Nerve Guard combines four nutrients: benfotiamine (a form of vitamin B1), methylcobalamin (a form of vitamin B12), L-5-MTHF (a form of folate), and acetyl-L-carnitine. This page explains why we chose them, what published research says about each one, and where that research falls short. We include studies that found no benefit, because you should see the whole picture.

Nerve Guard has not been tested in a clinical trial. The studies on this page tested individual ingredients or different combinations. Most enrolled adults with diabetes who had already been diagnosed with nerve problems (neuropathy), and many used different amounts or forms than we do. Their results may not apply to you or to Nerve Guard.

Nothing on this page says that Nerve Guard prevents, treats, or cures neuropathy or any other condition, or that it will produce the results reported in these studies. Nerve Guard is a dietary supplement intended to support normal nerve function in adults. It does not replace medical care or your diabetes management plan.

If you have numbness, tingling, burning, or pain in your hands or feet, see your healthcare provider. Those symptoms deserve a proper medical evaluation.

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

How to read the studies

• Placebo-controlled trial: one group takes the ingredient and another takes an inactive look-alike. This is the most reliable way to tell whether something works.
• Systematic review or meta-analysis: combines several trials. It is only as good as the trials inside it.
• “Not statistically significant”: the difference between groups was small enough that it could be chance.
• Who paid: several studies were funded by, or co-authored by people connected to, companies that sell the ingredient or a related product. We note this when we know it.

Benfotiamine (vitamin B1)

Why it is in Nerve Guard

Thiamine (vitamin B1) is a cofactor for enzymes involved in the body’s glucose, amino acid, and fat metabolism. [9] Benfotiamine is a synthetic, fat-soluble derivative that was developed to be absorbed better than ordinary thiamine.

What absorption studies show

In small studies of healthy volunteers, benfotiamine raised blood thiamine levels much more than standard thiamine did. In one 2014 study, the amount of thiamine reaching the bloodstream was about 11 times higher after benfotiamine than after thiamine hydrochloride, and about twice as high inside red blood cells. [6] Two earlier studies found the same direction. [7] [8] These studies measured vitamin levels, not nerve health, and blood thiamine is an imperfect marker of thiamine status. [9]

What trials in people with diabetes show

• 3 weeks, 40 adults with diabetes and nerve symptoms, 400 mg per day. A neuropathy score improved more than with placebo. [1] Small and short.
• 6 weeks, 165 adults, 300 or 600 mg per day (the BENDIP trial). The main symptom score was better than placebo in the per-protocol analysis (p = 0.033) but just missed statistical significance in the intention-to-treat analysis (p = 0.055). A second symptom score did not differ. Improvement was larger at 600 mg. A co-author is affiliated with a pharmaceutical company. [2]
• 24 months, 67 adults with type 1 diabetes, 300 mg per day. No significant effect on nerve function or on inflammatory markers. [3]
• 12 months, 57 adults with type 2 diabetes and symptomatic nerve problems, 600 mg per day (the BOND trial, published in 2026). No difference from placebo in the main measure (corneal nerve fibre length) or in the other nerve measures, symptoms, or quality of life. Benfotiamine was well tolerated. [4]
• A combination product. An older, small trial tested benfotiamine together with B6 and B12, so the effect of benfotiamine alone cannot be separated out. [5]

Bottom line: mixed. Benfotiamine is well absorbed and was generally well tolerated in these trials. The two shortest trials found some symptom-score improvements. The two longest trials, including the only long trial in type 1 diabetes, found no benefit. That is why we describe benfotiamine as a nutrient that supplies well-absorbed thiamine, not as a proven nerve remedy.

Methylcobalamin (vitamin B12)

Why it is in Nerve Guard

Vitamin B12 is needed for normal nerve function, and B12 deficiency can cause neurological changes. [15] Metformin, a common diabetes medicine, might reduce B12 absorption and lower blood B12. [15] If you take metformin, ask your healthcare provider about checking your B12 level.

