and l-theanine is readily available as a supplement.

People often take l-theanine supplements for anxiety, and studies do back up this claim somewhat. But l-theanine is more than just a ‘chill pill’, as you will see from the research on inflammation and brain health.

In tea, l-theanine makes up about 1 -2% of the dry weight of the leaves. It is true for both black and green teas, with different tea varieties containing different amounts.[ref]

On average, a cup of tea contains about 25mg of l-theanine. Interestingly, l-theanine takes away some of the bitter taste of caffeine through binding to the taste receptors for umami, a savory taste.[ref]

In the brain, l-theanine binds to glutamate receptors. But l-theanine doesn’t have as strong an affinity to the receptor as glutamate, so it doesn’t replace it entirely. Instead, it somewhat inhibits glutamate reuptake and increases brain levels of GABA.[ref]  GABA acts as an inhibitory neurotransmitter, putting the brakes on brain excitement.

Recent research also shows that l-theanine binds to cannabinoid receptor 1 (CB1). This competitive binding then inhibits the CB1 receptor.[ref]

Studies on l-theanine for anxiety:

L-theanine has been tested in clinical trials for anxiety. Let’s take a look at some of the results:

A 2006 cross-over trial found that theanine reduced heart rate and stress response molecules in response to acute stress tasks. The heart rate variability results showed that the reduction in heart rate was “attributable to an attenuation of sympathetic nervous activation.”[ref]

A randomized, placebo-controlled, cross-over, and double-blind trial looked at the effects of 200mg/d of l-theanine on adults with no mood issues. The results showed a decrease in depression and anxiety traits as well as better sleep. Cognitive function, executive function, and verbal fluency all improved.[ref]

On the other hand, an 8-week trial in people with Generalized Anxiety Disorder found that l-theanine did not reduce anxiety.[ref]

Researchers looked at different doses of l-theanine and measured the startle response. [ref] Doses of 200-400 mg did decrease the startle response, but at doses over 400 mg, there was no additional benefit.

Related article: Inflammation genes and anxiety

How does l-theanine stack up against benzos?

A clinical trial looked at the anxiety reduction from 200 mg of l-theanine vs. alprazolam (benzodiazepine) or a placebo. The study results showed that l-theanine helped with relaxation during non-stress conditions, but neither then alprazolam nor l-theanine had acute anxiety-reducing effects during anticipatory anxiety.[ref] To me, the difference between anticipatory stress and a suddenly anxious situation is similar to dreading a final exam for a week vs. having a pop-quiz.

Studies on l-theanine for depression:

Surprisingly, there isn’t a lot of published research on l-theanine for depression. Anxiety and depression often go hand-in-hand, so I expected to find more research on the combination.

A clinical trial using 250mg/day of l-theanine in adults with major depressive disorder showed that anxiety traits improved. Sleep disturbances were helped by the l-theanine also.[ref]

Sleep studies with l-theanine:

It would make sense that something that can decrease anxiety would help people who have sleep problems due to constantly worrying about things all night. Plus, supplement sellers of l-theanine often promote its use for sleep. But, to be honest, the research on the topic is slim.

• A randomized, double-blind, placebo-controlled trial using 100 mg of l-theanine 4x per day in boys with ADHD showed some improvements in sleep quality.[ref]
• Additionally, the clinical trial mentioned above for stress-related symptoms also noted improved sleep quality scores in participants taking l-theanine.[ref]

Will l-theanine give you nightmares?

An animal study showed that GABA plus l-theanine effectively decreased the time it took to fall asleep and the time spent sleeping. It also almost doubled the time spent in REM sleep.[ref] I mention this animal study because some people report that l-theanine causes vivid dreams for them, which may go along with changes in REM sleep.

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Caffeine plus l-theanine: taking the edge off

One benefit of l-theanine is to take the edge off the caffeine jitters.

