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Diabetic Neuropathy and Potential Food Supplement Interventions

Diabetic neuropathy is the most frequent chronic complication of diabetes and may attack sensory, motor or autonomous fibres. Researchers have explored various dietary interventions, including food supplements, as potential therapeutic strategies.

Author: Daria Šurić, Mpharm

Diabetic neuropathy, a debilitating complication of diabetes, is a significant public health concern affecting millions of individuals worldwide. This condition arises from the metabolic and vascular disturbances associated with prolonged hyperglycemia, leading to nerve damage and impaired function.1,2 Diabetic neuropathy is a clinical condition that can significantly impact the quality of life, presenting as numbness, tingling, and burning in the extremities. Current treatment options focus on symptom alleviation and reducing exposure to risk factors as treating the pathophysiological causes of diabetic neuropathy remains a significant challenge. Novel studies have proposed that the use of antioxidants, including alpha-lipoic acid, may represent a beneficial intervention for treating neuropathic pain in diabetic patients.3

Researchers have explored various dietary interventions, including food supplements, as potential therapeutic strategies. 4 One promising approach involves using functional foods and their bioactive compounds. A comparative in vitro study has shown that certain food supplement ingredients, such as quercetin, ascorbic acid, caffeine, and ellagic acid, may be efficient in targeting the underlying mechanisms of diabetic neuropathy.5


Alpha-lipoic acid and diabetic neuropathy

Alpha-lipoic acid (ALA), a potent antioxidant, has demonstrated beneficial effects in the management of diabetic neuropathy. Supplementation with alpha-lipoic acid has been found to improve nerve conduction, reduce oxidative stress, and alleviate neuropathic pain in individuals with diabetes.

ALA has been shown to play a significant role in mitigating the oxidative stress and nerve damage associated with diabetic neuropathy.

Alpha lipoic acid is a potent lipophilic antioxidant in vitro and in vivo conditions, which plays a main role as a cofactor in many mitochondrial reactions, is easily absorbed from the gastrointestinal tract and can easily cross the blood-brain barrier. Apoptosis is an important mechanism of degenerative diseases, which is induced by some factors like hyperglycemia toxicity. In vivo and in vitro studies showed that hyperglycemia affected cell survival and induced apoptotic changes in dorsal root ganglion neurons and Schwann cells. Experimental studies have demonstrated the protective effects of ALA on the loss of myelin sheath in the sciatic nerve, a hallmark of diabetic neuropathy.6 Furthermore, clinical trials have indicated that alpha-lipoic acid supplementation can improve glucose control and lipid profiles in individuals with type 2 diabetes and coronary heart disease.7 In a review study from 2021, randomized controlled trials investigated ALA treatment in diabetes mellitus patients with neuropathic pain and made an appropriate comparison. The reduction of neuropathic symptoms was the primary outcome, and the secondary outcome was the incidence of adverse events. Eight studies comprising 1,500 diabetic patients were evaluated in this systematic review. The findings were inconsistent among the literature concerning the effectiveness of ALA in the treatment of diabetic neuropathy, with three trials (37.5%) observing significant improvements in symptoms and five trials (62.5%) not observing any notable results. The doses used were from 600 mg to 1600 mg per day. All studies found ALA to be a safe and tolerable intervention, with no reported adverse effects. The administration of ALA may result in symptom reduction and offers a safe and tolerable treatment option.3

Research on alpha-lipoic acid has delved into its mechanisms of action in the context of diabetic neuropathy. In addition to its antioxidant properties, alpha-lipoic acid has been shown to exert anti-inflammatory effects, modulate intracellular signalling pathways, and enhance glucose metabolism. These multifaceted actions contribute to its potential in addressing the complex pathophysiology of diabetic neuropathy. Moreover, the ability of alpha-lipoic acid to improve nerve conduction and mitigate neuropathic pain underscores its role as a promising therapeutic agent for this condition.

The role of B vitamins

In addition to alpha-lipoic acid, B vitamins have shown promise in addressing diabetic neuropathy. Specifically, vitamin B12, B6, and folic acid have been the focus of several studies due to their potential role in nerve function and regeneration. Vitamin B12, also known as cobalamin, is essential for the maintenance of myelin, the protective sheath surrounding nerve fibres. Deficiency in vitamin B12 has been linked to neuropathy and nerve damage, particularly in diabetic individuals. Supplementation with vitamin B12 has shown improvement in nerve conduction and neuropathic symptoms in diabetic patients.