Why methylcobalamin, and what we do not claim

We use methylcobalamin because it is the form used in most of the diabetes nerve research cited here. We do not claim it works better than other forms of B12. A 2015 review concluded that the coenzyme forms of B12 are not likely to be superior to cyanocobalamin or hydroxocobalamin for preventing or treating B12 deficiency. [14]

What trials show

• 12 months, 90 adults with type 2 diabetes who had taken metformin for at least 4 years and had B12 below 400 pmol/L, 1 mg per day of oral methylcobalamin versus placebo. Nerve conduction measures, sweat-gland function, a pain score, and quality of life improved. A clinical examination score and autonomic reflex tests did not. [10] This trial enrolled people whose B12 was low or borderline. It does not tell us what happens when B12 is already normal.
• A 2020 meta-analysis of 15 trials (1,707 people with diabetic or herpes-related nerve problems). Methylcobalamin alone did better than comparison treatments on an overall “clinical efficacy” rating but not on pain, symptom scores, or nerve conduction. Combinations did better on efficacy and nerve conduction, but not on pain or symptom scores. The authors described the included trials as generally poor quality and called for better studies. No serious side effects were linked to methylcobalamin. [11]
• A 24-week trial of 232 adults. Methylcobalamin at 1.5 mg per day was the comparison arm against acetyl-L-carnitine at 1,500 mg per day. Symptom and disability scores improved in both groups with no clear difference between them. There was no placebo group, so this trial cannot show what either one does compared with nothing. [13] [23]
• Another meta-analysis compared injected lipoic acid plus methylcobalamin with injected methylcobalamin alone, so it does not tell us about oral methylcobalamin by itself. [12]

Bottom line: best supported when B12 is low. The strongest placebo-controlled trial enrolled people with low or borderline B12. Evidence for people with normal B12 is limited, and many of the trials are low quality.

L-5-MTHF (folate)

Why it is in Nerve Guard

Folate and B12 work together to convert homocysteine into methionine. [19] L-5-MTHF is considered the biologically active form of folate. [16]

Is it better absorbed than folic acid?

The evidence is mixed. In a crossover study of 24 women, a single dose of 5-MTHF raised blood folate more than folic acid did, whether or not they carried a common MTHFR gene variant. [17] A study in men found the two forms had equivalent short-term bioavailability. [18] We use L-5-MTHF because it is the form used in the research on folate and nerves, not because it has been proven superior.

Homocysteine

In the best-known combination trial, blood homocysteine fell by about 2.7 µmol/L with treatment and rose slightly with placebo. [16] Higher homocysteine has been linked to worse nerve outcomes in observational data, [20] but observational links do not show that lowering homocysteine protects nerves, and the trial authors said they could not tell whether it contributed to the symptom changes they saw. [16]

What trials and reviews show

• 24 weeks, 214 adults with type 2 diabetes and neuropathy, a combination of L-methylfolate 3 mg, methylcobalamin 2 mg, and vitamin B6 (pyridoxal-5′-phosphate) 35 mg versus placebo. The main measure (vibration perception threshold) showed no significant difference. A symptom questionnaire improved more with the combination (secondary measure). Side effects were similar to placebo. The trial was funded and run by the company that makes the product, which is sold as a prescription medical food. [16] Nerve Guard is a different combination: it has no vitamin B6, and it has about one-third of the folate.
• A 2025 systematic review of 12 studies (3,015 people) summarised the results narratively, without pooling them statistically. The authors reported symptom improvements. Two authors are affiliated with a pharmaceutical company. [21]
• A 2023 narrative review describes the mechanisms and trial data for L-methylfolate. It is not a systematic review, and the authors disclose relationships with pharmaceutical companies, including the maker of the combination product above. We cite it for background, not as proof. [22]

Bottom line: strong biochemistry, limited direct evidence. Folate’s role in the methylation cycle is well established. Evidence for L-5-MTHF alone on nerve outcomes is limited, and most of it comes from a single combination product studied by its manufacturer.

One safety note: high folate intake can hide the blood signs of B12 deficiency. [15] Folate and B12 should be considered together, and it is a good reason to tell your healthcare provider that you take Nerve Guard.

