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Statin muscle problems decreased in 4 out of 5 patients when vitamin D was added – June 2022

Association Between Vitamin D Supplementation and Statin-Associated Muscle Symptoms: A Systematic Review

High Blood Press Cardiovasc Prev . 2022 Jun 29. doi: 10.1007/s40292-022-00526-5 PDF behind paywall
Chong Boon Teo # 1, Pek Yan Tan # 1, Ryan Yong Kiat Tay # 1, Joan Khoo 2, Gerald F Watts 3 4, Wann Jia Loh 5

\Introduction: Although low vitamin D levels are associated with statin-associated muscle symptoms (SAMS), it remains unclear if vitamin D supplementation leads to symptom improvement.

Aim: We performed a systematic review to evaluate the association of vitamin D supplementation with resolution of SAMS.

Methods: We searched Medline (PubMed), Embase and Cochrane Library till 12 December 2021. Full length articles that reported on the association between vitamin D supplementation in adult patients with SAMS were included.

Results: We identified 8 interventional studies comprising 669 participants. Majority of the participants were of Caucasian ethnicity and the mean age of participants ranged from 59.5 to 64.8 years old. The studies recruited patients with initial mean pre-treatment vitamin D levels ranging from 17.8 to 22.0ng/mL. Follow up duration ranged from 2 to 24 months and mean post-treatment vitamin D levels ranged from 34.3 to 56.0ng/mL. We found that vitamin D supplementation was associated with improved statin tolerance in 509 out of 606 (83.9%) patients across the 7 studies which reported patient numbers after supplementation (95% CI = 0.81-0.87, I2 = 72% n = 7). None of the studies were randomized controlled trials (RCTs) and hence placebo effect of vitamin D could not be ruled out. Nocebo effect of statin was also not assessed by any of the studies.

Conclusion: Vitamin D supplementation in patients with mild-moderate vitamin D insufficiency was associated with improvement of SAMS. However, quantitative efficacy analysis was not possible and this observed association is likely confounded by nocebo and placebo effects. RCTs are required to conclusively assess the utility of vitamin D supplementation in improving SAMS.

VitaminDWiki pages with STATIN in title (25 as of June 2022)

This list is automatically updated

Items found: 25
Title Modified
Statins and Vitamin D - many studies 30 Nov, 2022
Statin muscle problems decreased in 4 out of 5 patients when vitamin D was added – June 2022 30 Jun, 2022
Statin pain reduces Vitamin D levels by 4 ng ( 9 studies) - Meta-analysis July 2021 23 Jul, 2021
Statin side-effects are reduced by Vitamin D – US patent Application – April 2019 14 Nov, 2019
Statin pain eliminated by 7100 IU vitamin D (50000 IU weekly) – July 2011 21 Jul, 2019
Most Profitable Pill in Medical History Is Based on Flawed Science (Statins) May 2019 02 Jun, 2019
Low-dose statin plaque formation stopped by Omega-3 – RCT Dec 2017 24 Jan, 2018
Statin-induced Myalgias corrected with 100000 weekly Vitamin D2 20 Jul, 2017
Statin use increased probability of diabetes in women by 48 percent – perhaps via vitamin D Jan 2012 19 Mar, 2017
Statin use increased probability of diabetes by 48 percent – perhaps via vitamin D Jan 2012 19 Mar, 2017
The statin Crestor dramatically increases levels of vitamin D in the blood – Jan 2012 17 May, 2016
Some statins increase skin cancer risk by 40 percent (reducing vitamin D levels) – Jan 2016 10 Jan, 2016
Theories on the interaction between statins and vitamin D – 2012 10 Jan, 2016
If you must take statins and want to avoid hardening of arteries, take vitamin K2 – RCT May 2015 22 May, 2015
One statin decreased vitamin D levels but the other did not – March 2010 14 Apr, 2015
Not all statins increase vitamin D levels – Dec 2010 14 Apr, 2015
Off topic – Hypertension and statin pain reduced by Coenzyme Q10 – 2010 26 Jan, 2015
Statins with low vitamin D increased chance of musculoskeletal pain by 2X – Jan 2015 29 Nov, 2014
Statin pain associated with 10 ng less vitamin D – meta-analysis Oct 2014 24 Oct, 2014
Diabetics have problems with low Magnesium , especially if taking statins – Aug 2013 08 May, 2014
Statin-induced Myalgias corrected with 100000 weekly Vitamin D 04 May, 2014
Off topic: Statins associated with increased cataracts (wonder about low vitamin D) - Sept 2013 29 Sep, 2013
Diabetics have problems with low Magnesium, especially if taking statins – Aug 2013 28 Aug, 2013
Breast cancer 2X more likely if have taken statins for 10 years – July 2013 11 Jul, 2013
Statins associated with 14X increase in Polymyalgia Rheumatica (a new disease) – Aug 2012 09 Nov, 2012

