Cólico (adultos)

Acetyl-L-Carnitine (ALC) has demonstrated neuroprotective and neurotrophic effects in multiple clinical trials involving peripheral neuropathy of various causes, including diabetic and chemotherapy-induced types. A landmark multicenter double-blind RCT (n=333, 12 months) showed significant improvement in nerve conduction velocity and a 39% reduction in pain scores versus 8% for placebo. A 2019 PMC systematic review of 14 clinical trials confirmed ALC's efficacy as both an etiological and symptomatic treatment with a good safety profile.

Alpha-Lipoic Acid is among the most extensively studied supplements for diabetic peripheral neuropathy, with multiple large-scale RCTs and meta-analyses supporting its use. The NATHAN I and SYDNEY trials demonstrated improvements in nerve conduction velocity and symptomatic neuropathy with 600 mg/day. A PMC meta-analysis found intravenous ALA (600 mg/day, 3 weeks) produces a clinically significant reduction in neuropathic pain (grade A recommendation). Evidence for long-term oral dosing remains more mixed per a 2024 Cochrane review.

Benfotiamine is a fat-soluble prodrug of thiamine (vitamin B1) with superior bioavailability in nerve tissue compared to water-soluble thiamine. Multiple RCTs have examined its use in diabetic and alcoholic neuropathy, with the BEDIP study (n=40, 3-week pilot RCT) confirming benefits in neuropathy symptom scores. A 2016 RCT (n=74) found 300 mg/day for 6 weeks significantly reduced neuropathic pain and burning versus placebo. A Cochrane-style systematic review found modest short-term benefit in vibration perception threshold.

GLA from borage oil has been investigated for diabetic peripheral neuropathy. Two of three RCTs using GLA (360–480 mg/day, 6–12 months) demonstrated statistically significant improvements in neuropathy scores, nerve conduction velocities, and sensory parameters. The mechanism involves bypassing the impaired delta-6-desaturase step seen in diabetics, restoring PGE1 production and improving endoneurial blood flow.

A prospective clinical study found a combination formula including Boswellia serrata effective for improving symptoms of chemotherapy-induced peripheral neuropathy with no significant toxicity. Mechanistic rationale involves anti-neuroinflammatory and antioxidant properties of boswellic acids.

B12 deficiency is a primary and well-established cause of peripheral neuropathy, characterized by demyelination of peripheral nerves. Bovine liver is the densest food source of B12. Correcting B12 deficiency with adequate dietary sources resolves or stabilizes B12-deficiency neuropathy in clinical practice.

Capsaicin is the primary vanilloid alkaloid that selectively activates TRPV1 receptors on sensory C-fiber nerve terminals, producing defunctionalization and prolonged pain relief in neuropathic conditions. An 8% topical capsaicin patch is FDA-approved for peripheral neuropathic pain. Systematic reviews confirm efficacy in post-herpetic neuralgia, HIV neuropathy, and evidence in painful diabetic neuropathy.

Capsaicinoids, particularly capsaicin, act on TRPV1 receptors on sensory C fiber nerve terminals, causing initial sensitization followed by prolonged defunctionalization of nociceptive nerve endings and pain relief. An 8% high-concentration capsaicin patch (Qutenza) is FDA- and EMA-approved for peripheral neuropathic pain. Systematic reviews and meta-analyses support efficacy in post-herpetic neuralgia, HIV-associated neuropathy, and painful diabetic neuropathy.

Capsaicin has robust clinical evidence — including a licensed pharmaceutical patch (Qutenza 8%) — for the treatment of peripheral neuropathic pain from postherpetic neuralgia, HIV-associated neuropathy, and diabetic peripheral neuropathy. A Cochrane review found moderate-quality evidence for the 8% patch in postherpetic neuralgia.

BCP selectively activates CB2 receptors to suppress neuropathic pain and neuroinflammation across multiple animal models including antiretroviral-, chemotherapy-, and diabetes-induced neuropathy. Mechanistic data from human cell lines are also available.

Topical capsaicin is clinically established for neuropathic pain, including diabetic peripheral neuropathy and postherpetic neuralgia. It desensitises C-fibre nociceptors by depleting substance P. Cochrane reviews rate evidence for low-concentration topical capsaicin as mildly positive for neuropathic pain, and high-concentration (8%) patches are prescription-approved.

