One of the earliest accounts of a wide-spread viral respiratory infection can be found in the Book of Epidemics written by Hippocrates around 400 BC. Since then there has been remarkable advances in virology and immunology to help elucidate how to best manage the spread and effectively treat viral illnesses. Despite these significant scientific advances, epidemics of viral respiratory tract infections continue to be highly prevalent and can have catastrophic consequences in susceptible individuals.¹

Host immune response (innate and adaptive immunity) is an important consideration when looking to reduce the incidence and severity of viral illness, as many viruses suppress innate immune responses to make for efficient virus replication.² This is compounded as incomplete, delayed or diminished host immune response may lead to a strong induction of inflammatory cytokines (cytokine storm) that is associated with widespread tissue damage.² Further, pathogenesis in the later stages of viral infections such as SARS-CoV and SARS-CoV-2, for example, results from direct viral toxicity as well as immune dysregulation and hyperactivity.^1,3

Due to the implications of inadequate host immune response discussed above, there is a need to provide patients with a broad scope of treatment options including herbal and nutritional considerations to help improve overall immune activity, reduce viral load and prevent systemic inflammation and tissue damage.

Elderberry

Elderberry has a broad range of phytotherapeutic applications including, antiviral, antibacterial, antioxidant, diaphoretic, and immune boosting actions to name a few. Additionally, the polyphenols and lectins found in Elderberry make it a consideration for reducing the incidence of viral illnesses.¹⁵

Evidence from a meta-analysis of several human trials concluded that Elderberry can significantly reduce total duration and severity of upper respiratory symptoms.¹⁶ This is likely due to its ability to stimulate the production of pro-inflammatory cytokines interleukin (IL)-1β, IL-6, IL-8, and tissue necrosis factor-alpha (TNF-α) while reducing the expression of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and COX-2.¹⁷

In a randomised, double-blind placebo-controlled clinical trial in travellers, Elderberry extract was given at 600 mg/day for 10 days before travel which was increased to 900 mg/day while travelling (4 to 5 days). Results found Elderberry supplementation to be associated with a
2-day shorter duration of cold episode days as well as a reduction in cold symptoms (Figure 2.).¹⁸

Additional research performed in elderly patients during the winter season found a combination of Elderberry (1,500 mg) and Reishi (500 mg) to be effective in lowering the severity and duration of the common cold, in addition to showing a significantly lower probability of high severity influenza-like illness.⁵

Zinc

Zinc has a multitude of functions in human immunology including gene regulation in lymphocytes, the development and function of cells mediating non-specific immunity such as neutrophils and natural killer cells, DNA replication, RNA transcription, and antioxidant and membrane stabilisation.¹⁹

In a double-blind, randomised, placebo controlled, pilot study patients were administered either 1000 mg vitamin C plus 10 mg zinc or equivalent placebo once daily for 5 days. Those in the zinc and vitamin C group experienced a reduced mean duration of rhinorrhoea by 9% when compared with placebo. Further, reported relief of discomfort due to nasal obstruction was more prevalent in the treatment group at day three compared to placebo (Figure 3.).²⁰

Zinc has also been reported as an important integrative consideration during SARS-CoV-2 infection due to its viral inhibitory action, preventing SARS-CoV-2 entry into cells, reducing its virulence.²¹ Further, zinc modulates antiviral and antibacterial immunity and regulates the inflammatory response through modulation of regulatory T-cell functions, which may limit cytokine storm in SARS-CoV-2.²²

Vitamin C

High dose vitamin C (up to 10 g/day) is considered a safe and effective treatment for respiratory viral infections, studies have also found vitamin C to be quickly metabolised in an overactive inflammatory response.²³ Further, vitamin C has been shown to shorten the frequency, severity and duration of the common cold and pneumonia as well as inhibit NLRP3 inflamasome activation, which is associated with the development of hCoV and is responsible for its ultimate virulence and symptoms.²¹

In a review by Hoang et al. 2020, researchers found that treatment with vitamin C can mitigate oxidative stress and pro-inflammatory markers demonstrating an antioxidant and anti-inflammatory response in patients with pneumonia as well as improve respiratory scores, mitigate lung injury and reduce mortality.²² It is thought that vitamin C plays an inherent role in neutrophil function and is essential for immune response and function and may therefore be useful to reduce the incidence and severity of viral infections.¹³

Conclusion

As viral respiratory tract infections continue to be highly prevalent, it is more important now than ever to provide patients with adequate immune support. Herbs such as Elderberry in combination with zinc and vitamin C help to offer our patients safe and effective immune support to help reduce the incidence of viral infections and their complications. In the case of acute viral illness/infection, these ingredients can further assist in promoting a healthy immune response while also reducing inflammation and help reduce the incidence of a cytokine storm.

The information contained within is intended to be used as an educational tool and it is not intended to be used to diagnose, treat, cure or prevent any disease, nor should it be used for therapeutic purposes or as a substitute for your own health professional's advice.

