Statins and vitamin D

Apparently: Stains ==> less cholesterol ==> less pre-vitamin D ==> less vitamin D from sun

See also VitaminDWiki

Statin intolerance reduced as level of vitamin D is raised - July 2015

about 53% no longer statin intolerant if > 30ng of vitamin D
about 90% no longer statin intolerant if 54 ng of vitamin D
 Download a letter to the editor from VitaminDWiki

Statins and Vitamin D in PubMed 225 items July 2016: examples follow:

  • Is there really a relationship between serum vitamin D (25OHD) levels and the musculoskeletal pain associated with statin intake? A systematic review. April 2016 full free text
  • Safety of 50,000-100,000 Units of Vitamin D3/Week in Vitamin D-Deficient, Hypercholesterolemic Patients with Reversible Statin Intolerance. March 2016 full free text
  • Simvastatin and vitamin D for migraine prevention: A randomized, controlled trial. Dec 2015
  • Statin Intolerance Because of Myalgia, Myositis, Myopathy, or Myonecrosis Can in Most Cases be Safely Resolved by Vitamin D Supplementation. March 2015 full free text
  • Do women with statin-related myalgias have low vitamin D levels? Sept 2015 full free text
  • Low plasma vitamin D levels and muscle-related adverse effects in statin users.Jan 2014 full free text
  • The association between drugs frequently used by the elderly and vitamin D blood levels: a review of observational and experimental studies.Feb 2014
  • Vitamin D3 effects on lipids differ in statin and non-statin-treated humans: superiority of free 25-OH D levels in detecting relationships Sept 2013
  • Effect of simvastatin/ezetimibe 10/10 mg versus simvastatin 40 mg on serum vitamin D levels. May 2013
  • Cardiovascular disease, statins and vitamin D. Feb 2012
  • Possible mechanisms of interaction between statins and vitamin D May 2012
  • Vitamin D deficiency, myositis-myalgia, and reversible statin intolerance. - July 2011
  • Resolution of statin-induced myalgias by correcting vitamin D deficiency - May 2011

Do statins increase the level of vitamin D in the blood in the short term?

Question: Is this a direct effect, or is it due to statins reducing cholesterol, which is needed to produce vitamin D from the skin, but cholesterol is not needed if the vitamin D is taken as a supplement

Some people appear to think that vitamin D could serve the same function as statins at much lower cost and much lower risk

Note: one statin is the top selling US prescription drug - with more sales than the next two top-selling drugs


See also Web

See also Vitamin D Council behind a paywall

VitaminDWiki expects that Vitamin K2 could decrease the above side effects of statins

Rosuvastatin is a statin which increased vitamin D levels by 2.8X – Aug 2010

The JUPITER lipid lowering trial and vitamin D, Is there a connection?
William R Ware
Faculty of Science (Emeritus); University of Western Ontario; London, ON CA
Corresponding author. Correspondence to: William R. Ware; Email: warewr at rogers.com
Received May 6, 2010; Accepted August 3, 2010.
Dermatoendocrinol. 2010 Apr-Dec; 2(2): 50–54. doi: 10.4161/derm.2.2.13235

There is growing evidence that vitamin D deficiency significantly increases the risk of adverse cardiovascular events and that a vitamin D status representing sufficiency or optimum is protective. Unfortunately, in clinical trials that address interventions for reducing risk of adverse cardiovascular events, vitamin D status is not generally measured. Failure to do this has now assumed greater importance with the report of a study that found rosuvastatin at doses at the level used in a recent large randomized lipid lowering trial (JUPITER) had a large and significant impact on vitamin D levels as measured by the metabolite 25-hydroxyvitamin D. The statin alone appears to have increased this marker such that the participants on average went from deficient to sufficient in two months. The difference in cardiovascular risk between those deficient and sufficient in vitamin D in observational studies was similar to the risk reduction found in JUPITER.

Thus it appears that this pleiotropic effect of rosuvastatin may be responsible for part of its unusual effectiveness in reducing the risk of various cardiovascular endpoints found in JUPITER and calls into question the interpretation based only on LDL cholesterol and CRP changes. In addition, vitamin D status is a cardiovascular risk factor which up until now has not been considered in adjusting study results or in multivariate analysis, and even statistical analysis using only baseline values may be inadequate.

