Supercharge your immune-strengthening supplementation with vitamins that pack an extra punch

You might start getting questions from your patients about natural ways to avoid infections as cold and flu season returns. And who can blame them?

There are so many products marketed specifically for bolstering the immune system that the choices must seem dizzying. Fortunately, you can bring some clarity. 

While each person responds differently to immune-strengthening nutrients, there are some general rules for recommending effective options: 

1. Does it have scientific research and/or traditional use to back it up? 
2. Is it a nutrient that may be commonly deficient or lacking in diets? 
3. Can it deliver results and reduce symptoms quickly? 

If you can answer yes to any of those questions, you may consider adding the nutrient to an immune protocol in your own practice. Here are a few of my favorites: 

Andrographis

Widely used in Ayurvedic medicine in India and throughout Asia for thousands of years, andrographis (Andrographis paniculata) is an especially powerful ally in fighting viral infections. 

For example, in a double-blind, placebo-controlled study, andrographis relieved the intensity of cold symptoms, including fatigue, sore throat, runny nose and restless sleep in just two days. By day four, there was a significant decrease in all symptoms, including headache, earache, phlegm production and the frequency and intensity of coughing spells.¹ 

Another clinical study of individuals with upper respiratory tract infection (URTI) showed comparable results. In this case, 223 patients either received andrographis or a placebo. By the third day, there was a dramatic difference in cough, headache, sore throat and disturbed sleep. Not surprisingly, those in the placebo group noticed no improvement; for some, symptoms got worse.² 

Andrographis can also stop the growth of dangerous bacteria, including Staphylococcus aureus (staph infection), by preventing the bacteria from enlisting its own antioxidant defenses that would otherwise allow it to thrive. Considering how overprescribed antibiotics have become in the past 20 years or so, and how much stronger bacterial infections have become as a result, this botanical could be a much more effective form of treatment.³ 

Vitamin D

 Vitamin D3 has a well-deserved reputation as an immune-strengthening nutrient. It can help your patients be less susceptible to allergy symptoms, respiratory ailments and viral infections. One review found each significant increase in vitamin D (10 nmol/l) was associated with a 7% lower risk of infection.⁴ Vitamin D also keeps immune responses in balance, so it is valuable for patients with autoimmune conditions who need a seasonal boost or relief from colds or flus.^5,6 

Suffice to say, many people are deficient in vitamin D. Individuals who work indoors or live in a northern climate very likely have low blood levels of vitamin D. Others may have genetic predispositions to low vitamin D levels because of alterations in the vitamin D receptor (VDR) protein. Additionally, anyone with autoimmune gastrointestinal diseases may simply have absorption issues with vitamin D, and patients taking cholesterol-lowering drugs may be inadvertently creating deficiencies since cholesterol is crucial for vitamin D synthesis. 

Finally, one grim statistic shows the critical importance of vitamin D: Researchers conducting a cohort study spanning 15 years estimated about 41% of deaths from respiratory disease in older adults were statistically attributable to insufficiencies or deficiencies of the nutrient.⁷

Zinc and selenium

 Zinc is critical for immune defenses. It is a requirement for T-lymphocyte white blood cell activity, and relays information about potential threats and maintains both the innate and adaptive immune systems. Therefore, it keeps your patients’ existing defenses strong, and it helps their immune systems adapt and fight bacteria or novel viruses they haven’t encountered in the past.⁸ 

Additionally, zinc interrupts a virus’s replication cycle, so getting extra help from zinc during the initial stages of illness can stop it from taking hold. And it can have a noticeable effect.^8,9 

In fact, researchers who pooled the results of three clinical studies found that zinc reduced the duration of cold symptoms by 42% compared to a placebo. But the timing of zinc is key; these same researchers also noted that getting zinc on board at the first sign of symptoms helps deliver results within the first 24 hours of a cold.⁴ 

Selenium is also exceptionally potent at fighting infections and shares many immune system pathways with zinc. Not surprisingly, a lack of either mineral can lead to increased oxidative stress, more inflammation and out–of–balance CD4/CD8 lymphocyte ratios — contributing factors to cytokine storms. 

