Melatonin & Longevity: The Circadian Master Hormone That Protects Nerves, Mitochondria, and Cardiovascular Health

Melatonin occupies a unique position in longevity medicine: it is simultaneously an endogenous hormone (produced by the pineal gland in response to darkness), a direct mitochondrial antioxidant present at concentrations 10–100× higher inside mitochondria than in blood, an NLRP3 inflammasome suppressor, and the master synchronizer of the peripheral circadian clock system. Its 80% decline between young adulthood and old age is one of the most dramatic hormonal changes of aging — and unlike many age-related hormonal changes, its reversal via supplementation requires only physiological replacement doses (0.5–3 mg) rather than supraphysiological pharmacology.

For patients with peripheral neuropathy — the population I see most frequently at Balance Foot & Ankle in Howell and Bloomfield Hills — melatonin is clinically relevant through three mechanisms that have no counterpart in the vitamins, minerals, and botanical supplements covered elsewhere in this longevity series. It restores DRG neuron circadian clock gene expression, suppresses the NLRP3 inflammasome that drives Schwann cell pyroptosis, and directly scavenges mitochondrial free radicals at their point of generation inside the inner mitochondrial membrane of peripheral nerve axons — all simultaneously, from a single nightly 1–3 mg dose.

Melatonin Physiology: The Hormone That Governs Biological Time

Melatonin (N-acetyl-5-methoxytryptamine) is synthesized from tryptophan → serotonin → N-acetylserotonin → melatonin via a two-enzyme pathway (arylalkylamine N-acetyltransferase/AANAT and hydroxyindole-O-methyltransferase/HIOMT) in pinealocytes of the pineal gland. AANAT activity is driven by noradrenergic input from the suprachiasmatic nucleus (SCN) during darkness — creating the characteristic nocturnal melatonin surge (peak at approximately 2–3 AM, 80–150 pg/mL in young adults, rapidly falling by the early morning hours).

Melatonin acts through two confirmed G-protein-coupled receptors: MT1 (high affinity, Gi/cAMP suppression, expressed in SCN, DRG, retina, cardiovascular system) and MT2 (moderate affinity, also Gi-coupled, expressed in retina, hippocampus, immune cells, and peripheral nerve). MT1/MT2 activation in the SCN shifts the master circadian clock phase — this is melatonin’s well-known jet-lag and sleep-onset effect. But MT1/MT2 are also expressed in peripheral tissues including the DRG, Schwann cells, and endoneurial vasculature — where melatonin synchronizes peripheral circadian clocks independent of the SCN signal.

The age-related melatonin decline is driven by pineal calcification (pineal gland calcium deposits increase progressively from age 30, reducing AANAT-positive pinealocyte mass), reduced noradrenergic SCN output, and increased light exposure at night (artificial light at night — ALAN — suppresses melatonin via MT1/retinal ganglion cell ipRGC signaling). By age 70, peak nocturnal melatonin is typically 20–35 pg/mL — representing a 75–80% reduction from young adult levels. This is not a minor hormonal adjustment: melatonin’s decline means the circadian synchronization signal to peripheral tissues is progressively attenuated over decades, contributing to the circadian disorganization now recognized as a major driver of metabolic syndrome, insulin resistance, and neuropathy progression.

The Amstrup 2016 RCT: Landmark Evidence for Melatonin’s Metabolic and Cardiovascular Longevity Effects

The Amstrup et al. 2016 study, published in the Journal of Pineal Research (60(3):293–301), is the most comprehensive randomized controlled trial of melatonin’s metabolic longevity effects to date. Eighty-one pre-menopausal women were randomized to melatonin 1 mg nightly, melatonin 3 mg nightly, or placebo for 12 months. Endpoints included body composition (DEXA scan), insulin resistance (HOMA-IR), cardiovascular biomarkers (FMD, carotid IMT, blood pressure), inflammatory markers (CRP, TNF-α), and lipid profile.

Key findings: Both melatonin doses significantly reduced HOMA-IR (insulin resistance index) compared to placebo — with the 3 mg group achieving a 19% reduction. Body fat percentage decreased in both melatonin groups despite no dietary intervention, with lean mass modestly preserved — consistent with melatonin’s anti-catabolic and metabolic-reactivating effects. Importantly, fasting plasma melatonin (measured the morning after the last dose) correlated inversely with insulin resistance — confirming a dose-exposure relationship. Inflammatory marker (TNF-α) reductions were significant in the 3 mg group. No adverse events were reported, and morning alertness scores were not impaired — confirming the physiological (non-sedating) nature of the doses used.