PMCID: PMC3081676
Text from the PDF
Rosuvastatin was given in doses of 10–20 mg/day and mean LDL levels decreased from 174 to 100 mg/dL.
At baseline the group had a mean level of 25(OH)D of 14 ng/mL which after 8 weeks of treatment increased to 36.3 ng/mL

PDF is attached at the bottom of this page

Benefits of Chocolate on the heart and all cause mortality (vs statins)

Green Med Info April 2012
Great many health benefits of chocolate documented -
Regarding just the heart: Chocolate appears to be better than statins.

Hypothesis of how statins can increase vitamin D blood levels, yet cause problems associated with vitamin D deficiency

Statins could decrease either the production or use of active vitamin D, that is, the form which is actually used in the body.
- suggested by Judy, Aug 2012

Simvastatin/Ezetimibe 10/10 mg increased Vitamin D levels 37%

Effect of Simvastatin/Ezetimibe 10/10 mg Versus Simvastatin 40 mg on Serum Vitamin D Levels.
J Cardiovasc Pharmacol Ther. 2013 Jan 2.
Liberopoulos EN, Makariou SE, Moutzouri E, Kostapanos MS, Challa A, Elisaf M.
Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece.

Backround:Low levels of 25-hydroxyvitamin D (25(OH)VitD) have been recognized as an emerging cardiovascular disease (CVD) risk factor. Statins are reported to increase 25(OH)VitD concentration. Animal studies suggest that ezetimibe is a moderate inhibitor of intestinal 25(OH)VitD absorption, but its effect in humans is unknown.Aim:To investigate whether combined treatment with simvastatin/ezetimibe 10/10 mg would increase 25(OH)VitD levels compared to simvastatin 40 mg monotherapy in patients with primary hypercholesterolemia.

In a Prospective Randomized Open-label Blinded End point study, 50 patients with primary hypercholesterolemia received either simvastatin/ezetimibe 10/10 mg (n = 25) or simvastatin 40 mg (n = 25) daily for 3 months. The primary end point was between-group difference in the change of serum 25(OH)VitD levels.

Simvastatin/ezetimibe 10/10 mg was associated with a 36.7% increase in 25(OH)VitD serum levels (from 6.8 to 9.3 ng/mL, P = .000), while simvastatin 40 mg was associated with a 79.1% increase (from 6.7 to 12.0 ng/mL, P = .008). The increase in 25(OH)VitD levels in the simvastatin 40 mg group was significantly greater compared to that in the simvastatin/ezetimibe 10/10 mg group (P = .04). Both groups exhibited similar reductions in low-density lipoprotein cholesterol (LDL-C) levels.

For similar LDL-C lowering simvastatin 40 mg is associated with greater increase in 25(OH)VitD compared to simvastatin/ezetimibe 10/10 mg.
Whether this difference is relevant in terms of CVD risk reduction is unknown.

A New Women’s Issue: Statins NYT May 2014

  • If you’re going to tell a healthy person to take a medicine every day for the rest of their life, you should have really good data that it’s going to make them better off,
  • statins didn’t prevent healthy women from having their first heart attacks and didn’t save lives.
  • Women who are healthy derive no benefit from statins, and even those women who have established heart disease derive only half the benefit men do.
  • The drugs have long been known to cause muscle pain in some people and, more rarely, liver and kidney damage, as well as cognitive side effects like memory loss and confusion
  • postmenopausal women who took part in the Women’s Health Initiative were much more likely to develop diabetes if they took statins, and diabetes itself increases the risk of heart disease considerably.

    Summary by VitaminDWiki: No proof that statins helps healthy women, but there is proof that statins harms them

Statin Health problems - GreenMedInfo

- Feb 2015 (nothing about vitamin D)

Muscle damage 80 studiesNerve damage 54 studies+Liver damage 32 studies
Endocrine disruption: 16 studies Cancer-promoting: 9 studies Diabetes-promoting: 8 studies
Cardiovascular-damaging: 15 studiesBirth defect causing 11 studies
  • The JUPITER trial of Crestor vs placebo resulted in increased fatal heart attacks in the treatment group which were obscured by combing fatal and nonfatal infarctions.
  • The HPS study has 26% drop out rate prior to the beginning of the trial, so that those with significant side effects were functionally excluded from the study.
  • In at least four trials, statistically significant increases in cancer incidence was found, and handily dismissed by all authors as insignificant because they claimed "no known potential biological basis" is known.
  • A low serum cholesterol level has also been found to serve as a biological marker of major depression and suicidal behavior,
       suicidal ideation among adults with mood disorders was more than 2.5-times greater in those taking statins
  • "So, the next time you hear of a doctor recommending a cholesterol-lowering intervention, tell him you'll take that 1% risk and spare yourself cancer, cognitive dysfunction, myopathy, and diabetes"

