Reviewed by the LongevityMap editorial team

Scientific Evidence byLongevity Treatment

The most comprehensive reference source in Spanish. Oxford CEBM evidence levels, key studies, mechanisms of action and regulatory status for the 27 most in-demand treatments in Spain.

27

Treatments analyzed

1964

Human RCTs included

Oxford CEBM

Classification system

Jan 2026

Last updated

Oxford CEBM Evidence Scale (2011)

Level 3 — Emerging evidence

Case-control studies or non-randomized studies

Level 4 — Preliminary evidence

Case series, low-quality cohort studies

Level 5 — Expert opinion

Expert opinion without explicit critical appraisal

Level 1a — Highest evidence

Systematic review of homogeneous randomized controlled trials (RCTs)

Level 1b — High evidence

Individual RCT with narrow confidence interval

Level 2a — Moderate-high evidence

Systematic review of homogeneous cohort studies

Level 2b — Moderate evidence

Individual cohort study or low-quality RCT

Methodological note: The evidence level indicates the quality of available studies for the treatment’s most studied indication, not for all its indications. A treatment with level 2b may have level 1b for some specific indications.

Oxygen Therapies

Hyperbaric Chamber (HBOT)

Level 1bMechanism alto68 human RCTs
Full guide

Strong evidence for classic medical indications (chronic wounds, decompression injuries, CO poisoning). Emerging but promising evidence in longevity and neurology.

What science confirms

  • FDA-approved for 14 medical indications (diabetic wounds, CO poisoning, etc.)
  • Increases dissolved O2 concentration in plasma by 10-15x at 2 ATA
  • Reduces senescent T cells and lengthens telomeres (Shamir 2020 study)
  • Activates angiogenesis and neurogenesis via VEGF and BDNF

What we still don’t know

  • Optimal dosing for longevity (pressure, frequency, number of sessions)
  • Differential benefit of 1.5 vs 2.0 vs 3.0 ATA chambers for different indications
  • Long-term efficacy (>12 months post-protocol) without follow-up data

Key studies

Effects of Hyperbaric Oxygen Therapy on Exercise-Induced Muscle Injury and Soreness: A Systematic Review and Meta-analysis

Archives of Physical Medicine and Rehabilitation (2026)

2026 SR/MA: HBOT statistically effective for recovery from exercise-induced muscle injury, but does NOT enhance recovery from delayed-onset muscle soreness (DOMS).

PubMed

Hyperbaric Oxygen Therapy for Chronic Venous Leg Ulcers: A Prospective Randomised Controlled Trial

International Wound Journal (2026)

2026 RCT (n=80, refractory chronic venous leg ulcers): adjunctive HBOT (20 sessions at 2.4 ATA) achieved 90-day complete healing in 62.5% vs 30.0% with standard care alone (NNT=3). Pain ↓ ΔVAS -5.0 vs -1.5.

PubMed

Effect of normobaric and hyperbaric hyperoxia treatment on symptoms and cognitive capacities in Long COVID patients: a randomised placebo-controlled trial

Diving and Hyperbaric Medicine (2025)

2025 placebo RCT (Long COVID): NEITHER normobaric NOR hyperbaric hyperoxia showed significant differences vs placebo in symptoms, functional scores or cognitive performance. Highly variable response, including in placebo group.

PubMed

Hyperbaric oxygen therapy for osteoporosis: A systematic review of preclinical evidence and mechanisms

Bone (2026)

2026 SR (6 preclinical rat studies): HBOT improves bone mineral density, trabecular microarchitecture and biomechanics via OPG/RANKL, Wnt/β-catenin and TNF-α reduction. Rigorous human studies pending.

PubMed

Regulatory status

FDA-approved (14 indications), AEMPS (Spain) approved for medical indications. Use in longevity is considered 'off-label'.

Ozone Therapy

Level 2bMechanism moderado38 human RCTs
Full guide

Moderate evidence in chronic pain, infections, and wounds. Nrf2 mechanism and hormetic oxidative stress well understood. Limited evidence specific to longevity.

What science confirms

  • Activation of Nrf2 factor and endogenous antioxidant response (hormetic effect)
  • Improved tissue oxygenation through increased erythrocyte 2,3-DPG
  • Virus and bacteria inactivation demonstrated in vitro and in vivo
  • Evidence in chronic low back pain, disc herniation, and arthritis

What we still don’t know

  • Optimal ozone concentration for different indications (range 10-80 mcg/ml)
  • Superiority of major autohemotherapy vs rectal insufflation for systemic indications
  • Direct effects on epigenetic longevity markers

Key studies

Ozone injections reduce pain in knee osteoarthritis: a systematic review and meta-analysis

Medical Gas Research (2026)

SR/MA 7 RCTs (n=409 knee OA): intra-articular ozone injections more effective than corticosteroids at reducing pain in the short and medium term, with comparable functional improvement. Methodological quality limited.

PubMed

A pilot randomized controlled trial of major ozone autohemotherapy for patients with post-acute sequelae of COVID-19

International Immunopharmacology (2024)

Pilot RCT 2024 (n=73, post-acute COVID-19 sequelae): major ozone autohemotherapy + conventional treatment achieved 71% response vs 45% with conventional alone. Improved symptoms, pulmonary function (6MWD), inflammation and cellular immunity.

PubMed

Efficacy of ozone therapy for oral mucosa wound healing: a systematic review and meta-analysis

Clinical Oral Investigations (2024)

SR/MA 12 studies: ozone therapy reduces the size of traumatic and autoimmune oral ulcers vs placebo (RR -0.44) and reduces pain more than placebo, equivalent to topical corticosteroid. Quality of evidence limited.

PubMed

Ozone therapy as an adjunctive strategy for MRONJ in oncology patients: A systematic review and meta-analysis

Supportive Care in Cancer (2025)

SR/MA 6 studies (n=178 medication-related osteonecrosis of the jaw in oncology): adjunctive ozone therapy achieved 71% clinical success rate (95% CI 55-84%) with no adverse events. Very low certainty of evidence; standardised RCTs pending.

PubMed

Regulatory status

Recognized as medical practice in Italy, Spain, Germany, and other European countries. Spanish Association of Medical Professionals in Ozone Therapy (AEPROMO) establishes practice guidelines.

Regenerative Medicine

PRP (Platelet-Rich Plasma)

Level 1bMechanism alto312 human RCTs
Full guide

Over 10,000 published studies. Meta-analyses demonstrate superiority over hyaluronic acid in knee osteoarthritis at 12 months. Consolidated evidence in androgenetic alopecia.

What science confirms

  • Growth factors (PDGF, TGF-beta, VEGF, EGF) stimulate cell proliferation and angiogenesis
  • Efficacy demonstrated in knee osteoarthritis (OARSI 2022), alopecia, and wound healing
  • Excellent safety profile: autologous, no risk of rejection
  • Platelet concentration >=5x is essential for clinical efficacy

What we still don’t know

  • Optimal activation protocol (thrombin, calcium, UV light)
  • Superiority of leukocyte-rich PRP (L-PRP) vs leukocyte-poor PRP (P-PRP) by indication
  • Optimal number of sessions for different indications

Key studies

Platelet-Rich Plasma Is More Effective Than Hyaluronic Acid Injections for Osteoarthritis of the Knee: A Meta-analysis Based on Randomized, Double-Blinded, Controlled Clinical Trials

Arthroscopy (2025)

Meta-analysis 15 double-blind RCTs (n=1,632 knee OA patients): intra-articular PRP significantly superior to hyaluronic acid in pain reduction (WOMAC, VAS) at 12 months, reaching the minimal clinically important difference.

PubMed

Comparative Efficacy and Safety of Platelet Rich Plasma (PRP) versus Topical Minoxidil for Androgenetic Alopecia: A Systematic Review and Meta-analysis

Aesthetic Plastic Surgery (2026)

SR/MA 9 RCTs (n=451, androgenetic alopecia): PRP showed no clear advantage over 5% minoxidil in hair density, but higher patient satisfaction (OR 2.77) and better negative pull-test results (82.75% vs 52.94%).

PubMed

Efficacy of platelet-rich plasma as a conservative and surgical adjuvant treatment for chronic midportion Achilles tendinopathy: a systematic review and meta-analysis

The Physician and Sportsmedicine (2026)

SR/MA 8 studies (n=507, chronic Achilles tendinopathy): PRP provides only short-term functional improvement (VISA-A); no significant long-term benefit nor as a surgical adjunct. Standardised protocols needed.

