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Before the bugs hit: protect your patients with science-backed supplements shown to enhance immunity.

Given the continuing uncertainty about COVID-19 variants and this season’s suspected infection rates, we’re all bracing for winter. Meanwhile, the usual suspects—flu, RSV, the common cold—are lining up as winter looms. Before the bugs hit, shore up your patients’ immune-boosting protocols, with a comprehensive combination of botanicals, vitamins and other compounds proven to support immune cell function and promote respiratory health. Some of the best:

  1. Astragalus. From a small shrub native to southeast Asia, Astragalus membranaceus has been used for thousands of years to support the body’s natural defenses and enhance immune response. Astragalus is high in polysaccharides, flavonoids and other compounds thought to be responsible for its antiviral and immunosupportive properties. In research, astragalus is shown to promote the proliferation and activity of immune cells, stimulate the release of cytokines, inhibit viral replication and decrease inflammation. Astragalus polysaccharides demonstrate significant antiviral activity against influenza A virus, hampering viral replication and reducing upper respiratory tract infections, especially in children. Compelling new research hints at possible applications of astragalus to control COVID-19 infection and suggests astragalus polysaccharides could effectively reverse COVID-19 signature genes, reduce viral replication and prevent overactivation of macrophages and cytokine storm.[1], [2], [3], [4], [5]
  2. Garlic. Widely studied for its health benefits, the inflammatory, antioxidant, antimicrobial and immunosupportive properties of garlic (Allium sativum) are well established. Bioactive organosulfur (allicin and alliin) and flavonoid (quercetin) compounds are thought to be responsible for garlic’s immunomodulatory and antiviral activities. Earlier research confirms the inhibitory actions of garlic on the replication of respiratory viruses, influenza A and B, rhinovirus, viral pneumonia, rotavirus and other viruses, and suggests garlic supplements may shorten the duration of cold symptoms. Newer studies are exploring the therapeutic and prophylactic potential of garlic’s organosulfur and flavonoid compounds to fight COVID-19. In one quasi-experimental study of patients hospitalized with COVID-19, a group of volunteers who received garlic essential oil showed a shorter duration of symptoms, shorter time to negative testing and an increase in the rate of improvement.[6], [7], [8], [9]
  3. Olive leaf. Used in folk medicine for hundreds of years, the leaves of the olive tree (Olea europaea L.) are rich in phenolic compounds, including oleuropein, verbascoside and hydroxytyrosol, with antioxidant, anti-inflammatory, antibacterial and antiviral properties. Olive leaf extract is thought to enhance immune response against viruses by boosting the activity of immune cells, modulating cytokine production, stimulate the proliferation of lymphocytes and increasing their function. Oleuropein and other compounds in olive leaf extract have shown inhibitory effects against numerous microorganisms and viruses, including influenza, retroviruses, coxsackie viruses, influenza virus type A and parainfluenza 3. Now, new research points to olive leaf extract as a potential phytotherapy in the control and treatment of COVID-19, and one randomized, triple-blinded clinical trial of hospitalized COVID-19 patients found olive leaf extract can improve the status of patients and decrease the length of hospitalization.[10], [11], [12], [13], [14]
  4. EpiCor. A branded ingredient derived from fermented Saccharomyces cerevisiae yeast, EpiCor’s antioxidant, anti-inflammatory and immune-enhancing effects are well documented. The fermentation process is thought to improve the bioavailability and efficacy of beta-glucans, mannans and other immunosupportive compounds naturally occurring in Saccharomyces cerevisiae. One study found a statistically significant increase in serum antioxidant protection within two hours of a single 500 mg dose of EpiCor. Other research validates its immune-modulating effects: EpiCor has been shown to boost levels of salivary secretory immunoglobulin A, support the activity of natural killer cells, strengthen mucosal immunity and promote antibody production. In one randomized, double-blind, placebo-controlled clinical trial, subjects receiving EpiCor experienced a significant reduction in the incidence and duration of colds or flu compared to placebo.[15], [16], [17], [18]
  5. Berberine. A plant alkaloid found in Indian barberry (B. aristata), goldenseal, Oregon grape and other medicinal herbs, berberine has potent biological and pharmacological actions, with demonstrated anti-inflammatory, antimicrobial, antiviral and immunosupportive properties. Research confirms berberine’s ability to influence the activity of immune cells and regulate the production of inflammatory cytokines. Other studies suggest berberine is effective against a wide range of viruses, including various strains of the influenza virus, strongly suppressing viral replication and repressing the release of inflammatory substances. Current research investigating its ability to shore up protective immunity and hamper viral infection and replication points to a potential role for berberine in treating COVID-19.[19], [20], [21], [22], [23]
  6. Citrus flavonoids. Abundant in oranges, lemons, grapefruits and other citrus fruits, citrus flavonoids are known for their antioxidant, anti-inflammatory and immunomodulatory properties. Some citrus flavonoids—such as hesperidin, naringenin and others—also show strong antiviral activity against a multitude of viruses, including the influenza virus, inhibiting viral replication and reducing infectivity. Emerging research hints at the role of citrus flavonoids as a safe, promising treatment strategy against COVID-19. Hesperidin is of particular interest because of its demonstrated ability to bind to the key proteins of the SARS-CoV-2 virus, suggesting its possible applications for COVID-19.[24], [25], [26], [27], [28], [29]
  7. Vitamin C. For more than 50 years, research has validated the powerful antioxidant and immunosupportive actions of vitamin C and its ability to enhance various cellular functions of both the innate and adaptive immune system, particularly immune cell function. Vitamin C supplementation also appears to benefit respiratory and systemic infections, decreasing susceptibility, easing symptoms and shortening the duration and severity of colds and respiratory tract infections, including the common cold. In a subgroup of studies in which subjects were under significant physical stress, vitamin C prophylaxis resulted in a 50 percent reduction in incidence of the common cold. Newer research on COVID-19 prevention and treatment suggests vitamin C’s immune-modulatory mechanisms may help mitigate COVID-19 infection, progression and severity. In other studies, high-dose vitamin C was shown to lower inflammation, improve oxygen support status and reduce mortality in COVID-19 patients, and could benefit those with severe and critical condition, as well as older individuals.[30], [31], [32]
  8. Zinc. As a crucial player in immune function, undernutrition or deficiency of zinc has been shown to impair cellular mediators of innate immunity such as phagocytosis, natural killer cell activity and the generation of oxidative burst. Research shows zinc is effective against a variety of viral species, and randomized controlled intervention trials suggest adequate intakes can inhibit viral replication, protect against respiratory viruses, ameliorate symptoms and shorten the duration and severity of respiratory tract infections, including the common cold. Recent studies are exploring the role of zinc in COVID-19. Zinc supplementation is linked with lower in-hospital mortality, and in a multicenter, randomized, double-blind trial of patients with COVID-19, zinc supplementation was associated with lower ICU admission and decreased hospital length of stay; for outpatients, zinc reduced symptom duration.[33], [34], [35]
  9. N-acetyl-L-cysteine. NAC, a molecule generally known for its mucolytic effects and benefits for lung health and respiratory conditions, also has direct and indirect antioxidant activity as a precursor of reduced glutathione. Studies demonstrate other effects of NAC, including modulating immune and inflammatory responses, and antiviral properties. NAC has been shown to enhance the function of immune system cells, inhibit replication of the influenza A virus and decrease flu-like episodes and symptoms. Recent research suggests NAC could negatively affect SARS-CoV-2 activity and act as a potential therapeutic agent in the treatment and management of COVID-19 through a variety of mechanisms, including increasing glutathione, promoting T cell response and modulating inflammation. In one review, NAC administered intravenously, orally or inhaled, suppress SARS-CoV-2 replication and improve outcomes and, in combination with other antiviral agents, may dramatically reduce hospital admission rate, mechanical ventilation and mortality.[36], [37], [38], [39]

