2023 · Human observational · Ageing / Functional capacity
Lower relative grip strength was associated with less favourable epigenetic ageing measures; findings varied by sex and clock.
Relevance to EPK. Helps motivate functional outcomes in an EPK study, alongside separate intake and body-mass measurements.
Limitations. Observational; one methylation time point. Does not establish causality or validate dietary targets.
2026 · Mechanistic · Mitochondria / Lipid oxidation / Ageing
A developmental mitochondrial signal altered lipid synthesis and preserved nuclear-envelope integrity in worms; related interventions were examined in cultured cells.
Relevance to EPK. Raises questions about membrane composition, redox signalling and cellular maintenance.
Limitations. Preclinical. Abstract and accessible figure descriptions assessed; no human dietary target established.
2002 · Human intervention · Stress / Energy expenditure / Brain
Mental stress increased oxygen consumption, with a different response after short-term underfeeding.
Relevance to EPK. Discussed in Mental fatigue, stress and energy needs, accompanying Room to Be Yourself. Motivates research rather than validating EPK.
Limitations. Acute laboratory study in healthy women; not a daily calorie allowance or autism trial.
2002 · Review · Stress / Energy expenditure / Brain
The brain has a large ongoing metabolic demand; task-related activity must be interpreted against that baseline.
Relevance to EPK. Discussed in Mental fatigue, stress and energy needs, accompanying Room to Be Yourself. Motivates research rather than validating EPK.
Limitations. Review and interpretation of brain energetics; not a dietary intervention.
2024 · Human observational · Stress / Mitochondria / Ageing
Greater reported childhood adversity was associated with lower ATPmax, but not Max OXPHOS, in 879 older adults.
Relevance to EPK. Discussed in Childhood adversity and the energy of muscle; companion to Controlling Intuitive Appetite, Volume 1, Chapter 16. No direct EPK validation.
Limitations. Observational, with recalled exposures; no test of dietary treatment, EPK or reversibility.
2019 · Mechanistic · Stress / Mitochondria / Behaviour
Mouse stress experiments and human panic-disorder blood samples implicated mitochondrial pathways, with contrasting responses between mouse strains.
Relevance to EPK. Discussed in Stress, anxiety and mitochondrial pathways; companion to Controlling Intuitive Appetite, Volume 3, Chapter 46. No direct EPK validation.
Limitations. Human blood expression is not direct brain energetics; the study does not establish a calorie, supplement or anxiety-treatment prescription.
2022 · Human observational · Energy expenditure / Individual variation / Thyroid
Healthy underweight participants had higher-than-predicted resting expenditure, with lower food intake and physical activity than normal-BMI controls.
Relevance to EPK. Discussed in Body size does not tell the whole energy story; companion to Controlling Intuitive Appetite, Volume 2, Chapter 27. No direct EPK validation.
Limitations. Selected observational cohort; not a test of weight-loss treatment, wearable accuracy or EPK targets.
2026 · Mechanistic · Mitochondria / Immunity / Redox biology
Experimental impairment of complex III altered cDC1 activation and immune priming; alternative oxidase rescued responsiveness, linking electron flow to regulatory readiness.
Relevance to EPK. Discussed in Mitochondrial electron flow and immune readiness; companion to Controlling Intuitive Appetite, Volume 3, Chapter 67. No direct EPK validation.
Limitations. Cell and mouse mechanistic evidence with human-cell experiments, not a dietary or clinical cancer trial. Figure 1S correction included.
2026 · Human tissue and animal experiments · Dietary composition / Energy metabolism
Human biopsies and mouse experiments linked LMNA-related lipodystrophy to disturbed lipid pathways, inflammation and regional adipocyte loss. Established human disease combined lower total fat with worse glucose and triglyceride measures. Direct respiratory impairment was demonstrated in particular mouse fat depots.
Relevance to EPK. Discussed in the linked EPK article: Less body fat does not always mean better metabolic health. No direct EPK validation.
Limitations. This small genetic-disease study does not show that ordinary dieting produces lipodystrophy, or that additional calories treat it. Human gene-expression changes are not direct measurements of mitochondrial ATP output.
2026 · Animal intervention · Dietary composition / Energy metabolism
Six mice per group received two approximately 9%-fat diets for 16 weeks. Replacing sucrose with additional corn starch was associated with poorer glucose tolerance, altered microbiota and intestinal/liver inflammation, without a body-weight difference.
Relevance to EPK. Discussed in the linked EPK article: Low-fat diets: carbohydrate source matters. No direct EPK validation.
Limitations. The diets changed carbohydrate source, not simply sugar presence. Microbiome mediation was not established. This does not prove humans need added sucrose, or that every low-fat diet is beneficial or harmful.
2026 · Animal and cell experiments · Dietary composition / Energy metabolism
Male mice consuming 60% versus 10% of calories from fat developed behavioural and inflammatory differences. Arachidonic-acid experiments reproduced aspects of the phenotype; aspirin improved some behavioural outcomes and inflammatory measures.
Relevance to EPK. Discussed in the linked EPK article: Dietary fat, brain inflammation and mood. No direct EPK validation.
Limitations. Mouse behavioural tests are not human depression diagnoses. The comparison establishes neither a human fat threshold nor harm from all PUFA. Aspirin was an experimental intervention, not an established dietary-mood treatment.
2026 · Human observational · Dietary composition / Energy metabolism
Blood sampled around 40-km and 171-km races showed oxidative and inflammatory alterations associated with reduced red-cell deformability.
Relevance to EPK. Discussed in the linked EPK article: Endurance exercise, red blood cells and recovery. No direct EPK validation.
Limitations. No fuelling intervention: cannot attribute changes to energy deficit or establish that additional carbohydrate prevents them. Does not demonstrate accelerated whole-body ageing.
