Vitamin D given daily, weekly, or monthly has similar response (116 RCTs) – meta-analysis Aug 2023

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Efficacy of intermittent versus daily vitamin D supplementation on improving circulating 25(OH)D concentration: a Bayesian network meta-analysis of randomized controlled trials

Front. Nutr., 24 August 2023 Vol 10 - 2023 | https://doi.org/10.3389/fnut.2023.1168115
Yan Zhuang1,2† Zhe Zhu3† Peihan Chi1,2 Haibo Zhou1,2 Zhicheng Peng1,2 Haoyue Cheng1,2 Xing Xin1,2 Wenliang Luo1,2 Shuting Si1,2 Minjia Mo1,2 Danqing Chen4 Hui Liu5* Yunxian Yu1,2*

• 1 Dept of Public Health, Second Affiliated Hospital of Zhejiang U, School of Medicine, Hangzhou, China
• 2 Dept of Anesthesiology, Second Affiliated Hospital of Zhejiang U. School of Medicine, Hangzhou, China
• 3 The Second School of Clinical Medicine, Southern Medical U,, Guangzhou, China
• 4 Dept of Obstetrics and Gynecology, Woman's Hospital, School of Medicine, Zhejiang U,, Hangzhou, China
• 5 Central Lab, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China

50,000 weekly results in 107 nmol, (43 ng)

Background: Vitamin D deficiency is a widespread issue globally, resulting in increased use of vitamin D supplements. However, it is unclear whether intermittent (weekly or monthly) vitamin D supplementation is as effective as daily supplementation in improving circulating 25-hydroxyvitamin D [25(OH)D] levels.

Methods: Three databases including Medline, EMBASE, and the Cochrane Library were systematically searched up to 10 November 2020. The risk of bias was evaluated according to Cochrane Collaboration’s tool for rating methodological quality assessment. Direct and indirect comparisons between interventions and controls were performed by a Bayesian network meta-analysis (NMA), where the mean difference (MD) and its 95% confidence interval (CI) were used to indicate the efficacy.

Results: This NMA analysis included 116 RCTs with a total of 11,376 participants. Generally, we observed that 25(OH)D concentrations were significantly elevated regardless of vitamin D supplementation frequency. Although the findings of SUCRA indicated that daily vitamin D supplementation had a higher rank value than intermittent supplementation when the supplement dosage was similar, no statistically significant pooled mean differences of 25(OH)D concentration were noted between the daily supplementation group and intermittent supplementation group. Additionally, weekly supplementation with a total of 600,000 IU vitamin D supplementation during 3 months had the best efficacy in elevating 25(OH)D concentration (pooled MD = 63 nmol/L, 95%CI: 49–77). To achieve optimal 25(OH)D concentration (>75 nmol/L), we recommend 60,000 IU vitamin D supplementation monthly (~2,000 IU/day).

Conclusion: The efficacy of intermittent vitamin D supplementation was similar to daily supplementation. Coupled with its convenience, the frequency and dosage of intermittent vitamin D supplements were recommended to reach the optimal 25(OH)D level.
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28 References

