Effectiveness of Growing-Up Milk Containing Only A2 β-Casein on Digestive Comfort in Toddlers: A Randomized Controlled Trial in China
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Setting and Design
2.2. Participants
2.3. Randomization and Interventions
2.4. Study Outcomes
2.5. Sample Size
2.6. Statistical Analyses
3. Results
3.1. Baseline Characteristics and Milk Intake
3.2. Digestive Comfort
3.3. Stool Characteristics
3.4. Temperament Characteristics
3.5. Anthropometric Parameters
3.6. Adverse Events
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Appendix A
A2 GUM | Conventional Milk | |||||
---|---|---|---|---|---|---|
Baseline | Day 7 | Day 14 | Baseline | Day 7 | Day 14 | |
A2 GUM/mL | 75 ± 152 | 285 ± 144 | 285 ± 142 | / | / | / |
GUM/mL | 112 ± 173 | 40 ± 110 | 36 ± 108 | 119 ± 175 | 269 ± 165 | 276 ± 167 |
Cow’s milk/mL | 11 | 8 | 8 | 7 | 26 | 21 |
Fortified cow’s milk/mL | 2 | 0 | 2 | 1 | 3 | 9 |
Yogurt (yogurt drinks)/g | 33 | 23 | 22 | 27 | 25 | 28 |
Toddler Gut Comfort Questionnaire Item | Total | A2 GUM | Conventional Milk | Adjusted Mean Difference (95% CI) | p |
---|---|---|---|---|---|
(n = 308) | (n = 180) | (n = 128) | |||
BASELINE | |||||
Total GCS | 15.1 ± 5.3 | 15.0 ± 5.2 | 15.2 ± 5.5 | / | 0.74 |
Gastrointestinal Symptoms | |||||
Stooling issues * | 1.5 ± 0.8 | 1.5 ± 0.8 | 1.5 ± 0.9 | / | 0.54 |
Constipation * | 1.5 ± 0.9 | 1.5 ± 0.9 | 1.5 ± 0.9 | / | 0.68 |
Diarrhea * | 1.3 ± 0.6 | 1.3 ± 0.6 | 1.3 ± 0.6 | / | 0.85 |
Gassiness * | 1.4 ± 0.7 | 1.3 ± 0.6 | 1.4 ± 0.8 | / | 0.19 |
Abdominal pain * | 1.2 ± 0.6 | 1.3 ± 0.6 | 1.2 ± 0.5 | / | 0.83 |
Bloated † | 1.3 ± 0.7 | 1.3 ± 0.7 | 1.4 ± 0.7 | / | 0.66 |
Gastrointestinal Related Behaviors | |||||
Fussy and irritable * | 1.6 ± 0.9 | 1.5 ± 0.8 | 1.6 ± 1.0 | / | 0.32 |
Sleep problem ‡ | 1.5 ± 0.8 | 1.5 ± 0.7 | 1.6 ± 0.9 | / | 0.75 |
Sleepy during the day * | 1.5 ± 0.7 | 1.5 ± 0.8 | 1.5 ± 0.7 | / | 0.88 |
Waking up during the night § | 2.2 ± 1.0 | 2.2 ± 1.0 | 2.1 ± 0.9 | / | 0.39 |
DAY 7 | |||||
Total GCS | 14.9 ± 5.5 | 14.8 ± 5.0 | 15.0 ± 6.1 | −0.13 (−1.12, 0.86) | 0.80 |
Gastrointestinal Symptoms | |||||
Stooling issues * | 1.5 ± 0.8 | 1.4 ± 0.8 | 1.5 ± 0.8 | −0.003 (−0.17, 0.16) | 0.97 |
Constipation * | 1.5 ± 0.8 | 1.4 ± 0.7 | 1.5 ± 0.9 | −0.08 (−0.21, 0.06) | 0.27 |
