Vitamin C is a micronutrient which regulates several biological mechanisms in the human body. Vitamin C world deficiency statistics are mostly unknown, but estimations suggest it is common in low to middle income countries and in some specific groups in high income countries. Age, race, dietary culture, socioeconomic status and other demographic and environmental factors are determinant for vitamin C deficiency prevalence (Carr & Rowe, 2020; Rowe & Carr, 2020).

Biological function

Vitamin C is absorbed in the distal small intestine and there is either diffused or transported by SVCTs (sodium-dependent vitamin C transporters) and hexose transporter, reaching every part of the body. Vitamin C shows anti-oxidant properties and is necessary for the biosynthesis of the protein collagen. Vitamin C plays an important role in iron absorption and in some enzymatic reactions related to essential biological functions like wound healing. Vitamin C levels are considered adequate when blood levels reach 50 µmol/L. Vitamin C deficiency is considered when blood levels are below 25 µmol/L (Abdullah et al., 2020; Njus et al., 2020).

Clinical relevance

The most common vitamin C deficiency medical condition is scurvy, but it has also been associated to clinical conditions like viral and bacterial infections, immune system-related diseases like chronic inflammatory bowel disease, neurological disorders and some types of cancer.

Supplementation of 40 to 200 mg/day is usually sufficient to maintain adequate blood levels, depending on age and gender. Also, vitamin C supplementation is considered safe and only high supplementation (in the order of grams per day) over long periods of time has been shown to be toxic (Abdullah et al., 2020; Rowe & Carr, 2020).

Scurvy

Scurvy is the name of the disease caused by general vitamin C deficiency. First symptoms start with irritability and anorexia, followed by dermatologic dysfunctions, gingival swelling, ecchymosis, hyperkeratosis, ocular problems, hemorrhages, bone fractures and papilledema. Treatment is based on vitamin C replacement, with up to 300 mg daily for children and 500 mg to 1000 mg daily for adults. The endpoint of replacement is one month or upon resolution of clinical symptoms (Maxfield & Crane, 2020).

Lung infection and COVID-19

During a COVID-19 infection, vitamin C levels drop in serum and leukocytes, which can be restored by vitamin C supplementation (Abobaker et al., 2020). Also, high doses of vitamin C could reduce the need of high doses of corticosteroids, antibacterials and antiviral drugs that may be immunosuppressive (Hoang et al., 2020).

Immune system disorders

Vitamin C has been shown to play an important role in cells of the immune system like leukocytes, natural killer cells, B and T lymphocytes, neutrophils, monocytes and macrophages. In fact, vitamin C deficiency reduces cellular and humoral immune responses, while its supplementation has been shown to stimulate immune response. In the case of immune-related gastrointestinal disorders like chronic inflammatory bowel disease vitamin C levels are reduced (Mousavi et al., 2019).

Cancer

The role of Vitamin C in the immune system can have an effect on the tumor environment, affecting the inflammatory response and the progression of the tumor. In fact, vitamin C has been shown to be beneficial as adjunct treatment option for colorectal cancer (Ang et al., 2018; Mousavi et al., 2019).

Neurological disorders

Vitamin C can reduce oxidative stress, levels of inflammatory cytokines, telomere attrition and disorganization of chromatin. It can also modulate age related inflammatory and immune system processes. These properties indicate that vitamin C could be beneficial during neurological disorders. In fact, it could reduce factors related to Alzheimer’s Disease for instance by suppression of amyloid-beta peptide fibrillogenesis (Monacelli et al., 2017).

Endocannabinoid System

Vitamin C and its analogs can stimulate cannabinoid receptor binding at low micromolar concentrations (Nye et al., 1989). However, vitamin C decreases the expression of cannabinoid receptors after UVA and UVB exposure, suggesting vitamin C might regulate the endocannabinoid system (Gęgotek et al., 2017). Cancer cells treated with cannabinoids showed reduced levels of vitamin C, but the underlying mechanisms are unknown (Cerretani et al., 2020). Vitamin C reduced THC-induced spermatoxicity but through mechanisms unrelated to cannabinoid receptors (Alagbonsi & Olayaki, 2020). In conclusion, it looks like vitamin C can modulate the endocannabinoid system, but this topic has not been further studied, so the potential interaction of vitamin C and the endocannabinoid system is unknown. Further research is warranted to understand this interaction.

Cannabinoid synergies

Due to the lack scientific evidence, the potential interaction of cannabinoids and vitamin C is unknown and needs to be investigated.

