Approaching Idiopathic Neuropathy: A Naturopathic Strategy Beyond Diabetes

A clinical overview of diagnosing and treating non-diabetic neuropathy through root-cause evaluation, including autoimmunity, infections, biotoxin exposure, and small fiber nerve pathology.

Dr. Jason Porter, NMD

Abstract

This article explores a naturopathic framework for evaluating and treating idiopathic peripheral neuropathy in patients without diabetes. It highlights comprehensive laboratory assessment, small fiber neuropathy diagnostics, and targeted nutritional and integrative interventions that can improve nerve regeneration and patient quality of life.

Why do patients develop neuropathies?

Neuropathy is a condition where nerves become damaged, dysfunctional, or reduced in number, leading to symptoms of numbness, tingling, burning, or pain—most often in the hands and feet. While diabetes is reported as the leading cause of peripheral neuropathy affecting 4-10 million people in the US, approximately 12-50% of all cases representing 5-8 million people are idiopathic.1-4 To provide some perspective, idiopathic neuropathy is as much as 2-4 times more prevalent than Alzheimer’s disease, and 10 times more common than Parkinson’s disease or Multiple Sclerosis.5 Known causes reported in the literature besides metabolic disorders include autoimmunity, nutritional deficiencies, toxic exposures, infections, chronic inflammatory disorders, mitochondrial disorders, genetic inheritance, and more recent COVID. The diagnosis of idiopathic neuropathy is often stymied and relegated to pain management with the most common prescription medications – including Gabapentin, Lyrica, SNRI’s, and Tramadol – with potential risks and generally poor management of the patient’s pain. Naturopathic physicians can greatly impact the quality of life of these undiagnosable and untreatable patients by guiding and treating them in a model of healthcare that can very often expose root causes of chronic pain and inflammation.

How can we correctly diagnose neuropathy?

Diagnosis of neuropathy can be complex with some individuals requiring referrals to specialists for nerve testing, small fiber nerve punch biopsies, and genetic testing. Keeping it simple the first step following presentation of unmanaged neuropathy is to rule out obvious and treatable disorders. An initial and simple lab workup should include an evaluation of the leading causes of metabolic disorders and nutritional deficiencies and should include: CBC, fasting CMP, fasting insulin, fasting lipids, HgA1c, Vitamin B12, Folic Acid, and Homocysteine. The evaluation and treatment of diabetes or insulin resistance and/or nutrient deficiencies utilizing diet, exercise, and methylated vitamins is a naturopathic physician’s specialty and can be extremely helpful to the patient. A more advanced approach would also include markers for inflammation and autoimmunity and would include: celiac panel, thyroid peroxidase Ab, thyroglobulin Ab, C-reactive protein, sedimentation rate, and ANA for connective tissue disorders. Any positive findings may require further evaluation and our best therapies to begin to evaluate and reduce chronic sources of inflammation. A deeper dive toward discovering root causes can also include testing for Lyme disease, Bartonella, and mold risk. Clinically we have observed that 50% of cases will present with positive labs supporting Lyme and Bartonella activity as well as Chronic Inflammatory Response Syndrome (CIRS), based on HLA testing patterns.

Examples of how to approach laboratory evaluation

The stages or options for lab testing are a progression or can be completed all at once based on the presentation of the patient. Your initial history and review of systems is of great value along with a comprehensive neurological exam to determine how to approach laboratory evaluation. As an example: if a patient presents with symptoms of neuropathy but also reports brain fog and fatigue as well, then the full work up is suggested as Lyme disease, Bartonella infection, autoimmunity, and mold could be leading aggravators along with uncontrolled diabetes. Another example is of a patient who presents with autonomic symptoms – such as dizziness or tachycardia on standing – could have celiac disease, Lupus, vector borne illness, or severe mycotoxin exposure. Another example can be easily missed when the patient reports symptoms of neuropathy outside of the typical locations of the hands and feet such as on the face, thighs, torso, or groin. This is a clear clue that is likely more than just a metabolic disorder and requires an extensive work up for all labs previously mentioned as well as possible referral to rheumatology and neurology. The extremity and depth of the initial reported symptoms can guide you to how deep you want to investigate.

