Study library

Abusidu M, et al. · Frontiers in Nutrition · 2026

In a mouse model, polysaccharides alleviated cisplatin-induced intestinal damage, improving the intestinal barrier and microbiota composition.

American Diabetes Association · Diabetes Care · 2026

Annually updated clinical guidelines emphasizing the importance of repeated measurements and clinical context when interpreting metabolic results.

Zhou Z, Wei X, Zhang X, Ainsworth BE, Lü J, Liu Y · Journal of Sport and Health Science · 2026

A network meta-analysis of 74 studies (5,331 participants) compared different exercise forms for their effect on bone mineral density in postmenopausal women. Combining multidirectional exercise with resistance training proved most effective for the lumbar spine, femoral neck, Ward's triangle, and whole skeleton, and interventions lasting 52 weeks or longer produced more consistent effects than shorter programs.

Lu X, et al. · Nature Aging · 2026

A paper identifying Bifidobacterium pseudocatenulatum and its metabolite 5-AVAB as factors linked to milder age-related inflammation (inflammaging) and improved cognitive and motor function in aging mice; it also describes the MicroAge microbiome-based biological age clock. Data come mainly from mouse models — direct human interventional trials have not yet been conducted.

Zhao J, Hu M, Li S, et al. · Nature Communications · 2026

A study on two NHANES cohorts (over 5,900 people total) building a machine-learning model that predicts chronological age from 64 genera of oral bacteria; the difference between predicted and actual age (the OMAA Score) was linked to mortality risk, frailty, and impaired kidney function.

Zhao J, Hu M, Li S, et al. · Nature Communications · 2026

The paper introducing the OMAA Score — based on two NHANES cohorts (n = 4,675) and an independent validation cohort (n ≈ 1,293), a model was built predicting age from 64 oral bacterial genera; the OMAA Score independently predicted overall mortality (HR = 1.05) and frailty (OR = 1.05), and improved prediction of cancer and heart attack risk.

McGuire F, Hughes E, Maak T, Cushman DM · Applied Sciences · 2026

A systematic scoping review searching PubMed, Europe PMC, and ClinicalTrials.gov through March 2026, identifying 80 eligible publications on thymosin beta-4 and TB-500. Evidence was predominantly preclinical (animal models and in vitro), concerned mainly full-length Tβ4 rather than the TB-500 fragment itself, and direct TB-500 evidence was limited to one identified study. Musculoskeletal tissue categories (tendon, ligament, muscle, cartilage) were sparsely represented relative to skin and corneal wounds.

Case report authors · Clinical journal (case report) · 2026

A case report of a patient using nasal spray Melanotan II before tanning-bed sessions, who developed oral mucosal melanoma. The authors hypothesize a possible link between exposure to the substance (including via the nasal route, not only injection) and oncological risk within mucous membranes, while noting that concurrent UV exposure from tanning beds is a significant confounding factor in this single case report.

Karaca B, et al. · Food Science & Nutrition · 2025

The extract showed activity against MRSA, limiting biofilm formation and bacterial quorum-sensing signaling. An in vitro study on bacterial cultures.

Erbiai E.H., et al. · International Journal of Molecular Sciences · 2025

Analysis of fruiting bodies showed a high content of phenolic compounds and a broad spectrum of antimicrobial activity.

Saldanha A, et al. · Separations · 2025

A comparative analysis of nutritional composition and phenolic profile, confirming the species' rich phenolic profile described in earlier work.

Aditya, Neeraj, Bhatia JN, Yadav AN · Heliyon · 2025

A review gathering available in vitro and animal studies — confirms the presence of antioxidant beta-glucans and phenols, with no clinical studies in humans.

Świderski G, Kalinowska M, Zapora E, et al. · International Journal of Molecular Sciences · 2025

An analysis of 30 European samples of Phellinus fungi showed in vitro antimicrobial and antioxidant activity.

George A, Jose R, Valsan C, et al. · Medical Mycology Case Reports · 2025

A case report of invasive fungal sinusitis caused by S. radiatum, confirmed by sequencing.

Muir CA, Zhang T, Jayadev V, Conway AJ, Handelsman DJ. · Clinical Endocrinology · 2025

A meta-analysis of 41 studies and 1,673 patients with hypogonadotropic hypogonadism treated with gonadotropins: after a median of 18 months, mean sperm concentration was 11.6 million/mL, and combining hCG with FSH significantly improved sperm count relative to hCG alone, with no significant difference in the effect on testosterone or testicular volume between groups.

Liu J i wsp. · Blood Advances · 2025

A systematic review of drug-induced erythrocytosis, including from testosterone, analyzing the quality of evidence behind the adopted intervention thresholds (including 50% and 54% hematocrit) and the effectiveness of available management approaches — the authors note the limited number of studies directly testing these thresholds in TRT patients and emphasize that current recommendations rely heavily on extrapolation from other causes of erythrocytosis.

Khashaba S, Khashaba S, Krishan A, Bruce A, Almaghlouth A, Huang J, Mima M, Niederberger C · Asian Journal of Urology · 2025

The most current meta-analysis (10 RCTs) on fertility: pregnancy rate was 10.4% on clomiphene versus 7.1% on placebo, odds ratio 1.30 (95% CI 0.27-6.17), p=0.74 — not statistically significant. The most reliable, current word on clomiphene's real effect on fertility outcomes.

Milanović Ž, et al. · Chemico-Biological Interactions · 2025

A paper analyzing the chemical mechanisms by which urolithin D neutralizes free radicals and repairs oxidative DNA damage — a theoretical and in vitro analysis, without data from living organisms.

Xu T, Niu Y, Deng C, Cheung Y, Li Y, Hu Z, Sun S, Chen Y, He F, Yang G, Chen F, Duan C, Huang Y, Deng X · iMetaOmics · 2025

The publication introducing the MicroAge model — a machine-learning model trained on 4,532 saliva samples from six continents that predicts biological age from the oral microbiome; performance (R² ≈ 0.80 in the healthy population) dropped to R² ≈ 0.16 in populations with disease.

Li TY, Gao AW, Yang R, et al. · Nature Cell Biology · 2025

A study in C. elegans describing the LySR mechanism — mild weakening of a component of the lysosomal proton pump extended lifespan by about 60% through activation of a transcriptional program strengthening lysosomal function and clearance of protein aggregates in models of neurodegenerative disease.

Kivimäki M, Frank P, Pentti J, et al. · The Lancet Digital Health · 2025

Independent validation of the organ-clock concept in the UK Whitehall II cohort with 20 years of follow-up, confirming the link between accelerated aging of individual organs and elevated risk of organ-specific diseases.

Mavrommatis C, Belsky DW, Ying K, Moqri M, Campbell A, Richmond A, Gladyshev VN, Chandra T, McCartney DL, Marioni RE. · Nature Communications · 2025

A large, independent comparison of 14 popular epigenetic clocks in a sample of 18,859 people as predictors of 174 diseases and all-cause mortality over 10 years of follow-up; second- and third-generation clocks consistently outperformed first-generation clocks.

Kong Y, Yu B, Guan G, Wang Y, He H · Frontiers in Physiology · 2025

A meta-analysis covering athletes and non-athletes found that sleep deprivation significantly impairs aerobic endurance, muscular function, speed, and technical control while raising subjectively perceived exertion (RPE).

Kim JW, Heo S, Lee D, Hong J, Yang D, Moon S · Healthcare · 2025

A polysomnographic study found that adaptive temperature regulation matched to sleep stages significantly increased the percentage of REM and deep sleep compared with constant ambient temperature.

Guldbrandsen BV, Baron K, Vedaa Ø, Bjorvatn B, Pallesen S · Frontiers in Sleep · 2025

The development and validation of the first orthosomnia measurement scale, identifying two factors: interference of sleep data with daily functioning, and rigidity of beliefs about 'correct' sleep.

American Diabetes Association Professional Practice Committee · Diabetes Care · 2025

The annual American Diabetes Association guidelines defining current diagnostic criteria for diabetes and prediabetes, including thresholds based on the oral glucose tolerance test.

Vargas-Uricoechea H, Castellanos-Pinedo A, Urrego-Noguera K, Pinzón-Fernández MV, Meza-Cabrera IA, Vargas-Sierra H · Medical Sciences · 2025

A scoping review summarizing prevalence data for Hashimoto's thyroiditis in adults across many world regions — found substantial geographic variation (from under 1% to over 20%) and a consistent female predominance.

Liu J et al. · Blood Advances · 2025

A systematic review of drug-induced erythrocytosis, including from testosterone, noting that accepted intervention thresholds (50% and 54% hematocrit) rely heavily on extrapolation from other causes of erythrocytosis and rarely account for measurement variability itself — which matters especially when interpreting single borderline results.

Aronne LJ, Horn DB, le Roux CW et al. (SURMOUNT-5 Investigators) · New England Journal of Medicine · 2025

The first published head-to-head trial comparing tirzepatide with semaglutide in adults with obesity without type 2 diabetes, randomized to the maximum tolerated dose of either drug for 72 weeks. Tirzepatide produced significantly greater weight loss (-20.2% vs. -13.7%; p<0.001) and waist-circumference reduction (-18.4 cm vs. -13.0 cm; p<0.001) than semaglutide in the same population.

Look M, Dunn JP, Kushner RF et al. · Diabetes, Obesity and Metabolism · 2025

DEXA body-composition analysis in a 160-person SURMOUNT-1 subgroup found that by week 72, body weight fell 21.3%, fat mass 33.9%, and lean body mass 10.9% with tirzepatide. Of the weight lost, about 74% was fat mass and 26% lean mass — a proportion similar to the placebo group and to earlier semaglutide data.

Ontawong A, Pengnet S, Thim-Uam A, et al. · Scientific Reports · 2024

An 8-week RCT: a fermented C. militaris beverage (2.85 mg cordycepin) increased NK cell activity and lowered pro-inflammatory markers (IL-1β, IL-6) in healthy adults.

Hao Y, Song W, Qu L · Food Science & Nutrition · 2024

A 4-week RCT on a multi-ingredient formula (Poria, Chinese hawthorn, GABA) showed improved sleep time, PSQI score, and skin hydration parameters — the effect cannot be attributed to Poria alone due to the preparation's complex composition.

Gitsomboon S, Ratanapornsompong G, Ongphiphadhanakul B, et al. · BMC Nutrition · 2024

A 12-week double-blind RCT in overweight people with prediabetes showed a small but statistically significant improvement in HbA1c and reduction in waist circumference after daily consumption of a Tremella beverage compared with placebo.

Rijia A., et al. · Pharmaceuticals (Basel) · 2024

Analysis of wild fruiting bodies showed a rich phytochemical composition, significant antioxidant activity, and antimicrobial action of the extract.

Bond P et al. · Endocrine Connections · 2024

A review critically examining the evidence behind testosterone-induced erythrocytosis and the rationale for phlebotomy as a standard intervention — the authors note that despite a real clotting risk tied to elevated hematocrit, evidence for the effectiveness and safety of routine blood removal is limited, and repeated phlebotomy can paradoxically worsen risk through tissue hypoxia and iron deficiency.

Loeb C, Miller JA, Schneider D et al. · International Journal of Impotence Research · 2024

A single-center survey of 140 men on TRT: 62.7% satisfied with their current treatment regimen, with significantly higher satisfaction among users of auto-injectors (91.7%) and subcutaneous implants (90.0%) than classic intramuscular injections (67.5%) — showing that even within injectable forms, the specific application method matters for perceived comfort.

Zitzmann M, Cremers JF, Krallmann C, Soave A, Kliesch S · Andrology · 2024

A nine-year real-world registry followed 650 patients across 4,362 treatment-years, all treated with intramuscular testosterone undecanoate 1000mg (the Nebido dose). Testosterone rose from 6.6±2.4 to 19.3±2.9 nmol/L (p<0.001). Hematocrit increases above 50% and PSA increases occurred at low but nonzero rates across the cohort over long-term follow-up.

Yang H, Wu B, Yang Q, Tan T, Shang D, Chen J, Cao C, Xu C · Journal of Natural Medicines · 2024

An in vitro and animal-model study showing that urolithin C inhibits proliferation and migration of colorectal cancer cells and arrests the cell cycle by blocking the AKT/mTOR pathway.

DeClercq V, Wright RJ, Nearing JT, Langille MGI · Scientific Reports · 2024

A cross-sectional study of 1,357 Canadian adults showing a link between oral microbiota diversity and composition (from saliva samples) and both chronological age and frailty index.

Wang H, Chen Y, Feng L, Lu S, Zhu J, Zhao J, Zhang H, Chen W, Lu W · Gut Microbes · 2024

A separate but conceptually related model (gAge) based on the gut microbiome, showing that a similar approach to 'microbiome clocks' recurs across different bacterial ecosystems in the body and correlates with health status and frailty risk.

Tariq MU, Rani A, Kayani N, Sattar AK, Vohra L, Idress R · Cureus · 2024

An analysis of the agreement between core-needle biopsy diagnoses and the final result after surgical excision in patients with fibroepithelial breast lesions.

Zhang Y et al. · Journal of Pharmaceutical and Biomedical Analysis (methodological study) · 2024

One of the few studies attempting to pharmacokinetically and biologically characterize a substance actually matching the name TB-500, using high-resolution mass spectrometry in vitro and in rats. Pro-healing activity was confirmed in cell assays, but the study did not involve humans and did not assess tendon or ligament healing.

Aronne LJ, Sattar N, Horn DB et al. · JAMA · 2024

Participants who achieved significant weight loss after 36 weeks of tirzepatide were randomized to continue the drug or switch to placebo for another 52 weeks. Those continuing tirzepatide achieved an additional 5.5 percentage points of weight loss, while the placebo group gained about 14% of weight relative to their weight at the start of the randomized withdrawal period — clearly showing the effect requires continued treatment.

Aledani EM, Kaur H, Kasapoglu M, Yadavalli R, Nawaz S, Althwanay A, Nath TS · Cureus · 2024

A systematic review of 11 articles (five RCTs, two systematic reviews, one narrative review, three case reports/series) comparing mesotherapy with 5% minoxidil. The two main comparative trials totaled just 95 patients combined. The authors cite the short follow-up duration (4-48 weeks), the diversity of substances used (from amino acids and vitamins to dutasteride and minoxidil), and an overall shortage of large, high-quality trials as the main limitations of the current evidence base.

Kazemian E, Pourali A, Sedaghat F, Karimi M, Basirat V, Sajadi Hezaveh Z, Davoodi SH, Holick MF · Nutrition Reviews · 2023

The meta-analysis found a beneficial effect of vitamin D3 supplementation on bone mineral density at the lumbar spine and femoral neck, with no significant effect on whole-body or total hip BMD; the effect depended on factors such as baseline 25(OH)D, age and bone health status.

Chen S.N., Nan F.H., Liu M.W., Yang M.F., Chang Y.C., Chen S. · Foods · 2023

An 84-day, double-blind RCT in healthy adults showed that beta-glucan from reishi increased T-cell counts, improved the CD4/CD8 ratio, raised NK-cell activity and IgA levels compared with placebo.

Ma KL, Kei N, Yang F, Lauw S, Chan PL, Chen L, Cheung PCK · Foods · 2023

An in vitro study using human fecal microbiota showed that Fu Ling polysaccharide increased acetic acid production and favored the growth of bacteria with anti-inflammatory activity — this is not an interventional study in living humans.

Kobayashi Y, et al. · DNA Research · 2023

Genome sequencing revealed features intermediate between mycorrhizal and saprotrophic fungi — a genomic study, not directly concerning health effects.

Wongkhieo S, et al. · Scientific Reports · 2023

A mycelial extract contained detectable lovastatin and inhibited HMG-CoA reductase activity in an in vitro liver spheroid model.

Tang SJ, Shao CX, Yang Y, Ren R, Jin L, Hu D, Wu SL, Lei P, He YL, Xu J · Journal of Ethnopharmacology · 2023

A peptide extract from the mycelium strongly inhibited HeLa cell proliferation in vitro and in a mouse xenograft model, inducing apoptosis.

Chaharmiri-Dokhaharani S, Ghobad-Nejhad M, Moghimi H, Norouzi H, Moghaddam M · Journal of Medicinal Plants and By-products · 2023

The only species-specific study found: chromatographic-spectrometric analysis identified phenolic compounds, with basic in vitro antibacterial tests.

Lincoff AM, Bhasin S, Flevaris P, et al. · New England Journal of Medicine · 2023

A large randomized trial (n>5000) assessing the cardiovascular safety of TRT in men with hypogonadism and risk factors — found no increased risk of major cardiovascular events.

Lincoff AM, Bhasin S, Flevaris P i wsp. (TRAVERSE Study Investigators) · New England Journal of Medicine · 2023

A randomized non-inferiority trial in over 5,200 men with hypogonadism and cardiovascular risk — TRT did not increase the risk of major cardiovascular events relative to placebo.

Agrawal P, Singh SM, Kohn T · European Urology Focus · 2023

A practical guide to assessing and monitoring hematocrit before and during testosterone therapy, with decision thresholds for dose reduction or discontinuation.

Lincoff AM et al. · New England Journal of Medicine · 2023

The large randomized TRAVERSE trial assessing the cardiovascular safety of TRT in men with hypogonadism and existing or elevated cardiovascular risk — testosterone proved non-inferior to placebo for major cardiovascular events (MACE), while the treated group showed more frequent pulmonary embolism, atrial fibrillation, and acute kidney injury.

Agrawal P, Singh SM, Kohn T · European Urology Focus · 2023

A practical guide covering the frequency of hematocrit checks during testosterone therapy and the decision thresholds for dose reduction, changing delivery form, or temporarily stopping treatment.

