What to Take With L-Theanine and When to Prescribe
L-theanine is a naturally occurring amino acid found in tea. It crosses the blood-brain barrier and affects brain activity by promoting a state of deep relaxation and mental alertness such as is often achieved via meditation, via effects on alpha brain wave activity.1 L-theanine is similar to glutamic acid in structure and appears to function as a glutamate reuptake inhibitor, glutamate receptor antagonist and exerts neuroprotective effects via its action on gamma-aminobutyric acid (GABA) A receptors. GABA can then influence levels of dopamine and serotonin in the brain.2,3
Numerous trials show beneficial acute effects from L-theanine and caffeine co-supplementation. Apart from these, L-theanine has been combined with cystine and many other nutraceuticals for indications that leverage its immune-enhancing, cognition-enhancing, stress-relieving, and sleep-supportive effects.
L-Theanine and Cystine
There is a plethora of research on theanine and cystine co-supplementation as these amino acids are related to glutathione synthesis and possibly modulate immune function. To summarise, benefits have been observed in the following conditions, at a dose to 280 mg of L-theanine and 700 mg of cystine in:
- Attenuating the adverse events of S-1 adjuvant chemotherapy and increased the
S-1 completion rate in patients with gastrointestinal cancer.4
- Attenuating oxaliplatin‑induced peripheral neuropathy in colorectal cancer.5
- Supressing perioperative inflammation and facilitating early rehabilitation and
recovery after oesophagectomy in patients with oesophageal cancer,6 and distal
gastrectomy in patients with gastric cancer.7
- Preventing the common cold in healthy males, with the addition of glycine.8
- Enhancing the immune response (seroconversion rate) to the influenza vaccine
in elderly participants with low serum total protein or haemoglobin (taken before
immunisation).9
- Suppressing intense endurance exercise-induced neutrophilia and
lymphopaenia in athletes.10,11
- Well-trained men as a means to restore high-intensity resistance and high-
frequency training-induced attenuation of natural killer (NK) cell activity.12
Other Nutraceuticals
L-theanine has been combined with other ingredients for various indications.
L-theanine (240 mg/day) and Green Tea extract in divided doses was able to improve memory and attention in older adults with mild cognitive impairment (MCI) [mean age 57.6 years]. Electroencephalograms (EEGs) recorded increased theta activity during mental states (eyes-open and reading).13 Brain theta waves are an indicator of working memory, associative learning14 and relaxed concentration.15
Subjective measures of cognitive function, perceived stress and depression in the elderly (mean age 66 years) were shown to improve in response to a combination of nutraceuticals that was administered short term. This combination included L-theanine (100 mg), Bacopa, Saffron, vitamin B6, biotin, folic acid, vitamin B12, vitamin D, and copper. Notably, all patients were also treated with angiotensin-converting enzyme (ACE)-inhibitors and statins.16
Both L-theanine (200 mg) alone and in combination with L-arginine could reduce short-term psychological stress in young adults (mean age 22.4 years). Psychological stress response was measured via salivary alpha-amylase activity after a stress-loading test.17
A drink containing L-theanine (200 mg) together with small doses of Chamomile, phosphatidylserine and alpha glycerylphosphorylcholine (GPC) has demonstrated anti-stress effects in healthy adults. Compared to placebo, subjective stress response to a multitasking cognitive stressor was significantly reduced one hour after the combination was administered, and salivary cortisol response to the stressor was reduced three hours post-dose compared to placebo in this crossover study.18
Chronic stress in otherwise healthy adults was alleviated with a combination of Green Tea extract (containing 50 mg of L-theanine); magnesium; Rhodiola; and vitamins B6, B9 and B12. Beneficial effects on daytime dysfunction due to sleepiness and reduced sensitivity to cold pain were also reported.19
L-theanine taken with alpha-s1-casein tryptic hydrolysate (doses not specified) was shown to improve sleep duration and sleep habitual efficiency in working adults affected by poor sleep quality. The supplement prolonged total sleeping time by an average of 45 minutes compared to placebo (p<0.001) in this crossover trial.20
L-theanine (200 mg/day) and GABA has been shown to improve sleep in adults with sleep problems in an exploratory study. Note that this is a preprint article and has not yet been peer-reviewed.21
A combination of L-theanine (200 mg), tryptophan, glycine, magnesium, and tart cherry powder reduced sleep onset latency by 24 minutes (p=0.002), increased total sleep time by 22 minutes (p=0.01) and increased sleep efficiency by 2.4% (p=0.03), while also reducing morning sleepiness (p=0.02) compared to placebo. This was a crossover trial in adults, 50% of whom initially had poor sleep quality and the other 50% reported good sleep quality.22
Supplementation with L-theanine (200 mg/day) and vitamin B6 (2.8 mg/day) in children and teenagers (mean age 10.4 years) affected by Tourette syndrome or chronic tic disorder with comorbid anxiety symptoms was shown to reduce the severity of tics to a greater extent than psychoeducation (mean total decrease -43.5% versus -18.3%, respectively; p=0.046) in a pilot study. Effects on anxiety symptoms were better in the supplemented group but difference to the psychoeducation group was not statistically significant, possibly attributable to the lower anxiety symptom levels considered as inclusion criteria.23
Preliminary evidence from an open-label pilot study suggests that adults with refractory obsessive-compulsive disorder (OCD) also stand to benefit from an L-theanine-containing combination of nutraceuticals with potential neuromodulatory effects on glutamatergic and serotonergic pathways. Aside from L-theanine, the combination contained N-acetylcysteine (NAC), zinc, magnesium, pyridoxal 5-phosphate (P5P), and selenium.24
Theanine (210 mg/day) and Green Tea catechins (378 mg/day) was related to a significantly lower incidence of clinically defined influenza infection compared to placebo in healthcare workers.25
More Ingredients, Better Outcomes?