PubMed

Effects of percutaneous platelet-rich plasma injection on return-to-play after acute hamstring muscle injury: a systematic review and meta-analysis

British Journal of Sports Medicine (2026)

SR/MA 6 RCTs (n=277, acute hamstring injury): percutaneous PRP reduced return-to-play time by 8.6 days (21.4 vs 30.0; p=0.045), especially when image-guided. No differences in re-injury or adverse events.

PubMed

Regulatory status

Medical use widely accepted. Not classified as a drug (autologous product). Regulated as a medical procedure.

Exosome Therapy

Level 3Mechanism moderado8 human RCTs
Full guide

Biological mechanism well understood. Clinical evidence in emerging phase (phase 1-2 trials). Enormous promise but still lacking high-quality RCTs in longevity.

What science confirms

  • Exosomes contain miRNA, bioactive proteins, and growth factors that modulate gene expression in recipient cells
  • Ability to reverse cellular senescence markers demonstrated in vitro
  • Excellent safety profile in all published phase 1 trials
  • Superior biodistribution vs whole stem cells (smaller size, no tumor formation)

What we still don’t know

  • Effective dose (particle concentration/ml and number of sessions)
  • Optimal source of donor stem cells (umbilical cord MSC vs adipose tissue vs bone marrow)
  • Standardization of product quality (enormous variability between manufacturers)
  • Comparative efficacy with PRP in shared indications (head-to-head RCTs lacking)

Key studies

Mechanistic Insights into the Cardioprotective Effects of Mesenchymal Stem Cell-Derived Exosomes in Myocardial Ischemic Injury: A Systematic Review

Pharmaceutics (2026)

Pharmaceutics 2026 SR: MSC-derived exosomes are a promising cell-free nanotherapeutic strategy for cardiac repair after MI and ischemia/reperfusion. Modulate cardiomyocyte apoptosis, inflammation, mitochondrial function, oxidative stress and angiogenesis. Predominantly preclinical evidence.

PubMed

Regenerative and Stem Cell-Based Therapies for Arthritis: Harnessing Mesenchymal Stem Cells, Exosomes, and Bioengineered Scaffolds for Functional Joint Restoration

Stem Cell Reviews and Reports (2026)

Stem Cell Reviews 2026: review on MSC, exosomes and bioengineered scaffolds for osteoarthritis and rheumatoid arthritis. Regenerative strategies beyond symptomatic treatment, with immunomodulatory and paracrine effects for cartilage restoration.

PubMed

Biologically Distinct, Clinically Convergent: A Comparative Study of Umbilical Cord- and Adipose-Derived Mesenchymal Stem Cell Exosomes in Human Skin

Aesthetic Surgery Journal (2026)

Aesthetic Surgery Journal 2026: comparative study of umbilical cord (UC)- vs adipose-derived (AD) MSC exosomes in human skin. Biologically distinct but clinically convergent in their effects on skin.

PubMed

Evaluation of Hypoxia-Conditioned MSC Exosomes' Effects on GM-CSF and IL-1α Expression in a Rat Model of Androgenic Alopecia

Medeniyet Medical Journal (2026)

2026 rat study (androgenic alopecia model): hypoxia-conditioned MSC exosomes (EH-MSC) modulate cytokines: ↑ GM-CSF (regenerative effect) and ↓ IL-1α (anti-inflammatory) dose-dependent. Minoxidil did NOT reduce IL-1α. Preclinical evidence.

PubMed

Regulatory status

Under regulatory review. In Spain, classified as Advanced Therapy Medicinal Products (ATMP) in process. Current use under prescribing physician's responsibility.

Mesenchymal Stem Cells (MSC)

Level 3Mechanism moderado22 human RCTs
Full guide

Solid scientific basis. Phase 1-2 clinical trials in multiple indications. No approval for general longevity. Market with enormous quality variability.

What science confirms

  • MSCs secrete anti-inflammatory, regenerative, and immunomodulatory paracrine factors
  • Safety demonstrated in phase 1 trials for multiple indications
  • Approved in Europe for graft-versus-host disease (Alofisel for Crohn's perianal fistula)
  • Anti-senescence activity demonstrated in aging models

What we still don’t know

  • Efficacy in general longevity without a specific medical indication
  • Optimal cell source (umbilical cord vs adipose tissue vs bone marrow)
  • Optimal dose, route of administration, and frequency
  • Theoretical risk of tumor stimulation in patients with occult cancer

Key studies

Efficacy and safety of intra-articular mesenchymal stem cell-based therapies in knee osteoarthritis: A systematic review and meta-analysis of randomized controlled trials

Clinical Rheumatology (2026)

SR/MA 28 RCTs (knee OA): intra-articular MSC significantly improved pain (VAS, KOOS) and function (KOOS ADL/sports/symptoms) vs control. No structural changes on MRI (WORMS); effect is primarily symptomatic.

PubMed

The efficacy and safety of MSCs in GVHD prevention and the treatment of SR-aGVHD: a systematic review and meta-analysis of randomized controlled trials

Stem Cell Research & Therapy (2026)

SR/MA 15 RCTs: MSC reduce acute (OR 0.47) and chronic (OR 0.50) graft-versus-host disease incidence after hematopoietic stem cell transplantation and improve response in steroid-refractory acute GVHD (OR 1.50).

PubMed

Efficacy and safety of single versus repeated injections of mesenchymal stem cells for the treatment of knee osteoarthritis: a systematic review and network meta-analysis of randomized controlled trials

Stem Cell Research & Therapy (2025)

SR + Network MA 16 RCTs (n=622 knee OA): repeated MSC injections provide greater pain and function improvement at 6-12 months than single dose, but with higher adverse event incidence. Risk/benefit must be weighed.

PubMed

Injection of human umbilical cord mesenchymal stem cells exosomes for the treatment of knee osteoarthritis: from preclinical to clinical research

Journal of Translational Medicine (2025)

2025 translational study: umbilical cord MSC exosomes (hUC-MSC-Exos) reduced joint inflammation and promoted cartilage regeneration in preclinical models. Randomised dose-ascending clinical trial confirmed safety and preliminary efficacy in OA patients.

PubMed

Regulatory status

Classified as Advanced Therapy Medicinal Products (ATMP) in the EU. Require AEMPS authorization for production and use. Off-label use in many private clinics — verify authorization.

Bioactive Peptides

Level 3Mechanism moderado12 human RCTs
Full guide

Bioactive peptides (BPC-157, Epithalon, Thymosin alpha-1, TB-500) represent one of the most active frontiers in longevity medicine. Extraordinary preclinical evidence; limited but growing human trials. Growing popularity among functional medicine physicians.

What science confirms

  • Thymosin alpha-1 is approved in >35 countries for immunodeficiencies and chronic hepatitis B/C
  • BPC-157 demonstrated accelerated healing of tendons, muscle, and gastric mucosa in multiple rodent studies
  • Epithalon activates telomerase in vitro and in vivo in animal models
  • TB-500 (Thymosin beta-4) improves stem cell mobilization and angiogenesis in cardiac injury (animal models)

What we still don’t know

  • Efficacy and safety in humans for most peptides (lack of high-quality RCTs)
  • Bioavailability and half-life after subcutaneous injection vs IV
  • Interactions between peptides when combined in 'stacks'
  • Theoretical oncogenic risk of pro-proliferative peptides in users with occult cancer

Key studies

Therapeutic peptides in gerontology: mechanisms and applications for healthy aging

Frontiers in Aging (2026)

Frontiers in Aging 2026: review of 9 peptides for healthy aging — metabolic restoration (tirzepatide), telomere (epitalon), dermal regeneration (GHK-Cu), tissue repair (BPC-157, TB-500), neuroprotection (Semax), GH modulation (CJC-1295, ipamorelin), sexual function (bremelanotide). FDA-approved with robust safety; non-approved show promising preclinical but limited human evidence.

PubMed

Safety and Efficacy of Approved and Unapproved Peptide Therapies for Musculoskeletal Injuries and Athletic Performance

Sports Medicine (2026)

Sports Medicine 2026: review of approved (tesamorelin) and unapproved (BPC-157, GHK-Cu, MOTS-C, TB-500) peptides for musculoskeletal injuries and athletic performance. Many unapproved peptides show favourable tissue repair in animal models, but rigorous human safety data are scarce. Potential for serious harm.

PubMed

From Regeneration to Analgesia: The Role of BPC-157 in Tissue Repair and Pain Management

International Journal of Molecular Sciences (2026)

2026 BPC-157 review: shows reparative and anti-inflammatory properties in preclinical (angiogenesis, collagen synthesis, NO modulation), pain modulation via peripheral and dopaminergic mechanisms. Human research limited to small pilot studies. Controlled trials needed before clinical translation.