Lincoff AM, Bhasin S, Flevaris P et al. (TRAVERSE trial) · New England Journal of Medicine · 2023

A large randomized trial involving more than 5,200 men with hypogonadism and existing or high cardiovascular risk. Despite a slight HDL drop in the testosterone group, the rate of major cardiovascular events after an average of 22 months of follow-up didn't differ significantly from placebo — key context for interpreting TRT-related lipid changes.

Lincoff AM, Bhasin S, Flevaris P et al. (TRAVERSE Study Investigators) · New England Journal of Medicine · 2023

A large, placebo-controlled randomized trial (over 5,200 men, 45–80 years, with hypogonadism and existing or elevated cardiovascular risk), commissioned by the FDA specifically to settle the question of TRT's cardiovascular safety. Testosterone was non-inferior to placebo for major cardiovascular events (MACE: 7.0% vs. 7.3%), while showing higher rates of atrial fibrillation (3.5% vs. 2.4%), pulmonary embolism (0.9% vs. 0.5%), and acute kidney injury (2.3% vs. 1.5%) in the treated group.

Graziani A, Grande G, Ferlin A · Frontiers in Reproductive Health · 2023

A literature review on the complex, bidirectional relationship between OSA, hypogonadism, and TRT. The authors note that the evidence behind treating OSA as a TRT contraindication is qualitatively limited, and that short-term, high-dose testosterone therapy appears to worsen OSA more than chronic use of lower doses.

Adam JA, Pastuszak AW, Christensen MB, Spencer R, Sandberg A, Hotaling JM, Lipshultz LI · International Journal of Impotence Research · 2023

A review of 48 articles, including 29 studies covering 7,978 patients treated with testosterone undecanoate, identified a combined 88 POME or post-injection cough episodes across 8 of those studies. One postmarketing review recorded 223 cases out of 3,107,652 injections given. Almost all cases resolved spontaneously within 60 minutes without intervention — conclusion: POME is rare but real.

Tan JX, Finkel T · EMBO Reports · 2023

A review of the evidence for the role of lysosomal dysfunction in cellular aging and senescence, describing the accumulation of unprocessed metabolites and the decline in lysosomal digestive capacity with age.

Picca A, Faitg J, Auwerx J, et al. · Nature Metabolism · 2023

A comprehensive review of mitophagy mechanisms and their significance for health, aging, and age-related diseases, summarizing the current state of basic-science knowledge and clinical implications of impaired mitophagy.

Oh HSH, Rutledge J, Nachun D, et al. · Nature · 2023

A landmark study building 11 organ-aging clocks from plasma proteomics in more than 5,600 people across 5 cohorts; showed that accelerated aging of a specific organ increases the risk of diseases affecting that organ and overall mortality.

Oh HSH, Rutledge J, Nachun D, et al. · Nature · 2023

The study introducing 11 organ-aging clocks based on plasma proteomics as a separate, younger family of biological age clocks that complements epigenetic clocks.

Baddam S, Khan KM, Jialal I · StatPearls (NCBI Bookshelf) · 2023

A clinical review covering the causes, mechanism, and diagnostic workup of folate deficiency, including the need to differentiate it from vitamin B12 deficiency and folate's role in neural tube defect prevention.

Gradel KO · Journal of Clinical Medicine · 2023

A literature review covering 30 prognostic indices based on plasma albumin, analyzing to what extent individual publications link its level to inflammation versus nutritional status.

Moman RN, Gupta N, Singh C, Varacallo MA · StatPearls (NCBI Bookshelf) · 2023

A physiological review describing albumin synthesis, transport and oncotic functions, and the mechanisms leading to hypoalbuminemia in various disease states.

Gupta AK, Polla Ravi S, Wang T, Talukder M, Starace M, Piraccini BM · Journal of Dermatological Treatment · 2023

A systematic review of 27 publications (out of 416 identified records) on mesotherapy for hair loss. The authors identified six classes of substances used (dutasteride, minoxidil, growth factors/autologous suspensions, botulinum toxin, stem cells, vitamin-mineral blends). Some studies report statistically significant improvement in hair density, but the authors note a lack of protocol standardization and call for larger, controlled comparative trials against established therapies.

Fanouriakis A, Kostopoulou M, Andersen J, et al. (EULAR Task Force) · Annals of the Rheumatic Diseases · 2023

Updated EULAR guidelines recommend hydroxychloroquine for nearly all lupus patients at a target dose of about 5 mg/kg actual body weight per day, with a consistent push to keep glucocorticoid doses below 5 mg/day and to add immunosuppressive or biologic drugs for insufficient response.

Akhgarjand C, Asoudeh F, Bagheri A, Kalantar Z, Vahabi Z, Shab-Bidar S, Rezvani H, Djafarian K · Phytotherapy Research · 2022

A meta-analysis of 12 RCTs (1,002 participants) found a significant reduction in anxiety and stress versus placebo; the certainty of evidence was rated low and results were highly heterogeneous.

Hu Q, Xie B · Acta Biochimica Polonica · 2022

A randomized trial in 141 patients with advanced laryngeal/pharyngeal cancer showed that maitake D-fraction given during chemoradiotherapy eased the severity of treatment side effects and improved quality of life.

Ku YH, Kang JH, Lee H · Medicine (Baltimore) · 2022

A randomized, double-blind trial with 98 participants showed a significant increase in NK cell activity after 8 weeks of supplementation with 1000 mg of extract daily versus placebo (p = 0.008).

Ku YH, Kang JH · Medicine (Baltimore) · 2022

A pilot trial (n = 30) observed a trend toward improved NK cell activity versus placebo at a dose of 1000 mg/day after 8 weeks.

Yen Y.-T. et al. · Frontiers in Pharmacology · 2022

A multicenter RCT (80 people) in adults with elevated GGT — 300 mg/day of extract for 12 weeks significantly lowered AST, ALT, and triglycerides versus placebo.

Bożek J, et al. · International Journal of Molecular Sciences · 2022

The extract dose-dependently limited melanoma cell proliferation and viability in vitro, with relatively low cytotoxicity toward normal fibroblasts.

Liao C, et al. · Molecules · 2022

The isolated polysaccharide showed strong antioxidant activity in chemical tests and protected human HepG2 liver cells from oxidative stress in vitro.

Kała K, et al. · Molecules · 2022

Analysis of the fruiting bodies found tryptophan, ergothioneine, lovastatin, and beta-glucans with potential antioxidant activity.

Zhou J, Gong J, Chai Y, Li D, Zhou C, Sun C, Regenstein JM · Glycoconjugate Journal · 2022

Isolated polysaccharide fractions showed the ability to disrupt the cell cycle and induce apoptosis in the HeLa cell line in in vitro tests.

Muñoz-Castiblanco T, et al. · International Journal of Molecular Sciences · 2022

The polysaccharide fraction showed high antioxidant activity and reduced the viability of osteosarcoma cells in vitro.

Kim M, et al. · Frontiers in Aging Neuroscience · 2022

A safety study showing good tolerance of doses up to 500 mg/day over 12 weeks in healthy adults.

Mohammadipoor N, Shafiee F, Rostami A, Kahrizi MS, Soleimanpour H, Ghodsi M, Ansari MJ, Bokov DO, Jannat B, Mosharkesh E, Pour Abbasi MS · Phytotherapy Research · 2022

A meta-analysis of 17 RCTs: resveratrol supplementation improved flow-mediated dilation (FMD, by 1.43 percentage points on average) and lowered ICAM-1, with no significant changes in VCAM-1, fibrinogen or PAI-1.

Ory J et al. · Journal of Urology · 2022

An analysis of a large, multicenter database of TRT patients comparing the risk of major cardiovascular events and venous thromboembolism between men who developed secondary polycythemia (hematocrit ≥52%) and those with normal hematocrit — risk was higher in the polycythemia group during the first year of therapy.

Hudson J, Cruickshank M, Quinton R et al. · The Lancet Healthy Longevity · 2022

An individual patient data meta-analysis of more than 3,000 participants from randomized trials, showing a moderate drop in total cholesterol, HDL, and triglycerides in testosterone-treated groups, without demonstrating increased cardiovascular event risk in short- and medium-term follow-up.

Choi EJ, Xu P, Barham D, El-Khatib FM, Yafi FA, Kavoussi PK · The Journal of Urology · 2022

A retrospective comparison of 234 hypogonadal men treated with intramuscular cypionate or subcutaneous testosterone enanthate. The subcutaneous-injection group had a lower rise in estradiol and hematocrit — a difference attributed to route of administration and the peak-trough profile rather than the ester molecule itself, since the comparison varied both the ester and the route simultaneously.

Choi EJ, Xu P, Barham D, El-Khatib FM, Yafi FA, Kavoussi PK · The Journal of Urology · 2022

234 hypogonadal men, IM cypionate 100mg/week vs. SC enanthate 100mg/week, 12 weeks. Trough T rose from 313.6 to 536.4 ng/dL (IM cypionate) and 246.6 to 552.8 ng/dL (SC enanthate), both p<0.001, no significant difference between modalities (p=0.057). SC route was associated with lower estradiol and hematocrit (both p<0.001); neither modality significantly raised PSA. Important caveat: the comparison changed both ester and route of administration simultaneously.

Locquet M, Sanchez-Rodriguez D, Bruyère O, Geerinck A, Lengelé L, Reginster JY. · The Journal of Nutrition, Health & Aging · 2022

A post-hoc analysis of a Belgian prospective cohort (n=534) followed for 5 years, showing that a 1 standard deviation increase in intrinsic capacity was linked to roughly a 49% lower mortality risk, with the locomotion and psychological well-being domains independently associated with lower mortality.

Mijakovac A, Frkatović A, Hanić M, et al. · Frontiers in Cell and Developmental Biology · 2022

An analysis estimating the average heritability of the glycan clock at about 39%, suggesting a substantial role for environmental factors in shaping the result.

Dório M, Benseñor IM, Lotufo P, Santos IS, Fuller R · Advances in Rheumatology · 2022

A cross-sectional analysis of more than 15,000 participants of the ELSA-Brasil cohort, establishing current reference ranges for uric acid and the prevalence of hyperuricemia by sex.

Reyes-Soffer G, Ginsberg HN, Berglund L, et al. · Arteriosclerosis, Thrombosis, and Vascular Biology · 2022

An official American Heart Association statement summarizing the evidence for Lp(a)'s causal role in atherosclerotic cardiovascular disease and its strong genetic basis.

Kronenberg F, Mora S, Stroes ESG, et al. · European Heart Journal · 2022

A European Atherosclerosis Society consensus on Lp(a)'s role in cardiovascular disease and aortic stenosis, with guidance on testing and management of elevated results.

Smith TP, Kelly S, Fahie-Wilson MN · Clinical Chemistry and Laboratory Medicine · 2022

An analysis of cross-reactivity of various prolactin assays with macroprolactin, and recommendations for an optimal macroprolactinemia screening policy.

Averina M, Stylidis M, Brox J, Schirmer H · ESC Heart Failure · 2022

Population-based study (Tromsø 7 Study) assessing age- and sex-specific reference values for NT-proBNP and troponin T and the usefulness of both markers as screening tools for detecting subclinical heart failure.

Cui Z, Zhao G, Liu X · Medicine (Baltimore) · 2022

A systematic review with meta-analysis of 13 studies covering over 20,000 patients with coronary artery disease, showing significantly higher risk of cardiovascular death and major adverse cardiovascular events with elevated fibrinogen.

Craven J, McCartney D, Desbrow B, Sabapathy S, Bellinger P, Roberts L, Irwin C · Sports Medicine · 2022

A systematic review and meta-analysis showing that acute sleep deficit significantly worsens athletic performance, with the magnitude of impact depending on the type of exercise and the time of day testing occurs.

Jastreboff AM, Aronne LJ, Ahmad NN et al. (SURMOUNT-1 Investigators) · New England Journal of Medicine · 2022

A randomized, double-blind phase 3 trial in 2,539 adults with obesity or overweight (without type 2 diabetes) who received tirzepatide 5, 10, or 15 mg weekly or placebo for 72 weeks. Mean weight reduction was 16.0% (5 mg), 21.4% (10 mg), and 22.5% (15 mg) versus 2.4% with placebo. At the highest dose, 63% of participants achieved at least 20% weight loss, versus 1.3% on placebo.

Shen YC, Chiu WK, Kang YN, Chen C · Aesthetic Plastic Surgery · 2022

A meta-analysis of 12 randomized controlled trials (414 participants) evaluating microneedling as a standalone treatment for acne scarring. Microneedling without radiofrequency produced a statistically significant improvement in objectively assessed scar severity (mean difference 0.42; 95% CI 0.12–0.73) versus control groups, with no cases of secondary scarring or infection in any of the included studies.

Zhan L et al. · Dental review / meta-analysis · 2022

A meta-analysis indicating that the most effective regimen is chewing or consuming xylitol 3–5 times per day after meals, at a total daily dose of 5–10 g — the authors stress that dosage and frequency should be considered when recommending xylitol as a preventive measure.

Goodwin GM, Aaronson ST, Alvarez O, et al. · New England Journal of Medicine · 2022

A randomized, double-blind phase 2b trial (COMPASS Pathways) in 233 patients with treatment-resistant depression, comparing a single 25 mg, 10 mg, or 1 mg (control) dose of synthetic psilocybin with psychological support. In the 25 mg group, 29.1% of participants achieved remission at week 3, versus a significantly lower rate in the 1 mg group. The trial also recorded adverse events, including worsening suicidal ideation in some high-dose participants, and highlighted limitations from functional unblinding.

Mah J, Pitre T · BMC Complementary Medicine and Therapies · 2021

A meta-analysis of 3 RCTs (151 older adults with insomnia): magnesium shortened sleep onset time by about 17 minutes versus placebo, while the gain in total sleep time (about 16 minutes) was not statistically significant; the quality of evidence was low to very low.

Spim SRV, Pistila AMH, Pickler TB, Silva MT, Grotto D · International Journal of Medicinal Mushrooms · 2021

A randomized, double-blind trial in 68 people with borderline elevated cholesterol showed that shiitake bars used for 66 days lowered triglycerides and improved oxidative stress markers versus placebo.

Yang M, Zhang Z, He Y, Li C, Wang J, Ma X · Food Science and Human Wellness · 2021

A laboratory study on an isolated, purified fraction of Tremella polysaccharide showed stronger moisture-loss-limiting properties than glycerin — concerning the isolated compound tested on a skin model, not a finished supplement.

Jia W, Luo S, Lai G, Li S, Huo S, Li M, Zeng X · BMC Complementary Medicine and Therapies · 2021

An in vitro study on human cell lines showed that a homogeneous Polyporus polysaccharide reprogrammed macrophages toward an M1 phenotype, inhibiting the proliferation and migration of bladder cancer cells.

Kuo PC, et al. · Bioorganic Chemistry · 2021

34 lanostane triterpenes were isolated, and their anti-inflammatory activity assessed in a human neutrophil model — a purely laboratory study.

İrez E.İ., Hacıoğlu Doğru N., Demir N. · Biologica Nyssana · 2021

Extracts showed higher antioxidant activity than the standard BHT along with significant antimicrobial and antibiofilm activity.

Lin H, et al. · Antioxidants (Basel) · 2021

Polysaccharides inhibited the formation of advanced glycation end products in an albumin glycation model and protected cells from damage induced by methylglyoxal.

Govindan S, Jayabal A, Shanmugam J, Ramani P · Food Science and Human Wellness · 2021

In a rat model, the HUP polysaccharide reduced oxidative stress and alcohol-induced liver damage.

Pawlik A, Ciołek B, Sulej J, et al. · Biomolecules · 2021

An experimental paper on the regulation of laccase gene expression under the influence of metal ions and temperature — a purely biotechnological study.

Yoshino M, et al. · Science · 2021

A randomized trial (n=25) in women with prediabetes showing improved muscle insulin sensitivity after 10 weeks of supplementation — no significant effect on body weight or other markers.

Salminen S, Collado MC, Endo A, et al. · Nature Reviews Gastroenterology & Hepatology · 2021

The official ISAPP consensus statement formally defining the term 'postbiotic' and organizing terminology in this area.

Shah R, Patil V, Sarathi V, et al. · Pituitary · 2021

hCG therapy (up to 2000 IU 3x/week or 5000 IU 2x/week) combined with hMG, titrated to testosterone ≥3.5 ng/mL, achieved spermatogenesis in 70% of patients, but those with prior exposure to testosterone alone reached significantly lower peak sperm counts (median 0.05 vs 9 million/mL; p=0.004) than gonadotropin-treatment-naive patients.

Fiesel FC, et al. · Autophagy · 2021

Development of a sensitive ELISA assay detecting phospho-ubiquitin (p-S65-Ub) — a marker of PINK1/Parkin pathway activity — in human cells, brain tissue, and blood plasma, able to distinguish PINK1 mutation carriers from healthy individuals; an early-stage research tool, not a standard clinical test.

Greto VL, Cvetko A, Štambuk T, et al. · International Journal of Obesity · 2021

An intervention study (low-calorie diet and bariatric surgery) showing that substantial weight loss is linked to a reduction in the calculated glycan age over a year-long follow-up.

Covarrubias AJ, Perrone R, Grozio A, Imai SI. · Nature Reviews Molecular Cell Biology · 2021

A comprehensive review systematizing knowledge of NAD+ metabolism, including the salvage pathway, the roles of NAMPT and CD38, and links between declining NAD+ and age-related disease.

Palmer BF, Carrero JJ, Clegg DJ, et al. · Mayo Clinic Proceedings · 2021

A clinical review of monitoring and management of hyperkalemia, with particular focus on patients with chronic kidney disease, diabetes, and heart failure.