Taken together, L-theanine appears to lend itself well to compounding with other synergistic nutrients and herbs or being prescribed alongside other products. Benefits have been reported in the following settings:
- Patients at risk of adverse events from chemotherapy or surgery
- Depleted immune function in athletes
- Influenza prophylaxis in adults
- Enhancing cognition, stress, mood, and sleep quality in children, adults and
elderly patients, including where this appears as a comorbidity to another
condition or for general wellbeing
Given the diversity of co-administered ingredients, these are by no means the only groups that may benefit from L-theanine supplementation. Practitioners are encouraged to use the information provided in this article and apply their best clinical judgment to discover other relevant applications (e.g. conditions where ‘brain fog’ is a symptom, in children with behavioural symptoms and poor sleep quality, high school or university students experiencing exam stress, etc.). Prescribing L-theanine with other indicated nutrients and herbs (e.g. nootropics and anxiolytics) may lead to better clinical outcomes.
For more information, please contact Clinical Support 1300 654 336.
References
1. Mason R. 200 mg of zen: L-theanine boosts alpha waves, promotes alert relaxation. Altern Complement Ther. 2001 Apr;91-95. DOI: 10.1089/10762800151125092
2. Examine. Theanine [Internet]. Toronto: Examine; 2023 [cited 2023 Nov 7]. Available from: https://examine.com/supplements/theanine/
3. Natural Medicines Database [Internet]. Denver (CO): TRC Healthcare; 2023. Theanine; Oct 2023 [cited 2023 Nov 6]. Available from: https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=1053
4. Tsuchiya T, Honda H, Oikawa M, Kakita T, Oyama A, Oishi H, et al. Oral administration of the amino acids cystine and theanine attenuates the adverse events of S-1 adjuvant chemotherapy in gastrointestinal cancer patients. Int J Clin Oncol. 2016 Dec;21(6):1085-1090. DOI: 10.1007/s10147-016-0996-7
5. Kobayashi M, Sato R, Komura T, Ichikawa H, Hirashima T, Otake S, et al. Protective effect of the oral administration of cystine and theanine on oxaliplatin-induced peripheral neuropathy: a pilot randomized trial. Int J Clin Oncol. 2020 Oct;25(10):1814-1821. DOI: 10.1007/s10147-020-01728-4
6. Okamoto H, Taniyama Y, Sakurai T, Kodama G, Sato C, Fukutomi T, et al. Perioperative administration of cystine and theanine suppresses inflammation and facilitates early rehabilitation and recovery after esophagectomy: a randomized, double-blind, controlled clinical trial. Nutrients. 2022 May;14(11):2319. DOI: 10.3390/nu14112319
7. Miyachi T, Tsuchiya T, Oyama A, Tsuchiya T, Abe N, Sato A, et al. Perioperative oral administration of cystine and theanine enhances recovery after distal gastrectomy: a prospective randomized trial. JPEN J Parenter Enteral Nutr. 2013;37(3):384-391. DOI: 10.1177/0148607112458798
8. Kurihara S, Hiraoka T, Akutsu M, Sukegawa E, Bannai M, Shibahara S. Effects of (L)-cystine and (L)-theanine supplementation on the common cold: a randomized, double-blind, and placebo-controlled trial. J Amino Acids. 2010;2010:307475. DOI: 10.4061/2010/307475
9. Miyagawa K, Hayashi Y, Kurihara S, Maeda A. Co-administration of L-cystine and L-theanine enhances efficacy of influenza vaccination in elderly persons: nutritional status-dependent immunogenicity. Geriatr Gerontol Int. 2008 Dec;8(4):243-250. DOI: 10.1111/j.1447-0594.2008.00483.x
10. Murakami S, Kurihara S, Titchenal CA, Ohtani M. Suppression of exercise-induced neutrophilia and lymphopenia in athletes by cystine/theanine intake: a randomized, double-blind, placebo-controlled trial. J Int Soc Sports Nutr. 2010 Jun;7(1):23. DOI: 10.1186/1550-2783-7-23
11. Murakami S, Kurihara S, Koikawa N, Nakamura A, Aoki K, Yosigi H, et al. Effects of oral supplementation with cystine and theanine on the immune function of athletes in endurance exercise: randomized, double-blind, placebo-controlled trial. Biosci Biotechnol Biochem. 2009 Apr;73(4):817-821. DOI: 10.1271/bbb.80663