Similarly, vitamin B6, or pyridoxine, plays a crucial role in neurotransmitter synthesis and regulation. Studies have suggested that vitamin B6 supplementation may alleviate neuropathic pain and improve nerve function in diabetic individuals.

Folic acid, another B-vitamin, is involved in DNA synthesis and repair, which are crucial for nerve cell development and function. Research has indicated that folic acid supplementation may have a protective effect against diabetic neuropathy by promoting nerve regeneration and reducing oxidative stress.

Incorporating alpha-lipoic acid and B-vitamins through food sources and supplements may offer a multifaceted approach to managing diabetic neuropathy, addressing both oxidative stress and supporting nerve health. Further exploration of these potential interventions could provide valuable insights into improving the quality of life for individuals living with diabetic neuropathy.

Potential of berberine and curcumin

Besides alpha-lipoic acid and B vitamins, other nutraceuticals such as berberine and curcumin have garnered attention for their potential in treating diabetic neuropathy.

Berberine, a plant-derived compound, has been shown to possess anti-inflammatory, antioxidant, and neuroprotective properties.8 Berberine is a bioactive constituent that displays effects on blood glucose; however, the mechanism underlying the role of BBR during the development of diabetic retinpathy is not completely understood. Berberine reversed the high glucose‑induced effects by decreasing the phosphorylation of IκB, inhibiting NF‑κB nuclear translocation and deactivating the NF‑κB signalling pathway. The results suggested that berberine protects against diabetic retinopathy by inhibiting oxidative stress and cell apoptosis via deactivation of the NF‑κB signalling pathway; therefore, suggesting that BBR may serve as a promising therapeutic agent for diabetic retinopathy.9

Curcumin, the active compound in turmeric, has also been explored for its ability to modulate oxidative stress, inflammation, and neural function in the context of diabetic neuropathy. The Banafshe et al. study was designed to investigate the effect of curcumin on diabetic peripheral neuropathic pain and the possible involvement of the opioid system. Study results suggest that curcumin can be considered as a new therapeutic potential for the treatment of diabetic neuropathic pain and the activation of opioid system may be involved in the antinociceptive effect of curcumin.10


The role of nucleotides, vitamin D and magnesium

In addition to the well-studied food supplements, emerging evidence suggests that other dietary components, such as nucleotides, vitamin D, and magnesium, may also play a role in the management of diabetic neuropathy.

Nucleotides are the building blocks of DNA and RNA, and they have been found to have neuroprotective properties. Further investigation into the potential role of nucleotides in managing diabetic neuropathy in human subjects is warranted to validate these findings and understand the underlying mechanisms.

Vitamin D, known for its crucial role in bone health, has also been associated with neurological function. Research has suggested that vitamin D deficiency may contribute to the development and progression of diabetic neuropathy. Supplementation with vitamin D has shown potential in improving nerve conduction and reducing neuropathic pain in diabetic individuals. The relationship between vitamin D status and neuropathy warrants deeper exploration to determine the extent of its impact and the optimal strategies for supplementation in this context.

Magnesium, an essential mineral involved in various physiological processes, has been implicated in neuropathic pain modulation. Studies have proposed that magnesium supplementation may help alleviate neuropathic pain by regulating N-methyl-D-aspartate receptor activity and calcium ion influx in nerve cells. Understanding the role of magnesium in diabetic neuropathy and its potential as a therapeutic adjunct could offer new insights into comprehensive dietary interventions for individuals with this condition.

Chromium, a trace mineral, has been studied for its potential role in improving insulin sensitivity and glucose metabolism, which are crucial factors in the development of diabetic neuropathy.  Chromium supplementation has shown promise in reducing neuropathic pain and improving nerve conduction in individuals with diabetes.

The potential of other ingredients

L-carnitine and coenzyme Q10 are also food supplements that have been investigated for their potential benefits in diabetic neuropathy. L-carnitine plays a crucial role in the metabolism of fatty acids, and it has been found to improve nerve conduction and reduce neuropathic pain in individuals with diabetes. Coenzyme Q10, an essential component of the electron transport chain in mitochondria, has also demonstrated neuroprotective effects in animal studies.

