Normal aging results in a progressive decline in immune function with a sharp fall occurring after age 65-70 years.

Experimental studies seek to restore stem cells in bone marrow, where all immune cells originate.^1,2

The dilemma is that these stem cell renewal therapies are not yet available outside research settings.

Healthy immunity at any age, however, can be supported using nutrients that function via multiple pathways.

This article summarizes what many readers of this publication are doing to optimize their immune function.

Garlic

A recent review found that garlic compounds show strong antibacterial activity against a wide range of harmful bacteria, including drug-resistant strains.³

Another review reported that garlic offers anti-microbial, antifungal, anticancer, wound-healing, antioxidant, anti-inflammatory, and other protective effects.⁴

Compounds in garlic boost proliferation of T cells and function of natural killer cells.^5-8

Garlic’s antiviral defense was demonstrated when volunteers took oral garlic containing the protective garlic compound allicin from November through February.⁹

The garlic group suffered 63% fewer cold infections than the placebo group. Those in the garlic group who did catch colds had symptoms for just 1.52 days on average, compared to 5.01 days for the placebo group.⁹

Although it contains no allicin, aged garlic extract has demonstrated potent antiviral and immune-enhancing properties.

In individuals taking an aged garlic extract, T cells and NK cells showed greater proliferation, compared to individuals taking placebo. After 90 days, the garlic group had experienced 21% fewer cold and flu symptoms and 58% fewer work/school days missed due to illness.⁵

Lactoferrin

Lactoferrin is a protein found in milk and produced in tears, saliva, mucus, and by some immune cells.¹⁰

It helps prevent a wide range of pathogens from entering through the linings of the oral cavity, nasal cavity, airways, and digestive system. This includes viruses that cause the common cold, flu, and hepatitis B and C.¹⁰

Lactoferrin disrupts viruses’ ability to bind to cells.¹¹ If a virus cannot attach to cells, it cannot cause illness.

Lactoferrin’s indirect antiviral effects include:

• Activating and increasing natural killer cells, which eliminate abnormal cells,^12,13 and
• Stimulating production of other antiviral compounds, including interferons, which trigger immune mechanisms.^10,14

If viruses are already inside body cells, lactoferrin may block these pathogens from reproducing, limiting the spread of an illness and reducing its severity.^10,15

Lactoferrin also enhances the immune system’s ability to monitor for potential carcinogenic cells.¹²

A 2022 study concluded that, by sequestering iron, lactoferrin reduces the pathogenic potential of microorganisms, which require iron to grow and reproduce. The study concluded that lactoferrin may help maintain health at all stages of life.¹⁶

Vitamin D

Vitamin D fortifies immunity and has anti-microbial effects.^17-21

Published studies show that vitamin D:

• Interferes with some forms of viral replication,
• Helps repair cell linings, including those in the lung airways,
• Boosts production of proteins that protect against infection, and
• Helps prevent production of excess pro-inflammatory compounds in the lungs.

Meta-analyses of clinical trials have shown that vitamin D helps protect against respiratory tract infections.^22,23

Low vitamin D levels have been associated with higher rates of many chronic diseases, including cancer.²⁴

In 2022, two reviews were published documenting vitamin D’s capacity to enhance protection against both infections and cancer.^25,26

The first review noted that studies support vitamin D’s role in preventing and reducing the severity of several infectious diseases.²⁵

It also found that higher blood 25-hydroxyvitamin D levels (a measure of vitamin D levels in the body) may benefit some autoimmune rheumatic diseases.²⁵

The second review found that vitamin D provides multi-level anti-cancer action and protects against several cancer types.²⁶

Zinc

Zinc deficiency, which is common among the elderly,²⁷ may compromise immune function and contribute to atherosclerosis, cancer, autoimmune diseases, and other age-related conditions.^28,29

Aging adults who replenish zinc levels may slow normal immune decline and protect against chronic inflammation.³⁰

Oral zinc intake in the elderly boosts the stress response of white blood cells, providing an immune anti-aging mechanism.³¹

A 2022 review study found that zinc’s anti-viral properties can disrupt the replication and infectivity of some respiratory viruses and help regulate immune response in the respiratory tract.³²

Mushrooms

A 2022 review article concluded that medicinal mushrooms possess anticancer, anti-aging, antiviral, anti-parasitic, antimicrobial, and other beneficial properties.³³

Another recent review concluded that mushrooms’ ability to inhibit tumor cells makes them a "natural pharmaceutical."³⁴

Among the most powerful of mushrooms’ immune-supporting compounds are beta glucans.

