Permeation of Boswellia extract in the Caco-2 model and possible interactions of its constituents KBA and AKBA with OATP1B3 and MRP2.

Pharmacokinetic studies yielded low plasma concentrations of the active ingredients 11-keto-beta-boswellic acid (KBA) and 3-acetyl-11-keto-beta-boswellic acid (AKBA).


Development of a nanoemulsion incorporating 3-acetyl-11-keto-β-boswellic acid (AKBA): solubility and oral bioavailability through in vitro and in vivo studies.

However, its poor oral bioavailability remains a critical limitation for clinical application.


[Polysaccharides of frankincense processed with vinegar promote absorption of boswellic acids via enzyme inhibition, transporters, and nanoparticles].

The results showed that the polysaccharides, especially those from vinegar-processed frankincense, significantly enhanced the oral bioavailability of AKBA and KBA.


Pharmacokinetics and distribution of [35S]methylsulfonylmethane following oral administration to rats.

Oral [35S]MSM was rapidly and efficiently absorbed with a mean tmax of 2.1 h, Cmax of 622 microg equiv/mL, and AUC0-inf of 15124 h.microg equiv/mL.


Toxicity and tissue distribution of methylsulfonylmethane following oral gavage in broilers.

In Study 1, plasma MSM concentrations were below 167 μg/mL at all time-points in birds receiving up to 300 mg/kg BW, and were significantly higher (P < 0.05) in birds receiving 1,000 or 2,000 mg/kg BW.


Lithium orotate: A superior option for lithium therapy?

Bipolar disorder (BD) poses a significant public health concern, with roughly one-quarter of sufferers attempting suicide.


Review of dietary supplements for the management of osteoarthritis in dogs in studies from 2004 to 2014.

The goals of this narrative review are to summarize the scientific data available in the literature on dietary supplements assessed in dog OA and to discuss some trails about how to improve several aspects of research and issues with dietary supplements, such as bioavailability and dosage regimen.


Prolonged retention of doubly labeled phosphatidylcholine in human plasma and erythrocytes after oral administration.

The plasma kinetics of a preparation of dilinoleoyl phosphatidylcholine (DLPC) specifically labeled with 3H in the choline moiety and with 14C in the 2-fatty acid (FA) were evaluated in six healthy volunteers after oral administration.


Choline supplemented as phosphatidylcholine decreases fasting and postmethionine-loading plasma homocysteine concentrations in healthy men.

Choline is the precursor for betaine, but the effects of choline supplementation on plasma total homocysteine (tHcy) concentrations in healthy humans are unknown.


Oral choline supplementation for postoperative pain.

Plasma choline concentration and tumour necrosis factor (TNF) were measured.


A comparison of the in vitro permeation of niacinamide in mammalian skin and in the Parallel Artificial Membrane Permeation Assay (PAMPA) model.

The in vitro skin penetration of pharmaceutical or cosmetic ingredients is usually assessed in human or animal tissue.


In vitro Percutaneous Absorption of Niacinamide and Phytosterols and in vivo Evaluation of their Effect on Skin Barrier Recovery.

In this study, we evaluated different strategies to optimize the percutaneous absorption of niacinamide (NA) and soy phytosterols (FITO) by making use of solid lipid nanoparticles (SLN) and penetration enhancers, such as the hydrogenated lecithin.


Assessment of in vitro percutaneous absorption of glycolic acid through human skin sections using a flow-through diffusion cell system.

The percutaneous absorption studies were performed using a flow-through diffusion cell system with skin specimens from 24 healthy women to assess the penetration of glycolic acid (GA).


Enhancing effect of alpha-hydroxyacids on "in vitro" permeation across the human skin of compounds with different lipophilicity.

The percutaneous penetration-enhancing effects of glycolic acid, lactic acid and sodium lauryl sulphate through the human epidermis was investigated using 5-fluorouracil as a hydrophilic model permeant and three compounds belonging to the phenylalcohols: 2-phenyl-ethanol, 4-phenyl-butanol and 5-phenyl-pentanol.


Human safety review of "nano" titanium dioxide and zinc oxide.

Multiple studies have shown that under exaggerated test conditions neither nano-structured TiO(2) nor ZnO penetrates beyond the stratum corneum of skin.


