Nootropics for mental energy and fatigue: what the evidence supports

People use "energy" loosely, so this hub starts with what researchers actually record. Most of the outcomes here are feelings that a person rates on a questionnaire, not lab measurements.

Feeling energetic and feeling fatigued are not simply two ends of one dial. Many fatigue questionnaires define fatigue as "a lack of energy", but a 2018 hypothesis paper argues that the two are independent feelings [1]. It cites factor-analysis studies that found them to be independent, and experiments in behavioral pharmacology and exercise science that often find a change in energy and not fatigue, or vice versa [1]. Its authors propose measuring each on its own scale and describe an experiment that could test the idea [1]. Four of the measurement and exercise sources on this hub share one author, P. J. O'Connor [1][2][5][6]. There is little agreement on how to measure fatigue at all: more than 250 instruments have been used in research [1].

For the feeling of energy, a review of mood measures concluded that strong evidence supports the validity of scales such as the vigor scale of the Profile of Mood States (POMS) [2]. The same review notes that mood ratings need self-awareness and literacy, and that people can fake them [2]. In clinical settings, mental fatigue is assessed mainly by self-report questionnaires, and a 2023 review called their validity questionable because they are highly subjective and open to response bias [3]. Researchers have tried objective markers instead, including heart rate variability, salivary cortisol, EEG and eye-movement tasks, and that review singled out the antisaccade task (looking away from a sudden target) as a promising lab test [3].

That gives four outcomes on this hub, which our evidence data keeps separate:

Table: Energy outcomes and examples of how studies measure them

As of November 12, 2026, no compound we grade has a grade for subjective energy itself. Every grade below rates fatigue, next-day fatigue or motivation, so read each badge for the outcome it names.

Sleep

A meta-analysis of 70 articles covering 147 cognitive tests looked at short-term (under 48 hours) total sleep deprivation across six cognitive domains, from simple attention to reasoning [4]. Effects ranged from small and nonsignificant for reasoning accuracy to large for lapses in simple attention (g = -0.776) [4]. The NHS lists not getting enough sleep among the common causes of tiredness, and advises sticking to the same sleep times and aiming for 6 to 9 hours [23].

Exercise

Exercise has been tested against control conditions in many randomized trials of these feelings [5]. A 2022 meta-analysis of 81 randomized trials (7,050 participants in healthy and clinical groups) found that exercise training lowered feelings of fatigue by a small amount (g = -0.374), raised energy by a small-to-moderate amount (g = 0.415) and raised vitality by a moderate amount (g = 0.537) compared with controls [5]. Its authors concluded that moderate-intensity training programs typically produced small-to-moderate average improvements [5].

The placebo question matters here too. An earlier meta-analysis found an overall effect of 0.37 in favor of exercise, but the studies that used a placebo control and tested exercise alone found no effect on feelings of energy and fatigue [6]. Its authors noted that some placebo conditions may themselves raise energy and lower fatigue in older adults or people with psychological distress [6]. Placebo conditions can move these ratings [6], which matters for every supplement trial below.

Caffeine, with its trade-offs

Caffeine is not graded for an energy outcome here, but it sits behind much of what people call energy. In people who are short on sleep, a meta-analysis concluded that caffeine is an effective counter-measure to the cognitive and physical impairments of sleep loss [8]. The cost falls on the next night: a meta-analysis of sleep studies found caffeine cut total sleep time by 45 minutes, and estimated that, to avoid losing sleep, a coffee containing 107 mg would need to be consumed at least 8.8 hours before bedtime [7]. The NHS advises against caffeine in the couple of hours before sleep [23].

Regular users also face withdrawal. A review of experimental studies found that fatigue, decreased energy, decreased alertness and drowsiness were among the validated withdrawal symptoms, usually starting 12-24 hours after the last dose [9]. Stopping doses as low as 100 mg/day produced symptoms, and the review cited research indicating that avoiding withdrawal plays a central role in habitual caffeine use [9]. Our guide to how long caffeine lasts covers timing.

