The Research
The science behind health, performance, and longevity is moving fast. This page tracks the research that informs how Nutri-Stasis protocols are built — organized by topic, written in plain English, and linked to the original source. Every study listed here meets a basic standard: peer-reviewed, published in an indexed journal, and relevant to a mechanism or outcome we actually care about.
We update this page as significant new research publishes. The goal is not comprehensiveness — it is signal over noise.
NAD+ Biology and Cellular Aging
NMN maintains walking speed and improves sleep quality in older adults (2024)
Morifuji et al. (2024) conducted a randomized, double-blind, placebo-controlled parallel-group trial of 250mg/day NMN in 60 adults aged 65–75 for 12 weeks. The NMN group maintained walking speed while the placebo group declined, and reported significantly better sleep quality. Blood NAD+ and its metabolites were significantly elevated at both 4 and 12 weeks — the first RCT to simultaneously demonstrate NMN supporting both gait function and sleep architecture in an older adult population.
Morifuji M, et al. GeroScience, 2024 →
NMN increases NAD+ and improves functional markers in older adults (2022)
Igarashi et al. (2022) administered 250mg/day NMN to healthy adults aged 65+ for 12 weeks. Blood NAD+ levels increased significantly, and participants showed improvements in gait speed and grip strength — objective functional measures of biological aging.
Igarashi M, et al. NPJ Aging, 2022 →
NMN supplementation improves muscle insulin sensitivity in prediabetic women (2021)
Yoshino et al. (2021) conducted a randomized placebo-controlled trial of 250mg/day NMN for 10 weeks. NMN significantly improved skeletal muscle insulin sensitivity and upregulated genes involved in muscle remodeling — the first human RCT to demonstrate NMN’s metabolic benefit in a clinically relevant population.
Yoshino M, et al. Science, 2021 →
CD38 is the dominant NAD-consuming enzyme in aging tissue (2016)
Camacho-Pereira et al. (2016) identified CD38 as the primary driver of age-related NAD+ decline. CD38 inhibition in aged mice restored NAD+ levels and improved mitochondrial function, establishing a direct mechanistic link between inflammation, NAD+ loss, and cellular energy decline.
Camacho-Pereira J, et al. Cell Metabolism, 2016 →
NAD+ declines ~50% between ages 40 and 60 (2015)
Zhu et al. (2015) used in vivo NAD assay techniques to establish that NAD+ levels in human brain tissue decline measurably with age, with approximately 50% reduction between the fourth and sixth decades of life. This decline impairs mitochondrial function, sirtuin activity, and DNA repair capacity.
The hallmarks of aging — the organizing framework (2013)
López-Otín et al. (2013) published the foundational classification of biological aging mechanisms, updated to thirteen hallmarks in 2023. This framework organizes how cellular dysfunction accumulates over time and identifies the most tractable intervention targets.
López-Otín C, et al. Cell, 2013 →
Sirtuins and Resveratrol
Resveratrol activates SIRT1 and improves vascular function in healthy adults (2023)
Gonçalinho et al. (2023) randomized 48 healthy adults aged 55–65 to resveratrol supplementation or caloric restriction for 30 days. Both interventions significantly increased circulating SIRT1, with resveratrol producing improvements in vascular reactivity comparable to energy restriction — the first RCT to directly compare resveratrol and caloric restriction on SIRT1 and endothelial function in humans.
Gonçalinho GHF, et al. Nutrients, 2023 →
Resveratrol mimics caloric restriction in obese humans (2011)
Timmers et al. (2011) administered 150mg/day resveratrol to obese men for 30 days and found metabolic changes comparable to those produced by caloric restriction — the first human trial to demonstrate resveratrol activating the caloric restriction mimetic pathway.
Timmers S, et al. Cell Metabolism, 2011 →
Resveratrol activates SIRT1 and improves mitochondrial function (2006)
Lagouge et al. (2006) demonstrated that resveratrol activated SIRT1 and PGC-1α, increased mitochondrial number and oxidative capacity, improved running endurance, and protected against diet-induced obesity.
Lagouge M, et al. Cell, 2006 →
Sirtuins extend lifespan via NAD-dependent deacetylase activity (2000)
Imai et al. (2000) established that Sir2 extends lifespan through NAD-dependent deacetylase activity, establishing the mechanistic link between NAD+ availability, sirtuin function, and biological aging.