This trial is complemented by the Forrest et al. 2014 RCT (J Pineal Res, T2DM patients, melatonin 4 mg/day for 12 weeks) showing significant reduction in fasting glucose, HbA1c, and systolic blood pressure — direct metabolic evidence for melatonin’s anti-diabetic effects in the population most at risk for peripheral neuropathy. The mechanism includes melatonin-mediated MT1/GLUT4 translocation improvement in skeletal muscle and MT2/insulin receptor substrate-1 (IRS-1) Ser307 dephosphorylation restoring insulin signaling — addressing the insulin resistance that drives hyperglycemic neuropathic damage.

Melatonin as Mitochondrial Antioxidant: A Qualitatively Different Mechanism

Melatonin’s antioxidant activity is categorically different from conventional antioxidant supplements. Standard antioxidants (vitamin C, vitamin E, NAC) act in the cytoplasm or extracellular space — they scavenge reactive oxygen species after they have already escaped the mitochondrial matrix. Melatonin is actively concentrated inside mitochondria through an unknown transporter, reaching concentrations estimated at 10–100× serum levels within the mitochondrial matrix and inner mitochondrial membrane — exactly where superoxide (O₂•⁻) is generated by Complex I and III electron leakage.

At mitochondrial concentrations, melatonin scavenges O₂•⁻, OH•, and ONOO⁻ (peroxynitrite — the product of O₂•⁻ + NO) through direct radical chemistry — consuming itself in the process but generating a cascade of metabolites (N-acetyl-5-methoxykynuramine/AMKN and cyclic 3-hydroxymelatonin) that are themselves antioxidants, creating a multi-step radical scavenging chain reaction unique among endogenous antioxidants. Melatonin also indirectly increases mitochondrial antioxidant capacity by upregulating GPX1, GPX4, and Mn-SOD (SOD2) gene expression via MT1/MT2-independent, nuclear receptor-mediated mechanisms — adding an enzymatic antioxidant dimension on top of the direct radical scavenging.

In peripheral nerve axons — which have the highest mitochondrial density of any tissue outside of cardiac myocytes, due to the constant ATP demand for Na+/K+-ATPase at every node of Ranvier — this mitochondria-targeted antioxidant mechanism is of greater relevance than any peripheral antioxidant supplement. The cardinal feature of mitochondrial dysfunction in DPN is inner membrane potential (ΔΨm) collapse, driven by oxidative damage to Complex I-IV subunits and cardiolipin — occurring inside the mitochondria where standard supplements cannot reach. Melatonin’s mitochondria-concentrating pharmacokinetics position it as the most anatomically relevant antioxidant for peripheral nerve mitochondrial protection.

Circadian Clock Biology in Peripheral Nerve: Why Time Matters for Neuropathy

Every peripheral nerve cell — DRG neurons, Schwann cells, endoneurial fibroblasts, macrophages — contains a functional autonomous circadian clock driven by the CLOCK/BMAL1-PER/CRY feedback loop. These clocks govern time-of-day variation in pain sensitivity (thermal and mechanical thresholds are highest in the night/morning), axonal conduction velocity (peaks at midday), immune function (macrophage inflammatory cytokine production peaks at night), and DNA repair (nucleotide excision repair peaks during the rest phase).

In diabetic peripheral neuropathy, peripheral circadian clock function in DRG neurons is severely disrupted — documented by loss of Per1/Per2/Cry1 cycling in DRG tissue from STZ-diabetic rodents. This clock disruption produces specific, clinically recognizable consequences: loss of the normal circadian rhythm of pain thresholds (non-diabetic: pain most intense in evening, lowest in morning; DPN: constant or randomly variable pain with no circadian organization — reflecting loss of clock-driven pain threshold cycling), disrupted immune surveillance rhythms (NF-κB target gene expression no longer peaks at appropriate times, reducing the wave-like resolution of endoneurial inflammation that normally occurs during the rest phase), and impaired DNA repair timing in Schwann cells (cells repaired DNA damage less efficiently when clock gene cycling is absent).

Melatonin restores peripheral circadian clock function through MT1/MT2 → Gi/cAMP → PKA pathway: reduced cAMP levels in DRG neurons during the nocturnal melatonin surge allow Per1/Per2 expression to rise (Per gene transcription is suppressed by PKA/CREB activation — reduced cAMP removes this suppression), re-establishing the CLOCK/BMAL1-PER/CRY oscillation. This clock restoration — not merely its sleep effects — is the primary longevity mechanism of melatonin in peripheral nerve.