2015 · Human controlled feeding · Dietary composition / Energy metabolism
In 19 adults studied under controlled feeding, carbohydrate restriction increased fat oxidation, but equal-calorie fat restriction produced greater calculated net fat loss over six days. Substrate use and net storage are different outcomes.
Relevance to EPK. Discussed in the linked EPK article: Fat oxidation is not the same as body-fat loss. No direct EPK validation.
Limitations. This short experiment cannot establish long-term superiority. Both interventions restricted energy. It does not demonstrate fat loss at maintenance intake or validate an EPK target.
1992 · Cell experiment · Dietary composition / Energy metabolism
Direct fatty-acid exposure inhibited protein synthesis in cultured cells, with arachidonic acid generally most potent among those tested. Calcium regulation contributed, and effects were reversible.
Relevance to EPK. Discussed in the linked EPK article: PUFA tracking: what cellular research can tell us. No direct EPK validation.
Limitations. Cell exposure is not dietary intake. The experiment measured neither human muscle growth nor a safe dietary ceiling. It cannot justify converting micromolar concentrations into grams per day.
2007 · Human crossover interventions · Dietary composition / Energy metabolism
Crossover studies in 17 men and a six-man isocaloric group compared 66%-fat/4%-carbohydrate with 35%-fat/35%-carbohydrate diets. The very-low-carbohydrate diet increased cortisol regeneration and reduced clearance, without changing plasma cortisol or its salivary rhythm.
Relevance to EPK. Discussed in the linked EPK article: Carbohydrate intake can change cortisol metabolism. No direct EPK validation.
Limitations. Subcutaneous abdominal 11β-HSD1 was unchanged. Small male-only studies do not demonstrate clinical harm, abdominal-fat gain, or a benefit from a particular EPK prescription. Neither comparator was a 20%-fat diet.
2025 · Animal experiments and small human trial · Dietary composition / Energy metabolism
Mouse experiments linked fasting to local fatty-acid release, oxidative stress and loss of activated hair-follicle stem cells. A short human trial also found slower hair growth; only 26 of 49 randomised participants had hair-growth measurements.
Relevance to EPK. Discussed in the linked EPK article: Fasting, hair regeneration and energy supply. No direct EPK validation.
Limitations. This does not establish permanent human baldness or universal harm from fasting. Timing and calorie reduction must be distinguished. Human participants were healthy young adults, and long-term hair outcomes were not established.
2017 · Animal intervention; indexed summary assessed · Dietary composition / Energy metabolism
A mouse experiment reported increased lung 11β-HSD1 expression alongside reduced obesity-associated pulmonary inflammation after exercise training. This review uses the indexed publication summary.
Relevance to EPK. Discussed in the linked EPK article: Cortisol signalling depends on tissue and context. No direct EPK validation.
Limitations. It does not establish lasting systemic cortisol excess or that exercise is harmful. Local glucocorticoid activity and clinical outcomes cannot be inferred from a single circulating measurement.
2022 · Small human crossover pilot · Dietary composition / Energy metabolism
A short crossover pilot tested a combined nicotinamide/D-ribose product and reported changes in NAD-related biomarkers. Fifty people were screened; the intention-to-treat population was 18 and the per-protocol population 17.
Relevance to EPK. Discussed in the linked EPK article: NAD precursors and evidence for energy support. No direct EPK validation.
Limitations. A combination product does not isolate niacinamide. Biomarker changes do not establish treatment of insulin resistance, durable functional benefit or equivalence to DCA. Independent replication and longer follow-up are needed.
2026 · Mechanistic preprint · Emerging mitochondrial mechanisms / Mitochondria / ATP
Yang, Gu and Song report a 71 THz infrared signal associated with intact mitochondria and propose light–membrane coupling as its explanation. In HEK-293T cells, ten minutes of illumination at 71 or 87 THz produced approximately 10% higher ATP readings than untreated controls (n = 8); a third frequency showed no significant effect. Posted 15 September 2026; not peer reviewed.
Relevance to EPK. An exploratory connection to EPK–003: how might mitochondrial function influence the relationship between dietary intake and usable cellular energy? This is a proposed mechanistic lead, separate from human feeding evidence; it does not directly support an EPK intake threshold.
Limitations. Assessment based on indexed methods and results, not a complete manuscript audit. The assay measured ATP content after illumination, not synthesis rate directly. A higher ATP pool cannot distinguish increased production from reduced use. The quantum explanation requires further testing and independent replication. No dietary-restriction, FAO, kcal/kg, fatigue-recovery or human-treatment outcomes were tested.
1995 · Human intervention · Carbohydrate availability / FAO / Energy expenditure
Randomised crossover overfeeding study: carbohydrate and fat produced different expenditure and oxidation responses. Most excess energy was stored in both conditions.
Relevance to EPK. Motivates testing dietary composition alongside EPK, especially in EPK–003. The linked article proposes a separate study of recovery from restriction.
Limitations. Small, short, male-only study. Storage estimates were calculated from intake and oxidation; measured body-fat gains did not differ significantly. Does not validate an EPK threshold.
2023 · Mechanistic · Mitochondria / Stress / Functional capacity
Chronic glucocorticoid exposure increased cellular energy expenditure and altered ageing endpoints.
Relevance to EPK. Context for energetic costs of sustained stress.
Limitations. Three human fibroblast lines; not a human lifespan or weight-management trial.
2023 · Mechanistic · Mitochondria / Stress / Functional capacity
Oxidative-phosphorylation defects could coexist with increased energy expenditure.
Relevance to EPK. Distinguishes metabolic rate from functional energy transformation.
Limitations. Cell experiments plus mitochondrial-disease evidence; not ordinary dieting.