  • Banach M, Rizzo M, Toth PP, Farnier M, Davidson MH, Al-Rasadi K, Aronow WS, Athyros V, Djuric DM, Ezhov MV, Greenfield RS, Hovingh GK, Kostner K, Serban C, Lighezan D, Fras Z, Moriarty PM, Muntner P, Goudev A, Ceska R, Nicholls SJ, Broncel M, Nikolic D, Pella D, Puri R, Rysz J, Wong ND, Bajnok L, Jones SR, Ray KK, Mikhailidis DP. Statin intolerance—an attempt at a unified definition. Position paper from an International Lipid Expert Panel. Arch Med Sci. 2015;11(1):1–23. https://doi.org/10.5114/aoms.2015.49807 . - DOI - PubMed - PMC
  • Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L, Chapman MJ, De Backer GG, Delgado V, Ference BA, Graham IM, Halliday A, Landmesser U, Mihaylova B, Pedersen TR, Riccardi G, Richter DJ, Sabatine MS, Taskinen MR, Tokgozoglu L, Wiklund O, Group ESCSD. 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J 2020;41(1):111–88. https://doi.org/10.1093/eurheartj/ehz455 .
  • Harper CR, Jacobson TA. The broad spectrum of statin myopathy: from myalgia to rhabdomyolysis. Curr Opin Lipidol. 2007;18(4):401–8. https://doi.org/10.1097/MOL.0b013e32825a6773 . - DOI - PubMed
  • Gupta A, Thompson D, Whitehouse A, Collier T, Dahlof B, Poulter N, Collins R, Sever P, Investigators A. Adverse events associated with unblinded, but not with blinded, statin therapy in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid-Lowering Arm (ASCOT-LLA): a randomised double-blind placebo-controlled trial and its non-randomised non-blind extension phase. Lancet. 2017;389(10088):2473–81. https://doi.org/10.1016/S0140-6736(17)31075-9 . - DOI - PubMed
  • Mendes P, Robles PG, Mathur S. Statin-induced rhabdomyolysis: a comprehensive review of case reports. Physiother Can. 2014;66(2):124–32. https://doi.org/10.3138/ptc.2012-65 . - DOI - PubMed - PMC
  • Michalska-Kasiczak M, Sahebkar A, Mikhailidis DP, Rysz J, Muntner P, Toth PP, Jones SR, Rizzo M, Kees Hovingh G, Farnier M, Moriarty PM, Bittner VA, Lip GY, Banach M. Analysis of vitamin D levels in patients with and without statin-associated myalgia—a systematic review and meta-analysis of 7 studies with 2420 patients. Int J Cardiol. 2015;15(178):111–6. https://doi.org/10.1016/j.ijcard.2014.10.118 . - DOI
  • Hou Q, Pang C, Chen Y. Association between vitamin D and statin-related myopathy: a meta-analysis. Am J Cardiovasc Drugs. 2021. https://doi.org/10.1007/s40256-021-00492-8 . - DOI - PubMed
  • Ahmed W, Khan N, Glueck CJ, Pandey S, Wang P, Goldenberg N, Uppal M, Khanal S. Low serum 25 (OH) vitamin D levels (<32 ng/mL) are associated with reversible myositis-myalgia in statin-treated patients. Transl Res. 2009;153(1):11–6. https://doi.org/10.1016/j.trsl.2008.11.002 . - DOI - PubMed
  • Compton ALP, Pepin MJ, Katzenberger DR, Kemp DW, Brown JN. Vitamin D supplementation during statin rechallenge in patients with a history of intolerance. Ann Pharmacother. 2021;55(6):814–5. https://doi.org/10.1177/1060028020966546 . - DOI - PubMed
  • Glueck CJ, Budhani SB, Masineni SS, Abuchaibe C, Khan N, Wang P, Goldenberg N. Vitamin D deficiency, myositismyalgia, and reversible statin intolerance. Curr Med Res Opin. 2011;27(9):1683–90. https://doi.org/10.1185/03007995.2011.598144 . - DOI - PubMed
