3X less muscle atrophy after ACL surgery if more than 40 ng of vitamin D – May 2022

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Anterior Cruciate Ligament Reconstruction Upregulates Vitamin D Activating Pathways within the Quadriceps

FASEB J . 2022 May;36 Suppl 1. doi: 10.1096/fasebj.2022.36.S1.L7890. abstract of presentation
Jean L. Fry,Camille R. Brightwell,Christine M. Latham,Brooke D. Munson,Brian Noehren,Christopher S. Fry
Supported by NIH R01 AR072061, R01 AR071398-04S1, K23 AR062069

Anterior cruciate ligament (ACL) tears are prevalent sport-related injuries that result in protracted quadriceps atrophy and weakness despite surgical reconstruction and physical therapy. Vitamin D and its receptor are integral for skeletal muscle development and homeostasis. In addition, vitamin D status is positively associated with muscle size and strength. If the vitamin D receptor and related enzymes are upregulated with ACL injury and reconstruction, then overall vitamin D status may be an important effector of recovery. Concentrations of vitamin D needed to support optimal recovery may differ from typical clinical cut points used to diagnose vitamin D deficiency, which could have powerful therapeutic implications following ACL injury and reconstruction. This is especially important given recent research showing over 50% of athletes have vitamin D inadequacy. We hypothesized that subjects with circulating vitamin D sufficient to suppress parathyroid hormone secretion (≥ 40 ng/mL) would be better protected against quadriceps atrophy at the conclusion of rehabilitation. Muscle biopsies (vastus lateralis) were obtained from ACL-injured and Healthy limbs of 16 participants (6M,10F; 19±5yr, body mass index: 25.1±3.7kg/m2) prior to surgical reconstruction, 1 week following reconstruction (Recon), and following the completion of post-surgical rehabilitation (6 months following surgery, Post-Rehab). RNA was isolated from all quadriceps biopsies, followed by library construction, sequencing, and bioinformatics analysis. Transcript abundance of vitamin D activating pathway regulators (vitamin D receptor [VDR], and Cytochrome P450 2R1 [CYP2R1] and Family 27 Subfamily B Member 1 [CYP27B1]) was assessed following analysis using DESeq2 and false discovery rate (FDR) adjustment of p-values. Additionally, 25-hydroxy vitamin D (25(OH)D) was assessed in serum samples obtained at the time of reconstruction surgery. Quadriceps fiber cross-sectional area was measured via laminin immunohistochemistry. Recon (1 week post-surgery) muscle showed increased transcript abundance of the vitamin D receptor, VDR(elevated 7.8 fold, FDR<0.05), and vitamin D-activating pathway regulators CYP2R1 (elevated 1.5 fold, FDR<0.05) and CYP27B1 (elevated 2.6 fold, FDR<0.05) when compared to the Healthy limb.

Following the completion of rehabilitation at the 6-month follow-up, participants with 25(OH)D

• above 40 ng/mL showed 6.4% atrophy of quadriceps fiber size compared to
• 22.8% atrophy in participants with 25(OH)D below 40 ng/mL (p=0.06).

These findings provide evidence for surgically induced elevations in the vitamin D activating pathway within skeletal muscle. Upregulation of the vitamin D activating pathway may support quadriceps mitochondrial health and satellite cell activity and self-renewal capacity, both of which are compromised following ACL reconstruction. In addition, elevated vitamin D concentrations may protect against protracted quadriceps atrophy. Future research should investigate if manipulation of vitamin D concentrations can enhance quadriceps functional recovery following ACL reconstruction.

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VitaminDWiki - Low Vitamin D resulted in 1.8X increase in ACL knee tears in next 2 years – April 2023

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VitaminDWiki - Optimum category contains

The RDA is barely enough for the bones to survive.
   Need an optimal level for the body to thrive

99 items in Optimum Vitamin D category

Example pages

• Is 50 ng of vitamin D too high, just right, or not enough
• More than 30 ng of vitamin D is needed for many diseases - Feb 2022 has

• Saudi study defines normal Vitamin D level to be 50 to 70 ng (diabetes, etc.) - June 2020
• Need 40 to 60 ng of Vitamin D – 48 scientists call for action – 2015
• Vitamin D RDA of 600 IU is not enough - global RCT meta-analysis March 2019
• Vitamin D sufficiency 10 to 30 ng, optimal 40 to 80 ng (no consensus)– May 2018
• 4 X fewer visits to Dr. after getting high level of vitamin D (Interview with transcript) - Jan 3, 2022
• Vitamin D sufficiency 10 to 30 ng, optimal 40 to 80 ng (no consensus)– May 2018
• Sports benefits from up to 50 ng of Vitamin – meta-analysis - Nov 2012
• Vitamin D of 32 to 60 ng is needed before, during, and after pregnancy – Dec 2012
• Hypothesis by VitaminDWiki – Vitamin D levels are no longer limited by evolution
• VitaminDWiki pages with HIGH-DOSE in title 878 as of Nov 2024

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Health problems often need >30 ng of Vitamin D

• Is 50 ng of vitamin D too high, just right, or not enough contains

• Vitamin D	Treats
  150 ng	Multiple Sclerosis *
  80 ng	Cluster Headache * Reduced office visits by 4X *
  70 ng	Sleep *
  60 ng	Breast Cancer death reduced 60% Preeclampsia RCT
  50 ng	COVID-19 Fertility Psoriasis Infections Review Infection after surgery
  40 ng	Breast Cancer 65% lower risk Depression ACL recovery Hypertension Asthma?
  30 ng	Rickets

* Evolution of experiments with patients, often also need co-factors

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VitaminDWiki - Consensus Vitamin D category contains

70 Vitamin D consensus publications

• French pediatric consensus: 30 – 60 ng of Vitamin D – Feb 2022
• 15 Clinical guidelines now recommend vitamin D – Nov 2021
• 34 clinical practice Vitamin D guidelines, huge diversity – Nov 2021
• Minimum National Vitamin D recommendations range from 200 to 4,000 IU – July 2021
• Controversies and consensus in Vitamin D – 3rd Conference Sept 2019
• Vitamin D Consensus 4,000 to 10,000 IU, upper limit 100 ng – Italy 2018
• 4,000 IU of Vitamin D is OK - 19 organizations agree - 2018 six say 10,000 IU is OK
• 17 reasons why are doctors reluctant to accept vitamin D
  • Doctors and medical communities appear to be poor audiences to convince that vitamin D is good