2018 · Human observational · Mitochondria / Stress / Functional capacity
Blood-cell mitochondrial health index was associated with caregiving stress and mood.
Relevance to EPK. Links cellular measurements with lived experience.
Limitations. Observational; blood cells do not measure brain mitochondria; no feeding intervention.
2015 · Mechanistic · Mitochondria / Stress / Functional capacity
Mitochondrial perturbations altered responses to acute psychological stress.
Relevance to EPK. Mechanistic context for stress and immune hypotheses.
Limitations. Mouse experiment; not a human calorie-restriction or EPK intervention.
2022 · Human intervention · Dietary adherence / Weight maintenance
At five years, average losses remained modest; group differences were not statistically significant.
Relevance to EPK. Longer-term commercial referral outcomes.
Limitations. Weight available for 69%; missing outcomes are not established failures.
2014 · Human intervention · Dietary adherence / Weight maintenance
About half of intensive-lifestyle participants had at least 5% loss at eight years.
Relevance to EPK. Counterevidence to universal failure claims.
Limitations. Adults with type 2 diabetes receiving sustained intensive support.
2003 · Human intervention · Dietary adherence / Weight maintenance
Intention-to-treat mean two-year loss was 2.9 kg in the commercial group versus 0.2 kg with self-help.
Relevance to EPK. Provides a controlled estimate of modest average benefit.
Limitations. Mean change is not a failure percentage; commercial programme funding.
2001 · Human observational · Dietary adherence / Weight maintenance
42.6% of the selected five-year group maintained at least 5% loss.
Relevance to EPK. Illustrates the denominator problem in commercial programme claims.
Limitations. Selected successful members; cannot estimate success among all starters.
1950 · Human intervention · Calorie restriction / Behaviour / Recovery
Historical semi-starvation and rehabilitation experiment documented physiological and behavioural changes.
Relevance to EPK. Foundational context for energy restriction and recovery.
Limitations. Monograph catalogue verified; detailed account triangulated with Kalm and Semba and reanalyses. Young male volunteers; no modern randomised control.
1997 · Human observational · Appetite / Recovery
Historical-data reanalysis connects post-starvation hyperphagia with tissue recovery.
Relevance to EPK. Appetite during rehabilitation is a testable physiological outcome.
Limitations. 12-men subgroup; not an independent replication of Minnesota.
1996 · Human observational · Metabolic adaptation / Recovery
Historical-data reanalysis links recovery patterns to partitioning and suppressed thermogenesis.
Relevance to EPK. Candidate adaptive physiology during recovery.
Limitations. Secondary analysis of severe semi-starvation; model-dependent interpretation.
1996 · Mechanistic · Stress / Cognition
Review distinguishes several forms of glucocorticoid-associated neural change and vulnerability.
Relevance to EPK. Background for a stress-cognition hypothesis.
Limitations. Largely preclinical; does not show ordinary dieting causes dementia.
2005 · Mechanistic · Stress / Behaviour
Review: social hierarchy and stress-related health relationships vary by social circumstances.
Relevance to EPK. Motivates measuring social context separately.
Limitations. Primate synthesis; not a human food-scarcity intervention.
2000 · Mechanistic · Stress / Hormonal function
Review: glucocorticoid effects vary with timing and physiological context.
Relevance to EPK. Context for stress and immune hypotheses.
Limitations. Review, not an EPK trial or evidence for a calorie threshold.
2010 · Human intervention · Stress / Calorie restriction
Restriction increased cortisol output; calorie monitoring increased perceived stress.
Relevance to EPK. Separates dietary exposure from monitoring burden.
Limitations. Three weeks in women; not proof of long-term weight-loss failure.
2007 · Human intervention · Sleep / Glucose regulation
Induced nocturnal hypoglycaemia produced more awakenings in healthy controls than in type 1 diabetes.
Relevance to EPK. Mechanistic boundary for glucose and waking claims.
Limitations. Insulin-induced 2.2 mmol/L glucose; not routine dieting.
2016 · Human intervention · Sleep / Calorie restriction
Brief severe restriction increased a deep-sleep measure without significantly changing awakenings.
Relevance to EPK. Demonstrates heterogeneous sleep responses.
Limitations. 12 men; two restriction days; fixed sequence.
2016 · Human intervention · Sleep / Calorie restriction
Moderate long-term calorie restriction did not worsen overall self-reported sleep.
Relevance to EPK. Essential counterevidence to a universal sleep-harm claim.
Limitations. Healthy adults without obesity; self-report; differs from severe under-fuelling.
2024 · Human observational · Sleep / Energy availability
Lower energy availability was associated with poorer overnight sleep measures in adolescent rugby players.
Relevance to EPK. Connects sports energy availability and sleep.
Limitations. 42 participants; estimated availability; observational; exploratory thresholds.
2025 · Human intervention · Sleep / Energy availability
Sleep fragmentation increased after a short reduction in energy availability.
Relevance to EPK. Direct candidate sleep outcome.
Limitations. 17 completers; non-randomised sequence; actigraphy; not a hypoglycaemia test.
2016 · Human intervention · Energy availability / Hormonal function
Four days of low energy availability reduced leptin and insulin without significant testosterone or T3 changes.
Relevance to EPK. Shows that early endocrine responses need not move together.
Limitations. Six exercising men; a short null testosterone result does not establish long-term safety.
2024 · Human intervention · Energy availability / Hormonal function / Fatigue
The most restricted four-day condition reduced testosterone and increased fatigue in male runners.
Relevance to EPK. Supports studying functional and endocrine outcomes together.
Limitations. Twelve men; energy availability uses exercise-adjusted intake per fat-free mass, not intake-based EPK.