A 2020 systematic review confirmed that in animal models of nerve damage citicoline stimulated regeneration and lessened pain, with citicoline also modulating MMP activity to promote axonal regeneration in peripheral nerve injury models. Human-level evidence for peripheral neuropathy remains limited, though citicoline's broader neuroprotective role in stroke and neurodegenerative disorders is established. It has been proposed as a novel adjuvant for painful diabetic polyneuropathy pending more human trials.

SKI306X, a standardized extract containing C. mandshurica, was tested in rodent models of neuropathic pain (chronic postischemic pain and spinal nerve ligation) and showed dose-dependent antiallodynic effects. Clematis has also been used traditionally in folk medicine for nervous disorders. Evidence remains preclinical.

Acquired copper deficiency is a recognized cause of myelopathy and peripheral neuropathy in humans. Clinical studies document that copper deficiency produces sensory ataxia, weakness, and demyelination reversible with copper supplementation. Risk is elevated after bariatric surgery, with excessive zinc supplementation, or with malabsorption.

Coenzyme Q10 is an endogenous mitochondrial electron carrier essential for ATP synthesis in metabolically demanding nerve cells. Mitochondrial dysfunction is a recognized mechanism in peripheral neuropathy, and CoQ10 supports nerve cell energy production. It is listed in authoritative neuropathy databases and is particularly relevant in statin-associated neuropathy (statins deplete CoQ10) and chemotherapy-induced peripheral neuropathy.

Curcumin, the principal polyphenol of turmeric, modulates neuroinflammatory pathways relevant to neuropathy through NF-κB inhibition and Nrf2 activation, reducing inflammatory cytokine expression and preserving nerve function in experimental neuropathy models. It has been used in traditional Ayurvedic and Chinese medicine for pain and inflammation for centuries. Combined DHA+curcumin has shown spinal cord neuroprotection in preclinical models.

Alpha-tocopherol deficiency causes peripheral neuropathy and spinocerebellar ataxia in humans, and high-dose supplementation is the established treatment for hereditary AVED (ataxia with vitamin E deficiency). Evidence also exists for α-tocopherol's role in preventing or slowing neuropathy associated with diabetes and other conditions of oxidative stress.

In a rat model of diabetic peripheral neuropathy, daidzein (the direct metabolite of daidzin) significantly attenuated neuropathic pain, improved nerve conduction velocity, and reduced oxidative stress in the sciatic nerve via NOX-4 inhibition. Evidence is preclinical.

Docosahexaenoic acid (DHA) is the principal omega-3 fatty acid incorporated into neuronal membrane phospholipids and is critical for neuronal membrane integrity and signal transduction. Preclinical studies confirm DHA-containing omega-3 sources improve nerve conduction velocity, intraepidermal nerve density, and corneal nerve fiber length in diabetic neuropathy models. Combined with curcumin, DHA demonstrated spinal cord neuroprotection with BDNF elevation in a myelopathy model.

DHA is a major structural component of peripheral and central nerve cell membranes, supporting axonal conduction and myelin integrity. DHA deficiency alters neuronal membrane composition including myelin and synaptosomes. DHA's anti-inflammatory and neuroprotective properties are relevant to peripheral neuropathy prevention and management.

Eicosapentaenoic acid (EPA) is a long-chain omega-3 fatty acid with well-documented anti-neuroinflammatory actions relevant to peripheral neuropathy. It competes with pro-inflammatory arachidonic acid at cyclooxygenase/lipoxygenase enzymes and serves as a precursor to E-series resolvins. Preclinical studies show EPA+DHA combination promotes peripheral nerve regeneration and reduces neuropathic pain behavior after nerve injury.

Evening primrose oil is the primary well-studied dietary source of GLA and has been directly tested in diabetic peripheral neuropathy RCTs, with significant improvements in nerve conduction and neuropathy symptom measures in the landmark multicenter trial. Animal studies show dose-dependent correction of reduced sciatic nerve conduction velocity and blood flow in diabetic models. Its benefit is attributed to its GLA content correcting the impaired delta-6-desaturase activity in diabetic patients.

Fisetin shows antihyperalgesic and antinociceptive effects in rodent neuropathic pain models via spinal serotonergic (5-HT7) system engagement. It also shows benefit in preclinical diabetic neuropathy models. Evidence is preclinical.

Fish oil omega-3s have been studied for peripheral neuropathy, particularly diabetic peripheral neuropathy. EPA and DHA support neuronal membrane integrity, reduce neuroinflammation, and promote nerve growth factor (NGF) expression. Clinical trials in diabetic patients show improvements in nerve conduction velocity and reduction in neuropathic pain symptoms with omega-3 supplementation.