1. Lips P. Worldwide status of vitamin D nutrition. J Steroid Biochem Mol Biol. (2010) 121:297-300. doi: 10.1016/j.jsbmb.2010.02.021
2. Autier P, Boniol M, Pizot C, Mullie P. Vitamin D status and ill health: a systematic review. Lancet Diabetes Endocrinol. (2014) 2:76-89. doi: 10.1016/S2213-8587(13)70165-7
3. Kahwati LC, LeBlanc E, Weber RP, Giger K, Clark R, Suvada K, et al. Screening for vitamin D deficiency in adults: updated evidence report and systematic review for the US preventive services task force. JAMA. (2021) 325:1443-63. doi: 10.1001/ jama.2020.26498
4. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. (2011) 96:1911-30. doi: 10.1210/jc.2011-0385
5. Mo M, Wang S, Chen Z, Muyiduli X, Wang S, Shen Y, et al. A systematic review and meta-analysis of the response of serum 25-hydroxyvitamin D concentration to vitamin D supplementation from RCTs from around the globe. Eur J Clin Nutr. (2019) 73:816-34. doi: 10.1038/s41430-019-0417-x
6. Ramezani Ahmadi A, Mohammadshahi M, Alizadeh A, Ahmadi Angali K, Jahanshahi A. Effects of vitamin D3 supplementation for 12 weeks on serum levels of anabolic hormones, anaerobic power, and aerobic performance in active male subjects: a randomized, double-blind, placebo-controlled trial. Eur J Sport Sci. (2020) 20:1355-67. doi: 10.1080/17461391.2020.1713218
7. Gronborg IM, Tetens I, Andersen EW, Kristensen M, Larsen REK, Tran TLL, et al. Effect of vitamin D fortified foods on bone markers and muscle strength in women of Pakistani and Danish origin living in Denmark: a randomised controlled trial. Nutr J. (2019) 18:82. doi: 10.1186/s12937-019-0504-9
8. Abdollahi R, Abiri B, Sarbakhsh P, Kashanian M, Vafa M. The effect of vitamin d supplement consumption on premenstrual syndrome in vitamin d-deficient young girls: a randomized, double-blind, placebo-controlled clinical trial. Complement Med Res. (2019) 26:336-42. doi: 10.1159/000500016
9. Rashad NM, Abd El-Fatah AH, Lashin ME-B, Abomandour HG, Allam RM. Impact of vitamin D supplementation on cardio-metabolic status and androgen profile in women with polycystic ovary syndrome: placebo-controlled clinical trial. Middle East Fertil Soc J. (2019) 24:24. doi: 10.1186/s43043-019-0005-y
10. Trummer C, Theiler-Schwetz V, Kollmann M, Wolfler M, Munzker J, Pilz S, et al. Effects of vitamin D supplementation on metabolic and endocrine parameters in healthy premenopausal women: a randomized controlled trial. Clin Nutr. (2020) 39:718-26. doi: 10.1016/j.clnu.2019.03.007
11. Al-Bayyari N, Al-Domi H, Zayed F, Hailat R, Eaton A. Androgens and hirsutism score of overweight women with polycystic ovary syndrome improved after vitamin D treatment: a randomized placebo controlled clinical trial. Clin Nutr. (2021) 40:870-8. doi: 10.1016/j.clnu.2020.09.024
12. Sari A, Akdogan Altun Z, Arifoglu Karaman C, Bilir Kaya B, Durmus B. Does vitamin D affect diabetic neuropathic pain and balance? J Pain Res. (2020) 13:171-9. doi: 10.2147/JPR.S203176
13. Mai S, Walker GE, Vietti R, Cattaldo S, Mele C, Priano L, et al. Acute vitamin D(3) supplementation in severe obesity: evaluation of multimeric adiponectin. Nutrients. (2017) 9:459. doi: 10.3390/nu9050459