They bind to receptors on cells important for immunity,^35,36 boosting their function and helping defend against infection. Beta glucans activate both the innate (the immediate, general defense) and adaptive (a later defense against specific threats) immune responses.^35,37-40

In animal models of aging, beta glucans help prevent or reverse immunosenescence.^39,41

They boost immune cell numbers and improve their function.⁴¹

In humans, beta glucans demonstrate infection-fighting effects, particularly against upper respiratory tract infections like cold and flu.⁴²

Ragweed allergy sufferers also had significant reductions in symptoms and severity after beta glucans intake.⁴³

Four mushroom strains that support the immune system are shiitake, maitake, reishi, and chaga.^38,44-52

Combining beta glucans with immune-supporting mushrooms may maximize immune support.

Melatonin

With aging, the thymus gland—which produces T cells—shrinks, diminishing immune function.

But in aged mice, the hormone melatonin stimulates new thymus growth, producing new T cells.⁵³

Melatonin also counters immune decline by: ^54-61

• Enhancing responses of antibodies that "tag" viruses, bacteria, and other invaders for destruction by immune system components,
• Improving T cell activity, and
• Reducing chronic inflammation, a cause of most age-related, chronic disease.

Preclinical studies show that melatonin improves immune response to infection by viruses, bacteria, and parasites by stimulating production and activity of T cells, natural killer cells, and macrophages that engulf and destroy invaders.⁵⁴

Melatonin has also been found to support the immune system’s protection againstcancer, inhibiting it at every stage.^62-66

A recent review study concluded that melatonin was a potentialoncostatic, an agent that blocks cancer spread.⁶⁷ Another 2022 report found thatmelatonin could mitigate cancer’s development, growth, and spread.⁶⁸

Vitamin C

The activity of phagocytes (cells that surround and kill invaders), T cells, and many other immune cells is closely tied to their vitamin C content.⁶⁹

So, it makes sense that immune functions are improved by taking vitamin C.^70,71

A clinical trial showed that oral vitamin C reduced duration of colds by 9.4% on average and may decrease the severity of respiratory tract infections.⁷² (Not all studies show vitamin C to be effective against the common cold.)

Researchers have found that vitamin C:

• Boosts function, growth, and survival of infection-fighting cells,^73,74
• Increases levels of immune-activating interferons,^75,76
• Neutralizes excess free radicals caused by infections, reducing illness severity,⁷⁷
• Promotes production of collagen, which maintains a barrier against infection, ⁷⁶
• Reduces histamine, a pro-inflammatory compound⁷⁶ that plays a role in infections⁷⁸ and causes allergy symptoms,⁷⁹ and
• Lowers pro-inflammatory compounds caused by infection, promoting tissue healing.⁸⁰

Optimal immunity requires daily intake of vitamin C and other immune-supporting nutrients.

Summary

Age-related immune system dysfunction increases risk of infectious disease, cancer, and chronic inflammatory conditions.

Oral intake of the key immune-supporting nutrients vitamin D, zinc, lactoferrin, mushrooms, garlic, melatonin, and vitamin C can enhance immune function and partially offset age-related immune decline.

If you have any questions on the scientific content of this article, please call a Life Extension Wellness Specialist at 1-866-864-3027.