A clinical trial showed that combining l-theanine with caffeine eliminated the negative effects of caffeine in people who weren’t used to drinking it.[ref]

Another study found that moderate levels of l-theanine and caffeine improved accuracy and alertness in participants.[ref]

A double-blind, placebo-controlled study found that 100mg of l-theanine plus 50mg of caffeine increased vigilance and decreased errors during a sustained attention task. In other words, it increased participants’ ability to focus.[ref]

Interestingly, caffeine jitters are something that happens based on genetic variants in the ADORA2A gene. Thus, if you naturally don’t feel anxious, then theanine may not have much of an impact as far as a combo with caffeine.

Targeting inflammation and the immune system:

Animal studies show that l-theanine decreases TNF-alpha levels and increases the anti-inflammatory cytokine IL-10.[ref]

Psoriasis is a skin inflammatory disease that involves an increased immune cell response in the epidermis. Studies show that l-theanine reduces the overactive inflammatory response by inhibiting IL-23, an inflammatory cytokine. The animal study also indicates that l-theanine regulates other inflammatory pathways, including IL-17A and NF-κB.[ref]

T cells are one of the body’s first lines of defense against microbial pathogens. Supplementing with l-theanine has been shown to prime a specific subset of T cells, called gamma-delta T lymphocytes. It may be why supplementing with l-theanine decreases cold and flu symptoms.[ref]

Brain health:

Animal studies show that l-theanine stimulates the growth of neural progenitor cells. Essentially, l-theanine inhibits glutamine uptake without affecting glutamic acid uptake. It stimulates an increase in SLCC38A1, which is the glutamine transporter. The overexpression of SLC38A1 facilitates the pathways required for neurogenesis.[ref]

Cell studies using neuronal cells show that the upregulation of SLC38A1 by l-theanine promotes the generation of new neurons.[ref]

Promoting neurogenesis may be why studies in older adults who drink green tea with high theanine concentrations have less cognitive decline than typically seen in aging.[ref]

L-theanine in aging:

Animal studies show that l-theanine may help to delay neurodegenerative diseases. The research shows that l-theanine activates SIRT1 and inhibits nuclear factor-κB (NF-kB), both of which should be beneficial in aging through reducing the expression of inflammatory factors.[ref]

Related article: SIRT1 and longevity

Absorption, transport, and dosage:

L-theanine dosage for anxiety:

The average cup of tea contains around 20 to 25mg of l-theanine. Someone drinking multiple cups of tea per day could be getting 100+ mg of theanine.

Clinical trials above used doses in the range of 100 to 900 mg/day without negative effects. There doesn’t seem to be any evidence, though, that the higher doses are more effective. Some trials split the dosage into several 100 mg capsules over the course of the day. It makes sense when you look at the short half-life of l-theanine.

Absorption in the gut:

For any supplement pill or medication capsule to work in the body, it needs to be absorbed in the intestines, moved into the bloodstream, and taken up into cells. Along the way, many substances are broken down or metabolized by the liver or other enzymes so the body can eliminate them.

• Both l-theanine in capsules and l-theanine in green tea are readily absorbed, with peak plasma values observed after 45 minutes.[ref]
• The addition of piperine increases the absorption of l-theanine.[ref]
• The half-life of l-theanine is about an hour to an hour and 15 minutes. Meaning l-theanine is absorbed and metabolized relatively quickly. It does cross the blood-brain barrier and is detectable in the brain about a half hour after oral administration.[ref]

Transport into the cell:

A transporter protein is needed to move l-theanine into a cell. Research shows that the LAT1 transporter, which moves several amino acids into cells, including l-leucine, is utilized by l-theanine.[ref]

L-theanine’s uptake is inhibited by l-leucine, a branch chain amino acid found in many proteins, including milk. Thus, to increase your ability to absorb l-theanine, drink your green tea without milk and away from branch-chain amino acid protein drinks.

Theanine levels in different types of tea:

The amount of l-theanine varies quite a bit by the type of tea.

Tracking Supplements:

Here’s a handy printable supplement tracker form to keep track of what you are taking, when you take it, and why.

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Conclusion:

Tea is one of the most popular beverages consumed worldwide, and l-theanine is a beneficial component.

Clinical trials on l-theanine show that there may be mild benefits for anxiety for some people.

More interesting, and also related to decreasing anxiety, are the benefits for reducing and modulating the immune response. Overall, theanine is generally regarded as safe and seems to have few safety concerns.

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