Low-dose naltrexone and NAD+ for the treatment of patients with persistent fatigue symptoms after COVID-19.

Isman A, Nyquist A, Strecker B, Harinath G, Lee V, Zhang X, Zalzala S

Brain, behavior, & immunity - health1 Feb 2024Cited by 35 (Europe PMC)

PMID38352659PMCIDPMC10862402DOI10.1016/j.bbih.2024.100733PepBankPUB-38352659

Summary

A subset of patients experiences persistent fatigue symptoms after COVID-19, and patients may develop long COVID, which is characterized by lasting systemic symptoms. No treatments for this condition have been validated and are urgently warranted. In this pilot study, we assessed whether treatment with low-dose naltrexone (LDN, 4.5 mg/day) and supplementation with NAD + through iontophoresis patches could improve fatigue symptoms and quality of life in 36 patients with persistent moderate/severe fatigue after COVID-19. We detected a significant increase from baseline in SF-36 survey scores after 12 weeks of treatment (mean total SF-36 score 36.5 [SD: 15.6] vs. 52.1 [24.8]; p < 0.0001), suggestive of improvement of quality of life. Furthermore, participants scored significantly lower on the Chalder fatigue scale after 12 weeks of treatment (baseline: 25.9 [4.6], 12 weeks: 17.4 [9.7]; p < 0.0001). We found a subset of 52 % of patients to be responders after 12 weeks of treatment. Treatment was generally safe, with mild adverse events previously reported for LDN, which could be managed with dose adjustments. The iontophoresis patches were associated with mild, short-lived skin irritation in 25 % of patients. Our data suggest treatment with LDN and NAD+ is safe and may be beneficial in a subset of patients with persistent fatigue after COVID-19. Larger randomized controlled trials will have to confirm our data and determine which patient subpopulations might benefit most from this strategy.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study5

No result from this study comes from a test of the peptide.

Studies that did not test the peptide alone5

In this study, NAD+ (nicotinamide adenine dinucleotide) was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking NAD+ (nicotinamide adenine dinucleotide).