Edinger JD, Arnedt JT, Bertisch SM, Carney CE, Harrington JJ, Lichstein KL, Sateia MJ, et al. · Journal of Clinical Sleep Medicine · 2021

Official AASM clinical guidelines based on a systematic review and GRADE assessment, strongly recommending multi-component CBT-I as first-line treatment for chronic insomnia in adults.

Sabia S, Fayosse A, Dumurgier J, van Hees VT, Paquet C, Sommerlad A, Kivimäki M, Dugravot A, Singh-Manoux A · Nature Communications · 2021

The Whitehall II cohort study (7,959 participants, 25 years of follow-up, 521 dementia cases) found that short sleep (≤6h) at ages 50 and 60 was associated with a 22% and 37% higher dementia risk, respectively, and persistent short sleep across three measurements with a 30% higher risk, independent of other risk factors.

Almond SM, Warren MJ, Shealy KM, Threatt TB, Ward ED · Senior Care Pharmacist · 2021

A systematic review in older adults found that melatonin had the strongest evidence of a statistically significant improvement in sleep parameters without significant safety concerns, valerian showed no significant effect, and diphenhydramine improved sedation but without a clear safety advantage over other options.

Laine L, Barkun AN, Saltzman JR, Martel M, Leontiadis GI · American Journal of Gastroenterology · 2021

American College of Gastroenterology guidelines on the role of urgent gastroscopy and endoscopic hemostasis methods in diagnosing and treating upper gastrointestinal bleeding.

Berzigotti A, Tsochatzis E, Boursier J, Castera L, Cazzagon N, Friedrich-Rust M, Petta S, Thiele M · Journal of Hepatology · 2021

An update to the European Association for the Study of the Liver guidelines on the use of non-invasive tests, including transient elastography, in assessing the severity and prognosis of liver diseases.

Al-Naseem A, Sallam A, Choudhury S, Thachil J · Clinical Medicine (London) · 2021

A review showing that iron deficiency without anemia is at least twice as common as overt iron-deficiency anemia, yet remains poorly recognized clinically.

Mallory JP, Lopategui DM, Cordon BH · Sexual Medicine · 2021

A case report of a patient with acute ischemic priapism after subcutaneous Melanotan II injection, unresponsive to conservative management (cavernosal aspiration and irrigation, phenylephrine injection), who ultimately required surgical penoscrotal decompression.

Vañó-Galván S, Pirmez R, Hermosa-Gelbard A et al. · Journal of the American Academy of Dermatology · 2021

A retrospective, multicenter study of 1404 patients (67% women, mean age 43) treated with low-dose oral minoxidil for at least 3 months for various types of hair loss. The most common side effect was hypertrichosis (15.1%, a reason for discontinuation in 0.5% of patients). Systemic adverse effects were reported in 5.5% of patients (dizziness, fluid retention/swelling, tachycardia, headaches), with no life-threatening events observed.

Boehme M, Guzzetta KE, Bastiaanssen TFS, van de Wouw M, Moloney GM, Gual-Grau A, et al. · Nature Aging · 2021

Transplanting microbiota from young mice into old, normally aging animals (not progeroid) didn't significantly extend their lifespan, but reversed some age-related differences in immunity and the hippocampus and eased selected, not all, cognitive deficits — a more limited result than in the progeroid model, but an important test of the hypothesis in normally aging animals.

Afrin LB, Ackerley MB, Bluestein LS, Brewer JH, Brook JB, Buchanan AD, Cuni JR, Davey WP, Dempsey TT, Dorff SR, Dubravec MS, Guggenheim AG, Hindman KJ, Hoffman B, Kaufman DL, Kratzer SJ, Lee TM, Marantz MS, Maxwell AJ, McCann KK, McKee DL, Menk Otto L, Pace LA, Perkins DD, Radovsky L, Raleigh MS, Rapaport SA, Reinhold EJ, Renneker ML, Robinson WA, Roland AM, Rosenbloom ES, Rowe PC, Ruhoy IS, Saperstein DS, Schlosser DA, Schofield JR, Settle JE, Weinstock LB, Wengenroth M, Westaway M, Xi SC, Molderings GJ · Diagnosis (Berlin) · 2021

A competing, substantially broadened proposal of diagnostic criteria (the "consensus-2"), allowing a wider range of mediators and lower thresholds for their rise than the 2012 Vienna consensus. The authors acknowledge their criteria may lead to overdiagnosis but argue that underdiagnosis under the stricter criteria is the larger problem — the dispute between these two approaches remains unresolved.

Barber MRW, Drenkard C, Falasinnu T, Hoi A, Mak A, Kow NY, Svenungsson E, Peterson J, Clarke AE, Ramsey-Goldman R · Nature Reviews Rheumatology · 2021

A comprehensive review of global lupus epidemiology from the preceding five years of research: confirms a clear predominance of cases among women of reproductive age and significantly higher incidence, with typically more severe disease, among Black populations compared with white populations.

Carhart-Harris R, Giribaldi B, Watts R, et al. · New England Journal of Medicine · 2021

A phase 2 randomized trial in 59 patients with long-standing, moderate-to-severe depression, comparing two 25 mg doses of psilocybin with six weeks of escitalopram treatment. On the primary outcome (QIDS-SR-16), the between-group difference was not statistically significant (p=0.17), though secondary measures (remission: 57% for psilocybin vs 28% for escitalopram) favored psilocybin — without correction for multiple comparisons, which limits the strength of this conclusion.

Davis AK, Barrett FS, May DG, et al. · JAMA Psychiatry · 2021

A Johns Hopkins University pilot trial in 24 participants, randomized to immediate treatment with two psilocybin sessions (20 mg and 30 mg) or an 8-week waitlist. 71% of participants showed a clinically significant response at weeks 1 and 4. The authors themselves described the trial as proof-of-concept due to the small sample, lack of placebo control, and short, one-month follow-up.

Bian C, Wang Z, Shi J · Molecules · 2020

Optimized extraction of the polysaccharides prolonged blood clotting time along both the intrinsic and extrinsic pathways.

Huang Y, et al. · Food Research International · 2020

A new triterpene, Resinacein S, reduced lipid droplet size and enhanced thermogenesis markers in adipocyte cultures.

Yang K, et al. · ACS Omega · 2020

The phenolic fraction inhibited alpha-glucosidase activity and improved glucose uptake by insulin-resistant liver cells in vitro.

Harada E, Morizono T, Kanno T, Saito M, Kawagishi H · International Journal of Medicinal Mushrooms · 2020

In mouse models of obesity and diabetes, the extract lowered blood glucose and triglycerides. In a very small clinical pilot (10 people, 4 weeks), a significant drop in triglycerides was recorded.

Lowe DA, et al. · JAMA Internal Medicine · 2020

An RCT comparing time-restricted eating (16:8) to three standard meals a day — similar weight loss in both groups after 12 weeks.

Frederiksen H i wsp. · Journal of Clinical Endocrinology & Metabolism · 2020

A large reference study establishing estrogen concentration ranges by LC-MS/MS across age and sex. In men aged 30–60, estradiol fell in a range of roughly 50–150 pmol/L (~14–41 pg/mL) and remained stable with age, unlike testosterone's clear age-related decline.

Pastuszak AW, Hu Y, Freid JD · Sexual Medicine · 2020

A postmarketing analysis explaining the rationale for the mandatory REMS program on the US product, introduced because of the POME and anaphylaxis risk. Over the March 2014–June 2018 surveillance period (4.3 years): 90,092 doses distributed, 633 safety reports reviewed, 28 confirmed POME cases — a yearly reporting rate under 0.1% per injection. 13 of 17 detailed cases resolved within 30 minutes or less, and over 60% needed no medical intervention. One death was reported 18 months after a POME event but judged unrelated on review; in 3 of 4 cases requiring emergency-room-level care, injection technique or dosing errors were implicated.

Ibba A, Corrias F, Guzzetti C, Casula L, Salerno M, di Iorgi N, Tornese G, et al. · Endocrine Connections · 2020

An ROC analysis assessing the accuracy of a single IGF-1 measurement in diagnosing growth hormone deficiency in children and adolescents, showing limited standalone sensitivity and specificity for this test.

Kanal E, Greenberg TD, Hoff MN, et al. (ACR Committee on MR Safety) · Journal of Magnetic Resonance Imaging · 2020

Updated American College of Radiology guidance on safe MRI practice, including the rules for screening patients with implants and implanted electronic devices.

Fontham ETH, Wolf AMD, Church TR, et al. · CA: A Cancer Journal for Clinicians · 2020

An update to American Cancer Society guidelines on cervical cancer screening, including the growing role of standalone HPV testing as the preferred screening method.

Dehlin M, Jacobsson L, Roddy E · Nature Reviews Rheumatology · 2020

A review of global epidemiological data found gout prevalence ranging from under 1% to 6.8% of the population, with incidence of 0.1-0.3% per year, a male-to-female ratio of roughly 3-4:1, and a clear rise in risk with age.

FitzGerald JD, Dalbeth N, Mikuls T, Brignardello-Petersen R, Guyatt G, Abeles AM, et al. · Arthritis Care & Research · 2020

Current American College of Rheumatology guidelines recommend a treat-to-target strategy for urate-lowering therapy, with allopurinol as first-line treatment and a target uric acid level below 6 mg/dl (lower in patients with tophi).

Ramos PM, Sinclair RD, Kasprzak M, Miot HA · Journal of the American Academy of Dermatology · 2020

A randomized trial comparing oral minoxidil 1 mg/day with topical 5% solution in women with female pattern hair loss. Both forms proved comparably effective in hair density after the treatment period, though hypertrichosis (unwanted facial and body hair growth) was significantly more common in the oral group.

Lyon P, Strippoli V, Fang B, Cimmino L · Nutrients · 2020

A review describing one-carbon metabolism as a network of linked pathways dependent on B vitamins — folate, B12, B6, and riboflavin — supplying methyl groups for DNA synthesis, amino acid balance, antioxidant production, and epigenetic regulation, along with the health consequences of its disruption.

Fokkens WJ, Lund VJ, Hopkins C, et al. · Rhinology · 2020

Current European guidelines on the definition, classification, and treatment of acute and chronic sinusitis, including the distinction between the polyp and non-polyp forms and recommendations on saline nasal irrigation, intranasal steroids, and indications for biologic and surgical treatment.

Choi FD, et al. · Journal of Drugs in Dermatology · 2019

A review of 11 studies suggesting improved skin elasticity and hydration, with the caveat of inconsistent methodology and partial manufacturer funding.

García-Coronado JM, et al. · International Orthopaedics · 2019

A meta-analysis pointing to a moderate improvement in joint pain symptoms in osteoarthritis after collagen supplementation.

Guo Z, Zang Y, Zhang L · Progress in Molecular Biology and Translational Science · 2019

A systematic review of more than 11,700 Chinese clinical cases suggested the efficacy of PPS in treating hepatitis B, mainly in combination with a vaccine or antiviral drugs.

Zhang M, Xie Y, Su X, Liu K, Zhang Y, Pang W, Wang J · Frontiers in Immunology · 2019

A cell study showed that a polyphenol-rich extract inhibited secretion of NO, TNF-α, IL-6, and MCP-1 by blocking the ERK, p38 MAPK, and STAT3 pathways.

Su X, Liu K, Xie Y, Zhang M, Wang Y, Zhao M, Guo Y, Zhang Y, Wang J · Life Sciences · 2019

In mice, supplementation with the extract inhibited inflammation and lung swelling induced by bleomycin, given for 3 weeks before the injury was induced.

Zhang Y, Jiang Y, Zhang M, Zhang L · Progress in Molecular Biology and Translational Science · 2019

A review chapter summarizing the anticancer, antioxidant and immunomodulatory action of GSP as an adjunctive therapy.

de Cabo R, Mattson MP. · New England Journal of Medicine · 2019

A review of the metabolic mechanisms of intermittent fasting — strong preclinical data, moderate and still developing clinical data in humans.

Arnett DK, Blumenthal RS, Albert MA, et al. · Journal of the American College of Cardiology · 2019

Clinical guidelines summarizing the evidence for LDL's causal role in the development of atherosclerotic cardiovascular disease and the principles of primary prevention.

Camaschella C · Blood · 2019

A review of the diagnosis and treatment of iron deficiency, including the role and limitations of ferritin as a marker of iron stores in the context of coexisting inflammation.

Duru KC, Kovaleva EG, Danilova IG, van der Bijl P · Chemico-Biological Interactions · 2019

A review of laboratory and animal studies on the pharmacological properties of Inonotus obliquus, including its exceptionally high antioxidant activity.

McGlade E, Locatelli A, Hardy J, et al. · Journal of Attention Disorders · 2019

A placebo-controlled trial showing improved psychomotor speed and attention measures after citicoline supplementation in healthy young men.

Ramachandran S, Hackett GI, Strange RC · Sexual Medicine Reviews · 2019

A review discussing how age and type 2 diabetes modify the relationship between SHBG and testosterone, and what prognostic significance SHBG level itself has independent of the total testosterone result.

Russell N, Grossmann M · European Journal of Endocrinology · 2019

A review of evidence that some effects traditionally attributed to testosterone in men actually depend on its aromatization to estradiol, and that estrogen circulates in men at genuinely physiological, not trace, concentrations.

Cignarelli A et al. · Frontiers in Endocrinology · 2019

A meta-analysis of 12 studies (10 cohort, 2 randomized) assessing CPAP therapy's effect on testosterone levels in men with OSA. Found no statistically significant change in total testosterone after CPAP treatment, indicating that treating apnea alone doesn't normalize hormone levels in every patient.

Cunningham GR, Ellenberg SS, Bhasin S i wsp. · Journal of Clinical Endocrinology & Metabolism · 2019

Analysis of data from a controlled trial (a Testosterone Trials substudy) showing a real, but for most men modest, scale of PSA rise on TRT: an average increase of 0.47 ng/mL after 12 months versus 0.06 ng/mL in the placebo group, with 5% of men reaching a rise of ≥1.7 ng/mL and 1.9% reaching a confirmed PSA >4.0 ng/mL (versus 0.3% on placebo). The authors note that despite the statistically significant difference, the proportion of men requiring biopsy remained small.

Hills RD Jr, Pontefract BA, Mishcon HR, Black CA, Sutton SC, Theberge CR · Nutrients · 2019

An extensive review discussing how diet and environmental factors shape the gut microbiome and its links to obesity, diabetes, irritable bowel syndrome, inflammatory bowel disease, depression, cardiovascular disease, and colorectal cancer.

Wheeler KM, Sharma D, Kavoussi PK, Smith RP, Costabile R · Sexual Medicine Reviews · 2019

A literature review noting headache, dizziness, gynecomastia and possible worsening of psychiatric illness as reported adverse effects; overall conclusion: 'generally safe and well tolerated.' Classic warnings about visual disturbance stem mainly from a different dosing context in women.

Kanakis GA, Nordkap L, Bang AK, et al. · Andrology · 2019

European Academy of Andrology clinical guidelines explicitly advise against using SERMs, aromatase inhibitors, and non-aromatizable androgens to treat gynecomastia in men (recommendation R14). Specific to the gynecomastia context, not general estradiol management on TRT, but reflects the same broader expert skepticism about routine use of this drug class in men.

Bayle M, Neasta J, Dall'Asta M, Gautheron G, Virsolvy A, Quignard JF, Youl E, Magous R, Guichou JF, Crozier A, Del Rio D, Cros G, Oiry C · British Journal of Pharmacology · 2019

A study on isolated pancreatic beta cells and islets showing that urolithin C enhances glucose-dependent insulin secretion by activating L-type calcium channels — a mechanism studied as a potentially safer alternative to classic insulin secretagogues.

Hipp MS, Kasturi P, Hartl FU · Nature Reviews Molecular Cell Biology · 2019

An extensive review describing the structure of the proteostasis network (chaperones, the proteasome, autophagy) and the mechanisms of its gradual weakening with age, linked to neurodegenerative diseases.

de Guia RM, Agerholm M, Nielsen TS, et al. · Physiological Reports · 2019

A human clinical study showing that aerobic and resistance training increases NAMPT content in skeletal muscle, reversing part of the age-related decline in NAD+ recovery capacity.

Benjafield AV, Ayas NT, Eastwood PR, Heinzer R, Ip MSM, Morrell MJ, Nunez CM, Patel SR, Penzel T, Pepin JL, Peppard PE, Sinha S, Tufik S, Valentine K, Malhotra A · The Lancet Respiratory Medicine · 2019

A literature-based analysis combining epidemiological data from more than a dozen countries with population modeling, estimating the global burden of obstructive sleep apnea at nearly a billion adults aged 30-69.

Roach GD, Sargent C · Frontiers in Physiology · 2019

A review discussing the directional asymmetry of jet lag and giving practical examples of using well-timed light exposure (and avoidance) and melatonin to speed up biological clock resynchronization after cross-time-zone flights in both directions.

Culnan E, McCullough LM, Wyatt JK · Neurologic Clinics · 2019

A review of circadian rhythm phase disorders, including delayed sleep phase syndrome, covering diagnostic criteria, mechanisms, and treatment options (light therapy, chronotherapy, melatonin).

Besedovsky L, Lange T, Haack M · Physiological Reviews · 2019

A comprehensive review of the bidirectional relationship between sleep and immunity, describing the mechanisms of nighttime T-cell redistribution, the role of pro-inflammatory cytokines in sleep architecture, and the effect of sleep deprivation on vaccine response and infection susceptibility.

Zullo A, Manta R, De Francesco V, Fiorini G, Hassan C, Vaira D · Digestive and Liver Disease · 2019

A systematic review showing that gastroscopy's diagnostic yield is significantly higher when the test is ordered according to appropriate clinical indications, particularly for bleeding and dysphagia.