References

1. Wilkinson AC, Igarashi KJ, Nakauchi H. Haematopoietic stem cell self-renewal in vivo and ex vivo. Nat Rev Genet. 2020 Sep;21(9):541-54.
2. Wahlestedt M, Erlandsson E, Kristiansen T, et al. Clonal reversal of ageing-associated stem cell lineage bias via a pluripotent intermediate. Nat Commun. 2017 Feb 22;8(1):14533.
3. Bhatwalkar SB, Mondal R, Krishna SBN, et al. Antibacterial Properties of Organosulfur Compounds of Garlic (Allium sativum). Front Microbiol. 2021 2021-July-27;12:613077.
4. Tesfaye A. Revealing the Therapeutic Uses of Garlic (Allium sativum) and Its Potential for Drug Discovery. ScientificWorldJournal. 2021 12/30;2021:8817288.
5. Nantz MP, Rowe CA, Muller CE, et al. Supplementation with aged garlic extract improves both NK and gammadelta-T cell function and reduces the severity of cold and flu symptoms: a randomized, double-blind, placebo-controlled nutrition intervention. Clin Nutr. 2012 Jun;31(3):337-44.
6. Percival SS. Aged Garlic Extract Modifies Human Immunity. J Nutr. 2016 Feb;146(2):433S-6S.
7. Xu C, Mathews AE, Rodrigues C, et al. Aged garlic extract supplementation modifies inflammation and immunity of adults with obesity: A randomized, double-blind, placebo-controlled clinical trial. Clin Nutr ESPEN. 2018 Apr;24:148-55.
8. Ishikawa H, Saeki T, Otani T, et al. Aged garlic extract prevents a decline of NK cell number and activity in patients with advanced cancer. J Nutr. 2006 Mar;136(3 Suppl):816S-20S.
9. Josling P. Preventing the common cold with a garlic supplement: a double-blind, placebo-controlled survey. Adv Ther. 2001 Jul-Aug;18(4):189-93.
10. Wakabayashi H, Oda H, Yamauchi K, et al. Lactoferrin for prevention of common viral infections. J Infect Chemother. 2014 Nov;20(11):666-71.
11. Rakowska PD, Tiddia M, Faruqui N, et al. Antiviral surfaces and coatings and their mechanisms of action. Communications Materials. 2021 2021/05/28;2(1):53.
12. Zhang Y, Lima CF, Rodrigues LR. Anticancer effects of lactoferrin: underlying mechanisms and future trends in cancer therapy. Nutr Rev. 2014 Dec;72(12):763-73.
13. Kuhara T, Yamauchi K, Tamura Y, et al. Oral administration of lactoferrin increases NK cell activity in mice via increased production of IL-18 and type I IFN in the small intestine. J Interferon Cytokine Res. 2006 Jul;26(7):489-99.
14. Drago-Serrano ME, Campos-Rodriguez R, Carrero JC, et al. Lactoferrin: Balancing Ups and Downs of Inflammation Due to Microbial Infections. Int J Mol Sci. 2017 Mar 1;18(3).
15. Berlutti F, Pantanella F, Natalizi T, et al. Antiviral properties of lactoferrin--a natural immunity molecule. Molecules. 2011 Aug 16;16(8):6992-7018.
16. Kowalczyk P, Kaczynska K, Kleczkowska P, et al. The Lactoferrin Phenomenon-A Miracle Molecule. Molecules. 2022 May 4;27(9).
17. Dancer RC, Parekh D, Lax S, et al. Vitamin D deficiency contributes directly to the acute respiratory distress syndrome (ARDS). Thorax. 2015 Jul;70(7):617-24.
18. Teymoori-Rad M, Shokri F, Salimi V, et al. The interplay between vitamin D and viral infections. Rev Med Virol. 2019 Mar;29(2):e2032.
19. Telcian AG, Zdrenghea MT, Edwards MR, et al. Vitamin D increases the antiviral activity of bronchial epithelial cells in vitro. Antiviral Res. 2017 Jan;137:93-101.
