Overview Muscles and Vitamin D

To build muscles you need more than just Vitamin D
   also need Exercise, Protein, Magnesium, Omega-3, and activated Vitamin D Receptors
     In fact, Vitamin D monotherapy sometimes DECREASES muscles.
Notes on Vitamin D Receptor:
Vitamin D Receptors get vitamin D in the blood to the muscle cells
Approximately 20% of people have poor vitamin D receptors
As people age, their Vitamin D receptors also become less activated
There are 12+ low-cost activators for the Vitamin D Receptor
122+ Vitamin D Life pages have MUSCLE in the title
Dr. Greger on Vitamin D and Muscles - May 2020
Vitamin D Supplements for Increasing Aging Muscle Strength

• "We have known for more than 400 years that muscle weakness is a common presenting symptom of vitamin D deficiency"
• conservative "U.S. Preventive Services Task Force, the official prevention guideline setting body, and the American Geriatric Society to “recommend vitamin D supplementation for persons who are at high risk of falls.”
• AGS recommends 4,000 IU to capture 92 percent of the population"

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The Role of Vitamin D in Skeletal Muscle Repair and Regeneration in Animal Models and Humans: A Systematic Review - Oct 2023

Nutrients 2023, 15(20), 4377; https://doi.org/10.3390/nu15204377
by Miguel Agoncillo 1,†,Josephine Yu 1,†ORCID andJenny E. Gunton 1,2,3,*ORCID
Portion of the table of contents

Vitamin D deficiency, prevalent worldwide, is linked to muscle weakness, sarcopenia, and falls. Muscle regeneration is a vital process that allows for skeletal muscle tissue maintenance and repair after injury. PubMed and Web of Science were used to search for studies published prior to May 2023. We assessed eligible studies that discussed the relationship between vitamin D, muscle regeneration in this review. Overall, the literature reports strong associations between vitamin D and skeletal myocyte size, and muscle regeneration. In vitro studies in skeletal muscle cells derived from mice and humans showed vitamin D played a role in regulating myoblast growth, size, and gene expression. Animal studies, primarily in mice, demonstrate vitamin D’s positive effects on skeletal muscle function, such as improved grip strength and endurance. These studies encompass vitamin D diet research, genetically modified models, and disease-related mouse models. Relatively few studies looked at muscle function after injury, but these also support a role for vitamin D in muscle recovery.
The human studies have also reported that vitamin D deficiency decreases muscle grip strength and gait speed, especially in the elderly population.
Finally, human studies reported the benefits of vitamin D supplementation and achieving optimal serum vitamin D levels in muscle recovery after eccentric exercise and surgery.
However, there were no benefits in rotator cuff injury studies, suggesting that repair mechanisms for muscle/ligament tears may be less reliant on vitamin D.
In summary, vitamin D plays a crucial role in skeletal muscle function, structural integrity, and regeneration, potentially offering therapeutic benefits to patients with musculoskeletal diseases and in post-operative recovery.
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Muscle Health and Vitamin D - Meta-analysis Sept 2021 (not help much - ignored dose size)

Vitamin D and Muscle Health: A Systematic Review and Meta‐analysis of Randomized Placebo‐Controlled Trials
Journal of Bone and Mineral Research, Vol 36, Issue 9, Pages 1651–1660, https://doi.org/10.1002/jbmr.4412
Lise Sofie Bislev, Diana Grove‐Laugesen, Lars Rejnmark

The objective of this study was to investigate the effects of vitamin D supplementation versus placebo on muscle health. For this systematic review and trial‐level meta‐analysis of placebo‐controlled trials, a systematic search of randomized controlled trials published until October 2020 was performed in Medline, Embase, and Google Scholar. We included studies in humans (except athletes) on supplementation with vitamin D2 or D3 versus placebo, regardless of administration form (daily, bolus, and duration) with or without calcium co‐supplementation. The predefined endpoints were physical performance reported as timed up and go test (TUG; seconds), chair rising test (seconds), 6‐minute walking distance (m), and Short Physical Performance Battery (SPPB; points). Furthermore, endpoints were maximum muscle strength (Newton) measured at handgrip, elbow flexion, elbow extension, knee flexion, and knee extension, as well as muscle (lean tissue) mass (kg). Falls were not included in the analysis. Cochrane Review Manager (version 5.4.1.) calculating mean difference (MD) using a random effect model was used.
In total, 54 randomized controlled trials involving 8747 individuals were included. Vitamin D versus placebo was associated with a