Titanium Dioxide and Zinc Oxide Nanoparticles in Sunscreens: A Review of Toxicological Data.

There are in vitro and in vivo studies: studies on animal and human skin; investigations of potential genotoxicity and cytotoxicity; generation of reactive oxygen species; penetration; skin irritation; acute, subchronic, and chronic toxicity; and carcinogenesis.


Adverse Reactions to Sunscreens.

Nearly all adverse effects due to active sunscreen ingredients reported to date are related to the organic UV filters, which are sometimes also referred to as "chemical UV filters." This imbalance is attributable to the lipophilic character and small molecular size of the organic UV filters that allow skin penetration, which is the basic requirement to initiate the sensitization [Stiefel et al.


Hyaluronic Acid in Topical Applications: The Various Forms and Biological Effects of a Hero Molecule in the Cosmetics Industry.

The analysis revealed HA below 100 kDa to penetrate skin, and lower molecular weight being able to reach the dermis.


Human skin penetration of hyaluronic acid of different molecular weights as probed by Raman spectroscopy.

Several techniques were developed to study molecules penetration into the human skin.


Biocompatible topical delivery system of high-molecular-weight hyaluronan into human stratum corneum using magnesium chloride.

We developed a safe method of administering hyaluronan into the human SC and determined its penetration route.


Decrypting the Potential of Lipidic Vesicular System for Delivery Enhancement of Tranexamic Acid in Melasma Hyperpigmentation Treatment.

Lipidic vesicular delivery systems including liposomes, ethosomes, niosomes, transferosomes and phytosomes showed extensive capability in the delivery of TA into deeper epidermal layers with improved stability and penetration efficacy.


Efficacy and Safety of tranexamic acid versus vitamin c after microneedling in treatment of melasma: Clinical and Dermoscopic study.

Skin microneedling acts as a transdermal delivery system that facilitates the penetration of lightening agents to deeper layers of skin.


Efficacy of Non-Ablative Fractional Laser Combined With Tranexamic Acid in Melasma Treatment: A Randomized Split-Face Trial.

The combination of NAFL and topical TXA provides significant short-term clinical benefits in treating melasma, likely by enhancing TXA penetration into target tissues and improving pigmentary clearance.


Topical application of vitamin C and its derivatives in dermatology and cosmetics.

Despite its biological efficacy, topical use of vitamin C represents a technological challenge due to its low stability and limited ability to penetrate the skin.


Stability, transdermal penetration, and cutaneous effects of ascorbic acid and its derivatives.

This article reviews the scientific data and clinical studies that underpin the stability, percutaneous absorption, and cutaneous effects of vitamin C together with its commonly utilized, commercially available derivatives.


Application of Antioxidant Mixture Prevents Cutaneous "Oxinflammaging" in Subjects Exposed to Particulate Matter.

Moreover, PM can penetrate damaged skin, exacerbating the effect of other pollutants and worsening the symptoms of existing skin conditions.


Vitamins and the skin: Vitamin C in dermatology.

Although L-ascorbic acid continues to be widely used, promising derivatives exhibit enhanced stability, but limited skin penetration is a challenge.


Novel nanocapsule of α-lipoic acid reveals pigmentation improvement: α-Lipoic acid stimulates the proliferation and differentiation of keratinocyte in murine skin by topical application.

Though α-lipoic acid is normally administered in oral or injection, it has not been used in a topical use via skin because of its bad penetration.


Microemulsions Improve the Cutaneous Co-Localization of Lipoic Acid and Quercetin and Antioxidant Effects in Cutaneous Cells and Tissue.

Skin penetration studies revealed a 2.4-fold increase in quercetin (Q) accumulation in the stratum corneum and a 3.5-fold increase in the delivery to viable epidermis and dermis (ED) after a 12 h-treatment with the ME compared to control solutions; α-lipoic acid (LA) penetration improved up to 1.9-fold in ED upon ME incorporation.


Percutaneous absorption of azelaic acid in humans.

Following the two treatments the renal excretion of the unchanged compound was measured.


Topical acne drugs: review of clinical properties, systemic exposure, and safety.