Diarrhea * | 1.3 ± 0.6 | 1.2 ± 0.5 | 1.4 ± 0.6 | −0.13 (−0.2, −0.02) | 0.027 |
Gassiness * | 1.3 ± 0.5 | 1.3 ± 0.6 | 1.5 ± 0.9 | −0.05 (−0.18, 0.07) | 0.41 |
Abdominal pain * | 1.3 ± 0.6 | 1.3 ± 0.5 | 1.3 ± 0.6 | −0.06 (−0.17, 0.05) | 0.28 |
Bloated † | 1.3 ± 0.6 | 1.3 ± 0.5 | 1.4 ± 0.7 | −0.07 (−0.19, 0.05) | 0.24 |
Gastrointestinal Related Behaviors | |||||
Fussy and irritable * | 1.5 ± 0.8 | 1.4 ± 0.7 | 1.5 ± 0.8 | −0.03 (−0.16, 0.11) | 0.70 |
Sleep problem ‡ | 1.5 ± 0.7 | 1.5 ± 0.7 | 1.5 ± 0.7 | −0.03 (−0.18, 0.12) | 0.69 |
Sleepy during the day * | 1.5 ± 0.6 | 1.5 ± 0.7 | 1.5 ± 0.6 | 0.01 (−0.12, 0.14) | 0.92 |
Waking up during the night § | 2.2 ± 1.0 | 2.3 ± 1.0 | 2.1 ± 0.9 | 0.19 (0.03, 0.35) | 0.022 |
DAY 14 | |||||
Total GCS | 14.1 ± 4.8 | 14.0 ± 4.3 | 14.3 ± 5.5 | −0.25 (−1.13, 0.64) | 0.59 |
Gastrointestinal Symptoms | |||||
Stooling issues * | 1.4 ± 0.7 | 1.3 ± 0.6 | 1.5 ± 0.9 | −0.10 (−0.24, 0.04) | 0.15 |
Constipation * | 1.4 ± 0.7 | 1.3 ± 0.6 | 1.4 ± 0.9 | −0.16 (−0.2, −0.04) | 0.010 |
Diarrhea * | 1.3 ± 0.5 | 1.2 ± 0.4 | 1.3 ± 0.5 | −0.06 (−0.17, 0.04) | 0.22 |
Gassiness * | 1.3 ± 0.6 | 1.2 ± 0.4 | 1.3 ± 0.6 | −0.08 (−0.19, 0.03) | 0.15 |
Abdominal pain * | 1.2 ± 0.5 | 1.2 ± 0.4 | 1.3 ± 0.5 | −0.07 (−0.17, 0.03) | 0.16 |
Bloated † | 1.3 ± 0.5 | 1.2 ± 0.4 | 1.3 ± 0.6 | −0.11 (−0.22, −0.01) | 0.038 |
Gastrointestinal Related Behaviors | |||||
Fussy and irritable * | 1.4 ± 0.7 | 1.4 ± 0.7 | 1.4 ± 0.7 | 0.01 (−0.12, 0.15) | 0.83 |
Sleep problem ‡ | 1.4 ± 0.7 | 1.4 ± 0.7 | 1.4 ± 0.6 | −0.01 (−0.15, 0.13) | 0.89 |
Sleepy during the day * | 1.4 ± 0.6 | 1.4 ± 0.6 | 1.4 ± 0.6 | −0.02 (−0.14, 0.10) | 0.77 |
Waking up during the night § | 2.2 ± 1.0 | 2.3 ± 1.1 | 1.9 ± 0.9 | 0.25 (0.07, 0.43) | 0.006 |
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Characteristics | Total (n = 387) | A2 GUM (n = 259) | Conventional Milk (n = 128) | p-Value |
Age (months) | 23.6 ± 6.6 | 23.3 ± 6.5 | 24.1 ± 6.8 | 0.225 |
Sex, n (%) | 0.637 | |||
Male | 199 (51.4) | 131 (50.6) | 68 (53.1) | |
Female | 188 (48.6) | 128 (49.4) | 60 (46.9) | |
Parity, n (%) | 0.750 | |||
Primipara | 268 (69.3) | 178 (68.7) | 90 (70.3) | |
Multipara | 119 (30.7) | 80 (31.3) | 38 (29.7) | |
Delivery mode, n (%) | 0.157 | |||
Vaginal delivery | 237 (61.2) | 165 (63.7) | 72 (56.2) | |