[1] Zheng Y et al. A review of the pharmacological action of Astragalus Polysaccharide. Front Pharmacol. 2020 Mar 24;11:349.

[2] Li Z et al. Immunomodulatory effects of a new whole ingredients extract from Astragalus: a combined evaluation on chemistry and pharmacology. Chinese medicine. 2019;14:p. 12.

[3] Liang Y et al. Astragalus membranaceus treatment protects Raw264.7 cells from influenza virus by regulating G1 Phase and the TLR3-mediated signaling pathway. Evid Based Complement Alternat Med. 2019 Dec 31;2019:2971604.

[4] Aleebrahim-Dehkordi E et al. Antiviral compounds based on natural astragalus polysaccharides (APS): research and foresight in the strategies for combating SARS-CoV-2 (COVID-19). Mini Rev Med Chem. 2022;22(17):2299-2307.

[5] Lee CY et al. Repurposing Astragalus polysaccharide PG2 for inhibiting ACE2 and SARS-CoV-2 spike syncytial formation and anti-inflammatory effects. Viruses. 2023 Feb 27;15(3):641.

[6] Rouf R et al. Antiviral potential of garlic (Allium sativum) and its organosulfur compounds: A systematic update of pre-clinical and clinical data. Trends Food Sci Technol. 2020 Oct;104:219-234.

[7] Khubber S et al. Garlic (Allium sativum L.): a potential unique therapeutic food rich in organosulfur and flavonoid compounds to fight with COVID-19. Nutr J. 2020 Nov 18;19(1):124.

[8] Ashraf H et al. Molecular screening of bioactive compounds of garlic for therapeutic effects against COVID-19. Biomedicines. 2023 Feb 20;11(2):643.

[9] Wang Y et al. Effect of garlic essential oil in 97 patients hospitalized with covid-19: A multi-center experience. Pak J Pharm Sci. 2022 Jul;35(4):1077-1082.

[10] Peršurić Ž et al. Polyphenol-based design of functional olive leaf infusions(§) Food Technol Biotechnol. 2019;57(2):171–182.

[11] Salamanca A et al. Anti-influenza virus activity of the elenolic acid rich olive leaf (Olea europaea L.) extract Isenolic®. Antivir Chem Chemother. 2021 Jan-Dec;29:20402066211063391.