20. Zdrenghea MT, Makrinioti H, Bagacean C, et al. Vitamin D modulation of innate immune responses to respiratory viral infections. Rev Med Virol. 2017 Jan;27(1).
21. Tsujino I, Ushikoshi-Nakayama R, Yamazaki T, et al. Pulmonary activation of vitamin D3 and preventive effect against interstitial pneumonia. J Clin Biochem Nutr. 2019 Nov;65(3):245-51.
22. Martineau AR, Jolliffe DA, Hooper RL, et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ. 2017 Feb 15;356:i6583.
23. Bergman P, Lindh AU, Bjorkhem-Bergman L, et al. Vitamin D and Respiratory Tract Infections: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. PLoS One. 2013;8(6):e65835.
24. Meehan M, Penckofer S. The Role of Vitamin D in the Aging Adult. J Aging Gerontol. 2014 Dec;2(2):60-71.
25. Giannini S, Giusti A, Minisola S, et al. The Immunologic Profile of Vitamin D and Its Role in Different Immune-Mediated Diseases: An Expert Opinion. Nutrients. 2022 Jan 21;14(3):473.
26. Munoz A, Grant WB. Vitamin D and Cancer: An Historical Overview of the Epidemiology and Mechanisms. Nutrients. 2022 Mar 30;14(7).
27. Barnett JB, Hamer DH, Meydani SN. Low zinc status: a new risk factor for pneumonia in the elderly? Nutr Rev. 2010 Jan;68(1):30-7.
28. Chasapis CT, Loutsidou AC, Spiliopoulou CA, et al. Zinc and human health: an update. Arch Toxicol. 2012 Apr;86(4):521-34.
29. Haase H, Rink L. The immune system and the impact of zinc during aging. Immun Ageing. 2009 Jun 12;6:9.
30. Cabrera AJ. Zinc, aging, and immunosenescence: an overview. Pathobiol Aging Age Relat Dis. 2015;5:25592.
31. Putics A, Vodros D, Malavolta M, et al. Zinc supplementation boosts the stress response in the elderly: Hsp70 status is linked to zinc availability in peripheral lymphocytes. Exp Gerontol. 2008 May;43(5):452-61.
32. Sadeghsoltani F, Mohammadzadeh I, Safari MM, et al. Zinc and Respiratory Viral Infections: Important Trace Element in Anti-viral Response and Immune Regulation. Biol Trace Elem Res. 2022 Jun;200(6):2556-71.
33. Bhambri A, Srivastava M, Mahale VG, et al. Mushrooms as Potential Sources of Active Metabolites and Medicines. Front Microbiol. 2022;13:837266.
34. Anusiya G, Gowthama Prabu U, Yamini NV, et al. A review of the therapeutic and biological effects of edible and wild mushrooms. Bioengineered. 2021 Dec;12(2):11239-68.
35. Ciecierska A, Drywien ME, Hamulka J, et al. Nutraceutical functions of beta-glucans in human nutrition. Rocz Panstw Zakl Hig. 2019;70(4):315-24.
36. Jin Y, Li P, Wang F. beta-glucans as potential immunoadjuvants: A review on the adjuvanticity, structure-activity relationship and receptor recognition properties. Vaccine. 2018 Aug 23;36(35):5235-44.
37. Dai X, Stanilka JM, Rowe CA, et al. Consuming Lentinula edodes (Shiitake) Mushrooms Daily Improves Human Immunity: A Randomized Dietary Intervention in Healthy Young Adults. J Am Coll Nutr. 2015;34(6):478-87.
38. Song L, Yuan J, Ni S, et al. Enhancement of adaptive immune responses of aged mice by dietary intake of beta-glucans, with special emphasis on anti-aging activity. Mol Immunol. 2020 Jan;117:160-7.
39. Zheng X, Zou S, Xu H, et al. The linear structure of beta-glucan from baker’s yeast and its activation of macrophage-like RAW264.7 cells. Carbohydr Polym. 2016 Sep 5;148:61-8.