2022 · Human intervention · Energy availability / Physical activity / Hormonal function
Reduced energy availability affected performance and well-being; testosterone findings differed between absolute-value and quartile analyses.
Relevance to EPK. Suggests multiple functional outcomes and individual responses should inform EPK testing.
Limitations. Small exploratory trial; significant quartile results are not equivalent to a significant absolute testosterone decline or a validated cutoff.
2011 · Human intervention · Sleep / Hormonal function
Restricted sleep was associated with lower daytime testosterone in young healthy men.
Relevance to EPK. Makes sleep and sampling conditions relevant to endocrine outcomes in EPK research.
Limitations. Small, short fixed-order experiment; subsequent sleep-restriction experiments have produced different findings.
2019 · Human intervention · Sleep / Hormonal function
Randomized acute and chronic sleep-restriction experiments did not show a clinically meaningful testosterone reduction under the tested conditions.
Relevance to EPK. Provides a counterpoint to assuming a fixed hormonal consequence of restricted sleep.
Limitations. Small secondary analyses not originally powered for testosterone; results depend on the tested protocols.
2018 · Guideline · Hormonal function / Clinical interpretation
Requires compatible symptoms or signs and consistently low testosterone, with repeat morning fasting measurement to confirm diagnosis.
Relevance to EPK. Defines the boundary between exploratory EPK measures and clinical diagnosis.
Limitations. Not an EPK trial, dietary threshold or recommendation to maximise testosterone.
2010 · Human intervention · Sleep / Dietary adherence
Shorter sleep opportunity during calorie restriction shifted weight loss toward less fat and more fat-free mass.
Relevance to EPK. Supports measuring recovery and body composition alongside intake and adherence.
Limitations. Ten-person, two-week crossover conditions; fat-free mass is not a direct measure of muscle protein.
2013 · Human intervention · Glucose regulation / Physical activity
Three 15-minute postmeal walking bouts improved 24-hour glucose control in older adults at risk of glucose intolerance.
Relevance to EPK. Tests the interaction of nutrient supply and activity timing.
Limitations. Ten participants and acute outcomes; does not establish long-term fat loss or an EPK threshold.
2012 · Human intervention · Glucose regulation / Physical activity
Interrupting sitting with brief walking bouts lowered postmeal glucose and insulin responses.
Relevance to EPK. Adds activity distribution to models of energy use.
Limitations. Acute crossover study in 19 adults with overweight or obesity; long-term outcomes were not established.
2011 · Human observational · Body composition / Energy requirements
Evaluated reference tissue-specific resting rates, including about 13 kcal/kg/day for muscle and 4.5 for adipose tissue.
Relevance to EPK. Explains why the tissue composition of body mass affects interpretation of RMR/kg.
Limitations. Reference model coefficients are not individual measurements or dietary minimums.
2015 · Human intervention · Fatty acid oxidation / Diet composition
Carbohydrate restriction increased fat oxidation, but matched fat restriction produced greater short-term net fat loss estimated from fat balance.
Relevance to EPK. Separates fuel selection from net fat loss in the EPK substrate-use model.
Limitations. Nineteen adults; six-day intervention periods cannot establish long-term dietary superiority.
2021 · Human intervention · Dietary adherence / Diet composition
Spontaneous intake was lower on the plant-based low-fat diet than on the animal-based ketogenic diet.
Relevance to EPK. Shows why achieved intake and food pattern matter alongside calorie prescriptions.
Limitations. Twenty adults, two weeks per diet; food sources and energy density also differed.
2017 · Human intervention · Mitochondria / Ageing / Physical activity
Training modes produced different adaptations; interval and combined training improved mitochondrial respiration.
Relevance to EPK. Supports measuring physical capacity and mitochondrial function rather than assuming expenditure measures both.
Limitations. Twelve-week exercise study, not a test of EPK or a dietary minimum.
2009 · Human intervention · Mitochondria / Substrate utilisation
Tracer measurements showed that the healthy human brain takes up and oxidizes circulating lactate.
Relevance to EPK. Refines the fuel-use model: lactate is not simply waste or proof of failed oxidation.
Limitations. Six people under infusion and exercise conditions; not evidence for a lactate-raising treatment.
2014 · Human intervention · Diet composition / Body composition
Saturated-fat overfeeding produced more liver and visceral-fat gain than n-6 polyunsaturated-fat overfeeding despite similar weight gain.
Relevance to EPK. Requires the EPK lipid discussion to consider human outcomes as well as proposed membrane mechanisms.
Limitations. Seven-week study in young, normal-weight adults; not a direct mitochondrial or EPK experiment.
2005 · Human observational · RMR / Ageing / Longevity
The abstract reports higher RMR in 28 long-lived women than in 27 younger elderly women, with no difference from 26 adult women.
Relevance to EPK. Motivates comparison of preserved resting metabolism in exceptional longevity.
Limitations. Abstract-level appraisal. Full tables and per-kilogram comparisons remain unverified. Survivor selection and the observational design prevent causal conclusions.
2003 · Human observational · RMR / Body composition / Lifespan
In 15 children and 13 young adults, brain and liver mass improved the expenditure model but did not remove the age effect. Published tissue coefficients underestimated measured expenditure in children.
Relevance to EPK. Qualifies explanations of energy per kilogram based solely on tissue proportions.
Limitations. Small cross-sectional comparison; abstract-level appraisal. Does not establish age-specific intake thresholds.
2007 · Human intervention · Cognition / Appetite / Energy intake
A within-person reading-and-writing versus seated-rest comparison found that mental work could increase subsequent freely chosen food intake.
Relevance to EPK. Separates the question of eating behaviour after cognitive effort from the energy cost of the task.