14. Malihi Z, Wu Z, Lawes CMM, Scragg R. Adverse events from large dose vitamin D supplementation taken for one year or longer. J Steroid Biochem Mol Biol. (2019) 188:29-37. doi: 10.1016/j.jsbmb.2018.12.002
15. Mortensen C, Tetens I, Kristensen M, Snitkjaer P, Beck AM. Adherence and barriers to the vitamin D and calcium supplement recommendation at Danish nursing homes: a cross-sectional study. BMC Geriatr. (2022) 22:27. doi: 10.1186/s12877-021-02719-4
16. Hutton B, Salanti G, Caldwell DM, Chaimani A, Schmid CH, Cameron C, et al. The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations. Ann Intern Med. (2015) 162:777-84. doi: 10.7326/M14-2385
17. Higgins JP, Altman DG, Gotzsche PC, Juni P, Moher D, Oxman AD, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. (2011) 343:d5928. doi: 10.1136/bmj.d5928
18. Higgins JPTTJ, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, et al. Cochrane handbook for systematic reviews of interventions version 6.2 (updated February 2021). Cochrane: (2021) Available at: www.training.cochrane.org/handbook.
19. Shi J, Luo D, Weng H, Zeng XT, Lin L, Chu H, et al. Optimally estimating the sample standard deviation from the five-number summary. Res Synth Methods. (2020) 11:641-54. doi: 10.1002/jrsm.1429
20. Lu G, Ades AE. Combination of direct and indirect evidence in mixed treatment comparisons. Stat Med. (2004) 23:3105-24. doi: 10.1002/sim.1875
21. Salanti G, Ades AE, Ioannidis JP. Graphical methods and numerical summaries for presenting results from multiple-treatment meta-analysis: an overview and tutorial. J Clin Epidemiol. (2011) 64:163-71. doi: 10.1016/j.jclinepi.2010.03.016
22. Dias S, Welton NJ, Caldwell DM, Ades AE. Checking consistency in mixed treatment comparison meta-analysis. StatMed. (2010) 29:932-44. doi: 10.1002/sim.3767
23. Jackson D, Riley R, White IR. Multivariate meta-analysis: potential and promise. Stat Med. (2011) 30:2481-98. doi: 10.1002/sim.4172
24. Farrokhyar F, Sivakumar G, Savage K, Koziarz A, Jamshidi S, Ayeni OR, et al. Effects of vitamin D supplementation on serum 25-Hydroxyvitamin D concentrations and physical performance in athletes: a systematic review and Meta-analysis of randomized controlled trials. Sports Med. (2017) 47:2323-39. doi: 10.1007/ s40279-017-0749-4
25. Farapti F, Fadilla C, Yogiswara N, Adriani M. Effects of vitamin D supplementation on 25(OH)D concentrations and blood pressure in the elderly: a systematic review and meta-analysis. F1000Res. (2020) 9:633. doi: 10.12688/f1000research.24623.3
26. Meekins ME, Oberhelman SS, Lee BR, Gardner BM, Cha SS, Singh RJ, et al. Pharmacokinetics of daily versus monthly vitamin D3 supplementation in non-lactating women. Eur J Clin Nutr. (2014) 68:632-4. doi: 10.1038/ejcn.2013.278
27. Takacs I, Toth BE, Szekeres L, Szabo B, Bakos B, Lakatos P Randomized clinical trial to comparing efficacy of daily, weekly and monthly administration of vitamin D3. Endocrine. (2017) 55:60-5. doi: 10.1007/s12020-016-1137-9
28. Ish-Shalom S, Segal E, Salganik T, Raz B, Bromberg IL, Vieth R. Comparison of daily, weekly, and monthly vitamin D3 in ethanol dosing protocols for two months in elderly hip fracture patients. J Clin Endocrinol Metab. (2008) 93:3430-5. doi: 10.1210/ jc.2008-0241

