Co-administration of l-cystine and l-theanine enhances efficacy of influenza vaccination in elderly persons: Nutritional status-dependent immunogenicity
Koichi Miyagawa
Department of Internal Medicine, Nagoya Kosein Hospital, Nagoya,
Search for more papers by this authorYoshimitsu Hayashi
Department of Internal Medicine, Nagoya Kosein Hospital, Nagoya,
Search for more papers by this authorShigekazu Kurihara
Research Institute for Health Fundamentals, Ajinomoto Co., Inc., Tokyo, and
Search for more papers by this authorAkiko Maeda
Department of Public Health, Osaka City University, Faculty of Medicine, Osaka, Japan
Search for more papers by this authorKoichi Miyagawa
Department of Internal Medicine, Nagoya Kosein Hospital, Nagoya,
Search for more papers by this authorYoshimitsu Hayashi
Department of Internal Medicine, Nagoya Kosein Hospital, Nagoya,
Search for more papers by this authorShigekazu Kurihara
Research Institute for Health Fundamentals, Ajinomoto Co., Inc., Tokyo, and
Search for more papers by this authorAkiko Maeda
Department of Public Health, Osaka City University, Faculty of Medicine, Osaka, Japan
Search for more papers by this authorAbstract
Aim: The immune response to influenza vaccine is attenuated in elderly persons, though they are at greatest risk for morbidity and mortality by influenza virus infection. Experimental studies demonstrate that co-administration of l-cystine and l-theanine enhanced antigen-specific production of immunoglobulin in aged mice infected with influenza virus. We thus investigated the effect of l-cystine and l-theanine on antibody induction by influenza vaccines in elderly persons.
Methods: Residents in a nursing home were randomly allocated to l-cystine and l-theanine (n = 32) or placebo (n = 33). The test substances were administered p.o. for 14 days before immunization. Serum influenza virus antibody titers were measured before and 4 weeks after vaccination.
Results: Vaccination significantly elevated hemagglutination inhibition (HI) titers for all the three strains of influenza viruses (A/New Caledonia [H1N1], A/New York [H3N2] and B/Shanghai) in both groups. HI titers after vaccination were not significantly different between the two groups for either strain. Also, the seroconversion rate was not significantly different between the two groups in the aggregate. A stratified analysis showed that the rate of seroconversion was significantly greater in the l-cystine and l-theanine group compared with the placebo group for influenza virus A (H1N1) among subjects with low serum total protein (63% vs 10%, P < 0.05) or low hemoglobin (71% vs 9%, P < 0.05).
Conclusion: Co-administration of l-cystine and l-theanine before vaccination may enhance the immune response to influenza vaccine in elderly subjects with low serum total protein or hemoglobin.
References
- 1 Mullooly JP, Bennett MD, Hornbrook MC et al. Influenza vaccination programs for elderly persons: cost-effectiveness in a health maintenance organization. Ann Intern Med 1994; 121: 947–952.
- 2 Nordin J, Mullooly J, Poblete S et al. Influenza vaccine effectiveness in preventing hospitalizations and deaths in persons 65 years or older in Minnesota, New York, and Oregon: data from 3 health plans. J Infect Dis 2001; 184: 665–670.
- 3 Jefferson T, Rivetti D, Rivetti A, Rudin M, Di Pietrantonj C, Demicheli V. Efficacy and effectiveness of influenza vaccines in elderly people: a systemic review. Lancet 2005; 366: 1165–1174.
- 4 Hak E, Buskens E, Van Essen GA et al. Clinical effectiveness of influenza vaccination in persons younger than 65 years with high-risk medical conditions. The PRISMA study. Arch Intern Med 2005; 165: 274–280.
- 5 Department of Health and Human Services, Centers for Disease Control. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2007; 56: 22–27.
- 6 Gardner EM, Bernstein ED, Dran S et al. Characterization of antibody responses to annual influenza vaccination over four years in a healthy elderly population. Vaccine 2001; 19: 4610–4617.
- 7 Gross PA, Hermogenes AW, Sacks HS, Lau J, Levandowski RA. The efficacy of influenza vaccine in elderly persons. Ann Intern Med 1995; 123: 518–527.