Limitations. Acute laboratory study; primary-study record inspected. Does not establish everyday requirements or the calorie cost of elite chess.
2013 · Human intervention · Cognition / Appetite / Energy expenditure
In a randomized crossover study of 35 young adults, the energy cost of mental work did not differ significantly from control. Subsequent intake responses differed between men and women.
Relevance to EPK. Supports measuring expenditure, food intake and appetite ratings separately when testing a brain-energy hypothesis.
Limitations. Small, homogeneous sample with substantial individual variation; acute outcomes do not establish long-term feeding needs. Full-text methods and results inspected.
2024 · Human observational · RMR / Measurement
Measured RMR in 324 young adults averaged 26.1 kcal/kg/day in men and 24.6 in women.
Relevance to EPK. Provides an empirical resting-expenditure comparison for intake per kilogram.
Limitations. Young adults only. Group averages are not universal minimum dietary requirements or validated EPK thresholds.
2021 · Guideline · Energy restriction / Clinical nutrition / Measurement
Specifies 25 kcal/kg actual body weight/day as minimum standard-diet provision, and 30 kcal/kg/day for its higher-energy hospital diet.
Relevance to EPK. An explicit clinical precedent for expressing intake requirements per kilogram.
Limitations. Good-practice consensus with different populations for each diet. Not a trial validating a universal EPK threshold; the higher-energy diet addresses older or nutritionally vulnerable patients.
2019 · Human observational · Muscle mass / Clinical nutrition / Energy restriction
Meeting the 25 kcal/kg/day reference did not adequately prevent muscle loss; higher intake was associated with better preservation.
Relevance to EPK. Shows that meeting a reference minimum need not ensure a functional or body-composition outcome.
Limitations. Cancer and treatment context; observational comparisons cannot establish a causal optimal intake for healthy adults.
2008 · Mechanistic · FAO / Mitochondria
Incomplete fat oxidation in experimental muscle insulin resistance.
Relevance to EPK. Motivates distinguishing substrate supply from completion and switching.
Limitations. Rodent and cell models; does not establish low EPK as the cause.
2026 · Mechanistic · FAO / Mitochondria / Function
Unrestrained cardiac FAO and cardiolipin loss in genetically modified mice.
Relevance to EPK. Tests the assumption that more fat oxidation always indicates better function.
Limitations. Extreme cardiac genetic model; normal FAO remains essential.
2021 · Mechanistic · Carbohydrate / Mitochondria / Function
Cardiac pyruvate handling studied through experimental manipulation and human disease samples.
Relevance to EPK. Separates mitochondrial fuel transport from dietary carbohydrate availability.
Limitations. Human observations do not turn model interventions into a dietary treatment.
2024 · Mechanistic · FAO / Aging
FAO-dependent senescence pathway in experimental systems.
Relevance to EPK. Suggests a specific cellular-aging hypothesis to test.
Limitations. Cellular senescence is not equivalent to human cognitive decline or lifespan.
2025 · Mechanistic · Sleep / Mitochondria
Mitochondrial regulation of sleep pressure in fruit flies.
Relevance to EPK. Encourages measuring sleep separately from energy intake and fatigue.
Limitations. Does not test human EPK or demonstrate that sleep pressure is an ATP deficit.
2025 · Mechanistic · Lipids / Mitochondria
Lipid–protein compatibility in respiratory complexes.
Relevance to EPK. Requires precise fatty-acid and membrane context in mitochondrial hypotheses.
Limitations. Evolutionary and engineered-cell experiments do not establish dietary PUFA toxicity.
2026 · Mechanistic · Immunity / Mitochondria
Complex III affects dendritic-cell regulation beyond ATP supply.
Relevance to EPK. Refines the meaning of physiological capacity in Proportional Danger Theory.
Limitations. Subtype-specific cellular evidence; EPK-to-immunity link remains untested. Published correction linked in the article bibliography. Published correction: https://doi.org/10.1016/j.cmet.2026.04.010. Included with the original report in EPK–007 v1.2.
2024 · Human intervention · FAO / Mitochondria / Function
A randomized crossover study of 12 endurance-trained women found poorer cycling performance after 14 days of low energy availability, with increased fat oxidation but unchanged measured muscle mitochondrial respiratory capacity. This supports a functional effect while challenging mitochondrial impairment as its necessary explanation.
Relevance to EPK. Separates performance loss from measured mitochondrial impairment.
Limitations. Selected PubMed record/abstract appraisal. Population, duration and measured outcomes limit extrapolation; no EPK validation.
2024 · Human intervention · Immunity / Mitochondria
A randomized crossover investigation in 12 female endurance athletes examined immune-cell redox responses during low energy availability. It adds a human link between the exposure and cellular physiology, but biomarkers do not establish infection risk or vaccine effectiveness. This report and Caldwell et al. appear to concern the same intervention cohort and should not be counted as independent replications.
Relevance to EPK. Provides human cellular evidence alongside the dendritic-cell experiments.
Limitations. Selected PubMed record/abstract appraisal. Population, duration and measured outcomes limit extrapolation; no EPK validation.
2021 · Human intervention · Cognition
Twenty women completed three-day conditions. Diet-induced low energy availability did not alter the measured cognitive outcomes; exercise-induced low availability affected mental-rotation accuracy relative to balanced intake, while other outcomes were unchanged. This limits a general claim that short-term low energy availability broadly impairs cognition.
Relevance to EPK. Provides a direct human cognitive test with substantial null findings.
Limitations. Selected PubMed record/abstract appraisal. Population, duration and measured outcomes limit extrapolation; no EPK validation.
2016 · Human intervention · Behaviour / Sleep
The two-year CALERIE 2 trial reported improvements in some mood and quality-of-life outcomes with calorie restriction, rather than the predicted general deterioration. Structured moderate restriction in selected healthy adults should be distinguished from severe low availability in athletes or symptomatic undernutrition.