PubMed

Tendon, Ligament, and Muscle Injury, Osteotendinous, Myotendinous, and Muscle-to-Bone Junction Therapy Perspectives with Growth Factors and Stable Gastric Pentadecapeptide BPC 157

Pharmaceuticals (2026)

2026 SR (growth factors + BPC-157 in musculoskeletal and junctional injuries): BPC-157 systemic or local, without scaffolds, demonstrated consistent efficacy in tendon, ligament, muscle and osteotendinous/myotendinous junctions in rat studies. Human clinical validation pending.

PubMed

Regulatory status

Most are not approved as medications in Spain/EU (except Thymosin alpha-1 in some countries). Frequently obtained as 'research' or through specialized compounding pharmacies. Use under sole responsibility of the prescribing physician.

Plasmapheresis / Young Plasma Exchange

Level 3Mechanism moderado7 human RCTs
Full guide

Classic plasmapheresis has decades of evidence in autoimmunity. The use in longevity ('young plasma' and aged plasma dilution) is the most disruptive frontier: the Conboy study (2022) in Nature Aging suggests that dilution of aged plasma can rejuvenate tissues independently of young plasma.

What science confirms

  • Therapeutic plasmapheresis is the standard of care for myasthenia gravis, Guillain-Barre, TTP, and other autoimmune conditions
  • Heterochronic parabiosis in animals demonstrates that the systemic plasma environment regulates tissue aging
  • Inhibitory aging factors (TGF-beta-1, CCL11, beta-2-microglobulin) increase with age in human plasma
  • The AMBAR trial shows that plasma exchange slows Alzheimer's progression

What we still don’t know

  • Whether the benefit comes from added young plasma or from removal of old plasma (Conboy 2022 suggests the latter)
  • Optimal protocol: frequency, exchange volume, need for albumin vs saline
  • Safety of repeated use in healthy individuals (without classic medical indication)
  • Regulation of access to young donor plasma (very complex ethical and logistical context)

Key studies

Plasma-based strategies for systemic rejuvenation: critical perspectives on clinical translation

GeroScience (2026)

2026 GeroScience (critical review): clinical translation of heterochronic plasma transfer for human systemic rejuvenation remains UNCERTAIN despite promising preclinical evidence (parabiosis, modulation of neuroinflammation/cognition). Critical of available human studies.

PubMed

Blood as the mirror and modulator of aging: mechanistic insights and rejuvenation strategies

Experimental & Molecular Medicine (2026)

2026 Exp Mol Med: blood as mirror and modulator of aging. Multi-omics (proteomics, metabolomics, single-cell immunomics) show circulating components predict healthspan, longevity and disease risk. Blood components may modulate aging tempo.

PubMed

Modulating Systemic Immune-Inflammatory Indices via Double Filtration Plasmapheresis: Implications for Aging and Low-Grade Inflammation

Hormone and Metabolic Research (2025)

2025 retrospective analysis: double filtration plasmapheresis (2 sessions for hypercholesterolemia/hyperlipoproteinemia(a)) modulates systemic immune-inflammatory indices derived from routine CBC. Implications for aging and low-grade inflammation.

PubMed

Confronting medical grifting: Fraudulent and unproven products and interventions in apheresis, transfusion and biotherapies

British Journal of Haematology (2025)

2025 Br J Haematol: critical review explicitly identifying 'therapeutic plasma exchange for longevity' as unfounded intervention causing medical waste and patient harm. Framework to distinguish legitimate care from commercial claims.

PubMed

Regulatory status

Plasmapheresis for established medical indications is regulated as an apheresis procedure (AEMPS, Blood Bank). Specific use in longevity has no regulatory authorization. The FDA issued a warning in 2019 against commercial 'young plasma' use outside clinical trials.

IV Therapies

Intravenous NAD+

Level 2bMechanism alto14 human RCTs
Full guide

Solid preclinical evidence (mice). Promising human trials with oral precursors. Direct IV evidence in humans limited but growing. Sirtuin/PARP mechanism very well documented.

What science confirms

  • NAD+ is a cofactor in over 500 cellular enzymatic reactions
  • 50% decline in NAD+ between ages 40-70 in human tissues
  • NMN/NR supplementation raises blood NAD+ (evidence in humans)
  • Sirtuin activation (SIRT1-7) and improved mitochondrial metabolism demonstrated in animal models

What we still don’t know

  • Superiority of IV route vs oral precursors (NMN/NR) in humans
  • Optimal IV dosing for different objectives
  • Long-term effects on mortality in humans (no studies exist)
  • Safety in oncological context (NAD+ may nourish tumor cells)

Key studies

NAD+ supplementation for anti-aging and wellness: A PRISMA-guided systematic review of preclinical and clinical evidence

Ageing Research Reviews (2026)

PRISMA systematic review 2026 (113 studies, 33 in humans): oral NAD+ precursors (NR, NMN) show biochemical engagement and good tolerance; however, clinical efficacy for anti-aging remains inconclusive and no controlled trials of intravenous NAD+ for anti-aging indications exist.

PubMed

Safety and efficacy of individualised exercise and NAD+ precursor supplementation in patients with Friedreich's ataxia in the USA: a single-centre, 2 × 2 factorial, randomised controlled trial

The Lancet Neurology (2026)

Phase 2 RCT Lancet Neurology 2026 (n=66, Friedreich's ataxia): 12 weeks of nicotinamide riboside + individualised exercise significantly improved cardiopulmonary fitness (peak VO2) vs control. Combination was safe and well tolerated.

PubMed

Anti-inflammatory effects of nicotinamide mononucleotide (NMN) in human skeletal muscle after BFR-exercise

Journal of the International Society of Sports Nutrition (2026)

2026 crossover RCT (n=11 untrained men): oral NMN (1,200 mg/d × 7 d) suppressed muscle inflammatory signaling (TNF-α, IL-10 mRNA) after blood-flow-restriction exercise, though it also attenuated mitochondrial replenishment.

PubMed

Double-Pronged NAD Preservation: Delaying Cellular Senescence and Initiating Musculoskeletal Regeneration

Aging Cell (2026)

Aging Cell 2026 (mouse model): NMN + apigenin formulation increased NAD+ reserves, alleviated cellular senescence and promoted cartilage, bone and muscle regeneration in aged mice. Preclinical evidence with translational potential.

PubMed

Regulatory status

IV NAD+ is not approved as a medication in Spain. Used as a compounded or individualized preparation under medical prescription.

High-Dose IV Vitamin C

Level 2bMechanism alto43 human RCTs
Full guide

Strong evidence in severe infection and chronic fatigue. Promising evidence in integrative oncology (selective pro-oxidant). Limited evidence in pure longevity.

What science confirms

  • At IV doses >10g: plasma levels 100x higher than oral route (Levine et al., NIH)
  • Essential cofactor for collagen synthesis (proline and lysine hydroxylation)
  • Selective pro-oxidant effect on tumor cells at doses >=25g IV (in vitro and in vivo)
  • Safety demonstrated even at very high doses (50-75g) with prior G6PD testing

What we still don’t know

  • Real benefit of IV vs liposomal oral at doses below 10g
  • Optimal protocol in integrative oncology (dose, frequency, combinations)
  • Direct effects on epigenetic longevity markers

Key studies

Clinical benefits and risks of high-dose intravenous vitamin C: a systematic review

Journal of Medicine and Life (2026)

PRISMA systematic review 2026: high-dose intravenous vitamin C shows benefits in oncology (quality of life, survival in phase II pancreatic RCT) and antioxidant/immunomodulatory mechanisms. NOT supported for routine use in sepsis. Risks: oxalate nephropathy and hemolysis in G6PD deficiency; pre-screening mandatory.

PubMed

Intravenous nutrient therapy: the 'Myers' cocktail'

Alternative Medicine Review (2002)

Gaby 2002 review (15,000 patients): the Myers cocktail (magnesium + calcium + B vitamins + IV vitamin C) shows clinical effectiveness in acute asthma, migraine, chronic fatigue, fibromyalgia, muscle spasm, chronic sinusitis and respiratory infections. Observational clinical evidence, not randomised.

PubMed

Effect of intravenous vitamin C administration on chemotherapy-induced adverse events in patients with nasopharyngeal cancer

PLOS ONE (2026)

2026 double-blind placebo RCT (nasopharyngeal cancer + chemoradiation): IV vitamin C 2 g pre-chemo did NOT reduce GI toxicities vs placebo, but significantly attenuated platelet count decline. Potential hematologic supportive effect.