FMN and FAD are required for maintenance of myelin integrity and neuronal energy metabolism. Riboflavin transporter deficiency causes secondary FMN/FAD depletion and progressive motor neuropathy (Brown-Vialetto-Van Laere syndrome), which is treated with high-dose riboflavin. FMN deficiency from any cause can produce degeneration of the nervous system.

GE is clinically used in China for sciatic neuropathy and has preclinical evidence for diabetic peripheral neuropathy via AMPK activation and MMP9 inhibition. GE promotes nerve regeneration and survival and is listed for neuropathy indications in Chinese clinical practice.

Ginkgo biloba extract (EGb 761) contains ginkgolides, bilobalide, and flavone glycosides that improve peripheral nerve blood flow, reduce oxidative stress, and promote nerve cell survival. Listed in authoritative peripheral neuropathy evidence databases alongside ALC and methylcobalamin, it has traditional use in Chinese medicine for nerve conditions dating to the Ming Dynasty and scientific evidence for microvascular and neuroprotective benefits.

Ginkgo flavone glycosides are the principal polyphenolic antioxidant fraction of standardized Ginkgo biloba extract (EGb 761), comprising flavonoid glycosides of quercetin, kaempferol, and isorhamnetin. They protect peripheral nerve cell membranes from oxidative damage and contribute to microcirculatory improvements supporting peripheral nerve perfusion, with relevance to neuropathy management.

Gamma-linolenic acid (GLA) is an omega-6 fatty acid whose supplementation has been shown in multiple RCTs to benefit diabetic peripheral neuropathy by correcting a metabolic deficiency in GLA conversion seen in diabetic patients. A GLA Multicenter Trial Group RCT (n=111, 12 months) showed significant improvement across 16 neuropathy measures. A 2019 noninferiority RCT demonstrated GLA was comparable to alpha-lipoic acid for painful diabetic neuropathy.

Glutamic acid is a structural component of glutathione (GSH), the body's principal antioxidant tripeptide (comprising glutamic acid, cysteine, and glycine), which protects peripheral nerves from oxidative damage. Reduced glutathione levels are linked to increased nerve degeneration in neuropathic conditions. GSH administration has shown neuroprotective effects in clinical studies of chemotherapy-induced peripheral neuropathy.

LBP has demonstrated neuroprotective effects in models of diabetic neuropathy, stroke, and retinal ischemia. In a stroke model, 7-day oral LBP pretreatment reduced infarct size, cerebral edema, and blood-brain barrier disruption. Diabetic nephropathy models show LBP reduces renal injury partly via nerve-related mechanisms. Reviews confirm neuroprotective activity as one of LBP's established properties.

Gotu Kola accelerates peripheral nerve regeneration in animal models and promotes neurite elongation in vitro. Preclinical studies show improved nerve conduction velocity in diabetic neuropathy models. A published animal study (Soumyanath et al., J Pharm Pharmacol, 2005) demonstrated oral administration accelerates axonal regeneration. Direct human clinical trials for neuropathy specifically are limited.

Hericenones are aromatic meroterpenoid compounds isolated exclusively from Hericium erinaceus fruiting bodies that potently stimulate NGF synthesis in vitro. Specific hericenones (C, D, E, H) induce NGF secretion from mouse astroglial cells at measurable concentrations, and their low molecular weight enables blood-brain barrier crossing. They are a principal bioactive fraction underlying Lion's Mane mushroom's neuroprotective and nerve-regenerating properties.

Hesperidin exhibits neuroprotective properties relevant to peripheral and central nerve health via antioxidant, anti-inflammatory, and anti-apoptotic mechanisms. Preclinical studies show hesperidin protects dopaminergic neurons in Parkinson's models and reduces diabetic neuropathy-associated nerve damage. Diabetic neuropathy models show hesperidin preserves nerve function through reduction of oxidative and inflammatory stress.

A 2015 systematic review and meta-analysis of RCTs (PLoS ONE) found ALC has a moderate effect in reducing peripheral neuropathic pain on VAS, with stronger effects in diabetic neuropathy. Multiple trials confirm ALC reduces pain and increases sensation in diabetic peripheral neuropathy.