When tiredness lasts

The NHS advises seeing a GP when someone has felt tired for a few weeks without knowing why [23]. It lists lifestyle factors, medicines and some illnesses among the causes, and notes that blood tests, for example for anemia, may be needed [23].

Iron supplements have been tested against placebo in women with fatigue, in two primary-care trials. In a 4-week trial in Switzerland of 144 non-anemic women aged 18 to 55 with unexplained fatigue, the dose used was 80 mg/day of elemental iron, and fatigue scores fell by 29%, against 13% with placebo [10]. A subgroup analysis found that only women with ferritin (stored iron) at or below 50 µg/L improved [10]. A 12-week trial in France of 198 non-anemic menstruating women with fatigue and ferritin below 50 µg/L, using the same dose, found fatigue scores fell 47.7% with iron and 28.8% with placebo, with no significant effect on quality of life [11]. Both trials enrolled women with fatigue and measured ferritin in blood, and the benefit was confined to, or tested only in, women with low iron stores, so the results may not apply to others. The NIH Office of Dietary Supplements notes that high-dose iron supplements can cause gastrointestinal effects, including constipation, nausea and abdominal pain, and quotes the required label warning that accidental overdose of iron-containing products is a leading cause of fatal poisoning in children under 6 [24]. This page does not otherwise cover iron safety.

Each grade badge below renders from our evidence data for one compound and one outcome. The order in the module above comes from those grades; the sections that follow are alphabetical. Our page on how we grade evidence explains the rubric, and the evidence matrix shows every outcome side by side. Each monograph linked below has the compound's safety section and known interactions.

Acetyl-L-carnitine

The fatigue evidence for acetyl-L-carnitine comes from clinical populations and one research team. In a trial of 96 adults over 70 (aged 71-88), indexed in PubMed as a randomized controlled trial, who met research criteria for a fatigue syndrome, mental-fatigue scores changed by -3.3 with acetyl-L-carnitine against 0.6 with the comparison group, on the Wessely and Powell scale [16]. Every fatigue trial we found comes from the same research team, and a 2019 Cochrane review of that team's five trials in liver disease found all at high risk of bias, found no clear difference from placebo in fatigue, and rated all the evidence very low quality [21]. These were older adults with a clinical fatigue diagnosis, so the results may not apply to healthy adults. See the acetyl-L-carnitine monograph.

Alpha-GPC

Alpha-GPC is a precursor of the brain chemical acetylcholine [17]. In a single-blind, placebo-controlled study of 39 healthy volunteers over 2 weeks, alpha-GPC showed a tendency to raise self-rated motivation, with significantly higher motivation at night than placebo and no effect on anxiety [17]. The single-blind design and the self-reported outcome limit confidence in the result. See the alpha-GPC monograph.

Glycine

Glycine's energy-related evidence is about the day after short sleep. In a randomized, single-blinded crossover trial run by researchers employed by Ajinomoto, 10 healthy men had their sleep cut by 25% for three nights, and glycine before bed led to lower next-day fatigue ratings and faster psychomotor vigilance reaction times than placebo [18]. Other performance tests did not differ, and only 7 participants were analyzed [18]. See the glycine monograph.

Mucuna pruriens

Extracts of authenticated Mucuna pruriens seeds contain levodopa [19], and one laboratory analysis of 16 US products found no detectable levodopa in one and 2 mg to 241 mg per serving in the others, often far more than the amount estimated from the label, with labels such as "Supports dopamine production and motivation" [19]. As of November 11, 2026 we found no controlled human study of Mucuna that measured motivation (PubMed and Europe PMC searches, November 11, 2026). Its badge reflects that absence of evidence. See the Mucuna pruriens monograph.