• significantly longer time spent performing the TUG (MD 0.15 [95% confidence interval (CI) 0.03 to 0.26] seconds, N = 19 studies, I2 = 0%, n = 5223 participants) and a
• significant lower maximum knee flexion strength (MD –3.3 [−6.63 to −0.03] Newton, N = 12 studies, I2 = 0%, n = 765 participants).

Total score in the SPPB showed a tendency toward worsening in response to vitamin D compared with placebo (MD −0.18 [−0.37 to 0.01] points, N = 8 studies, I2 = 0%, n = 856 participants).
Other measures of muscle health did not show between‐group differences. In subgroup analyses, including studies with low vitamin D levels, effects of vitamin D supplementation did not differ from placebo.
Available evidence does not support a beneficial effect of vitamin D supplementation on muscle health. Vitamin D may have adverse effects on muscle health, which needs to be considered when recommending vitamin D supplementation. © 2021 American Society for Bone and Mineral Research (ASBMR).
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Vitamin D Promotes Skeletal Muscle Regeneration and Mitochondrial Health – April 2021

Front. Physiol., 13 April 2021 Vol 12 - 2021 | https://doi.org/10.3389/fphys.2021.660498

• 1 Department of Athletic Training and Clinical Nutrition, University of Kentucky, Lexington, KY, United States
• 2 Center for Muscle Biology, College of Health Sciences, University of Kentucky, Lexington, KY, United States

Vitamin D is an essential nutrient for the maintenance of skeletal muscle and bone health. The vitamin D receptor (VDR) is present in muscle, as is CYP27B1, the enzyme that hydroxylates 25(OH)D to its active form, 1,25(OH)D. Furthermore, mounting evidence suggests that vitamin D may play an important role during muscle damage and regeneration. Muscle damage is characterized by compromised muscle fiber architecture, disruption of contractile protein integrity, and mitochondrial dysfunction. Muscle regeneration is a complex process that involves restoration of mitochondrial function and activation of satellite cells (SC), the resident skeletal muscle stem cells. VDR expression is strongly upregulated following injury, particularly in central nuclei and SCs in animal models of muscle injury. Mechanistic studies provide some insight into the possible role of vitamin D activity in injured muscle. In vitro and in vivo rodent studies show that vitamin D mitigates reactive oxygen species (ROS) production, augments antioxidant capacity, and prevents oxidative stress, a common antagonist in muscle damage. Additionally, VDR knockdown results in decreased mitochondrial oxidative capacity and ATP production, suggesting that vitamin D is crucial for mitochondrial oxidative phosphorylation capacity; an important driver of muscle regeneration. Vitamin D regulation of mitochondrial health may also have implications for SC activity and self-renewal capacity, which could further affect muscle regeneration. However, the optimal timing, form and dose of vitamin D, as well as the mechanism by which vitamin D contributes to maintenance and restoration of muscle strength following injury, have not been determined. More research is needed to determine mechanistic action of 1,25(OH)D on mitochondria and SCs, as well as how this action manifests following muscle injury in vivo. Moreover, standardization in vitamin D sufficiency cut-points, time-course study of the efficacy of vitamin D administration, and comparison of multiple analogs of vitamin D are necessary to elucidate the potential of vitamin D as a significant contributor to muscle regeneration following injury. Here we will review the contribution of vitamin D to skeletal muscle regeneration following injury.
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Vitamin D helps muscles in many ways – Sept 2021

Muscle Regeneration and Function in Sports: A Focus on Vitamin D
Medicina 2021, 57(10), 1015; https://doi.org/10.3390/medicina57101015
by Giovanni Iolascon 1,Antimo Moretti 1,*OrcID,Marco Paoletta 1OrcID,Sara Liguori 1 andOmbretta Di Munno 2