Cesarean delivery | 150 (38.8) | 94 (36.3) | 56 (43.8) | |
Family history of digestive diseases | 1 (0.3) | 0 (0) | 1 (0.8) | 0.331 |
Breastfeeding | 0.150 | |||
Still breastfeeding | 78 (20.2) | 50 (19.3) | 28 (21.9) | |
Ever breastfed | 292 (75.5) | 194 (74.9) | 98 (76.6) | |
Never breastfed | 17 (4.4) | 15 (5.8) | 2 (1.6) | |
Breastfeeding duration, months | 14.2 ± 6.5 | 13.9 ± 6.2 | 14.7 ± 6.6 | 0.260 |
Toddler Gut Comfort Questionnaire Item (Mean ± SD) | All Participants | Baseline GCS < 17 | Baseline GCS >= 17 | |||||||
---|---|---|---|---|---|---|---|---|---|---|
Total | A2 GUM | Conventional Milk | p | A2 GUM | Conventional Milk | p | A2 GUM | Conventional Milk | p | |
(n = 387) | (n = 259) | (n = 128) | (n = 175) | (n = 88) | (n = 84) | (n = 40) | ||||
BASELINE | ||||||||||
Total GCS | 15.2 ± 5.5 | 15.1 ± 5.5 | 15.2 ± 5.5 | 0.91 | 12.0 ± 1.7 | 12.0 ± 1.8 | 0.92 | 21.7 ± 4.9 | 22.2 ± 4.4 | 0.60 |
Gastrointestinal Symptoms | ||||||||||
Stooling issues * | 1.5 ± 0.8 | 1.5 ± 0.8 | 1.5 ± 0.9 | 0.75 | 1.1 ± 0.3 | 1.1 ± 0.4 | 0.17 | 2.3 ± 1.0 | 2.3 ± 1.0 | 0.99 |
Constipation * | 1.5 ± 1.0 | 1.6 ± 1.0 | 1.5 ± 0.9 | 0.41 | 1.1 ± 0.4 | 1.1 ± 0.2 | 0.042 | 2.5 ± 1.3 | 2.4 ± 1.2 | 0.91 |
Diarrhea * | 1.3 ± 0.6 | 1.3 ± 0.6 | 1.3 ± 0.6 | 0.95 | 1.1 ± 0.2 | 1.1 ± 0.3 | 0.43 | 1.9 ± 0.7 | 1.9 ± 0.8 | 0.90 |
Gassiness * | 1.4 ± 0.7 | 1.3 ± 0.6 | 1.4 ± 0.8 | 0.42 | 1.0 ± 0.2 | 1.1 ± 0.3 | 0.14 | 2.0 ± 0.9 | 2.2 ± 0.9 | 0.42 |
Abdominal pain * | 1.3 ± 0.6 | 1.3 ± 0.6 | 1.2 ± 0.5 | 0.74 | 1.0 ± 0.2 | 1.1 ± 0.3 | 0.20 | 1.8 ± 0.8 | 1.7 ± 0.6 | 0.45 |
Bloating † | 1.4 ± 0.7 | 1.4 ± 0.8 | 1.4 ± 0.7 | 0.84 | 1.0 ± 0.1 | 1.0 ± 0.2 | 0.21 | 2.1 ± 1.0 | 2.1 ± 0.9 | 0.82 |
Gastrointestinal-related Behaviors | ||||||||||
Fussy and irritable * | 1.6 ± 0.9 | 1.5 ± 0.8 | 1.6 ± 1.0 | 0.29 | 1.2 ± 0.6 | 1.2 ± 0.4 | 0.40 | 2.1 ± 0.9 | 2.6 ± 1.2 | 0.016 |
Sleep problems ‡ | 1.5 ± 0.8 | 1.5 ± 0.8 | 1.6 ± 0.9 | 0.64 | 1.2 ± 0.4 | 1.2 ± 0.5 | 0.91 | 2.2 ± 0.9 | 2.4 ± 1.0 | 0.32 |
Sleepy during the day * | 1.6 ± 0.8 | 1.6 ± 0.8 | 1.5 ± 0.7 | 0.95 | 1.2 ± 0.5 | 1.2 ± 0.5 | 0.81 | 2.2 ± 0.8 | 2.2 ± 0.8 | 0.93 |
Waking up during the night § | 2.2 ± 1.0 | 2.2 ± 1.1 | 2.1 ± 0.9 | 0.51 | 2.0 ± 0.9 | 2.0 ± 0.9 | 0.81 | 2.6 ± 1.2 | 2.5 ± 1.0 | 0.50 |
DAY 7 | ||||||||||