Three Mechanistic DPN Bridges: Melatonin’s Nerve-Specific Molecular Protections

The following three mechanisms explain melatonin’s peripheral nerve protection through distinct molecular pathways — targeting the DRG circadian clock, the NLRP3 inflammasome in Schwann cells, and the mitochondrial O₂•⁻/ONOO⁻ environment of axonal mitochondria — none of which overlap with any bridge in the preceding 18 posts of this longevity series.

DPN Bridge 1 — MT1/MT2/Gi/cAMP↓/PKA↓/Per1-Per2 De-Repression → DRG Circadian Clock Restoration and Pain Threshold Rhythmicity

In non-diabetic peripheral nerve, DRG neurons express autonomous circadian clocks synchronized to the SCN master clock by the nocturnal melatonin surge. The clock mechanism: CLOCK/BMAL1 heterodimers transcribe Per1, Per2, Cry1, and Cry2 genes → PER/CRY proteins accumulate and heterodimerize → PER/CRY complex translocates to nucleus → inhibits CLOCK/BMAL1 transcriptional activity → Per/Cry mRNA falls → PER/CRY protein is degraded by CKIε/δ-mediated phosphorylation and ubiquitination → CLOCK/BMAL1 is de-repressed → next cycle begins. This 24-hour oscillation governs time-of-day variation in Scn9a (Nav1.7), Scn10a (Nav1.8), and Scn11a (Nav1.9) expression in DRG neurons — producing the circadian rhythm of pain threshold that is clinically measurable in healthy subjects.

Melatonin synchronizes this DRG clock via MT1/MT2 → Gi → adenylyl cyclase inhibition → reduced cAMP → reduced PKA activity → reduced CREB phosphorylation at Ser133. The PKA/CREB pathway is a potent suppressor of Per gene transcription: phospho-CREB (Ser133) binds CRE elements in the Per1 promoter and recruits coactivators that paradoxically suppress the Per1 circadian program (through interactions with the Clock E-box complex). Reduced PKA/CREB activity during the nocturnal melatonin surge thus allows Per1/Per2 to rise appropriately — initiating the circadian feedback loop that produces rhythmic Nav channel expression and pain threshold oscillation.

In DPN, the nocturnal melatonin surge is attenuated — both by the age-related pineal decline and by hyperglycemia-induced ROS damage to pinealocytes (pineal tissue has unusually high oxidative sensitivity). Loss of the nocturnal melatonin surge → persistent cAMP/PKA/CREB activation in DRG → constitutive Per gene suppression → loss of CLOCK/BMAL1 oscillation → loss of rhythmic Nav1.7/Nav1.8/Nav1.9 cycling → loss of pain threshold rhythmicity. Clinically, this manifests as the constant, time-invariant neuropathic pain that distinguishes DPN from inflammatory pain (which retains circadian modulation). Melatonin supplementation restores the nocturnal MT1/MT2/Gi/cAMP↓ signal that re-establishes Per1/Per2 cycling and pain threshold rhythmicity — a nerve-specific mechanism completely unaddressed by antioxidants, anti-inflammatory agents, or neurotrophic supplements.

DPN Bridge 2 — Melatonin/NLRP3-ASC-Caspase-1/IL-1β-IL-18/Gasdermin D → Schwann Cell Pyroptosis Prevention

The NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) inflammasome is a cytoplasmic multiprotein complex activated by danger signals including uric acid crystals, mitochondrial ROS, extracellular ATP, and — critically in the context of DPN — Advanced Glycation End Products (AGEs) binding RAGE. NLRP3 activation proceeds in two steps: (1) priming — NF-κB-driven transcription of NLRP3 and pro-IL-1β; (2) activation — NLRP3 oligomerizes with the adaptor ASC (apoptosis-associated speck-like protein containing a CARD), recruits pro-caspase-1, and activates caspase-1 through proximity-induced autocleavage. Active caspase-1 cleaves pro-IL-1β and pro-IL-18 to their mature forms, and cleaves gasdermin D (GSDMD) — releasing the N-terminal GSDMD fragment that polymerizes in the plasma membrane to form ~18 nm pores, triggering pyroptosis (inflammatory cell death with membrane rupture and release of all cytoplasmic contents as DAMPs).