This review examines the commonly available topical acne agents and factors that determine their percutaneous absorption.


Cosmetic Commentary: Response to "Is bakuchiol the new 'skincare hero'?".

This commentary is intended to expand the discussion around comparisons of topical bakuchiol to topical retinol.


Metabolism of topical retinaldehyde.

In order to circumvent the tolerance problems encountered with topical application of retinoic acid - a biologically active metabolite of vitamin A - we performed in various models a series of experiments aimed at assessing the bio-availability of topical retinaldehyde and its conversion into either retinoid stores or biologically active metabolites.


Spectral and mass characterization of kinetic conversion from retinoids to retinoic acid in an in vitro 3-D human skin equivalent model.

Spectral changes were revealed that the CO maximum absorbance occurred between 1600∼1800 cm-1 and was greater from ROL than that from RAL and RP, indicating conjugation of R-OH to R-CHO or R-COOH could strongly occur after ROL treatment.


Retinoids in cosmeceuticals.

They are lipophilic molecules and easily penetrate the epidermis.


Favourable dermal penetration of diclofenac after administration to the skin using a novel spray gel formulation.

The study was designed to evaluate the relative bioavailability of diclofenac in plasma, subcutaneous adipose and skeletal muscle tissue after repeated topical administration using MIKA Diclofenac Spray Gel (4%), a novel formulation, and after oral dosing using VOLTAREN 50 mg enteric coated tablets.


A new topical formulation enhances relative diclofenac bioavailability in healthy male subjects.

• Therapy with topical non-steroidal anti-inflammatory drugs (NSAIDs) relies on the ability of the active drug to penetrate the skin in sufficiently high amounts to exert a clinical effect, which is linked to the specific galenic properties of the formulation.


An alternative topical treatment of osteoarthritis of the knee with cutaneous diclofenac solution.

Cutaneous diclofenac solution (Pennsaid) was developed for the treatment of symptomatic OA of the knee and contains diclofenac sodium as an active ingredient and dimethyl sulfoxide (DMSO), a penetration enhancer.


[Preparation and in vitro and in vivo evaluations of topically applied capsaicin transfersomes].

Capsaicin transfersomes were prepared by high shear dispersing machine and evaluated by entrapment efficiency, release rate, in vitro skin permeation and distribution in different tissues in vivo.


Topical agents: a thoughtful choice for multimodal analgesia.

For over a thousand years, various substances have been applied to the skin to treat pain.


Mechanistic Modelling of Lidocaine and Prilocaine Absorption from EMLA Cream upon Topical Application using Physiologically Based Pharmacokinetic Modelling.

The purpose of this study was to develop a mechanistic skin absorption model to predict the absorption of lidocaine and prilocaine following topical application of EMLA cream (lidocaine/prilocaine topical cream, 2.5%/2.5%) in virtual subjects.


Absorption of lidocaine following topical application in microvascular procedures on rabbits.

Fifty rabbits were used to investigate the absorption of lidocaine following its topical application to blood vessels.


Dermal absorption of camphor, menthol, and methyl salicylate in humans.

The authors report the plasma concentrations of the intact compounds as a function of dose following dermal patch application.


The absorption and metabolism of a single L-menthol oral versus skin administration: Effects on thermogenesis and metabolic rate.

We investigated the absorption and metabolism pharmacokinetics of a single L-menthol oral versus skin administration and the effects on human thermogenesis and metabolic rate.


Menthol concentration in topical cold gel does not have significant effect on skin cooling.

Topical menthol gels are used in the treatment of various pain conditions.


Potential dangers from topical preparations containing methyl salicylate.

Ingestion of methyl salicylate poses the threat of severe, rapid-onset salicylate poisoning because of its liquid, concentrated form and lipid solubility.


Bioavailability of marine n-3 fatty acid formulations.

Prostaglandins Leukot Essent Fatty Acids

Bioavailability of EPA+DHA from re-esterified triglycerides was superior (124%) compared with natural fish oil, whereas the bioavailability from ethyl esters was inferior (73%).


Plasma Creatine Kinetics After Ingestion of Microencapsulated Creatine Monohydrate with Enhanced Stability in Aqueous Solutions.

Three hours after ingestion, plasma creatine concentrations were unchanged during PLA, and averaged ∼45 μM.