  • Jetty V, Glueck CJ, Wang P, Shah P, Prince M, Lee K, Goldenberg M, Kumar A. Safety of 50,000–100,000 units of vitamin D3/week in vitamin D-deficient, hypercholesterolemic patients with reversible statin intolerance. N Am J Med Sci. 2016;8(3):156–62. https://doi.org/10.4103/1947-2714.179133 . - DOI - PubMed - PMC
  • Kang JH, Nguyen QN, Mutka J, Le QA. Rechallenging statin therapy in veterans with statin-induced myopathy post vitamin D replenishment. J Pharm Pract. 2017;30(5):521–7. https://doi.org/10.1177/0897190016674407 . - DOI - PubMed
  • Khayznikov M, Hemachrandra K, Pandit R, Kumar A, Wang P, Glueck CJ. Statin intolerance because of myalgia, myositis, myopathy, or myonecrosis can in most cases be safely resolved by vitamin D supplementation. N Am J Med Sci. 2015;7(3):86–93. https://doi.org/10.4103/1947-2714.153919 . - DOI - PubMed - PMC
  • Linde R, Peng L, Desai M, Feldman D. The role of vitamin D and SLCO1B1*5 gene polymorphism in statin-associated myalgias. Dermatoendocrinology. 2010;2(2):77–84. https://doi.org/10.4161/derm.2.2.13509 . - DOI
  • Riche KD, Arnall J, Rieser K, East HE, Riche DM. Impact of vitamin D status on statin-induced myopathy. J Clin Transl Endocrinol. 2016;6:56–9. https://doi.org/10.1016/j.jcte.2016.11.002 . - DOI - PubMed - PMC
  • Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ. 2009;21(339): b2700. https://doi.org/10.1136/bmj.b2700 . - DOI
  • Rosenson RS, Baker SK, Jacobson TA, Kopecky SL, Parker BA, The National Lipid Association's Muscle Safety Expert P. An assessment by the statin muscle safety task force: 2014 update. J Clin Lipidol 2014;8(3 Suppl):S58-71. https://doi.org/10.1016/j.jacl.2014.03.004 .
  • Wells G, Shea B, O’Connell D, Peterson J, Welch V, Losos M, Tugwell P. The Newcastle-Ottawa Scale (NOS) for assessing the quality of non-randomized studies in meta-analysis. Gastric Cancer. 2010;223:423–34.
  • White CM. A review of the pharmacologic and pharmacokinetic aspects of rosuvastatin. J Clin Pharmacol. 2002;42(9):963–70. - DOI
  • Bitzur R, Cohen H, Kamari Y, Harats D. Intolerance to statins: mechanisms and management. Diabetes Care. 2013;36(Suppl 2):S325–30. https://doi.org/10.2337/dcS13-2038 . - DOI - PubMed - PMC
  • Barilla D, Prasad P, Hubert M, Gumbhir-Shah K. Steady-state pharmacokinetics of fluvastatin in healthy subjects following a new extended release fluvastatin tablet, Lescol XL. Biopharm Drug Dispos. 2004;25(2):51–9. https://doi.org/10.1002/bdd.378 . - DOI - PubMed
  • Bruckert E, Hayem G, Dejager S, Yau C, Begaud B. Mild to moderate muscular symptoms with high-dosage statin therapy in hyperlipidemic patients–the PRIMO study. Cardiovasc Drugs Ther. 2005;19(6):403–14. https://doi.org/10.1007/s10557-005-5686-z . - DOI - PubMed
  • Neuvonen PJ, Niemi M, Backman JT. Drug interactions with lipid-lowering drugs: mechanisms and clinical relevance. Clin Pharmacol Ther. 2006;80(6):565–81. https://doi.org/10.1016/j.clpt.2006.09.003 . - DOI - PubMed
