Table 1.
Characteristics of the included studies.
| Author | Region | Country | Population Characteristics | N | Study Design | Fortified Food | Baseline Calcium Intake mg/day | Intervention and Control Group Used for this Analysis | Food Fortification Level < 0.5; 0.5–1; >1 g/assigned Daily Portion | Calcium Intake Difference between Intervention and Control Group (mg/day) | Duration of Fortification (Months) | Main Outcome | Outcomes Assessed Included in This Review |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Bass 2007 [32] | Western Pacific Region | Australia | Healthy boys between 7–11 years old | 88 | RCT | Cakes/cookies | I: 931 P:934 |
Intervention: one out of 10 varieties of muffins and cookies a day. Muffins and cookies were fortified with 4 g of milk minerals powder, which provided participants with an additional 800 mg of elemental calcium per day. Placebo: one out of 10 varieties of muffins and cookies without added calcium. |
0.5–1 | 800 | 8.5 | Bone health | Calcium Intake, Weight, Height, BMC (total body, lumbar spine, leg (Femur + Tibia-Fibula), arm (Humerus + Ulna-Radius) |
| Bonjour 1997 [33] | Europe | Switzerland | Healthy prepubertal Caucasian girls. Mean age 7.93 years old |
149 |
RCT | Cakes | NA | Intervention: Two food products every day in place of similar foods taken for breakfast or snacks fortified with calcium from milk extract. The calcium contents (mg/serving) of calcium-enriched food products was as follows: chocolate cakes, 516; caramel cakes, 512; biscuits, 548; fruit juices, 383; powdered drinking chocolate, 530; chocolate bars, 429; yogurts, 478. Calcium from milk extract was used to fortify food products. Placebo: Two food products every day in place of similar foods taken for breakfast or snacks without added calcium. The calcium contents (mg/serving) of placebo food products was as follows: chocolate cakes, 33; caramel cakes, 41; biscuits, 8; fruit juices, 11; powdered drinking chocolate, 4; chocolate bars, 80; yogurts, 174. |
0.5–1/>1 | -Chocolate cakes, 483 -Caramel cakes, 471 -Biscuits, 540 -Fruit juices, 372 -Powdered drinking chocolate, 526 -Chocolate bars, 349 -Yogurts, 304 |
11 | Bone health | Weight, Height, BMI, BMD (lumbar spine, femoral neck) |
| Cheng 2005 [34] | Europe | Finland | Girls aged 10–12 years old | 195 |
RCT | Cheese | I: 706 P: 664 |
Intervention: dairy products such as natural low-fat cheese (110 g Edam with 17% fat and 100 g Turunmaa with 15% fat) which provided a quantity equivalent to 1000 mg of elemental calcium a day. Placebo: calcium plus vitamin D supplements placebo. |
0.5–1 | 1000 | 24 | Bone health | Weight, Height, aBMD (lumbar spine, femoral neck, total femur), BMC total body. |
| Cleghorn 2001 [35] | Western Pacific Region | Australia | Women who were less than five years postmenopausal. | 142 | RCT-c | Milk | I: 967 C: 918 |
Intervention: one litre of calcium-fortified milk thrice weekly (428 mL/d). Milk was fortified by adding to reduced-fat milk the retentate from ultrafiltration of low-fat milk. It contains 1600 mg of elemental calcium and 1200 mg phosphorus per litre providing an average of 685 mg of elemental calcium a day. Control: Usual diet |
0.5–1 | 686 | 24 | Bone health | Weight, BMD (Forearm, Lumbar spine L2–L4) |
| Du 2004 [36] | Western Pacific Region | China | Healthy girls aged 10 years old | 757 | RCT | Milk | I: 418.2 C: 455.3 |
Intervention: 330 mL ultra-heat-treated (UHT) milk 5 days a week, which had been fortified to contain 560 mg of elemental calcium. It provided 245 mg of elemental calcium a day. Control: Usual diet |
<0.5 | 245 | 24 | Bone health | Calcium Intake, Height, PTH, Plasma 25(OH)D, Plasma Ca, BMD Total body, BMI, Urine Ca/creatinine. |
| Ferrar 2011 [37] | Europe | UK | Young women ages 20 to 39 years old | 76 | RCT | Ice cream | I 1: 735 I 2: 663 I 3: 754 P: 714 |
One per day Ice cream low in fat—Calcium, magnesium, phosphorus and zinc. Milk minerals (Arla Foods Ingredients, Redhill, Surrey, UK) Intervention Group 1: 60 g ice cream containing 244 mg of elemental Calcium fortified with milk minerals. Intervention Group 2: 60 g ice cream containing 459 mg of elemental Calcium fortified with milk minerals. Intervention Group 3: 60 g ice cream containing 676 mg of elemental Calcium fortified with milk minerals. Placebo: consumed 60 g of ice cream containing 96 mg calcium per unit. |