Comparative Pharmacokinetic Study of Standard Astaxanthin and its Micellar Formulation in Healthy Male Volunteers.

Astaxanthin is a naturally occurring carotenoid with high anti-oxidant properties, but it is a very lipophilic compound with low oral bioavailability.


Plasma appearance of unesterified astaxanthin geometrical E/Z and optical R/S isomers in men given single doses of a mixture of optical 3 and 3'R/S isomers of astaxanthin fatty acyl diesters.

Comp Biochem Physiol C Toxicol Pharmacol

The plasma astaxanthin concentration-time curves were measured during 76 h.


Bioavailability of AREDS1 micronutrients from softgel capsules and tablets: a pilot study.

However, the choices of excipient, dosage form, and ingredient chemistry as well as the patient physiologies and pathologies can influence bioavailability and efficacy.


Relative Bioavailability of Silybin A and Silybin B From 2 Multiconstituent Dietary Supplement Formulations Containing Milk Thistle Extract: A Single-dose Study.

The purpose of this study was to compare the bioavailability between 2 milk thistle-containing dietary supplements, Product B and IsaGenesis, in healthy volunteers.


Superior silybin bioavailability of silybin-phosphatidylcholine complex in oily-medium soft-gel capsules versus conventional silymarin tablets in healthy volunteers.

Therefore, we sought to assess and compare the pharmacokinetic properties and bioavailability of silybin-phosphatidylcholine complex in oily-medium soft-gel capsules and conventional silymarin tablets in healthy Mexican volunteers.


Effects of dosing condition on the oral bioavailability of green tea catechins after single-dose administration of Polyphenon E in healthy individuals.

The oral bioavailability of the major green tea constituents, green tea catechins, is low, resulting in systemic catechin levels in humans many fold less than the effective concentrations determined in in vitro systems.


Capillary gas chromatography-mass spectrometry quantitative determination of hydroxytyrosol and tyrosol in human urine after olive oil intake.

One of the prerequisites to extrapolate these data to an in vivo situation is the knowledge of their bioavailability in humans.


Investigations on the pharmacokinetics of alpha-lipoic acid in healthy volunteers.

Plasma concentrations of alpha-lipoic acid were determined using a validated reversed-phase HPLC method with electrochemical detection having a lower limit of quantitation of 1 ng/ml.


Plasma kinetics, metabolism, and urinary excretion of alpha-lipoic acid following oral administration in healthy volunteers.

Exogenous racemic alpha-lipoic acid orally administered for the symptomatic treatment of diabetic polyneuropathy is readily and nearly completely absorbed, with a limited absolute bioavailability of about 30% caused by high hepatic extraction.


Bioavailability and Sustained Plasma Concentrations of CoQ10 in Healthy Volunteers by a Novel Oral Timed-Release Preparation.

This bioavailability study intended to explore the plasma concentration levels of a novel CoQ10 oral preparation (COQUN®, Coenzyme Q10 Miniactives Retard 100 mg capsules) mimicking assumption on a regular basis.


Absorption, metabolism, and antioxidant effects of pomegranate (Punica granatum l.) polyphenols after ingestion of a standardized extract in healthy human volunteers.

This study investigated the absorption and antioxidant effects of a standardized extract from pomegranate in healthy human volunteers after the acute consumption of 800 mg of extract.


Effect of slow-release β-alanine tablets on absorption kinetics and paresthesia.

The aim of this single-blinded, randomized three-arm clinical trial was to compare plasma kinetics and symptoms following βA bolus administration in solution or in slow-release tablet form.


Plasma kinetics of lutein, zeaxanthin, and 3-dehydro-lutein after multiple oral doses of a lutein supplement.

The objective was to characterize lutein plasma kinetics in a multiple dosing design and to assess the effects of lutein intake on concentrations of other plasma carotenoids.


Revisiting the bioavailability of flavan-3-ols in humans: A systematic review and comprehensive data analysis.

This systematic review summarizes findings from human studies investigating the different routes of absorption, metabolism, distribution and excretion (ADME) of dietary flavan-3-ols and their circulating metabolites in healthy subjects.


Bioavailability of apigenin from apiin-rich parsley in humans.