• 1 Department of Medical and Surgical Specialties and Dentistry, University of Campania “Luigi Vanvitelli”, Via de Crecchio, 6, 80138 Naples, Italy
• 2 Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Pisa, 56122 Pisa, Italy

Muscle is one of the main targets for the biological effects of vitamin D. This hormone modulates several functions of skeletal muscles, from development to tissue repair after injury, through genomic and non-genomic mechanisms. Vitamin D deficiency and supplementation seem to significantly affect muscle strength in different populations, including athletes, although optimal serum 25(OH)D3 level for sport performance has not been defined so far.
Additionally, vitamin D deficiency results in myopathy characterized by

• fast-twitch fiber atrophy,
• fatty infiltration, and
• fibrosis.

However, less is known about regenerative effects of vitamin D supplementation after sport-related muscle injuries. Vitamin D receptor (VDR) is particularly expressed in the embryonic mesoderm during intrauterine life and in satellite cells at all stages of life for recovery of the skeletal muscle after injury. Vitamin D supplementation enhances muscle differentiation, growth, and regeneration by increasing the expression of myogenic factors in satellite cells. The objective of this narrative review is to describe the role of vitamin D in sport-related muscle injury and tissue regeneration.
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138+ Vitamin D Life pages with MUSCLE, etc in the title

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Muscles and Seniors in Vitamin D Life

• Age-related loss of strength (Dynapenia) 1.7X more likely if low Vitamin D – Sept 2022
• Low muscle mass at least 2X more likely if low Vitamin D (Korea, all ages) – Dec 2020
• Less muscle loss associated with eating more fish (Omega-3, Vitamin D, Magnesium, etc) – Jan 2020
• Vitamin D supplementation help muscles of seniors who are vitamin D deficient – meta-analysis July 2014
• Dietary Protein, Muscle and Physical Function in the Very Old – July 2018
• Low Vitamin D breaks down muscle by interferring with protein - Editorial Nov 2013
• Seniors gained 0.3 kg of muscle in 6 weeks with 800 IU and Leucine protein – Aug 2017
• Sarcopenia (muscle loss) fought by Vitamin D, exercise and protein - many studies
• MRI of elderly skeletal muscle lacking vitamin D – April 2014
• Overview Fractures and Falls and Vitamin D - poor muscles ==> fall more frequently

Exercise helps build muscles

• Exercise plus vitamin D increases elderly muscles (Nordic walking in this case) – RCT Sept 2018
• Muscle strength of Judo athletes increased 13 percent following single dose of 150,000 IU vitamin D – RCT Nov 2015

Omega-3

• Sarcopenia reduction: Protein, Leucine, Omega-3, Vitamin D, and exercise - hypothesis Aug 2018
• Muscle loss (sarcopenia) may be both prevented and treated by Omega-3 – Feb 2019

Overview Sports and vitamin D

Overview Sports and vitamin D has the following summary
Athletes are helped by vitamin D by:

1. Faster reaction time
2. Far fewer colds/flus during the winter
3. Less sore/tired after a workout
4. Fewer micro-cracks and broken bones
5. Bones which do break heal much more quickly
6. Increased VO2 and exercise endurance Feb 2011
7. Indoor athletes especially need vitamin D
8. Professional indoor athletes are starting to take vitamin D and/or use UV beds
9. Olympic athletes have used UV/vitamin D since the 1930's
10. The biggest gain from the use of vitamin D is by those who exercise less than 2 hours per day.
11. Reduced muscle fatigue with 10,000 IU vitamin D daily
12. Muscle strength improved when vitamin D added: 3 Meta-analysis
13. Reduced Concussions
    See also: Sports and Vitamin D category 273 items

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The Roles of Vitamin D in Skeletal Muscle Feb 2013

