According to a report published in the journal Aging and Disease gender, race, age, expression levels and genetic variations of the vitamin C transporters that might make them less efficient all may be factors in the effectiveness of vitamin C therapy against COVID-19 and other maladies. As such the corresponding author, Dr. Sadanand Fulzele and the team recommend that those factors be taken into consideration in the design and execution of clinical trials and when trial results are analyzed for COVID-19 or any other condition.
Lack of immunity has prompted a global pursuit of effective treatments which includes repurposing drugs with known safety profiles. Vitamin C is an established immune system booster and antioxidant which makes a logical choice to explore against COVID-19 as both strategies are needed in response to infection with the virus to ensure a strong immune response to be able to stop the virus from replicating in the body as well as to avoid the destructive immune response that the virus itself can generate.
Currently, there are at least 30 clinical trials underway which include vitamin C either alone or in combination with other treatments being evaluated against COVID-19 with some of the doses being up to 10 times the recommended 65-90 milligrams of vitamin C per day.
Factors such as whether or not the vitamin is able to get inside the cell will likely be an issue in the effectiveness of the therapy that will be ultimately shown, says Dr. Carlos M. Isales, co-director of the MCG Center for Healthy Aging and chief of the MCG Division of Endocrinology, Diabetes and Metabolism.
Without adequate transporters on a cell’s surface to get the water-soluble vitamin past the lipid layer of cell membranes, large doses of the vitamin may help to enable the vitamin to cluster around the outside of the cells where it can start to produce oxidants such as damaging reactive oxygen species rather than helping to eliminate them suggests study coauthor Fulzele.
Low transporter expression is believed to be a factor in the mixed results from vitamin C use in a variety of other conditions. For example, clinical trials in osteoarthritis which is an autoimmune disease where a misdirected immune system attacks the joints yielded mixed results. However, the use of vitamin C in other viral-induced problems such as sepsis have shown benefit in reducing organ failure and improving lung function in acute respiratory distress syndrome which is a major cause of sickness and death with COVID-19.
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.
In fact, 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 enable the vitamin to be of benefit if they get more, Fulzele says.
Many of those most at risk from COVID-19, including individuals who are older, Black, male and with chronic medical conditions like osteoarthritis, hypertension and diabetes, tend to have lower levels of vitamin C, another reason vitamin C therapy would be considered a reasonable treatment, Isales says. The investigators 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 augment the damage done by an overzealous immune response.
While not routinely done, transporter expression can be measured today using PCR technology, a method also used for novel coronavirus as well as influenza testing. While increasing transporter expression is not yet doable in humans, one of Fulzele’s many research goals is to find a drug or other method to directly increase expression, which should improve the health of older individuals as well as those with other medical conditions that compromise those levels.
He notes that reduced transporter levels that occur naturally with age are a factor in the reduced immune function that also typically accompanies aging. That means that even when a 60-year-old and 20-year-old both have a healthy diet in which they consume similar, sufficient amounts of vitamin C, the vitamin is not as effective at boosting the older individual’s immune response. Reduced immune function in older individuals is known to put them at increased risk for problems like cancer and COVID-19.
Low vitamin C levels also have been correlated with higher mortality in older individuals from causes like cardiovascular disease. High oxidative stress, a major factor in conditions like cardiovascular disease as well as aging and now COVID-19, also is associated with significantly reduced expression of the vitamin C transporter.
Isales and Fulzele doubt that taking a lot of vitamin C is a good preventive strategy against COVID-19, except in those individuals with a known deficiency.
Vitamin C is an essential vitamin, which means people have to consume it in their food or supplements. Foods naturally high in vitamin C include oranges, potatoes, tomatoes, broccoli and Brussels sprouts. The vitamin’s diverse roles in the body also include the formation of blood vessels, collagen and cartilage.
Gregory Patterson, a medical student who worked with Fulzele over the summer between his first and second year of medical school as part of MCG’s Medical Scholars Program, is the first author of the study. The research was supported in part by the National Institutes of Health.
