High doses of vitamin C under study for ameliorating COVID-19 suggest the vitamin may benefit certain populations. Now researchers at the Medical College of Georgia Center (MCGC) for Healthy Aging have taken it a step further, suggesting that the key in vitamin C’s effectiveness lies in the levels of the natural transporter that gets the vitamin inside cells.
“Overall, this manuscript aims to present existing information regarding the extent to which vitamin C can be an effective treatment for COVID-19 and possible explanations as to why it may work in some individuals but not in others,” the researchers note.
Factors to consider
In a commentary in the journal Aging and Disease, the researchers point out that age, race, gender, as well as expression levels and genetic variations of vitamin C transporters may be factors in the effectiveness of vitamin C therapy to help COVID-19 sufferers cope better with their infections.
Dr. Sadanand Fulzele, who conducts research into the aging process and who is the article's corresponding author, suggests that these factors should be considered in the design and execution of clinical trials as well as when trial results are analyzed.
The researchers highlight that a worldwide treatment for COVID-19 is being pursued, including the idea of repurposing drugs with known safety profiles — including vitamin C. (In 2017, Ascor, an ascorbic acid injection for intravenous use, was approved in the US for short‑term treatment of scurvy.)
Exploring the effectiveness of vitamin C
Currently, there are at least 30 clinical trials underway in which vitamin C, alone or in combination with other treatments, is being evaluated in the fight against COVID-19. Some of these trials involve doses up to 10 times the recommended 65 to 90 milligrams of daily vitamin C.
Dr. Carlos M. Isales, co-director of the MCG Center for Healthy Aging and chief of the MCG Division of Endocrinology, Diabetes and Metabolism, said factors like whether or not vitamin C can get inside the cell are likely key in solving the issue of effectiveness.
According to Isales, who is also co-author of the study, treatment with vitamin C is two-fold. He explained that adequate transporters on a cell's surface are needed to get the water-soluble vitamin past the lipid layer of cell membranes. Larger doses of vitamin C may allow the vitamin to cluster around the outside of cells where it actually starts producing oxidants, like damaging reactive oxygen species, rather than helping to eliminate them.
Beyond COVID-19, researchers suspect low transporter expression is a factor in the mixed results from vitamin C's use in a variety of other conditions.
Fulzele, who works on vitamin C in aging, and others have shown that some conditions, like osteoarthritis and even normal aging, are associated with significant downregulation of at least one subtype of vitamin C transporter.
While clinical trials in osteoarthritis have gotten mixed results, the vitamin’s use in other viral-induced problems, like sepsis, has shown benefit in reducing organ failure and improving lung function in acute respiratory distress syndrome, which is also a major cause of sickness and death with COVID-19.
Fulzele said part of the paradox and concern with COVID-19 is that those most at risk mostly have both lower levels of vitamin C before they get sick and fewer transporters to allow the vitamin to be of benefit, even if they get more.
Many of those most at risk from COVID-19 include those who are older, Black, and/or male may have conditions like osteoarthritis, hypertension and diabetes. Those populations also tend to have lower levels of vitamin C.
The researchers also note that patients may develop a vitamin C deficiency over the course of their COVID-19 illness since, during an active infection, vitamin C is consumed at a more rapid rate. Insufficient levels can increase the damage done by an overzealous immune response.
Age also plays a major role. Fulzele explained that reduced transporter levels occur naturally with age and are also a factor in the reduced immune function that also typically comes with aging. Simply put, vitamin C is just not as effective at boosting an older individual's immune response.
Measuring transporter expression
Although not a routine practice, it is possible to measure transporter expression by using PCR technology. However, increasing the expression of this transporter is not yet possible in humans. Fulzele said one of his research goals is to find a way to directly increase expression, which could improve the health of older individuals as well as those with other medical conditions.
Isales and Fulzele say they doubt that taking a lot of vitamin C is a good preventive strategy against COVID-19, except in those individuals with a known deficiency.
"We think it's important to look at transporter expression," Fulzele said.
Source: Aging and Disease
“Low level of Vitamin C and dysregulation of Vitamin C transporter might be involved in the severity of COVID-19 Infection”
Authors: P. Gregory et al.