The Roles of Vitamin D in Skeletal Muscle: Form, Function, and Metabolism
Endocrine Reviews February 1, 2013 vol. 34 no. 1 33-83
Christian M. Girgis, Roderick J. Clifton-Bligh, Mark W. Hamrick, Michael F. Holick and Jenny E. Gunton
Garvan Institute of Medical Research (C.M.G., J.E.G.) and St. Vincent's Clinical School (J.E.G.), University of New South Wales, Sydney, New South Wales 2010, Australia; Faculty of Medicine (C.M.G., R.J.C.-B., J.E.G.), University of Sydney, Sydney, New South Wales 2052, Australia; The Kolling Institute of Medical Research (R.J.C.-B.) and Royal North Shore Hospital (R.J.C.-B.), Sydney, New South Wales 2065, Australia; Georgia Health Sciences University (M.W.H.), Augusta, Georgia 30912; Boston University Medical Center (M.F.H.), Boston, Massachusetts 02118; and Department of Endocrinology and Diabetes (J.E.G.), Westmead Hospital, Sydney, New South Wales 2145, Australia
Address requests for reprints to: Dr. Christian M. Girgis or Associate Professor Jenny E. Gunton, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, New South Wales, Australia. E-mail: c.girgis at garvan.org.au or j.gunton at garvan.org.au.

Beyond its established role in bone and mineral homeostasis, there is emerging evidence that vitamin D exerts a range of effects in skeletal muscle. Reports of profound muscle weakness and changes in the muscle morphology of adults with vitamin D deficiency have long been described. These reports have been supplemented by numerous trials assessing the impact of vitamin D on muscle strength and mass and falls in predominantly elderly and deficient populations. At a basic level, animal models have confirmed that vitamin D deficiency and congenital aberrations in the vitamin D endocrine system may result in muscle weakness. To explain these effects, some molecular mechanisms by which vitamin D impacts on muscle cell differentiation, intracellular calcium handling, and genomic activity have been elucidated. There are also suggestions that vitamin D alters muscle metabolism, specifically its sensitivity to insulin, which is a pertinent feature in the pathophysiology of insulin resistance and type 2 diabetes. We will review the range of human clinical, animal, and cell studies that address the impact of vitamin D in skeletal muscle, and discuss the controversial issues. This is a vibrant field of research and one that continues to extend the frontiers of knowledge of vitamin D's broad functional repertoire.

I. Introduction

II. Background Physiology

A. The vitamin D pathway
B. Skeletal muscle physiology
C. Calcium and muscle contraction
D. Calcium and exercise-related glucose uptake
E. Calcium and insulin-stimulated glucose uptake

III. Vitamin D and Muscle: Cell Models

A. VDR in muscle
B. Calcium homeostasis
C. Phosphate homeostasis
D. Proliferation and differentiation
E. Muscle contractile proteins
F. Phospholipid composition
G. Bone-muscle cross-talk and vitamin D
H. Cell models and molecular pathways for insulin signaling and diabetes

IV. Vitamin D and Muscle: Studies in Animal Models

A.1 VDRKO mice
B. Other animal models
C. Animal studies on insulin sensitivity and diabetes
D. Summary: vitamin D and muscle function in animal studies

V. VDR Polymorphisms and Muscle Function

A. FokI polymorphisms
B. BsmI polymorphisms
C. VDR polymorphisms and insulin resistance/type 2 diabetes

VI. Vitamin D and Muscle: Human Studies

A. Myopathy
B. Myalgia and vitamin D deficiency
C. Fibromyalgia
D. Drug-related myopathy and vitamin D
E. Falls and vitamin D
F. Muscle strength and physical performance
G. Muscle morphology and electromyography (EMG)
H. Insulin sensitivity and glucose handling VII. Conclusions

Conclusions

• Vitamin D exerts rapid and genomic effects in primary muscle cells and cell lines.
  These effects relate to intracellular calcium handling,differentiation and contractile protein composition.
• In vivo, it is not clear whether VDR is expressed in adult skeletal muscle.
• Whole-body VDRKO mice and vitamin D-deficient animals display significant defects in muscle function and development.
• In humans, single nucleotide polymorphisms in the gene encoding VDR have been associated with differences in muscle strength.
• Changes in muscle morphology in humans with severe vitamin D deficiency have been reported since the 1970s.
• Proximal myopathy and muscle pain in subjects with severe vitamin D deficiency resolve following vitamin D supplementation.
• Associations between vitamin D deficiency, muscle weakness and falls are confounded by factors including frailty and lower exposure to sunlight.
  Clinical parameters of muscle function are not standardized making data aggregation difficult.
• Randomized data suggest that vitamin D supplementation may reduce falls in older individuals but not all studies support this conclusion.
• The recommended dose of vitamin D supplementation and vitamin D targets remain hotly contested issues.

