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. 2022 Nov 11;81(7):804–822. doi: 10.1093/nutrit/nuac091

Table 4.

Supplementation with vitamin D alone and in combination with other nutrients or therapies and its effect on health outcomes

Reference Type of study Recruitment locations Country No. of participants Age, mean±SD, y Sex Type of intervention Duration Primary outcome measures Main conclusions a

  • Bogaerts et al (2011)65

  • RCT

  • NHs

 Belgium

  • 113 P

  • 111 C

  • WBV+CD: 80.3 (5.3)

  • WBV+HD: 79.8 (5.3)

  • CD group: 78.7 (5.6)

  • HD group: 79.6 (5.2)

 111 F; 0 M

  • Type ND:

  • WBV+CD (n = 28) 880 IU/d vit D3

  • WBV+HD (n = 26) 1600 IU/d vit D3

  • CD group (n = 28)

  • HD group (n = 29)

  • All received 1000 mg Ca

  • WBV (exercise 3 times/wk on a vibration platform)

 6 mo

  • Balance: computerized posturography

  • Functionality: 10-m walk test, TUG, shuttle walk

  • Fall risk

 HD vitamin D supplementation is not more efficient than conventional dosing in improving functionality in institutionalized elderly. WBV training on top of vitamin D supplementation provided an added benefit with regard to walking, TUG performance, and endurance capacity.

  • Bonjour et al (2011)66

  • Crossover RCT

  • 6 NHs/institutions for elderly

 France

  • 29 P

  • 21 C

 86.9 (6.3) 29 F; 0 M

  • Fortified vs standard cheese;

  • Intervention: 2 × 100g/d fortified cheese (total: 100 IU vit D + 302 mg Ca)

  • Control: 2 × 100g/d standard cheese (total: 0 IU vit D + 236 mg Ca)

  • 12 wk total:

  • 6 wk on control; 6 wk on intervention

  • CTX

  • TRAP-5b

  • 25(OH)D

  • PTH

 Consumption of soft plain cheese increasing the supply of vitamin D, calcium and proteins, could reduce bone resorption and thereby reduce the risk of incidental fragility fractures in the long term.

  • Verschueren et al (2011)67

  • RCT

  • NHs/service apartments/cloistered communities

 Belgium

  • 113 P

  • 111 C

  • WBV+CD: 80.3 (5.3)

  • WBV+HD: 79.8 (5.3)

  • CD group: 78.7 (5.6)

  • HD group: 79.6 (5.2)

 111 F; 0 M

  • Type ND:

  • WBV+CD (n = 28) 880 IU/d vit D3

  • WBV+HD (n = 26) 1600 IU/d vit D3

  • CD group (n = 28)

  • HD group (n = 29)

  • All received 1000 mg Ca

  • WBV (exercise 3 times/wk on a vibration platform)

 6 mo Isometric and dynamic strength; leg-mass muscle; hip BMD In institutionalized older women over 70 y old, the WBV training program described herein does not provide additional musculoskeletal benefit over vitamin D supplementation. Compared with conventional doses of vitamin D (880 IU), a higher dose of 1600 IU induced significantly higher levels of circulating vitamin D but was not more efficient in enhancing either muscle mass or strength or increasing hip BMD in this population.

  • Kaviani et al (2012)68

  • Interventional prospective

  • 1 NH

 Iran 76 P 78.7 (8) 52 F; 24 M Oral pill; 50 000 IU vit D3/wk 8 wk

  • Insulin resistance

  • Fasting plasma glucose

  • 25(OH)D

 Before and after the intervention, vitamin D deficiency had no relationship with FPG level and insulin resistance. Vitamin D intake had no significant effect on FPG level, but it increased the prevalence of insulin resistance significantly.

  • Bonjour et al (2013)69

  • Double-blinded RCT

  • 10 NHs

 France

  • 59 P

  • 56 C

  • CY: 85.1 (1.3)b

  • FY: 85.8 (1.2)

 58 F; 0 M

  • FY vs CY:

  • FY group (n = 32): 2 × 125 g/d (total: 400 IU vit D3 + 800 mg Ca)

  • CY group (n = 27): 2 × 125 g/d (total: 400 IU vit D3 + 280 mg Ca)

 8 wk

  • 25(OH)D

  • PTH

  • Bone resorption markers: TRAP5b and CTX

 This study in institutionalized elderly at high risk for osteoporotic fracture suggests that fortification of dairy products with vitamin D3 and calcium provides a greater prevention of accelerated bone resorption as compared with nonfortified equivalent foods.

