What is it about?

A Mendelian randomization (MR) study concluded that vitamin C was not effective for pneumonia. We showed that the MR study corresponds to the comparison of two groups with similar vitamin C levels of 47.3 vs. 52.7 μM, whereas the plasma vitamin C level range in the population is from 10 to 100 μM.

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Why is it important?

In a Mendelian randomization (MR) study, Hui (2001) (https://pubmed.ncbi.nlm.nih.gov/34462559) concluded that there is no support for the use of vitamin C in the prevention and treatment of pneumonia or COVID-19. However, they used single nucleotide polymorphisms (SNPs) that were associated with plasma vitamin C levels in the genome-wide association study in 52,018 people of European ancestry. The cited study states “the variance of plasma vitamin C explained by the 11 lead SNPs was 1.87% on average”. Explaining such a very small proportion of the variance is not a valid measure of the possible effects of vitamin C. We calculated that the analysis by Hui et al. corresponds to the comparison of two population groups of equal size with vitamin C levels of 47.3 vs. 52.7 μM. Such a very small difference in the mean vitamin C levels is not clinically meaningful.. A study of vitamin C and pneumonia should ideally compare plasma levels between 10–20 μM and 60–100 μM.

Perspectives

In the early literature, low vitamin C intake was associated with increased risk of pneumonia (https://pubmed.ncbi.nlm.nih.gov/18048704) and a few intervention trials indicated that vitamin C may have preventive and treatment effects on pneumonia (https://pubmed.ncbi.nlm.nih.gov/23925826). With very low dietary vitamin C intakes, plasma vitamin C level can fall below 10 μM, whereas with particularly high dietary intakes, plasma level can increase to around 100 μM. Thus, to evaluate the effects of plasma vitamin C on specific conditions, the relevant plasma range should cover around 10 to 100 μM.

Dr Harri Hemila
Helsingin Yliopisto

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This page is a summary of: Assessment of vitamin C effects on pneumonia and COVID-19 using Mendelian randomization: analysis may be misleading, European Journal of Clinical Nutrition, February 2022, Springer Science + Business Media,
DOI: 10.1038/s41430-022-01091-9.
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