There is a renewed interest in vitamin C (ascorbic acid), but in reality the “C” never goes out of style. You hear more about it in cold and flu season, or in relation to treatment of wounds, cold sores and other herpetic infections, protocols to treat urinary tract infections (UTI) among others. It is hard not to mention vitamin C containing skin products, tonics, creams, serums. They promise refreshed and healthier skin by boosting collagen production and cell renewal. In the time of pandemic there is constant talk and ongoing debates (at times supported by science)about possible treatments, supplements and other methods to improve immunity and survival success of those afflicted with Covid19 virus, or those trying to fend it off. The science and clinicians looked again at the vitamin C, and ascorbic acid infusions were utilized to treat Covid19, mostly based on prior data of administration in severe infections.

Vitamin C has potent anti-infective and anti-inflammatory properties. It is an essential part of collagen, the builder of healthy connective tissues and the skin. Lack of it predisposes to easy bruising, gum bleeds and poor wound healing among other ailments. To exemplify the severe deficiency state of ascorbic acid I recall the case of a patient who did not consume any fresh fruits and vegetables and was struggling with systemic illness that was diagnosed as vitamin C deficiency about two years after the original presentation to the doctors office. This patient journey started with fatigue, weakness, rash, joint pain and later on was complicated by heart failure, such is the importance of that vitamin on healthy tissues. I was also surprised to diagnose a few of my patients with that disorder after a patient's complaint of easy-bruises and skin thinning. Perhaps the most interesting fact is that despite good access to food in America in general, we are not always able to predict dietary habits of our patients, and even more their access to fresh food. 

The vitamin C cleanses the body from free radicals and physiologically plays an important role in healthy renewal of the immune system. The interest in vitamin C is related to this feature and there are studies of how it can prevent or fight cancer and other immune disorders. Vitamin C is important in iron absorption and when I prescribe the iron to my chronic anemia patients that is related to inflammation, I do remind them about this interesting iron and vitamin C link.

Vitamin C is water-soluble and easily absorbed in the stomach. It is plentiful in most fruits and vegetables, if consumed fresh. Hot water will markedly reduce the amount of active vitamin C in any product. Vitamin C requirements vary by gender and age, but it is generally considered that if one goes over the threshold absorptive value, which is about 70% if you consume about 70-130 mg in a given day, to just 50% if more than 1 gram of vitamin C is delivered orally to the system; then the rest of if is excreted by the kidneys.

The interest in vitamin C and cancer treatment is ongoing.  Based on randomized trials there is not enough conclusive evidence that vitamin C alone is sufficient to fight cancer, but there are additional data that may be a reason for hope, or at least better understanding how vitamin C could help with cancer. The small study by Padayatty and co. published in Annals of Internal medicine in 2004, of physiology and absorption of vitamin C and its concentration in plasma and urine suggests that intravenous administration of the vitamin C reaches much higher values if provided this route. When the oral dose was given to patients at 3 g every 4 hours serum peak plasma vitamin concentrations was 220 micromol/L, compared to the 50 gram iv dose that resulted in concentration that was 140-fold higher. Authors concluded that this argues that more research is needed to see if infusions of vitamin C would fare better as supplemental treatment to standard chemotherapies for various cancers compared to previous negative studies that used orally administered ascorbic acid. There are natural medicine practitioners who use very high doses of vitamin C infusions for cancer treatment augmentation. 

How about Coronavirus? The supraphysiological doses of vitamin C were used in many hospitals at the most desperate time of pandemic, where the influx of very sick patients was exceeding capabilities of hospitals and evidence-based data needed to treat were not available yet, or scarce at best. 

Looking back there are at least two recent studies, one published in journal Chest in 2017 and one more recent reporting data from CITRIS-ALI clinical trial, suggesting that vitamin C may improve short and longer term outcomes in patients with severe lung infections complicated by acute respiratory distress syndrome, more commonly known as ARDS. Study from Chest used steroids and thiamine in addition to vitamin C. 

Building on the experience with treatment of severe lung infections and vitamin C positive effects on lung tissue (possibly through reduction of damage and oxidative stress), clinicians and scientists look again at the use of vitamin C during current pandemic and race to find a treatment. The main reason while patients suffering with Coronavirus are seriously ill is related to irreversible damage to lung tissue among other factors, and a garden variety of remedies to slow that destructive process is being investigated. It is also believed that later stages of Covid19 infection are related more to unsuppressed inflammation rather than just normal response to viral particles. That is why potent anti-inflammatory agents, like tocilizumab and dexamethasone, are considered to a certain extent effective, in particular in combination with other supportive treatments, in fighting the illness. It is interesting that I am very familiar with both medicines treating many inflammatory rheumatic disorders. This anti-inflammatory effect of vitamin C is a factor in selecting it to support treatment with Covid19. The mechanisms by which vitamin C may play a role here are related to its antioxidant properties, preventing cytokine production, free radical generation and battling cell damage. The early, non randomized and small report suggested benefits of vitamin C use in Covid19 patients in China, and later on this practice was mirrored in Europe and in the USA. The supraphysiologic doses of vitamin C are believed to enhance circulating lymphocytes which are part of virus combatting adaptive immunity. There is a large variation in doses of ascorbic acid used in the critical patients, but one of the prospective studies registered at clinicaltrials.gov uses a protocol of 2-hour ascorbic acid infusion daily for 6 days with dose escalation (0.3g/kg, 0.6g/kg, 0.9g/kg). The study is to be conducted at Thomas Jefferson University and details are upon press of the button below.

What struck me most about my review of many, but not all studies (over 2200 are listed as off June 23) of Covid19 at NIH.org is the diversity of agents evaluated for use with this infection, e.g. nitric oxide, lactoferrin, sildenafil, and the large list of rheumatic remedies, among them colchicine, infliximab, baricitinib, tofacitinib and other JAKs inhibitors. This speaks to the mechanism of damage in severe Covid19 infections, concentrating efforts not only on antiviral and more standard approaches to treatment of the viral illness, but exploring later stage inflammatory pathways so detrimental to survival of patients infected with SARS-CoV-2. And despite a rollercoaster of almost daily news reports on antimalarial agents in Coronavirus treatment or infection prevention, the jury is still out on hydroxychloroquine, which is either being actively studied or planned to be studied in multiple registered trials. 

This article would not be complete without mentioning the benefits of ascorbic acid in persons suffering from gout, the disorder that I so frequently encounter in my office. Although not officially endorsed by American College Of Rheumatology in its gout guidelines released this spring, the vitamin C is uricosuric and plentiful in cherries, and their supplementary effect on gout treatment I described elsewhere. 

My final take on the ascorbic acid: I think it is a good strategy to have extra vitamin C handy. Based on limited data it can at least augment recovery from viral illness, stimulate production of cells fighting the infection and reduce oxidative damage to the tissues. While the most interest in it is currently related to treatment of Covid19 there are some positive features of ascorbic acid that could be deployed as supporting skin health, treatment of wounds, urinary infections, herpes virus infections and cancer treatment and prevention. The side effects are mild and range from stomach irritation with oral doses, to kidney stones formation and even hemorrhage, the latter based on small cancer study data. Overall even large doses of vitamin C are considered safe, especially in patients with normal kidneys who will be able to excrete most of the unabsorbed ascorbic acid through the urinary tract.