  • Mocanu et al (2013)70

  • Single-arm clinical trial

  • 1 NH

 Romania

  • 45 P

  • 23 C

 68.3 28 F; 17 M

  • Fortified bread:

  • Follow up after 1 y and 3 y after discontinuation of 100 g bread bun/d for 12 mo containing 5000 IU vit D3 + 320g Ca

 3 y

  • 25(OH)D

  • PTH

  • BMD

 Vitamin D nutritional status exhibits a long half-life in the body, and a true steady-state plateau may not even be reached 1 year after a discontinuation in dose. Furthermore, once the need for vitamin D has been established, based on a low baseline serum 25(OH)D concentrations, the appropriate action is to maintain corrective vitamin D supplementation over the long term.

  • Costan et al (2014)71

  • Longitudinal prospective

  • 1 NH

 Romania

  • 45 P

  • 40 C

  • VFX: 71.6 (7.2)

  • VF: 69.9 (5.2)

 28 F; 17 M

  • Fortified bread:

  • 1 × 100 g bread roll/d containing 5000 IU vit D3 + 320 g Ca

 12 mo Health-related quality of life (pain, physical function, social function, general health perception, and mental function) Daily consumption of bread fortified with 125 g vitamin D3 was efficient and safe to raise serum 25(OH)D concentrations to > 75 nmol/L and to induce significant improvement of the total score of QUALEFFO-41. Vitamin D supplementation also significantly diminished pain perception and ameliorated physical functions.

  • Abizanda et al (2015)72

  • Multicentric prospective observation

  • 4 NHs

 Spain

  • 91 P

  • 69 C

 85.6 (5.6) 27 M; 64 F

  • Oral drink:

  • 2 × 200 mL ONS daily + exercise 5 × d/wk

  • Each ONS contains: 300 kcal, 20 g protein, 3 g fiber, 500 IU vit D, 480 mg Ca

 12 wk

  • SPPB

  • SF-LLFDI

  • Handgrip strength

  • EQ5DVAS

  • BMI

  • Mini-nutrition assessment

 A 12-wk intervention with oral nutritional supplementation plus physical exercise improves function, nutritional status, and quality of life in frail institutionalized older adults.

  • Heijboer et al (2015)73

  • Intervention

  • NH residents

 The Netherlands 49 P

  • Median (range):

  • 82 (71–97)

 0 F; 49 M

  • Oral tablet:

  • 600 IU vit D/d vs placebo

  • All participants received 500 mg Ca carbonate

 16 wk

  • 25(OH)D status

  • Testosterone concentration

 In this post hoc analysis of three small clinical trials, vitamin D treatment (600–2000 IU daily) for 6 wk to 4 months does not affect the, at baseline normal, testosterone concentrations in male patients with heart failure, male nursing home residents or male non-Western immigrants living in the Netherlands.

  • Corcoran et al (2017)74

  • Cluster RCT

  • 20 senior living facilities

 USA

  • 121 P

  • 93 C

 82.3 (8) 101 F; 20 M

  • Oral drink:

  • ENP (n = 47): drink + exercise 3 d/wk

  • SAP (n = 46): 3 d/wk

  • Each drink contains 300 kcal, 13 g fat, 24 g carbohydrate, 20 g milk protein, 500 IU vit D, 480 mg Ca

 6 mo

  • SPPB

  • Handgrip strength

  • Mini-nutrition assessment

 This facility-led exercise-nutritional supplement program was not effective at improving physical function or blood levels of 25-hydroxyvitamin D and IGF-1, possibly due to a decline in nutritional status observed in the intervention group coupled with challenges related to program implementation and fidelity.

  • Ginde et al (2017)75

  • RCT

  • 25 skilled nursing and assisted living facilities

 USA

  • 107 P

  • 77 C

  • HD: 80 (10)

  • STD: 82 (10)

  • HD: 33 F; 22 M

  • STD: 29 F; 23 M

  • Capsule:

  • HD (n = 55): 100 000 IU/L × monthly dose vit D3

  • STD (n = 52): placebo (if currently taking 400–1000 IU vit D3/d) or 12 000 IU/mo (if currently taking <400 IU vit D3/d)

 12 mo

  • Incidence of ARIs

  • Falls/fractures

  • 25(OH)D

  • Hypercalcemia

  • Kidney stones

 Monthly high dose vitamin D3 supplementation reduced the incidence of ARI in older long-term care residents but was associated with a higher rate of falls without an increase in fractures.

