TABLE 1.
RCTs of supplementation with micronutrients in older adults on immune response1
| Author, year (reference) | Micronutrient | Participants | Intervention and control group | Baseline serum concentration, mg/dL | Endpoint serum concentration, mg/dL | Immune-related results |
|---|---|---|---|---|---|---|
| Hunt et al., 1994 (27) | Vitamin C | Older patients (66–93 y); acute respiratory infections | 0 (n = 29) or 200 mg/d (n = 28); 4 wk | 0.41 ± 0.402 | PG: 0.43 ± 0.352IG: 1.67 ± 0.572,* | Increased plasma and white blood cell vitamin C concentration even during infection; better recovery, particularly in those most severely ill on admission |
| Sasazuki et al., 2006 (100) | Vitamin C | Patients; chronic atrophic gastritis (40–69 y; mean 57 y) | 50 (n = 120) or 500 mg/d (n = 124); 5 y | LD: 1.38 ± 0.032HD: 1.35 ± 0.032 | NA | Reduced risk (RR: 0.34; 95% CI: 012, 0.97) of suffering from a common cold ≥3 times during the survey period; no effect on severity and duration of common cold |
| Thomas et al., 2021 (31) | Vitamin C | Patients; SARS-CoV-2 infection (≥18 y) | 0 (n = 108) or 8000 mg/d with or without 50 mg zinc (n = 106); 10 d | NA | NA | No effect on time to reach 50% reduction in symptoms, composite 4-symptom score, hospitalization, or death |
| Aloia and Li-Ng, 2007 (101) | Vitamin D | Postmenopausal African-American women (50–75 y) | 0 (n = 104) or 800 IU/d (2 y) + 2000 IU/d (1 y) (+ Ca for 3 y) (n = 104) | NA | NA | Reduced reported cold and influenza symptoms (P < 0.002) |
| Bischoff-Ferrari et al., 2010 (42) | Vitamin D | Older people; recent hip fracture (≥65 y) | 800 (n = 89) or 2000 IU/d + Ca; 3 mo (n = 100) | HD: 13.2 ± 8.12LD: 12.3 ± 7.72 | HD: 44.7 ± 10.42LD: 35.4 ± 10.12,* | Decreased number of participants with hospital readmission due to infection (–39%; 95% CI: -62%, -1%) |
| Li-Ng et al., 2009 (43) | Vitamin D | Adults (18–80 y) | 0 (n = 70) or 2000 IU/d; 3 mo (n = 78) | IG: 25.7 ± 11.482PG: 25.2 ± 10.322 | IG: 35.5 ± 9.32PG: NAΔ IG: 9.6 (95% CI: 8.7, 12.3)3Δ PG: –0.84 (95% CI: –2.8, 1.1)3, * | No effect on duration or severity of upper respiratory infection symptoms |
| De la Fuente et al., 2008 (102) | Vitamin E | Healthy older adults (70.4 ± 5.1 y) | 200 mg/d (n = 33) or CG (29.7 ± 4.9 y) (n = 30); 3 mo | NA | NA | Normalization of a range of immune parameters (lymphocytes, neutrophils, etc.) |
| Pallast et al., 1999 (103) | Vitamin E | Healthy older adults (65–80 y) | 0 (n = 50), 50 (n = 54), or 100 mg/d (n = 53); 6 mo | PG: 1.27 ± 0.302LD: 1.24 ± 0.302HD: 1.34 ± 0.262v | ΔPG: 0.02 ± 0.162ΔLD: 0.44 ± 0.222, *ΔHD: 0.68 ± 0.322, * | Trend to increased delayed-type hypersensitivity and IL-6 production with increasing dose of vitamin E |
| Meydani et al., 1990 (104) | Vitamin E | Healthy older adults (≥60 y) | 0 (n = 14) or 800 mg/d (n = 18); 30 d | PG: 1.13 ± 0.072IG: 1.10 ± 0.062 | PG: 1.03 ± 0.062IG: 3.05 ± 0.272,* | Increased peripheral blood mononuclear cells, delayed-type hypersensitivity skin test, mitogen-stimulated lymphocyte proliferation and other immune markers |
| Meydani et al., 1997 (47) | Vitamin E | Free-living healthy older adults (≥65 y) | 0 (n = 19), 60 (n = 20), 200 (n = 20), 800 mg/d (n = 19); 235 d | PG: 1.06 ± 0.202LD: 1.17 ± 0.262ID: 1.10 ± 0.252HD: 1.11 ± 0.272 | PG: 1.00 ± 0.092LD: 1.65 ± 0.232,*ID: 2.20 ± 0.592,*HD: 3.08 ± 1.142,* | Increased a range of markers of adaptive immunity, including delayed type hypersensitivity skin test and response to vaccination, plateauing at 200 mg/d |
| Graat et al., 2002 (48) | Vitamin E | Noninstitutionalized older adults (≥60 y) | 0 (n = 153) or 200 mg/d (n = 164); 15 mo | PG: 1.25 ± 0.272IG: 1.23 ± 0.272 | NA | No effect on incidence of acute respiratory tract infections; severity of infection was greater in the vitamin E group |