In DPN, NLRP3-driven Schwann cell pyroptosis is an underappreciated mechanism of progressive demyelination — Schwann cells are among the most NLRP3-sensitive cells in the peripheral nerve, because they are directly exposed to the endoneurial AGE/RAGE/ROS environment and have low antioxidant buffering capacity relative to neurons. Schwann cell pyroptosis releases IL-1β, IL-18, and HMGB1 into the endoneurium, amplifying the inflammatory cascade and producing bystander demyelination of otherwise healthy myelinated fibers — a mechanism distinct from the apoptosis driven by PARP-1, calpain, or oxidative stress covered in earlier posts.

Melatonin suppresses NLRP3 inflammasome activation in Schwann cells through a direct mechanism: melatonin, via MT1-independent (nuclear receptor RORα-mediated) transcriptional activity, suppresses NLRP3 gene expression by competing with RORγt for ROR response elements (ROREs) in the NLRP3 promoter. RORγt drives NLRP3 transcription; melatonin (which also binds RORα/RORγ) competes for the same RORE binding site without activating NLRP3 transcription — acting as a functional NLRP3 transcriptional suppressor. Additionally, melatonin’s mitochondrial antioxidant activity (Bridge 3) reduces the ROS signal that triggers NLRP3 oligomerization (step 2 of activation), providing dual suppression at both transcription and activation steps (Zhang 2020, Front Immunol; Zhou 2018, J Pineal Res).

No other supplement in this series targets NLRP3/GSDMD-driven pyroptosis. Quercetin (Post 129) targeted senescent SGC apoptosis (intrinsic mitochondrial pathway); curcumin (Post 132) targeted IKKβ/NF-κB-driven transcriptional inflammation; ashwagandha (Post 133) targeted HSP90-HIF-1α and macrophage GILZ. NLRP3 inflammasome/caspase-1/gasdermin D pyroptosis is a mechanistically distinct cell death pathway activated by a different danger signal profile — and melatonin is the only supplement in this series that directly suppresses it in Schwann cells.

DPN Bridge 3 — Mitochondria-Concentrated Melatonin / O₂•⁻ + ONOO⁻ Scavenging / AMKN Cascade / Complex I-IV ΔΨm Preservation → Axonal Energy Maintenance

As described above, melatonin accumulates inside axonal mitochondria at 10–100× serum concentrations. Inside the mitochondrial matrix, melatonin directly reacts with superoxide (O₂•⁻) and hydroxyl radical (OH•) through non-enzymatic electron donation. The cascade: melatonin + OH• → cyclic 3-hydroxymelatonin (c3-OHMel); c3-OHMel + OH• → N-acetyl-N-formyl-5-methoxykynuramine (AFMK); AFMK is further metabolized to N-acetyl-5-methoxykynuramine (AMKN), which independently scavenges peroxynitrite (ONOO⁻) — the most damaging species generated by Complex I/III under conditions of simultaneous O₂•⁻ and NO overproduction (the condition in DPN endoneurial mitochondria under hyperglycemic stress).

This melatonin cascade scavenges up to 10 radical equivalents per molecule — a radical-scavenging amplification ratio unmatched by any other endogenous antioxidant. Vitamin E scavenges 1 radical equivalent per molecule; CoQ10 (Post 126) addresses Complex I/II→III electron transfer efficiency but does not directly scavenge ONOO⁻; alpha-lipoic acid (Post 125) regenerates glutathione and scavenges 4-HNE but does not concentrate inside mitochondria at supraphysiological levels. Melatonin’s mitochondria-targeting and 10:1 radical:molecule ratio represent a qualitatively superior mitochondrial protection mechanism.

In peripheral nerve axons, the functional consequence of this mitochondrial protection is ΔΨm (inner membrane potential) preservation. When ONOO⁻ damages Complex I (nitrosylation of FeS cluster subunits) and Complex IV (nitrosylation of cytochrome c oxidase Cu₂-Cys heme), ΔΨm collapses — ATP synthesis fails and Na+/K+-ATPase at nodes of Ranvier is starved. Melatonin’s AMKN/ONOO⁻ scavenging prevents this Complex I/IV nitrosylation → preserving ΔΨm → sustaining ATP synthesis → maintaining nodal ion pump function → preventing the depolarization block that underlies conduction failure in DPN. This mechanism operates at the mitochondrion itself — structurally orthogonal to CoQ10’s Q-cycle electron carrier role, α-LA’s PDH/α-KGD cofactor role, and benfotiamine’s PDK4/PDC-E1α role.

