Faster growth in infants getting 1200 IU of Vitamin D – RCT July 2022

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Collagen X biomarker (CXM), linear growth, and bone development in a Vitamin D intervention study in Infants

J Bone Miner Res. 2022 Jul 15. doi: 10.1002/jbmr.4650   PDF is behind paywall
Helena H Hauta-Alus 1 2 3 4, Elisa M Holmlund-Suila 1 2, Saara M Valkama 1 2, Maria Enlund-Cerullo 1 2, Jenni Rosendahl 1 2, Ryan F Coghlan 5, Sture Andersson 1, Outi Mäkitie 1 6 7

Collagen X biomarker (CXM) is suggested to be a biomarker of linear growth velocity. However, early childhood data are limited. This study examines the relationship of CXM to the linear growth rate and bone development, including the possible modifying effects of vitamin D supplementation. We analyzed a cohort of 276 term-born children participating in the Vitamin D Intervention in Infants (VIDI) study. Infants received 10 μg/d (group-10) or 30 μg/d (group-30) vitamin D3 supplementation for the first two years of life. CXM and length were measured at 12 and 24 months of age. Tibial bone mineral content (BMC), volumetric bone mineral density (vBMD), cross-sectional area (CSA), polar-moment of inertia (PMI), and periosteal circumference (PsC) were measured using peripheral quantitative computed tomography (pQCT) at 12 and 24 months. We calculated linear growth as length velocity (cm/year) and the growth rate in length (SD unit).

The mean (SD) CXM values were 40.2 (17.4) ng/ml at 12 months and 38.1 (12.0) ng/ml at 24 months of age (p=0.12).
CXM associated with linear growth during the two years follow-up (p=0.041) but not with bone (p=0.53). Infants in group-30 in the highest tertile of CXM exhibited an accelerated mean growth rate in length compared with the intermediate tertile (mean difference (95% CI): -0.50 (-0.98, -0.01) SD unit, p=0.044) but not in the group-10 (p=0.062) at 12 months.

Linear association of CXM and growth rate until 12 months was weak, but at 24 months CXM associated with both length velocity (B for 1 increment of √CXM (95% CI): 0.32 (0.12, 0.52) cm/year, p=0.002) and growth rate in length (0.20 (0.08, 0.32) SD unit, p=0.002).

To conclude, CXM may not reliably reflect linear growth from birth to 12 months of age, but its correlation with growth velocity improves during the second year of life.

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VitaminDWiki - Infant-Child category has 854 items and starts with__

• No consensus on MINIMUM International Units (IU) for healthy infant of normal weight
• 400 IU Vitamin D is no longer enough
  Was OK in the past century, but D levels have been dropping for a great many reasons.
  FDA doubles the amount of vitamin D permitted in milk – July 2016
• No consensus: range is 600 to 1600 IU – based on many randomized controlled trials
• Review of 400 IU to 2000 IU daily and higher if non-daily
• Fewer pre-infants were vitamin D deficient when they got 800 IU – RCT Feb 2014
• 1600 IU was the conclusion of three JAMA studies
     1000 IU recommended in France and Finland – 2013 - appears to be a good level
• 5X less mite allergy after add vitamin D
• Child bone fractures with low vitamin D were 55X more likely to need surgery
• 75 % of SIDS had low vitamin D
• Children stayed in ICU 3.5 days longer if low vitamin D – Dec 2015
• 5 out of 6 children who died in pediatric critical care unit had low vitamin D – May 2014
• Infants have gotten free 400 IU of vitamin D in Turkey since 2005, More for longer would be even better – Feb 2022
• Preemies should have vitamin D supplements – reaching an agreement – April 2021
• Vitamin D loading dose was as effective as daily dosing (rickets in this case) – RCT July 2021

Having a good level of vitamin D cuts in half the amount of:

• Asthma, Chronic illness, Doctor visits, Allergies, infection
  Respiratory Tract Infection, Growing pains, Bed wetting

Need even more IUs of vitamin D to get a good level if;

• Have little vitamin D: premie, twin, mother did not get much sun access
• Get little vitamin D: dark skin, little access to sun
• Vitamin D is consumed faster than normal due to sickness
• Older (need at least 100 IU/kilogram, far more if obese)
• Not get any vitamin D from formula (breast fed) or (fortified) milk
  Note – formula does not even provide 400 IU of vitamin D daily

Infants-Children need Vitamin D

• Sun is great – well known for 1,000’s of years.
  US govt (1934) even said infants should be out in the sun
• One country recommended 2,000 IU daily for decades – with no known problems
• As with adults, infants and children can have loading doses and rarely need tests
• Daily dose appears to be best, but monthly seems OK
• Vitamin D is typically given to infants in the form of drops
     big difference in taste between brands
     can also use water-soluable form of vitamin D in milk, food, juice,
• Infants have evolved to get a big boost of vitamin D immediately after birth
  Colostrum has 3X more vitamin D than breast milk - provided the mother has any vitamin D to spare
• 100 IU per kg of infant July 2011, Poland etc.
  
  More than 100 IU/kg is probably better

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Less frequent dosing is effective (and often better than daily)

• Vitamin D loading dose was as effective as daily dosing (rickets in this case) – RCT July 2021
• Vitamin D for infants – 100,000 IU monthly is better than 400 IU daily – RCT Oct 2020
• 100,000 IU Vitamin D weekly for 4 weeks is safe and effective for children – May 2019

Better than Daily has the following

33 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 dose many days later
   • Fewer times to have to take a pill - for those who dislike doing so
2. Non-daily gets more vitamin D to the cells for 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

• Weekly Vitamin D better than daily – lower cost, less pill burden, perhaps 1.5X better response – meta-analysis Oct 2024
• Vitamin D given daily, weekly, or monthly has similar response (116 RCTs) – meta-analysis Aug 2023
• 44 percent of successful RCTs in VitaminDWiki used non-daily dosing - Nov 2020
• Monthly vitamin D dosing better for children than daily (again) - Oct 2023

Obese need more vitamin D - including obese childen

• Obese children had 2.2 X less response to a single dose of Vitamin D – Oct 2020