<0.5/0.5–1 | I 1: 148 I 2: 363 I 3: 580 |
1 | Bone health | Calcium Intake, PTH, Serum 1,25D. |
| Green 2000 [38] | Western Pacific Region | New Zealand | Healthy volunteers aged over 40 years, 19 men and 19 women. |
38 | RCT-c | Milk | 1120 | A 4-week washout period separated consecutive milk interventions. Each volunteer consumed each of the milks in randomized order. Intervention: 50 g of high Calcium skim milk powder diluted in tap water to provide 480 mL of milk per day containing 1075 mg of elemental Calcium. Control: 50 g of skim milk powder diluted in tap water to provide 480 mL of milk per day containing 720 mg of Calcium. |
>1 | 355 | 1 | Blood Pressure | Office sitting SBP (mmHg), office sitting DBP (mmHg), office standing SBP (mmHg), office standing DBP (mmHg). |
| Green 2002 [39] | Western Pacific Region | New Zealand | Healthy postmenopausal women (at least 5 years postmenopausal) | 50 | RCT | Milk | I: 850 C: 900 |
Intervention: 400 mL of high-calcium skim milk powder containing 1200 mg of calcium supplemented with 172 mg magnesium per 50 g milk powder a day. Control: 400 mL of apple drink containing no more than 25% apple juice a day. |
>1 | 1200 | 1 | Bone Health | Calcium Intake, Serum PTH (pmol/L), Serum Calcium. |
| Gui 2012 [40] | Western Pacific Region | China | Postmenopausal women without osteoporosis, aged 45–65, and postmenopausal for more than 2 years. |
141 | RCT | Soymilk | NA | Intervention: 250 mL calcium-fortified soymilk daily. Calcium-fortified soymilk contained 6.5 g soy protein, 2.5 g fat, 2.5 g lactose, 250 mg calcium, and 3.75 to 4.5 mg soy isoflavones. Control: Usual diet. They abstain from any other dietary supplementation, including other milk, other soymilk, vitamin D, vitamin K, complex vitamins, and calcium tablets. |
<0.5 | 250 | 18 | Bone Health | BMD (spine, femoral neck, hip). |
| Kukuljan 2009 [41] | Western Pacific Region | Australia | Healthy community- dwelling Caucasian men aged 50–79 years | 180 | RCT- 2 by 2factorial design |
Milk | I: 1039 C: 996 |
Intervention: 400 mL milk per day of reduced-fat (1%) ultrahigh temperature (UHT) milk. Milk was fortified with milk salts containing 1000 mg calcium and 800 IU vitamin D3 and 500 mg phosphorous/day Control: Usual Diet. |
0.5–1 | 1000 | 18 | Bone Health | Calcium intake |
| Gibbons 2004 [42] | Western Pacific Region | New Zealand | Children, aged 8–10 years | 154 |
RCT | Milk | I: 934 P: 985 |
Intervention: 8O g of chocolate milk drink per day. The high calcium milk provided 1200 mg of elemental calcium and 776 mg phosphorus per day. Placebo: 8O g of chocolate milk drink per day. The milk provided 400 mg of elemental calcium and 320 mg of phosphorus per day. |
>1 | 800 | 18 | Bone Health | Weight, Height, BMD (Lumbar spine, femoral Neck, total hip, trochanter, total body) and BMC (total body, trochanter, hip, femoral neck and spine) |
| Palacios 2005 [43] | Europe | Spain | Healthy white women, postmenopausal for 10 years or more, between 49 and 71 years old and with a dietary calcium intake lower than 750 mg/day | 79 | RCT | Milk | I: 508 P: 502 |
Intervention: 750 mL of skimmed milk enriched with calcium 1200 mg, phosphorus 945 mg, lactose, and vitamin D3 5.7 mg per day. Placebo: 750 mL skimmed milk enriched with vitamin D3 (5.7 mg/750 mL) of identical appearance, taste, and composition to that of intervention group except for the amount of calcium (900 mg/750 mL) and this milk was not fortified with phosphorus or lactose. |
>1 | 300 | 6 | Bone Health | Weight, 250H vitamin D3, Calcemia (mg/dL), calcium urine (mg/dL), calcium/creatinine (mg/mg) |
| Trautvetter 2012 [44] | Europe | Germany | Men and women omnivorous, moderately hypercholesterolemic subjects; aged 25.5 y and had a BMI of 22.3 kg/m2. | 32 | RCT-c | Bread | 873 | All subjects consumed 100 mL of the probiotic drink daily. Intervention: 135 g of bread a day fortified with 1000 mg of elemental calcium as pentacalcium hydroxy- triphosphate Control: 135 g of bread a day without added calcium. |