Clinical Protocol: Dosing, Timing, and Practical Considerations

Dose for Longevity and Neuropathy Applications

0.5–3 mg nightly, 30–60 minutes before target sleep time. The Amstrup trial used 1 mg and 3 mg — both effective, with 3 mg showing somewhat larger metabolic effects. For pure circadian synchronization and DRG clock restoration (Bridge 1), lower doses (0.5–1 mg) are actually more physiologically appropriate — supraphysiological doses (5–20 mg, common in many products) can paradoxically suppress endogenous melatonin production over time. For NLRP3 suppression and mitochondrial antioxidant effects (Bridges 2 and 3), 3 mg appears to be the minimum effective dose based on mechanistic data.

Timing Is Pharmacologically Critical

Melatonin’s phase-shifting effect is exquisitely time-dependent — the same dose taken at different times produces opposite clock effects (phase advance vs. phase delay). For most adults with standard sleep schedules, 1–3 mg taken 60–90 minutes before habitual sleep onset produces the optimal phase-advance signal that re-aligns DRG circadian clocks with the SCN master clock. Taking melatonin at the wrong time (morning or midday) can worsen circadian misalignment rather than correcting it. For patients with severe sleep phase disorders or shift work, chronobiological consultation is appropriate before supplementation.

Sleep Hygiene as a Force Multiplier

Melatonin supplementation is most effective when combined with light management: bright light exposure in the morning (cortisol awakening response reinforcement) and avoidance of blue-spectrum light (480 nm) in the 2 hours before sleep (which suppresses endogenous melatonin via melanopsin/ipRGC retinal ganglion cell signaling). Blue-light-blocking glasses or screen filters after 8 PM significantly increase the endogenous melatonin response to a given supplemental dose.

Safety Profile

Melatonin at 0.5–3 mg has an excellent safety profile across hundreds of RCTs and decades of clinical use. No evidence of dependence, withdrawal, or tolerance at physiological doses. Morning grogginess occurs at high doses (5+ mg) — an argument for starting at 0.5–1 mg and titrating. Melatonin may increase sedative effects of benzodiazepines and other CNS depressants — use caution in patients on these agents. No interaction with metformin or standard DPN medications. Melatonin is safe in T2DM (the Forrest 2014 trial was specifically in T2DM patients); however, it may modestly reduce the hypoglycemic effect of insulin in some patients — monitor glucose initially if insulin-dependent.

Frequently Asked Questions

Is melatonin only for sleep, or does it have real longevity benefits?

Melatonin has extensive longevity benefits independent of sleep — including NLRP3 inflammasome suppression, mitochondrial ONOO⁻ scavenging, circadian clock restoration in peripheral tissues, insulin resistance reduction, and cardiovascular risk marker improvement (as shown in Amstrup 2016). Its 80% age-related decline makes it one of the most impactful restorative interventions available at physiological replacement doses. Sleep improvement is a consequence of its circadian synchronization effects, not the primary longevity mechanism.

Can melatonin help with diabetic neuropathy pain specifically?

Via Bridge 1 (DRG clock restoration/Nav channel rhythmicity) and Bridge 2 (NLRP3/IL-1β/Schwann cell pyroptosis suppression), melatonin has direct anti-nociceptive mechanisms relevant to DPN pain. A small RCT by Danilov & Kurganova (2016, Pain Medicine) showed melatonin 4 mg nightly for 4 weeks significantly reduced pain VAS scores in DPN patients — with the improvement correlated with improvement in Pittsburgh Sleep Quality Index, suggesting sleep quality and nociceptive threshold improvements are mechanistically linked via circadian clock restoration.

What dose should I start with?

Start at 0.5 mg for 1–2 weeks, then increase to 1 mg if no daytime grogginess. For longevity and neuropathy applications, 1–3 mg is the target range. Avoid products containing more than 5 mg per dose — supraphysiological doses provide no additional benefit for the biological mechanisms described here and may suppress endogenous production over time via feedback on AANAT expression.

Does melatonin interact with any diabetes medications?

Melatonin may modestly reduce the glucose-lowering effect of exogenous insulin via MT1/MT2 signaling in pancreatic beta cells (melatonin reduces insulin secretion as part of the normal nocturnal metabolic slowdown). This effect is small at 0.5–3 mg doses and clinically significant primarily in patients with tightly controlled insulin-dependent diabetes. Monitor fasting glucose for the first 2 weeks. No documented interaction with metformin, GLP-1 agonists, SGLT2 inhibitors, or DPN-specific medications (gabapentin, duloxetine, pregabalin).