Relevance to EPK. Challenges an inevitable deterioration-with-restriction model.
Limitations. Selected PubMed record/abstract appraisal. Population, duration and measured outcomes limit extrapolation; no EPK validation.
2007 · Human intervention · Mitochondria
In a six-month randomized study of 36 adults, calorie restriction increased muscle mitochondrial DNA content while key mitochondrial enzyme activities remained unchanged. The result separates mitochondrial quantity from measured functional capacity and challenges a universal decline-with-restriction model.
Relevance to EPK. Separates mitochondrial quantity from functional assay results.
Limitations. Selected PubMed record/abstract appraisal. Population, duration and measured outcomes limit extrapolation; no EPK validation.
2017 · Human intervention · Mitochondria / FAO
In a small 16-week comparison of weight loss (7 participants) and exercise (10), insulin sensitivity improved similarly while mitochondrial adaptations differed. This shows why insulin sensitivity and mitochondrial capacity should not be treated as equivalent outcomes.
Relevance to EPK. Shows that insulin sensitivity and mitochondrial adaptations can dissociate.
Limitations. Selected PubMed record/abstract appraisal. Population, duration and measured outcomes limit extrapolation; no EPK validation.
2026 · Human intervention · Carbohydrate / FAO / Energy availability
In 16 adults over four-day crossover conditions, higher carbohydrate availability attenuated the IGF-1 decline during low energy availability. Maximal performance was unchanged.
Relevance to EPK. Directly motivates separating carbohydrate availability from total energy exposure.
Limitations. Short intervention; several hormonal interactions were nonsignificant. It does not establish a general carbohydrate rescue of low energy availability.
2025 · Human intervention · Carbohydrate / FAO
Twelve participants completed acute diet conditions that separated carbohydrate restriction from energy restriction. Several fuel-use responses were similar with and without energy restriction.
Relevance to EPK. Helps design a comparison that avoids attributing carbohydrate effects to EPK.
Limitations. One-day exposure with next-day testing; changes in metabolic markers do not establish long-term health benefit.
2024 · Human intervention · Mitochondria / Function / FAO
Fifty adults were randomized to dietary advice alone or with exercise for 16 weeks. Exercise modified the mitochondrial enzyme responses to the dietary programme.
Relevance to EPK. Makes activity and sex relevant modifiers rather than simple nuisance variables.
Limitations. Enzyme activity and protein abundance are specific endpoints, not a complete assessment of mitochondrial function. No untreated control isolates restriction itself.
2022 · Human intervention · Function / Aging
A six-month randomized trial found distinct functional and body-composition effects of weight loss with versus without exercise.
Relevance to EPK. Directly informs functional endpoints and the need to account for exercise during weight loss.
Limitations. Older adults with obesity; findings should not be generalized to every low-EPK population.
2016 · Human intervention · Adherence / Energy restriction
Modelling a 52-week drug trial estimated appetite compensation of about 100 kcal/day per kilogram lost.
Relevance to EPK. Supports appetite feedback as a barrier to maintaining weight loss.
Limitations. Abstract-level appraisal. Model-inferred intake during canagliflozin treatment, not direct measurement of voluntary dieting behaviour.
2011 · Human intervention · Adherence / Energy restriction
After a very-low-energy diet, increased hunger and several appetite-related hormonal changes persisted at one year.
Relevance to EPK. Supports measuring hunger and maintenance difficulties alongside intended deficits.
Limitations. Abstract-level appraisal. Fifty participants enrolled; an intensive intervention without a parallel control cannot show that all calorie deficits cause diet failure.
2005 · Human intervention · Adherence
In 160 adults, one-year weight loss was associated with reported adherence rather than assigned diet type.
Relevance to EPK. Makes sustained adherence a useful outcome across dietary approaches.
Limitations. Abstract-level appraisal. Adherence was self-reported and not randomized; substantial dropout limits causal interpretation.
2019 · Human intervention · Carbohydrate / Performance
Sixteen adults had lower cycling power and intermittent-running performance after four days of ketogenic eating with similar reported energy intake.
Relevance to EPK. Separates carbohydrate availability from calorie intake when studying performance.
Limitations. Abstract-level appraisal. Short adaptation period; impaired anaerobic performance is not evidence of reduced RMR or permanent metabolic damage.
2023 · Human intervention · Carbohydrate / RMR
Six athletes showed no significant fasting energy-expenditure differences after 14-day ketogenic and high-carbohydrate phases.
Relevance to EPK. A null result to include when testing claims of low-carb metabolic decline.
Limitations. Abstract-level appraisal. Very small, short, ad libitum study; lack of significance does not demonstrate equivalence.
2016 · Human intervention · Carbohydrate / RMR
Seventeen men showed small increases in chamber and sleeping energy expenditure after switching to an isocaloric ketogenic diet; body-fat loss did not increase.
Relevance to EPK. Counters a universal claim that carbohydrate restriction suppresses energy expenditure.
Limitations. Abstract-level appraisal. Fixed diet order, short inpatient study and concurrent weight loss limit generalisation; sleeping expenditure is not identical to a standard RMR test.
2005 · Human observational · Ageing / Performance
In 810 adults, longitudinal aerobic-capacity decline accelerated with age, including when indexed to body mass or fat-free mass.
Relevance to EPK. Supports repeated aerobic testing as an ageing-related functional outcome.
Limitations. Abstract-level appraisal. Observational; it does not identify low energy intake as the cause or show that raising EPK reverses decline.
2006 · Human observational · Ageing / Muscle mass / Performance
Over three years in 1,880 older adults, strength declined about three times faster than leg lean mass.
