Supplements for Mental Fatigue, Alertness and Sleep Loss: What Trials Found
What reviews and trials found for caffeine, L-theanine, creatine, rhodiola and others for mental tiredness and alertness, and why constant tiredness calls for a clinician.
Content last updated . This page has not been medically reviewed.
Start here: tiredness can be a health signal
Ongoing tiredness, falling asleep in the day or poor concentration can come from conditions that supplements do not fix. NHS pages list difficulty concentrating among symptoms of sleep apnoea and of an underactive thyroid, and describe memory and thinking changes with vitamin B12 or folate deficiency. [1][2][3] The NHS notes sleep apnoea carries a higher chance of a serious accident caused by tiredness, such as a car accident. [1] If you are drowsy while driving or working with machinery, that is a safety issue; see sleep safety and drowsy driving and why am I so tired?. In the US, call 911 for an emergency.The question and the short answer
Can a supplement reduce mental fatigue or keep people alert after poor sleep? Caffeine has the most trial evidence for alertness after sleep loss, mainly from short tests. Evidence for other ingredients is thinner. A supplement is not a substitute for sleep. This page is information only.What the research found
Labels: evidence in adequately nourished people (short-term trials), promising but limited, mixed, insufficient evidence.| Ingredient | What the source found (who, comparator) | Label |
|---|---|---|
| Caffeine after sleep loss | A review of 45 publications of sleep-deprived or sleep-restricted people concluded that caffeine is an effective counter-measure to cognitive and physical impairments from sleep loss. [4] | Evidence in adequately nourished people (short term) |
| Caffeine in shift work and jet lag | Cochrane: 13 trials, none measured injuries. Results largely come from young participants under simulated conditions, with a high risk of bias in some areas. [5] | Promising but limited |
| L-theanine | In 31 trials, no significant effect on fatigue was observed. [6] | No good evidence of benefit (fatigue) |
| Caffeine plus L-theanine | Small differences in cognition and mood in healthy people, with wide uncertainty. [7] | Mixed |
| Creatine during sleep loss | A small experiment (19 people) over 24 hours of sleep deprivation found less decline in some tasks and mood. [8] A single-dose study during 21 hours of sleep deprivation reported partial reversal of fatigue-related decline. [9] | Promising but limited |
| Tyrosine | 15 studies, almost all single sessions: it counteracted drops in working memory under demanding conditions. [10] | Promising but limited |
| Rhodiola | 11 trials: three of five on mental fatigue reported benefit, but flaws limit assessment. [11] | Insufficient evidence |
| Iron (in iron-deficient people) | Iron improved fatigue in non-anemic children, teens and menstruating adults, but effects were absent when people without iron deficiency were analyzed. [12] | Mixed (depends on iron status) |
Creatine in the brain has its own page: creatine for older adults, women and cognition. Caffeine detail: caffeine supplements, half-life, tolerance and withdrawal. In the Cochrane review, trials comparing caffeine with other options (a nap, bright light, modafinil) found no significant differences. [5] Prescription drugs are covered in modafinil and armodafinil: status and risks and are not alternatives to supplements.
Proper evidence not found: for supplements other than those above, a systematic review on mental fatigue or sleep-loss performance that we could read (PubMed searches for mental fatigue and dietary supplements in healthy people, and for sleep deprivation with caffeine and creatine).
Frequently asked questions
What helps mental fatigue the most?
We did not find a trial in the sources we read that compares a supplement with enough sleep. Caffeine has the most evidence for alertness after sleep loss. [4]
Does L-theanine reduce fatigue?
A 31-trial meta-analysis found no significant effect on fatigue. [6]
Is caffeine proven to help shift workers?
A Cochrane review found caffeine may help performance, but no trial measured injuries, and evidence came largely from young people in simulated conditions. [5]
Can creatine help after a bad night's sleep?
Two small experiments reported benefits during sleep deprivation, so it is promising but limited; they do not show it is advisable for any person. [8][9]
When should tiredness be checked by a doctor?
When it is ongoing, comes with snoring or gasping, mood or memory change, or makes driving unsafe. [1][2]
More details: evidence, limits and cautions
The details behind this page: cautions, limits of the evidence and where sources disagree. Open any note to read it.
Limits and uncertainty
- Sleep-loss trials are short experiments, often with young volunteers. Everyday shift work is different. [5]
- Most studies of supplements in healthy young adults were rated low quality, with inconsistent findings. [13]
- Test and simulator results do not show real-world safety, and the Cochrane review found no injury data. [5]
Safety and who should ask first
Iron supplements carry risks, including death in the case of overdose, so never use iron because of tiredness without testing and clinician advice. [15] If a child has swallowed iron or other supplements, call 911 or Poison Help at 1-800-222-1222 (US); see iron overdose and child safety. Read how interactions work and talk to a clinician or pharmacist, especially with heart, kidney, liver, seizure or sleep conditions, or before surgery.
References
- NHS (UK), Sleep apnoea (page last reviewed 11 May 2026). Read 2026-10-23.
- NHS (UK), Underactive thyroid: symptoms (page last reviewed 28 April 2025). Read 2026-10-23.
- NHS (UK), Vitamin B12 or folate deficiency anaemia: symptoms (page last reviewed 20 February 2023). Read 2026-10-23.
- Irwin C et al. Neurosci Biobehav Rev 2020. Effects of acute caffeine consumption following sleep loss on cognitive, physical, occupational and driving performance: A systematic review and meta-analysis. Read 2026-10-23.
- Ker K et al. Cochrane Database Syst Rev 2010. Caffeine for the prevention of injuries and errors in shift workers. Read 2026-10-23.
- Gerolymos C et al. Mol Psychiatry 2026. Cognitive and affective effects of L-Theanine: a systematic review and meta-analysis of 31 randomized trials. Read 2026-10-23.
- Payne ER et al. Nutr Rev 2025. Effects of Tea (Camellia sinensis) or its Bioactive Compounds l-Theanine or l-Theanine plus Caffeine on Cognition, Sleep, and Mood in Healthy Participants. Read 2026-10-23.
- McMorris T et al. Psychopharmacology 2006. Effect of creatine supplementation and sleep deprivation, with mild exercise, on cognitive and psychomotor performance, mood state, and plasma concentrations of catecholamines and cortisol. Read 2026-10-23.
- Gordji-Nejad A et al. Sci Rep 2024. Single dose creatine improves cognitive performance and induces changes in cerebral high energy phosphates during sleep deprivation. Read 2026-10-23.
- Hase A et al. Pharmacol Biochem Behav 2015. Behavioral and cognitive effects of tyrosine intake in healthy human adults. Read 2026-10-23.
- Ishaque S et al. BMC Complement Altern Med 2012. Rhodiola rosea for physical and mental fatigue: a systematic review. Read 2026-10-23.
- Fiani D et al. Neurosci Biobehav Rev 2025. Psychiatric and cognitive outcomes of iron supplementation in non-anemic children, adolescents, and menstruating adults: a meta-analysis and systematic review. Read 2026-10-23.
- Pomeroy DE et al. Nutrients 2020. A Systematic Review of the Effect of Dietary Supplements on Cognitive Performance in Healthy Young Adults and Military Personnel. Read 2026-10-23.
- Bagheri Davisaraei Y et al. Prog Brain Res 2024. Coffee and sleep: Benefits and risks. Read 2026-10-23.
- Elliott SD et al. J Neuropsychiatry Clin Neurosci 2024. Iron Supplementation in Management of Neurodevelopmental Disorders: Systematic Review, Meta-Analysis, and Qualitative Synthesis. Read 2026-10-23.