Outstanding questions

• Does the VDR exist in fully differentiated adult muscle and does it have physiological relevance at this site?
  Or rather, as suggested by in vitro studies, is its role predominantly related to the function of immature muscle cells such as in myogenesis?
• Are changes in muscle function and morphology directly related to vitamin D or indirectly to its effects in calcium and mineral homeostasis?
• Does skeletal muscle possess the ability to 1-a-hydroxylate 25D at any stage in its development?
• As suggested by studies on phosphate handling in myocytes, does 25D itself exert direct effects on muscle?
• Is vitamin D deficiency or its reversal an important consideration among those with other muscle disorders such as congenital dystrophies and acquired immune-related myositis?

56 page PDF is attached at the bottom of this page

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Small Vitamin D doses given for a few months do not improve muscles - meta-analysis Oct 2023

 Download the PDF from Vitamin D Life
Most of the trials were 3 months or shorter
Only one trial lasted 4 months
Full response to Vitamin D takes at least 4 months
At which point muscle growth is possible, provided there is exercise, etc

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48,000 IU monthly for a year did not help elderly muscles- June 2019

No effect of monthly supplementation with 12000 IU, 24000 IU or 48000 IU vitamin D3 for one year on muscle function: The vitamin D in older people study.
J Steroid Biochem Mol Biol. 2019 Jun;190:256-262. doi: 10.1016/j.jsbmb.2018.12.008. Epub 2018 Dec 21.Ranathunga RMTK1, Hill TR2, Mathers JC2, Francis RM3, Prentice A4, Schoenmakers I5, Aspray TJ6; Vitamin D in Older People Study group.

Vitamin D plays a role in muscle function through genomic and non-genomic processes. The objective of this RCT was to determine the effect of monthly supplemental vitamin D3 onmuscle function in 70+ years old adults. Participants (n = 379) were randomized to receive, 12,000 IU, 24,000 IU or 48,000 IU of vitamin D3 monthly for 12 months. Standardized Hand Grip Strength (GS) and Timed-Up and Go (TUG) were measured before and after vitamin D3 supplementation. Fasting total plasma 25 hydroxyvitamin D (25OHD) and Parathyroid Hormone (PTH) concentrations were measured by Liquid Chromatography Tandem Mass Spectrometry (LC-MSMS) and immunoassay, respectively. Baseline plasma 25OHD concentrations were 41.3 (SD 19.9), 39.5 (SD 20.6), 38.9 (SD 19.7) nmol/L; GS values were 28.5 (SD 13.4), 28.8 (SD 13.0) and 28.1 (SD 12.1) kg and TUG test values were 10.8 (SD 2.5), 11.6 (SD 2.9) and 11.9 (SD 3.6) s for the 12,000 IU, 24,000 IU and 48,000 IU dose groups, respectively. Baseline plasma 25OHD concentration < 25 nmol/L was associated with lower GS (P = 0.003). Post-interventional plasma 25OHD concentrations increased to 55.9 (SD 15.6), 64.6 (SD15.3) and 79.0 (SD 15.1) nmol/L in the 12,000 IU, 24,000 IU and 48,000 IU dose groups, respectively and there was a significant dose-related response in post-interventional plasma 25OHD concentration (p<0.0001). Post-interventional GS values were 24.1 (SD 10.1), 26.2 (SD10.6) and 25.7 (SD 9.4) kg and TUG test values were 11.5 (SD 2.6), 12.0 (SD 3.7) and 11.9 (SD 3.2) s for 12,000 IU, 24,000 IU and 48,000 IU dose groups, respectively. The change (Δ) in GS and TUG from pre to post-intervention was not different between treatment groups before and after the adjustment for confounders, suggesting no effect of the intervention. Plasma 25OHD concentration was not associated with GS and TUG test after supplementation. In conclusion, plasma 25OHD concentration < 25 nmol/L was associated with lower GS at baseline. However, monthly vitamin D3 supplementation with 12,000 IU, 24,000 IU and 48,000 IU, for 12 months had no effect on muscle function in older adults aged 70+ years. Trial Registration : EudraCT 2011-004890-10 and ISRCTN35648481.
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Sarcopenia: 3.3 X higher risk if low bio-available vitamin D - August 2021