Graham BL, Steenbruggen I, Miller MR, Barjaktarevic IZ, Cooper BG, Hall GL, Hallstrand TS, et al. · American Journal of Respiratory and Critical Care Medicine · 2019

The official ATS/ERS technical statement standardizing the performance and interpretation of spirometry, defining acceptability and repeatability criteria for breathing maneuvers.

Rundo JV, Downey R 3rd · Handbook of Clinical Neurology · 2019

A review of polysomnography methodology — the recorded signals (EEG, EOG, EMG, ECG, airflow, pulse oximetry) and its role as the gold standard for diagnosing sleep-related breathing disorders.

Al-Hijji MA, Lennon RJ, Gulati R, El Sabbagh A, Park JY, Crusan D, Frick M, et al. · Circulation: Cardiovascular Interventions · 2019

An analysis of a large cohort of patients undergoing diagnostic catheter cardiac angiography, assessing the frequency and risk factors of major complications from the procedure.

Camaschella C · Blood · 2019

A review of iron deficiency diagnosis describing the sequence of changes: from depletion of storage reserves (ferritin) to changes in red-cell parameters.

Cacoub P, Vandewalle C, Peoc'h K · Critical Reviews in Clinical Laboratory Sciences · 2019

A systematic review confirming the diagnostic value of transferrin saturation alongside ferritin, particularly as a first-line test in patients with chronic inflammatory disease.

Russell N., Grossmann M. · European Journal of Endocrinology · 2019

A review of evidence that estradiol circulates in men at physiologically meaningful concentrations and serves real functions, rather than being merely a trace byproduct of testosterone metabolism.

Harrison DE, Strong R, Reifsnyder P, Flurkey K, Astle CM, Fernandez E, et al. · Aging Cell · 2019

A dose-response study confirmed and extended the original 2014 result by testing acarbose at three doses within the same multi-site ITP program — the lifespan-extension effect, stronger in males than females, was independently confirmed, substantially strengthening confidence in the original finding.

Bárcena C, Valdés-Mas R, Mayoral P, Garabaya C, Durand S, Rodríguez F, et al. (López-Otín C, senior author) · Nature Medicine · 2019

Progeroid mice (two independent premature-aging models) showed gut dysbiosis similar to that seen in elderly humans, while human centenarians showed the opposite, more favorable profile (more Verrucomicrobia). Microbiota transplant from healthy, normally aging donors extended lifespan and improved health in the progeroid mice in both models, and transferring Akkermansia muciniphila alone reproduced part of this effect.

Chen Y, Zhao JW, Zhang LY, et al. · Journal of Rehabilitation Medicine · 2019

A systematic review of eight placebo-controlled trials in knee osteoarthritis: PEMF showed no significant advantage over placebo in reducing pain and stiffness, but was associated with improved physical joint function — the authors call for further research to establish optimal parameters and treatment protocols.

Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyère O, Cederholm T et al. · Age and Ageing · 2019

Updated international guidelines from the European Working Group on Sarcopenia in Older People, establishing low grip strength as the main screening criterion for sarcopenia, with approximate thresholds below 27 kg for men and below 16 kg for women. The document summarizes evidence that grip strength correlates more strongly with the functional consequences of sarcopenia (falls, disability) than muscle mass measured by imaging methods alone.

Aringer M, Costenbader K, Daikh D, et al. (EULAR/ACR working group) · Arthritis & Rheumatology · 2019

The current lupus classification criteria, replacing the older 1997 ACR criteria: a positive ANA is required as an entry condition, followed by scoring across seven clinical and three immunological domains with a threshold of at least 10 points. In the validation study, the criteria achieved 96.1% sensitivity and 93.4% specificity.

Popova V, Daly EJ, Trivedi M, et al. · American Journal of Psychiatry · 2019

A randomized, double-blind, active-controlled phase 3 trial (one of the two TRANSFORM registration trials) showed that flexibly dosed intranasal esketamine combined with a newly initiated oral antidepressant produced a significantly greater reduction in depression symptoms (a 4.4-point MADRS difference at day 28) than the oral antidepressant alone with intranasal placebo in patients with treatment-resistant depression. This is the only one of the two main short-term TRANSFORM trials that reached statistical significance on the primary endpoint.

Fedgchin M, Trivedi M, Daly EJ, et al. · International Journal of Neuropsychopharmacology · 2019

The second phase 3 registration trial (TRANSFORM-1) compared fixed doses of esketamine (56 mg or 84 mg) with intranasal placebo, each combined with a newly initiated oral antidepressant. The 84 mg dose did not reach statistical significance on the primary endpoint versus placebo, though the 56 mg dose showed a numerically favorable trend. The authors stressed the need for larger, longer trials — the result illustrates that not every esketamine registration trial produced an unambiguously positive outcome, despite the drug's eventual approval based on the overall research program.

Avgerinos KI, et al. · Experimental Gerontology · 2018

A review pointing to a potential improvement in short-term memory and processing speed, stronger under sleep deprivation or in older adults.

Le Thi Nhu Ngoc, Oh YK, Lee YJ, Lee YC · International Journal of Molecular Sciences · 2018

A systematic review of 33 RCTs — all in animal models — showed, among other things, a significant reduction in serum insulin and faster wound healing. No studies in humans.

Chen XQ, et al. · Molecules · 2018

Fourteen triterpenes were isolated, two of which showed stronger α-glucosidase inhibition than acarbose in an in vitro enzymatic assay.

Loyd AL, Richter BS, Jusino MA, Truong C, Smith ME, Blanchette RA, Smith JA · Frontiers in Microbiology · 2018

A DNA analysis of 20 commercial products marketed as Ganoderma lucidum found that 93% contained material genetically corresponding to G. lingzhi, and none contained true European G. lucidum.

Sun Y, Zhong S, Yu J, Zhu J, Ji D, Hu G, Wu C, Li Y · PLoS ONE · 2018

A study in mice with induced intestinal inflammation showed that an aqueous extract lowered pro-inflammatory cytokine levels.

Estruch R, et al. (PREDIMED) · New England Journal of Medicine · 2018

A large randomized trial (n>7,000) showing a significant reduction in major cardiovascular events in groups following a Mediterranean diet supplemented with olive oil or nuts.

García-Hermoso A, et al. · Archives of Physical Medicine and Rehabilitation · 2018

A meta-analysis showing an inverse relationship between muscle strength and the risk of death from any cause.

Bhasin S, Brito JP, Cunningham GR, et al. · Journal of Clinical Endocrinology & Metabolism · 2018

Official Endocrine Society clinical guidelines on the diagnosis, form selection, and monitoring of testosterone therapy.

Bhasin S, Brito JP, Cunningham GR, et al. · Journal of Clinical Endocrinology & Metabolism · 2018

Clinical guidelines defining the diagnostic criteria for hypogonadism and the principles for differentiating the primary and secondary forms.

Bhasin S, Brito JP, Cunningham GR, et al. · Journal of Clinical Endocrinology & Metabolism · 2018

Clinical guidelines defining the recommended monitoring schedule for testosterone therapy safety.

Mandsager K, Harb S, Cremer P, et al. · JAMA Network Open · 2018

An analysis of more than 122,000 patients undergoing exercise stress testing showing a continuous decline in mortality risk with increasing cardiorespiratory fitness, with no clear upper threshold of benefit.

Petersen MC, Shulman GI · Physiological Reviews · 2018

An extensive review of the molecular mechanisms of insulin action and the signaling defects underlying insulin resistance.

Teede HJ, Misso ML, Costello MF, et al. · Fertility and Sterility · 2018

International evidence-based guidelines on the diagnosis and treatment of PCOS, emphasizing the central role of insulin resistance in the syndrome's pathophysiology.

Whelton PK, Carey RM, Aronow WS, et al. · Hypertension · 2018

Comprehensive clinical guidelines for the diagnosis, assessment, and treatment of hypertension in adults, covering both lifestyle modification and pharmacotherapy.

Zondervan KT, Becker CM, Missmer SA · Nature Reviews Disease Primers · 2018

A comprehensive review of the epidemiology, mechanisms, diagnostics and treatment of endometriosis.

Bhasin S, Brito JP, Cunningham GR i wsp. · Journal of Clinical Endocrinology & Metabolism · 2018

The Endocrine Society clinical guideline defining diagnostic criteria for hypogonadism, indications for TRT, and rules for monitoring therapy.

Ponce OJ, Spencer-Bonilla G, Alvarez-Villalobos N i wsp. · Journal of Clinical Endocrinology & Metabolism · 2018

An RCT meta-analysis showing a moderate improvement in sexual function with TRT, with no confirmed benefit for mood, energy, or cognitive function, and an increased risk of erythrocytosis.

Bhasin S, Brito JP, Cunningham GR i wsp. · Journal of Clinical Endocrinology & Metabolism · 2018

Clinical guidelines describing the full diagnostic panel before TRT, including hematocrit and PSA criteria as contraindications to immediately starting therapy.

Mulhall JP, Trost LW, Brannigan RE i wsp. · The Journal of Urology · 2018

American Urological Association guidelines defining the <300 ng/dL threshold that supports a diagnosis of testosterone deficiency and the scope of testing preceding qualification for treatment.

Bhasin S, Brito JP, Cunningham GR i wsp. · Journal of Clinical Endocrinology & Metabolism · 2018

The Endocrine Society clinical guideline establishing the CDC-harmonized lower threshold for total testosterone (approx. 264 ng/dL) in healthy, non-obese young men and the principles for interpreting a result in the context of symptoms.

Bhasin S, Brito JP, Cunningham GR, et al. · Journal of Clinical Endocrinology & Metabolism · 2018

The Endocrine Society clinical guideline defining, among other things, the requirements for regular, long-term safety monitoring of testosterone therapy — the basis for the recurring monitoring cost described in this piece.

Fiers T, Wu F, Moghetti P, Vanderschueren D, Lapauw B, Kaufman JM · Journal of Clinical Endocrinology & Metabolism · 2018

A newer validation comparing free testosterone calculated with the Vermeulen formula against direct measurement by LC-MS/MS combined with equilibrium dialysis, confirming good agreement in the typical SHBG range and larger discrepancies at the extremes.

Bhasin S, Brito JP, Cunningham GR et al. · Journal of Clinical Endocrinology & Metabolism · 2018

Clinical guidelines defining a detailed TRT monitoring schedule — checks at months 3 and 6, prostate risk assessment in the 3–12 month window, and annual checks once therapy has stabilized.

Mulhall JP, Trost LW, Brannigan RE et al. · The Journal of Urology · 2018

American Urological Association guidelines describing the principles of monitoring men during testosterone therapy, including decision thresholds for PSA and hematocrit.

Bhasin S, Brito JP, Cunningham GR, et al. · Journal of Clinical Endocrinology & Metabolism · 2018

Clinical guidelines defining TRT qualification criteria, including severe, untreated obstructive sleep apnea as a condition requiring caution and additional assessment before starting testosterone therapy.

Bhasin S, Brito JP, Cunningham GR i wsp. · Journal of Clinical Endocrinology & Metabolism · 2018

Clinical practice guideline defining, among other things, the prostate monitoring protocol during TRT: PSA and digital rectal exam before starting therapy in men ≥40 with a baseline PSA above the median (0.6 ng/mL), follow-up at 3–6 months, and referral to a urologist for a confirmed PSA rise of >1.4 ng/mL within 12 months, a confirmed PSA >4.0 ng/mL, or an abnormal digital rectal exam.

Mulhall JP, Trost LW, Brannigan RE i wsp. · Journal of Urology · 2018

American Urological Association guideline on the diagnosis and treatment of testosterone deficiency, including a PSA/DRE monitoring protocol analogous to the Endocrine Society's — before therapy, at 3–6 months, and thresholds qualifying for urological referral. The guideline also notes that patients with a prostate cancer history should have PSA monitored at least at the standard rhythm, with clinicians free to increase frequency.

Bhasin S i wsp. · The Journal of Clinical Endocrinology & Metabolism · 2018

The Endocrine Society's key clinical guideline on diagnosing and treating hypogonadism in men, including concrete recommendations for hematocrit monitoring during TRT — including a recommendation to pause therapy at a hematocrit above 54% until the value normalizes, with the option to resume at a lower dose, and phlebotomy as one option for managing erythrocytosis.

Mulhall JP i wsp. · The Journal of Urology · 2018

American Urological Association guideline on evaluating and treating testosterone deficiency, specifying the numerical hematocrit thresholds relevant to clinical practice — above 50%, an explanation of the cause is recommended, and at ≥54%, dose reduction or temporarily pausing testosterone therapy.

Ohlander SJ, Varghese B, Pastuszak AW · Sexual Medicine Reviews · 2018

A literature review on erythrocytosis (excessive hematocrit rise) following testosterone therapy, pointing to delivery forms and dosing schedules that produce high peak testosterone concentrations as carrying higher risk of this side effect than profiles with a more stable, flattened concentration course.

Bi Y, Perry PJ, Ellerby M, Murry DJ · CPT: Pharmacometrics & Systems Pharmacology · 2018

31 healthy men received 14 weekly intramuscular injections at research doses of 100, 250, or 500mg/week (supraphysiologic doses, used for dose-response modeling, not standard TRT doses). One-compartment model: clearance 2.6 kL/day, volume of distribution 14.4 kL. Potency of total testosterone for LH suppression estimated at 9.33 ng/mL.

Wilson DM, Kiang TKL, Ensom MHH · American Journal of Health-System Pharmacy · 2018

Dose-normalized AUC comparable between routes (SC 1.7±0.6 vs. IM 1.9±0.6 nmol·days/L/mg); SC route was associated with lower pre-injection anxiety reported by patients — a finding about patient experience, not a hormonal parameter.

Klaips CL, Jayaraj GG, Hartl FU · Journal of Cell Biology · 2018

A review of cellular proteostasis pathways and evidence for their role in aging and diseases linked to protein aggregation, based largely on studies in model organisms and cell lines.

Horvath S, Raj K. · Nature Reviews Genetics · 2018

A foundational review of epigenetic clock theory, describing different generations of methylation clocks and their use as aging biomarkers.

Horvath S, Raj K. · Nature Reviews Genetics · 2018

A foundational review of epigenetic clock theory, describing the different generations of methylation clocks and the logic behind their increasing predictive accuracy for health and mortality.

Cesari M, de Carvalho IA, Thiyagarajan JA, Cooper C, Martin FC, Reginster JY, Vellas B, Beard JR. · The Journals of Gerontology: Series A · 2018

The paper formalizing the five domains of intrinsic capacity (locomotion, vitality, cognition, psychological well-being, sensory function) based on the International Classification of Functioning (ICF) framework and the available scientific evidence.

Pawelec G. · Experimental Gerontology · 2018

A review defining immunosenescence and summarizing its key clinical consequences: weaker vaccine response, reduced ability to fight cancer, heightened inflammation, and susceptibility to autoimmunity.

Nikolich-Žugich J. · Nature Immunology · 2018

A comprehensive review of immune-aging mechanisms, including the role of thymic involution, the shrinking T-cell repertoire, and the impact of chronic latent infections.

Fulop T, Larbi A, Dupuis G, et al. · Frontiers in Immunology · 2018

A review describing immunosenescence and inflammaging as two tightly linked, mutually reinforcing aspects of immune-system aging.

Fulop T, Larbi A, Dupuis G, et al. · Frontiers in Immunology · 2018

A review describing the tight, bidirectional link between inflammaging and immunosenescence as two aspects of the same immune-aging process.

Rajman L, Chwalek K, Sinclair DA. · Cell Metabolism · 2018

A review of in vivo evidence on NAD+-boosting compounds, distinguishing supplying precursors from the efficiency of NAD+ metabolism itself.

Chrysant SG, Chrysant GS · Expert Review of Cardiovascular Therapy · 2018

A review of literature from 2010–2017 summarizing the evidence for homocysteine's link to cardiovascular risk and the controversy surrounding the benefit of lowering it pharmacologically.

Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, White HD, et al. · Circulation · 2018

International ESC/ACC/AHA/WHF consensus document defining criteria for diagnosing myocardial infarction based on the trend of high-sensitivity cardiac troponin concentration relative to the 99th percentile upper reference limit.

Castelnovo A, Lopez R, Proserpio P, Nobili L, Dauvilliers Y · Nature Reviews Neurology · 2018

A review of the neurophysiological mechanisms of NREM parasomnias (sleepwalking, night terrors, confusional arousals) as disorders of sleep-wake state dissociation, based on electrophysiological and neuroimaging studies.

Doubeni CA, Corley DA, Quinn VP, et al. · Gut · 2018

A large population-based study showing a comparable reduction in the risk of death from colorectal cancer for both right- and left-sided colon cancer in people who underwent screening colonoscopy.

Curry SJ, Krist AH, Owens DK, et al., on behalf of the U.S. Preventive Services Task Force · JAMA · 2018

A recommendation defining current cervical cancer screening strategies — cytology alone, HPV testing alone, or a combination — along with recommended intervals by age.

Williams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier M, et al. · European Heart Journal · 2018

European guidelines on diagnosing and treating arterial hypertension, including the role of ambulatory blood pressure monitoring (ABPM) in confirming a diagnosis and detecting white-coat and masked hypertension.

Needleman L, Cronan JJ, Lilly MP, Merli GJ, Adhikari S, Hertzberg BS, DeJong MR, Streiff MB, Meissner MH · Circulation · 2018

Multi-society consensus recommendations regarding the protocol and interpretation of Doppler ultrasound in diagnosing deep vein thrombosis of the legs.