Mitochondrial Function and CoQ10
CoQ10 reduces exercise-induced muscle damage markers across 28 RCTs (2024)
Tabrizi et al. (2024) conducted a GRADE-assessed dose-response meta-analysis of 28 RCTs (830 subjects) examining CoQ10’s effect on exercise-induced muscle damage and oxidative stress. CoQ10 significantly reduced creatine kinase, lactate dehydrogenase, myoglobin, and malondialdehyde. Each 100mg/day increase in CoQ10 produced a measurable, dose-dependent reduction in these markers.
Tabrizi R, et al. Clinical Nutrition ESPEN, 2024 →
CoQ10 significantly reduces cardiovascular mortality in heart failure (2014)
The Q-SYMBIO trial (Mortensen et al., 2014) randomized 420 chronic heart failure patients to 300mg/day CoQ10 or placebo for two years. The CoQ10 group showed significant reductions in major adverse cardiovascular events and cardiovascular mortality.
Mortensen SA, et al. JACC Heart Failure, 2014 →
Declining NAD+ disrupts nuclear-mitochondrial communication (2013)
Gomes et al. (2013) — Sinclair Lab at Harvard — demonstrated that NAD+ decline disrupts the signaling between the nucleus and mitochondria required for coordinated electron transport chain function. NMN administration in aged mice restored this communication within one week.
Statins reduce plasma CoQ10 by 40% (2004)
Rundek et al. (2004) demonstrated that 30 days of atorvastatin therapy reduced plasma CoQ10 levels by approximately 40% in patients at cardiovascular risk — making CoQ10 repletion particularly relevant for adults on statin therapy.
Rundek T, et al. Archives of Neurology, 2004 →
AMPK and Metabolic Flexibility
AMPK is the master regulator of energy homeostasis (2012)
Hardie et al. (2012) documented AMPK’s role as the cellular energy sensor that responds to energy stress by activating fat oxidation, glucose uptake, mitochondrial biogenesis, and autophagy.
Hardie DG, et al. Nature Reviews Molecular Cell Biology, 2012 →
Berberine matches metformin for glucose reduction in type 2 diabetes (2008)
Yin et al. (2008) found HbA1c reduced from 9.5% to 7.5% with 500mg 3x/day Berberine for 3 months — comparable to metformin in a parallel group. The landmark human trial establishing berberine’s clinical efficacy through AMPK activation.
Yin J, et al. Metabolism, 2008 →
Time-restricted eating improves insulin sensitivity without caloric restriction (2018)
Sutton et al. (2018) found that early time-restricted feeding significantly improved insulin sensitivity, blood pressure, and oxidative stress markers with no difference in caloric intake between conditions.
Sutton EF, et al. Cell Metabolism, 2018 →
Autophagy and Fasting
Fasting requires 14–16 hours minimum for meaningful autophagy induction (2018)
Bagherniya et al. (2018) concluded that significant autophagic activity requires a minimum of 14–16 hours of fasting in humans, with deeper autophagy flux occurring at 24+ hours.
Bagherniya M, et al. Ageing Research Reviews, 2018 →
Prolonged fasting triggers immune system regeneration (2014)
Cheng et al. (2014) demonstrated that 72-hour fasting triggered hematopoietic stem cell-based regeneration of immune cells and produced a more youthful immune cell population in healthy controls.
Cheng CW, et al. Cell Stem Cell, 2014 →
Cardiovascular Research
Omega-3 supplementation reduces cardiovascular events and coronary revascularization across 134,000+ participants (2024)
Dinu et al. (2024) meta-analyzed 18 RCTs involving 134,144 participants. Omega-3 supplementation reduced the risk of myocardial infarction (RR 0.89), cardiovascular death, and coronary revascularization (RR 0.90) — with the strongest effects seen in EPA-alone trials, independent of background statin therapy.
Dinu M, et al. European Journal of Preventive Cardiology, 2024 →
Omega-3 supplementation reduces major cardiovascular events (2021)
Bernasconi et al. (2021) meta-analyzed 40 RCTs (135,267 participants) and found omega-3 supplementation significantly reduced risk of myocardial infarction, coronary heart disease events, and cardiovascular death.
Bernasconi AA, et al. Mayo Clinic Proceedings, 2021 →
Insufficient evidence to recommend reducing unprocessed red meat (2019)
Johnston et al. (2019) reviewed 61 RCTs and 73 cohort studies and concluded that the evidence linking unprocessed red meat to cardiovascular disease was weak, low-certainty, and based largely on observational data with significant confounding.