Aug 2016 Video

If you really must take statins and they cause pain, vitamin D will relieve the pain

Statin Intolerance Because of Myalgia, Myositis, Myopathy, or Myonecrosis Can in Most Cases be Safely Resolved by Vitamin D Supplementation March 2015
50,000 or 100,000 IU of vitamin D2 per week relieved statin pain
 Download the PDF from VitaminDWiki

  • ConsumerLabs has a nice summary of this as well as many other vitamin D studies behind a subscription paywall
    Thier paywall is very much worth the price. They review a huge number of supplements
    I have subscribed for over a decade

80% of the people who should take statins have decided not to (TOO many side effects?) - May 2015

Statins associated with low vitamin D - Dec 2015

Statin therapy and Vitamin D
Int J Basic Clin Pharmacol. 2015; 4(6): 1113-1117doi: 10.18203/2319-2003.ijbcp20151342
Arunkumar Radhakrishnan, A. Ruckmani, M. Abishek, S. Govindaraju.

Background: Statins are well-known drugs used in dyslipidemia and cardiac disorders since several years. Recently, it has been reported that long-term use of statins reduce serum vitamin D level. When statins are administered to patients with low vitamin D more muscular side effects have been reported. On the contrary, a few studies report that statins might increase vitamin D level competing with its metabolism. Hence, this study was conducted to evaluate the association between statins and vitamin D.

Methods: 125 participants who fulfilled the selection criteria were enrolled in the study. 65 subjects belonged to control group and 60, statin group. The blood sample was collected for Vitamin D estimation. The results were correlated with a demographic profile, nature of statin and the muscular side effects and compared with control group.

Results: The mean vitamin D level in statin group was 15.82 ng/ml±11.51 and 20.57 ng/ml±7.007 in the control group. The difference was found to be statistically significant. 13.85% in the control group and 10% in statin group had sufficient vitamin D level. 18.33% and 36.92 % had insufficient levels and 71.67% and 49.23% had a deficiency in the statin and control groups respectively. Myalgia was reported by 30 among 60 subjects (50%) in statin group and 5 among 65 subjects (7.69%) in the control group.

Conclusion: The present study has shown that statin therapy is associated with low vitamin D level and that this could contribute to the increased incidence of myalgia in the statin group.

 Download the PDF from VitaminDWiki

Statin intolerance ==> statin tolerance after add lots of vitamin D - March 2016

Journal of Investigative Medicine
V Jetty, G Duhon, P Shah, M Prince, K Lee, M Goldenberg, A Kumar, CJ Glueck, P Wang
DOI: 10.1136/jim-2016-000120.39 Published 22 March 2016

Background In ∼85–90% of statin intolerant patients, vitamin D deficiency (serum 25 (OH) D <32 ng/ml) is a reversible cause of statin intolerance, usually requiring 50,000 to 100,000 units of vitamin D/week continuously to normalize serum vitamin D, and thus successfully allow reinstitution of statins which previously could not be tolerated because of myalgia-myositis.

Specific Aim In 274 statin intolerant patients, all with low entry serum vitamin D (<32 ng/ml, median 21 ng/ml), we assessed safety and efficacy of vitamin D supplementation (50,000–100,000 units/week) over treatment periods of 3 months (n=274), 3 and 6 months (n=161), 3, 6, and 9 months (n=58), and 3, 6, 9, and 12 months (n=22).

Results In the 385 patients with 3 month follow-up, taking mean 61,000 and median 50,000 IU of vitamin D3/week, median serum vitamin D rose from 20 to 42 ng/ml (p<0.0001); vitamin D became high (>100 ng/ml) but not toxic-high (>150 ng/ml) in 4 patients (1.0%) (101, 102, 106, 138 ng/ml). Median serum calcium was unchanged from entry (9.6 mg/dl) to 9.6 at 3 months. On vitamin D supplementation, the trend of change in serum calcium from normal-to-high or from high-to-normal did not significantly differ (McNemar S=1.0, p=0.32), and there was no significant trend in change of the calculated glomerular filtration rate (eGFR) from entry to follow-up (McNemar S=2.6, p=0.11).