Absorption and excretion of apigenin after the ingestion of apiin-rich food, i.e.


Alpha-lactalbumin Effect on Myo-inositol Intestinal Absorption: In vivo and In vitro.

Myo-inositol is a natural molecule with important therapeutic applications and an impaired oral absorption may result in a reduced clinical effect.


Bioavailability and metabolism of orange juice flavanones in humans: impact of a full-fat yogurt.

The bioavailability of dietary phytochemicals may be influenced by the food matrix in which they are consumed.


Plasma kinetics and urinary excretion of the flavanones naringenin and hesperetin in humans after ingestion of orange juice and grapefruit juice.

No data are available regarding plasma concentrations or plasma kinetics of flavanones.


Pharmacokinetics of oral betaine in healthy subjects and patients with homocystinuria.

Large oral doses of betaine have proved effective in lowering plasma homocysteine in severe hyperhomocysteinaemia.


Intestinal absorption and tissue distribution of [14C]pyrroloquinoline quinone in mice.

Consequently, the present study was undertaken to determine the extent to which PQQ is absorbed by the intestine, its tissue distribution, and route of excretion.


[6S]-5-methyltetrahydrofolate increases plasma folate more effectively than folic acid in women with the homozygous or wild-type 677C-->T polymorphism of methylenetetrahydrofolate reductase.

The metabolism of [6S]-5-MTHF and FA was evaluated by measuring plasma folate derivatives.


Enhanced bioavailability and pharmacokinetics of a novel hybrid-hydrogel formulation of fisetin orally administered in healthy individuals: a randomised double-blinded comparative crossover study.

However, the clinical effectiveness of fisetin may be limited by its poor bioavailability when ingested.


Identification of absolute conversion to geraldol from fisetin and pharmacokinetics in mouse.

J Chromatogr B Analyt Technol Biomed Life Sci

The concentration of fisetin and geraldol in mouse plasma was determined by LC-MS/MS, following direct protein precipitation.


Improving water dispersibility and bioavailability of luteolin using microemulsion system.

We have studied the physiological effects and health functions of luteolin, especially focusing on its absorption and metabolism.


effect of dose size on bioavailability of acylated and nonacylated anthocyanins from red cabbage (Brassica oleracea L. Var. capitata).

Recent studies indicate that anthocyanin intake conveys a variety of health benefits, which depend on absorption and metabolic mechanisms that deliver anthocyanins and their bioactive metabolites to responsive tissues.


The pharmacokinetic profile of crocetin in healthy adult human volunteers after a single oral administration.

Plasma concentrations of crocetin were determined by high-performance liquid chromatography (HPLC).


Pharmacokinetics, Tissue Distribution and Excretion of Demethyleneberberine, a Metabolite of Berberine, in Rats and Mice.

However, the pharmacokinetics, tissue distribution and excretion of demethyleneberberine have not been reported.


Liposomal glutathione outperforms plain glutathione in uptake, cell regeneration and systemic availability: evidence from cellular and human models.

However, oral glutathione supplementation is limited by poor bioavailability due to gastrointestinal degradation and low membrane permeability.


Pharmacokinetics of micronized and water dispersible palmitoylethanolamide in comparison with standard palmitoylethanolamide following single oral administration in male Sprague-Dawley rats.

It has poor water solubility and, therefore, is not readily absorbed in the human body.


Pharmacokinetics of solid lipid Boswellia serrata particles in healthy subjects.

One of the limitations of BAs is their poor oral bioavailability.


Single-dose comparative pharmacokinetic/pharmacodynamic study of a micellar formulation versus a native Boswellia serrata dry extract in healthy volunteers.

Micellar formulations have been developed to increase the oral bioavailability of bioactive boswellic and lupeolic acids.


Pharmacokinetics of a Natural Self-emulsifying Reversible Hybrid-Hydrogel (N'SERH) Formulation of Full-Spectrum Boswellia serrata Oleo-Gum Resin Extract: Randomised Double-Blinded Placebo-Controlled Crossover Study.

AUC (U-BE) = 2365.87 ± 346.89 ng * h/mL], with the absorption maximum (Tmax) at 6.3 h post-administration and elimination half-life (T1/2) of 15.5 h (p < 0.001).