Johnston BC, et al. Annals of Internal Medicine, 2019 →
Sugar industry funded research to shift blame from sugar to dietary fat (2016)
Kearns et al. (2016) documented that the Sugar Research Foundation funded Harvard researchers in the 1960s to minimize sugar’s role in cardiovascular disease while emphasizing dietary fat. The funding was not disclosed and shaped decades of dietary policy.
Kearns CE, et al. JAMA Internal Medicine, 2016 →
Higher fat intake associated with lower mortality across 18 countries (2017)
Dehghan et al. (2017) followed 135,335 individuals across 18 countries for 7.4 years and found that higher total fat and saturated fat intake were associated with lower risk of total mortality.
Dehghan M, et al. The Lancet, 2017 →
J-shaped relationship between sodium intake and cardiovascular risk (2014)
O’Donnell et al. (2014) analyzed data from 101,945 participants across 49 countries and found that both very low and very high sodium intake were associated with increased cardiovascular risk, with moderate intake (3–6g/day) associated with the lowest risk.
O’Donnell M, et al. New England Journal of Medicine, 2014 →
No significant association between saturated fat and cardiovascular disease (2010)
Siri-Tarino et al. (2010) analyzed 21 prospective studies (347,747 subjects) and found no significant independent association between saturated fat consumption and cardiovascular disease or stroke.
Siri-Tarino PW, et al. American Journal of Clinical Nutrition, 2010 →
Cognitive Performance and Neuroscience
Lion’s Mane shows acute cognitive benefits in healthy younger adults (2025)
Surendran et al. (2025) conducted a randomized, double-blind, placebo-controlled crossover study in 18 adults aged 18–35 using a single acute dose of 3g fruiting body extract of Hericium erinaceus. The study focused exclusively on immediate effects — a gap in the literature — and assessed cognitive performance and mood. Published in Frontiers in Nutrition (April 2025), it adds to accumulating evidence that Lion’s Mane’s hericenone compounds produce measurable short-term cognitive effects, not only chronic ones.
Surendran G, et al. Frontiers in Nutrition, 2025 →
Lion’s Mane improves cognitive speed and reduces stress in healthy young adults (2023)
Docherty et al. (2023) conducted a randomized, double-blind, placebo-controlled parallel-groups trial of 1.8g/day Hericium erinaceus in 41 healthy adults aged 18–45 for 28 days. A single acute dose produced significantly faster performance on the Stroop task (p=0.005) — the first RCT to demonstrate both acute and chronic cognitive effects of Lion’s Mane in healthy, non-impaired adults.
Docherty S, et al. Nutrients, 2023 →
Ashwagandha significantly reduces anxiety across 15 RCTs (2025)
Bachour et al. (2025) conducted a systematic review and meta-analysis of 15 RCTs (873 participants) searching PubMed, Web of Science, Scopus, and Cochrane through September 2024. Ashwagandha supplementation significantly reduced anxiety measured by the Hamilton Anxiety Rating Scale at both baseline and 8-week timepoints — published in BJPsych Open (Cambridge University Press, June 2025), the first comprehensive meta-analysis of ashwagandha’s effects on cortisol, stress, and anxiety jointly assessed across this breadth of trials.
Bachour G, et al. BJPsych Open, 2025 →
Ashwagandha reduces serum cortisol 27.9% and significantly improves cognitive performance (2012)
Chandrasekhar et al. (2012) found serum cortisol reduced 27.9% vs. placebo with 300mg KSM-66 twice daily. Choudhary et al. (2017) demonstrated the same dose produced significant improvements in memory, executive function, and processing speed.
Chandrasekhar K, et al. Indian Journal of Psychological Medicine, 2012 →
Lion’s Mane significantly improves cognitive function in mild cognitive impairment (2009)
Mori et al. (2009) conducted a double-blind placebo-controlled RCT of 3g/day Lion’s Mane for 16 weeks. Cognitive function scores improved significantly vs. placebo, and scores declined after cessation — confirming a treatment-dependent effect.
Mori K, et al. Phytotherapy Research, 2009 →
Cortisol directly impairs prefrontal cortex function (2009)
Arnsten (2009) documented the mechanism by which cortisol impairs prefrontal cortex function: surges rapidly reduce PFC neuronal firing while strengthening amygdala responses, shifting cognitive processing from rational to reactive circuits.