Total GCS | 14.8 ± 5.4 | 14.7 ± 5.0 | 15.0 ± 6.1 | 0.54 | 13.0 ± 4.0 | 12.2 ± 2.7 | 0.11 | 18.2 ± 5.1 | 21.2 ± 6.8 | 0.004 |
Gastrointestinal Symptoms | ||||||||||
Stooling issues * | 1.5 ± 0.9 | 1.5 ± 0.9 | 1.5 ± 0.8 | 0.70 | 1.3 ± 0.7 | 1.1 ± 0.3 | 0.09 | 1.9 ± 1.0 | 2.2 ± 1.1 | 0.076 |
Constipation * | 1.5 ± 0.8 | 1.5 ± 0.8 | 1.5 ± 0.9 | 0.32 | 1.3 ± 0.6 | 1.1 ± 0.3 | 0.07 | 1.8 ± 0.9 | 2.3 ± 1.1 | 0.001 |
Diarrhea * | 1.3 ± 0.5 | 1.3 ± 0.5 | 1.4 ± 0.6 | 0.057 | 1.1 ± 0.4 | 1.1 ± 0.3 | 0.90 | 1.6 ± 0.6 | 1.9 ± 0.7 | 0.004 |
Gassiness * | 1.4 ± 0.7 | 1.3 ± 0.6 | 1.5 ± 0.9 | 0.19 | 1.1 ± 0.4 | 1.1 ± 0.3 | 0.34 | 1.7 ± 0.7 | 2.1 ± 0.8 | 0.002 |
Abdominal pain * | 1.3 ± 0.5 | 1.3 ± 0.5 | 1.3 ± 0.6 | 0.22 | 1.1 ± 0.4 | 1.1 ± 0.3 | 0.28 | 1.5 ± 0.6 | 1.8 ± 0.7 | 0.003 |
Bloating † | 1.3 ± 0.6 | 1.3 ± 0.5 | 1.4 ± 0.7 | 0.10 | 1.1 ± 0.4 | 1.1 ± 0.3 | 0.67 | 1.6 ± 0.6 | 2.0 ± 0.8 | 0.002 |
Gastrointestinal-related Behaviors | ||||||||||
Fussy and irritable * | 1.4 ± 0.7 | 1.4 ± 0.7 | 1.5 ± 0.8 | 0.40 | 1.3 ± 0.6 | 1.2 ± 0.4 | 0.40 | 1.7 ± 0.7 | 2.2 ± 1.1 | 0.014 |
Sleep problems ‡ | 1.4 ± 0.7 | 1.4 ± 0.7 | 1.5 ± 0.7 | 0.38 | 1.2 ± 0.5 | 1.2 ± 0.3 | 0.53 | 1.9 ± 0.9 | 2.2 ± 0.8 | 0.033 |
Sleepy during the day * | 1.5 ± 0.7 | 1.5 ± 0.7 | 1.5 ± 0.6 | 0.83 | 1.3 ± 0.5 | 1.2 ± 0.4 | 0.42 | 2.0 ± 0.7 | 2.1 ± 0.7 | 0.17 |
Waking up during the night § | 2.2 ± 1.0 | 2.3 ± 1.0 | 2.1 ± 0.9 | 0.026 | 2.1 ± 0.9 | 1.9 ± 0.8 | 0.053 | 2.6 ± 1.2 | 2.3 ± 1.0 | 0.29 |
DAY 14 | ||||||||||
Total GCS | 14.1 ± 4.9 | 14.0 ± 4.5 | 14.3 ± 5.5 | 0.51 | 12.5 ± 3.1 | 11.9 ± 2.7 | 0.15 | 17.1 ± 5.3 | 19.6 ± 6.3 | 0.026 |
Gastrointestinal Symptoms | ||||||||||
Stooling issues * | 1.4 ± 0.8 | 1.4 ± 0.7 | 1.5 ± 0.9 | 0.29 | 1.2 ± 0.4 | 1.1 ± 0.5 | 0.53 | 1.8 ± 1.0 | 2.1 ± 1.1 | 0.030 |
Constipation * | 1.3 ± 0.7 | 1.3 ± 0.6 | 1.4 ± 0.9 | 0.020 | 1.2 ± 0.5 | 1.2 ± 0.5 | 0.74 | 1.7 ± 0.8 | 2.1 ± 1.2 | 0.008 |
Diarrhea * | 1.2 ± 0.5 | 1.2 ± 0.5 | 1.3 ± 0.5 | 0.31 | 1.1 ± 0.3 | 1.1 ± 0.3 | 0.28 | 1.5 ± 0.6 | 1.8 ± 0.7 | 0.014 |
Gassiness * | 1.2 ± 0.5 | 1.2 ± 0.5 | 1.3 ± 0.6 | 0.16 | 1.1 ± 0.3 | 1.1 ± 0.2 | 0.47 | 1.5 ± 0.7 | 1.9 ± 0.8 | 0.008 |
Abdominal pain * | 1.2 ± 0.4 | 1.2 ± 0.4 | 1.3 ± 0.5 | 0.19 | 1.1 ± 0.3 | 1.1 ± 0.2 | 0.29 | 1.4 ± 0.6 | 1.2 ± 0.5 | 0.018 |
Bloating † | 1.3 ± 0.5 | 1.3 ± 0.5 | 1.3 ± 0.6 | 0.070 | 1.1 ± 0.3 | 1.1 ± 0.3 | 0.74 | 1.6 ± 0.7 | 1.9 ± 0.8 | 0.005 |