L-serine is the primary substrate of serine palmitoyltransferase (SPT). Mutations in SPT shift enzyme specificity toward alanine, generating neurotoxic 1-deoxysphingolipids that cause hereditary sensory and autonomic neuropathy type 1 (HSAN1). Supplemental L-serine competitively restores normal SPT substrate use, lowering 1-deoxysphingolipid levels and slowing neuropathy progression. A randomized placebo-controlled trial provides Class I clinical evidence for this mechanism.

Lion's Mane mushroom (Hericium erinaceus) contains hericenones and erinacines — small molecules that stimulate nerve growth factor (NGF) synthesis in vitro and in vivo and cross the blood-brain barrier. Animal studies demonstrate peripheral nerve regeneration after crush injury. Human double-blind RCTs show significant cognitive improvements vs. placebo, and the mushroom's neurotrophic mechanism is directly relevant to peripheral nerve health.

Luteolin demonstrates neuroprotective and analgesic effects in models of neuropathic pain including chronic constriction injury and sciatic nerve damage. It reduces thermal hyperalgesia and cold allodynia. The PEA+luteolin combination has clinical evidence from neuropathic pain settings.

Magnesium plays a critical role in nerve excitability by blocking NMDA receptors and regulating calcium and potassium channels; deficiency is associated with heightened neuropathic pain and peripheral nerve hyperexcitability. Clinical evidence supports magnesium supplementation for nerve excitability modulation, neuropathic pain reduction, and sleep improvement in neuropathy patients. Deficiency is common in diabetic patients and clinically recognized as worsening neuropathy symptoms.

Methylcobalamin is the bioactive coenzyme form of vitamin B12 that directly participates in nerve tissue metabolism without requiring hepatic conversion, making it the preferred form for neuropathy applications. RCTs demonstrate that methylcobalamin significantly improves nerve conduction velocity and reduces pain in diabetic peripheral neuropathy. Animal studies show ultra-high dose methylcobalamin promotes nerve regeneration by upregulating gene transcription and protein synthesis in peripheral nerve fibers.

N-Acetyl Cysteine is a precursor to glutathione, the body's primary endogenous antioxidant, and has demonstrated relevance to peripheral neuropathy through reduction of oxidative stress in nerve tissue. A 2022 MDPI peer-reviewed review identifies it as an amino acid-derived supplement with evidence for neuropathic pain treatment alongside acetyl-L-carnitine. It is included in authoritative neuropathy supplement evidence databases and used in chemotherapy-induced neuropathy management.

Naringin reduces diabetic neuropathic pain and ameliorates neuronal, glial, and myelin sheath damage in diabetic models. It dose-dependently reduces sciatic nerve pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) and improves nerve growth factor levels. Evidence is preclinical; no human neuropathy trials exist.

Nicotinamide riboside (NR) is an NAD+ precursor with clinical evidence specifically in chemotherapy-induced peripheral neuropathy. It is listed in authoritative peripheral neuropathy evidence databases alongside methylcobalamin and ALC. Preclinical studies show NR protects dorsal root ganglion neurons from chemotherapy toxicity through NAD+-dependent mitochondrial protection mechanisms.

NMN is a direct precursor to NAD+, a cofactor essential for mitochondrial energy production and sirtuin-mediated neuroprotection in peripheral nerve cells. NAD+ depletion is mechanistically implicated in axonal degeneration via the Wallerian pathway. NMN is listed in authoritative peripheral neuropathy evidence databases alongside methylcobalamin and ALC, and preclinical studies support its protective effects against neuropathy.

Omega-3 polyunsaturated fatty acids (EPA and DHA) have demonstrated anti-neuroinflammatory and nerve-regenerating properties in preclinical models and emerging clinical trials. Animal models confirm EPA+DHA accelerates nerve regeneration after injury and prevents neuropathic pain behavior. Multiple sources of omega-3 (fish oil, krill oil, algal oil) have been confirmed effective for diabetic peripheral neuropathy endpoints in a preclinical study.

GLA supplementation has RCT evidence for improvement in diabetic peripheral neuropathy, with a double-blind trial of 111 patients showing vibration and touch sensitivity improvements after 1 year. Longitudinal cohort data further show that low plasma omega-6 fatty acids (including AA) predict accelerated decline of peripheral nerve function over 3 years. The relationship is bidirectional: while adequate omega-6 levels support nerve function, excessive omega-6 intake may exacerbate neuropathic pain via pro-nociceptive oxylipins.

