Table S1.
Micronutrient Modulation of Vaccine Efficacy
| Dosage | Timing (before/after vaccination) | Control | Population | Vaccine Type | Outcome | Citation | |
|---|---|---|---|---|---|---|---|
| Vitamin A | n/a | n/a | n/a | 65+ years, n=205. Not considered vitamin A deficient | TIV | No association between vitamin A status and vaccine responsea | Sundaram et al12 |
| Vitamin D | 100000 IU every 15 days | 3 months prior to vaccination | Placebo supplementation, not specified | 65+ years, n=38, serum 25-(OH)D<30 ng/mL | TIV | No improvement in antibody response. Significant negative response for H3N2b | Goncalves-Mendes et al14 |
| Vitamin D | n/a | n/a | n/a | Mean age 64 years. n=200 patients with CKD |
Hepatitis B | <10 ng/mL 25-(OH)D associated with reduced seroconversion and seroprotectionb | Zitt et al15 |
| Vitamin E | 60, 200, or 800 mg/day all racalpha-tocopherol in soybean oil | 5 months prior to vaccination | Soybean oil only | 65+ years; serum vitamin E < 27.9 μmol/L n=89 |
Hepatitis B Diphtheria | Vitamin E group showed greater delayed-type hypersensitivity response to Hep B vaccine. 200 mg/d group had greater antibody response to Hep B vaccineb No difference in response to diphtheria vaccine No change in T cell or B cell level | Meydani et al19 |
| Vitamin E | n/a | n/a | n/a | 65+ years; not considered vitamin E deficient n=205 |
TIV | No association between vitamin E status and vaccine responsea | Sundaram et al12 |
| Vitamin E | 200 or 400 mg/day | 1 month prior to and 5 months after vaccination | Placebo identified as “0 mg vitamin E” | 24-104 years; patients of a chronic care facility n=103 |
TIV | No improvement in vaccine response in whole population or in those older than 69a | Harman et al20 |
| Zinc | 400 mg/day zinc sulfate, or 400 mg/day zinc sulfate plus 4 g/day arginine | 15 days prior to vaccination | Vaccine only | 64-100 years; mean age 82 n=384 |
TIV | No improvement in vaccine responsea | Provinciali et al23 |
| Zinc | n/a | n/a | n/a | 65+ years; 20 percent had low serum zinc <70 μg/dL n=205. |
TIV | No association between zinc status and vaccine responsea | Sundaram et al12 |
| Zinc | 220 mg zinc sulfate BID 440mg total daily dose | 1 month prior to vaccination | Vaccine only | 70+ years n=30 |
Tetanus | Significant improvement in antibody response to vaccineb | Duchateau et al24 |
| Zinc | n/a | n/a | Two control groups - one was young blood donors <30 years, the other age-matched elderly individuals >70 years | Mean age 65; n=16 (intervention), n=21 (controls >70), n=20 (controls <30) |
Diphtheria | Non-responders to vaccine had significantly decreased serum zinc levelsb | Kreft et al25 |
| Zinc | 70 mg/day zinc sulfate alongside chemotherapy | 16 weeks after vaccination | Control-placebo, control-Zn, and chemo-placebo groups. Control group consisted of non-cancer patients. Placebo was wheat starch capsules. | Mean age 63; undergoing chemotherapy for colon cancer (chemo-Zn group) n=57 |
Pneumococcal | Non-significant trend towards better seroconversion in the chemo-Zn group and protected against antibody decline during chemotherapya | Braga et al26 |
| Combination Micronutrients | Either (1) 20 mg zinc and 100 μg selenium daily; (2) 6 mg beta carotene (vitamin A precursor), 15 mg alpha tocopherol (vitamin E), 120 mg vitamin C daily; or (3) supplements from (1) and (2) combined daily. | 2 years, with vaccination at 15-17 months | Calcium phosphate and microcrystalline cellulose | 65+ years n=725 |
TIV | Significantly improved serological protection in groups (1) and (3) compared to control. Group (2) achieved significantly lower seroprotection, though nonsignificantly lower incidence of respiratory infection, compared to controlb | Girodon et al27 |
| Combination Micronutrients | Multivitamin and mineral with 30-160% US RDA plus antioxidants and 250 kcal energy (14% protein, 40% fat, 46% carbohydrate) dosed BID | 7 months, with vaccination at 6 months | Noncaloric placebo drink (ingredients not specified) | 65+ years; mean age 84 n=19 |
TIV | Significantly improved serological protection for H3N2 but not other strainsb | Bunout et al29 |
| Combination with Micronutrients | Nutritional formula that included 120 IU vitamin E, 3.8 mcg vitamin B12, 400 mcg folic acid, 10 bn CFU Lactobacillus paracasei (NCC 2461), 6 g fructo- oligosaccharide prebiotics and 480 kcal energy (25% protein, 23% fat, 51% carbohydrate) daily | 12 months, with vaccination after 4 months | No nutritional supplementation | 70+ years n=60 |
TIV and pneumococcal | No improvement in vaccine responsea | Bunout et al29 |
| Combination with Micronutrients | 8 oz liquid multivitamin and mineral plus beta-carotene, taurine, carnitine, omega- 3 fatty acids, medium chain triglycerides and fermentable oligosaccharides (prebiotics) daily | 183 days with vaccination on day 15 ± 2 | 8 oz of an isonitrogenous/isoenergetic standard liquid nutritional formula (brand unspecified) 77% maltodextrin 23% sucrose | 65+ years, mean age 82-84 n=66 |
TIV | Significantly improved serological protection for H3N2 but not other strainsb | Langkamp-Henken et al30 |
| Combination with Micronutrients | 240 mL liquid multivitamin and mineral plus beta-carotene, taurine, carnitine, omega-3 fatty acids, medium chain triglycerides and fermentable oligosaccharides (prebiotics) daily | 4 weeks prior to, and 6 weeks after vaccination | 240mL of an isonitrogenous/isoenergetic standard liquid nutritional formula (brand: EnsurePlus, Abbott Laboratories) 0% FOS 77% maltodextrin | 65+ years; mean age 81-85. n=92 |
TIV | Significantly improved serological protection for H1N1 but not other strainsb | Langkamp-Henken et al31 |
aNo significant effect on/association with vaccine response
bSignificant effect on/association with vaccine response for at least one vaccine strain/subgroup