Comparative analysis of the association between various serum vitamin D biomarkers and sarcopenia
J Clin Lab Anal. 2021 Aug 5;e23946. doi: 10.1002/jcla.23946
Jun-Il Yoo 1, Hye Jin Chung 2, Bo Gyu Kim 3, Youn-Kwan Jung 3, Kyung-Wan Baek 1, Myung-Geun Song 1, Min-Chul Cho 4 5

Total Vitamin D - not bio-available

 Download the PDF from Vitamin D Life

Background: Vitamin D status is associated with muscle strength and maintenance of muscle fibers. However, which serum vitamin D biomarker better reflects sarcopenia remains unclear. The aim of this study was to investigate associations between various serum vitamin D biomarkers (total 25-hydroxy vitamin D [25(OH)D], bioavailable 25(OH)D, 24,25-dihydroxyvitamin D [24,25(OH)2 D], and vitamin D metabolite ratio [VMR]) and sarcopenia.

Methods: The data for 83 hip fracture patients were finally included in the analysis. Sarcopenia was defined according to the Asia Working Group for Sarcopenia (AWGS) criteria. Measurements of 24,25(OH)2 D and 25(OH)D were made using solid-phase extraction (SPE) and subsequent liquid chromatography-tandem mass spectrometry (LC-MS/MS). Vitamin D binding protein (VDBP) concentration was measured using an enzyme-linked immunosorbent assay. The VMR was calculated by dividing serum 24,25(OH)2 D by serum 25(OH)D and then multiplying by 100. Based on total 25(OH)D, VDBP, and albumin concentrations, bioavailable 25(OH)D concentrations were calculated using the equations from the other previous studies.

Results: Bioavailable 25(OH)D levels were significantly (p = 0.030) decreased in the sarcopenia group compared with the non-sarcopenia group. Results of ROC analysis for the diagnosis of sarcopenia using serum level of bioavailable of 25(OH)D revealed that the cutoff point for bioavailable 25(OH)D was 1.70 ng/ml (AUC = 0.649, p < 0.001). In the group with a bioavailable 25(OH)D less than 1.70 ng/ml, the incidence of sarcopenia increased by 3.3 times (odds ratio: 3.33, p = 0.013).

Conclusion: We demonstrated that bioavailable 25(OH)D was associated with sarcopenia among the various serum vitamin D biomarkers. Bioavailable vitamin D might be helpful for assessing the risk of sarcopenia.

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Some reduced muscle function associated with many Vitamin D genes - Review Sept 2021

Association between Polymorphisms in Vitamin D Pathway-Related Genes, Vitamin D Status, Muscle Mass and Function: A Systematic Review
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35+ Vitamin D Life pages with STRENGTH (but not bone/evidence/sarcopenia) in title

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17+ Vitamin D Life pages containing SARCOPENIA in title

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See also: Muscular Dystrophy probably treated by high-dose Vitamin D plus muscle rehab

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Creatine might help grow senior muscles when added to exercise

• Effect of 12 months of creatine supplementation and whole-body resistance training on measures of bone, muscle and strength in older males - 2021, Vol. 27(2) 151–159 DOI: 10.1177/0260106020975247 FREE PDF
• Creatine allows muscle growth with exercise by reducing muscle pain Greger - Sept 2023

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