Pyridoxal-5-phosphate (PLP) is the active coenzyme form of vitamin B6 directly utilized by nerve tissue for neurotransmitter biosynthesis and amino acid metabolism, without requiring hepatic conversion. It is the preferred B6 form in evidence-based clinical neurovitamin combinations for neuropathy. In vitro research demonstrates B1/B6/B12 combinations including PLP produce dramatically enhanced neural cell repair compared to B12 alone.

Propionyl-L-Carnitine (PLC) is a naturally occurring L-carnitine ester with vascular and mitochondrial-supporting properties relevant to peripheral nerve blood supply. PLC improves endoneurial blood flow, reduces oxidative stress, and supports energy metabolism in nerve tissue. It is listed in authoritative peripheral neuropathy evidence databases alongside Acetyl-L-Carnitine, and animal studies show PLC improves nerve conduction velocity in diabetic models.

Pycnogenol (French maritime pine bark extract) is a standardized polyphenolic extract that improves microcirculation and reduces oxidative stress and neuroinflammation relevant to peripheral nerve blood supply. It is listed in authoritative peripheral neuropathy evidence databases alongside methylcobalamin, ALC, and ALA. Clinical studies in diabetic microvascular complications show it significantly improves microvascular function and neuropathic symptoms.

Catalpol from Rehmannia protects neurons from ischemia, apoptosis, and diabetic nephropathy-associated damage. A 2022 PMC study demonstrated catalpol restores motor function in spinal cord injury rats by inhibiting endoplasmic reticulum stress-mediated apoptosis. Rehmannia Six Formula reviews show benefits for diabetic neuropathy. The herb's neuroprotective properties are supported across Alzheimer's, Parkinson's, and spinal cord injury models.

Catalpol from R. glutinosa demonstrates significant neuroprotective effects across multiple models, including spinal cord injury, Parkinson's disease, Alzheimer's disease, and hypoxic/ischemic injury. It inhibits neuronal apoptosis via ER stress pathways and promotes nerve regeneration markers (GAP-43, MAP-2, NeuN).

Resveratrol, a stilbenoid polyphenol from grapes and berries, activates SIRT1 and inhibits NF-κB, producing anti-neuroinflammatory and neuroprotective effects relevant to peripheral neuropathy. A 2025 Frontiers in Pharmacology systematic review identified it as demonstrating anti-inflammatory effects through SIRT1 pathway activation relevant to neuropathy. Multiple rodent neuropathy models show resveratrol reduces pain behaviors and preserves nerve fiber density.

Rosmarinic acid mitigates peripheral neuropathy in preclinical models, including oxaliplatin-induced peripheral neuropathy where it reduced mitochondrial dysfunction and spinal glial activation. RA's neuroprotective mechanisms include antioxidant activity, anti-neuroinflammatory effects, and protection of neuronal mitochondrial function. Human-specific clinical evidence for neuropathy is not yet available.

Rutin has demonstrated neuroprotective effects in preclinical models relevant to diabetic neuropathy and nerve injury, mediated through antioxidant, anti-inflammatory, and anti-apoptotic mechanisms. It crosses or its metabolites cross the blood-brain barrier and can modify nerve tissue function.

Silymarin has demonstrated neuroprotective effects in preclinical models and is studied in the context of diabetic neuropathy. Clinical evidence includes studies in patients with diabetic nephropathy and neuropathy, and preclinical data showing protection of neuronal integrity via antioxidant and anti-inflammatory pathways. The evidence base is predominantly preclinical; controlled human trials specific to peripheral neuropathy are limited.

SPMs reduce neuropathic pain in preclinical models via TRP channel and neuroinflammation modulation. Clinical trials suggest SPM precursors reduce pain in diabetic neuropathy. SPMs are produced in peripheral nerves and DRG, and resolvin D6 isomer was found to stimulate nerve regeneration and reduce neuropathic pain.

Sulforaphane exerts neuroprotective effects against diabetic and neuropathic pain via Nrf2-driven antioxidant enzyme induction in peripheral nerve tissue. Animal data show SFN reduces nociception and analgesic tolerance in neuropathic pain models. Diabetic neuropathy prevention is supported by Nrf2 activation studies.

CX and its constituents TMP and ligustilide are neuroprotective across multiple experimental models, including spinal cord injury, cerebral ischemia, and neurodegeneration. TMP accelerates functional recovery after traumatic spinal cord injury by attenuating neuroinflammation. Ligustilide crosses the blood-brain barrier and exerts anti-apoptotic, anti-inflammatory, and neuroprotective effects.