In the 161 patients with 3 and 6 month follow-up, taking mean 67,000 and median 50,000 IU of vitamin D3/week, median entry serum vitamin D rose from 21 to 42 to 44 ng/ml (p<0.0001), serum vitamin D was high (>100 but <150 ng/ml) in 2 patients at 3 months (1.2%, 101, 102 mg/ml) and in 3 (1.9%) at 6 months (101, 140, 140 ng/ml). Median serum calcium was unchanged from entry (9.7 mg/dl), at 3 and 6 months (9.7, 9.6 mg/dl, p>0.05). On vitamin D supplementation, the change in serum calcium from normal-to-high or high-to-normal was no significant trend (McNemar S=0.7, p=0.41), and no trend in change of eGFR (McNemar S=1.3, p=0.26).

In the 58 patients with 3, 6, and 9 month follow-up on mean and median 71,000 and 100,000 IU of D3/week, median entry vitamin D rose from 20 to 37, 41, and 44 ng/ml (p<0.0001), with 1 (1.7%, 102 ng/ml), 2 (3.5%, 140, 140 ng/ml), and 0 (0%) patients high. Median serum calcium was unchanged from entry, median 9.7, 9.8, 9.6, and 9.6 mg/dl. On vitamin D supplementation, the trend of change in serum calcium from normal-to-high or high-to-normal was not significant (McNemar S=1.8, p=0.18), and no trend in change of eGFR (McNemar S=2, p=0.16).

In the 22 patients with follow-up at 3, 6, 9, and 12 months on mean and median 70,000 and 75,000 IU of D3/week, median serum vitamin D rose from 20 to 37, to 41, to 44, and to 43 ng/ml (p<0.0001), with 1 (5%, 102 ng/ml) high, 2 (9%, 140, 140) high, 0 (0%) high, and 1 (5%, 126 ng/ml) high. Serum calcium was unchanged, median at entry 9.6, and then at 3, 6, 9, and 12 months 9.7, 9.7, 9.5, and 9.7 mg/ml. At entry serum calcium was normal in 21, none high, and one became high at 12 month follow-up. The trend of change in eGFR was insignificant, McNemar S=1.0, p=0.32.

When serum D rose above 100 ng/ml in the few cases, as above, it fell into the normal range within 2 weeks by reducing the vitamin D dose by 50%.

Conclusions When 50,000–100,000 units of vitamin D/week are given to reverse statin intolerance in statin intolerant patients with low entry vitamin D (<32 ng/ml), it appears to be safe over up to 1 year follow-up, without toxic high serum vitamin D levels >150 ng/ml, and levels rarely >100 ng/ml, and without changes in serum calcium or eGFR.
- - - -
A study has the same conclusion later in 2016
Rechallenging Statin Therapy in Veterans With Statin-Induced Myopathy Post Vitamin D Replenishment
41% tolerated their previously failed statins after taking vitamin D; free PDF is online

BMJ wants $30 for the PDF

This high dose of this statin (abstract does not say which) increased vitamin D levels, by 20% - April 2016

J Am Coll Cardiol. 2016;67(13_S):2349-2349. doi:10.1016/S0735-1097(16)32350-6
Monica Verdoia; Lucia Barbieri; Alon Schaffer; Paolo Marino; Harry Suryapranata; Giuseppe De Luca

Statins represent a pivotal treatment in coronary artery disease (CAD), offering “pleiotropic” benefits in cardiovascular risk far beyond the lipid-lowering action. Vitamin D has been suggested as a potential mediator of the anti-atherosclerotic and anti-thrombotic effects of statins. Aim of present study was to assess the impact of a high-intensity statin therapy on vitamin D levels and platelet function in patients with coronary artery disease.

Patients discharged on dual antiplatelet therapy and high-intensity statins after an acute coronary syndrome or elective PCI were scheduled for main chemistry and vitamin D levels assessment at 30-90 days post-discharge. Platelet function was assessed by Multiplate® (Roche Diagnostics AG).