40. Xu X, Yang J, Ning Z, et al. Lentinula edodes-derived polysaccharide rejuvenates mice in terms of immune responses and gut microbiota. Food Funct. 2015 Aug;6(8):2653-63.
41. Zhong K, Liu Z, Lu Y, et al. Effects of yeast beta-glucans for the prevention and treatment of upper respiratory tract infection in healthy subjects: a systematic review and meta-analysis. Eur J Nutr. 2021 Dec;60(8):4175-87.
42. Talbott SM, Talbott JA, Talbott TL, et al. beta-Glucan supplementation, allergy symptoms, and quality of life in self-described ragweed allergy sufferers. Food Sci Nutr. 2013 Jan;1(1):90-101.
43. Cor D, Knez Z, Knez Hrncic M. Antitumour, Antimicrobial, Antioxidant and Antiacetylcholinesterase Effect of Ganoderma Lucidum Terpenoids and Polysaccharides: A Review. Molecules. 2018 Mar 13;23(3).
44. Avtonomova AV, Krasnopolskaya LM. [Antiviral properties of basidiomycetes metabolites]. Antibiot Khimioter. 2014;59(7-8):41-8.
45. Ren G, Xu L, Lu T, et al. Structural characterization and antiviral activity of lentinan from Lentinus edodes mycelia against infectious hematopoietic necrosis virus. Int J Biol Macromol. 2018 Aug;115:1202-10.
46. Rincao VP, Yamamoto KA, Ricardo NM, et al. Polysaccharide and extracts from Lentinula edodes: structural features and antiviral activity. Virol J. 2012 Feb 15;9:37.
47. Masterson CH, Murphy EJ, Gonzalez H, et al. Purified beta-glucans from the Shiitake mushroom ameliorates antibiotic-resistant Klebsiella pneumoniae-induced pulmonary sepsis. Lett Appl Microbiol. 2020 Oct;71(4):405-12.
48. Hou L, Meng M, Chen Y, et al. A water-soluble polysaccharide from Grifola frondosa induced macrophages activation via TLR4-MyD88-IKKbeta-NF-kappaB p65 pathways. Oncotarget. 2017 Oct 17;8(49):86604-14.
49. Vetvicka V, Vetvickova J. Immune-enhancing effects of Maitake (Grifola frondosa) and Shiitake (Lentinula edodes) extracts. Ann Transl Med. 2014 Feb;2(2):14.
50. Kim YR. Immunomodulatory Activity of the Water Extract from Medicinal Mushroom Inonotus obliquus. Mycobiology. 2005 Sep;33(3):158-62.
51. Szychowski KA, Skora B, Pomianek T, et al. Inonotus obliquus - from folk medicine to clinical use. J Tradit Complement Med. 2021 Jul;11(4):293-302.
52. Tian YM, Zhang GY, Dai YR. Melatonin rejuvenates degenerated thymus and redresses peripheral immune functions in aged mice. Immunol Lett. 2003 Aug 5;88(2):101-4.
53. Carrillo-Vico A, Lardone PJ, Alvarez-Sanchez N, et al. Melatonin: buffering the immune system. Int J Mol Sci. 2013 Apr 22;14(4):8638-83.
54. Espino J, Pariente JA, Rodriguez AB. Oxidative stress and immunosenescence: therapeutic effects of melatonin. Oxid Med Cell Longev. 2012;2012:670294.
55. Espino J, Bejarano I, Paredes SD, et al. Melatonin is able to delay endoplasmic reticulum stress-induced apoptosis in leukocytes from elderly humans. Age (Dordr). 2011 Dec;33(4):497-507.
56. Maestroni GJ. The immunotherapeutic potential of melatonin. Expert Opin Investig Drugs. 2001 Mar;10(3):467-76.
57. Sainz RM, Mayo JC, Uria H, et al. The pineal neurohormone melatonin prevents in vivo and in vitro apoptosis in thymocytes. J Pineal Res. 1995 Nov;19(4):178-88.
58. Tian YM, Li PP, Jiang XF, et al. Rejuvenation of degenerative thymus by oral melatonin administration and the antagonistic action of melatonin against hydroxyl radical-induced apoptosis of cultured thymocytes in mice. J Pineal Res. 2001 Oct;31(3):214-21.
