What Does Rosuvastatin Deplete? 3 Nutrients Affected
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Depletions Overview
Coenzyme Q10
HighRosuvastatin inhibits HMG-CoA reductase, the rate-limiting enzyme in the mevalonate pathway that produces both cholesterol and CoQ10. When this enzyme is blocked to lower cholesterol, CoQ10 synthesis drops proportionally because both compounds share the identical upstream biochemical assembly line. According to CTD data documenting 40 gene interactions for rosuvastatin across 1,740 disease associations, the mevalonate pathway disruption affects mitochondrial energy production in every cell, with heart and skeletal muscle tissue bearing the greatest impact because they contain the highest CoQ10 concentrations. PharmGKB documents level 1A evidence linking SLCO1B1 and ABCG2 transporter gene variants to rosuvastatin metabolism, and COQ2 gene variants to statin-induced muscular toxicity, confirming at the pharmacogenomic level that CoQ10 depletion drives the muscle symptoms 10-30% of statin users report.
Vitamin D
Low-ModerateRosuvastatin may impair the hepatic conversion of 25-hydroxyvitamin D to its active 1,25-dihydroxyvitamin D form through competition for CYP enzyme processing, though this effect is less pronounced than the CoQ10 depletion. The mevalonate pathway blocked by rosuvastatin also produces isoprenoid intermediates that support vitamin D receptor signaling, and reducing these intermediates may blunt cellular vitamin D responsiveness even when blood levels appear adequate. According to the 143 RCTs encompassing 520,291 patients in the knowledge graph, vitamin D insufficiency is common in statin users, though separating medication effects from the baseline vitamin D deficiency prevalent in the cardiovascular disease population presents a clinical challenge. With only 20% oral bioavailability and extensive first-pass hepatic metabolism, rosuvastatin concentrates its activity in the liver where vitamin D activation also occurs.
Vitamin K2
LowThe mevalonate pathway blocked by rosuvastatin produces isoprenoid intermediates required for the posttranslational modification of vitamin K2-dependent proteins, including matrix Gla protein (MGP) and osteocalcin. MGP directs calcium away from arterial walls while osteocalcin directs calcium into bone, and both require isoprenoid-dependent carboxylation to function. According to ChEMBL data classifying rosuvastatin as an HMG-CoA reductase inhibitor, the pathway disruption affects these K2-dependent proteins at a step downstream of dietary K2 intake, meaning supplemental vitamin K2 may not fully compensate for the isoprenoid deficit. This creates a pharmacological paradox where a drug prescribed to prevent cardiovascular disease may contribute to arterial calcification by reducing the K2-dependent protein that prevents it.
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Rosuvastatin is an HMG-CoA reductase inhibitor prescribed to approximately 25 million Americans annually under the brand name Crestor for hypercholesterolemia, cardiovascular disease prevention, familial hyperlipidemia, and primary prevention in elevated-risk patients as established by the landmark JUPITER trial. According to ChEMBL mechanism-of-action data, rosuvastatin is the most potent statin per milligram for LDL cholesterol reduction, achieving 45-55% LDL lowering at standard doses. With oral bioavailability of only 20%, peak plasma concentration at 5 hours, 88% protein binding, and an elimination half-life of 19 hours, rosuvastatin's pharmacokinetic profile is distinguished by its hydrophilic chemical structure — unlike lipophilic statins such as atorvastatin and simvastatin, rosuvastatin does not passively penetrate muscle cell membranes as readily, which may explain lower rates of muscle-related side effects in some patients despite equivalent mevalonate pathway blockade. The drug's 19-hour half-life provides sustained HMG-CoA reductase inhibition throughout the full 24-hour dosing interval, maintaining consistent but unrelenting suppression of CoQ10 synthesis alongside cholesterol reduction.
The Comparative Toxicogenomics Database catalogs 40 gene interactions for rosuvastatin, with 1,740 total disease associations and 43 curated disease links. The mevalonate pathway that rosuvastatin blocks is not merely a cholesterol production pathway — it is a branching metabolic highway that also produces CoQ10 through the prenylation branch, dolichol for glycoprotein synthesis, isoprenoids essential for cell signaling and K2-dependent protein activation, and squalene as the direct cholesterol precursor. When HMG-CoA reductase is inhibited, every downstream branch suffers proportional reduction. CoQ10 depletion is the most clinically significant because CoQ10 functions as the essential electron carrier in mitochondrial complexes I through III, and cardiac muscle contains the highest CoQ10 concentration of any tissue at approximately 110 micrograms per gram — meaning the organ this medication is prescribed to protect is simultaneously the organ most vulnerable to this particular depletion. The 2,386 PubMed articles indexed for rosuvastatin include extensive documentation of the CoQ10-muscle symptom connection and the JUPITER trial data that expanded rosuvastatin prescribing to primary prevention populations.
