The role of diet and non-pharmacologic supplements in the treatment of chronic neuropathic pain: A systematic review.

2023-08-31
Pain practice : the official journal of World Institute of Pain 24(1)
- Jennifer K Frediani
- Asim A Lal
- Esther Kim
- Sharon L Leslie
- David W Boorman
- Vinita Singh

PubMed: 37654090
DOI: 10.1111/papr.13291

Study Design

Type: Systematic Review
Population: adult humans with chronic neuropathic pain
Methods: Systematic review following PRISMA guidelines, registered with PROSPERO (#CRD42022300312). Ten databases and gray literature systematically searched for studies published between 2000 and 2021.

Background/importance

Dietary interventions, vitamins, and nutritional supplementation are playing an increasingly important role in the management of neuropathic pain. Current pharmacological treatments are poorly tolerated and ineffective in many cases.

Objective

This systematic review aims to study the efficacy of dietary interventions, vitamins, and nutritional supplementation in the management of chronic neuropathic pain in adults.

Evidence review

The review followed PRISMA guidelines and was registered with PROSPERO (#CRD42022300312). Ten databases and gray literature, including Embase.com, MEDLINE and Web of Science, were systematically searched using a combination of keywords and controlled vocabulary related to chronic neuropathic pain and oral non-pharmacological supplements. Studies on adult humans published between 2000 and 2021 were considered for inclusion. The Cochrane Handbook was used to assess risk of bias, and Grading of Recommendations Assessment, Development, and Evaluation was used to determine overall quality of evidence.

Findings

Forty studies were included in the final review, and results were categorized according to pain type including pain related to chemotherapy-induced peripheral neuropathy (CIPN, 22 studies, including 3 prospective cohorts), diabetic peripheral neuropathy (DPN, 13 studies, including 2 prospective), complex regional pain syndrome (CRPS-I, 3 studies, including 1 prospective), and other (2 studies, both RCT). The CIPN studies used various interventions including goshajinkigan (4 studies), vitamin E (5), vitamin B12 (3), glutamine (3), N-acetyl-cysteine (2), acetyl-l-carnitine (2), guilongtonluofang (1), ninjin'yoeito (1), alpha-lipoic acid (1), l-carnosine (1), magnesium and calcium (1), crocin (1), and antioxidants (1), with some studies involving multiple interventions. All CIPN studies involved varying cancers and/or chemotherapies, advising caution for generalizability of results. Interventions for DPN included alpha-lipoic acid (5 studies), vitamin B12 (3), acetyl-l-carnitine (3), vitamin E (1), vitamin D (2), and a low-fat plant-based diet (1). Vitamin C was studied to treat CRPS-I (3 studies, including 1 prospective). Magnesium (1) and St. John's wort (1) were studied for other or mixed neuropathologies.

Conclusions

Based on the review, we cannot recommend any supplement use for the management of CIPN, although further research into N-acetyl-cysteine, l-carnosine, crocin, and magnesium is warranted. Acetyl-l-carnitine was found to be likely ineffective or harmful. Alpha-lipoic acid was not found effective. Studies with goshajinkigan, vitamin B12, vitamin E, and glutamine had conflicting results regarding efficacy, with one goshajinkigan study finding it harmful. Guilongtonluofang, ninjin'yoeito, and antioxidants showed various degrees of potential effectiveness. Regarding DPN, our review supports the use of alpha-lipoic acid, acetyl-l-carnitine, and vitamin D. The early use of vitamin C prophylaxis for the development of CRPS-I also seems promising. Further research is warranted to confirm these findings.

Research Insights

Acetyl-Carnitine→Reduced Chemotherapy-Induced Peripheral Neuropathy
The CIPN studies used various interventions including ... crocin (1), ...
Effect
Neutral
Effect size
Small
Acetyl-Carnitine→Reduced Diabetic Peripheral Neuropathy
Interventions for DPN included ... vitamin D (2), ...
Effect
Beneficial
Effect size
Small
Acetyl-Carnitine→Reduced Neuropathic Pain
Magnesium (1) and St. John's wort (1) were studied for other or mixed neuropathologies.
Effect
Neutral
Effect size
Small
Gardenia→Reduced Chemotherapy-Induced Peripheral Neuropathy
The CIPN studies used various interventions including ... crocin (1), ...
Effect
Neutral
Effect size
Small
Gardenia→Reduced Neuropathic Pain
Magnesium (1) and St. John's wort (1) were studied for other or mixed neuropathologies.
Effect
Neutral
Effect size
Small
L-Carnosine→Reduced Chemotherapy-Induced Peripheral Neuropathy
The CIPN studies used various interventions including ... crocin (1), ...
Effect
Neutral
Effect size
Small
L-Carnosine→Reduced Neuropathic Pain
Magnesium (1) and St. John's wort (1) were studied for other or mixed neuropathologies.
Effect
Neutral
Effect size
Small
L-Glutamine→Reduced Chemotherapy-Induced Peripheral Neuropathy
The CIPN studies used various interventions including ... crocin (1), ...
Effect
Neutral
Effect size
Small
L-Glutamine→Reduced Neuropathic Pain
Magnesium (1) and St. John's wort (1) were studied for other or mixed neuropathologies.
Effect
Neutral
Effect size
Small
Magnesium→Reduced Neuropathic Pain
Magnesium (1) and St. John's wort (1) were studied for other or mixed neuropathologies.
Effect
Neutral
Effect size
Small
St. John's Wort→Reduced Neuropathic Pain
Magnesium (1) and St. John's wort (1) were studied for other or mixed neuropathologies.
Effect
Neutral
Effect size
Small
Vitamin B12→Reduced Chemotherapy-Induced Peripheral Neuropathy
The CIPN studies used various interventions including ... crocin (1), ...
Effect
Neutral
Effect size
Small
Vitamin B12→Reduced Diabetic Peripheral Neuropathy
Interventions for DPN included ... vitamin D (2), ...
Effect
Beneficial
Effect size
Small
Vitamin B12→Reduced Neuropathic Pain
Magnesium (1) and St. John's wort (1) were studied for other or mixed neuropathologies.
Effect
Neutral
Effect size
Small
Vitamin C→Reduced Complex Regional Pain Syndrome
The early use of vitamin C prophylaxis for the development of CRPS-I also seems promising.
Effect
Beneficial
Effect size
Small
Vitamin C→Reduced Complex Regional Pain Syndrome Type I
Vitamin C was studied to treat CRPS-I (3 studies, including 1 prospective).
Effect
Beneficial
Effect size
Small
Vitamin D→Reduced Diabetic Peripheral Neuropathy
Interventions for DPN included ... vitamin D (2), ...
Effect
Beneficial
Effect size
Small
Vitamin D→Reduced Neuropathic Pain
Magnesium (1) and St. John's wort (1) were studied for other or mixed neuropathologies.
Effect
Neutral
Effect size
Small
Vitamin E→Reduced Chemotherapy-Induced Peripheral Neuropathy
The CIPN studies used various interventions including ... crocin (1), ...
Effect
Neutral
Effect size
Small
Vitamin E→Reduced Diabetic Peripheral Neuropathy
Interventions for DPN included ... vitamin D (2), ...
Effect
Beneficial
Effect size
Small
Vitamin E→Reduced Neuropathic Pain
Magnesium (1) and St. John's wort (1) were studied for other or mixed neuropathologies.
Effect
Neutral
Effect size
Small

Adverse Events Reported

Acetyl-Carnitine→Overall tolerability
Acetyl-l-carnitine was found to be likely ineffective or harmful.
Finding
Increased risk