Relevance to EPK. Measure strength and function separately from muscle mass.
Limitations. Abstract-level appraisal. Observational associations do not establish nutritional causation; maintaining mass alone did not ensure preserved strength.
2014 · Human intervention · Ageing / Healthspan / Performance
In 1,635 older adults, structured activity reduced major mobility disability over 2.6 years: 30.1% versus 35.5%.
Relevance to EPK. Provides a clinically meaningful healthspan outcome and an activity intervention comparator.
Limitations. Abstract-level appraisal. Does not test dietary EPK, centenarian survival or extension of lifespan.
2015 · Human intervention · Energy restriction / Healthspan / RMR
The restriction group achieved about 11.7% calorie restriction and maintained 10.4% weight loss, with improved cardiometabolic risk factors. RMR residual differed at 12 but not 24 months.
Relevance to EPK. Shows why lower expenditure and calorie restriction cannot automatically be equated with poorer health.
Limitations. Abstract-level appraisal. Risk markers and quality of life, not demonstrated lifespan extension. Shares the CALERIE programme with other library papers; do not count these as independent trials.
1995 · Human observational · Centenarians / Ageing / RMR
Fifteen healthy adults over 100 were compared with younger and older groups. Estimated RMR was higher than in the older group after adjustment for activity and disability, but not in the unadjusted comparison.
Relevance to EPK. A relevant lead for preserved energetic function in exceptional longevity.
Limitations. Abstract-level appraisal. RMR was calculated with a formula, not measured by calorimetry. Small selected cross-sectional sample; no established high RMR per kilogram or causal survival benefit.
1999 · Human observational · Ageing / RMR / Measurement
An apparent exerciser advantage in RMR per kilogram disappeared after correcting for the non-zero intercept of RMR versus body mass.
Relevance to EPK. Directly cautions against interpreting a simple per-kilogram ratio as independent metabolic superiority.
Limitations. Abstract-level appraisal. Older men, not centenarians; observational. Compare measured RMR using body-composition adjustment as well as ratios.
2023 · Guideline · Elite sport / Energy availability
Explains sports energy availability and uncertainty around universal cutoffs.
Relevance to EPK. Defines a comparator for EPK.
Limitations. Consensus guidance; not a validation study of EPK.
2024 · Human observational · Elite sport / Performance
A single elite cyclist had high measured expenditure during a multistage race.
Relevance to EPK. Demonstrates the importance of recording competition workload.
Limitations. One athlete; not a population requirement or threshold.
2004 · Guideline · Pregnancy / Lifespan
Provides trimester-specific additional maternal energy estimates.
Relevance to EPK. Separates maternal intake from fetal energy accounting.
Limitations. Assumption-dependent maternal estimates; not fetal kcal/kg.
2004 · Guideline · Infancy / Lifespan
Estimates infant energy needs including growth.
Relevance to EPK. Documents how the purpose of energy intake changes with development.
Limitations. Historical population reference estimates; feeding type matters.
2004 · Guideline · Childhood / Lifespan
Provides age- and sex-specific reference requirements with growth and activity assumptions.
Relevance to EPK. Supports age-stratified EPK research.
Limitations. Reference values are not minimum thresholds or individual prescriptions.
2023 · Guideline · Infancy / Lifespan
Distinguishes total enteral nutrition from resting expenditure in healthy growing preterm infants.
Relevance to EPK. Shows why growth and feeding route belong in the definition.
Limitations. Does not supply a universal fetal or critically ill neonatal requirement.
2021 · Human observational · Ageing / Lifespan / RMR
Finds distinct age phases in body-composition-adjusted energy expenditure.
Relevance to EPK. Tests a simple age-independent interpretation of kcal/kg.
Limitations. Adjusted expenditure is not raw expenditure/kg or dietary intake.
2022 · Guideline · Ageing / Disease
Uses an individualised energy guide for older people.
Relevance to EPK. Links nutritional assessment to function.
Limitations. Clinical guidance does not prove an EPK threshold.
2021 · Guideline · Disease / Energy requirements
Provides a weight-based estimate when individual expenditure is unavailable.
Relevance to EPK. Clarifies the role of 25–30 kcal/kg in clinical practice.
Limitations. Energy requirements vary between patients.
2023 · Guideline · Disease / Energy requirements
Distinguishes early acute illness from later progressive energy delivery.
Relevance to EPK. Tests the boundaries of a fixed intake threshold.
Limitations. ICU feeding guidance must not be transferred to healthy adults.
1983 · Human intervention · Energy expenditure / Carbohydrate
Seven men had higher basal expenditure and body weight after carbohydrate overfeeding.
Relevance to EPK. Supports testing changes in expenditure over time.
Limitations. Small fixed-order study; added energy and carbohydrate cannot be separated.
2004 · Mechanistic · Ageing / Mitochondria
Higher metabolic intensity associated with longer survival in an outbred mouse cohort.
Relevance to EPK. Challenges a universal rate-of-living rule.
Limitations. Animal association; primary abstract reviewed, full-text methods audit pending.
2008 · Human observational · Ageing / Energy expenditure
Higher BMR associated with higher mortality in the Baltimore cohort.
Relevance to EPK. Requires clinical context when interpreting expenditure.
Limitations. Observational; no evidence that deliberately lowering BMR improves survival.
2020 · Human observational · Mitochondria / Energy expenditure
Higher RMR associated with greater muscle oxidative capacity after adjustment.
Relevance to EPK. Connect expenditure to a separately measured functional mechanism.
Limitations. Cross-sectional; not proof of improved longevity.
1997 · Human intervention · Illness / Energy expenditure
Cooling febrile sedated patients lowered measured energy expenditure.