- 8 Govaert TM, Thijs CT, Masurel N, Sprenger MJ, Dinant GJ, Knottnerus JA. The efficacy of influenza vaccination in elderly individuals. JAMA 1994; 272: 1661–1665.
- 9 McElhaney JE, Beattie BL, Devine R et al. Age-related decline in interleukin 2 production in response to influenza vaccine. J Am Geriatr Soc 1990; 38: 652–658.
- 10 Dorrell L, Hassan I, Marshall S et al. Clinical and serological response to an inactivated influenza vaccine in adults with HIV infection, diabetes, obstructive airway disease, elderly adults and healthy volunteers. Int J STD AIDS 1997; 8: 776–779.
- 11 Vu T, Farish S, Jenkins M, Kelly H. A meta-analysis of effectiveness of influenza vaccine in persons aged 65 years and over living in the community. Vaccine 2002; 20: 1831–1836.
- 12 Remarque EJ, Cools HJM, Boere TJ, Van Der Klis RJ, Masurel N, Ligthart GJ. Functional disability and antibody response to influenza vaccine in elderly patients in a Dutch nursing home. Br Med J 1996; 312: 1015.
- 13 Samiec PS, Drews-Botsch C, Flagg EW et al. Glutathione in human plasma: decline in association with aging, age-related macular degeneration, and diabetes. Free Radic Biol Med 1998; 24: 699–704.
- 14 Palamara AT, Perno C-F, Ciriolo MR et al. Evidence for antiviral activity of glutathione: in vitro inhibition of herpes simplex virus type 1 replication. Antiviral Res 1995; 27: 237–253.
- 15 Kurihara S, Shibahara S, Arisaka H, Akiyama Y. Enhancement of antigen-specific immunoglobulin G production in mice by co-administration of l-cystine and l-theanine. J Vet Med Sci 2007; 69: 1263–1270.
- 16 Rimaniol AC, Mialocq P, Clayette P, Dormont D, Gras G. Role of glutamate transporters in the regulation of glutathione levels in human macrophages. Am J Physiol Cell Physiol 2001; 281: C1964–C1970.
- 17 Panel on Macronutrients, Panel on the Definition of Dietary Fiber, Subcommittee on Upper Reference Levels of Nutrients, Subcommittee on Interpretation and Uses of Dietary Reference Intakes, and the Standing Committee on the Scientific Evaluation of Dietary Reference Intakes. Protein and amino acids. In: Food and Nutrition Board, Institute of Medicine of the National Academies, ed. Dietary Reference Intakes: Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol. Washington, DC: The National Academic Press, 2005; 711–712.
- 18 Panel of Health and Nutrition Promotion, Committee of Hygiene, Ministry of Health and Labor. Nutritional Requirements of Japanese, 6th edn [monograph on the Internet]. Tokyo: Ministry of Health and Labor, 1999 [Cited 10 Jan 2008.] Available from URL: http://www1.mhlw.go.jp/shingi/s9906/s0628-1_11.html/
- 19 Hirota Y, Kaji M, Ide S et al. Antibody efficacy as a keen index to evaluate influenza vaccine effectiveness. Vaccine 1997; 15: 962–967.
- 20 Clements ML, Betts R, Tierney EL, Murphy BR. Serum and nasal wash antibodies associated with residence to experimental challenge with influenza A wild-type virus. J Clin Microbiol 1986; 24: 157–160.
- 21 Keitel WA, Atmar RL, Cate TR et al. Safety of high doses of influenza vaccine and effect on antibody responses in elderly persons. Arch Intern Med 2006; 166: 1121–1127.
- 22 Potter JM, O'Donnell B, Carman WF, Roberts MA, Stott DJ. Serological response to influenza vaccination and nutritional and functional status of patients in geriatric medical long-term care. Age Ageing 1999; 28: 141–145.
- 23 Chandra RK, Puri S. Nutritional support improves antibody response to influenza virus vaccine in the elderly. Br Med J 1985; 291: 705–706.
