Peripheral neuropathy is nerve damage outside the brain and spinal cord, and diabetes is its leading cause. It often starts as burning, tingling or numbness in both feet. Doctors treat the cause and use gabapentinoids, SNRIs or tricyclics for pain. Alpha lipoic acid at 600 mg a day eased symptoms in short trials, but a 4-year trial missed its main goal.
On this page
- What is peripheral neuropathy?
- What are the symptoms of peripheral neuropathy?
- What causes peripheral neuropathy?
- How do doctors diagnose neuropathy in feet?
- What is the first-line peripheral neuropathy treatment?
- Does alpha lipoic acid help peripheral neuropathy?
- How much alpha lipoic acid was used in the trials?
- Is alpha lipoic acid safe, and who should avoid it?
- When should you see a doctor right away for neuropathy?
- How can you protect your feet with peripheral neuropathy?
- What should you do next? A decision table
- Practical checklist
- Bottom line
- FAQ
Peripheral neuropathy is damage to the nerves outside the brain and spinal cord, and it most often starts as burning, tingling or numbness in the feet. For this guide we read the NINDS and NIDDK pages on neuropathy, the American Diabetes Association 2026 Standards of Care, the American Academy of Neurology treatment guideline, the NCCIH supplement summary and the main alpha lipoic acid trials, including NATHAN 1, using the method on our how we review page.[1][2][5][6][7][8]
Alpha lipoic acid (ALA) at 600 mg a day eased symptoms modestly in short trials, but a 4-year trial missed its main goal, and guidelines still put prescription nerve pain medicines and blood sugar control first.[5][8][9]
| What it is | Damage to the peripheral nerves that carry signals between the brain, spinal cord and the rest of the body. There are more than 100 types.[1][4] |
|---|---|
| Most common cause | Diabetes. Up to half of people with diabetes, about 1 in 2, have peripheral neuropathy.[1][2] |
| Typical first symptoms | Burning, tingling, numbness or pain in both feet, often worse at night.[2] |
| First-line medicines | Gabapentinoids, SNRIs, tricyclic antidepressants and sodium channel blockers, per ADA and AAN guidance.[5][6] |
| Alpha lipoic acid evidence | Limited. 600 mg a day reduced symptom scores in short trials; a 4-year trial missed its main end point.[8][9][10] |
| ALA safety | Common side effects are headache, heartburn, nausea and vomiting. Rare cases of autoimmune low blood sugar are reported.[7][12] |
| Daily must-do | Check your feet every day and get a foot exam at least once a year.[3][5] |
What is peripheral neuropathy?
Peripheral neuropathy is the name for many conditions that damage the peripheral nervous system, the network that links the brain and spinal cord to the rest of the body. When these nerves fail, signals are lost, sent when they should not be, or garbled. NINDS says it affects millions of people in the U.S.[1]
Peripheral nerves come in three kinds. Motor nerves move your muscles. Sensory nerves report touch, temperature and pain. Autonomic nerves run things you do not think about, such as heartbeat, digestion, sweating and blood pressure.[1][4]
Some neuropathies hit one nerve, such as carpal tunnel syndrome. Most often, many nerves are affected at once. Doctors call that polyneuropathy. Most forms are “length-dependent,” which means the longest nerves, the ones that reach the feet, show damage first.[1]
What are the symptoms of peripheral neuropathy?
The most common symptoms are burning, tingling (“pins and needles”), numbness, pain and weakness, usually in both feet first and later in the hands. NIDDK notes the symptoms are often worse at night. Some people feel strong pain from a light touch, such as bedsheets, while others lose the ability to feel pain or heat.[1][2]
Symptoms depend on which nerves are hurt:
- Sensory nerves: tingling, numbness, loss of vibration sense, poor balance, not noticing a cut on the foot.[1][4]
- Motor nerves: muscle weakness, cramps, twitching and muscle shrinking.[1]
- Autonomic nerves: too much or too little sweating, dizziness on standing, bowel or bladder changes and sexual problems.[1][4]
Neuropathy in the feet can also change how you walk, cause falls and lead to swollen feet.[2] It can be silent. The ADA says up to 50% of diabetic peripheral neuropathy cases may have no symptoms at all, which is why screening matters.[5]
What causes peripheral neuropathy?
