Daily energy
Also searched as Fatigue.
In depth
The gap between what you intend and what your body will fund. Distinct from sleepiness — you can be exhausted and wide awake — and it splits into a peripheral limb (the muscle) and a central limb (the drive), which respond to different things.
What drives it
Parasite burden increases it.
10.1093/cid/ciu629 — A natural experiment: the Bergen 2004 waterborne Giardia outbreak in a non-endemic population, with a matched control cohort — replicated independently in US insurance data. Verbatim: “Giardia infection in a nonendemic setting is associated with an increased risk for irritable bowel syndrome and chronic fatigue 6 years later.” (25115874; 29378314). doi 10.1093/cid/ciu629
Builds mitochondria reduces it.
Lin 2002, Nature 418:797 — PGC-1α drives oxidative slow-twitch fibers and mitochondrial biogenesis, raising fatigue resistance. doi 10.1038/nature00904
Glycine calming reduces it.
Same independence problem: every human trial is from one research group, no large independent replication. The serotonin mechanism is rat and the 5-HT rise lasted about 10 minutes. PMID 21414089
Thyroid reduces it.
Low T3 is felt as tiredness even when the standard test looks normal: selenium is required by DIO1 and DIO2 to convert T4 into T3, and when selenium is deficient that conversion falls — producing hypothyroid symptoms including fatigue, weight gain and cold intolerance even though T4 levels may appear normal (PMC12672807, PMC8472829). Note: excess selenium is harmful, not better — the same review warns of gastrointestinal and neurological effects from over-supplementation. PMC12672807
Brain inflammation increases it.
Inflammation seems to have a key role in fatigue before, during and after cancer treatment; in newly diagnosed acute myelogenous leukemia or myelodysplastic syndrome, IL-6, IL-1 receptor antagonist and TNF-α correlated with fatigue ratings (Bower, Nat Rev Clin Oncol 2014;11:597). Guided by research on neuro-immune interactions, a review examines the hypothesis that cancer-related fatigue is driven by activation of the pro-inflammatory cytokine network. doi 10.1016/j.bbi.2012.06.011
Sleep reduces it.
sleep problems measured at 12 weeks were also found to mediate part of the effect of CBT and get on fatigue at 1-year follow-up, when compared to standard medical care. doi 10.3389/fpsyg.2018.01764 · PMC7260280
Training load reduces it.
the results yielded a positive effect of physical training on fatigue in all cancer populations, SMD = -0.33 (-0.43, -0.23); only systematic reviews of low risk of bias were included to restrict reporting of high-quality publications. doi 10.1080/0284186X.2021.1962543 · PMC11948276
Iron status reduces it.
The positive trial is specific and the subgroup is the 144 non-anemic women aged 18-55 with unexplained fatigue, elemental iron daily for four weeks, double-blind and placebo-controlled. Fatigue fell 29 percent on iron versus 13 percent on placebo (difference 0.95 points, 95% CI 0.32 to 1.62, P = 0.004), and subgroup analysis showed that only women with ferritin at OR below 50 micrograms per liter improved. And the negative trials ARE why this edge is conditional rather than simple. 154 female blood donors, iron-deficient without anemia, four weeks of oral ferrous sulfate: hemoglobin and ferritin both rose significantly (P < 0.01) and fatigue did not move (-0.15 points, P = 0.697). Then a larger trial closed the obvious escape routes: 405 non-anemic donors with ferritin at or below 50, given a single intravenous dose of iron-carboxymaltose — which bypasses absorption and compliance entirely. Fatigue 3.9 versus 4.0, P = 0.819. And the pre-specified subgroups included ferritin below 25 and fatigue at OR above 4 points, with exploratory analyses at lower cut-offs: NO between-group differences anywhere. So the distinction is not about dose, route, OR how low the ferritin is. It is about WHO walked in. Women who presented with fatigue and had low ferritin improved. People selected for iron deficiency who were not complaining did not — and the donor trial supplies the reason it is easy to confuse the two: blood donation did not induce overt symptoms of fatigue in spite of the significant biological changes it produces. A low ferritin is not a symptom. the positive evidence is almost entirely in menstruating women. Nothing here establishes the effect in men or post-menopausal women. PMC7449957
Physical performance reduces it.