Newby DE, Adamson PD, Berry C, Boon NA, Dweck MR, Flather M, Forbes J, et al. (SCOT-HEART Investigators) · New England Journal of Medicine · 2018

The multicenter randomized SCOT-HEART trial showing that adding coronary CT angiography to standard workup in patients with stable chest pain reduces the 5-year risk of coronary death or myocardial infarction.

Stovner LJ, Nichols E, Steiner TJ et al. · The Lancet Neurology · 2018

An analysis of Global Burden of Disease Study 2016 data estimated that migraine affected roughly 1.04 billion people worldwide, ranking sixth among 328 assessed diseases by prevalence, and together with tension-type headache accounted for 6.5% of all years lived with disability.

O'Byrne PM, FitzGerald JM, Bateman ED, Barnes PJ, Zhong N, Keen C, Jorup C, Lamarca R, Ivanov S, Reddel HK · New England Journal of Medicine · 2018

The SYGMA 1 trial enrolled over 3,800 patients with mild asthma, assigned to as-needed terbutaline, as-needed budesonide-formoterol, or regular budesonide with as-needed terbutaline. As-needed budesonide-formoterol significantly reduced the risk of severe exacerbations compared with as-needed terbutaline alone, with symptom control comparable to the regular-treatment group.

Fiers T, Wu F, Moghetti P, Vanderschueren D, Lapauw B, Kaufman JM · Journal of Clinical Endocrinology & Metabolism · 2018

A validation comparing free testosterone calculated by the Vermeulen formula with a direct measurement by LC-MS/MS combined with equilibrium dialysis — good agreement in the typical SHBG range, larger discrepancies at the extremes.

Dignass A, Farrag K, Stein J · International Journal of Chronic Diseases · 2018

A review discussing how inflammation in conditions such as inflammatory bowel disease, chronic heart failure, and kidney disease elevates ferritin and complicates diagnosis of true iron deficiency.

Pickart L, Margolina A · International Journal of Molecular Sciences · 2018

A review summarizing GHK-Cu's mechanisms of action in light of gene-expression analyses (Connectivity Map), covering effects on over four thousand human genes linked to collagen synthesis, metalloproteinases, antioxidant response, and DNA repair. Cites an earlier clinical trial in which 12 weeks of GHK-Cu applied to thigh skin increased collagen production in 70% of women, versus 50% in the vitamin C group and 40% in the retinoic acid group.

Wu Z, Ding X, Lei G, et al. · BMJ Open · 2018

A meta-analysis of placebo-controlled trials of PEMF in osteoarthritis: for the knee, it found a statistically significant pain reduction versus placebo, though the confidence interval sat close to the no-effect boundary (SMD -0.54; 95% CI -1.04 to -0.04). The authors note substantial heterogeneity in studied protocols and device parameters.

Holfinger S, Roy A, Schmidt M · Journal of Clinical Sleep Medicine · 2018

A case report of a 21-year-old woman who developed Stevens-Johnson syndrome after starting armodafinil (a close relative of modafinil, carrying the same label warning) — the authors emphasize this is a rare but real, documented risk in this drug class, requiring clinical vigilance from the first weeks of therapy.

Kreider RB, et al. · Journal of the International Society of Sports Nutrition · 2017

A position-stand review summarizing decades of research — confirms the effectiveness and safety of creatine monohydrate in athletic populations.

Martineau AR, et al. · BMJ · 2017

An individual patient data meta-analysis (n>10,000) showing a protective effect of supplementation against acute respiratory tract infections, stronger in people with a baseline deficiency.

Boyle NB, et al. · Nutrients · 2017

A review pointing to a potential, though methodologically limited, link between magnesium supplementation and a reduction in subjectively perceived stress.

Hirsch KR, Smith-Ryan AE, Roelofs EJ, Trexler ET, Mock MG · Journal of Dietary Supplements · 2017

Randomized, double-blind, placebo-controlled trial (28 people; 4 g/day of a mushroom blend containing Cordyceps militaris): after one week there were no significant differences, but after 3 weeks (a subgroup of 10) VO2max rose significantly in the mushroom group (+4.8 ml/kg/min) versus +0.9 with placebo. Small sample and a mushroom blend rather than pure C. militaris — the result needs confirmation.

Pleszczyńska M, Lemieszek MK, Siwulski M, Wiater A, Rzeski W, Szczodrak J · World Journal of Microbiology and Biotechnology · 2017

A literature review describing historical and modern laboratory research — documented in vitro antibacterial, antiparasitic, anti-inflammatory, and anti-cancer activity, with no clinical studies.

Jiang Y, et al. · Biomedicine & Pharmacotherapy · 2017

A review describing GSP as an adjunctive drug registered in China since 2010. The authors note that publicly available, published clinical trial data are practically nonexistent.

Laukkanen T, et al. · Age and Ageing · 2017

An analysis of the same KIHD cohort pointing to an inverse relationship between sauna-bathing frequency and dementia risk.

Shaffer F, Ginsberg JP · Frontiers in Public Health · 2017

A review of HRV measurement and interpretation methods, emphasizing the strong dependence on individual and methodological context.

Freedberg DE, Kim LS, Yang YX · Gastroenterology · 2017

An American Gastroenterological Association expert position statement summarizing the evidence on the benefits and potential risks of long-term proton pump inhibitor use.

Levine H, Jørgensen N, Martino-Andrade A, et al. · Human Reproduction Update · 2017

A systematic review and meta-analysis showing a significant decline in sperm concentration and total sperm count among men in Western countries over several decades.

Travison TG, Vesper HW, Orwoll E, et al. · Journal of Clinical Endocrinology & Metabolism · 2017

Pooling more than 9,000 men from four US and European cohorts and re-measuring reference samples with a CDC-certified mass-spectrometry method, this study derived standardized, age-specific total testosterone reference ranges — in healthy, non-obese men aged 19-39, roughly 264-916 ng/dL — addressing long-standing inconsistency between labs' internally defined 'normal' ranges.

Goldman AL, Bhasin S, Wu FCW, Krishna M, Matsumoto AM, Jasuja R · Endocrine Reviews · 2017

An extensive review of the physiology of testosterone binding by SHBG and albumin, including a discussion of the limitations of the classic free hormone hypothesis and the clinical consequences of misinterpreting total testosterone without accounting for SHBG.

Liu TZ, Xu C, Rota M, Cai H, Zhang C, Shi MJ, Yuan RX, Weng H, Meng XY, Kwong JS, Sun XT · Sleep Medicine Reviews · 2017

A meta-analysis of 40 prospective cohort studies (2,200,425 participants, 271,507 deaths) found a J-shaped relationship between sleep duration and all-cause mortality, with the lowest risk at 7 hours of sleep. Risk rose with both shorter and longer sleep, with the risk increase at very long sleep (10-11 hours) markedly larger than at short sleep (4-6 hours).

McFarland J, Craig W, Clarke NJ, Spratt DI · Journal of the Endocrine Society · 2017

11 patients on weekly subcutaneous cypionate, sampled at 8 time points across the week. Mean total T 627±206 ng/dL (range 205-1410), free T 146±51 pg/mL (range 38-348), stable throughout the week. Cohort was transgender men — authors assume results extend to hypogonadal men, but the study doesn't directly confirm this in that group.

Kwo PY, Cohen SM, Lim JK · The American Journal of Gastroenterology · 2017

American College of Gastroenterology guideline defining the hepatocellular and cholestatic patterns and the diagnostic algorithm for abnormal liver chemistries.

Linkins LA, Takach Lapner S · International Journal of Laboratory Hematology · 2017

A clinical review discussing the strengths and weaknesses of D-dimer testing in diagnosing venous thromboembolic disease, including causes of false-positive results and principles of correct interpretation.

Kapur VK, Auckley DH, Chowdhuri S, Kuhlmann DC, Mehra R, Ramar K, Harrod CG · Journal of Clinical Sleep Medicine · 2017

American Academy of Sleep Medicine guidelines on diagnosing obstructive sleep apnea in adults, including the conditions under which home sleep apnea testing (HSAT) is an accepted alternative to full polysomnography.

Freeman D, Sheaves B, Goodwin GM, Yu LM, Nickless A, Harrison PJ, et al. · The Lancet Psychiatry · 2017

The largest randomized intervention trial to date (3,755 students) comparing internet-based CBT-I with a control group, showing significant reductions in paranoia, hallucinations, anxiety, depression, and nightmares after treating insomnia, with mediation analysis confirming this effect was mediated by improved sleep.

Baron KG, Abbott S, Jao N, Manalo N, Mullen R · Journal of Clinical Sleep Medicine · 2017

A paper describing three patient cases in which excessive focus on sleep-tracker data led to anxiety and self-diagnosed sleep disorders — the paper that introduced the term orthosomnia into the medical literature.

Kapur VK, Auckley DH, Chowdhuri S, Kuhlmann DC, Mehra R, Ramar K, Harrod CG · Journal of Clinical Sleep Medicine · 2017

American Academy of Sleep Medicine guidelines specifying the indications for polysomnography and home sleep apnea tests in diagnosing obstructive sleep apnea in adults.

Heerink WJ, de Bock GH, de Jonge GJ, Groen HJM, Vliegenthart R, Oudkerk M · European Radiology · 2017

A meta-analysis of 32 studies covering over 8,000 procedures assessing the complication rate of core-needle and fine-needle lung biopsy under CT guidance.

Lee SWH, Chan EMC, Lai YK · Scientific Reports · 2017

A systematic review and meta-analysis of 31 prevalence estimates from 25 countries found a lifetime prevalence of symptomatic BPH of 26.2% (95% CI 22.8–29.6%).

Goldman AL, Bhasin S, Wu FCW, Krishna M, Matsumoto AM, Jasuja R · Endocrine Reviews · 2017

An extensive review of the physiology of testosterone binding by SHBG and albumin and the clinical consequences of misinterpreting total testosterone without accounting for SHBG.

Goldman AL, Bhasin S, Wu FCW, Krishna M, Matsumoto AM, Jasuja R · Endocrine Reviews · 2017

A review of the physiology of testosterone binding by SHBG and albumin and the clinical consequences of misinterpreting total testosterone without accounting for SHBG.

Kohn T.P. et al. · Fertility and Sterility · 2017

A retrospective analysis of men with infertility linked to prior testosterone therapy, showing that both older age and a longer prior duration of TRT significantly extend the time needed for sperm count to return after restorative therapy.

Klupp N.L., Kiat H., Bensoussan A., Steiner G.Z., Chang D.H. · Scientific Reports · 2016

A 16-week RCT in 84 people with type 2 diabetes and metabolic syndrome found no significant effect of Ganoderma lucidum extract on HbA1c, fasting glucose, or other cardiometabolic parameters — an important counterpoint to reishi's marketing claims.

Arata S., Watanabe J., Maeda M., Yamamoto M., Matsuhashi H., Mochizuki M., Kagami N., Honda K., Inagaki M. · Heliyon · 2016

In a mouse model of lung cancer, daily administration of an aqueous chaga extract for 3 weeks inhibited tumor growth and metastasis. A promising preclinical result, but its extrapolation to people with cancer has not been confirmed by clinical trials.

Liu MM, Zeng P, Li XT, Shi LG · International Journal of Biological Macromolecules · 2016

The isolated polysaccharide significantly inhibited proliferation of HeLa and SGC-7901 cells in vitro and stimulated macrophage activity.

Im KH, Nguyen TK, Choi J, Lee TS · Molecules · 2016

Extracts showed antioxidant and digestive-enzyme-inhibiting activity in vitro, and in an animal model reduced carrageenan-induced paw swelling by up to 46%.

Siqueira JPZ, Sutton DA, Gené J, et al. · Journal of Clinical Microbiology · 2016

A phylogenetic analysis of 23 clinical isolates showed that 22 of them, previously classified as S. commune, belonged to S. radiatum.

Toledo CV, Barroetaveña C, Fernandes Â, Barros L, Ferreira ICFR · Molecules · 2016

Chemical profiling of wild mushrooms from Patagonian forests, including G. gargal — high trehalose content and moderate antioxidant activity.

Appleby PN, Key TJ · Proceedings of the Nutrition Society · 2016

A review of data from the EPIC-Oxford cohort study linking plant-based diets with lower risk of ischemic heart disease and lower BMI, while also flagging the risk of B12 and vitamin D deficiencies.

Snyder PJ, Bhasin S, Cunningham GR, et al. · New England Journal of Medicine · 2016

A set of large, randomized studies (the Testosterone Trials) evaluating the effects of testosterone therapy in older men with confirmed low hormone levels.

Barzilai N, Crandall JP, Kritchevsky SB, Espeland MA · Cell Metabolism · 2016

A review paper presenting the scientific rationale for the TAME trial — the hypothesis that metformin might slow age-related diseases in people without diabetes.

Wexler A. · Frontiers in Human Neuroscience · 2016

A bioethical analysis of the social context of biohacking and neurohacking practices, describing their position at the boundary of self-knowledge, self-experimentation, and medicine.

Fothergill E, Guo J, Howard L, et al. · Obesity · 2016

A study showing persistently reduced resting energy expenditure in participants of a massive body-mass reduction program six years after its conclusion.

McLellan TM, Caldwell JA, Lieberman HR · Neuroscience & Biobehavioral Reviews · 2016

An extensive literature review confirming caffeine's consistent, positive effect on alertness, reaction time and physical performance across a wide range of doses.

Buijze GA, Sierevelt IN, van der Heijden BC, Dijkgraaf MG, Frings-Dresen MH · PLOS ONE · 2016

A large randomized trial showing that regular cold showers are associated with significantly lower sick-leave absence, though not with a lower frequency of infections themselves.

Snyder PJ, Bhasin S, Cunningham GR i wsp. · New England Journal of Medicine · 2016

A set of large randomized trials assessing the effects of TRT in older men with confirmed testosterone deficiency across sexual function, energy, cognitive function, and other domains.

Snyder PJ, Bhasin S, Cunningham GR, et al. · New England Journal of Medicine · 2016

A set of randomized trials (the Testosterone Trials) confirming that the benefits of testosterone therapy persist with continuous treatment — supporting the case for planning TRT as a long-term cost rather than a one-time expense.

Sender R, Fuchs S, Milo R · PLoS Biology · 2016

A paper revising popular estimates of bacterial cell counts in the human body, showing the ratio of bacterial to human cells is much closer to 1:1 (roughly 3.8×10^13 bacterial cells versus roughly 3.0×10^13 human cells) than the previously widely cited 10:1.

Global BMI Mortality Collaboration, Di Angelantonio E, Bhupathiraju ShN, Wormser D, Gao P, Kaptoge S, et al. · The Lancet · 2016

A meta-analysis of individual participant data from 239 prospective studies (10,625,411 participants), restricted to never-smokers without chronic disease at baseline, found the lowest death risk at a BMI of 22.5-25.0. Risk rose approximately log-linearly above a BMI of 25.0, reaching HR=2.76 at grade III obesity (BMI 40-60) relative to the reference range.

Finkelstein JS, Lee H, Leder BZ, et al. · Journal of Clinical Investigation · 2016

When aromatization was pharmacologically blocked, spine bone mineral density, measured by both DXA and QCT, fell significantly across all tested testosterone-dose groups — confirms that estrogen, not testosterone, is the primary hormonal driver of bone density maintenance in men, mechanistically explaining the Burnett-Bowie et al. 2009 finding.

Perna L, Zhang Y, Mons U, Holleczek B, Saum KU, Brenner H. · Clinical Epigenetics · 2016

A cohort study (n=1863) showing that each 5-year increase in epigenetic age acceleration according to the Horvath clock was linked to about a 23% higher all-cause mortality risk, independent of chronological age.

Beard JR, Officer A, de Carvalho IA, et al. · The Lancet · 2016

The landmark WHO report that introduced intrinsic capacity as the central element of a new definition of healthy ageing, based on a person's functional ability rather than solely on the presence or absence of disease.

Camacho-Pereira J, Tarragó MG, Chini CCS, et al. · Cell Metabolism · 2016

A mouse study identifying CD38 as the main enzyme responsible for the age-related degradation of NAD+ and externally administered NMN — CD38 knockout mice did not show the typical NAD+ decline.

Sheehan MT · Clinical Medicine & Research · 2016

A review explaining pituitary-thyroid physiology and the proper interpretation of TSH, fT4, and anti-TPO antibodies in primary care.

Tripodi A, Lippi G, Plebani M · Clinical Chemistry and Laboratory Medicine · 2016

A review discussing the various ways PT and aPTT results have been reported (clotting time in seconds, percentage activity, patient-to-normal ratio, INR) and the resulting interpretive difficulties across different clinical contexts.

Safari S, Yousefifard M, Hashemi B, et al. · Clinical and Experimental Nephrology · 2016

A systematic review with meta-analysis assessing how accurately CK concentration predicts the risk of acute kidney injury in patients with rhabdomyolysis, showing limited standalone predictive value for CK.

Stallman HM, Kohler M · PLoS ONE · 2016

A meta-analysis of 51 studies (over 100,000 participants) assessing sleepwalking prevalence — 6.9% lifetime, with significantly higher current prevalence in children (5.0%) than adults (1.5%).

St-Onge MP, Grandner MA, Brown D, Conroy MB, Jean-Louis G, Coons M, Bhatt DL · Circulation · 2016

The American Heart Association's official scientific statement summarizing the evidence for the impact of sleep duration and quality on lifestyle behaviors and cardiovascular and metabolic health.

Siu AL, on behalf of the U.S. Preventive Services Task Force · Annals of Internal Medicine · 2016

A recommendation based on a review of randomized clinical trials, confirming reduced breast cancer mortality from screening mammography in women aged 50 and older.