Acetyl-L-carnitine (ALCAR)

Why it is in Nerve Guard

The body makes carnitine and uses it to move long-chain fatty acids into mitochondria, where they are used for energy. Acetyl-L-carnitine is an acetylated form. [23]

What trials and reviews show

• A 2019 Cochrane review (4 trials, 907 people, 1,500 to 3,000 mg per day). Cochrane reviewers concluded that it is very uncertain whether acetyl-L-carnitine reduces pain compared with placebo. On average, pain scores improved about 9 points on a 100-point scale, but the certainty of that finding was rated very low. At 1,500 mg per day or less there was no clear difference from placebo. Larger effects appeared only above 1,500 mg per day, and the authors cautioned that this comparison was even less certain. Two of the four trials were funded by an acetyl-L-carnitine manufacturer, and the other two had a co-author who consulted for one. [23]
• A 2015 meta-analysis of 4 placebo-controlled trials (523 people). Acetyl-L-carnitine lowered pain scores more than placebo on average, and the authors noted the evidence was limited. [24]
• The 24-week trial versus methylcobalamin described above found both improved with no placebo comparison. [13]

Our amount

Nerve Guard contains 750 mg, which is half of the lowest daily dose used in these trials. That means the trial results above do not apply directly to this amount, and we do not present them as if they do. We include acetyl-L-carnitine for its role in cellular energy metabolism, not because trials have shown a benefit at 750 mg.

Bottom line: limited, and at a higher dose than ours. The trial evidence is low quality, partly industry-linked, and was collected at doses above what Nerve Guard provides.

What the research says about the combination

No one has tested this exact four-ingredient combination in a clinical trial, including us. Here is what the broader research shows.

• A 2026 meta-analysis of 13 randomized trials (834 people) of B vitamins in diabetic neuropathy found improvements in some symptom scores and in one nerve measurement (the sural nerve), no significant effect on pain measured with general pain scales, and inconsistent results for other nerves. The authors noted that combination regimens looked more promising than single vitamins, but a formal test did not confirm that difference for most outcomes. They concluded that inconsistent results and risk of bias prevent firm recommendations for routine use. [28]
• The same authors observed that benfotiamine alone and methylcobalamin alone generally did not show robust improvements in nerve conduction, while some combinations did. [28]
• An earlier Cochrane review (2008) concluded there was not enough evidence to say whether B vitamins help or harm peripheral neuropathy, as summarised in the 2026 review. [28] [29]
• Combination trials also included other ingredients, such as vitamin B6 [16] or superoxide dismutase and lipoic acid. [27] We have not seen a trial of benfotiamine, methylcobalamin, L-5-MTHF, and acetyl-L-carnitine taken together.

For that reason, we describe Nerve Guard as daily nutritional support built from ingredients with well-documented roles in the body. We do not describe it as a proven remedy for anything.

Safety, and who should ask a healthcare provider first

Talk to your physician or pharmacist before taking Nerve Guard if you:

• are pregnant, planning to become pregnant, or nursing;
• have a history of seizures. Carnitine supplements can increase seizure risk in people with seizure disorders. [25]
• have kidney disease. High carnitine amounts can cause muscle weakness in people with uremia. [25]
• take a blood thinner such as warfarin or acenocoumarol, or thyroid hormone medication. Reference monographs report possible interactions with acetyl-L-carnitine. [26]
• take metformin or acid-reducing medicines, which can lower B12. [15]
• take other products that contain vitamin B1, B12, folate, or carnitine, so you do not double up;
• have any other medical condition or take any prescription medication.

Tell your healthcare provider you take Nerve Guard, including before lab work. Take it as directed on the label and do not exceed the serving size. Keep following your diabetes care plan, and do not change insulin or other medicines because of a supplement.

At very high carnitine amounts (around 3 g per day), nausea, vomiting, stomach cramps, diarrhea, and fishy body odor can occur. [25] Nerve Guard provides 750 mg, but people differ. Stop taking it and contact your healthcare provider if you have side effects that concern you.

To report a side effect or ask a question, contact us at [ADVERSE EVENT CONTACT].