| Meydani et al., 2004 (49) | Vitamin E | Nursing home residents (≥65 y) | One-half of the RDA (n = 220) or 200 IU/d (n = 231); 1 y | PG: 1.15 ± 0.432IG: 1.14 ± 0.392 | PG: 1.21 ± 0.412IG: 2.12 ± 0.692,* | No effect on incidence or number of days with infection for all, upper, or lower respiratory infections; fewer vitamin E–supplemented subjects acquired 1 or more respiratory infections or upper respiratory infections, common colds and shorter duration of colds |
| Hemilä et al., 2016 (105) | Vitamin E | Male smokers (50–69 y) | 0 (n = 1265) or 50 mg/d (n = 1286); 5–8 y | NA | NA | Decreased incidence of pneumonia (–69%; 95% CI: –83%, –43%) |
| Hemilä et al., 2006 (106) | Vitamin E | Male smokers (50–69 y) | 50 mg/d (n = NA) or control group (n = NA); 5–8 y | NA | NA | Reduced risk of common cold (RR: 0.54; 95% CI: 0.37, 0.80) in those who smoked 5–14/d cigarettes; increased risk (RR: 1.58; 95% CI: 1.23, 2.01) in those smoking more |
| Bentley-Hewitt et al., 2014 (107) | Selenium | Adults (24–65 y) | 200 μg selenium/d from enriched broccoli; crossover with normal broccoli (n = 18); 3 d | F: 1.3 (0.97–1.72)4M: 1.2 (0.95–1.54)4 | N.S. change from baseline; actual values NA | Increased several markers of immune response |
| Ivory et al., 2017 (108) | Selenium | 82 adults (50–64 y) | 0, 50, 100, or 200 μg/d; 12 wk | NA | NA | Mixed results on cellular immune response to influenza vaccine |
| Duchateau et al., 1981 (109) | Zinc | Institutionalized healthy older adults (>70 y) | 100 mg/d (n = 15) or control group (n = 15); 1 mo | NA | NA | Increased some (e.g., number of circulating T lymphocytes), but not all markers of immune function measured |
| Bogden et al., 1988 (110) | Zinc | Community-dwelling older adults (60–89 y) | 0 (n = 36), 15 (n = 36) or 100 mg/d + vitamin-mineral capsule (n = 31); 3 mo | PG: 85.0 ± 9.82LD: 83.7 ± 19.02HD: 85.6 ± 13.12 | PG: 81.7 ± 13.12LD: 85.6 ± 13.72HD: 109.8 ± 22.92,* | No effect on delayed type hypersensitivity skin test |
| Bogden et al., 1990 (111) | Zinc | Community-dwelling older adults (60–89 y) | 0 (n = 22), 15 (n = 20) or 100 mg/d + vitamin-mineral capsule (n = 19); 1 y | PG: 87.0 ± 2.62LD: 84.3 ± 3.32HD: 85.6 ± 3.32 | PG: 88.9 ± 2.62LD: 87.0 ± 17.02HD: 109.8 ± 3.92,* | No effect on immune cell numbers; NK cell activity was transiently increased at the higher zinc dose; progressive improvement in delayed type hypersensitivity skin test |
| Cossack, 1989 (112) | Zinc | Zinc-deficient older adults (60–89 y) | 60 mg/ d (n = 8); 4.5 mo compared with baseline | 75 ± 152 | 115 ± 192,* | Increase in erythrocytes, lymphocytes, neutrophils, and erythrocyte nucleoside phosphorylase |
| Boukaïba et al., 1993 (113) | Zinc | Institutionalized older adults (73–106 y) | 0 or 20 mg/d crossover (n = 44); 8 wk | HBW: 79.8 ± 2.92LBW: 70.0 ± 1.82 | PG HBW: 81.7 ± 4.42PG LBW: 69.3 ± 2.12IG HBW: 94.8 ± 5.92IG LBW: 88.0 ± 2.02 | Increased serum thymulin activity |
| Prasad et al., 1993 (114) | Zinc | Zinc-deficient older adults (50–80 y) | 30 mg/d (n = 13); 6 mo compared with baseline | 105.85 ± 14.82 | 140.75 ± 31.482,* | Increased delayed type hypersensitivity skin test and normalization of various immune markers |
| Fortes et al., 1998 (115) | Zinc | Retirement home residents (≥65 y) | 0 (n = 61) or 25 mg/d ± vitamin A (n = 57); 3 mo | NA | NA | Increased cell-mediated immune response |
| Provinciali et al., 1998 (116) | Zinc | Institutionalized older adults (64–100 y) | 90 mg/d (n = 33) or CG (n = 31); 60 d | CG: 69.7 ± 18.82IG: 66.1 ± 13.62 | CG: 5.8 ± 14.82,5IG: 89.0 ± 26.52,* | No effect on immune parameters measured |