Bouma HK, Labos C, Gore GC, Wolfson C, Keezer MR · European Journal of Neurology · 2016

A systematic review and meta-analysis assessing the sensitivity and specificity of a routine EEG test performed after a first unprovoked seizure in adults and children.

Hashemi SA, Alavian SM, Gholami-Fesharaki M · Caspian Journal of Internal Medicine · 2016

A systematic review and meta-analysis assessing the diagnostic accuracy of transient elastography in detecting and staging liver fibrosis in patients with non-alcoholic fatty liver disease.

Ness-Jensen E, Hveem K, El-Serag H, Lagergren J · Clinical Gastroenterology and Hepatology · 2016

A systematic review of 15 studies assessing the effect of lifestyle interventions on gastroesophageal reflux disease symptoms found that among the many commonly recommended modifications, only weight loss and raising the head of the bed had a consistent, multi-study-confirmed symptom-relieving effect.

Hill NR, Fatoba ST, Oke JL, Hirst JA, O'Callaghan CA, Lasserson DS, Hobbs FDR · PLOS ONE · 2016

A systematic review and meta-analysis found a global chronic kidney disease prevalence of 11–13%, with the large majority of cases falling into disease stage 3.

Benowitz NL, Burbank AD · Trends in Cardiovascular Medicine · 2016

A review of the mechanisms behind nicotine's own cardiotoxicity (independent of tobacco combustion) — showing that nicotine increases heart rate and blood pressure through sympathetic nervous system activation, contributes to vascular endothelial dysfunction, and may accelerate atherosclerotic plaque progression, which matters for assessing the long-term safety of nicotine products other than cigarettes.

Rodriguez P, Zhou W, Barrett DW, Altmeyer W, Gutierrez JE, Li J, Lancaster JL, Gonzalez-Lima F, Duong TQ · Radiology · 2016

A randomized, double-blind, placebo-controlled trial in 26 healthy adults: low-dose methylene blue (0.5 mg/kg) increased fMRI activity in the insular cortex during a vigilance task and in frontal, parietal, and occipital regions during a short-term memory task, alongside a 7% increase in correct memory-retrieval responses (P = .01). A small, single-dose study in healthy people — it does not prove an effect in patients with cognitive impairment.

Chong LY, Head K, Hopkins C, Philpott C, Burton MJ, Schilder AGM · Cochrane Database of Systematic Reviews · 2016

A systematic review assessing the effectiveness of saline nasal irrigation in chronic rhinosinusitis as part of a broader series of Cochrane reviews on treatment of this disease — points to a benefit of irrigation in easing symptoms, with no clear advantage of low-volume nebulized spray over intranasal steroids alone.

Cadegiani FA, Kater CE · BMC Endocrine Disorders · 2016

A systematic review of 58 studies evaluating cortisol profiles in relation to fatigue or energy levels. The authors found no scientifically consistent, reproducible evidence for a cortisol-deficiency state resulting from adrenal 'exhaustion' — cortisol measures varied too inconsistently across studies, and the methodology of studies claiming to have found such a state was assessed as weak. Conclusion: no scientific basis to treat 'adrenal fatigue' as a distinct medical condition.

Bornstein SR, Allolio B, Arlt W, et al. · Journal of Clinical Endocrinology & Metabolism · 2016

An Endocrine Society guideline (co-developed with the European Society of Endocrinology) describing the objective, validated diagnostic criteria for real primary adrenal insufficiency — low morning cortisol, elevated ACTH, and a cosyntropin (250 µg) stimulation test as the gold standard for confirming the diagnosis — in clear contrast to the absence of any validated criteria for the 'adrenal fatigue' construct.

Tarleton EK, Littenberg B. · Journal of the American Board of Family Medicine · 2015

An observational study describing an inverse relationship between magnesium intake and depressive symptoms in adults.

Dai X, Stanilka JM, Rowe CA, Esteves EA, Nieves C Jr, Spaiser SJ, Christman MC, Langkamp-Henken B, Percival SS · Journal of the American College of Nutrition · 2015

A randomized trial in 52 healthy adults showed that consuming 5 or 10 g of dried shiitake daily for 4 weeks increased proliferation of γδ-T and NK-T cells, raised sIgA levels, and lowered CRP.

Zhao S, et al. · Carbohydrate Polymers · 2015

In rats on a hypercholesterolemia-inducing diet, the polysaccharide lowered total cholesterol by as much as 33–35% after 29 days.

Chen ML, Hsieh CC, Chiang BL, Lin BF · Evidence-Based Complementary and Alternative Medicine · 2015

The triterpene fraction significantly inhibited the release of histamine and Th2 cytokines from activated mast cells in vitro.

Milovanovic I, Stanojkovic T, Stajic M, Brceskic I, Knezevic A, Cilerdzic J, Vukojevic J · Current Pharmaceutical Biotechnology · 2015

An in vitro study on selenium-enriched mycelium showed antioxidant activity and cytotoxicity against cancer cell lines.

Vasina DV, et al. · Biochimie · 2015

A molecular study identified five laccase genes and described their regulation by copper ions — an enzymology study, not related to health.

Melappa G, Chandrasekhar N, Pramod SN, Rangappa Nagaraj K · Pharmacognosy Journal · 2015

A methanol extract showed antioxidant, antimicrobial, and anti-inflammatory activity in vitro — the only published study of this species.

Milovanovic I, et al. · Current Pharmaceutical Biotechnology · 2015

Selenium-enriched mycelium showed stronger antioxidant and cytotoxic effects in vitro than unenriched mycelium.

Mizerska-Dudka M, Jaszek M, Błachowicz A, et al. · International Journal of Biological Macromolecules · 2015

An in vitro study of three fractions showed antiviral activity of laccase against HSV, macrophage stimulation by the polysaccharide fraction, and cytotoxicity toward cervical cancer cells.

Postemsky PD, Curvetto NR · International Journal of Medicinal Mushrooms · 2015

Methanol extracts from mycelium grown in submerged culture showed radical-scavenging ability in vitro — the only available data on this species' biological activity.

Postemsky PD, Curvetto NR · International Biodeterioration & Biodegradation · 2015

A biotechnological study on cultivation using cheap agricultural substrates for producing mycelial biomass and antioxidant compounds.

Morris MC, et al. · Alzheimer's & Dementia · 2015

A cohort study showing significantly lower Alzheimer's disease risk in people most closely following the MIND diet.

Laukkanen JA, et al. · JAMA Internal Medicine · 2015

A cohort study (KIHD, n≈2,300 Finnish men) showing an inverse relationship between sauna-bathing frequency and cardiovascular mortality.

Lan J, et al. · Journal of Ethnopharmacology · 2015

A meta-analysis showing a significant reduction in fasting glucose and HbA1c comparable to some oral drugs.

Manheimer EW, van Zuuren EJ, Fedorowicz Z, Pijl H · American Journal of Clinical Nutrition · 2015

A meta-analysis of several small studies showed short-term improvement in waist circumference, blood pressure, and triglycerides, while noting the low quality and small number of available studies.

Leidy HJ, Clifton PM, Astrup A, et al. · American Journal of Clinical Nutrition · 2015

A systematic review showing that diets with elevated protein content consistently improve satiety and support the preservation of muscle mass during weight loss.

U.S. Food and Drug Administration · FDA Drug Safety Communication · 2015

An official FDA safety communication from March 2015, narrowing approved testosterone indications to documented hypogonadism and adding a warning about possible increased heart attack and stroke risk — a decision based partly on the Vigen and Finkle studies, rescinded in 2025 following the TRAVERSE results.

Kaminetsky J, Jaffe JS, Swerdloff RS · Sexual Medicine · 2015

A phase II study comparing weekly subcutaneous doses of testosterone enanthate (50 or 100 mg) with a standard 200 mg intramuscular injection every two weeks. Weekly subcutaneous dosing kept testosterone within the reference range across the entire seven-day interval, with less variability than the two-week schedule.

Trauer JM, Qian MY, Doyle JS, Rajaratnam SM, Cunnington D · Annals of Internal Medicine · 2015

A systematic review and meta-analysis of 20 randomized trials (1,162 participants) comparing CBT-I to control groups found clinically meaningful improvement in sleep onset latency (by 19 minutes), wake time after sleep onset (by 26 minutes), and sleep efficiency (by 9.9 percentage points), with effects sustained in long-term follow-up and no reported adverse effects.

Giorgio C, Mena P, Del Rio D, Brighenti F, et al. · Molecular Nutrition & Food Research · 2015

An in vitro study on prostate cancer cell lines showing that urolithin D selectively inhibits EphA2 receptor phosphorylation more strongly than the other urolithins tested — a cell-level study only.

Singh G, Hamdan H, Singh V · Practical Laboratory Medicine · 2015

An analysis of over 5,000 serum folate measurements showing that patients with results below 5.5 ng/mL had lower albumin and hemoglobin levels, supporting an argument for revising the traditionally low reference thresholds.

Shen Y, Zhang J, Zhao Y, Yan Y, Liu Y, Cai J · European Journal of Pediatrics · 2015

A meta-analysis of 12 studies assessing the sensitivity and specificity of IGF-1 and IGFBP-3 as auxiliary diagnostic markers of growth hormone deficiency relative to stimulation tests.

Irish LA, Kline CE, Gunn HE, Buysse DJ, Hall MH · Sleep Medicine Reviews · 2015

A critical review of the empirical evidence for individual, commonly recommended sleep hygiene practices, finding that this evidence is more limited and inconsistent than commonly assumed in educational materials.

Kawai N, Sakai N, Okuro M, Karakawa S, Tsuneyoshi Y, Kawasaki N, Takeshita S, et al. · Neuropsychopharmacology · 2015

An animal study showing that glycine's sleep-promoting and hypothermic effects depend on NMDA receptor activation in the suprachiasmatic nucleus and are abolished by its ablation, explaining the mechanism observed clinically in humans.

Scammell TE · New England Journal of Medicine · 2015

A comprehensive clinical review in NEJM summarizing the neurobiology of narcolepsy, including the role of hypocretin neuron loss, and a practical approach to diagnosis and treatment.

Prather AA, Janicki-Deverts D, Hall MH, Cohen S · Sleep · 2015

An experimental study of 164 healthy adults in which, after objective actigraphy-based sleep measurement, participants were exposed to a cold virus — showing a dose-response relationship between shorter sleep and higher risk of developing a symptomatic infection, independent of age, season, BMI, and stress level.

Culpepper L, Wingertzahn MA · The Primary Care Companion for CNS Disorders · 2015

A systematic review evaluating the efficacy and safety evidence for popular over-the-counter sleep agents (diphenhydramine, doxylamine, melatonin, valerian), finding markedly uneven evidence quality between substances.

Whitworth M, Bricker L, Mullan C · Cochrane Database of Systematic Reviews · 2015

A Cochrane systematic review of 11 trials involving over 37,000 women, showing that routine early-pregnancy ultrasound improves detection of multiple pregnancies and the accuracy of pregnancy dating.

Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, et al. · European Heart Journal – Cardiovascular Imaging · 2015

A joint ASE and EACVI document establishing updated standards for measuring chamber dimensions and ejection fraction in adult echocardiography.

Chen AC, Martin AJ, Choy B, Fernandez-Penas P, Dalziell RA, McKenzie CA, et al. · New England Journal of Medicine · 2015

The ONTRAC trial: 386 high-risk patients (at least two non-melanoma skin cancers in the previous 5 years) were assigned to 500 mg nicotinamide twice daily or placebo for 12 months. Nicotinamide reduced the rate of new non-melanoma skin cancers by 23% (30% reduction for basal cell carcinoma, 20% for squamous cell carcinoma) and significantly reduced the number of actinic keratosis lesions, with a good safety profile.

Oschman JL, Chevalier G, Brown R · Journal of Inflammation Research · 2015

A review-and-hypothesis paper proposing a mechanism by which electrons from the earth act as circulating antioxidants reducing inflammation — partly funded by Clinton Ober (through EarthFx Inc.), the creator of the commercial earthing concept. The authors themselves note that the proposed mechanism requires further, independent confirmation at the cellular level in humans.

Leong DP, Teo KK, Rangarajan S, Lopez-Jaramillo P, Avezum A, Orlandini A et al. · The Lancet · 2015

One of the largest cohort analyses in the history of grip strength research — 139,691 participants from 17 countries at different income levels, followed for a median of 4 years. Every 5 kg drop in grip strength was associated with a 16% increase in all-cause mortality risk (HR 1.16; 95% CI 1.13-1.20), a 17% increase in cardiovascular and non-cardiovascular mortality risk, and higher risk of heart attack and stroke. Grip strength turned out to be a stronger predictor of overall and cardiovascular mortality than systolic blood pressure. Measurement was performed with a Jamar dynamometer on both hands.

Battleday RM, Brem AK · European Neuropsychopharmacology · 2015

A systematic review of 24 studies from 1990–2014 found that modafinil consistently improved performance on complex tasks requiring planning, decision-making, and higher-order cognitive flexibility, but showed no significant difference from placebo on simpler working-memory tests — an effect dependent on task complexity, not a universal cognitive boost.

Scheffers CS, Armstrong S, Cantineau AEP, Farquhar C, Jordan V · Cochrane Database of Systematic Reviews · 2015

A systematic review of 28 RCTs (1,273 women, over 95% postmenopausal). No evidence of improved quality of life was found; DHEA was associated with a statistically significant higher risk of androgenic effects, mainly acne (OR 3.77; 95% CI 1.36–10.4; p=0.01). Evidence on menopausal symptoms was uncertain; a small possible improvement in sexual function versus placebo.

Riley P, Moore D, Ahmed F, Sharif MO, Worthington HV · Cochrane Database of Systematic Reviews · 2015

A systematic review of 10 trials with nearly 6,000 participants. The only reasonably convincing, though low-quality, result was fluoride toothpaste with 10% xylitol, which may reduce caries by about 13% versus fluoride-only toothpaste over 2.5–3 years. For other products, including chewing gum, the authors found no clear evidence of benefit — 7 of 10 trials had a high risk of bias.

Brinjikji W, Luetmer PH, Comstock B, et al. · American Journal of Neuroradiology · 2015

A systematic review of 33 studies covering over 3,100 asymptomatic people showed that disc degeneration prevalence rises with age even with no pain at all: from about 37% in 20-year-olds to about 96% in 80-year-olds, with a similar trend for bulges, protrusions, and annular fissures.

Theodoratou E, et al. · BMJ · 2014

An umbrella review of 107 meta-analyses — confirms strong evidence for vitamin D's role in bone health, while more cautiously assessing other associations as needing further research.

Li JP, Lei YL, Zhan H · International Journal of Medicinal Mushrooms · 2014

In diabetic mice, the extract significantly lowered glucose and HbA1c levels and increased insulin secretion.

Liu K, Wang JL, Zhao L, Wang Q · International Journal of Medicinal Mushrooms · 2014

An ethanolic extract showed strong cytotoxic activity against the MDA-MB-231 breast cancer cell line and moderate activity against bacteria and fungi.

Kongkeaw C, et al. · Journal of Ethnopharmacology · 2014

A meta-analysis indicating a consistent improvement in information-processing speed and memory with supplementation lasting at least 12 weeks.

Hannibal KE, Bishop MD. · Physical Therapy · 2014

A review describing the consequences of chronic HPA axis dysregulation, including its effect on pain perception and inflammation.

Ford AC, Quigley EM, Lacy BE, Lembo AJ, Saito YA, Schiller LR, Soffer EE, Spiegel BM, Moayyedi P · American Journal of Gastroenterology · 2014

A systematic review pointing to moderate improvement in IBS symptoms with probiotics, with significant heterogeneity between the strains studied.

Jonklaas J, Bianco AC, Bauer AJ, et al. · Thyroid · 2014

American Thyroid Association guidelines on the diagnosis and treatment of hypothyroidism, including principles of levothyroxine dosing and monitoring.

Halmos EP, Power VA, Shepherd SJ, Gibson PR, Muir JG · Gastroenterology · 2014

A randomized crossover trial showing a significant reduction in gastrointestinal symptoms in IBS patients following a diet low in FODMAPs.

Amanatkar HR, Chibnall JT, Seo BW i wsp. · Annals of Clinical Psychiatry · 2014

A meta-analysis of 16 RCTs showing a significant, though moderate, positive effect of testosterone on mood, more pronounced in men under 60 and in those with hypogonadism than in eugonadal men.

Kelsey TW, Li LQ, Mitchell RT, Whelan A, Anderson RA, Wallace WHB · PLOS ONE · 2014

A validated normative model based on thirteen population studies that found no further decline in total testosterone after age 40, instead noting growing variance in results between men — an important counterpoint to the simple picture of 'linear decline with age.'

Kovac JR, Rajanahally S, Smith RP, Coward RM, Lamb DJ, Lipshultz LI · Journal of Sexual Medicine · 2014

A survey of 382 men on TRT: 53% chose injections, 31% gel, 17% implants; overall satisfaction with therapy was around 70% and similar across forms — differences were mainly in cost (injections) and convenience (implants/gel), not effectiveness.

Finkle WD, Greenland S, Ridgeway GK et al. · PLOS ONE · 2014

An analysis of a large insurance database (over 55,000 men) showing an increased rate of non-fatal heart attacks within 90 days of starting TRT, with an especially pronounced increase in men 65 and older. Like the Vigen study, observational and susceptible to systematic bias, but a significant factor in the FDA's decision to add a warning.

Handelsman DJ i wsp. · Clinical Chemistry · 2014

A comparison of five popular direct estradiol immunoassays against the reference LC-MS/MS method on blood samples from more than a hundred healthy men. All five immunoassays showed a positive bias (result inflation) of roughly 6–74% depending on the assay, and only the LC-MS/MS result correlated sensibly with testosterone and SHBG — evidence of the limited reliability of standard immunoassays in the low, male estradiol concentration range.