How we keep this page honest

• We include studies that found no benefit.
• We say when a study used a different dose, form, combination, or population than Nerve Guard.
• We say when a study was funded by, or connected to, a company with a commercial interest, when we know it.
• We update this page when important new research is published. Last reviewed: September 2026.
• If you find an error, tell us and we will check it.

References

1. Haupt E, Ledermann H, Köpcke W. Benfotiamine in the treatment of diabetic polyneuropathy: a three-week randomized, controlled pilot study (BEDIP study). Int J Clin Pharmacol Ther. 2005;43(2):71–77. PMID 15726875.
2. Stracke H, Gaus W, Achenbach U, Federlin K, Bretzel RG. Benfotiamine in diabetic polyneuropathy (BENDIP): results of a randomised, double blind, placebo-controlled clinical study. Exp Clin Endocrinol Diabetes. 2008;116(10):600–605. doi:10.1055/s-2008-1065351
3. Fraser DA, Diep LM, Hovden IA, et al. The effects of long-term oral benfotiamine supplementation on peripheral nerve function and inflammatory markers in patients with type 1 diabetes: a 24-month, double-blind, randomized, placebo-controlled trial. Diabetes Care. 2012;35(5):1095–1097. doi:10.2337/dc11-1895
4. Ziegler D, Sipola G, Strom A, et al. Effects of benfotiamine treatment over 12 months on morphometric, neurophysiological and clinical measures in type 2 diabetes patients with symptomatic polyneuropathy: a randomized, placebo-controlled, double-blind clinical trial (BOND study). BMJ Open Diabetes Res Care. 2026;14:e005773. doi:10.1136/bmjdrc-2025-005773
5. Stracke H, Lindemann A, Federlin K. A benfotiamine-vitamin B combination in treatment of diabetic polyneuropathy. Exp Clin Endocrinol Diabetes. 1996;104:311–316. doi:10.1055/s-0029-1211460
6. Xie F, et al. Pharmacokinetic study of benfotiamine and the bioavailability assessment compared to thiamine hydrochloride. J Clin Pharmacol. 2014. doi:10.1002/jcph.261. PMID 24399744.
7. Greb A, Bitsch R. Comparative bioavailability of various thiamine derivatives after oral administration. Int J Clin Pharmacol Ther. 1998;36(4):216–221. PMID 9587048.
8. Bitsch R, Wolf M, Möller J, Heuzeroth L, Grüneklee D. Bioavailability assessment of the lipophilic benfotiamine as compared to a water-soluble thiamin derivative. 1991. PMID 1776825.
9. National Institutes of Health, Office of Dietary Supplements. Thiamin: fact sheet for health professionals. ods.od.nih.gov/factsheets/Thiamin-HealthProfessional
10. Didangelos T, Karlafti E, Kotzakioulafi E, et al. Vitamin B12 supplementation in diabetic neuropathy: a 1-year, randomized, double-blind, placebo-controlled trial. Nutrients. 2021;13(2):395. doi:10.3390/nu13020395
11. Sawangjit R, Thongphui S, Chaichompu W, Phumart P. Efficacy and safety of mecobalamin on peripheral neuropathy: a systematic review and meta-analysis of randomized controlled trials. J Altern Complement Med. 2020;26(12):1117–1129. doi:10.1089/acm.2020.0068
12. Xu Q, Pan J, Yu J, et al. Meta-analysis of methylcobalamin alone and in combination with lipoic acid in patients with diabetic peripheral neuropathy. Diabetes Res Clin Pract. 2013;101(2):99–105. doi:10.1016/j.diabres.2013.03.033
13. Li S, Chen X, Li Q, et al. Effects of acetyl-L-carnitine and methylcobalamin for diabetic peripheral neuropathy: a multicenter, randomized, double-blind, controlled trial. J Diabetes Investig. 2016;7(5):777–785. doi:10.1111/jdi.12493
14. Obeid R, Fedosov SN, Nexo E. Cobalamin coenzyme forms are not likely to be superior to cyano- and hydroxyl-cobalamin in prevention or treatment of cobalamin deficiency. Mol Nutr Food Res. 2015;59:1364–1372.