For some patients, it’s important to note that selenium and zinc levels tend to be lower in individuals with asthma, with notable effects. Clinical research reports this deficiency ramps up C-reactive protein levels, creates an imbalance of lymphocytes and lowers levels of antioxidant enzyme activity (like glutathione). So it’s imperative patients with this condition have sufficient levels of selenium and zinc.^12,13 

As an add-on therapy for treating viral and bacterial infections, selenium can also be used to fight influenza-A (a common flu) and appears to stop (or at least slow down) other, more contagious viruses as well.¹⁴ 

Quercetin and vitamin C

While quercetin may not sound as familiar to your patients as other immune-strengthening nutrients, the compound itself is quite common, found in apples, grapes, onions, teas, tomatoes and various herbs.¹⁵ 

Scientific studies show pretreatment with quercetin is the best way to stop viruses from replicating, effectively blocking H1N1 within 48 hours. In vitro research reported quercetin inhibited rhinovirus replication within 24 hours.¹⁶ 

Quercetin activates T-helper cells (Th-1) that produce interferon-gamma (INF-y), a cytokine that, in turn, activates macrophages that hunt down and destroy viral and bacterial invaders. And quercetin balances Th-2 cells to keep the immune responses helpful, but not severe.¹⁶ 

Additionally, quercetin inhibits mast cell and eosinophil activation (which otherwise trigger allergic symptoms), reduces histamine release, relaxes the trachea and reduces inflammatory compounds in cells that line the inside of the lungs. It can balance the production of immunogloblulin-E (IgE) production in the lymph nodes, inhibiting the inflammatory effects of IgE in tissues throughout the body.^15,17 

Quercetin is also a bronchodilator, making it an excellent option for treating chronic obstructive pulmonary disease (COPD) and asthma. Scientific study on cells from COPD patients report that quercetin may also make conventional medications for COPD more effective when patients develop resistance to them.⁴ 

In other research, quercetin’s ability to inhibit mast cell release from pro-inflammatory cytokines IL-6 and TNF proved superior to cromoglicic acid (cromolyn sodium), and it was effective as a preventative in cases of contact dermatitis and photosensitivity, where the drug was not.^15,19 

The vitamin C and quercetin connection

Vitamin C is probably one of the best-known immune boosters. Taken as a preventative nutrient, vitamin C may reduce the incidence of colds by as much as 50% and appears to have a natural antihistamine effect, alleviating allergy and other respiratory symptoms. Plus, its strong ability to scavenge cellular reactive oxygen species (ROS) allows it to intercept or preempt the ROS-required signals that fire up pro-inflammatory cytokines.^20-23 

With its multitude of duties, vitamin C is in high demand by tissues throughout the body, so a consistent dosage of at least around 200 mg per day may be ideal for immune responses. Prior to entering an allergy season, patients may want to consider adding that level of vitamin C to their regimens before they notice symptoms start in order to prep their immune systems for the challenges ahead.²³ 

Quercetin and vitamin C appear to work better as a duo than they do individually. A randomized, double-blind clinical study found a combination of quercetin and vitamin C was more effective in reducing C-reactive protein levels and the inflammatory marker IL-6, than either nutrient used alone. 

That’s because vitamin C regenerates oxidized quercetin metabolites, making them able to fight free radical damage again. So combining quercetin with vitamin C is one way to help make quercetin — a difficult–to–absorb compound — more active.²⁴ But it’s not the only way. Gamma cyclodextrin can assist quercetin’s absorbability and by extension, effectiveness, too. 

Gamma cyclodextrin is an oligosaccharide that envelops fat-soluble nutrients in an open-ended microscopic structure, which has been described as bucket-shaped, or as a truncated cone. The exterior of this molecule is water–soluble, which allows it to escort ingredients through intestinal walls for better absorption. Essentially, it gives a fat-soluble nutrient the absorption qualities of a water-soluble one, in some cases, improving absorption by as much as eight times.²⁵   

Final thoughts

To many of your patients, the supplemental choices for cold and flu season may seem overwhelming. That’s why your expertise is so necessary. Recommending nutrients that repair deficiencies, shorten duration and reduce symptoms safely and effectively will ensure your patients have the immune protection they can count on, this season and beyond. 