Ramasamy R, Scovell JM, Kovac JR, Lipshultz LI · Journal of Urology · 2014

A head-to-head comparison found a median total testosterone of 504 ng/dL on clomiphene — lower than typically achieved with testosterone injections — with comparable patient satisfaction (qADAM questionnaire) across clomiphene, injection and gel groups.

Jovaisaite V, Mouchiroud L, Auwerx J · Journal of Experimental Biology · 2014

A review of UPRmt mechanisms and evidence for its evolutionarily conserved role in maintaining mitochondrial health and links to aging in model organisms.

Bennett CF, Vander Wende H, Simko M, Klum S, Barfield S, Choi H, Pineda VV, Kaeberlein M · Nature Communications · 2014

A study in nematodes showing that UPRmt activation is neither necessary nor sufficient for lifespan extension — an important caution against oversimplified claims about a direct link between UPRmt and longevity.

Krištić J, Vučković F, Menni C, et al. · The Journals of Gerontology: Series A · 2014

A foundational study in large human cohorts showing that the IgG glycan profile correlates with both chronological age and physiological parameters typical of biological aging.

Franceschi C, Campisi J. · The Journals of Gerontology: Series A · 2014

A review systematizing evidence linking chronic, low-grade inflammation to diseases of old age, including cardiovascular, metabolic, and neurodegenerative conditions.

Spasovski G, Vanholder R, Allolio B, et al. · European Journal of Endocrinology · 2014

A joint guideline from three European scientific societies (ESICM, ESE, ERA-EDTA) on the diagnosis and treatment of hyponatremia, the most common electrolyte disorder in clinical practice.

Levy JH, Szlam F, Wolberg AS, Winkler A · Clinics in Laboratory Medicine · 2014

A comprehensive literature review on the use of PT and aPTT as screening tests, including a discussion of the sensitivity and specificity of both tests and current guidelines for their use before surgical procedures.

Sofi F, Cesari F, Casini A, Macchi C, Abbate R, Gensini GF · European Journal of Preventive Cardiology · 2014

A meta-analysis of 13 prospective cohort studies (122,501 participants) showing a 45 percent increase in the risk of developing or dying from cardiovascular disease in people with insomnia compared to people without sleep disturbances.

Vehapoglu A, Ozgurhan G, Demir AD, et al. · Anemia · 2014

An analysis of hematological indices, including MCH, used to differentiate beta-thalassemia trait from iron-deficiency anemia in children.

Bachman E et al. · The Journals of Gerontology: Series A · 2014

A study showing that the rise in hemoglobin and hematocrit under testosterone is linked to increased erythropoietin and decreased ferritin and hepcidin as early as 1–3 months into therapy, pointing to a new, higher equilibrium set point for erythropoiesis established under the androgen.

Harrison DE, Strong R, Allison DB, Ames BN, Astle CM, Atamna H, et al. · Aging Cell · 2014

A study within the NIA's Interventions Testing Program, testing genetically diverse mice in parallel at three sites, found that acarbose increased median male lifespan by 22% (p<0.0001) and female lifespan by only 5% (p=0.01) — a difference not explained by body weight.

Villeda SA, Plambeck KE, Middeldorp J, Castellano JM, Mosher KI, Luo J, et al. (Wyss-Coray T, senior author) · Nature Medicine · 2014

This study found that exposing old mice to young animals' blood (via parabiosis or repeated plasma injections) improved cognitive function and synaptic plasticity in the hippocampus — one of the studies most often cited as the scientific basis for the commercial 'young plasma' narrative, though it was conducted exclusively in mice, not humans.

Top WMC, Gillman PK, de Langen CJ, Kooy A · Netherlands Journal of Medicine · 2014

A case report of the first documented death from serotonin syndrome caused by an interaction between methylene blue (given intravenously during surgery) and venlafaxine (an SNRI) the patient was taking. The authors note the reaction can present atypically after general anesthesia and is entirely preventable by stopping serotonergic drugs before methylene blue administration.

Dodds RM, Syddall HE, Cooper R, Benzeval M, Deary IJ, Dennison EM et al. · PLOS ONE · 2014

An analysis of data from 12 British cohort studies (over 49,000 participants total) establishing reference normative values for grip strength by age and sex in the British population, widely cited as a reference point in clinical and epidemiological research on aging and sarcopenia.

Kox M, van Eijk LT, Zwaag J, van den Wildenberg J, Sweep FC, van der Hoeven JG, Pickkers P · Proceedings of the National Academy of Sciences (PNAS) · 2014

A proof-of-principle study in 24 healthy men: 12 underwent a 10-day training program in the breathing technique, cold exposure, and meditation under Wim Hof's guidance; 12 served as untrained controls. After all participants received a low dose of E. coli bacterial endotoxin, the trained group (practicing the technique during the endotoxin challenge) showed significantly higher adrenaline, a stronger anti-inflammatory IL-10 response, and a blunted pro-inflammatory response (TNF-α, IL-6, IL-8) compared to controls, with milder accompanying flu-like symptoms.

Wang CR, Qiao WT, Zhang YN, Liu F · Molecules · 2013

In mice, injection of the adenosine fraction increased IL-10 expression and SOD activity while lowering IL-2, IL-6, and IFN-gamma.

Slavin J · Nutrients · 2013

A review of the mechanisms by which fiber and prebiotics affect gut health, immune function, and metabolic regulation.

Rasch B, Born J · Physiological Reviews · 2013

An extensive review of the neurobiological mechanisms through which sleep supports consolidation of various types of memory.

Hsieh TC, Pastuszak AW, Hwang K, Lipshultz LI. · The Journal of Urology · 2013

A clinical study found that men on TRT with concurrent low-dose hCG (500 IU every other day) did not develop azoospermia over an average 6-month follow-up, while TRT alone without hCG leads to azoospermia in a substantial proportion of patients.

Avci P, Gupta A, Sadasivam M, et al. · Seminars in Cutaneous Medicine and Surgery · 2013

A review of photobiomodulation applications in dermatology, including wound healing, reduction of inflammation, and support of collagen production.

Wallace IR, McKinley MC, Bell PM, Hunter SJ · Clinical Endocrinology · 2013

A review systematizing the relationship between SHBG and insulin resistance — discussing why low SHBG is one of the best-documented markers of insulin resistance and how this affects the interpretation of total testosterone in people with obesity.

Finkelstein JS i wsp. · New England Journal of Medicine · 2013

A classic study using a GnRH agonist and an aromatase inhibitor, showing that changes in fat mass in men are primarily linked to changes in estradiol rather than testosterone, and that deficiency of either androgens or estrogens worsens libido and sexual function.

Vigen R, O'Donnell CI, Barón AE et al. · JAMA · 2013

A retrospective analysis of a veterans registry (over 8,700 men after coronary angiography) suggesting a roughly 29% increase in risk of a composite endpoint (death, heart attack, stroke) in men on TRT. An observational study, later heavily criticized for methodological flaws and comparison-group problems — one of the two sources that launched the 2015 FDA warning.

Finkelstein JS, Lee H, Burnett-Bowie SA, et al. · New England Journal of Medicine · 2013

An RCT of 400 men in whom endogenous sex-hormone production was pharmacologically suppressed (goserelin), then given graded testosterone doses with or without anastrozole (not exemestane, but the same aromatase-inhibition class), designed to separate androgen from estrogen effects. Estrogen deficiency specifically drove increased body fat, while androgen deficiency specifically drove loss of lean mass and strength. A key mechanistic trial explaining why estradiol deficiency in men has distinct, documented health consequences — relevant to any potent aromatase inhibitor as a class, exemestane included, despite the lack of direct outcome data for exemestane itself.

Stabler SP · New England Journal of Medicine · 2013

A comprehensive clinical review in NEJM's respected Clinical Practice series, summarizing the causes, diagnosis and treatment of vitamin B12 deficiency — including the role of gastric mucosal atrophy, bowel disease, bariatric surgery, and chronic use of metformin and acid-reducing medications as acquired causes of deficiency, along with recommendations for confirming the diagnosis with additional markers (methylmalonic acid, homocysteine) when the total B12 result is ambiguous.

Stevens PE, Levin A, for the KDIGO CKD Guideline Development Work Group Members · Annals of Internal Medicine · 2013

A synopsis of the KDIGO guideline defining chronic kidney disease staging based on eGFR and the principles of monitoring and further workup.

Steele T, Kolamunnage-Dona R, Downey C, Toh C, Welters I · Critical Care · 2013

A study comparing albumin-adjusted total calcium with ionized calcium in critically ill patients, showing that albumin correction doesn't reliably improve the accuracy of diagnosing calcium disturbances.

Rasch B, Born J · Physiological Reviews · 2013

A comprehensive review of the mechanisms through which NREM and REM sleep support memory consolidation, including the role of hippocampal-cortical dialogue and active, systems-level reorganization of memories during sleep.

Xie L, Kang H, Xu Q, Chen MJ, Liao Y, Thiyagarajan M, et al. · Science · 2013

A landmark mouse-model study showing that during natural sleep, the brain's interstitial space increases by about 60%, dramatically intensifying convective removal of metabolites, including beta-amyloid, via the glymphatic system.

Nishihara R, Wu K, Lochhead P, et al. · New England Journal of Medicine · 2013

A long-term cohort study showing that, unlike sigmoidoscopy, colonoscopy is associated with reduced incidence of both proximal and distal colorectal cancer.

Wallace IR, McKinley MC, Bell PM, Hunter SJ · Clinical Endocrinology · 2013

A review systematizing the relationship between SHBG and insulin resistance — discussing why low SHBG is one of the best-documented markers of insulin resistance, independent of BMI.

Dhurat R, Sukesh M, Avhad G, Dandale A, Pal A, Pund P · International Journal of Trichology · 2013

A randomized pilot study in 100 men with androgenetic alopecia (Norwood-Hamilton grade III-IV), comparing weekly microneedling (1.5 mm needles) plus twice-daily 5% minoxidil against minoxidil alone, over 12 weeks. The microneedling+minoxidil group achieved a hair density increase of 91.4 hairs/cm² versus 22.2 hairs/cm² in the minoxidil-only group (p=0.039) — a fourfold difference. 12 men who had previously failed finasteride/minoxidil therapy responded positively after adding microneedling.

Corona G, Rastrelli G, Giagulli VA, et al. · The Journal of Clinical Endocrinology & Metabolism · 2013

A meta-analysis of 25 RCTs in 1,353 aging men. DHEA supplementation was linked to a small, significant reduction in fat mass, dependent on conversion to active hormones, with no significant effect on lipid metabolism, glycemia, bone density, or sexual function.

Hickey SE, Curry CJ, Toriello HV · Genetics in Medicine · 2013

A practice guideline from the American College of Medical Genetics and Genomics stating that growing evidence points to minimal clinical utility for MTHFR polymorphism testing, which shouldn't be ordered as part of routine thrombophilia evaluation, recurrent pregnancy loss workup, or testing of asymptomatic family members.

Chandrasekhar K, Kapoor J, Anishetty S. · Indian Journal of Psychological Medicine · 2012

A randomized, placebo-controlled trial (n=64) showing a significant reduction in perceived stress and cortisol levels in the group supplemented with ashwagandha root extract.

Ishaque S, et al. · BMC Complementary and Alternative Medicine · 2012

A systematic review pointing to promising but methodologically heterogeneous evidence for an anti-fatigue effect.

Torkelson CJ, Sweet E, Martzen MR, Sasagawa M, Wenner CA, Gay J, Putiri A, Standish LJ · ISRN Oncology · 2012

A phase 1 trial in 11 women with breast cancer after completing radiotherapy showed that oral doses of Trametes versicolor extract up to 9 g/day for 6 weeks were safe and well tolerated.

Lima CUJO, Souza VC, Morita MC, Chiarello MD, de Oliveira Karnikowski MG · Scandinavian Journal of Immunology · 2012

A randomized, double-blind, placebo-controlled study in 57 older women found no significant effect of 900 mg of Agaricus blazei extract daily on the inflammatory markers IL-6, IFN-gamma, and TNF-alpha.

Li H, Liu X, Li Y, Hua Y, Zhi D, Pang G · International Journal of Biological Macromolecules · 2012

A small study in healthy volunteers analyzing the effect of the PNPS-1 polysaccharide on 39 serum cytokines — significant anti-inflammatory activity was observed.

Yu YH, Kuo HP, Hsieh HH, Li JW, Hsu WH, et al. · Evidence-Based Complementary and Alternative Medicine · 2012

The extract inhibited the proliferation of doxorubicin-resistant lung cancer cells through cell-cycle arrest and apoptosis induction.

Cao Y, Wu SH, Dai YC · Fungal Diversity · 2012

The paper that formally split Ganoderma lingzhi off as a species distinct from Ganoderma lucidum based on phylogenetic analysis of ITS sequences.

Westcott WL. · Current Sports Medicine Reports · 2012

A review summarizing the evidence for the benefits of resistance training on metabolic, bone, and functional health at every age.

Hempel S, et al. · JAMA · 2012

A meta-analysis showing a significant reduction in the risk of antibiotic-associated diarrhea with selected probiotic strains.

Gibala MJ, Little JP, MacDonald MJ, Hawley JA · The Journal of Physiology · 2012

A review showing that low-volume, high-intensity interval training triggers metabolic and cardiovascular adaptations comparable to traditional endurance training.

Roenneberg T, Allebrandt KV, Merrow M, Vetter C · Current Biology · 2012

A study introducing the concept of social jet lag and demonstrating its link to increased obesity risk.

Yang L, Zhang SX, Dong Q, Xiong ZB, Li X. · International Urology and Nephrology · 2012

In 242 men with hypogonadotropic hypogonadism, hCG monotherapy increased testicular volume in 50% of patients (from 2.0 to 6.8 mL), and hCG plus hMG in 75.7% (to 8.8 mL); the group treated with testosterone alone showed no significant increase in testicular volume — direct evidence that testosterone alone does not replicate hCG's effect on the testes.

Miller MG, Rogol AD, ZumBrunnen TL · Current Medical Research and Opinion · 2012

A review of five phase 1 studies assessing testosterone transfer to female partners after skin contact with men using 1.62% gel — confirms a measurable rise in testosterone concentration in unmedicated women, along with the effectiveness of washing and covering the application site in reducing that risk.

Miller MG, Rogol AD, ZumBrunnen TL · Current Medical Research and Opinion · 2012

A review of five phase 1 studies assessing testosterone transfer to female partners after skin contact with men using gel — confirms a measurable rise in testosterone concentration in exposed people and the meaningful effectiveness of washing and covering the application site in reducing this transfer.

Martinez-Pajares JD, Diaz-Morales O, Ramos-Diaz JC, Gomez-Fernandez E · Journal of Pediatric Endocrinology and Metabolism · 2012

A case report of an 18-month-old boy who developed precocious puberty from unintended testosterone exposure through gel used by his father, along with a review of similar previously published cases — illustrating that transfer risk in household settings is real, not merely theoretical.

Kivimäki M, Nyberg ST, Batty GD, Fransson EI, et al. (IPD-Work Consortium) · The Lancet · 2012

An individual-participant-data meta-analysis of 13 European cohort studies (197,473 people) found that job strain (a combination of high demands and low control) was linked to a 23% higher risk of coronary heart disease (HR=1.23; 95% CI 1.10-1.37) after adjusting for age and sex, though the effect was markedly smaller than for classic risk factors.

Moskovic DJ, Katz DJ, Akhavan A, Park K, Mulhall JP · BJU International · 2012

In 46 patients followed long-term, testosterone rose from a baseline of 228 ng/dL to 612 ng/dL after one year and remained stable through 3 years. Femoral neck and lumbar spine bone density improved significantly, with no reported adverse events.

Katz DJ, Nabulsi O, Tal R, Mulhall JP · BJU International · 2012

In 86 men (mean age 29), most seeking treatment specifically to preserve fertility, testosterone and gonadotropins rose significantly after a mean 19 months of therapy with no major adverse events — clomiphene was concluded to be an effective, safe alternative to exogenous testosterone in this population.

Slater G, Steier J · Journal of Thoracic Disease · 2012

A clinical review discussing excessive daytime sleepiness as a significant public health problem with an estimated prevalence of up to 18% in the general population, covering its most common causes — sleep apnea and periodic limb movement disorder.

Okamoto-Mizuno K, Mizuno K · Journal of Physiological Anthropology · 2012

A review of the mechanisms through which heat and cold exposure affect sleep and circadian rhythm, showing that extreme ambient temperatures increase awakenings and shorten REM and slow-wave sleep.

Banerjee A, Newman DR, Van den Bruel A, Heneghan C · International Journal of Clinical Practice · 2012

A systematic review and meta-analysis assessing the sensitivity and specificity of exercise stress testing (with and without echocardiography) for detecting coronary artery disease.

Quanjer PH, Stanojevic S, Cole TJ, Baur X, Hall GL, Culver BH, Enright PL, et al. · European Respiratory Journal · 2012

A Global Lung Function Initiative report presenting multi-ethnic reference equations for spirometry across the 3–95 year age range, now the current standard for result interpretation.

Page MJ, Massy-Westropp N, O'Connor D, Pitt V · Cochrane Database of Systematic Reviews · 2012

A Cochrane systematic review assessing the effectiveness of wrist splinting for treating carpal tunnel syndrome found that splinting provides symptomatic benefit compared with no treatment, though the quality of available evidence was rated as moderate to low, indicating a need for further, better-designed studies.