12. Kawada S, Kobayashi K, Ohtani M, Fukusaki C. Cystine and theanine supplementation restores high-intensity resistance exercise-induced attenuation of natural killer cell activity in well-trained men. J Strength Cond Res. 2010 Mar;24(3):846-851. DOI: 10.1519/JSC.0b013e3181c7c299
13. Park SK, Jung IC, Lee WK, Lee YS, Park HK, Go HJ, et al. A combination of green tea extract and L-theanine improves memory and attention in subjects with mild cognitive impairment: a double-blind placebo-controlled study. J Med Food. 2011 Apr;14(4):334-343. DOI: 10.1089/jmf.2009.1374
14. Soltani Zangbar H, Ghadiri T, Seyedi Vafaee M, Ebrahimi Kalan A, Fallahi S, Ghorbani M, et al. Theta oscillations through hippocampal/prefrontal pathway: importance in cognitive performances. Brain Connect. 2020 May;10(4):157-169. DOI: 10.1089/brain.2019.0733
15. Laukka SJ, Järvilehto T, YuI AI, Lindqvist J. Frontal midline theta related to learning in a simulated driving task. Biol Psychol. 1995 Jun;40(3):313-320. DOI: 10.1016/0301-0511(95)05122-Q
16. Cicero AF, Bove M, Colletti A, Rizzo M, Fogacci F, Giovannini M, et al. Short-term impact of a combined nutraceutical on cognitive function, perceived stress and depression in young elderly with cognitive impairment: a pilot, double-blind, randomized clinical trial. J Prev Alz Dis. 2017;4(1):12-15. DOI: 10.14283/jpad.2016.10
17. Furushima D, Sugiyama I, Nomura Y, Unno K, Yamada H. Effect of combined ingestion of L-theanine and L-arginine for short-term psychological stress in young adults: a randomized placebo-controlled study. J Nutr Sci Vitaminol (Tokyo). 2022;68(6):540-546. DOI: 10.3177/jnsv.68.540
18. White DJ, De Klerk S, Woods W, Gondalia S, Noonan C, Scholey AB. Anti-stress, behavioural and magnetoencephalography effects of an L-theanine-based nutrient drink: a randomised, double-blind, placebo-controlled, crossover trial. Nutrients. 2016 Jan;8(1):53. DOI: 10.3390/nu8010053
19. Noah L, Morel V, Bertin C, Pouteau E, Macian N, Dualé C, et al. Effect of a combination of magnesium, B vitamins, rhodiola, and green tea (L-theanine) on chronically stressed healthy individuals-a randomized, placebo-controlled study. Nutrients. 2022 Apr;14(9):1863. DOI: 10.3390/nu14091863
20. Thiagarajah K, Chee HP, Sit NW. Effect of alpha-s1-casein tryptic hydrolysate and L-theanine on poor sleep quality: a double blind, randomized placebo-controlled crossover trial. Nutrients. 2022 Feb;14(3):652. DOI: 10.3390/nu14030652
21. Konno H, Murotani R, Kamada Y. An exploratory study to detect the effects of the combined intake of gamma-aminobutyric acid (GABA) and L-theanine on sleep by wearable device. medRxiv preprint. 2023 Oct. DOI: 10.1101/2023.10.01.23296182
22. Langan-Evans C, Hearris MA, Gallagher C, Long S, Thomas C, Moss AD, et al. Nutritional modulation of sleep latency, duration, and efficiency: a randomized, repeated-measures, double-blind deception study. Med Sci Sports Exerc. 2023 Feb;55(2):289-300. DOI: 10.1249/MSS.0000000000003040
23. Rizzo R, Prato A, Scerbo M, Saia F, Barone R, Curatolo P. Use of nutritional supplements based on L-theanine and vitamin B6 in children with Tourette syndrome, with anxiety disorders: a pilot study. Nutrients. 2022 Feb;14(4):852. DOI: 10.3390/nu14040852
24. Sarris J, Byrne GJ, Oliver G, Cribb L, Blair-West S, Castle D, et al. Treatment of refractory obsessive-compulsive disorder with nutraceuticals (TRON): a 20-week, open label pilot study. CNS Spectr. 2022 Oct;27(5):588-597. DOI: 10.1017/S1092852921000638
25. Matsumoto K, Yamada H, Takuma N, Niino H, Sagesaka YM. Effects of green tea catechins and theanine on preventing influenza infection among healthcare workers: a randomized controlled trial. BMC Complement Altern Med. 2011 Feb;11:15. DOI: 10.1186/1472-6882-11-15