Relevance to EPK. Illness-related expenditure must be distinguished from healthy capacity.
Limitations. Critical-care conditions; no universal fever correction factor.
1998 · Human intervention · Stress / Energy expenditure
Prolonged epinephrine infusion increased measured resting expenditure.
Relevance to EPK. Adrenergic activity can alter energy use independently of visible movement.
Limitations. Small male infusion experiment; not a daily-life stress calorie estimate.
2001 · Human intervention · Illness / Muscle mass
Beta blockade reduced expenditure and improved muscle protein balance after severe burns.
Relevance to EPK. Higher expenditure and better tissue preservation are distinct outcomes.
Limitations. Specialist paediatric burn treatment; not general medication advice.
2020 · Human observational · Ageing / Illness
Several diseases accompanied higher initial RMR and faster subsequent decline.
Relevance to EPK. Repeated measures may distinguish energetic burden from later tissue loss.
Limitations. Observational; proposed mechanisms are not established by the association.
1997 · Human intervention · Recovery / Functional capacity
Metabolic measures recovered before muscle force after intermittent contractions.
Relevance to EPK. Functional recovery cannot be inferred from one energy marker.
Limitations. Eight men; not a feeding trial. Primary abstract reviewed; full text unavailable.
2011 · Human intervention · Carbohydrate / Recovery
Low glycogen was associated with impaired muscle calcium release after exercise.
Relevance to EPK. Connect substrate availability with contraction mechanisms.
Limitations. Task-specific physiology; not proof that all fatigue is carbohydrate shortage.
2011 · Human intervention · Recovery / Performance
Force, glycogen, soreness and calcium handling recovered on different timelines.
Relevance to EPK. Measure function as well as intake and expenditure.
Limitations. Seven male players; results cannot prescribe recovery for every sport.
2010 · Mechanistic · Ageing / Mineral regulation
Genetic phosphate reduction improved abnormalities in Klotho-deficient mice; dietary elevation reversed benefits.
Relevance to EPK. Highlights mineral handling beyond calorie sufficiency.
Limitations. Genetically altered mice; limited follow-up is not a demonstrated normal lifespan.
2018 · Human intervention · Mineral regulation / Cardiovascular
Higher phosphate exposure increased blood pressure in a small controlled human study.
Relevance to EPK. A human lead for investigating nutrient regulation and function.
Limitations. Supplement/binder comparison; short duration and no disease or survival endpoint.
2019 · Human intervention · Mineral regulation / Cardiovascular
Acute phosphate affected endothelial function without increasing exercise pressor responses.
Relevance to EPK. Keep physiological endpoints separate when interpreting mineral effects.
Limitations. Acute exposure; not a long-term dietary outcome trial.
2017 · Mechanistic · Cellular energy / ATP
ATP prevented and dissolved protein aggregates under experimental conditions.
Relevance to EPK. Additional ATP roles may matter to cellular organisation.
Limitations. Mechanistic experiment; no demonstrated dietary EPK or human disease benefit.
2007 · Mechanistic · Cellular energy / ATP
X-ray structure and functional characterisation identified ion-binding features of Na+,K+-ATPase.
Relevance to EPK. Provides a mechanism for ATP-dependent maintenance work.
Limitations. A protein study does not quantify individual daily dietary needs.
1977 · Mechanistic · Cellular energy / ATP
Reconstituted preparations showed ATP-dependent sodium and potassium transport.
Relevance to EPK. Functional evidence for membrane pumping, beyond structural observations.
Limitations. Artificial membrane system; not a nutritional intervention.
2001 · Mechanistic · Cellular energy / ATP
A physiological model estimated energy costs of grey-matter signalling.
Relevance to EPK. Explains ion-gradient restoration as part of neural energy demand.
Limitations. Model largely based on rodent data, not a human cognitive calorie allowance.
1977 · Mechanistic · Cellular energy / ATP
Reconstituted bacterial ATPase supported proton-gradient-driven ATP synthesis.
Relevance to EPK. Tests energy coupling in a reduced experimental system.
Limitations. Does not measure whole-human mitochondrial or dietary responses.
1974 · Mechanistic · Cellular energy / ATP
Reconstituted membrane vesicles supported light-driven proton uptake and ATP formation.
Relevance to EPK. Tests whether selected components can support energy conversion.
Limitations. Historical model-system experiment, not a clinical trial.
1997 · Mechanistic · Cellular energy / ATP
Individual F1-ATPase molecules showed ATP-driven rotation.
Relevance to EPK. Direct evidence of molecular energy-to-motion coupling.
Limitations. Hydrolysis direction observed; not direct human dietary evidence.
2023 · Cell culture · Stress / Dietary behaviour
Chronic glucocorticoid exposure increased estimated energy expenditure in cultured human fibroblasts.
Relevance to EPK. Supports investigating the energetic burden of sustained stress.
Limitations. Three donor lines; cannot translate the percentage into human calorie needs.
2014 · Human experimental · Stress / Dietary behaviour
Acute stress reduced reported appetite in 31 participants without reducing measured food intake.
Relevance to EPK. Separates appetite from actual fuelling.
Limitations. Short laboratory exposure; does not establish long-term dietary adequacy.
1992 · Human experimental · Stress / Dietary behaviour
A stressful film reduced food consumption in men; increases in women were not statistically significant.
Relevance to EPK. Shows that stress-related undereating can occur.
Limitations. Context-specific response; not a population prevalence estimate.
2012 · Human observational · Stress / Dietary behaviour
Higher stress was associated with a stronger drive to eat and less favourable reported food patterns in 457 women.
Relevance to EPK. Connects stress with dietary quality as well as quantity.
Limitations. Self-report and observational design; causality and generalisability remain limited.