01HumanNot a test of NAD+ (nicotinamide adenine dinucleotide) aloneNon-randomized trialEfficacy outcome
In patients with post-COVID fatigue, naltrexone with NAD patches increased SF-36 scores from baseline after 12 weeks.
In plain wordsIn patients with post-COVID fatigue, naltrexone with NAD patches improved quality-of-life scores compared with baseline.
Peptide
NAD+ (nicotinamide adenine dinucleotide)
Outcome
IncreaseSF-36 total score
Study
n = 36
Outcome group
Quality of life · Whole body
Measurements
SF-36 total score
36.5 score
baseline
SF-36 total score
52.1 score
after treatment
SF-36 total score SD
15.6 score
baseline
SF-36 total score SD
24.8 score
after 12 weeks of naltrexone with NAD patches
P value for SF-36 total score change
< 0.0001 p value
baseline versus 12 weeks of naltrexone with NAD patches
Source sentences
Summary
We detected a significant increase from baseline in SF-36 survey scores after 12 weeks of treatment (mean total SF-36 score 36.5 [SD: 15.6] vs. 52.1 [24.8]; p < 0.0001), suggestive of improvement of quality of life.
1 context sentence(design, population, supporting numbers)
Summary · context
In this pilot study, we assessed whether treatment with low-dose naltrexone (LDN, 4.5 mg/day) and supplementation with NAD + through iontophoresis patches could improve fatigue symptoms and quality of life in 36 patients with persistent moderate/severe fatigue after COVID-19.
In this study, NAD+ (nicotinamide adenine dinucleotide) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking NAD+ (nicotinamide adenine dinucleotide).
Show in the study text Report a problemFND-3835265901
02HumanNot a test of NAD+ (nicotinamide adenine dinucleotide) aloneNon-randomized trialEfficacy outcome
In patients with post-COVID fatigue, naltrexone with NAD patches reduced Chalder fatigue scores from baseline after 12 weeks.
In plain wordsIn patients with post-COVID fatigue, naltrexone with NAD patches reduced fatigue scores compared with baseline.
Peptide
NAD+ (nicotinamide adenine dinucleotide)
Outcome
DecreaseChalder fatigue score
Study
n = 36
Outcome group
Exercise and physical function · Whole body
Measurements
Chalder fatigue score
25.9 score
baseline
Chalder fatigue score
17.4 score
12 weeks
Chalder fatigue score bracketed variability, type not stated
4.6 score
baseline
Chalder fatigue score bracketed variability, type not stated
9.7 score
12 weeks of naltrexone with NAD patches
P value for Chalder fatigue score change
< 0.0001 p value
baseline versus 12 weeks of naltrexone with NAD patches
Source sentences
Summary
Furthermore, participants scored significantly lower on the Chalder fatigue scale after 12 weeks of treatment (baseline: 25.9 [4.6], 12 weeks: 17.4 [9.7]; p < 0.0001).
1 context sentence(design, population, supporting numbers)
Summary · context
In this pilot study, we assessed whether treatment with low-dose naltrexone (LDN, 4.5 mg/day) and supplementation with NAD + through iontophoresis patches could improve fatigue symptoms and quality of life in 36 patients with persistent moderate/severe fatigue after COVID-19.
In this study, NAD+ (nicotinamide adenine dinucleotide) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking NAD+ (nicotinamide adenine dinucleotide).
Show in the study text Report a problemFND-3835265902
03HumanNot a test of NAD+ (nicotinamide adenine dinucleotide) aloneNon-randomized trialEfficacy outcome
In patients with post-COVID fatigue, 52 % responded after 12 weeks of naltrexone with NAD patches.
In plain wordsIn patients with post-COVID fatigue, 52 % responded after 12 weeks of naltrexone with NAD patches.
Peptide
NAD+ (nicotinamide adenine dinucleotide)
Outcome
Not applicableTreatment responders
Study
n = 36
Outcome group
Overall treatment effect · Whole body
Measurements
Responders
52%
12 weeks
Source sentences
Summary
We found a subset of 52 % of patients to be responders after 12 weeks of treatment.
1 context sentence(design, population, supporting numbers)
Summary · context
In this pilot study, we assessed whether treatment with low-dose naltrexone (LDN, 4.5 mg/day) and supplementation with NAD + through iontophoresis patches could improve fatigue symptoms and quality of life in 36 patients with persistent moderate/severe fatigue after COVID-19.
In this study, NAD+ (nicotinamide adenine dinucleotide) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking NAD+ (nicotinamide adenine dinucleotide).
Show in the study text Report a problemFND-3835265903
04HumanNot a test of NAD+ (nicotinamide adenine dinucleotide) aloneNon-randomized trialSafety outcome
In patients with post-COVID fatigue, combined naltrexone and NAD treatment had mild adverse events that could be managed with dose adjustments.
In plain wordsIn patients with post-COVID fatigue, combined naltrexone and NAD treatment had mild adverse events that could be managed with dose changes.
Peptide
NAD+ (nicotinamide adenine dinucleotide)
Outcome
Not applicableMild adverse events
Study
n = 36
Outcome group
Adverse events · Whole body
Source sentences
Summary
Treatment was generally safe, with mild adverse events previously reported for LDN, which could be managed with dose adjustments.
1 context sentence(design, population, supporting numbers)
Summary · context
In this pilot study, we assessed whether treatment with low-dose naltrexone (LDN, 4.5 mg/day) and supplementation with NAD + through iontophoresis patches could improve fatigue symptoms and quality of life in 36 patients with persistent moderate/severe fatigue after COVID-19.
In this study, NAD+ (nicotinamide adenine dinucleotide) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking NAD+ (nicotinamide adenine dinucleotide).
Show in the study text Report a problemFND-3835265904
05HumanNot a test of NAD+ (nicotinamide adenine dinucleotide) aloneNon-randomized trialSafety outcome
In patients receiving naltrexone with NAD patches, the patches were associated with mild, short-lived skin irritation in 25 %.
In plain wordsIn patients receiving naltrexone with NAD patches, patches were linked to mild, brief skin irritation in 25 %.
Peptide
NAD+ (nicotinamide adenine dinucleotide)
Outcome
Not applicableSkin irritation
Study
n = 36
Outcome group
Adverse events · Skin and wound
Measurements
Skin irritation
25%
patients
Source sentences
Summary
The iontophoresis patches were associated with mild, short-lived skin irritation in 25 % of patients.
1 context sentence(design, population, supporting numbers)
Summary · context
In this pilot study, we assessed whether treatment with low-dose naltrexone (LDN, 4.5 mg/day) and supplementation with NAD + through iontophoresis patches could improve fatigue symptoms and quality of life in 36 patients with persistent moderate/severe fatigue after COVID-19.
In this study, NAD+ (nicotinamide adenine dinucleotide) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking NAD+ (nicotinamide adenine dinucleotide).
Show in the study text Report a problemFND-3835265905

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Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
14 Oct 2026, 05:02 UTC
Study results updated
Version 1
14 Oct 2026, 01:46 UTC
First added · source update from Europe PMC

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