  • Dzik KP, Kaczor JJ. Mechanisms of vitamin D on skeletal muscle function: oxidative stress, energy metabolism and anabolic state. Eur J Appl Physiol. 2019;119(4):825–39. https://doi.org/10.1007/s00421-019-04104-x . - DOI - PubMed - PMC
  • Seldeen KL, Pang M, Leiker MM, Bard JE, Rodriguez-Gonzalez M, Hernandez M, Sheridan Z, Nowak N, Troen BR. Chronic vitamin D insufficiency impairs physical performance in C57BL/6J mice. Aging (Albany NY). 2018;10(6):1338–55. https://doi.org/10.18632/aging.101471 . - DOI - PubMed - PMC
  • Yoshikawa S, Nakamura T, Tanabe H, Imamura T. Osteomalacic myopathy. Endocrinol Jpn. 1979;26(Suppl):65–72. https://doi.org/10.1507/endocrj1954.26.supplement_65 . - DOI - PubMed
  • Sorensen OH, Lund B, Saltin B, Lund B, Andersen RB, Hjorth L, Melsen F, Mosekilde L. Myopathy in bone loss of ageing: improvement by treatment with 1 alpha-hydroxycholecalciferol and calcium. Clin Sci (Lond). 1979;56(2):157–61. https://doi.org/10.1042/cs0560157 . - DOI
  • Koundourakis NE, Androulakis NE, Malliaraki N, Margioris AN. Vitamin D and exercise performance in professional soccer players. PLoS ONE. 2014;9(7): e101659. https://doi.org/10.1371/journal.pone.0101659 . - DOI - PubMed - PMC
  • Han Q, Li X, Tan Q, Shao J, Yi M. Effects of vitamin D3 supplementation on serum 25(OH)D concentration and strength in athletes: a systematic review and meta-analysis of randomized controlled trials. J Int Soc Sports Nutr. 2019;16(1):55. https://doi.org/10.1186/s12970-019-0323-6 . - DOI - PubMed - PMC
  • Emerging Risk Factors Collaboration E-CVDVDSC. Estimating dose-response relationships for vitamin D with coronary heart disease, stroke, and all-cause mortality: observational and Mendelian randomisation analyses. Lancet Diabetes Endocrinol. 2021;9(12):837–46. https://doi.org/10.1016/S2213-8587(21)00263-1 . - DOI
  • Merke J, Milde P, Lewicka S, Hugel U, Klaus G, Mangelsdorf DJ, Haussler MR, Rauterberg EW, Ritz E. Identification and regulation of 1,25-dihydroxyvitamin D3 receptor activity and biosynthesis of 1,25-dihydroxyvitamin D3. Studies in cultured bovine aortic endothelial cells and human dermal capillaries. J Clin Invest. 1989;83(6):1903–15. https://doi.org/10.1172/JCI114097 . - DOI - PubMed - PMC
  • Weishaar RE, Kim SN, Saunders DE, Simpson RU. Involvement of vitamin D3 with cardiovascular function. III. Effects on physical and morphological properties. Am J Physiol. 1990;258(1 Pt 1):E134–42. https://doi.org/10.1152/ajpendo.1990.258.1.E134 . - DOI - PubMed
  • Fleet JC, DeSmet M, Johnson R, Li Y. Vitamin D and cancer: a review of molecular mechanisms. Biochem J. 2012;441(1):61–76. https://doi.org/10.1042/BJ20110744 . - DOI - PubMed
  • Makrani AH, Afshari M, Ghajar M, Forooghi Z, Moosazadeh M. Vitamin D and fibromyalgia: a meta-analysis. Korean J Pain. 2017;30(4):250–7. https://doi.org/10.3344/kjp.2017.30.4.250 . - DOI - PubMed - PMC
  • de Carvalho JF, da Rocha Araujo FAG, da Mota LMA, Aires RB, de Araujo RP. Vitamin D supplementation seems to improve fibromyalgia symptoms: preliminary results. Isr Med Assoc J. 2018;20(6):379–81. - PubMed
  • Tepper S, Dabush Y, Shahar DR, Endevelt R, Geva D, Ish-Shalom S. Vitamin D status and quality of life in healthy male high-tech employees. Nutrients. 2016;8:6. https://doi.org/10.3390/nu8060366 . - DOI