Panax ginseng

Evidence on ginseng and fatigue is mixed. A 2016 meta-analysis of 12 placebo-controlled trials (630 participants) found less fatigue with ginseng in a pooled analysis of four of those trials (SMD = 0.34), but its authors judged the evidence insufficient because the trials were few and small [14]. A 2023 meta-analysis of 19 trials of ginseng and ginseng herbal formulas found no significant overall reduction in fatigue severity [15]. Some subgroups, including herbal formulas and general (non-disease-specific) fatigue (SMD -0.48), showed significant reductions, and effect sizes were small [15]. Many included trials were in people with chronic or illness-related fatigue, so the results may not apply to healthy adults [15]. See the Panax ginseng monograph.

Rhodiola

Rhodiola rosea is a plant grown at high altitudes and northern latitudes, studied for performance in healthy people because of its purported adaptogenic properties [12]. A systematic review of 11 controlled trials found that three of five randomized trials on mental fatigue reported a benefit, but every included study had a high risk of bias or reporting flaws, and the authors called the research contradictory [12]. In a later 42-day randomized trial of 48 shift-working nursing students, 364 mg of rhodiola worsened fatigue compared with placebo, though the authors urged caution in reading the result [13]. See the rhodiola monograph.

B vitamins carry authorized label wording about tiredness. The Great Britain nutrition and health claims register authorizes the wording that vitamin B6, vitamin B12 and folate each "contributes to the reduction of tiredness and fatigue", and that B6 and B12 contribute to normal energy-yielding metabolism [22]. The vitamin B12 claims may be used only for foods that are at least a source of vitamin B12 [22]. Those are authorized label wordings, not trial results. A meta-analysis of 16 randomized trials (6,276 participants) of vitamin B12, alone or with folic acid and B6, in people without overt deficiency or advanced neurological disorders found that only one study reported fatigue, so no pooled analysis was possible [20]. The B vitamins monograph grades the outcomes that trials did measure. Taurine is also sold for energy, but its monograph grades endurance performance and reaction time, not an energy outcome.

• How long caffeine lasts: half-life, timing and sleep.
• What to check first when thinking feels foggy: common causes before supplements.
• Nootropic coffee and drinks: what is in them and how the doses compare with studies.

The newest syntheses cited on this hub are from 2023: a meta-analysis of ginseng and ginseng herbal formulas for fatigue [15] and a meta-analysis of caffeine and sleep [7]. A Europe PMC search on November 11, 2026 returned 13 randomized-trial records with fatigue or energy in the title for CoQ10, PQQ, schisandra or NAD+ precursors (nicotinamide riboside or mononucleotide). We have not yet appraised or graded them, and this hub will list each compound once its monograph is graded.

What are the best nootropics for energy?

None of the supplements graded on this page has consistent, well-controlled trials showing more energy or less mental fatigue in healthy adults. The trials for rhodiola, Panax ginseng, acetyl-L-carnitine, alpha-GPC and glycine are small, mixed or limited to one study or one research group [12][15][16][17][18]. In randomized trials, regular exercise improved feelings of energy and fatigue compared with controls [5], though trials that used a placebo control found no effect of exercise alone [6].

Is mental fatigue the same as low energy?

Not quite, on current evidence. A 2018 hypothesis paper argued that energy and fatigue are independent feelings, citing factor-analysis studies and experiments that often find a change in one but not the other [1]. That is why this hub keeps energy ratings and fatigue ratings as separate outcomes.

Do B vitamins help with tiredness?

The Great Britain claims register authorizes the wording that vitamins B6, B12 and folate contribute to the reduction of tiredness and fatigue, and the vitamin B12 claims may be used only for foods that are at least a source of vitamin B12 [22]. In a meta-analysis of 16 trials of vitamin B12, alone or with folic acid and B6, in people without overt deficiency or advanced neurological disorders, only one study reported fatigue, so no pooled estimate was possible [20].

Does caffeine help with tiredness?

In people short on sleep, a meta-analysis concluded that caffeine is an effective counter-measure to the cognitive and physical impairments of sleep loss [8]. In sleep studies, caffeine also cut total sleep time by 45 minutes on average [7], and stopping regular use brought on fatigue and decreased energy in withdrawal studies [9].