Health Claims (EU/EFSA)

• Vitamin C contributes to maintain the normal function of the immune system during and after intense physical exercise
• Vitamin C contributes to normal collagen formation for the normal function of blood vessels
• Vitamin C contributes to normal collagen formation for the normal function of bones
• Vitamin C contributes to normal collagen formation for the normal function of cartilage
• Vitamin C contributes to normal collagen formation for the normal function of gums
• Vitamin C contributes to normal collagen formation for the normal function of skin
• Vitamin C contributes to normal collagen formation for the normal function of teeth
• Vitamin C contributes to normal energy-yielding metabolism
• Vitamin C contributes to normal functioning of the nervous system
• Vitamin C contributes to normal psychological function
• Vitamin C contributes to the normal function of the immune system
• Vitamin C contributes to the protection of cells from oxidative stress
• Vitamin C contributes to the reduction of tiredness and fatigue
• Vitamin C contributes to the regeneration of the reduced form of vitamin E
• Vitamin C increases iron absorption

References

Abdullah, M., Jamil, R. T., & Attia, F. N. (2020). Vitamin C (Ascorbic Acid). In StatPearls. StatPearls Publishing. http://www.ncbi.nlm.nih.gov/books/NBK499877/

Abobaker, A., Alzwi, A., & Alraied, A. H. A. (2020). Overview of the possible role of vitamin C in management of COVID-19. Pharmacological Reports: PR, 72(6), 1517–1528. https://doi.org/10.1007/s43440-020-00176-1

Alagbonsi, A. I., & Olayaki, L. A. (2020). Vitamin C ameliorates tetrahydrocannabinol-induced spermatotoxicity in-vitro. BMC Nutrition, 6(1), 59. https://doi.org/10.1186/s40795-020-00387-y

Ang, A., Pullar, J. M., Currie, M. J., & Vissers, M. C. M. (2018). Vitamin C and immune cell function in inflammation and cancer. Biochemical Society Transactions, 46(5), 1147–1159. https://doi.org/10.1042/BST20180169

Carr, A. C., & Rowe, S. (2020). Factors Affecting Vitamin C Status and Prevalence of Deficiency: A Global Health Perspective. Nutrients, 12(7). https://doi.org/10.3390/nu12071963

Cerretani, D., Collodel, G., Brizzi, A., Fiaschi, A. I., Menchiari, A., Moretti, E., Moltoni, L., & Micheli, L. (2020). Cytotoxic Effects of Cannabinoids on Human HT-29 Colorectal Adenocarcinoma Cells: Different Mechanisms of THC, CBD, and CB83. International Journal of Molecular Sciences, 21(15). https://doi.org/10.3390/ijms21155533

Gęgotek, A., Bielawska, K., Biernacki, M., Zaręba, I., Surażyński, A., & Skrzydlewska, E. (2017). Comparison of protective effect of ascorbic acid on redox and endocannabinoid systems interactions in in vitro cultured human skin fibroblasts exposed to UV radiation and hydrogen peroxide. Archives of Dermatological Research, 309(4), 285–303. https://doi.org/10.1007/s00403-017-1729-0

Hoang, B. X., Shaw, G., Fang, W., & Han, B. (2020). Possible application of high-dose vitamin C in the prevention and therapy of coronavirus infection. Journal of Global Antimicrobial Resistance, 23, 256–262. https://doi.org/10.1016/j.jgar.2020.09.025

Maxfield, L., & Crane, J. S. (2020). Vitamin C Deficiency. In StatPearls. StatPearls Publishing. http://www.ncbi.nlm.nih.gov/books/NBK493187/

Monacelli, F., Acquarone, E., Giannotti, C., Borghi, R., & Nencioni, A. (2017). Vitamin C, Aging and Alzheimer’s Disease. Nutrients, 9(7). https://doi.org/10.3390/nu9070670

Mousavi, S., Bereswill, S., & Heimesaat, M. M. (2019). Immunomodulatory and Antimicrobial Effects of Vitamin C. European Journal of Microbiology & Immunology, 9(3), 73–79. https://doi.org/10.1556/1886.2019.00016

Njus, D., Kelley, P. M., Tu, Y.-J., & Schlegel, H. B. (2020). Ascorbic acid: The chemistry underlying its antioxidant properties. Free Radical Biology & Medicine, 159, 37–43. https://doi.org/10.1016/j.freeradbiomed.2020.07.013

Nye, J. S., Snowman, A. M., Voglmaier, S., & Snyder, S. H. (1989). High-affinity cannabinoid binding site: Regulation by ions, ascorbic acid, and nucleotides. Journal of Neurochemistry, 52(6), 1892–1897. https://doi.org/10.1111/j.1471-4159.1989.tb07273.x

Rowe, S., & Carr, A. C. (2020). Global Vitamin C Status and Prevalence of Deficiency: A Cause for Concern? Nutrients, 12(7). https://doi.org/10.3390/nu12072008