Scales CD Jr, Smith AC, Hanley JM, Saigal CS (Urologic Diseases in America Project) · European Urology · 2012

Analysis of a nationally representative population survey (NHANES) found that kidney stone prevalence in the United States had risen significantly compared with earlier decades, with clear differences by sex and age group.

Newhouse P, Kellar K, Aisen P, White H, Wesnes K, Coderre E, Pfaff A, Wilkins H, Howard D, Levin ED · Neurology · 2012

A randomized, double-blind, placebo-controlled trial in 74 non-smokers with mild cognitive impairment (amnestic MCI), using a transdermal nicotine patch (15 mg/day) or placebo for 6 months. The nicotine group showed significant improvement in attention (primary endpoint, Conners' Continuous Performance Test), memory and psychomotor speed versus placebo, with good safety and tolerability — no serious adverse events and no withdrawal syndrome after the trial ended.

Chevalier G, Sinatra ST, Oschman JL, Sokal K, Sokal P · Journal of Environmental and Public Health · 2012

A broad narrative review summarizing then-available pilot studies on grounding (sleep, pain, cortisol levels, blood clotting parameters), authored by a team with strong ties to the commercial promotion of the practice — the lead author is affiliated with Earth FX Inc., a maker of grounding accessories. The review describes promising but methodologically preliminary small-study results, not independently replicated clinical evidence.

Jones CD, Loehr L, Franceschini N, Rosamond WD, Chang PP, Shahar E, Couper DJ, Rose KM · Hypertension · 2012

An analysis of 12,363 people free of heart failure at baseline in the American ARIC study, with a mean follow-up of about 17.5 years. Orthostatic hypotension was linked to a significantly higher risk of developing heart failure (HR 1.54; 95% CI 1.30–1.82), with a stronger association in people aged 55 or younger (HR 1.90) than in those over 55 (HR 1.37; interaction p=0.034), and the association held after excluding people with diabetes, coronary disease, or those taking blood-pressure, psychiatric, or Parkinson's disease medications.

Valent P, Akin C, Arock M, Brockow K, Butterfield JH, Carter MC, Castells M, Escribano L, Hartmann K, Lieberman P, Nedoszytko B, Orfao A, Schwartz LB, Sotlar K, Sperr WR, Triggiani M, Valenta R, Horny HP, Metcalfe DD · International Archives of Allergy and Immunology · 2012

The consensus classification of mast cell disorders (the "consensus-1" / Vienna criteria), which refines the three-part MCAS diagnostic criteria and clearly distinguishes the syndrome from mastocytosis — still the most frequently cited, stricter diagnostic criteria in this field.

AAGL Advancing Minimally Invasive Gynecology Worldwide · Journal of Minimally Invasive Gynecology · 2012

A practice guideline naming hysteroscopic polypectomy as the primary treatment method, discouraging 'blind' polyp removal when equipment for guided removal is available, and allowing conservative management in selected patients — with spontaneous regression reaching up to 25% of cases, especially for lesions under 10 mm.

Schneider I, Kressel G, Meyer A, Krings U, Berger RG, Hahn A · Journal of Functional Foods · 2011

A 21-day study in 20 healthy adults: daily consumption of a soup made with 30 g of dried oyster mushroom significantly lowered triglycerides and oxidized LDL.

Abrams DI, et al. · BMC Complementary and Alternative Medicine · 2011

An 8-week study with supplementation of 15 g of freeze-dried oyster mushroom daily showed a significant drop in triglycerides.

Alam N, Yoon KN, Lee JS, Cho HJ, Shim MJ, Lee TS · Saudi Journal of Biological Sciences · 2011

A 42-day rat study: fruiting body powder supplementation lowered total cholesterol, triglycerides, and LDL by 24–62%.

Zan LF, Qin JC, Zhang YM, Yao YH, Bao HY, Li X · Chemical & Pharmaceutical Bulletin · 2011

New hispidin derivatives with significant in vitro radical-scavenging activity were isolated from fruiting bodies.

Leproult R, Van Cauter E. · JAMA · 2011

Experimentally restricting sleep to 5 hours a night for 8 days lowered daytime testosterone levels by 10–15% in healthy young men.

Walle T · Annals of the New York Academy of Sciences · 2011

A classic paper describing resveratrol's pharmacokinetics in humans and explaining the mechanism behind its very low systemic bioavailability.

Mozaffarian D, Wu JHY · Journal of the American College of Cardiology · 2011

An extensive review of the mechanisms and clinical evidence regarding the effect of omega-3 fatty acids on cardiovascular risk factors and events.

Bhasin S, Pencina M, Jasuja GK i wsp. · Journal of Clinical Endocrinology & Metabolism · 2011

A study establishing reference ranges for total and free testosterone by LC-MS/MS in a sample of healthy, non-obese young men from the Framingham Heart Study, validated across three independent cohorts.

de Ronde W, de Jong FH · Reproductive Biology and Endocrinology · 2011

A review concluding that the long-term efficacy and safety of aromatase inhibitors in men has not yet been established, and that their routine use is not yet recommended — a direct, citable statement of the ongoing controversy from a review focused specifically on this drug class in men.

Settembre C, Di Malta C, Polito VA, et al. · Science · 2011

A landmark paper showing that TFEB coordinates autophagosome formation, fusion with the lysosome, and substrate degradation through a single, coherent transcriptional program regulated by nutrient availability.

Baird GS · Clinica Chimica Acta · 2011

A review of the physiology, measurement methods, and clinical significance of ionized calcium as the biologically active fraction of blood calcium.

Melmed S, Casanueva FF, Hoffman AR, Kleinberg DL, Montori VM, Schlechte JA, Wass JAH · Journal of Clinical Endocrinology & Metabolism · 2011

The Endocrine Society's clinical practice guideline on diagnosing and treating hyperprolactinemia, including an algorithm for differentiating physiological, drug-related, and structural causes.

Baglioni C, Battagliese G, Feige B, Spiegelhalder K, Nissen C, Voderholzer U, Lombardo C, Riemann D · Journal of Affective Disorders · 2011

A meta-analysis of prospective epidemiological studies showing that people with insomnia without prior depression had over twice the risk of developing depression (OR=2.60) compared to people without sleep difficulties.

ter Haar G · Interface Focus · 2011

A review of laboratory and epidemiological evidence on the safety of diagnostic ultrasound, discussing the potential thermal and mechanical effects of sound waves in the context of routine clinical use.

Magnus MC, Ping M, Shen MM, Bourgeois J, Magnus JH · Journal of Women's Health · 2011

A meta-analysis of randomized trials showing a significant reduction in breast cancer mortality from screening mammography also in the younger 39–49 age group.

Chou R, Arora B, Dana T, Fu R, Walker M, Humphrey L · Annals of Internal Medicine · 2011

An evidence review for the USPSTF assessing the value of resting and exercise ECG screening in asymptomatic adults.

Bartoli E, Fra GP, Carnevale Schianca GP · European Journal of Internal Medicine · 2011

A review of the history and contemporary significance of the oral glucose tolerance test, comparing its diagnostic value with fasting glucose alone in detecting early carbohydrate metabolism disturbances.

Zvejniece L, Svalbe B, Veinberg G, Grinberga S, Vorona M, Kalvinsh I, Dambrova M · Basic & Clinical Pharmacology & Toxicology · 2011

A mouse study comparing the R and S enantiomers of phenotropil found that memory improvement in the passive avoidance test occurred only with the R-enantiomer (already at a 1 mg/kg dose), while the S-enantiomer showed no activity in this test despite comparable brain concentrations — both enantiomers showed antidepressant-like and locomotor-increasing activity, though at different doses.

Samotrueva MA, et al. · Bulletin of Experimental Biology and Medicine · 2011

A study in rats with lipopolysaccharide-induced immune stress found that phenotropil prevented some of the behavioral changes (reduced locomotor activity, increased anxiety) associated with immune stress — a study in rodents in a specific immune-stress model, not a study of cognitive effects in healthy animals or humans.

Freeman R, Wieling W, Axelrod FB, et al. · Clinical Autonomic Research · 2011

The official consensus statement from the American Autonomic Society and American Academy of Neurology, establishing the criterion still used today for diagnosing orthostatic hypotension: a fall in systolic pressure of at least 20 mmHg and/or diastolic pressure of at least 10 mmHg within 3 minutes of standing or head-up tilt to at least 60 degrees. The document also defines related syndromes — neurally mediated syncope and postural orthostatic tachycardia syndrome (POTS) — and remains the reference point for all subsequent clinical research in this area.

Nagano M, et al. · Biomedical Research · 2010

A small study in women showing reduced anxiety and depressive symptoms after 4 weeks of eating cookies containing Lion's Mane.

Chen S, Li Z, Krochmal R, Abrazado M, Kim W, Cooper CB. · Journal of Alternative and Complementary Medicine · 2010

A 12-week RCT in 20 healthy older adults using fermented mycelium (Cs-4 strain, not the wild fruiting body) — improvement in metabolic and ventilatory threshold, but no significant change in VO2max versus placebo.

Wu FC, Tajar A, Beynon JM, et al. · New England Journal of Medicine · 2010

A large European cohort study (EMAS) establishing criteria for diagnosing late-onset hypogonadism based on the co-occurrence of low testosterone and specific sexual symptoms.

Geng J, Dong J, Ni H, et al. · Cochrane Database of Systematic Reviews · 2010

A Cochrane systematic review assessing ginseng's effect on cognitive function — results promising but methodologically heterogeneous.

Cholesterol Treatment Trialists' (CTT) Collaboration · The Lancet · 2010

A meta-analysis of 26 randomized trials showing that statin-driven LDL reduction translates into a proportional reduction in the risk of major cardiovascular events.

Panossian A, Wikman G · Pharmaceuticals · 2010

A comprehensive review of the mechanisms of action of classic adaptogens, including eleuthero, in the context of the response to physical and mental stress.

Seiler S · International Journal of Sports Physiology and Performance · 2010

A review of training-intensity distribution models in elite endurance athletes, pointing to the dominance of low-intensity training in their programs.

Wu FCW, Tajar A, Beynon JM, et al. · New England Journal of Medicine · 2010

A population-based survey of 3,369 men aged 40-79 across eight European centers (the European Male Ageing Study) found that only a cluster of three sexual symptoms showed a genuine syndromic association with declining androgens, and that association became statistically robust specifically when combined with both a total testosterone below roughly 11 nmol/L and a free testosterone below roughly 220 pmol/L — the basis for a widely used research definition of late-onset hypogonadism.

Stanczyk FZ, Jurow J, Hsing AW · Cancer Epidemiology, Biomarkers & Prevention · 2010

An analysis showing that direct estradiol immunoassays without a sample purification step are insufficiently sensitive and specific for reliable measurement in men and postmenopausal women, due to antibody cross-reactivity with numerous steroid metabolites present in the blood.

Wang C, Harnett M, Dobs AS, Swerdloff RS · Journal of Andrology · 2010

An 84-week phase III trial of testosterone undecanoate given every 10 weeks after loading doses. Steady state was reached after the third injection; at that point, 94% of men maintained an average testosterone concentration within normal range across the third dosing interval, with small peak-trough swings characteristic of this ester's very long half-life.

Cappuccio FP, D'Elia L, Strazzullo P, Miller MA · Sleep · 2010

A meta-analysis of 16 studies (27 cohorts, 1,382,999 participants, 112,566 deaths) found that both short (RR=1.12) and long (RR=1.30) sleep were linked to significantly higher death risk compared to moderate sleep duration — one of the first large papers confirming a U/J-shaped relationship for this topic.

Wang C, Harnett M, Dobs AS, Swerdloff RS · Journal of Andrology · 2010

In 130 hypogonadal men, 750mg of testosterone undecanoate given at weeks 0 and 4, then every 10 weeks for 84 weeks, kept trough testosterone within 300–1000 ng/dL (10.4–34.7 nmol/L) from the first injection onward, with stable DHT, estradiol and their ratios to testosterone at steady state. The trial used the 750mg/3mL dose (the formulation registered in the US as Aveed), not the European 1000mg/4mL dose.

Herzog AG, Farina EL, Drislane FW, et al. · Epilepsy & Behavior · 2010

Sexual function normalized in 72.2% of the anastrozole+testosterone group versus 47.4% on testosterone alone; sexual-function scores correlated inversely with estradiol levels. A positive finding for anastrozole, directly contradicting the null results of the two studies above — conducted in a specific population of men with epilepsy, an additional limitation on generalizability.

Ceriotti F, Henny J, Queraltó J, et al. · Clinical Chemistry and Laboratory Medicine · 2010

An international IFCC multicenter study establishing common reference intervals for ALT, AST, and GGT, accounting for differences between populations and sexes.

Sack RL · The New England Journal of Medicine · 2010

A clinical review describing the mechanism of jet lag as a mismatch between the internal circadian clock, driven by the suprachiasmatic nucleus, and the new light-dark cycle, along with evidence-based clock-resetting strategies — light exposure and melatonin.

Matsushita K, van der Velde M, Astor BC, et al. (Chronic Kidney Disease Prognosis Consortium) · The Lancet · 2010

A collaborative meta-analysis of individual participant data from 21 general-population cohorts (over one million people) found that both reduced eGFR and elevated albuminuria are independently associated with increased risk of death from any cause and cardiovascular death.

Donga E, van Dijk M, van Dijk JG, et al. · Journal of Clinical Endocrinology & Metabolism · 2010

An experimental study showing that just one night of restricted sleep significantly lowers insulin sensitivity in healthy, lean people, independent of body weight.

Van Vranken M · American Family Physician · 2010

A review of the practical approach to diagnosing microcytosis, including differentiating mild iron deficiency from alpha- and beta-thalassemia trait with normal or near-normal hemoglobin.

Heishman SJ, Kleykamp BA, Singleton EG · Psychopharmacology · 2010

A meta-analysis of 41 placebo-controlled studies (1994–2008) in healthy adults who were non-smokers or minimally nicotine-deprived (≤2h) found significant, positive effects on six domains: fine motor control, alerting attention (accuracy and reaction time), orienting attention (reaction time), short-term episodic memory (accuracy), and working memory (reaction time), with effect sizes ranging from 0.16 to 0.44. The authors note these effects aren't explained by withdrawal relief alone, since the study population wasn't meaningfully nicotine-deprived.

Fedorowski A, Stavenow L, Hedblad B, Berglund G, Nilsson PM, Melander O · European Heart Journal · 2010

A prospective Swedish cohort study of more than 33,000 people (mean age 45.7) with a mean follow-up of 22.7 years. Orthostatic hypotension occurred in 6.2% of participants. A systolic drop of at least 30 mmHg was linked to significantly higher all-cause mortality (HR 1.6; 95% CI 1.3–1.9) and coronary event risk (HR 1.6; 95% CI 1.2–2.1), independent of classic cardiovascular risk factors; a slightly weaker association was seen with a diastolic drop of at least 15 mmHg.

Akin C, Valent P, Metcalfe DD · Journal of Allergy and Clinical Immunology · 2010

The first formal proposal of MCAS diagnostic criteria as a basis for further validation studies: the authors note the prior absence of a generally accepted definition and propose a requirement of typical symptoms, a documented mast cell mediator rise, and a response to targeted treatment.

Piscitelli CM, Dunayer EK, Aumann M · Compendium: Continuing Education for Veterinary Medicine · 2010

A veterinary review describing the mechanism and course of xylitol poisoning in dogs: doses above 0.1 g/kg body weight carry a risk of hypoglycemia, and above 0.5 g/kg a risk of acute liver failure. Prognosis is good for uncomplicated hypoglycemia but guarded to poor for severe liver damage.

Lee SC, Kaunitz AM, Sanchez-Ramos L, Rhatigan RM · Obstetrics & Gynecology · 2010

A meta-analysis of 17 studies covering 10,572 women who underwent polypectomy. Neoplasia (malignant or premalignant change) was found in 5.4% of polyps in postmenopausal women versus 1.7% premenopausally (relative risk about 3.9). Abnormal bleeding was associated with neoplasia at 4.2% versus 2.2% without bleeding, but the effects of menopausal status and bleeding weren't additive. Polyp size, in the pooled data, showed no clear link to malignancy risk.

Olsson EM, von Schéele B, Panossian AG. · Planta Medica · 2009

An RCT (n=60) showing improvement in stress-related fatigue symptoms after 28 days of supplementation.

Mori K, Inatomi S, Ouchi K, Azumi Y, Tuchida T · Phytotherapy Research · 2009

A small study (n=30) in older adults with mild cognitive impairment showing improved test scores after 16 weeks — the effect faded after discontinuation.

Deng G, Lin H, Seidman A, Fornier M, D'Andrea G, Wesa K, Yeung S, Cunningham-Rundles S, Vickers AJ, Cassileth B · Journal of Cancer Research and Clinical Oncology · 2009

A dose-escalation phase I/II trial in 34 breast cancer survivors found a complex, nonlinear dose-response relationship in select immune parameters after oral maitake extract, with a good safety profile.

Chida Y, Steptoe A. · Biological Psychology · 2009

A systematic review describing the relationship between psychosocial stress levels and the cortisol response after waking.

Frassetto LA, Schloetter M, Mietus-Synder M, et al. · European Journal of Clinical Nutrition · 2009

A very small pilot study (n=9) showing short-term improvement in lipid profile and blood pressure after switching to a paleolithic diet.

Chan GC, Chan WK, Sze DM · Journal of Hematology & Oncology · 2009

A review of the mechanisms by which beta-glucans activate immune cells, including macrophages and NK cells, via the dectin-1 receptor.

Ophir E, Nass C, Wagner AD · Proceedings of the National Academy of Sciences · 2009

A study showing that people who regularly practice media multitasking perform worse on tests requiring filtering out irrelevant information and switching tasks.