Diabetes is the leading cause of peripheral neuropathy in the U.S., and about two thirds of people with diabetes have some nerve problems. Over time, high blood glucose and high blood fats such as triglycerides damage nerves and the small blood vessels that feed them.[1][2]
If your numbers are creeping up, our guide to prediabetes A1C ranges and how to lower them covers the early stage. Other causes include:[1][4]
- Low vitamin B12, or too much vitamin B6.[1]
- Heavy alcohol use and toxins such as lead or mercury.[1][4]
- Kidney or liver disease, an underactive thyroid and autoimmune diseases such as lupus or rheumatoid arthritis.[1][4][5]
- Infections, including shingles, HIV and Lyme disease.[1][4]
- Chemotherapy and some medicines for HIV, heart conditions and seizures.[1]
- Injury or pressure on a nerve, and inherited conditions such as Charcot-Marie-Tooth disease.[1]
Sometimes no cause is found. Doctors call that idiopathic neuropathy.[1]
How do doctors diagnose neuropathy in feet?
Doctors diagnose peripheral neuropathy with your history, a foot and nerve exam, and tests that rule out other causes. The exam uses a tuning fork to check vibration and a thin nylon strand, called a monofilament, to check touch. Your doctor will also watch you walk and test your balance.[2]
For people with diabetes, the ADA recommends a nerve check starting at diagnosis of type 2 diabetes and 5 years after a type 1 diagnosis, then at least once a year. That yearly check should include a 10-gram monofilament test and a 128-Hz tuning fork.[5]
Blood tests look for diabetes, thyroid problems, kidney disease and low B12. Metformin is one known cause of low B12, and NIDDK says metformin can usually continue with B12 added.[2][5] When the picture is unclear, a doctor may order nerve conduction studies, an EMG, a skin biopsy or an MRI of the spine.[1]
What is the first-line peripheral neuropathy treatment?
The first step is treating the cause, and for diabetes that means steady blood glucose, blood pressure and cholesterol control. NINDS notes that when the cause is corrected, neuropathy can sometimes improve as nerves recover. The ADA says good glucose management can prevent or delay neuropathy in type 1 diabetes and slow it in type 2.[1][5]
For nerve pain, the ADA 2026 Standards and the 2022 AAN guideline both name four first-line medicine classes. They give moderate pain relief and do not repair nerves.[2][5][6]
| Class | Examples | What the guideline says |
|---|---|---|
| Gabapentinoids | Gabapentin (Neurontin), pregabalin | Recommended first line; effect size 0.44 in the AAN review[1][5][6] |
| SNRIs | Duloxetine, venlafaxine | Recommended first line; effect size 0.47[2][5][6] |
| Tricyclic antidepressants | Amitriptyline, nortriptyline | Recommended; larger effect but low confidence in the estimate[2][6] |
| Sodium channel blockers | Drugs in this class, chosen by a doctor | Recommended first line; effect size 0.56[5][6] |
| Topical | Capsaicin 8% patch, lidocaine | Capsaicin 8% patch is FDA approved for this pain; an option for people who prefer topical care[5] |
Both groups advise against opioids, including tramadol and tapentadol, as a first choice.[5][6] If one medicine class does not help or causes side effects, the AAN says to try a different class.[6] Physical therapy for strength and balance, and a bed cradle to keep sheets off sore feet, can help too.[2]
Does alpha lipoic acid help peripheral neuropathy?
Alpha lipoic acid is an antioxidant compound that has been studied for diabetic nerve pain, and the trials point to a modest, short-term drop in symptoms with no proof of nerve repair. NCCIH calls the evidence weak: one 2022 review of 8 studies found benefit in 3 and none in 5, while another review of 9 studies with 2,062 people found it might reduce pain. A 2019 review of 10 studies with 553 people found ALA no better than placebo for lowering blood sugar.[7]
Almost all of the strong trials were in people with diabetes. Most were led by the same research group, and the 2004 pooled analysis drew on the manufacturer’s trial database, so treat the results as promising but limited.[8][9][10]
| Study | Who and how long | Dose | Result |
|---|---|---|---|
| IV pooled analysis (ALADIN I, ALADIN III, SYDNEY, NATHAN II), 2004 | 1,258 people, 3 weeks | 600 mg a day by IV drip | Symptom score 24.1% better than placebo; 52.7% vs 36.9% responded[10] |
| SYDNEY 2, 2006 | 181 people, 5 weeks | 600, 1,200 or 1,800 mg by mouth | Symptoms fell 51% at 600 mg (48% to 52% across doses) vs 32% on placebo; higher doses added side effects, not benefit[9] |
| NATHAN 1, 2011 | 460 people with mild to moderate neuropathy, 4 years | 600 mg by mouth | Main end point no different from placebo; some exam scores better[8] |
| Oral ALA meta-analysis, 2023 | Randomized trials vs placebo | Various oral doses | Symptom scores better; no gain on nerve tests or vibration sense[11] |
NATHAN 1 is the key long trial. Its placebo group did not get much worse over 4 years, so the study could not show that ALA slowed damage. Serious adverse events were 38.1% on ALA and 28.0% on placebo, though tolerability ratings did not differ.[8]
How much alpha lipoic acid was used in the trials?