Intestinal absorption of polyenephosphatidylcholine in man.

More than 90% of both isotopes was absorbed from the intestine.


Topical L-ascorbic acid: percutaneous absorption studies.

Maximal concentration for optimal percutaneous absorption was 20%.


Penetration of topical diclofenac into synovial tissue and fluid of osteoarthritic knees: a multicenter, randomized, placebo-controlled, pharmacokinetic study.

We investigated penetration of topical diclofenac into knee synovial tissue and fluid (primary objective) and evaluated relative exposure in the knee versus plasma (secondary objective).


Penetration of topical diclofenac sodium 4 % spray gel into the synovial tissue and synovial fluid of the knee: a randomised clinical trial.

The present study was designed to evaluate the penetration of diclofenac sodium 4 % spray gel in synovial tissue, synovial fluid and blood plasma after topical application in subjects with joint effusions and planned total knee arthroplasty (TKA) due to osteoarthritis.


Pharmacokinetic analysis of capsaicin after topical administration of a high-concentration capsaicin patch to patients with peripheral neuropathic pain.

To determine systemic capsaicin exposure after single 60- or 90-minute NGX-4010 applications, plasma samples were collected from 173 patients with postherpetic neuralgia (PHN), painful human immunodeficiency virus-associated neuropathy (HIV-AN), and painful diabetic neuropathy (PDN).


A role for the antioxidants coenzyme Q10 and pyrroloquinoline quinone in mitigating obesity-associated reproductive dysfunction

Pyrroloquinoline quinone enhances mitochondrial biogenesis, regulates fatty acid metabolism, and ameliorates inflammation, with preclinical studies showing improved fertility and pregnancy rates, as well as protective effects against the development of adult metabolic diseases in offspring of pregnancies complicated with obesity.


Maternal Pyrroloquinoline Quinone Supplementation Improves Offspring Liver Bioactive Lipid Profiles throughout the Lifespan and Protects against the Development of Adult NAFLD

Our findings suggest that PQQ supplementation during gestation and lactation augments pathways involved in the biosynthesis of long-chain fatty acids and plays a unique role in modifying specific bioactive lipid species critical for protection against NAFLD risk in later life.


Thirty days of supplementation with PQQ reprograms immunometabolic networks in Western diet-fed female baboons

Preprint, not yet peer-reviewed: PQQ rapidly reprograms systemic immunometabolic networks in a nonhuman primate model of diet-induced metabolic stress — 30 days at a human-equivalent dose lowered C-reactive protein, soluble CD163 and atherogenic lipoprotein fractions in Western diet-fed female baboons.


Identification of lactate dehydrogenase as a mammalian pyrroloquinoline quinone (PQQ)-binding protein

Our results suggest that PQQ, modulating LDH activity to facilitate pyruvate formation through its redox-cycling activity, may be involved in the enhanced energy production via mitochondrial TCA cycle and oxidative phosphorylation.


Structural and Functional Basis of G Protein-Coupled Receptor 35 Activation by Pyrroloquinoline Quinone

These findings indicate that PQQ functions as a food-derived agonist of GPR35 and provide new insights into the molecular mechanisms underlying the potential beneficial effects of PQQ.


Proresolving Lipid Mediators in the Respiratory System.

The omega-3 fatty acids (e.g., DHA and EPA) are precursors to resolvins, protectins, and maresins, which are families of chemically distinct mediators with potent functions in resolution of acute and chronic inflammation in the respiratory system.


Specialized pro-resolving mediators in vascular inflammation and atherosclerotic cardiovascular disease.

Specialized pro-resolving mediators are a superfamily of signalling molecules that initiate anti-inflammatory and pro-resolving actions.


Evidence: Cardiorespiratory fitness (VO2max)

Regular exercise improves cardiorespiratory fitness and physiological function, enhancing quality of life and promoting life expectancy, though it does not extend genetically determined lifespan.

no-difference-cue: "does not extend" | favorable-cue: "improve"

What are the age-related physiological adaptations to regular exercise training, specifically concerning the lung, heart, and skeletal muscles, and how does exercise training impact life expectancy in clinically referred populations?