- 24 Hara M, Tanaka K, Hirota Y. Immune response to influenza vaccine in healthy adults and the elderly: association with nutritional status. Vaccine 2005; 23: 1457–1463.
- 25 Thomas DR. The clinical link between health-related quality of life and age-related changes. J Gerontol A Biol Sci Med Sci 2001; 56: M599–M602.
- 26 Webster RG. Immunity to influenza in the elderly. Vaccine 2000; 18: 1686–1689.
- 27
Tajima O,
Nagura E,
Ishikawa-Tanaka K,
Furumoto S,
Ohta T.
Nutritional assessment of elderly Japanese nursing home residents of differing mobility using anthropometric measurements, biochemical indicators and food intake.
Geriatr Gerontol Int
2004; 4: 93–99.
10.1111/j.1447-0594.2004.00128.x Google Scholar
- 28 Field CJ, Jonson IR, Schley PD. Nutrients and their role in host resistance to infection. J Leukocyte Biol 2002; 71: 16–32.
- 29 Wouters-Wesseling W, Rozendaal M, Snijder M et al. Effect of a complete nutritional supplement on antibody response to influenza vaccine in elderly people. J Gerontol A Biol Sci Med Sci 2002; 57: M563–M566.
- 30 Miyagawa K, Ohashi M, Yamashita S et al. Increased oxidative stress impairs endothelial modulation of contractions in arteries from spontaneously hypertensive rats. J Hypertens 2007; 25: 415–421.
- 31 Meydani M. Nutrition interventions in aging and age-associated disease. Ann NY Acad Sci 2001; 928: 226–235.
- 32 Bukowski JF, Morita CT, Brenner MB. Human γδ T cells recognize alkylamines derived from microbes, edible plants, and Tea: implications for Innate Immunity. Immunity 1999; 11: 57–65.
- 33 Martensson J. The effect of fasting on leukocyte and plasma glutathione and sulfur amino acid concentrations. Metabolism 1986; 35: 118–121.
- 34 Robinson MK, Rodrick ML, Jacobs DO et al. Glutathione depletion in rats impairs T-cell and macrophage immune function. Arch Surg 1993; 128: 29–35.
- 35 Malorni W, Straface E, Di Genova G et al. Oxidized low-density lipoproteins affect natural killer cell activity by impairing cytoskeleton function and altering the cytokine network. Exp Cell Res 1997; 236: 436–445.
- 36 Peterson JD, Herzenberg LA, Vasquez K, Waltenbaugh C. Glutathione levels in antigen-presenting cells modulate Th1 versus Th2 patterns. Proc Natl Acad Sci USA 1998; 95: 3071–3076.
- 37 Bernstein ED, Gardner EM, Abrutyn E, Gross P, Murasko DM. Cytokine production after influenza vaccination in a healthy elderly population. Vaccine 1998; 16: 1722–1731.
- 38 Smith DJ. Anemia in the elderly. Am Fam Physician 2000; 62: 1565–1572.
- 39 Izaks GJ, Westendorp RGJ, Knock DL. The definition of anemia in older persons. JAMA 1999; 281: 1714–1717.
- 40 Seward SJ, Safran C, Marton KI, Robinson SH. Does the mean corpuscular volume help physicians evaluate hospitalized patients with anemia? J Gen Intern Med 1990; 5: 187–191.
- 41 McElhaney JE. Nutrition, exercise, and influenza vaccination. J Gerontol A Biol Sci Med Sci 2002; 57: M555–M556.
- 42 Hirota Y, Kaji M, Ide S, Goto S, Oka T. The hemagglutination inhibition antibody response to an inactivated influenza vaccine among healthy adults: with special reference to the prevaccination antibody and its interaction with age. Vaccine 1996; 14: 1597–1602.
- 43 Fedson DS. Pandemic influenza: a potential role for statins in treatment and prophylaxis. Clin Infect Dis 2006; 43: 199–205.
- 44 McClure DL, Valuck RJ, Glanz M, Murphy JR, Hokanson JE. Statin and statin-fibrate use was significantly associated with increased myositis risk in a managed care population. J Clin Epidemiol 2007; 60: 812–818.