In addition to the aforementioned food supplements, bitter melon and omega-3 fatty acids have also shown promise in the management of diabetic neuropathy.

Bitter melon, a popular vegetable in many Asian cuisines, has been studied for its antioxidant, anti-inflammatory, and hypoglycemic properties. Research has suggested that bitter melon may help alleviate neuropathic pain and improve nerve function in individuals with diabetes.

Omega-3s have been shown to possess anti-inflammatory and neuroprotective effects, which could contribute to their ability to mitigate the progression of diabetic neuropathy.

The synergistic effects of food supplements

The synergistic effects of combining different food supplements have become a focal point in ongoing research. By investigating the interactions between bioactive compounds, researchers aim to develop comprehensive dietary strategies tailored for the management of diabetic neuropathy. Understanding how these compounds work in tandem and their impact on individual variations in nutrient metabolism could help to find a better way for personalized dietary interventions that address the diverse needs of individuals with diabetic neuropathy.

In conclusion, the exploration of food supplements and bioactive compounds as potential interventions for diabetic neuropathy has gained significant attention in the scientific community.


  1. Wooton, A K., & Melchior, L M. (2018, November 1). Diabetic autonomic neuropathy resulting in sexual dysfunction. Lippincott Williams & Wilkins, 43(11), 39-45.
  2. Ma, J., Jiang, C., Fu, X., Chen, J., Hu, W., & Ye, L. (2023, March 1). Editorial: Novel insights into the pathophysiology of diabetes-related complications: Implications for improved therapeutic strategies. Frontiers Media, 14.
  3. Abubaker SA, Alonazy AM, Abdulrahman A. Effect of Alpha-Lipoic Acid in the Treatment of Diabetic Neuropathy: A Systematic Review. Cureus. 2022;14(6):e25750. Published 2022 Jun 8. doi:10.7759/cureus.25750
  4. Mirmiran, P. (2014, January 1). Functional foods-based diet as a novel dietary approach for management of type 2 diabetes and its complications: A review. 5(3), 267-267.
  5. Mehta, V., Verma, P., Sharma, N., Sharma, A., Thakur, A., & Malairaman, U. (2017, June 1). Quercetin, ascorbic acid, caffeine and ellagic acid are more efficient than rosiglitazone, metformin and glimepiride in interfering with pathways leading to the development of neurological complications associated with diabetes: A comparative in-vitro study. 55(1), 115-121.
  6. Taşçı, İ., Demir, C F., & Kuloğlu, T. (2018, January 1). Effects of Alpha Lipoic Acid on Loss of Myelin Sheath of Sciatic Nerve in Experimentally Induced Diabetic Rats. Academy of Medical Sciences of Bosnia and Herzegovina, 72(3), 178-178.
  7. Akbari, M., Ostadmohammadi, V., Lankarani, K B., Tabrizi, R., Kolahdooz, F., Khatibi, S R., & Asemi, Z. (2018, October 1). The effects of alpha-lipoic acid supplementation on glucose control and lipid profiles among patients with metabolic diseases: A systematic review and meta-analysis of randomized controlled trials. Elsevier BV, 87, 56-69.
  8. Gupta R. Active phytoconstituents for diabetes management: A review. J Complement Integr Med. 2018;15(3):/j/jcim.2018.15.issue-3/jcim-2017-0123/jcim-2017-0123.xml. Published 2018 Jan 19. doi:10.1515/jcim-2017-0123
  9. Zhai J, Li Z, Zhang H, et al. Berberine protects against diabetic retinopathy by inhibiting cell apoptosis via deactivation of the NF‑κB signaling pathway. Mol Med Rep. 2020;22(5):4227-4235. doi:10.3892/mmr.2020.11505
  10. Banafshe HR, Hamidi GA, Noureddini M, Mirhashemi SM, Mokhtari R, Shoferpour M. Effect of curcumin on diabetic peripheral neuropathic pain: possible involvement of opioid system. Eur J Pharmacol. 2014;723:202-206. doi:10.1016/j.ejphar.2013.11.033
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