| Mocchegiani et al., 1999 (117) | Zinc | Older adults; chronic obstructive bronchitis (63–75 y) | 0 (n = 14) or 12 mg/d (n = 15); 1 mo | 76.8 ± 4.31 | NA | Increased CD4+ count |
| Mocchegiani et al., 2003 (118) | Zinc | Healthy older adults (63–75 y) | 0 (n = 23) or 12 mg/d (n = 24); 1 mo | NA | NA | Restored NK cell activity and decreased incidence of severe infections |
| Kahmann et al., 2006 (119) | Zinc | Healthy older adults (65–82 y) | 10 mg/d (n = 19); 7 wk compared with baseline | 72.6 ± 2.72 | 79.9 ± 2.32,* | Decreased number of activated T-helper cells, but no change in ratio of Th1:Th2 cells |
| Hodkinson et al., 2007 (120) | Zinc | Healthy older adults (55–70 y) | 0 (n = 31), 15 (n = 28), or 30 mg/d (n = 34); 6 mo | PG: 86.3 ± 1.82LD: 85.0 ± 2.02HD: 84.3 ± 1.22 | PG: 81.1 ± 1.82LD: 85.0 ± 3.12HD: 93.5 ± 5.02,* | Increased ratio of CD4 to CD8 T lymphocytes, but no effect on long-term immune status |
| Meydani et al., 2007 (62) | Zinc | Nursing home residents (≥65 y) | 7 mg/d (n = 420); 12 mo | NA | NA | Lower incidence of pneumonia; fewer new antibiotic prescriptions; shorter duration of pneumonia; fewer days of antibiotic use |
| Prasad et al., 2007 (121) | Zinc | Healthy older adults (55–87 y) | 0 (n = 25) or 45 mg/d (n = 24); 12 mo | NA | NA | Lower incidence of infections, ex vivo generation of TNF-α and lower plasma markers for oxidative stress |
| Barnett et al., 2016 (69) | Zinc | Nursing home residents (≥65 y) | 0 (n = 16) or 30 mg/d (n = 14); 3 mo | PG: 66.3 ± 10.02IG: 63.9 ± 9.72 | PG: 65.4 ± 8.82IG: 73.2 ± 14.62, a | Increased T-cell function |
| Thomas et al., 2021 (31) | Zinc | Patients; SARS-CoV-2 infection (≥18 y) | 0 (n = 50) or 50 mg/d with or without 8,000 mg vitamin C (n = 116); 10 d | NA | NA | No effect on time to reach 50% reduction in symptoms, composite 4-symptom score, hospitalization, or death |
| Girodon et al., 1997 (29) | Multiple vitamins and trace elements | Nursing home residents (≥65 y) | 0 (n = 20) or 120 mg/d vitamin C, 6 mg/d β-carotene, 15 mg/d vitamin E, 20 mg/d Zn, 100 μg/d Se (n = 21); 2 y | Improvement in the status for the supplemented nutrients | Decreased incidence of respiratory and urogenital infections (P <0.01); no effect on mortality | |
| Girodon et al., 1999 (30) | Multiple vitamins and trace elements | Nursing home residents (≥65 y) | 0 (n = 182) or 120 mg/d vitamin C, 6 mg/d β-carotene, 15 mg/d vitamin E, 20 mg/d Zn, 100 μg/d Se (n = 181); 2 y | Significant improvement in α-tocopherol, β-carotene, vitamin C, Zn, and Se status | Increased antibody response to influenza vaccine; higher number of serologically protected patients; no effect on the incidence of respiratory tract events | |
| Lenhart et al., 2020 (123) | Multiple vitamins and trace elements | Healthy (asymptomatic) adults (18–65 y) | Placebo (n = 130) or multi-micronutrient supplement (129); 12 wk | NA | NA | Trend for reduced odds of upper respiratory infection (P = 0.14); lower odds of reporting symptoms for runny nose (OR: 0.53; P = 0.01) and cough (OR: 0.51; P = 0.04); no effect on severity |
| Schmoranzer et al., 2009 (124) | Multiple vitamins and trace elements | Residents of nursing homes (62–98 y) | Placebo (n = 42) or micronutrient supplement (n = 40); 3 mo | NA | NA | Increased number of various types of immune cells; no effect on specific antibody response to influenza vaccination |
1 *
P < 0.05. CG, control group; HBW, high body weight (BMI ≥24 kg/m2); HD, high-dose group; ID, intermediate-dose group; IG, intervention group; LBW, low body weight (BMI ≤21 kg/m2); LD, low-dose group; NA, not available; PG, placebo group; RCT, randomized controlled trial; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.
2
Mean ± SD.
3
Mean (95% CI).
4
Mean (range).
5
Reported in error as 5.8 ±14.8 μg dL.