59. Vishwas DK, Mukherjee A, Haldar C, et al. Improvement of oxidative stress and immunity by melatonin: an age dependent study in golden hamster. Exp Gerontol. 2013 Feb;48(2):168-82.
60. Akbulut KG, Gonul B, Akbulut H. The effects of melatonin on humoral immune responses of young and aged rats. Immunol Invest. 2001 Feb;30(1):17-20.
61. Srinivasan V, Pandi-Perumal SR, Brzezinski A, et al. Melatonin, immune function and cancer. Recent Pat Endocr Metab Immune Drug Discov. 2011 May;5(2):109-23.
62. Li Y, Li S, Zhou Y, et al. Melatonin for the prevention and treatment of cancer. Oncotarget. 2017 Jun 13;8(24):39896-921.
63. Maroufi NF, Vahedian V, Hemati S, et al. Targeting cancer stem cells by melatonin: Effective therapy for cancer treatment. Pathol Res Pract. 2020 May;216(5):152919.
64. Reiter RJ, Rosales-Corral SA, Tan DX, et al. Melatonin, a Full Service Anti-Cancer Agent: Inhibition of Initiation, Progression and Metastasis. Int J Mol Sci. 2017 Apr 17;18(4).
65. Talib WH. Melatonin and Cancer Hallmarks. Molecules. 2018 Feb 26;23(3).
66. Nikolaev G, Robeva R, Konakchieva R. Membrane Melatonin Receptors Activated Cell Signaling in Physiology and Disease. Int J Mol Sci. 2021 Dec 31;23(1).
67. Wang L, Wang C, Choi WS. Use of Melatonin in Cancer Treatment: Where Are We? Int J Mol Sci. 2022 Mar 29;23(7).
68. Ströhle A, Wolters M, Hahn A. Micronutrients at the interface between inflammation and infection--ascorbic acid and calciferol: part 1, general overview with a focus on ascorbic acid. Inflammation & allergy drug targets. 2011;10 1:54-63.
69. Wintergerst ES, Maggini S, Hornig DH. Immune-enhancing role of vitamin C and zinc and effect on clinical conditions. Ann Nutr Metab. 2006;50(2):85-94.
70. Johnston CS, Barkyoumb GM, Schumacher SS. Vitamin C supplementation slightly improves physical activity levels and reduces cold incidence in men with marginal vitamin C status: a randomized controlled trial. Nutrients. 2014 Jul 9;6(7):2572-83.
71. Hemila H. Vitamin C and Infections. Nutrients. 2017 Mar 29;9(4).
72. Huijskens MJ, Walczak M, Koller N, et al. Technical advance: ascorbic acid induces development of double-positive T cells from human hematopoietic stem cells in the absence of stromal cells. J Leukoc Biol. 2014 Dec;96(6):1165-75.
73. Huijskens MJ, Walczak M, Sarkar S, et al. Ascorbic acid promotes proliferation of natural killer cell populations in culture systems applicable for natural killer cell therapy. Cytotherapy. 2015 May;17(5):613-20.
74. Adrian F. Gombart PD. Immunity In Depth. 2016.
75. Carr AC, Maggini S. Vitamin C and Immune Function. Nutrients. 2017 Nov 3;9(11).
76. Iqbal K, Khan A, Khan MMA. Biological Significance of Ascorbic Acidn(Vitamin C) in Human Health - A Review. Pakistan Journal of Nutrition. 2003 01/01;3(1):5-13.
77. Smuda C, Bryce PJ. New developments in the use of histamine and histamine receptors. Curr Allergy Asthma Rep. 2011 Apr;11(2):94-100.
78. Wheatley LM, Togias A. Clinical practice. Allergic rhinitis. N Engl J Med. 2015 Jan 29;372(5):456-63.
79. Mohammed BM, Fisher BJ, Kraskauskas D, et al. Vitamin C promotes wound healing through novel pleiotropic mechanisms. Int Wound J. 2016 Aug;13(4):572-84.