Reduced aerobic capacity presents as fatigue.
Recovery reduces it.
Incomplete recovery presents as fatigue. PMC10692865
Curbs appetite increases it.
This link rests on the reviews of this outcome as a whole. No effect size specific to this arm has been reported, so it is shown at reduced weight. (from the reviews of this outcome).
Stress resilience reduces it.
10.1186/s12905-024-03187-9 — This link rests on the reviews of this outcome as a whole. No effect size specific to this arm has been reported, so it is shown at reduced weight. (from the reviews of this outcome). doi 10.1186/s12905-024-03187-9
Liver clearance reduces it.
This link rests on the reviews of this outcome as a whole. No effect size specific to this arm has been reported, so it is shown at reduced weight. (from the reviews of this outcome).
Men's hormone balance reduces it.
This link rests on the reviews of this outcome as a whole. No effect size specific to this arm has been reported, so it is shown at reduced weight. (from the reviews of this outcome).
What it drives
It reduces Physical performance.
Cancer-related fatigue is described alongside decreased CARDIORESPIRATORY fitness as co-occurring adverse effects that can persist years after therapy ends. The two ARE partly the same measurement: reduced exercise capacity is both a cause and a symptom of fatigue, and no retrieved source separates them. Shown at reduced weight because the direction is not established - the Fatigue → Aerobic Capacity link and the Aerobic Capacity → Fatigue link are equally defensible from what was retrieved. PMC11264125
It reduces Mood.
Worth remembering from an earlier pass: the two dissociate under treatment - antidepressants move mood without moving fatigue - which is why they are separate nodes at all. Drawing both directions records that they co-travel without claiming they are one thing. PMID 29961146 · PMC11264125
It reduces Stress resilience.
The aging outcome lists the thirteen hallmarks themselves, each mapped to its pathway and labeled with its hallmark number. (from the reviews of this outcome). Sources: doi 10.1002/med.21743; doi 10.26444/aaem/213417; PMC12680924. doi 10.1002/med.21743 · PMC12680924
It increases Calm pain signaling.
The defining feature is that the pain is real and the tissue is not damaged: central sensitization manifests as hyperalgesia, allodynia, expanded receptive fields, and impaired endogenous pain inhibition, and in osteoarthritis the same phenomenon does not correlate with radiographic findings - severe pain may persist despite stable joint structure. The mechanism is a balance failure in both directions at once: in the dorsal horn there is excessive release of glutamate, ATP, and substance P, leading to activation of NMDA receptors - while at the same time descending inhibitory mechanisms, notably those mediated by GABA, ARE weakened. Too much excitation and too little inhibition. And mast cells carry a specific hypothesis: thalamic mast cells releasing histamine, IL-1-beta, IL-6, TNF, CGRP and substance P, either stimulating thalamic nociceptive neurons directly or via microglia. Stated by the authors as a hypothesis, not an established mechanism. The reviewers ARE blunt about the state of knowledge: the pathophysiology and etiopathogenesis remain largely unknown, and there is NO definitive pathogenesis except for altered central pain pathways. doi 10.3390/biomedicines12071543 · PMC6687840
It reduces Balance & falls.
10.1093/geroni/igaa061 — Drawn from reviews of neighboring outcomes rather than from studies of this outcome itself, which is weaker evidence, and the map marks it so. doi 10.1093/geroni/igaa061
Blends that modulate it
Each blend page names this pathway and carries the study behind its claim.
See it on the map
Open the causal map to follow this pathway upstream and downstream, arrow by arrow, each with its study.