PubMed

Intravenous vitamin C for bleeding control in elective C-sections: a randomized clinical trial study

Annals of Medicine and Surgery (2026)

2026 RCT (elective C-sections): IV vitamin C reduced intraoperative gauze use by 30%, sponges by 31% and suction volume by 13% (all p<0.001), with 31% fewer uterotonic requirements (p=0.003).

PubMed

Regulatory status

IV vitamin C available as a compounded preparation in Spain under medical prescription. G6PD testing mandatory before first infusion.

IV Therapy (Myers' Cocktail)

Level 2bMechanism moderado31 human RCTs
Full guide

The Myers' Cocktail is the most widely administered IV treatment in wellness clinics worldwide. Limited direct evidence as a 'cocktail', but strong for its individual components (magnesium, B vitamins, vitamin C). Ideal for rehydration, fatigue, and performance.

What science confirms

  • IV bioavailability is 100% vs 50-60% of the oral route for magnesium and B vitamins
  • IV magnesium reduces vasoconstriction, improves neuromuscular function and arterial relaxation
  • IV vitamin B12 corrects deficiency with minimal doses vs oral megadoses
  • Rapid rehydration with balanced electrolytes: documented effect in 30-60 minutes
  • Excellent safety profile with medical monitoring and adequate infusion rate

What we still don’t know

  • Benefit of the combined 'cocktail' vs individual components (lack of comparative RCTs)
  • Optimal frequency for different objectives (1/week vs 1/month vs cycles)
  • Superiority of premium formulations (added glutathione, NAD+) over standard Myers'
  • Long-term effects on longevity biomarkers (no published studies)

Key studies

Clinical benefits and risks of high-dose intravenous vitamin C: a systematic review

Journal of Medicine and Life (2026)

PRISMA systematic review 2026: high-dose intravenous vitamin C shows benefits in oncology (quality of life, survival in phase II pancreatic RCT) and antioxidant/immunomodulatory mechanisms. NOT supported for routine use in sepsis. Risks: oxalate nephropathy and hemolysis in G6PD deficiency; pre-screening mandatory.

PubMed

Intravenous nutrient therapy: the 'Myers' cocktail'

Alternative Medicine Review (2002)

Gaby 2002 review (15,000 patients): the Myers cocktail (magnesium + calcium + B vitamins + IV vitamin C) shows clinical effectiveness in acute asthma, migraine, chronic fatigue, fibromyalgia, muscle spasm, chronic sinusitis and respiratory infections. Observational clinical evidence, not randomised.

PubMed

Effect of intravenous vitamin C administration on chemotherapy-induced adverse events in patients with nasopharyngeal cancer

PLOS ONE (2026)

2026 double-blind placebo RCT (nasopharyngeal cancer + chemoradiation): IV vitamin C 2 g pre-chemo did NOT reduce GI toxicities vs placebo, but significantly attenuated platelet count decline. Potential hematologic supportive effect.

PubMed

Intravenous vitamin C for bleeding control in elective C-sections: a randomized clinical trial study

Annals of Medicine and Surgery (2026)

2026 RCT (elective C-sections): IV vitamin C reduced intraoperative gauze use by 30%, sponges by 31% and suction volume by 13% (all p<0.001), with 31% fewer uterotonic requirements (p=0.003).

PubMed

Regulatory status

Administered as an individualized compounded preparation in Spain under medical prescription. No specific drug authorization. Individual components are approved by AEMPS.

IV Chelation (EDTA / DMPS)

Level 2bMechanism moderado19 human RCTs
Full guide

The TACT study (the largest RCT in chelation: 1,708 patients) showed significant reduction in cardiovascular events in diabetics with prior MI. Strong evidence for heavy metal detoxification. Use in preventive longevity emerging but debated.

What science confirms

  • EDTA chelates divalent metals (calcium, lead, mercury, arsenic) and eliminates them renally
  • Demonstrated reduction of blood levels of lead, mercury, and other heavy metals
  • Evidence of cardiovascular benefit in diabetics post-MI (TACT study, JAMA 2013)
  • DMPS is more specific for mercury and cadmium with better renal safety profile

What we still don’t know

  • Benefit in patients without documented heavy metal burden
  • Exact mechanism of cardiovascular benefit (vascular calcium chelation? antioxidant effect?)
  • Superiority of EDTA vs DMPS by type of metal contamination
  • Renal safety with repeated high-dose protocols (requires creatinine monitoring)

Key studies

Edetate Disodium-Based Chelation for Patients With a Previous Myocardial Infarction and Diabetes: TACT2 Randomized Clinical Trial

JAMA (2024)

JAMA 2024 TACT2 RCT (n=959, post-MI + diabetes, median 48-month follow-up): edetate disodium chelation did NOT reduce the composite cardiovascular endpoint (all-cause mortality, MI, stroke, revascularization, hospitalization for unstable angina) vs placebo: 35.6% vs 35.7% (HR 0.93; 95% CI 0.76-1.16; p=0.53). Did NOT confirm positive results from TACT 2013.

PubMed

Chelation Therapy in Coronary Artery Disease: Fact or Fiction?

Cardiology in Review (2025)

Cardiology in Review 2025 ('Fact or Fiction?'): TACT (2013) showed modest CV benefits in diabetics, but TACT2 (2024) did NOT confirm efficacy in reducing CV events. Risks: renal dysfunction, electrolyte imbalances. NOT recommended as standard CAD treatment.

PubMed

Chelation Therapy in Patients With Cardiovascular Disease: A Systematic Review

Journal of the American Heart Association (2022)

J Am Heart Assoc 2022 SR: studies on EDTA in cardiovascular disease show inconsistent results; one large RCT (TACT) showed benefit while smaller studies were heterogeneous. Limited evidence quality; additional RCTs needed.

PubMed

Chelation therapy for atherosclerotic cardiovascular disease

Cochrane Database of Systematic Reviews (2020)

Cochrane SR/MA 2020 (5 studies, n=1,993): evidence on EDTA chelation in atherosclerotic cardiovascular disease is limited and of moderate-low certainty. Inconsistent results across studies on clinical events.

PubMed

Regulatory status

EDTA approved by FDA for lead poisoning. Cardiovascular use as 'off-label'. In Spain, available as compounded preparation with medical prescription. Requires renal and electrolyte monitoring.

Wellness & Recovery

Whole-Body Cryotherapy

Level 2bMechanism alto47 human RCTs
Full guide

Moderate evidence in sports recovery and acute inflammation reduction. Norepinephrine and dopamine mechanism well documented. Evidence in longevity still emerging.

What science confirms

  • Documented increase in norepinephrine (200-300%) and dopamine (250%) in humans
  • Reduction of inflammatory markers IL-6, TNF-alpha after series of sessions
  • Improved athletic performance and post-exercise muscle recovery
  • Vagus nerve activation and HRV improvement

What we still don’t know

  • Superiority vs ice bath for longevity (comparative trials scarce)
  • Long-term effects on telomeres and epigenetic markers
  • Optimal dosing for different objectives (temperature, frequency, duration)

Key studies

Whole-body cryotherapy can reduce the inflammatory response in humans: a meta-analysis based on 11 randomized controlled trials

Scientific Reports (2025)

Meta-analysis of 11 RCTs (n=274): WBC significantly reduces serum IL-1β and increases IL-10, with greater benefit in athletes and obese individuals.

PubMed

Pre-exercise cryotherapy reduces myoglobin and creatine kinase levels after eccentric muscle stress in young women

Frontiers in Physiology (2024)

20 WBC sessions at –120 °C in young women significantly reduced muscle damage markers (myoglobin and CK) after eccentric exercise.

PubMed

A single session of whole-body cryotherapy boosts maximal cycling performance and enhances vagal drive at rest

Experimental Brain Research (2023)

A single WBC session (–150 °C, 3 min) increased cycling endurance by 12-14% and enhanced resting vagal drive (~70% of exercise effect).

PubMed

Efficacy of Whole-Body Cryotherapy in Ankylosing Spondylitis: A Systematic Review with Meta-Analysis

Journal of Integrative and Complementary Medicine (2026)

Meta-analysis (5 studies, n=310 ankylosing spondylitis patients): WBC significantly improves pain (VAS), function (BASFI) and disease activity (BASDAI/ASDAS).

PubMed

Regulatory status

Not regulated as a medical device for most wellness indications. Sports and wellness use without restrictions.

Red Light Therapy (Photobiomodulation)

Level 2bMechanism alto89 human RCTs
Full guide

Cytochrome c oxidase mechanism very well documented. Multiple RCTs in pain, skin, and recovery. Evidence in cellular longevity emerging but mechanistically solid.