Taurine protects peripheral and central neurons from oxidative stress, excitotoxicity, and mitochondrial dysfunction. Diabetic neuropathy is a specific area of relevance, given that plasma taurine is depleted in diabetes and taurine supplementation reduces oxidative and inflammatory markers associated with neuropathic progression.

A phase II double-blind RCT showed tocotrienol-rich vitamin E significantly improved nerve conduction velocity in both sensory and motor nerves in T2DM patients with diabetic peripheral neuropathy over 12 months. Earlier phase II RCTs also support positive effects on nerve conduction parameters.

Curcumin has demonstrated anti-nociceptive and nerve-protective effects in preclinical models of diabetic neuropathy, sciatic nerve injury, and chemotherapy-induced peripheral neuropathy. Turmeric bioactive compounds suppress glial activation and improve mitochondrial function in neuropathic pain models. Human clinical data are emerging but limited.

Thiamine (vitamin B1) is a critical cofactor in carbohydrate metabolism and ATP production in neurons; its deficiency causes beriberi and Wernicke's encephalopathy, both characterized by severe peripheral nerve degeneration. Vitamin B1 is classified as a neurotropic vitamin alongside B6 and B12, with evidence supporting its role in nerve cell metabolism and myelin formation. A 2025 PMC study demonstrated that B1/B6/B12 combinations enhance neural cell maturation and connectivity superior to single B vitamins.

Vitamin B12 (cobalamin) is critically required for myelin synthesis, DNA synthesis, and fatty acid metabolism in nerve cells; its deficiency is one of the most common and clinically recognized reversible causes of peripheral neuropathy. Multiple systematic reviews confirm B12 promotes nerve cell survival, remyelination, and maintenance of myelin sheaths. Methylcobalamin is the preferred bioactive form directly utilized by nerve tissue.

Riboflavin deficiency is linked to neuromuscular symptoms including peripheral neuropathy and muscle weakness. Riboflavin transporter deficiency (a genetic disorder) causes severe progressive neuropathy (Brown-Vialetto-Van Laere syndrome) that responds to high-dose riboflavin supplementation. FAD-dependent enzymes are indispensable for neuronal energy metabolism and membrane potential maintenance.

Pyridoxine (vitamin B6) is an established neurotropic vitamin essential for neurotransmitter synthesis and nerve function. Deficiency causes peripheral neuropathy with sensory symptoms, and it is included in clinical B-complex formulations for nerve support. Evidence shows higher-dose B-complex (including B6) significantly reduces neuropathic pain and paresthesiae compared to lower-dose B complex, although chronic high-dose excess can itself cause neuropathy.

Folate deficiency is a documented cause of peripheral neuropathy, presenting as slowly progressive axonal sensory neuropathy predominantly in the lower extremities. Folate supports nerve health via myelin maintenance, reduction of neurotoxic homocysteine, and neuronal DNA repair. A 2025 systematic review found folate supplementation consistently improved neuropathy biomarkers and nerve conduction parameters in clinical trials, though definitive efficacy data remain limited.

Vitamin D receptors are expressed throughout the nervous system, and vitamin D plays a documented role in neuroprotection and nerve repair by regulating neurotrophic factors and myelination. Deficiency is strongly associated with peripheral neuropathy and neuropathic pain. A 2025 PRISMA systematic review identified vitamin D alongside B vitamins and E as vitamins with demonstrated benefits in nerve regeneration.

Vitamin E (tocopherols and tocotrienols) is a lipid-soluble antioxidant protecting peripheral nerve myelin from oxidative damage. Vitamin E deficiency causes a well-recognized progressive peripheral neuropathy. A 2025 PRISMA systematic review identified vitamin E among vitamins with demonstrated benefits in nerve regeneration alongside B vitamins and vitamin D.

Yohimbine has been studied in the context of diabetic neuropathy, specifically diabetic autonomic neuropathy and associated neurogenic orthostatic hypotension. It is listed as a pharmacological option for neurogenic orthostatic hypotension, including that arising from diabetic autonomic neuropathy, though with very low quality of evidence. It has also historically been noted as a use for diabetic nerve pain.

Zanthoxylum's sanshool compounds directly interact with TRPV1 and TRPA1 sensory ion channels, providing a mechanistically documented neuroactive profile. Z. nitidum extract suppressed central sensitization in a chronic pain model via ERK/NF-κB pathways. Z. bungeanum isorhamnetin shows neuroprotective activity against neuroinflammation.