References

1. Moriyama M, Hugentobler WJ, Iwasaki A. Seasonality of Respiratory Viral Infections. Annu Rev Virol. 2020 Sep 29;7(1):83-101. doi: 10.1146/annurev-virology-012420-022445.
2. Kikkert M. Innate Immune Evasion by Human Respiratory RNA Viruses. J Innate Immun. 2020;12(1):4-20. doi: 10.1159/000503030.
3. Zhu H, Rhee JW, Cheng P et al. Cardiovascular Complications in Patients with COVID-19: Consequences of Viral Toxicities and Host Immune Response. Curr Cardiol Rep. 2020 Apr 21;22(5):32. doi: 10.1007/s11886-020-01292-3.
4. Channappanavar R, Perlman S. Age-related susceptibility to coronavirus infections: role of impaired and dysregulated host immunity. J Clin Invest. 2020 Dec 1;130(12):6204-6213. doi: 10.1172/JCI144115.
5. Gracián-Alcaide C, Maldonado-Lobón JA, Ortiz-Tikkakoski E et al. Effects of a Combination of Elderberry and Reishi Extracts on the Duration and Severity of Respiratory Tract Infections in Elderly Subjects: A Randomized Controlled Trial. Appl Sci. 2020; 10(22):8259. doi: 10.3390/app10228259
6. Barak V, Halperin T, Kalickman I. The effect of Sambucol, a black elderberry-based, natural product, on the production of human cytokines: I. Inflammatory cytokines. Eur Cytokine Netw. 2001 Jun;12(2):290-6.
7. Duke, JA et al. Handbook of Medicinal Herbs. 2nd Edition, CRC Press, London, 2002, pp.267-268.
8. Hunter J, Arentz S, Goldenberg J et al. Zinc for the prevention or treatment of acute viral respiratory tract infections in adults: a rapid systematic review and meta-analysis of randomised controlled trials. BMJ open. 2021 Nov 1;11(11):e047474.
9. Lomaestro BM, Bailie GR. Absorption interactions with fluoroquinolones. 1995 update. Drug Saf. 1995 May;12(5):314-33. doi: 10.2165/00002018-199512050-00004.
10. Hemila H, Chalker E. Vitamin C for preventing and treating the common cold. The Cochrane Database Syst Rev 2013:CD000980.
11. Douglas RM, Hemila H, Chalker E et al. Vitamin C for preventing and treating the common cold. Cochrane Database Syst Rev 2007:CD000980.
12. 
    
13. Holford P, Carr AC, Jovic TH et al. Vitamin C - An Adjunctive Therapy for Respiratory Infection, Sepsis and COVID-19. Nutrients. 2020 Dec 7;12(12):3760.  doi: 10.3390/nu12123760.
14. Patterson T, Isales CM, Fulzele S. Low level of Vitamin C and dysregulation of Vitamin C transporter might be involved in the severity of COVID-19 Infection. Aging Dis. 2021 Feb 1;12(1):14-26. doi: 10.14336/AD.2020.0918
15. Zhang M, Jativa DF. Vitamin C supplementation in the critically ill: A systematic review and meta-analysis. SAGE open medicine. 2018 Oct;6:2050312118807615.
16. Mocanu ML, Amariei S. Elderberries—A Source of Bioactive Compounds with Antiviral Action. Plants. 2022 Mar 10;11(6):740.
17. Hawkins J, Baker C, Cherry L et al. Black elderberry (Sambucus nigra) supplementation effectively treats upper respiratory symptoms: A meta-analysis of randomized, controlled clinical trials. Complement Ther Med. 2019 Feb;42:361-365. doi: 10.1016/j.ctim.2018.12.004.
18. Brendler T, Al-Harrasi A, Bauer R et al. Botanical drugs and supplements affecting the immune response in the time of COVID-19: Implications for research and clinical practice. Phytother Res. 2021 Jun;35(6):3013-3031. doi: 10.1002/ptr.7008
19. Tiralongo E, Wee SS, Lea RA. Elderberry Supplementation Reduces Cold Duration and Symptoms in Air-Travellers: A Randomized, Double-Blind Placebo-Controlled Clinical Trial. Nutrients. 2016 Mar 24;8(4):182. doi: 10.3390/nu8040182.
20. Joachimiak MP. Zinc against COVID-19? Symptom surveillance and deficiency risk groups. PLoS Negl Trop Dis. 2021 Jan 4;15(1):e0008895.  doi: 10.1371/journal.pntd.0008895
21. Maggini S, Beveridge S, Suter M. A combination of high-dose vitamin C plus zinc for the common cold. J Int Med Res. 2012;40(1):28-42.  doi: 10.1177/147323001204000104.
22. Alschuler L, Weil A, Horwitz R et al. Integrative considerations during the COVID-19 pandemic. Explore (NY). 2020 Nov-Dec;16(6):354-356.  doi: 10.1016/j.explore.2020.03.007
23. Skalny AV, Rink L, Ajsuvakova OP et al. Zinc and respiratory tract infections: Perspectives for COVID‑19 (Review). Int J Mol Med. 2020 Jul;46(1):17-26.  doi: 10.3892/ijmm.2020.4575.
24. Hoang BX, Shaw G, Fang W et al. Possible application of high-dose vitamin C in the prevention and therapy of coronavirus infection. J Glob Antimicrob Resist. 2020 Dec;23:256-262. doi: 10.1016/j.jgar.2020.09.025