  • Thompson PD, Clarkson P, Karas RH. Statin-associated myopathy. JAMA. 2003;289(13):1681–90. https://doi.org/10.1001/jama.289.13.1681 . - DOI - PubMed
  • Gupta A, Thompson PD. The relationship of vitamin D deficiency to statin myopathy. Atherosclerosis. 2011;215(1):23–9. https://doi.org/10.1016/j.atherosclerosis.2010.11.039 . - DOI - PubMed
  • Vladutiu GD. Genetic predisposition to statin myopathy. Curr Opin Rheumatol. 2008;20(6):648–55. https://doi.org/10.1097/BOR.0b013e328314b7b4 . - DOI - PubMed
  • Group HTC. HPS2-THRIVE randomized placebo-controlled trial in 25 673 high-risk patients of ER niacin/laropiprant: trial design, pre-specified muscle and liver outcomes, and reasons for stopping study treatment. Eur Heart J. 2013;34(17):1279–91. https://doi.org/10.1093/eurheartj/eht055 . - DOI
  • Group SC, Link E, Parish S, Armitage J, Bowman L, Heath S, Matsuda F, Gut I, Lathrop M, Collins R. SLCO1B1 variants and statin-induced myopathy–a genomewide study. N Engl J Med. 2008;359(8):789–99. https://doi.org/10.1056/NEJMoa0801936 . - DOI
  • Voora D, Shah SH, Spasojevic I, Ali S, Reed CR, Salisbury BA, Ginsburg GS. The SLCO1B1*5 genetic variant is associated with statin-induced side effects. J Am Coll Cardiol. 2009;54(17):1609–16. https://doi.org/10.1016/j.jacc.2009.04.053 . - DOI - PubMed - PMC
  • Nct. Vitamin D replacement: the effect on statin-related myalgias. 2009. https://clinicaltrialsgov/show/NCT01022398.
  • Nct. Vitamin D replacement in statin-induced myopathy. 2011. https://clinicaltrialsgov/show/NCT01400009.
  • Irct20180422039379N. Evaluation of oral and injection vitamin D3 on reducing statin-induced myopathy. 2018. http://wwwwhoint/trialsearch/Trial2aspx?TrialID=IRCT20180422039379N1.
  • Howard JP, Wood FA, Finegold JA, Nowbar AN, Thompson DM, Arnold AD, Rajkumar CA, Connolly S, Cegla J, Stride C, Sever P, Norton C, Thom SAM, Shun-Shin MJ, Francis DP. Side effect patterns in a crossover trial of statin, placebo, and no treatment. J Am Coll Cardiol. 2021;78(12):1210–22. https://doi.org/10.1016/j.jacc.2021.07.022 . - DOI - PubMed - PMC
  • Ward NC, Watts GF, Eckel RH. Statin toxicity: mechanistic insights and clinical implications. Circ Res. 2019;124(2):328–50. https://doi.org/10.1161/CIRCRESAHA.118.312782 . - DOI - PubMed
  • Herrett E, Williamson E, Brack K, Beaumont D, Perkins A, Thayne A, Shakur-Still H, Roberts I, Prowse D, Goldacre B, van Staa T, MacDonald TM, Armitage J, Wimborne J, Melrose P, Singh J, Brooks L, Moore M, Hoffman M, Smeeth L, Statin WTG. Statin treatment and muscle symptoms: series of randomised, placebo controlled n-of-1 trials. BMJ. 2021;24(372): n135. https://doi.org/10.1136/bmj.n135 . - DOI
  • Wood FA, Howard JP, Finegold JA, Nowbar AN, Thompson DM, Arnold AD, Rajkumar CA, Connolly S, Cegla J, Stride C, Sever P, Norton C, Thom SAM, Shun-Shin MJ, Francis DP. N-of-1 trial of a statin, placebo, or no treatment to assess side effects. N Engl J Med. 2020;383(22):2182–4. https://doi.org/10.1056/NEJMc2031173 . - DOI - PubMed

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