HOLLY LUCILLE, ND, RN, is a nationally recognized and licensed naturopathic doctor, educator, natural products consultant and television and radio host. She is also the author of several books and an acclaimed expert in the field of integrative medicine. Lucille lectures on a variety of natural health topics and is an expert contributor to consumer and peer journals. She has her own talk show, “Myth-Defying with Dr. Holly,” and is the host of the podcast “Mindful Medicine.” Lucille’s private practice in Los Angeles, Healing from Within Healthcare, focuses on comprehensive naturopathic medicine and individualized care. 

References

1. Cáceres DD, et al. Use of visual analogue scale measurements (VAS) to assess the effectiveness of standardized Andrographis paniculata extract SHA-10 in reducing the symptoms of common cold. A randomized double blind-placebo study. Phytomedicine. 1999;6(4):217-223. PubMed website. https://pubmed.ncbi.nlm.nih.gov/10589439/. Accessed Nov. 7, 2023.
2. Saxena RC, et al. A randomized double blind placebo controlled clinical evaluation of extract of Andrographis paniculata (KalmCold) in patients with uncomplicated upper respiratory tract infection. Phytomedicine. 2010;17(3-4):178-185. PubMed website. Accessed Nov. 8, 2023. 
3. Hussain RM, et al. Mechanism of antagonistic effects of Andrographis paniculata methanolic extract against Staphylococcus aureus. Asian Pac J Trop Med. 2017;10(7):685-695. PubMed website. https://pubmed.ncbi.nlm.nih.gov/28870345/. Accessed Nov. 8, 2023. 
4. Berry DJ, et al. Vitamin D status has a linear association with seasonal infections and lung function in British adults. Br J Nutr. 2011;106(9):1433-1440. PubMed website. https://pubmed.ncbi.nlm.nih.gov/21736791/. Accessed Nov. 8, 2023.
5. Yang CY, et al. The implication of vitamin D and autoimmunity: a comprehensive review. Clin Rev Allergy Immunol. 2013;45(2):217–226. PubMed website. https://pubmed.ncbi.nlm.nih.gov/23359064/. Accessed Nov. 8, 2023.
6. Illescas-Montes R, et al. Vitamin D and autoimmune diseases. Life Sci. 2019;233:116744. PubMed website.⁴ Accessed Nov. 8, 2023.
7. Brenner H, et al. Vitamin D insufficiency and deficiency and mortality from respiratory diseases in a cohort of older adults: Potential for limiting the death toll during and beyond the COVID-19 pandemic? Nutrients. 2020;12(8):2488. PubMed website. https://pubmed.ncbi.nlm.nih.gov/32824839/. Accessed Nov. 8, 2023. 
8. Keflie TS, Biesalski HK. Micronutrients and bioactive substances: Their potential roles in combating COVID-19. Nutrition. 2021;84:111103. PubMed website. https://pubmed.ncbi.nlm.nih.gov/33450678/. Accessed Nov. 8, 2023.
9. Kido H, et al. Proteases essential for human influenza virus entry into cells and their inhibitors as potential therapeutic agents. Curr Pharm Des. 2007;13(4):405-414. PubMed website. https://pubmed.ncbi.nlm.nih.gov/17311557/. Accessed Nov. 8, 2023.
10. Hemilä H. Zinc lozenges may shorten the duration of colds: a systematic review. Open Respir Med J. 2011;5:51-58. PubMed website. https://pubmed.ncbi.nlm.nih.gov/21769305/. Accessed Nov. 8, 2023. 
11. Godfrey JC, et al. Zinc gluconate and the common cold: a controlled clinical study. J Int Med Res. 1992 Jun;20(3):234-246. PubMed website. https://pubmed.ncbi.nlm.nih.gov/1397668/. Accessed Nov. 8, 2023.
