Mixed-methods assessment and immunomodulatory role of dietary vitamin C 2022

Mixed-methods assessment and immunomodulatory role
of dietary vitamin C
Abstract
Vitamin C (ascorbic acid) is a well-known antioxidant and biological factor that guarantees the
efficiency of bodily homeostatic mechanisms. Existing evidence suggests that it has an essential
function in modulating the immune response at multiple sites. The recent outbreak of COVID-19
has become a pandemic with tens of thousands of people getting infected. Based on clinical
features, a combination of excessive inflammation, oxidation, and a maladaptive immune
response contributes to the COVID-19 pathology. Vitamin C acts as an anti-oxidative molecule
protecting immune cell populations during infection caused by viral and other pathogens. It has
been shown to support antiviral activity and proved useful in critical care patients with reduced
lung function. Significant data is showing that managing the status of vitamin C might be
beneficial for better clinical outcomes for COVID-19 patients, although further studies are
required to confirm this speculation. Supplemental and intravenous vitamin C research studies
are currently underway in the United States and China for the attenuation of COVID-19 based on
its putative pathogenesis with excellent results. Nutritional strategies that prevent the virus from
docking to our cells and prevent its replication are part and parcel of responding to COVID-19.
Addressing poor nutrition in people at risk requires reliable dietary evaluation methods, in
particular for those already burdened by toxicants or chronic illness. The present study focuses
on the comparative assessment of dietary vitamin C intake by weighed records and biochemical
methods in college students. We report primary data on the estimated vitamin C concentration of
a standardised meal with the duplicate diet method and assess agreement between this value and
that obtained from a weighed inventory using a food database and 24-hour dietary recall. We
expected to see variability in nutrient concentrations between methods. The results showed
discrepancy particularly between the weighed inventory and dietary recall data. This article

summarises the factors that may impact the evaluation of nutrient intake as well as the possible
benefits of dietary vitamin C adequacy in the attenuation of COVID-19.
Introduction
Vitamin C is a water-soluble vitamin obtained from food and is essential to life. Using a well-
balanced diet to manage vitamin C status is relatively easy due to its ubiquitousness in our fresh-
food supply. The best sources of vitamin C in the diet are raw and gently cooked, fresh fruit and
vegetables. For example, one can achieve optimum intake (150 mg per day) of vitamin C from
one serving (100 g) of yellow or green bell peppers, guavas, or currants; from two servings of
kale, broccoli, kiwifruit, or mustard spinach; or from three to five servings of oranges,
strawberries, lemons, or Brussels sprouts [1]. It is, however, one of the least stable vitamins and
can be easily destroyed by cooking and during storage [2]. This effect of cooking loss ultimately
impacts the assessment and absolute values of vitamin C intake.
In response to increasing oral vitamin C intake, the vitamin accumulates in specific body
tissues. Pharmacokinetic experiments show that vitamin C concentrations are highest in the
pituitary and adrenal glands [3]. This is of importance to this discussion as there is a bi-
directional communication network between the hypothalamus-pituitary-adrenal (HPA) axis
and immune system [4]. When the HPA axis gets activated, high levels of the hormone cortisol
are released, which in turn suppresses immune responses. There is a high vitamin C turnover in
the adrenal cortex during times of stress [5,6], and that is, arguably, because vitamin C plays a
role in reducing cortisol reactivity and associated suppressive effects on the immune system [7].
As such, vitamin C may be considered an effect modifier of the stress response: promoting an
adaptive stress response and enhanced immunity, as opposed to a stress-related disorder
increases the risk of infectious diseases.
Preliminary research into COVID-19 pathophysiology also suggests that patients have a
distinct gut microbiome environment that aggravates the progression of the infection [8]. Due to
the extensive immune activity in the gastrointestinal tract [9], one could theorise that preventing
gut dysbiosis pre-emptively would lower the risk of acute respiratory distress syndrome (ARDS)
that older patients are exhibiting. The most critical patients typically present with insulin

resistance or diabetes as well [10], which is a state that often coexists with endotoxemia in the
gut [11,12] and depletes vitamin C further [13].
Vitamin C is also believed to affect the immune system more directly. In cell mechanistic
models of vitamin C effects, it was shown that the vitamin could stimulate the production [14-18]
and function [19,20] of leukocytes, especially lymphocytes – which are one of the first immune
responders. Vitamin C also seems to promote more effective chemotaxis of lymphokines and
monokines to the site of infection [19,20]. More generally, its antioxidant functions help ward
against oxidative damage to different immune cell types [21], promoting a more robust immune
response. Other studies suggested that vitamin C can increase interferon production [22], which
is thought to be a marker of higher antiviral activity. However, this is currently a point of
contention in the research community, as interferon in SARS-like viruses is a trigger for the
“cytokine storm” that causes inflammatory damage in the lungs [23]. Therefore, it is difficult to
predict whether vitamin C would make things better or worse during the inflammatory
destruction of the lungs that happens with the new coronavirus.
In humans, vitamin C can be helpful in dire situations. One study found that high dose
vitamin C doubled the chance of survival for patients whose lung function was rapidly
deteriorating [24]. A meta-analysis found that vitamin C significantly shortened the length of
stay in the intensive care unit [25] and that vitamin C reduces the duration of mechanical
ventilation for critical patients [26]. These are significant findings given the global shortages of
hospital beds in the fight against COVID-19. However, there have been no studies testing
vitamin C against any of the coronaviruses yet. Based on available evidence, the
recommendation should be to eat a diet that provides enough vitamin C for general immune
support.
Here, we first used an updated food database to calculate vitamin C intake and design our
reference meal. Then we evaluated the effect of cooking procedures by biochemical assay and
compared this with estimated vitamin intake derived from food composition tables. Besides, we
also compared dietary intake assessment methods and addressed the intrinsic and extrinsic
factors affecting these methods.
Methods and Materials