What science confirms

  • Mechanism: activation of mitochondrial cytochrome c oxidase by red light (630-700nm) and NIR (800-1000nm)
  • Demonstrated increase in cellular ATP production (20-37%)
  • Improved collagen and elastin synthesis in skin
  • Reduction of local inflammatory markers
  • FDA-approved for musculoskeletal pain (specific devices)

What we still don’t know

  • Optimal wavelength for different indications (660 vs 850 nm vs combination)
  • Minimum effective irradiance for deep tissues
  • Systemic effects of PBM vs local effects

Key studies

Effects of photobiomodulation on oral mucositis, oral pain, xerostomia, salivary flow rate, and quality of life in patients with head and neck cancer: a systematic review and meta-analysis

Supportive Care in Cancer (2026)

SR/MA 30 RCTs (n=1,748 head and neck cancer): photobiomodulation reduces the risk of severe oral mucositis (RR 0.46) and severe oral pain (RR 0.35), and improves salivary flow (SMD 0.75). Quality of evidence very low to low.

PubMed

Efficacy and Safety of 590 Nm and 590/630 Nm Light-Emitting Diode Therapy for Sensitive Skin: A Prospective Randomized Controlled Trial

Photodermatology, Photoimmunology & Photomedicine (2026)

2026 RCT (n=30 sensitive skin): 590 nm yellow + 630 nm red LED three times/week significantly improved SS-10 score, reduced erythema, melanin and transepidermal water loss, with no adverse events.

PubMed

Photobiomodulation Acutely Augments Resting Metabolism in Women with Obesity

Nutrients (2025)

2025 crossover RCT (n=16 women with obesity + 16 normal-weight): 12-min NIR/red photobiomodulation increased resting energy expenditure +9.3% in women with obesity (1,624 vs 1,486 kcal/day; p<0.001) without changes in respiratory exchange ratio.

PubMed

The Healing Effect of Photobiomodulation on Venous Leg Ulcers: A Systematic Review and Meta-Analysis

Wound Repair and Regeneration (2026)

SR/MA 11 RCTs (n=340 venous leg ulcers): photobiomodulation did NOT show significant benefit on ulcer closure vs control (MD 3.77 cm², p=0.37). Substantial heterogeneity; protocol standardisation pending.

PubMed

Regulatory status

FDA-cleared devices for pain and dermatology. Use in longevity as wellness without specific regulation.

Therapeutic Sauna

Level 2aMechanism alto156 human RCTs
Full guide

Exceptional epidemiological evidence. The KIHD study (2,315 men, 20-year follow-up) is one of the strongest in human longevity. 27-50% reduction in cardiovascular mortality.

What science confirms

  • 27-50% reduction in cardiovascular mortality with frequent use (KIHD study, n=2315)
  • Improved endothelial function and reduced arterial stiffness
  • Effect similar to moderate exercise on cardiovascular markers
  • Activation of heat shock proteins (HSPs) with cytoprotective effect
  • Demonstrated reduction of systolic/diastolic blood pressure

What we still don’t know

  • Optimal temperature for longevity (80-100C Finnish vs infrared)
  • Exact dose (minutes per session, weekly frequency)
  • Superiority of Finnish sauna vs infrared for mortality outcomes

Key studies

Association between sauna bathing and fatal cardiovascular and all-cause mortality events

JAMA Internal Medicine (2015)

Prospective cohort 20.7-yr follow-up (n=2,315 Finnish men): 4-7 sauna sessions/week were associated with 50% reduction in sudden cardiac death, 51% in fatal coronary heart disease and 40% in cardiovascular mortality vs 1 session/week.

PubMed

Non-acute effects of passive heating interventions on cardiometabolic risk and vascular health: systematic review and meta-analysis of randomized controlled trials

American Journal of Preventive Cardiology (2025)

2025 SR/MA 20 RCTs (sauna, hot bathing, hot yoga): most cardiometabolic markers (FMD, PWV, HRV, glucose, HbA1c, lipids, CRP) did NOT improve significantly. SBP reduction only with systemic heating (-4.11 mmHg) and in patients with cardiovascular risk (-2.52 mmHg).

PubMed

The multifaceted benefits of passive heat therapies for extending the healthspan: A comprehensive review with a focus on Finnish sauna

Temperature (2024)

2024 comprehensive review on Finnish sauna: passive heat therapies extend healthspan via cardiovascular improvements, neuroprotection, pulmonary function, immunomodulation and inflammation reduction. Regular use associated with reduced risk of dementia, CVD, hypertension and all-cause mortality.

PubMed

Effects of Sauna bathing on Exercise Capacity and Muscle Function in HFpEF

European Journal of Heart Failure (2026)

2026 study (n=18 HFpEF): regular sauna sessions significantly improved peak VO2 (+13%), 6-minute walk test (+33 m), anaerobic threshold, quadriceps strength, diastolic function (E/e'), depression and quality of life; no adverse events. Partial reversibility on cessation.

PubMed

Regulatory status

No specific regulation as a medical device. Use in wellness and cardiovascular prevention widely accepted.

Pressotherapy

Level 2bMechanism alto29 human RCTs
Full guide

Moderate evidence in lymphedema, venous recovery, and DOMS reduction. Mechanism very well understood. Widely used in elite sports.

What science confirms

  • Improved venous and lymphatic return demonstrated via Doppler
  • Reduction of DOMS (delayed onset muscle soreness) in athletes
  • Standard treatment in post-oncological lymphedema
  • Improved post-marathon recovery speed

What we still don’t know

  • Additional benefit of compression boots vs manual massage for longevity
  • Optimal frequency for sports recovery vs medical use

Key studies

Effect of Advanced Pneumatic Compression Devices in the Treatment of Lymphedema: A Systematic Review and Meta-Analyses

Lymphology (2025)

2025 SR/MA (12 studies, advanced pneumatic compression devices): effective for lymphedema treatment with consistent limb volume reduction and improved patient-reported outcomes. Significant decreases in cellulitis rates and need for manual therapy.

PubMed

Intermittent pneumatic compression devices for the prevention and treatment of breast cancer-related lymphedema—a systematic review and meta-analysis

Supportive Care in Cancer (2025)

2025 SR/MA (14 RCTs, n=1,397, breast cancer-related lymphedema): IPC significantly reduces BCRL incidence after surgery (RR 0.36) and improves affected limb extension. Optimal effects: lymphedema ≤24 months duration, ≤40 mmHg pressure, >2 weeks treatment.

PubMed

Intermittent Pneumatic Compression to Prevent Venous Thromboembolism in Critically Ill Adult Patients

American Journal of Critical Care (2026)

2026 RCT (n=150 critically ill): intermittent pneumatic compression reduced VTE and deep vein thrombosis incidence vs control; significantly increased femoral vein blood flow velocity. No mortality differences.

PubMed

Effect of pneumatic and cold compression on muscle performance and recovery in combat sports athletes

Scientific Reports (2025)

2025 RCT (n=48 combat sports athletes): compared pneumatic intermittent compression (25 and 100 mmHg), cryo-compression and passive rest on muscle recovery after combat-sport-typical fatigue.

PubMed

Regulatory status

Class IIa medical device in the EU for vascular and lymphatic indications.

Electrical Muscle Stimulation (EMS)

Level 2bMechanism moderado35 human RCTs
Full guide

EMS has strong evidence in rehabilitation, sarcopenia, and body composition. Studies show +12% strength and -19% abdominal fat in 6 weeks of whole-body training.

What science confirms

  • EMS activates up to 90% of muscle fibers vs 40-60% in maximum voluntary contraction
  • Efficacy in post-injury rehabilitation and sarcopenia well documented
  • Significant improvements in body composition (fat reduction, muscle mass increase)

What we still don’t know

  • Direct comparison of EMS vs conventional exercise for long-term longevity (no RCTs exist)
  • Cardiovascular effects compared to aerobic exercise

Key studies

Low-Frequency Whole-Body Electromyostimulation (WB-EMS) for Nonspecific Chronic Back Pain: A Systematic Review and Meta-Analysis

Cureus (2025)

2025 SR/MA (5 studies, nonspecific chronic back pain): WB-EMS 20 min 1×/wk (8-16 wks) significantly reduces pain (-0.87 NRS) and improves function (SMD 0.84). Comparable efficacy to established methods. Time-efficient and joint-friendly.

PubMed

Effects of Whole-Body Electromyostimulation on Metabolic Syndrome in Adults at Moderate-to-High Cardiometabolic Risk—A Systematic Review and Meta-Analysis

Sensors (2024)

2024 SR/MA (5 studies, n=234 central obesity + moderate-high cardiometabolic risk): WB-EMS shows small but significant effect on metabolic syndrome markers (SMD -0.30) with low heterogeneity (I²=0%). Feasible option for time-constrained individuals.