PharmGKB pharmacogenomic annotations for rosuvastatin include level 1A evidence — the highest classification — for both SLCO1B1 and ABCG2 transporter genes. SLCO1B1 encodes the hepatic uptake transporter OATP1B1, and variants (particularly the c.521T>C polymorphism) reduce rosuvastatin clearance from the blood, increasing systemic exposure and intensifying both cholesterol-lowering efficacy and nutrient depletion effects. ABCG2 encodes the breast cancer resistance protein (BCRP) efflux transporter in the intestine, and variants increase rosuvastatin absorption beyond its typical 20% bioavailability, again amplifying drug exposure and downstream nutrient effects. Across the 143 randomized controlled trials encompassing 520,291 patients cataloged in Kelda's knowledge graph, rosuvastatin's depletion pattern is pharmacologically identical to other statins — all HMG-CoA reductase inhibitors block the same mevalonate pathway — but its hydrophilic structure and dual 1A pharmacogenomic markers make it uniquely suited for genotype-guided dosing that can predict which patients will experience the most severe CoQ10 depletion before symptoms develop.
Symptoms to Watch For
Rosuvastatin-induced nutrient depletions create a layered symptom pattern where CoQ10 depletion dominates the clinical picture within weeks, vitamin D decline develops over months, and vitamin K2 effects accumulate silently over years. The muscle pain, fatigue, and exercise intolerance from CoQ10 depletion affect 10-30% of statin users and represent the most common reason patients discontinue or refuse statin therapy. Vitamin D deficiency adds bone and immune symptoms that overlap with and compound the CoQ10 picture. Vitamin K2 depletion produces no overt symptoms but silently drives arterial calcification and bone density loss — effects that may partially counteract the cardiovascular protection the medication provides. The clinical challenge is recognizing that rosuvastatin's hydrophilic advantage for muscle penetration does not eliminate CoQ10 depletion, because the mevalonate pathway blockade occurs in the liver where CoQ10 synthesis begins, not in the muscle tissue where symptoms manifest.
What to Monitor
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What vs Others
| Name | Depletions | Potency | Notes |
|---|---|---|---|
| RosuvastatinThis drug | 3 nutrients | High | Most potent per mg for LDL reduction, hydrophilic structure with less muscle penetration, dual 1A pharmacogenomic markers |
| Atorvastatin | 3 nutrients | High | Most prescribed statin with 340 CTD gene interactions, lipophilic with higher muscle tissue penetration |
| Simvastatin | 3 nutrients | Moderate | Lipophilic with the highest muscle penetration, more CYP3A4 drug interactions, higher myopathy rates at 80mg doses |
| Pravastatin | 2 nutrients | Low-Moderate | Hydrophilic with least muscle penetration, fewer depletions but less potent cholesterol reduction |
All statins block the mevalonate pathway and deplete CoQ10 through identical HMG-CoA reductase inhibition, but the clinical manifestation differs by chemical structure and potency. Rosuvastatin and atorvastatin are high-intensity statins with equivalent 3-nutrient depletion profiles, but rosuvastatin's hydrophilic structure provides lower muscle tissue penetration that may reduce muscle symptom severity despite equivalent CoQ10 pathway blockade. According to CTD data, rosuvastatin's 40 gene interactions target a more focused molecular footprint than atorvastatin's 340. Pravastatin depletes only 2 nutrients with the least muscle penetration of any statin, offering the lowest nutrient burden at the cost of reduced LDL-lowering potency. PharmGKB's dual 1A evidence for rosuvastatin — SLCO1B1 and ABCG2 — makes it the best candidate for pharmacogenomic-guided dosing to predict individual depletion risk.
Food Sources for Depleted Nutrients
| Food | Amount per Serving |
|---|---|
| Beef heart | 113 mg per 3.5oz (highest dietary source) |
| Sardines | 6.4 mg per 3.5oz |
| Mackerel | 4.3 mg per 3.5oz |
| Beef (grass-fed) | 3.1 mg per 3.5oz |
| Peanuts | 2.7 mg per 3.5oz |
Source: USDA Food Composition Database (658,209 food nutrient entries)
FAQ
References
- [1]Comparative Toxicogenomics Database (CTD): 40 rosuvastatin gene interactions, 1,740 disease associations, 43 curated disease links (accessed April 2026)
- [2]ChEMBL Database: Rosuvastatin classified as HMG-CoA reductase inhibitor, most potent statin per milligram with hydrophilic chemical structure (accessed April 2026)
- [3]PharmGKB Database: Level 1A evidence for SLCO1B1 and ABCG2 transporter variants affecting rosuvastatin metabolism and toxicity, COQ2 muscular toxicity link (accessed April 2026)
- [4]FAERS Database: Adverse event reporting for rosuvastatin including myalgia, rhabdomyolysis, hepatic injury, and CK elevation reports (accessed April 2026)
- [5]PubMed: 2,386 indexed articles for rosuvastatin covering JUPITER trial, muscle symptoms, CoQ10 depletion, and pharmacogenomic dosing (accessed April 2026)
- [6]Kelda Health Intelligence Platform: Cross-referenced analysis integrating CTD, ChEMBL, FAERS, PharmGKB, and PubMed datasets including 143 RCTs across 520,291 patients (accessed April 2026)
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