0.5–1 | 1000 | 3 | Cholesterol | Calcium Intake, Total cholesterol [mmol/L], LDL-cholesterol [mmol/L], HDL-cholesterol [mmol/L], LDL/HDL ratio, triacylglycerol [mmol/L] |
| Zhang 2014 [45] | Western Pacific Region | China | Healthy adolescents aged 12–14 years (111 girls and 109 boys) | 220 | RCT | Milk | Girls: I 1: 651 I 2: 707 C: 701 Boys: I 1: 758 I 2: 704 C: 680 |
The subjects were assigned to receive 40 g of milk powder daily. Each daily dose was administered in two packages (approximately 20 g/package). Intervention 1: 40 g of milk powder containing 900 mg of calcium and 200 IU of vitamin D. For this fortification daily dose of 2g of isolated milk salt (containing 29.2% calcium and 15% phosphorus) was added to 40 g of milk. Intervention 2: 40 g of milk powder containing 600 mg of calcium and 200 IU of vitamin D. For this fortification daily dose of 1g of isolated milk salt (containing 29.2% calcium and 15% phosphorus) was added to 40 g of milk. Control: 40 g of milk powder containing 300 mg of calcium and 200 IU of vitamin D. |
<0.5/0.5–1 | I 1: 600 I 2: 300 |
24 | Bone Health | Calcium Intake, Weight, Height, BMD and BMC (spine, femoral neck, left hip, total body, femoral shaft) |
| Zhang 2016 [46] | Western Pacific Region | China | Postpartum women aged 20–35 years. All were primipara who had delivered a normal single infant at full term and intended to be breast-feeding | 150 | RCT | Milk | I 1: 822 I 2: 811 C: 807 |
The subjects were assigned to receive 40 g of milk powder daily for 12 months. Each daily dose was administered in two packages (approximately 20 g/package). Intervention 1: 40 g of milk powder containing 900 mg of calcium and 5 μg of vitamin D. For this fortification daily dose of 2g of isolated milk salt (containing 29.2% calcium and 15% phosphorus) was added to 40 g of milk. Intervention 2: 40 g of milk powder containing 600 mg of calcium and 5 μg of vitamin D. For this fortification daily dose of 1g of isolated milk salt (containing 29.2% calcium and 15% phosphorus) was added to 40 g of milk. Control: 40 g of milk powder containing 300 mg of calcium and 5 μg of vitamin D. |
<0.5/0.5–1 | I 1: 600 I 2: 300 |
12 | Bone Health | Calcium Intake, Weight, BMD (spine, femoral neck, left hip, trochanter, total body) |
| Barnuevo 2018 [47] | Europe | Spain | Healthy female young volunteers. Mean age 39.2 ± 4.6 years old | 181 | RCT analyzed as UBAS | Milk | NA | Intervention: 250 mL a day of partly skimmed milk with 240 mg calcium and 105 mg of phosphorus. | <0.5 | NA | 18 | Bone health | BMD (lumbar spine, femoral neck, total hip, throcanteric region) |
| Gonzalez Sanchez 2012 [48] | Europe | Spain | Postmenopausal women, aged between 36 and 84 years, and who had low intake of calcium and vitamin D. | 261 | UBAS | Fermented Milk | 747.9 | Intervention: 125 g of Fermented milk (Densia®) per day, fortified with 400 mg of elemental calcium and 200 UI of Vit D. | <0.5 | 400 | 1 | Dietary Intake | Calcium intake |
| Osler 1998 [49] | Europe | Denmark | Men and women, aged 35–65 years at first examination in 1987, 1988 | 329 | UBAS | Flour | 1215 | Intervention: Flour fortified with calcium, 200 mg of elemental calcium per 100 g wheat flour and 400 mg of calcium per 100 g rye flour, since 1954, and until 1987 when the mandatory fortification was stopped. | <0.5 | NA | 72 | Dietary Intake | Calcium intake |
RCT: Randomized controlled trial; RCT-C: Cross over Randomized controlled trial; UBAS: Uncontrolled before-after study; NA: Not available; BMD: bone mineral density; BMC: bone mineral content; BMI: body mass index (w/h2); PTH: Parathyroid hormone; SBP: Systolic blood pressure; DBP: Diastolic blood pressure; LDL: low-density lipoprotein; HDL: High-density lipoprotein.Excluded studies. Out of the 124 excluded studies, 7 were initially included so we detailed the final exclusion reason. Two did not have the intervention under study, one had a non-eligible comparison group and four a non-eligible study design. The reasons for exclusion are provided in Appendix A Table A2)