Arnsten AF. Nature Reviews Neuroscience, 2009 →
The glymphatic system clears brain waste 10x faster during sleep (2013)
Xie et al. (2013) demonstrated that the brain’s waste clearance system is approximately 10 times more active during sleep than during wakefulness, clearing metabolic waste products including amyloid-beta.
Aerobic exercise increases hippocampal volume and reverses age-related atrophy (2011)
Erickson et al. (2011) demonstrated that one year of aerobic exercise increased hippocampal volume by 2% in older adults — reversing approximately one to two years of age-related hippocampal atrophy.
Erickson KI, et al. PNAS, 2011 →
Six hours of sleep per night for two weeks equals two nights of total deprivation (2003)
Van Dongen et al. (2003) established that 6 hours of sleep nightly for 14 days produces cognitive impairment equivalent to two nights of total sleep deprivation — with subjects largely unaware of their own impairment.
Van Dongen HP, et al. Sleep, 2003 →
Sleep and Recovery
Magnesium bisglycinate significantly reduces insomnia severity in 155-person RCT (2025)
Schuster et al. (2025) conducted the largest placebo-controlled trial of magnesium bisglycinate for sleep to date — 155 adults aged 18–65 with self-reported poor sleep, randomized to 250mg elemental magnesium daily or placebo. The magnesium group showed significantly greater reduction in Insomnia Severity Index scores from baseline to Week 4 versus placebo (p=0.049), with the largest gains in participants with lower baseline dietary magnesium intake. Published in Nature and Science of Sleep (August 2025).
Schuster J, et al. Nature and Science of Sleep, 2025 →
Magnesium supplementation significantly improves sleep quality and mood (2024)
Breus et al. (2024) conducted a randomized, double-blind, placebo-controlled crossover trial of magnesium in adults with poor sleep. The magnesium group showed significant improvements over placebo in sleep duration, deep sleep, sleep efficiency, HRV readiness, and mood outcomes. No adverse events were reported and adherence was 100%.
Breus M, et al. Medical Research Archives, 2024 →
One week of sleep restriction reduces testosterone 10–15% in young men (2011)
Leproult & Van Cauter (2011) demonstrated that restricting sleep to 5 hours per night for one week reduced daytime testosterone levels by 10–15% in healthy young men.
Leproult R, Van Cauter E. JAMA, 2011 →
Active recovery outperforms passive rest for performance restoration (2018)
Dupuy et al. (2018) meta-analyzed 99 studies and found active recovery demonstrated the highest evidence base for reducing muscle soreness and recovering performance capacity.
Dupuy O, et al. Frontiers in Physiology, 2018 →
Protein and Muscle
Creatine + resistance training superior to training alone for muscle strength and mass in older adults (2025)
Zhou et al. (2025) conducted a systematic review and meta-analysis of 8 RCTs across eight major databases (search completed February 2025). Creatine monohydrate combined with resistance training demonstrated superior efficacy versus training plus placebo in enhancing lower-extremity muscle strength and lean tissue mass in older adults, with results remaining statistically significant under robust variance estimation (Hedges’ g = 0.327, p = 0.017). Published in European Review of Aging and Physical Activity (December 2025).
Zhou et al. European Review of Aging and Physical Activity, 2025 →
Whey protein supplementation improves appendicular muscle mass and lower-body strength in older adults (2024)
Al-Rawhani et al. (2024) conducted a systematic review and meta-analysis of 30 RCTs involving 2,105 participants aged 60+ through June 2024. Whey protein supplementation combined with resistance training produced significant improvements in appendicular skeletal muscle mass and lower-body strength — the most comprehensive pooled analysis to date on whey protein in older adults.
Al-Rawhani AH, et al. Clinical Nutrition, 2024 →
Protein supplementation significantly increases muscle mass and strength (2018)
Morton et al. (2018) meta-analyzed 49 studies and found dietary protein supplementation significantly augments gains in muscle mass and strength, with a threshold of approximately 1.62g/kg/day for maximizing hypertrophy.
Morton RW, et al. British Journal of Sports Medicine, 2018 →
Older adults require more protein per meal to maximally stimulate muscle protein synthesis (2015)
Moore et al. (2015) demonstrated that older adults require approximately 40g of protein per meal — compared to ~20g for younger adults — to maximally stimulate muscle protein synthesis due to age-related anabolic resistance.
Moore DR, et al. Journal of Physiology, 2015 →
This page reflects research cited across Nutri-Stasis protocols. Studies are selected for methodological quality, journal credibility, and mechanistic relevance. Links open the PubMed abstract or original source. Educational use only. Not medical advice.
