Randomized study suggests 5-ALA–SFC supplement may support immune response following COVID-19 vaccination

A combination of 5-aminolevulinic acid (5-ALA) phosphate and sodium ferrous citrate (SFC) demonstrates potential immune support in individuals recently vaccinated against COVID-19, a randomized study indicates.¹ The combination is a food and dietary supplement, the study explains, adding that previous research may suggest that the combination of 5-ALA and SFC could enhance immune cells through improvement of energy availability.

The proof-of-concept study, “5-Aminolevulinic Acid Phosphate as an Immune System Enhancer Along with Vaccination Against SARS-CoV-2 Virus Infection: An Open-Label, Randomized Pilot Study,” was conducted by Vedic Lifesciences and published in Life in June 2025.

Study design: safety, tolerability, and efficacy

Conducted from March to June 2022 in India, the goal of the study was to assess the safety and efficacy of the supplementation. The two-arm study involved 200 participants between the ages of 18 and 70. The test group received a second dose or booster of the Covishield or Covaxin vaccine for COVID-19 along with capsules containing a 150 mg daily dose of 5-ALA Phosphate and SFC for up to 21 days. Each of the three daily capsules contained 50 mg 5-ALA-Phosphate and 28.68 mg SFC. The control group received only the vaccine.

The main measurement in the study was the safety of the test supplement. Adverse effects were tracked, and tolerability of the test product was measured with questionnaires from the participants. As a secondary measurement, changes in Immunoglobulin G (IgG) levels were measured to assess immune response.

Results: changes in immune response

Supplementation during the 21-day intervention period showed trends in immune response from the test product group.

• The increase in geometric mean titer (GMT) levels of IgG antibodies from baseline to 21 days in the test group was 850 U/mL and 337 U/mL in the control group
• In the test group, the estimated marginal means of IgG from baseline to day 21 was 1469 U/mL, while the levels decreased in the control group by 221 U/mL
• After 21 days, the geometric mean fold rise (GMFR) in the test group was 1.38 while it was 1.11 in the control group
• Participants in both arms of the study demonstrated increases in well-being scores, suggesting an improvement in well-being over 21 days

The difference in IgG levels between the groups was not statistically significant, though the supplement showed signals of boosting of immune support properties of 5-ALA-phosphate and SFC, the researchers explained.

Furthermore, none of the adverse effects reported in the study were determined to be related to the test supplement, and administration of the supplement resulted in five times higher odds of having no adverse effects after the vaccine. “The evaluation of the subject questionnaires showed that the administration did not limit the well-being of the participants, which confirms the excellent tolerability of this food supplement,” the researchers concluded, while also suggesting direction for future studies. “However, further studies would be recommended for verification of the results and to investigate the transferability to other types of vaccines and target indications, e.g., influenza,” they added.

Measuring biological relevance in nutraceutical trials

The proof-of-concept study was conducted by Vedic Lifesciences, which also recently published an article on how the European Food Safety Authority (EFSA) measures biological relevance in nutraceutical trials.² Authored by Dr. Sachin Dighe, associate director, claim substantiation at Vedic Lifesciences, the article explains EFSA’s framework for biological relevance and how to design trials to meet EFSA standards, including best practices beyond p-values.

References

1. Berenzen, N.; Rehani, R.; Ebeling, A.; Stocker, M.; Nakajima, M. 5-Aminolevulinic Acid Phosphate as an Immune System Enhancer Along with Vaccination Against SARS-CoV-2 Virus Infection: An Open-Label, Randomized Pilot Study. Life. 2025, 15(6), 953. DOI: 10.3390/life15060953
2. Dighe, S. Beyond P-Values: How EFSA assesses biological relevance in nutraceutical trials. November 20, 2025. https://www.nutritionaloutlook.com/view/beyond-p-values-how-efsa-assesses-biological-relevance-in-nutraceutical-trials (Accessed 2025-12-17).