Gastrointestinal-related Behaviors | ||||||||||
Fussy and irritable * | 1.4 ± 0.7 | 1.4 ± 0.7 | 1.4 ± 0.7 | 0.89 | 1.2 ± 0.6 | 1.1 ± 0.3 | 0.34 | 1.7 ± 0.8 | 2.0 ± 0.8 | 0.24 |
Sleep problems ‡ | 1.4 ± 0.7 | 1.4 ± 0.7 | 1.4 ± 0.6 | 0.99 | 1.2 ± 0.5 | 1.2 ± 0.3 | 0.32 | 1.8 ± 0.8 | 2.0 ± 0.8 | 0.25 |
Sleepy during the day * | 1.4 ± 0.6 | 1.4 ± 0.6 | 1.4 ± 0.6 | 0.66 | 1.2 ± 0.4 | 1.2 ± 0.3 | 0.42 | 1.8 ± 0.7 | 1.9 ± 0.6 | 0.16 |
Waking up during the night § | 2.2 ± 1.0 | 2.2 ± 1.0 | 1.9 ± 0.9 | 0.009 | 2.1 ± 1.0 | 1.9 ± 0.9 | 0.030 | 2.4 ± 1.1 | 2.1 ± 0.8 | 0.16 |
Temperament Question | A2 GUM | Conventional Milk | p |
---|---|---|---|
Irritability: When having trouble completing a task (e.g., building, drawing, dressing), how often did your child get easily irritated? | 5.2 ± 1.4 | 5.4 ± 1.6 | 0.66 |
Irritability: When s/he asked for something and you said “no”, how often did your child have a temper tantrum? | 4.2 ± 1.6 | 4.5 ± 1.6 | 0.37 |
Attention focusing: When engaged in play with his/her favorite toy, how often did your child play for more than 10 min? | 4.8 ± 1.8 | 4.5 ± 1.9 | 0.061 |
Effortful control: During everyday activities, how often did your child pay attention to you right away when you called to him or her? | 4.8 ± 1.7 | 4.5 ± 1.9 | 0.099 |
Sociability: When a familiar adult, such as a relative or friend, visited your home, how often did your child want to interact with the adult? | 4.9 ± 1.7 | 4.7 ± 1.8 | 0.028 |
Sociability: When a familiar child came to your home, how often did your child seek out the company of the child? | 4.5 ± 1.8 | 4.2 ± 1.9 | 0.047 |
Activity level: While playing indoors, how often did your child run through the house? | 3.1 ± 1.7 | 3.4 ± 1.8 | 0.030 |
Soothability: When s/he was upset, how often did your child cry for more than 3 min, even when being comforted? | 5.1 ± 1.6 | 5.2 ± 1.4 | 0.99 |
Soothability: When s/he was upset, how often did your child become easily soothed? | 4.5 ± 1.6 | 4.2 ± 1.6 | 0.004 |
A2 GUM | Conventional Milk | p | |
---|---|---|---|
BASELINE | |||
Weight (kg) | 12.61 ± 2.36 | 12.44 ± 2.11 | 0.50 |
Weight (Z-score) | 0.63 ± 1.25 | 0.41 ± 0.94 | 0.08 |
Length (cm) | 86.11 ± 7.03 | 87.11 ± 7.09 | 0.19 |
Length (Z-score) | 0.20 ± 1.35 | 0.30 ± 1.31 | 0.52 |