  • Kotlarczyk et al (2017)76

  • Secondary analysis

  • Long-term care facilities

 USA

  • 137 P

  • 137 C

  • Def: 85.8 (1)

  • Insuff: 85.6 (0.8)

  • Suff: 84.9 (0.6)

 137 F; 0 M

  • Oral supplement: ND

  • Deficient (n = 26): 50 000 IU/wk for 8 wk initially

  • Then Def, Insuff (n = 40) and Suff (n = 71) participants received 800 IU vitamin D3/d

 24 mo

  • Physical function: ADL, PPT, gait speed

  • cognitive function: cognition, mental health

  • Falls

 Even after correction of vitamin D deficiency and maintenance of adequate levels (above 20 ng/ml) for two years, women who were deficient at baseline had the greatest functional declines and risk of falling.

  • Franzke et al (2019)77

  • RCT, observer-blinded

  • 5 senior residences

 Austria

  • 96 P

  • 80 C

 83.1 (6.1) 84 F; 12 M

  • Oral liquid drink;

  • CT (n = 40): cognitive training twice/wk

  • RT (n = 41): resistance training twice/wk

  • RTS (n = 36): RT + supplement twice/wk= 2× liquid drinks with each containing 150 kcal, 20.7 g protein, 9.3 g carbohydrate, 3.0 g fat, 1.2 g roughage, 800 IU vit D, 250 g of Ca, vit C, E, B6, B12, folic acid, magnesium

 6 mo

  • Micronutrient assessment

  • physical fitness: 6-min walking, chair-rise test, isokinetic dynamometry, handgrip strength

 Six months of elastic band resistance training with or without protein-vitamin supplementation improved physical function, but had no biological impact on the status on fat soluble micronutrients.

  • Veleva et al (2020)78

  • RCT

  • 3 NHs

 The Netherlands

  • 78 P

  • 52 C

  • UVB: 84.2 (79.5–87.5)

  • vit D: 83.6 (77.5–88.5)

 54 F; 24 M

  • UVB light vs vit D capsule; half-body UVB irradiation twice/wk

  • Vit D: 5600 IU vit D3 once/wk

 6 mo Well-being: CMAI and the Cornell scale The exposure of nursing home residents with dementia to UVB light showed no positive benefits in terms of wellbeing. UVB treatment may have a positive effect on the restless/tense behavior characteristic of advanced dementia, but more research is needed to confirm this finding.

Data are presented as mean (standard deviation).

a

Quoted directly from the cited articles.

b

Standard error of the mean.

Abbreviations: 25(OH)D, 25-hydroxyvitamin D; ADL, activities of daily living; ARI, acute respiratory infection; BMD, bone mineral density; BMI, body mass index; C, completed; Ca, calcium; CMAI, Cohen Mansfield Agitation Inventory; CT, cognitive training; CTX, carboxyl-terminal cross-linked telopeptide of type 1 collagen; CY, nonfortified control yogurt; DD, daily dose; DDG, daily-dose group; DEF, deficient; ENP, exercise program + nutritional supplement; EQ5DVAS; EuroQoL-5 Dimensions visual analogic scale; F, female; FY, calcium-fortified yogurt; GDS-SF, geriatric depression scale-short form; IG-1, insulin-like growth factor 1; IM, intramuscular; Insuff, insufficient; IQR, interquartile range; LD, loading dose; M, male; MD, maintenance dose; MED, minimal erythema dose; MNA-SF, Short-Form Mini Nutritional Assessment; N/A, not applicable; ND, not defined; NH, nursing home; NR, not reported; ONS, oral nutritional supplement; P, participated; PPT, physical performance test; PTH, parathyroid hormone; RCT, randomized control trial; Resp, responder; RT, resistance training; RTS, resistance training combined with calcium and protein supplementation; SAP, health education program; SF-LLFDI, Short-Form Late-Life Function and Disability Instrument; signif, significant; SPPB, Short Physical Performance Battery; STD, standard dose; SUFF, sufficient; TRAP-5b, tartrate-resistant phosphate isoform-5b; TUG, timed up and go; USA, United States of America; UV, ultraviolet light; UVB, ultraviolet B light; VF, vertebral fracture; VFX, without vertebral fracture; vit, vitamin; WDG, weekly dose group; FPG, fasting plasma glucose.