PubMed

Effectiveness of whole-body electromyostimulation on knee pain and physical function in knee osteoarthritis: a randomized controlled trial

Scientific Reports (2024)

2024 RCT (n=72 overweight + symptomatic knee OA): WB-EMS 3 sessions/fortnight × 7 months significantly reduced KOOS pain (+9.0 points vs usual care; p=0.004) and improved physical function, strength and QoL.

PubMed

Enhancing Physical and Cognitive Efficiency in Elderly Individuals at Risk for Dementia Using Whole-Body Electrostimulation: A Randomized Controlled Trial

Journal of Functional Morphology and Kinesiology (2024)

2024 RCT (n=61 healthy or dementia-risk elderly, 71±5 yrs): 12 wks WB-EMS + aerobic exercise 2×20 min/wk improved memory (PROSA, RAVLT immediate recall p<0.001), attention, arm/grip strength and 6-min walk vs control.

PubMed

Regulatory status

CE/FDA medical device for muscle rehabilitation. Use in fitness and toning as wellness.

PEMF Therapy (Pulsed Electromagnetic Fields)

Level 2aMechanism moderado30 human RCTs
Full guide

PEMF has moderate-high evidence in bone fractures, osteoarthritis, and chronic pain. FDA-cleared since 1979. Use in longevity emerging, focused on mitochondrial health and tissue regeneration.

What science confirms

  • PEMF approved by FDA for non-union bone fractures (since 1979)
  • Demonstrated efficacy in osteoarthritis pain and bone regeneration
  • Documented mechanism of mitochondrial stimulation and ATP production

What we still don’t know

  • Efficacy in general longevity and systemic wellness (outside bone/joint indications)
  • Optimal frequency and intensity protocols for preventive use

Key studies

Pulsed Electromagnetic Field Therapy for Mild-to-Moderate Knee Osteoarthritis: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial

Journal of Cachexia, Sarcopenia and Muscle (2026)

2026 double-blind placebo RCT (mild-moderate knee OA): PEMF increased knee extensor peak torque by 72% at 6 months vs 25% in SHAM (p=0.003). Significant effect on extensor; no effect on flexor.

PubMed

The effectiveness of pulsed electromagnetic field therapy in patients with shoulder impingement syndrome: A systematic review and meta-analysis of randomized controlled trials

PLOS ONE (2025)

2025 SR/MA (4 RCTs, n=252, shoulder impingement syndrome): PEMF significantly reduces short-term pain (SMD -0.34) and improves both short-term (SMD 0.40) and long-term functional capacity (SMD 0.60). Clinically significant benefits.

PubMed

Effects of pulsed electromagnetic fields on bone fractures: a systematic review update

European Journal of Physical and Rehabilitation Medicine (2024)

2024 updated SR: evidence does NOT support PEMF use for improving bone healing in acute fractures. Controversial evidence on pain and functional recovery. Higher-quality studies needed.

PubMed

Feasibility, acceptance and effects of pulsed magnetic field therapy in patients with post-COVID-19 fatigue syndrome: A randomized controlled pilot study

Wiener Klinische Wochenschrift (2025)

2025 pilot RCT (post-COVID fatigue syndrome): PEMF notably improved 6-min walk test, fatigue (BFI, MFI), depression (HADS), insomnia (ISI), work ability and quality of life (SF-36). Zero dropouts in active group.

PubMed

Regulatory status

FDA-cleared for bone fractures (1979) and musculoskeletal pain (2004). Class IIa medical device in the EU.

Medical Aesthetics

HIFU (High-Intensity Focused Ultrasound)

Level 1bMechanism alto67 human RCTs
Full guide

Strong evidence for non-invasive facial tightening. Multiple RCTs with objective collagen and elastin measurements. HIFU for non-invasive lifting has the strongest evidence base of all aesthetic devices.

What science confirms

  • Produces focal thermal coagulation in deep dermis and SMAS at temperatures of 60-70C
  • Stimulates type I and III neocollagenesis documented histologically
  • Demonstrated effectiveness in facial, neck, and submental laxity
  • Durability of 12-18 months with a single session

What we still don’t know

  • Direct comparison between platforms (Ulthera vs Doublo vs Ultraformer) with standardized methodology
  • Optimal protocol for different skin phototypes and ages
  • Maintenance of effect beyond 18 months

Key studies

Radiofrequency Microneedling for Facial Rejuvenation: A Systematic Review

Journal of Cosmetic Dermatology (2026)

2026 SR (20 studies, n=558 participants): radiofrequency microneedling (RFMN) consistently improves skin texture and facial tightening, with high Global Aesthetic Improvement Scale scores. Adverse events predominantly mild and transient; patient satisfaction >90% in most studies.

PubMed

Clinical Efficacy and Safety of Shallow-Dermal Linear HIFU for Fine-Wrinkle Reduction in Asian Skin

Journal of Craniofacial Surgery (2026)

2026 clinical study (n=30 Asian women, Fitzpatrick III-IV): single shallow-dermal HIFU session reduced wrinkle depth -19.3% and surface roughness -15.9%, increased gross elasticity +21.6% and net +18.1% at 12 wks. 93% rated improved by blinded evaluators.

PubMed

Analysis of US Food and Drug Administration Data on Radiofrequency Microneedling Device Complications

Dermatologic Surgery (2026)

2026 FDA RFMN device data analysis: 224 adverse events reported. Most frequent: textural changes (25%), pigmentary alteration (18%), fat loss (12%), inflammatory reactions (8%) and burns (6%). Clinical experience and proper training critical to minimise risks.

PubMed

Lasers and ultrasound in Aesthetic medicine: a hybrid review of efficacy, safety, and future directions

Journal of Cosmetic and Laser Therapy (2026)

2026 hybrid review: energy-based devices (lasers + HIFU/MFU-V) have transformed aesthetic medicine. Synthesises RCTs, observational series and meta-analyses with focus on Fitzpatrick IV-VI skin, BMI subgroups and AI-guided planning.

PubMed

Regulatory status

FDA-cleared devices (Ultherapy, 2009) for brow and chin lifting. CE marking in Europe.

Medical Laser Therapy (Fractional CO2 / Nd:YAG)

Level 1bMechanism alto118 human RCTs
Full guide

Fractional laser therapy is one of the most scientifically supported treatments in dermatology and medical aesthetics. Multiple RCTs with objective histological collagen measurements. Ablative CO2 laser is the gold standard for skin rejuvenation.

What science confirms

  • CO2 laser creates ablation microcolumns that stimulate histologically measurable type I and III neocollagenesis
  • Reduction of age spots, telangiectasias, and lentigines through selective absorption (selective photothermolysis)
  • Improved skin laxity through collagen contraction at 60-65C
  • FDA-cleared and CE-marked devices for multiple dermatological indications
  • Non-ablative fractional laser (Fraxel) allows treatment with minimal downtime

What we still don’t know

  • Optimal protocol for skin phototypes IV-VI (increased risk of post-inflammatory hyperpigmentation)
  • Optimal number of sessions vs clinical outcome for different indications
  • Direct comparison of ablative vs non-ablative fractional laser in skin longevity at 3-5 years

Key studies

Fractional CO2 Laser Versus Micro Needling Radiofrequency for Post Acne Scarring: A Meta-Analysis of RCTs

Journal of Cosmetic Dermatology (2026)

2026 MA (fractional CO2 vs RF microneedling for acne scarring): fractional CO2 superior in scar improvement (MD 0.31; p=0.0005) and patient satisfaction (MD 0.32; p=0.005), but with significantly higher pain, increased post-inflammatory hyperpigmentation risk (RR 4.44), and longer erythema.

PubMed

Effects of Near Infrared Light on Surgical Wound Healing: A Systematic Review and Meta-Analysis

International Wound Journal (2026)

2026 SR/MA (56 studies, n=4,920): NIR light significantly improves surgical wound healing (SMD 0.78) and reduces postoperative pain (SMD 0.71). Optimal: 700-850 nm, 4-10 sessions, non-contact. Very low certainty of evidence.

PubMed

Analgesic Efficacy of Low-Level Laser Therapy for Postoperative Endodontic Pain: A Systematic Review and Meta-Analysis

Australian Endodontic Journal (2026)

2026 SR/MA (9 studies LLLT post-endodontic): LLLT more effective than placebo in pain reduction at 1 day (VAS MD -0.56; 95% CI -0.74 to -0.38; p<0.001). Higher-quality studies needed.