Hypothesis: The review aims to emphasize that regular exercise training leads to age-related physiological adaptations in organs involved in oxygen delivery and utilization, and that it is important for promoting life expectancy in clinically referred populations.

This is a review article that synthesizes existing evidence regarding cardiorespiratory fitness (VO2max), age-related physiological adaptations to exercise, and the impact of exercise training on life expectancy in clinically referred populations.

Cardiorespiratory fitness (VO2max) is a strong and independent predictor of all-cause and disease-specific mortality. Regular exercise training induces age-related physiological adaptations in the lung, heart, and skeletal muscles, which are the main organs involved in oxygen delivery and utilization.

Regular exercise training is crucial for promoting life expectancy in clinically referred populations by inducing physiological adaptations in key organs. While it cannot extend the genetically fixed lifespan, it can improve the quality of life during those years.

The review acknowledges that regular exercise training cannot extend the genetically fixed lifespan.


Aging-associated decline of phosphatidylcholine synthesis is a malleable trigger of natural mitochondrial aging.

In worms and human cells, restoring phosphatidylcholine reversed key features of mitochondrial aging — making dietary PC/choline a promising, testable lever, but one not yet proven in human trials.

Why do mitochondria become dysfunctional during normal ("natural") aging — and can that decline be reversed?

Hypothesis: A specific, modifiable molecular change — not only genetic damage — drives the mitochondrial-network disruption of normal aging, so correcting it could restore mitochondrial function.

Researchers combined proteomics, lipidomics, genetics and functional tests in wild-type C. elegans and in long-lived clk-1 and isp-1 mitochondrial mutants, then cross-checked with transcriptomics and metabolomics in humans, and tested dietary phosphatidylcholine supplementation in nematodes and in human cell culture.

Aging was accompanied by a decline in phosphatidylcholine (PC) synthesis that triggered disruption of the mitochondrial network and contributed to mitochondrial dysfunction. Boosting PC through the diet restored late-life mitochondrial integrity in living nematodes and reinstated metabolic resilience in human cell-culture tests.

An age-related decline in phosphatidylcholine synthesis is a previously unrecognized, natural driver of mitochondrial aging — and, importantly, it is malleable by dietary intervention in these model systems.

The in-vivo reversal was shown in nematodes and in human cell cultures, not in living people. The study does not establish that a phosphatidylcholine supplement slows aging or improves health outcomes in humans.


Effects of Gabapentin and Pregabalin on Calcium Homeostasis: Implications for Physical Rehabilitation of Musculoskeletal Tissues

Gabapentin and pregabalin relieve nerve pain by blocking the α2δ1 calcium-channel subunit — but that same subunit matters in bone, muscle and cartilage, so long-term use is linked to worse musculoskeletal outcomes and higher fracture risk: a key consideration in physiatry and rehab.

How do the nerve-pain drugs gabapentin and pregabalin affect bone, muscle and cartilage — and what does that mean for physical rehabilitation?

Hypothesis: Because gabapentinoids act on the α2δ1 calcium-channel subunit that is also expressed in musculoskeletal tissues, long-term use may disrupt the calcium-mediated signaling important for skeletal formation, mechanosensation and tissue repair.

A narrative review of the mechanism of action of gabapentinoids and the evidence on how chronic treatment affects the musculoskeletal system.

Gabapentin (GBP) and pregabalin (PGB), originally antiepileptics and now first-line for neuropathic pain (and often prescribed off-label for migraine and back pain), produce analgesia by selectively binding the α2δ1 auxiliary subunit of voltage-sensitive calcium channels and inhibiting channel function. The same α2δ1 subunit is expressed in bone, muscle and cartilage, where it has important roles in skeletal formation, mechanosensation and normal tissue function and repair. Long-term gabapentinoid use is associated with detrimental musculoskeletal outcomes, including increased fracture risk.

Clinicians guiding rehabilitation should weigh the potential musculoskeletal complications of chronic gabapentinoid use, since these drugs may interfere with the calcium signaling that bone, muscle and cartilage rely on to adapt and heal.

Much of the mechanistic evidence comes from preclinical and tissue-level studies; the authors call for more research to define the clinical magnitude of the musculoskeletal risk.