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Daily vs. monthly oral vitamin D3 for treatment of symptomatic vitamin D deficiency in infants: a randomized controlled trial

Anupriya Gora , Preeti Singh , Ekta Debnath , Rajeev Kumar Malhotra and Anju Seth ORCID logo EMAIL logo
ournal of Pediatric Endocrinology and Metabolism https://doi.org/10.1515/jpem-2023-0146

Objectives
Compare the efficacy and safety of daily vs. monthly oral vitamin D3 in treating symptomatic vitamin D deficiency in infants.

Methods
90 infants with symptomatic vitamin D deficiency were randomized into Daily (D) [46 infants] and Bolus (B) [44 infants] groups to receive oral vitamin D3, daily (2000 IU/day) and bolus (60,000 IU/month) for three months respectively. Both groups received daily oral calcium @50 mg/kg/day. Serum calcium (Ca), phosphate (P), alkaline phosphatase (ALP), 25-hydroxy cholecalciferol [25(OH)D], parathyroid hormone (PTH) levels, urine calcium: creatinine ratio and radiological score were assessed at baseline, 4 and 12 weeks. At the end of 12 weeks, 78 infants were available for evaluation of efficacy and safety of both regimens.

Results
Both regimens led to a statistically significant increase in Ca and P levels and fall in ALP and PTH levels from baseline to 4 and 12 weeks of therapy, with no inter-group difference. Infants in group D had statistically significant higher mean 25(OH)D levels as compared to group B at 4 weeks (group D 130.89 ± 43.43 nmol/L, group B – 108.25 ± 32.40 nmol/L; p – 0.012) and 12 weeks (group D – 193.69 ± 32.47 nmol/L, group B – 153.85 ± 33.60 nmol/L; p<0.001). Eight infants [group D – 6/41 (14.6 %); group B – 2/37 (5.4 %), p=0.268] developed mild asymptomatic hypercalcemia without hypercalciuria at 12 weeks that corrected spontaneously within a week.

Conclusions
Both daily and monthly oral vitamin D3 in equivalent doses are efficacious and safe for treating symptomatic vitamin D deficiency in infants.

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Comparing efficacy and safety of monthly vs daily administration of oral cholecalciferol to correct vitamin D deficiency in adolescents

Jinjoo Choi 1 , Yunsoo Choe 2 & Seung Yang 1

Objectives: Vitamin D deficiency is prevalent in pediatric population. Since low compliance may inhibit appropriate vitamin D supplementation in daily dosing regimen, intermittent high dose administration may be considered. We aimed to evaluate the efficacy and safety of monthly administration of oral cholecalciferol compared with daily dosing regimen in adolescents with vitamin D deficiency.

Methods: This retrospective study included 175 vitamin D deficient (serum 25-hydroxyvitamin D 25OHD < 20 ng/mL) children with precocious puberty (64 boys, 10.5 ± 1.5 years) who received gonadotropin-releasing hormone agonist every 4 weeks between December 2019 and September 2021. Among them, 93 children received 1,000 IU of oral cholecalciferol every day [daily group] and 82 children received 25,000 IU of oral cholecalciferol every 4 weeks [monthly group]. Serum calcium and 25OHD levels were measured before and after treatment.

Results: Baseline 25OHD levels did not differ between two groups (13.9 ± 3.1 in daily group vs. 13.6 ± 3.5 ng/mL in monthly group, P=0.511). After median follow-up of 5.8months (interquartile range 4.7 – 6.8 months), increase in serum 25OHD concentrations were higher in monthly group than in daily group (9.7 ± 5.1 vs. 8.4 ± 7.1 ng/mL, P=0.027). The corrected dose-response was also higher in monthly group than in daily group (10.9 ± 5.7 vs. 8.4 ± 7.1 ng/mL increase per 1,000IU/daily, respectively, P=0.001). The proportion of patients attaining non-deficient vitamin D status (25OHD > 20 ng/mL) after treatment was 76.8% and 58.1% in monthly and daily groups, respectively (P=0.013). Hypercalcemia was not observed in both groups.

Conclusions: Monthly administration of oral cholecalciferol 25,000IU every 4 weeks showed higher efficacy and equivalent safety profiles compared with conventional daily administration in adolescents with vitamin D deficiency. It needs to be further investigated whether monthly administration of cholecalciferol have more benefits in pediatric population.

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Vitamin D Life – Weekly, Monthly Vitamin D are typically better than daily - many studies

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Vitamin D Life – Better than Daily contains:

31 items in BETTER THAN DAILY category

Non-daily (Bolus) is better:

1. Better compliance for everyone
   • Fewer opportunities to forget.
   • If happen to forget, just take the pill days or weeks later
   • Fewer times to have to take a pill - for those who dislike doing so
2. Non-daily is better the ~20% who have a poor Vitamin D Receptor
   • A high concentration gradient is one of 14 ways to get past Vitamin D Receptor limitations
   • So, while 80% get no extra benefit from non-daily dosing, 20% will get an extra benefit

• Vitamin D given daily, weekly, or monthly has similar response (116 RCTs) – meta-analysis Aug 2023
• 44 percent of successful RCTs in Vitamin D Life used non-daily dosing - Nov 2020
• Monthly vitamin D dosing better for children than daily (again) - Oct 2023

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