PubMed

Hydroxybutyl Chitosan Hydrogel Promotes Ablative Fractional CO2 Laser Wound Healing: A Prospective, Randomized, Split-Face Trial and Animal Model Evaluation

Lasers in Surgery and Medicine (2026)

2026 split-face RCT (hydroxybutyl chitosan hydrogel post-CO2 laser): comparable effects to standard protocol at 7 and 28 days, better skin hydration, no steroid-related irritation. Promotes macrophage M2 polarisation via IRF7/CTSS.

PubMed

Regulatory status

Class IIb/III medical devices regulated by the EU (MDR 2017/745). Administration in Spain restricted to physicians and authorized healthcare centers. No prescription required but medical supervision mandatory.

Hormonal Optimization

Bioidentical Hormone Therapy (TRT / BHRT)

Level 1bMechanism alto284 human RCTs
Full guide

Hormone replacement therapy (HRT/BHRT) has one of the richest evidence bodies in all of longevity medicine. RCTs in menopause (ELITE trial) and male hypogonadism show cardiovascular, bone, metabolic, and cognitive benefits when initiated early.

What science confirms

  • Estradiol prevents postmenopausal bone loss (fracture risk -30% to -50%)
  • TRT improves bone mineral density, muscle mass, and insulin sensitivity in hypogonadism
  • The 'window of opportunity' is critical: greater cardiovascular benefit if initiated <6 years post-menopause
  • Biomimetic bioidentical hormones have the same action profile as endogenous hormones
  • Micronized progesterone (bioidentical) has a better breast risk profile than synthetic progestins

What we still don’t know

  • Superiority of bioidentical vs synthetic beyond individual safety profile
  • Cardiovascular risk of TRT in men without clear hypogonadism (use in 'optimization')
  • Optimal dosing of DHEA, pregnenolone, and testosterone for longevity without clinical indication
  • Long-term effect of subcutaneous hormone pellets (scarcity of specific RCTs)

Key studies

Long-Term Cardiovascular Safety of Testosterone-Replacement Therapy in Middle-Aged and Older Men: A Meta-analysis of Randomized Controlled Trials

American Journal of Cardiovascular Drugs (2025)

Meta-analysis 23 RCTs (n=9,280 men with testosterone deficiency, mean age 64.6): TRT does NOT increase mortality or major cardiovascular events vs placebo, but SIGNIFICANTLY INCREASES cardiac arrhythmia incidence (RR 1.53; 95% CI 1.20-1.97; p<0.01). Cardiac monitoring recommended.

PubMed

Menopausal Hormone Therapy and Cardiovascular Diseases in Women With Vasomotor Symptoms: A Secondary Analysis of the Women's Health Initiative Randomized Clinical Trials

JAMA Internal Medicine (2025)

2025 WHI secondary analysis (n=27,347 postmenopausal women): menopausal hormone therapy in women with moderate-severe vasomotor symptoms at age <60 was associated with reduced cardiovascular risk; in women ≥70 the risk-benefit balance reverses. Age at initiation critical.

PubMed

Menopause hormone therapy and risk of mild cognitive impairment or dementia: a systematic review and meta-analysis

The Lancet Healthy Longevity (2025)

Lancet Healthy Longevity 2025 SR/MA (10 studies, n=1,016,055): NO significant association found between MHT use and risk of mild cognitive impairment or dementia. Subgroup analyses (timing, duration, type) also showed no significant effects.

PubMed

Long-term amyloid PET and MRI outcomes in a menopausal hormone therapy trial

Alzheimer's & Dementia (2026)

2026 Alzheimer's & Dementia RCT (10-year post-MHT follow-up): NEITHER oral CEE NOR transdermal estradiol (4 years) modified amyloid-β biomarkers or brain MRI structure vs placebo. Supports long-term safety of short-term MHT use on brain health.

PubMed

Regulatory status

Estradiol and testosterone available with medical prescription in Spain (AEMPS). Bioidentical compounded preparations (pellets, creams) formulated in authorized pharmacies. Require periodic lab monitoring.

Neurology & Mind

Therapeutic IV Ketamine

Level 1bMechanism alto76 human RCTs
Full guide

IV ketamine has driven the most important revolution in psychiatry in the last 60 years. Antidepressant efficacy in hours versus weeks with SSRIs. FDA-approved (intranasal esketamine). Growing use in pain management and treatment-resistant depression.

What science confirms

  • NMDA antagonism and AMPA receptor activation: rapid documented neurosynaptogenesis
  • Antidepressant effect in <4 hours in 50-70% of patients with treatment-resistant depression
  • Efficacy in chronic neuropathic pain, fibromyalgia, and CRPS
  • FDA approved esketamine (Spravato) intranasal for major treatment-resistant depression and high suicide risk
  • Neuroprotective and neurotrophic effect (increased BDNF) documented in human and animal models

What we still don’t know

  • Optimal number of infusions and long-term maintenance protocol
  • Risk of abuse and dependence with repeated use (low rate in supervised clinical context, but real)
  • Comparative effectiveness of IV ketamine vs intranasal esketamine in real-world conditions
  • Indications in longevity (beyond psychiatry): cognitive decline, general neuroplasticity

Key studies

Long-term treatment with esketamine nasal spray in patients with treatment resistant depression: Results from the ESCAPE-LTE study

European Neuropsychopharmacology (2026)

Phase IV ESCAPE-LTE 2026 (2-year / 104-week extension): evaluated long-term safety, tolerability and efficacy of intranasal esketamine in treatment-resistant depression. Primary endpoints: treatment-emergent adverse events and suicidal ideation.

PubMed

Comparative Efficacy and Safety of Ketamine Versus Midazolam for Suicidality: A GRADE-Assessed Systematic Review and Meta-Analysis of Randomized Controlled Trials

Brain and Behavior (2026)

2026 SR/MA GRADE (10 RCTs, n=649): ketamine vs midazolam for suicidality — ketamine significantly reduces suicidal ideation (MADRS-SI -1.23; BSS -4.30) and depressive symptoms (MADRS -6.23). Adverse events more frequent (nausea, dissociative effects).

PubMed

Efficacy and safety of esketamine on major depression, postpartum depression and perioperative depression: a systematic review and meta-analysis

Molecular Psychiatry (2026)

Mol Psychiatry 2026 SR/MA: esketamine shows significant efficacy in major depression/TRD, prevention of postpartum and perioperative depression. Intra- and inter-administration comparisons. Adverse events reported in >2 comparisons.

PubMed

Ketamine treatment alleviates suicide ideation in high-risk populations: a systematic review and meta-analysis

Epidemiology and Psychiatric Sciences (2026)

2026 SR/MA (21 studies, n=927): ketamine significantly reduces suicidal ideation in high-risk populations (large effect -1.40; 95% CI -2.15 to -0.66; p<0.001). Adverse events: dissociation 39%, nausea 32%, dizziness 25%, headache 22%, anxiety 16%. Low quality evidence.

PubMed

Regulatory status

Ketamine: anesthetic approved by AEMPS. Use as antidepressant is 'off-label'. Esketamine (Spravato) approved by EMA for treatment-resistant depression in 2019. Mandatory administration in medical setting with monitoring.

Transcranial Magnetic Stimulation (TMS / rTMS)

Level 1bMechanism alto98 human RCTs
Full guide

Repetitive TMS (rTMS) is the non-invasive neuromodulation with the strongest scientific backing. FDA-approved in 2008 for major depression. Ongoing trials for cognitive decline, ADHD, and cognitive performance optimization in healthy individuals.

What science confirms

  • FDA-approved (2008) for treatment-resistant major depression and OCD (2018), migraine (2013)
  • The pulsed magnetic field induces electrical currents in the cerebral cortex non-invasively
  • High-frequency rTMS (10 Hz) on left DLPFC increases cortical excitability and improves mood
  • EMA-approved: CE marking for depression, OCD, and migraine in Europe
  • Neuroprotective effect in cognitive decline models: increased BDNF and neurogenesis

What we still don’t know

  • Efficacy in mild cognitive impairment (MCI) and Alzheimer's disease (trials ongoing)
  • Use in 'cognitive enhancement' in healthy individuals: promising but no protocol consensus
  • Direct comparison of accelerated protocols (SAINT) vs standard in real-world practice
  • Duration of effect without maintenance sessions (relapse in 3-6 months documented in depression)

Key studies

Effects of Transcranial Magnetic Stimulation on Patients with Major Depressive Disorder: A Systematic Review and Meta-analysis

Clinical Medicine & Research (2026)

2026 SR/MA (12 studies, n=1,318): TMS significantly reduces depressive symptomatology (HAMD -4.47 points; p<0.00001) and MADRS in major depressive disorder patients.