Head circumference (cm) | 47.54 ± 3.17 | 47.80 ± 2.83 | 0.44 |
Head circumference (Z-score) | 0.06 ± 2.20 | 0.15 ± 1.78 | 0.70 |
BMI (kg/m2) | 17.03 ± 2.86 | 16.39 ± 1.88 | 0.02 |
BMI (Z-score) | 0.73 ± 1.75 | 0.32 ± 1.26 | 0.02 |
DAY 14 | |||
Weight (kg) | 13.09 ± 2.85 | 13.11 ± 2.59 | 0.95 |
Weight (Z-score) | 0.85 ± 1.36 | 0.77 ± 1.34 | 0.67 |
Length (cm) | 86.78 ± 6.97 | 87.27 ± 7.11 | 0.56 |
Length (Z-score) | 0.29 ± 1.23 | 0.24 ± 1.32 | 0.75 |
Head circumference (cm) | 48.27 ± 2.36 | 47.93 ± 3.06 | 0.27 |
Head circumference (Z-score) | 0.54 ± 1.61 | 0.21 ± 2.08 | 0.13 |
BMI (kg/m2) | 17.34 ± 2.91 | 17.21 ± 2.81 | 0.72 |
BMI (Z-score) | 0.94 ± 1.79 | 0.87 ± 1.71 | 0.75 |
A2 GUM | Conventional | Milk | p | ||||
---|---|---|---|---|---|---|---|
Participants (n) | % Events (n) | Participants (n) | % | Events (n) | |||
All Adverse Events | 10 | 3.9 | 19 | 5 | 3.9 | 8 | >0.999 |
Individual Adverse Events | |||||||
Weepiness or crying for no apparent reason | 2 | 0.8 | 2 | 0 | 0 | 0 | >0.999 |
Fever | 2 | 0.8 | 2 | 1 | 0.8 | 1 | 0.549 |
Constipation | 1 | 0.4 | 1 | 0 | 0 | 0 | >0.999 |
Hard stool | 1 | 0.4 | 3 | 1 | 0.8 | 1 | 0.553 |
Diarrhea | 1 | 0.4 | 1 | 0 | 0 | 0 | >0.999 |
Respiratory infection | 3 | 1.2 | 3 | 3 | 2.3 | 3 | 0.875 |
Others | 4 | 1.5 | 7 | 2 | 1.6 | 3 | 0.705 |
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Share and Cite
Meng, Y.; Zhou, Y.; Li, H.; Chen, Y.; Dominik, G.; Dong, J.; Tang, Y.; Saavedra, J.M.; Liu, J. Effectiveness of Growing-Up Milk Containing Only A2 β-Casein on Digestive Comfort in Toddlers: A Randomized Controlled Trial in China. Nutrients 2023, 15, 1313. https://doi.org/10.3390/nu15061313
Meng Y, Zhou Y, Li H, Chen Y, Dominik G, Dong J, Tang Y, Saavedra JM, Liu J. Effectiveness of Growing-Up Milk Containing Only A2 β-Casein on Digestive Comfort in Toddlers: A Randomized Controlled Trial in China. Nutrients. 2023; 15(6):1313. https://doi.org/10.3390/nu15061313
Chicago/Turabian StyleMeng, Ying, Yubo Zhou, Hongtian Li, Yipu Chen, Grathwohl Dominik, Jie Dong, Youchi Tang, Jose M. Saavedra, and Jianmeng Liu. 2023. "Effectiveness of Growing-Up Milk Containing Only A2 β-Casein on Digestive Comfort in Toddlers: A Randomized Controlled Trial in China" Nutrients 15, no. 6: 1313. https://doi.org/10.3390/nu15061313