The dose that shows up again and again is 600 mg once a day. SYDNEY 2 tested 600, 1,200 and 1,800 mg by mouth for 5 weeks. All three beat placebo by about the same amount, but nausea, vomiting and vertigo rose with the dose, so the authors judged 600 mg the best balance.[9]
Response rates were close too: 62% of the 600 mg group improved by half or more, against 50% at 1,200 mg, 56% at 1,800 mg and 26% on placebo.[9] The IV results came from drips given in a clinic for 3 weeks, which a capsule cannot copy.[10]
The 2023 meta-analysis did see a dose trend for symptom scores, but no study shows that going above 600 mg helps nerves heal.[9][11] Diabetes experts have not made formal supplement recommendations, so this is a conversation to have with your doctor.[2]
Is alpha lipoic acid safe, and who should avoid it?
In trials, ALA was generally well tolerated, and its most common side effects are headache, heartburn, nausea and vomiting. A 2020 review of 71 studies with 4,749 people found it safe in healthy people and in people with diabetes and other conditions.[7] Stomach upset and dizziness climb at higher doses.[9]
A rarer and more serious problem is insulin autoimmune syndrome, and ALA is one of its more often reported triggers. The body makes antibodies to its own insulin, which causes repeated low blood sugar, and it usually settles once ALA is stopped.[12] Learn the warning signs in our guide to low blood sugar symptoms and what to do right away.
Ask a doctor before taking ALA if you:[2][7]
- Take insulin or other diabetes medicines, since any extra drop in glucose matters.[12]
- Are pregnant or breastfeeding. We found no safety data for this group in the sources we read.
- Have kidney disease. NCCIH asks people at risk to have supplement use monitored.[7]
- Are already on a prescription nerve pain medicine you are thinking of stopping. Talk with a doctor before you stop any medicine.[1]
When should you see a doctor right away for neuropathy?
Call a doctor quickly if a foot injury is not healing or if new weakness is building over days. Lost feeling means a small sore can become infected without pain, and diabetes slows healing.[2][3]
See a doctor right away if you notice:
- A cut, blister or sore on the foot that is not getting better, or any sign of infection.[2][3]
- A red, warm, swollen foot, which can be the first sign of Charcot foot.[3]
- Weakness, numbness or trouble walking that develops over days, which can happen in immune nerve disorders such as Guillain-Barre syndrome.[1]
- Fainting or dizziness when you stand, or sudden bowel or bladder changes.[1][4]
- Shaking, sweating and confusion after starting ALA, which can signal low blood sugar.[12]
How can you protect your feet with peripheral neuropathy?
Daily foot care is the most reliable way to prevent ulcers and amputations when feeling is reduced. NIDDK suggests checking your feet every evening when you take off your shoes, including between the toes, with a mirror if you cannot bend.[3]
A simple daily routine based on NIDDK and ADA guidance:
- Look at the tops, soles and between the toes for cuts, red spots, blisters or warm areas.[3]
- Wash in warm water, 90 to 95 F, tested with your elbow or a thermometer. Do not soak.[3]
- Dry well, then use lotion on tops and soles but not between the toes.[3]
- Trim nails straight across, and let a foot doctor trim thick or ingrown nails.[3]
- Never walk barefoot or in socks alone, even indoors, and check inside shoes first.[3]
- Take off your socks and shoes at every visit so your feet get checked.[2][5]
What should you do next? A decision table
Most people do best by matching their next step to their situation, with the doctor visit first and any supplement last. Use this as a starting point for that talk.[2][5]
| If you | Then |
|---|---|
| Have new tingling or numbness in both feet | Ask for a foot and nerve exam plus blood tests for glucose, B12 and thyroid[2][5] |
| Have diabetes but no symptoms | Still get a yearly monofilament and tuning fork check[5] |
| Take metformin | Ask whether your B12 level should be checked[2][5] |
| Have nerve pain that disturbs sleep | Ask about a first-line medicine and switch class if it fails[5][6] |
| Want to try ALA | Discuss 600 mg a day with your doctor, watch for low glucose, and stop if symptoms do not change[9][12] |
Practical checklist
- Book a yearly foot exam, or one at every visit if you already have lost feeling.[5]
- Keep blood glucose, blood pressure and cholesterol near your goals.[2]
- Limit alcohol and stop smoking; both harm nerves.[1]
- If you are over 50, ask about the shingles vaccine.[1]
- If you buy ALA, check that the label lists the amount per capsule, and read how we review supplements before choosing.[9]
- Tell every doctor about every supplement you take.[2]
Bottom line
Peripheral neuropathy has many causes, and diabetes leads the list. Finding the cause, controlling glucose and checking your feet every day do the most to keep it from getting worse.[1][2][3] For pain, the guideline medicines have the best evidence.[5][6]
Alpha lipoic acid at 600 mg a day may take the edge off burning and tingling for some people with diabetes, but the long trial did not show it protects nerves.[8][9] For most people, a doctor visit and a nerve pain plan are the better first step, with ALA as an optional add-on discussed openly. More reading sits in our nerve health guides.