PubMed

Efficacy and safety of accelerated transcranial magnetic stimulation on suicidality in depressive disorders: A systematic review and meta-analysis

Journal of Affective Disorders (2026)

2026 SR/MA (13 studies, n=625; 6 RCTs): accelerated TMS showed NO significant advantage over sham or standard TMS for suicidality reduction. Adverse effects more frequent (OR 1.95). Non-significant favourable trend for aTMS.

PubMed

Circuit-based neuromodulation for obsessive-compulsive disorder: a systematic review, meta-analysis, and translational case study

Journal of Psychiatry & Neuroscience (2026)

2026 SR/MA (27 RCTs, n=868): neuromodulation significantly reduces OCD symptoms vs control. Fronto-limbic deep brain stimulation showed largest Y-BOCS improvements. Invasive neuromodulation more effective than non-invasive approaches.

PubMed

A meta-analysis of the effect of non-invasive neuromodulation techniques on improving cognitive function in patients with Alzheimer's disease

Neurological Sciences (2026)

2026 network meta-analysis (77 studies, Alzheimer's and MCI): rTMS, tACS and tDCS significantly improve global cognitive function (MMSE, MoCA and ADAS-cog). tDCS superior to rTMS in MMSE/MoCA, but rTMS more effective in ADAS-cog.

PubMed

Regulatory status

TMS devices approved by FDA (NeuroStar, BrainsWay, MagVenture) for depression and OCD. In Spain, CE marking and established clinical use in psychiatry. Variable coverage by private insurers.

Diagnostics & Longevity

Longevity Biomarker Panel

Level 2aMechanism alto42 human RCTs
Full guide

Advanced biomarker panels (epigenetic biological age, metabolomics, proteomics) are the foundation of precision medicine in longevity. Epigenetic clocks like GrimAge predict mortality better than any other known clinical biomarker.

What science confirms

  • Epigenetic clocks (DNAm) predict mortality better than chronological age
  • GrimAge, PhenoAge, and DunedinPACE are validated in cohorts of >10,000 individuals
  • Cardiometabolic panel (HbA1c, hs-CRP, Lp(a), ApoB, homocysteine) identifies 10-year risk with high precision
  • Cellular senescence markers (p16INK4a, GDF-15) are modifiable with interventions
  • Proteomics (SomaScan, Olink) can measure >5,000 proteins with biological age predictive value

What we still don’t know

  • Which epigenetic clock is most actionable for guiding interventions (GrimAge vs DunedinPACE vs Horvath)
  • Optimal measurement frequency to detect real changes vs technical variability
  • Cost-effectiveness of extensive panels vs key simple markers
  • Predictive value in Mediterranean populations vs North American/Nordic cohorts

Key studies

The association of epigenetic age acceleration with internal smoking dose, risk of lung cancer, and all-cause mortality in cigarette smokers: the Multiethnic Cohort Study

Clinical Epigenetics (2026)

2026 study (Multiethnic Cohort): GrimAge epigenetic acceleration predicted lung cancer risk (HR 1.40; 95% CI 1.16-1.71) and all-cause mortality in smokers. DunedinPACE also predicted risk (HR 1.31). Solid clinical predictive validation.

PubMed

Association between phenotypic age acceleration and all-cause and cardiovascular mortality risk among individuals with cardiovascular-kidney-metabolic syndrome

Maturitas (2026)

2026 cohort (median 5.83-yr follow-up, cardiovascular-kidney-metabolic risk): PhenoAge acceleration is associated with all-cause mortality (HR 2.81 top vs bottom quartile) and cardiovascular mortality. Each 1-yr acceleration significantly elevates risk.

PubMed

Metformin and epigenetic age in non-diabetic older people with HIV in Madrid (METFORAGING): a double-blind, randomised, placebo-controlled, pilot trial

EClinicalMedicine (2026)

2026 double-blind placebo METFORAGING RCT (n=40, non-diabetic older adults with HIV): 96 weeks of metformin vs placebo to assess epigenetic age changes. 97.5% adherence. Study halted at n=40<60 target due to slow recruitment.

PubMed

Multi-Omics Signatures of Organ Clocks in Biological Aging and Disease: A Conceptual Framework for Organ-Specific Aging Clocks

Aging Cell (2026)

Aging Cell 2026 (multi-omics clocks review): organ biological clocks integrate genomic, epigenetic, transcriptomic, proteomic and metabolomic data. Different organs age at different rates, explaining variability in age-associated diseases. Clinical implementation still limited.

PubMed

Regulatory status

Standard blood tests do not require prescription. Epigenetic clocks (saliva/blood DNAm tests) are laboratory products, not regulated diagnostics. Medical interpretation is mandatory.

Advanced Diagnostic Imaging (Full-Body MRI / DEXA / CT)

Level 2aMechanism alto38 human RCTs
Full guide

Advanced diagnostic imaging is the cornerstone of the premium longevity check-up. Full-body MRI detects silent subclinical pathology. DEXA measures body composition with research-grade precision. Low-dose chest CT (LDCT) reduces lung cancer mortality in smokers by 20%.

What science confirms

  • Chest LDCT reduces lung cancer mortality by 20% in high-risk smokers (USPSTF Grade B)
  • DEXA allows precise measurement of muscle mass, visceral fat, and bone mineral density with minimal radiation dose
  • Full-body MRI detects subclinical pathology in >13% of asymptomatic individuals
  • Cardiac MRI is the gold standard for ejection fraction measurement and silent myocardial fibrosis
  • Coronary artery calcium score (CAC-CT) is the most powerful available cardiovascular risk predictor

What we still don’t know

  • Cost-effectiveness of total screening in young general population (vs risk-directed screening)
  • Optimal management of 'incidental findings' (incidentalomas): anxiety curve vs diagnostic benefit
  • Optimal repetition frequency based on age and risk profile
  • Diffusion and spectroscopy MRI protocols for early neurodegeneration detection (under validation)

Key studies

Cumulative incidence of advanced breast cancer in women aged 40-49 years in the Japan Strategic Anti-cancer Randomised Trial (J-START)

The Lancet (2026)

2026 Lancet J-START RCT (n=72,661 asymptomatic women aged 40-49, median 11.4-yr follow-up): adding ultrasound to mammography detected advanced breast cancers in 26% intervention vs 33% control group (HR 0.83; 95% CI 0.70-0.98; p=0.026).

PubMed

Colonoscopy and fecal immunochemical testing versus usual care in diagnostic colorectal cancer screening: the SCREESCO randomized controlled trial

Nature Medicine (2026)

2026 Nature Medicine SCREESCO RCT (n=278,280, age 60): compared single colonoscopy vs biennial two-stool FIT (low cutoff 10 µg/g) vs usual care without screening. Quantifies benefits and harms in diagnostic phase.

PubMed

Significant Incidental Findings in the National Lung Screening Trial and Diagnosis of Extrapulmonary Cancer

JAMA Network Open (2026)

2026 NLST analysis (n=26,445, 75,104 LDCT rounds): suspicious incidental cancer findings in 3% of rounds. Extrapulmonary cancer diagnosis following finding in 13.89/1,000 participants (urinary cancers and other SEER types significantly higher).

PubMed

Is blood the new stool? Status of blood tests for CRC screening

Best Practice & Research Clinical Gastroenterology (2026)

2026 SR/MA: blood-based colorectal cancer screening tests may improve population participation vs FIT (faecal immunochemical test), but comparative accuracy data required before widespread implementation.

PubMed

Regulatory status

Medical imaging devices regulated as class III (CT, MRI) by AEMPS/European MDR. Centers must have healthcare authorization. Medical prescription is mandatory. Ionizing radiation exposure (CT) requires documented clinical justification per the ALARA principle.

Review methodology

Inclusion criteria

  • Randomized controlled clinical trials (RCTs) in humans
  • Meta-analyses and systematic reviews with PRISMA methodology
  • Studies with sample ≥20 participants
  • Published in peer-reviewed journals
  • Studies from 2010 onwards (except fundamental historical studies)

Limitations

  • This review is not a formal systematic review or meta-analysis
  • Evidence levels are assigned to the main studied indication
  • Longevity science advances rapidly — we review every 6 months
  • The number of RCTs is approximate based on PubMed and Cochrane searches

Reviewed by: LongevityMap editorial team — Our team. Last reviewed: March 2026. Sources: PubMed, Cochrane Library.

Important notice

This page is an information and education tool. It does not constitute medical advice, diagnosis or treatment prescription. Evidence levels refer to studied populations and may not apply to your individual situation. Always consult a qualified healthcare professional before starting any longevity treatment.

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