Skin biopsy and antibody testing

Studies show that diabetic neuropathy often presents with small nerve fiber injury, affecting sensations of pain, temperature, and even autonomic functions (e.g., sweat glands) before damage to large nerve‑fiber symptoms emerge.6 Because standard nerve‑conduction studies focus primarily on large myelinated fibers (which the majority are normal), they may miss early small‑fiber damage. Specialized tests or skin biopsies are required to identify small‑fiber neuropathy and are often performed in neurology and in some podiatry offices.7 When a patient describes having pain in the hands or feet or burning sensation anywhere in the body, a naturopathic physician should look for symptoms of autonomic dysfunction. Or if a patient reports POTS or dysautonomia symptoms, evaluate for neuropathic pain. If they have both symptoms, then they absolutely need to be worked up for small fiber neuropathy with biopsy and bloodwork for autoimmune causes of neuropathy such as antibodies against fibroblast growth factor receptor-3 (FGFR-3) and trisulfated heparin disaccharide (TS-HDS). Both biopsy and autoimmune antibodies against the nerves are too often ignored. Positive findings can remove the mystery from the diseases or symptoms providing hope as we discover root causes. These evaluations should be done sooner, and are appropriate following a naturopathic physician’s initial thorough laboratory assessment as described above.

Case Study

A 43yo male presents August 2017 to the office with new onset vertigo and dizzy spells of 2 months. The patient is a dentist and has episodes of feeling suddenly off balance, difficulty standing, and needing to lean over to balance himself. He reports increase in neck tension/stiffness/pain, new chronic low back pain, headaches (no prior history), joint pain which appears to move from joint to joint from one day to the next, reduced quality of sleep, mental confusion and cognitive difficulties, restlessness, and irritability. He was evaluated by an orthopedic specialist with findings of possible impingement in the cervical spine with steroid injections recommended. On evaluation with ENT he was diagnosed with vestibular neuritis. He agreed to do steroid injections in his neck and low back with no following benefit. By May of 2018, all of the original symptoms persisted with the patient, and now he was presenting with numbness, tingling, and weakness of hands and lower arms bilateral as well as bilateral legs. The severity of his symptoms by this time left him unable to be employed due to the associated pain, dizziness, and weakness by this time was constant. In the attempt to avoid invasive neck and back surgery, he came to our clinic for evaluation and potential treatments. 

Lab testing was negative for diabetes or pre-diabetes. He was not deficient in vitamin B12, folic acid, nor did he have elevated homocysteine. Autoimmune panels for celiac panel, Hashimoto’s, connective tissue disorders, and C-reactive protein were all negative. On other hand, lab testing was positive for HLA multi-susceptible 4-3-53, raising suspicion for mold exposure as a root cause, yet TGF-β 1 and complement C4a were within normal limits. Additional testing exposed Bartonella history with elevated IgG antibodies and CDC negative WB for Lyme, though a few markers were present on IgG and a single positive marker for IgM. The patient labs were also sent to Washington State University Neuromuscular disease lab for autoimmune antibody testing with positive findings for IgM Ab against TS-HDS >30,000 (NML<10,000). A Small Fiber Nerve Biopsy determined the patient had a length dependent small fiber neuropathy with the left upper thigh nerve fiber density at 14.72 (NML>6.2/mm) but the left calf nerve fiber density of 2.4 (NML > 3.8/mm) out of range, confirming loss of small fiber nerves. With a positive biopsy and confirmed autoimmune antibodies, the patient is confirmed to have autoimmune small fiber neuropathy. This presentation will cause neuropathic pain in various areas of the body as well as produce autonomic symptoms such as dizziness and fatigue. 

The treatment plan was extensive and broad to match the degree of disability and suspicious root cause and included: avoidance of white refined sugar, herbal prescriptions for treatment of suspected Lyme and Bartonella infection. Treatment from mold and mycotoxin exposure was also aggressively instituted based on risk due to HLA immune typing even without evidence of mycotoxin exposure. We have found clinically 100% of our patients diagnosed with small fiber loss are HLA mold sensitive patients with greater than 80% having some diagnosable autoimmune marker present associated with connective tissue disorders or antibodies for neuromuscular disorders.