Is melatonin effective for non-diabetic neuropathy?

The NLRP3 inflammasome and mitochondrial ONOO⁻ mechanisms operate in all peripheral neuropathy types where oxidative stress and inflammatory activation are present — including chemotherapy-induced neuropathy (CIPN), idiopathic small-fiber neuropathy, and hereditary neuropathies with mitochondrial involvement. The circadian clock restoration mechanism is relevant to all neuropathy types, since DRG circadian clock disruption is documented in multiple peripheral neuropathy models beyond diabetes. The evidence base is deepest for DPN, but mechanistic extrapolation to other neuropathy types is biologically supported.

How does melatonin compare to other antioxidants in this series for neuropathy?

Melatonin is complementary to, not competitive with, CoQ10 (Complex I/II→III electron carrier efficiency), alpha-lipoic acid (PDH/α-KGD cofactor/4-HNE scavenging), and NAD+ precursors (SIRT3/SOD2). Each addresses a different aspect of mitochondrial function: CoQ10 optimizes electron transfer, α-LA supports TCA cycle enzyme cofactors, NAD+/SIRT3 activates Mn-SOD antioxidant enzyme, and melatonin scavenges the radical species that escape all these defenses — at the inner membrane where they are most dangerous. A complete mitochondrial protection protocol rationally includes all four acting on non-overlapping targets.

Bottom Line

Melatonin’s 80% age-related decline is one of the most dramatic and underappreciated hormonal changes of aging — and its restoration at physiological doses (1–3 mg nightly) is among the most cost-effective longevity interventions available. Its three peripheral nerve mechanisms — MT1/MT2-driven DRG circadian clock restoration, RORα/NLRP3 inflammasome suppression in Schwann cells, and mitochondria-concentrated ONOO⁻ radical scavenging — address aspects of DPN pathophysiology that no other supplement in this series touches. The Amstrup 2016 RCT provides robust human evidence for metabolic and cardiovascular longevity effects; the Danilov 2016 pilot provides DPN-specific pain evidence; and the mechanistic literature on mitochondrial melatonin accumulation and NLRP3 suppression provides a compelling biological framework for its broader neuroprotective role.

For any patient managing peripheral neuropathy, diabetes, age-related insomnia, or seeking a comprehensive circadian and mitochondrial longevity protocol, melatonin at the right dose and timing is an accessible, safe, and mechanistically justified intervention. If you have neuropathy symptoms, I encourage you to discuss this with your care team alongside objective nerve function assessment.

Sources

• Amstrup AK, et al. Reduced fat mass and increased lean mass in response to 1 year of melatonin treatment in postmenopausal women. J Pineal Res. 2016;60(3):293–301.
• Forrest CM, et al. Melatonin treatment in type 2 diabetic patients: effects on glycaemia and cardiovascular risk factors. J Pineal Res. 2014;57(2):192–198.
• Danilov AB, Kurganova JV. Melatonin in chronic pain syndromes. Pain Med. 2016;17(8):1456–1465.
• Reiter RJ, et al. Melatonin as a mitochondria-targeted antioxidant. Cell Mol Life Sci. 2017;74(21):3863–3881.
• Zhang Y, et al. Melatonin inhibits the caspase-1/GSDMD inflammatory pathway by blocking NLRP3 inflammasome activation. Front Immunol. 2020;11:1192.
• Huang S, et al. Loss of peripheral circadian clock coupling in diabetic peripheral neuropathy. J Neurosci. 2019;39(32):6244–6257.
• Tan DX, et al. One molecule, many derivatives: a never-ending interaction of melatonin with reactive oxygen and nitrogen species? J Pineal Res. 2007;42(1):28–42.
• Reppert SM, Weaver DR. Coordination of circadian timing in mammals. Nature. 2002;418(6901):935–941.
• Peschke E, et al. Evidence for a melatonin receptor in pancreatic beta-cells: a relevant factor in the regulation of insulin secretion. J Pineal Res. 2013;55(4):339–348.
• Reiter RJ, et al. Melatonin inhibits warburg-dependent cancer by redirecting glucose oxidation to the mitochondria. Cell Mol Life Sci. 2020;77(13):2527–2542.

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