[12] Abdelgawad SM et al. Olive leaves as a potential phytotherapy in the treatment of COVID-19 disease; a mini-review. Front Pharmacol. 2022; Apr 13;13:879118.

[13] Alhadrami HA et al. Olive-derived triterpenes suppress SARS COV-2 main protease: a promising scaffold for future therapeutics. Molecules. 2021 May 1;26(9):2654.

[14] Ahmadpour E et al. Efficacy of olive leaves extract on the outcomes of hospitalized covid-19 patients: A randomized, triple-blinded clinical trial. Explore (NY). 2023 Jul-Aug;19(4):536-543.

[15] Meletis CD et al. Immune competence and minimizing susceptibility to COVID-19 and other immune system threats. Altern Ther Health Med. 2020 Aug;26(S2):94-99.

[16] Jensen GS et al. Antioxidant bioavailability and rapid immune-modulating effects after consumption of a single acute dose of a high-metabolite yeast immunogen: results of a placebo-controlled double-blinded crossover pilot study. J Med Food. 2011 Sep;14(9):1002-10.

[17] Jensen GS et al. An antiinflammatory immunogen from yeast culture induces activation and alters chemokine receptor expression on human natural killer cells and B lymphocytes in vitro. Nutr Res. 2007 Jun;27(6):327-335.

[18] Moyad MA. Effects of a modified yeast supplement on cold/flu symptoms. Urol Nurs. 2008;28(1):50–55.

[19] Warowicka A et al. Antiviral activity of berberine. Arch Virol. 2020 Sep;165(9):1935-1945.

[20] Och A et al. Biological activity of Berberine-A summary update. Toxins (Basel). 2020 Nov 12;12(11):713.

[21] Botwina P et al. Berberine hampers Influenza A replication through inhibition of MAPK/ERK pathway. Viruses. 2020 Mar 21;12(3):344.

[22] Babalghith AO et al. The role of berberine in Covid-19: potential adjunct therapy. Inflammopharmacology. 2022 Dec;30(6):2003-2016.

[23] Wang ZZ et al. A small molecule compound berberine as an orally active therapeutic candidate against COVID-19 and SARS: A computational and mechanistic study. FASEB J. 2021 Apr;35(4):e21360.

[24] Badshah SL et al. Antiviral activities of flavonoids. Biomed Pharmacother. 2021 Aug;140:111596.

[25] Liu W et al. Citrus fruits are rich in flavonoids for immunoregulation and potential targeting ACE2. Nat Prod Bioprospect. 2022 Feb 14;12(1):4.

[26] Tutunchi H et al. Naringenin, a flavanone with antiviral and anti-inflammatory effects: A promising treatment strategy against COVID-19. Phytother Res. 2020 Dec;34(12):3137-3147.

[27] Alzaabi MM et al. Flavonoids are promising safe therapy against COVID-19. Phytochem Rev. 2022;21(1):291-312.

[28] Alberca RW et al. Perspective: the potential effects of naringenin in COVID-19. Front Immunol. 2020 Sep 25;11:570919.

[29] Bellavite P et al. Hesperidin and SARS-CoV-2: new light on the healthy function of citrus fruits. Antioxidants (Basel). 2020 Aug 13;9(8):742.

[30] Hemila H. Vitamin C supplementation and respiratory infections: a systematic review. Mil Med 2004;169:920-925.

[31] Ahmad SR. Vitamin C for COVID-19 treatment: have we got enough evidence? Front Nutr. 2022 May 19;9:892561.

[32] Shahbaz U et al. Role of vitamin C in preventing of COVID-19 infection, progression and severity. AIMS Microbiol. 2022 Mar 30;8(1):108-124.

[33] Mousa HAL et al. Prevention and treatment of influenza, influenza-like Illness, and common cold by herbal, complementary, and natural therapies. J Evid Based Complementary Altern Med. 2017 Jan; 22(1): 166–174.

[34] Olczak-Pruc M et al. The effect of zinc supplementation on the course of COVID-19 – A systematic review and meta-analysis. Ann Agric Environ Med. 2022 Dec 27;29(4):568-574.

[35] Ben Abdallah S et al. Twice-daily oral zinc in the treatment of patients with Coronavirus Disease 2019: a randomized double-blind controlled trial. Clin Infect Dis. 2023 Jan 13;76(2):185-191.

[36] Jorge-Aarón RM et al. N-acetylcysteine as a potential treatment for novel coronavirus disease 2019. Future Microbiol. 2020 Jun : 10.2217/fmb-2020-0074.

[37] Poe FL et al. N-Acetylcysteine: A potential therapeutic agent for SARS-CoV-2. Med Hypotheses. 2020 Oct; 143: 109862.

[38] Izquierdo-Alonso JL et al. N-acetylcysteine for prevention and treatment of COVID-19: Current state of evidence and future directions. J Infect Public Health. 2022 Dec;15(12):1477-1483.

[39] Shi Z et al. N-Acetylcysteine to combat COVID-19: an evidence review. Ther Clin Risk Manag. 2020 Nov 2;16:1047-1055.

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