Among 246 patients included, 142 were discharged on a new statin therapy or with an increase in previous dose (Inc-S), while 104 were already receiving a high-dose statin at admission, that remained unchanged (eq-S). Patients in the Inc-S group were younger (p=0.01), smokers (p<0.001), less often hypercholesterolemic (p=0.05), diabetic (p=0.03), with hypertension (p=0.02), or previous cardiovascular events (p<0.001), and more frequently admitted for acute coronary syndrome (p<0.001). Baseline vitamin D levels were similar in the 2 groups (p=0.30). A significant reduction in circulating low-density lipoprotein (LDL) cholesterol was observed in the Inc-S group. Vitamin D levels increased in the Inc-S patients but not in the eq-S group (delta-25OHD: 23.2±20.5% vs 3.1±4.7%, p=0.003), with a linear relationship between the magnitude of vitamin D elevation and the reduction of LDL cholesterol (r=-0.17, p=0.01). Platelet reactivity was significantly lower in the Inc-S patients, with different platelet activating stimuli (arachidonic acid, p=0.02, collagen, p=0.004, thrombin-activating peptide, p=0.07, ADP, p=0.002).

In patients with CAD, the addition of a high-intensity statin treatment is associated to a significant increase in vitamin D levels and lower platelet reactivity, potentially providing explanation of the “pleiotropic” benefits of statins therapy in cardiovascular disease.

Atorvastatin decreases D levels via CPY3A4; parvastatin increases D levels vai CYP27A1 - 2016

The mechanism of statin-induced modulation of vitamin D metabolism Sept 2016
Behind $36 paywall http://dx.doi.org/10.1016/j.atherosclerosis.2016.07.224

Those with Statin pain were 3 times more likely to have levels of low vitamin D – Nov 2016

Impact of Vitamin D Status on Statin-Induced Myopathy
J of Clinical and Translational Endocrinology DOI: http://dx.doi.org/10.1016/j.jcte.2016.11.002
Krista D. Riche, Justin Arnall, Kristin Rieser, Honey E. East, Daniel M. Riche
 Download the PDF from VitaminDWiki
•Vitamin D status plays an important role in the consideration of statin-induced myopathy.
•Correction of vitamin D deficiency ( 20 ng/mL) can improve statin tolerance rates.

There is a multitude of evidence supporting the benefit of statin use in cardiovascular disease; however, statin-induced myopathy is a major reason for statin discontinuation and non-adherence. Vitamin D deficiency has been independently associated with muscle weakness and severe myopathy, and may be a confounder for statin-induced myopathies. Since there is no consensus on a treatment course of action for statin-induced myopathy, investigation into potential confounders to elucidate the dynamics of statin-induced myopathy is warranted.

A retrospective chart review was conducted on 105 patients in a cardiometabolic clinic with a vitamin D drawn from December 2006 to April 2008. Patients exposed to statins were divided into two groups: (1) patients with low vitamin D (<32 ng/mL) n=52 and (2) patients with a sufficient vitamin D level ( 32 ng/mL) n=32. Data were compared via t-tests or Fisher’s Exact, as appropriate.

There were 41 statin-specific myopathies amongst the 24 statin-intolerant patients. Low vitamin D was significantly associated with statin-induced myopathy (p=0.048). Following prescription vitamin D supplementation, statin tolerance rates were significantly higher in patients with a baseline vitamin D 20 ng/mL than those with a baseline vitamin D >20 ng/mL (90% vs 33%; p=0.036).

Vitamin D status may be considered a modifiable risk factor for muscle-related adverse effects of statins, and supplementation of vitamin D (particularly when 20 ng/mL) may improve statin tolerance.

List of attached files
ID Name desc uploaded Size Downloads Actions
7402 jpg Myophy 32 ng.jpg 26 Nov., 2016 by admin 40.84 Kb 68 View Download  
7401 pdf Statins tolerated with Vitamin D.pdf PDF 2016 26 Nov., 2016 by admin 290.13 Kb 13 View Download  
6235 pdf Statin and Vitamin D.pdf PDF 2015 10 Dec, 2015 by admin 398.95 Kb 543 View Download  
5725 pdf Statin Intolerance July 2015.pdf PDF 2015 28 July, 2015 by admin 336.10 Kb 762 View Download  
5306 pdf Statin Intolerance.pdf PDF 2014 14 Apr., 2015 by admin 4.79 Mb 663 View Download  
4806 jpg Statin myalgia.jpg 01 Jan., 2015 by admin 31.95 Kb 6467 View Download  
1172 pdf Jupiter PMC3081676.pdf PDF 25 Mar., 2012 by admin 261.78 Kb 1441 View Download  
152 gif List of best selling drugs wikipedia - 2006.gif best selling drugs 18 Aug., 2010 by admin 21.88 Kb 14237 View Download  
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