12. Avery JC, Hoffmann PR. Selenium, Selenoproteins, and Immunity. Nutrients. 2018;10(9):1203. PubMed website. https://pubmed.ncbi.nlm.nih.gov/30200430/. Accessed Nov. 8, 2023. 
13. Mahmoodpoor A, et al. The Effect of Intravenous Selenium on Oxidative Stress in Critically Ill Patients with Acute Respiratory Distress Syndrome. Immunol Invest. 2019;48(2):147-159. PubMed website. https://pubmed.ncbi.nlm.nih.gov/30001171/. Accessed Nov. 8, 2023. 
14. Steinbrenner H, et al. Dietary selenium in adjuvant therapy of viral and bacterial infections. Adv Nutr. 2015;6(1):73-82. PubMed website. https://pubmed.ncbi.nlm.nih.gov/25593145/. Accessed Nov. 8, 2023. 
15. Mlcek J, et al. Quercetin and Its Anti-Allergic Immune Response. Molecules. 201612;21(5):623. PubMed website. https://pubmed.ncbi.nlm.nih.gov/27187333/. Accessed Nov. 8, 2023.
16. Colunga Biancatelli RML, et al. Quercetin and Vitamin C: An Experimental, Synergistic Therapy for the Prevention and Treatment of SARS-CoV-2 Related Disease (COVID-19). Front Immunol. 2020;11:1451. PubMed website. https://pubmed.ncbi.nlm.nih.gov/32636851/. Accessed Nov. 8, 2023. 
17. Janeway CA Jr, et al. Immunobiology: The Immune System in Health and Disease. 5th edition. New York: Garland Science; 2001. The production of IgE. NCBI website. https://www.ncbi.nlm.nih.gov/books/NBK27117/. Accessed Nov. 8, 2023.
18. Mitani A, et al. Quercetin restores corticosteroid sensitivity in cells from patients with chronic obstructive pulmonary disease. Exp Lung Res. 2017;43(9-10):417-425. PubMed website. https://pubmed.ncbi.nlm.nih.gov/29227717/. Accessed Nov. 8, 2023.
19. Weng Z, et al. Quercetin is more effective than cromolyn in blocking human mast cell cytokine release and inhibits contact dermatitis and photosensitivity in humans. PLoS One. 2012;7(3):e33805. PubMed website. https://pubmed.ncbi.nlm.nih.gov/22470478/. Accessed Nov. 8, 2023.
20. Cerullo G, et al. The Long History of Vitamin C: From Prevention of the Common Cold to Potential Aid in the Treatment of COVID-19. Front Immunol. 2020;11:574029. PubMed website. https://pubmed.ncbi.nlm.nih.gov/33193359/. Accessed Nov. 8, 2023.
21. Hunt C, et al. The clinical effects of vitamin C supplementation in elderly hospitalised patients with acute respiratory infections. Int J Vitam Nutr Res.1994;64(3):212-219. PubMed website. https://pubmed.ncbi.nlm.nih.gov/7814237/. Accessed Nov. 8, 2023.
22. Berger MM, et al. Strengthening the immunity of the Swiss population with micronutrients: A narrative review and call for action. Clin Nutr ESPEN. 2021;43:39-48. PubMed website. https://pubmed.ncbi.nlm.nih.gov/34024545/. Accessed Nov. 8, 2023. 
23. Carr AC, Maggini S. Vitamin C and Immune Function. Nutrients. 2017;9(11):1211. PubMed website. https://pubmed.ncbi.nlm.nih.gov/29099763/. Accessed Nov. 8, 2023.
24. Askari G, et al. The effect of quercetin supplementation on selected markers of inflammation and oxidative stress. J Res Med Sci. 2012;17(7):637-641. NCBI website. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3685779/. Accessed Nov. 8, 2023
25. Wüpper S, et al. Cyclodextrins, natural Compounds, and plant bioactives-A nutritional perspective. Biomolecules. 2021;11(3):401. PubMed website. https://pubmed.ncbi.nlm.nih.gov/33803150/. Accessed Nov. 8, 2023.