The right nutrients can grow new nerves

Regardless of lab evidence of Vitamin B12 or folic acid deficiency or elevated homocysteine, biopsy supported small fiber nerve loss can be reversed. Prescription medical foods containing L‑methylfolate, methylcobalamin and pyridoxal‐5‑phosphate (P5P) have shown promise in restoring intra‑epidermal nerve fiber density (IENFD) and improving sensory perception.8 For example, a study of type 2 diabetes patients with documented small fiber neuropathy reported a statistically significant increase in epidermal nerve fiber density and improved monofilament sensation after approximately six months of treatment.8 The mechanism is thought to involve enhanced methylation, reduced oxidative/nitrosative stress, and improved endothelial and nerve microvascular function—supporting the notion that addressing nutritional and metabolic requirements may aid nerve regeneration. The patient was prescribed high doses of specific vitamins and mitochondrial supports to promote growth of new nerves. It should be noted that acute cases, particularly in children who develop sudden onset neuropathies, respond well to intravenous immunoglobulin (IVIG) treatment. In adult trials the percent of success is less than 10 percent from IVIG. During a follow up visit in December 2021, over 4 years from the onset of the disabling symptoms, the patient reported 80% recovery with the ability to return to work 3-4 days out of the week.

Naturopathic physicians can treat neuropathy successfully

Neuropathy, especially when labeled idiopathic, is often overlooked or inadequately treated in conventional care models. Idiopathic neuropathy is not a metabolic disorder. It is often a mix between immune and toxin related disorders. A correct diagnosis via laboratory, biopsies, and nerve conduction studies will provide hope, clarity, and direction to the physician and patient. Current research is still ongoing, but naturopathic physicians have many of the tools to provide the best support in growing new nerves and guide the patient as you discover and treat the underlying root causes that damage small fiber nerves.

Dr. Jason Porter, NMD, BCN is a licensed naturopathic physician and Board-Certified Neurotherapist who co-founded East Valley Naturopathic Doctors and the Brain Regeneration Clinic in Mesa, Arizona. A graduate of the Southwest College of Naturopathic Medicine, he combines naturopathic medical principles with advanced neurofeedback, biofeedback, hyperbaric oxygen therapy, and precision-based approaches to support recovery from chronic and complex illness by restoring endocrine, immune, and nervous system function. Dr. Porter’s work emphasizes evidence-informed, root-cause investigation and integrative therapies that optimize cognition, mood, energy, sleep, and stress resilience.

REFERENCES

1. Hicks CW, Wang D, Windham BG, Matsushita K, Selvin E. Prevalence of peripheral neuropathy defined by monofilament insensitivity in middle-aged and older adults in two US cohorts. Sci Rep. 2021;11:19159. Published September 27, 2021. https://doi.org/10.1038/s41598-021-98565-w
2. Castelli G, Desai KM, Cantone RE. Peripheral Neuropathy: Evaluation and Differential Diagnosis. Am Fam Physician. 2020;102(12):732–739. https://www.aafp.org/pubs/afp/issues/2020/1215/p732.html
3. Foundation for Peripheral Neuropathy. Idiopathic Neuropathy. Accessed November 23, 2025. https://www.foundationforpn.org/causes/idiopathic-neuropathy
4. Winsvold BS, Kitsos I, Thomas LF, Skogholt AH, Gabrielsen ME, Zwart J-A, Nilsen KB; on behalf of HUNT All-In Pain. Genome-wide association study of 2,093 cases with idiopathic polyneuropathy and 445,256 controls identifies first susceptibility loci. Front Neurol. 2021;12:789093. Published December 16, 2021. https://doi.org/10.3389/fneur.2021.789093
5. Singer MA, Vernino SA, Wolfe GI. Idiopathic neuropathy: new paradigms, new promise. J Peripher Nerv Syst. 2012;17(1):43–49. https://doi.org/10.1111/j.1529-8027.2012.00395.x
6. Alkotami AS, Elkholy SH, Elshamy AM, Elseidy EA, Fadel WA. Diabetic small fiber neuropathy: clinical and electrophysiological study. Egypt J Neurol Psychiatr Neurosurg. 2024;60:148. Published December 23, 2024. https://doi.org/10.1186/s41983-024-00923-8
7. Goldenberg D. Small Fiber Neuropathy: Clinical Scenarios and Differential Diagnoses. Pract Pain Manag. 2021;21(6). Updated November 9, 2021. https://www.practicalpainmanagement.com/small-fiber-neuropathy-clinical-scenarios
8. McNamara VF, Vinik AI, Barrentine L, De Vol EB. Effectiveness of Metanx prescription medical food on small nerve fibers and monofilament sensation in patients with diabetic peripheral polyneuropathy. J Diabetes Mellit. 2016;6(2):67–75. https://www.scirp.org/journal/paperinformation.aspx?paperid=66263 DOI: 10.4236/jdm.2016.62018