Zinc is an essential trace mineral required for nerve tissue antioxidant defense (Cu/Zn-SOD), nerve growth factor signaling, myelin maintenance, and the delta-6-desaturase enzyme that converts linoleic acid to neuroprotective GLA. Zinc deficiency is a recognized cause of peripheral neuropathy, and lower zinc levels are found in diabetic patients with more severe neuropathy.

A. racemosus has documented neuroprotective properties in preclinical models and asparagus seeds have historically been used in remedies for neuritis. PubMed reviews classify asparagus nutraceuticals as having neuroprotective and nootropic activity. Traditional Chinese and folk medicine use for nerve-related conditions is recorded.

Bacopa has been used in Ayurvedic and Siddha medicine as a neural tonic for brain and nerve fatigue. Preclinical evidence demonstrates efficacy in rodent models of neuropathic pain, including chronic constriction injury and diabetic neuropathy. No human clinical trials have specifically evaluated Bacopa for neuropathy.

Borage seed oil has been promoted for diabetic neuropathy based on the role of GLA in peripheral nerve membrane phospholipid composition. MSKCC and other institutional sources list diabetic neuropathy as a promoted indication, but human clinical trial evidence is limited and not specific to borage oil alone.

California poppy has a documented Western herbal tradition for nerve pain (neuralgia), including sciatica and shingles-related pain. The EMA assessment report and Bartram's Encyclopedia list neuralgia as a traditional indication. Case reports describe E. californica tincture resolving post-surgical neuropathic pain and opioid dependence simultaneously. Preclinical analgesic mechanisms (glycinergic, serotonergic) are mechanistically relevant to neuropathic pain.

Cowage seed has documented traditional use as a nerve tonic in Ayurveda and Unani medicine, and is described in classical texts as specific to healthy neurons. Preclinical studies confirm neuroprotective effects against oxidative stress and neuroinflammation. No human clinical trials specifically targeting neuropathy have been published.

Jamaican dogwood has a long traditional use for neuralgia, nerve pain, and sciatica, documented in 19th-century Western herbalism and Eclectic medical literature. Animal studies show analgesic effects of bark extracts. Cornus officinalis has preclinical neuroprotective data. No controlled human trials exist for either species.

Polygala root has traditional documented use for neurasthenia (nerve weakness/exhaustion) in TCM. Preclinical data show protection of dopaminergic and other neurons from toxin-induced damage, reducing neuronal apoptosis and supporting nerve cell survival.

Prickly ash has documented traditional use for nerve pain, neuralgia, and peripheral neuropathy in multiple materia medica traditions. Eclectic physicians prescribed it 'where nerve force is low' and for recovery from neuritis. Herbalist practitioners identify it as a leading herb for peripheral neuropathy, used internally and externally. Sanshool alkaloids interact with TRPV1/TRPA1 nerve channels providing a mechanistic basis.

Pharmacological reviews consistently identify purslane as neuroprotective and antinociceptive, with animal studies demonstrating protection against hypoxia-induced neuronal injury and pain reduction. Omega-3 fatty acids and alkaloids are the proposed active constituents. Clinical evidence in human neuropathy is absent; the evidence is preclinical and ethnopharmacological.

Rosemary has traditional use for nerve pain, including sciatica, and its bioactives show antinociceptive effects in preclinical neuropathic pain models. Animal studies specifically demonstrate protection against diabetic neuropathy and pain relief in neuropathy models, but human clinical trial evidence in neuropathy populations specifically is lacking.

S. lateriflora has a documented traditional use for neuralgia and nerve pain in Eclectic medical texts. Preclinical studies show baicalein reduces neuropathic pain and anxiety in PTSD models. The leaves of American skullcap are currently used in traditional/integrative practice for neuropathy symptoms.

SJW has traditional use for neuralgia and nerve pain. Preclinical animal studies demonstrate hypericin-mediated inhibition of protein kinase C reduces neuropathic pain. However, a controlled clinical trial in 54 patients with polyneuropathy found no significant benefit over placebo.

Bacopa monnieri has documented traditional use as a nerve tonic ('brahmi' means brain/nerve tonic in Sanskrit), and bacosides are shown to enhance nerve impulse transmission and dendritic growth. A preclinical study in the CCI neuropathic pain model showed antinociceptive activity.