15. National Institutes of Health, Office of Dietary Supplements. Vitamin B12: fact sheet for health professionals. ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional
16. Fonseca VA, Lavery LA, Thethi TK, et al. Metanx in type 2 diabetes with peripheral neuropathy: a randomized trial. Am J Med. 2013;126(2):141–149. doi:10.1016/j.amjmed.2012.06.022
17. Prinz-Langenohl R, Brämswig S, Tobolski O, et al. [6S]-5-methyltetrahydrofolate increases plasma folate more effectively than folic acid in women with the homozygous or wild-type 677C→T polymorphism of methylenetetrahydrofolate reductase. Br J Pharmacol. 2009;158(8):2014–2021. doi:10.1111/j.1476-5381.2009.00492.x
18. Pentieva K, McNulty H, Reichert R, et al. The short-term bioavailabilities of [6S]-5-methyltetrahydrofolate and folic acid are equivalent in men. J Nutr. 2004;134:580–585. doi:10.1093/jn/134.3.580
19. Shane B, Stokstad ELR. Vitamin B12-folate interrelationships. Annu Rev Nutr. 1985;5:115–141. doi:10.1146/annurev.nu.05.070185.000555
20. Wile DJ, Toth C. Association of metformin, elevated homocysteine, and methylmalonic acid levels and clinically worsened diabetic peripheral neuropathy. Diabetes Care. 2010;33:156–161.
21. Alves Maues AC, Moren Abat MG, Benlloch M, Mariscal G. Folate supplementation for peripheral neuropathy: a systematic review. Nutrients. 2025;17(20):3299. doi:10.3390/nu17203299
22. Christofides EA, Valentine V. L-methylfolate in diabetic peripheral neuropathy: a narrative review. Endocr Pract. 2023;29(8):663–669. doi:10.1016/j.eprac.2023.04.005
23. Rolim LCSP, da Silva EMK, Flumignan RLG, Abreu MM, Dib SA. Acetyl-L-carnitine for the treatment of diabetic peripheral neuropathy. Cochrane Database Syst Rev. 2019;(6):CD011265. doi:10.1002/14651858.CD011265.pub2
24. Li S, Li Q, Li Y, Li L, Tian H, Sun X. Acetyl-L-carnitine in the treatment of peripheral neuropathic pain: a systematic review and meta-analysis of randomized controlled trials. PLoS One. 2015;10(3):e0119479. doi:10.1371/journal.pone.0119479 (see also the correction, doi:10.1371/journal.pone.0129991).
25. National Institutes of Health, Office of Dietary Supplements. Carnitine: fact sheet for health professionals. ods.od.nih.gov/factsheets/Carnitine-HealthProfessional
26. RxList. Acetyl-L-carnitine: health benefits, side effects, uses, dose and precautions (reference monograph). rxlist.com/supplements/acetyl-l-carnitine.htm
27. Didangelos T, Karlafti E, Kotzakioulafi E, et al. Efficacy and safety of the combination of superoxide dismutase, alpha lipoic acid, vitamin B12, and carnitine for 12 months in patients with diabetic neuropathy. Nutrients. 2020;12(11):3254. doi:10.3390/nu12113254
28. Mandra EV, Parfenov VA, Stupin VA, Silina EV. Vitamin B supplementation for diabetic peripheral neuropathy: a review and meta-analysis. J Clin Med. 2026;15(13):5156. doi:10.3390/jcm15135156
29. Ang CD, Alviar MJ, Dans AL, et al. Vitamin B for treating peripheral neuropathy. Cochrane Database Syst Rev. 2008;CD004573. (Cited as summarised in reference 28.)

*Disclaimers. These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

This page is educational and describes published research on individual ingredients. It is not medical advice, and it is not a claim that Nerve Guard will produce the results reported in any study. Nerve Guard is not a substitute for medical care, prescription medications, or a diabetes management plan. Always consult a physician or qualified healthcare professional before using this product, especially if you have diabetes, neuropathy, are pregnant or nursing, have a medical condition, or take any medication.