Frequently asked questions
What is polyneuropathy?
Polyneuropathy means many peripheral nerves are damaged at the same time, which is the most common pattern. It usually starts in both feet because the longest nerves are hit first. Diabetes is the leading cause, but B12 deficiency, alcohol and some medicines can also cause it.
Is Neurontin used for neuropathy?
Yes. Neurontin is a brand of gabapentin, one of the gabapentinoid medicines that the ADA and the American Academy of Neurology list as a first-line choice for diabetic nerve pain. It can ease pain but does not repair nerves, and it needs a prescription.
Can peripheral neuropathy go away?
Sometimes. NINDS says that when the cause is found and corrected, such as low B12 or a medicine side effect, nerves can recover and symptoms can fade. Diabetic neuropathy usually does not reverse, but good glucose control can slow it.
Can low vitamin B12 cause neuropathy?
Yes. Low B12 is one of the best-known vitamin causes of nerve damage, and long-term metformin use can lower B12 levels. A simple blood test checks for it. If B12 is low because of metformin, NIDDK says the metformin can usually continue with B12 added.
Why is neuropathy pain worse at night?
NIDDK and NINDS both note nerve pain is often worse at night. Damaged nerves can fire on their own, and light touch, such as bedsheets, can feel painful. A bed cradle that lifts sheets off the feet and a first-line pain medicine can help sleep.
Sources
- Peripheral Neuropathy. National Institute of Neurological Disorders and Stroke, NIH
- Peripheral Neuropathy. NIDDK, National Institutes of Health
- Diabetes and Foot Problems. NIDDK, National Institutes of Health
- Peripheral Nerve Disorders. MedlinePlus, National Library of Medicine
- 12. Retinopathy, Neuropathy, and Foot Care: Standards of Care in Diabetes 2026. American Diabetes Association, Diabetes Care, 2026
- Oral and Topical Treatment of Painful Diabetic Polyneuropathy: Practice Guideline Update Summary. American Academy of Neurology, Price et al., Neurology, 2022
- Diabetes and Dietary Supplements. NCCIH, National Institutes of Health
- Efficacy and safety of antioxidant treatment with alpha-lipoic acid over 4 years in diabetic polyneuropathy: the NATHAN 1 trial. Ziegler et al., Diabetes Care, 2011
- Oral treatment with alpha-lipoic acid improves symptomatic diabetic polyneuropathy: the SYDNEY 2 trial. Ziegler et al., Diabetes Care, 2006
- Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: a meta-analysis. Ziegler et al., Diabetic Medicine, 2004
- Effects of Oral Alpha-Lipoic Acid Treatment on Diabetic Polyneuropathy: A Meta-Analysis and Systematic Review. Hsieh et al., Nutrients, 2023
- Alpha-lipoic acid as a trigger of insulin autoimmune syndrome. Vallianou et al., Metabolism Open, 2026
Maya Ellison is the Reviews Editor at The Well Brew, a slow, plain-language supplement review blog for everyday adults. Maya reads each label in full, sets every dose beside the amounts used in human studies, grades the research with sources such as the NIH Office of Dietary Supplements and NCCIH, and works out the real cost and refund fine print. Maya has no medical credentials and is not a doctor, dietitian, nurse or pharmacist. Reviews give pros, cons and who a product suits, never scores. How we review supplements.
This article is general information, not medical advice. Dietary supplements are not reviewed by the FDA for safety or effectiveness before they are sold. Talk to your doctor before you start any supplement, especially if you are pregnant, nursing, take medication or have a health condition.