Protocol development in integrative medicine is not typically a simple process. Individuals require individualized care, and what works for one patient may not work for another.

To establish these protocols, we first developed a Rating Scale that could be used to discern the rigor of evidence supporting a specific nutrient’s therapeutic effect.

The following protocols were developed using only A through D-quality evidence.

Class
Qualifying studies
Minimum requirements
A
Systematic review or meta-analysis of human trials
 
B
RDBPC human trials
2+ studies and/or 1 study with 50 + subjects
C
RDBPC human trials
1 study
D
Non-RDBPC human or In-vivo animal trials
 

The use of HMG CoA reductase inhibitors (statins) to lower cholesterol is known to cause various nutrient depletions, particularly of coenzyme Q10 (CoQ10), beta-carotene, and vitamin E. Different statins may result in varying degrees of depletion, necessitating careful discernment and lab testing by healthcare providers to determine the clinical appropriateness of supplementation. CoQ10 supplementation may help prevent or reverse deficiency without impacting the efficacy of statins. (Langsjoen 2003)(Littarru 2007) Similarly, statin therapy may significantly reduce beta-carotene and vitamin E levels, and targeted supplementation may be required to maintain optimal antioxidant capacity. (Jula 2002)(Vasankari 2004) Practitioners should consider individual patient profiles and monitor nutrient levels to ensure comprehensive care.

CoQ10

100–600 mg per day (Qu 2018)(Caso 2017)(Langsjoen 2003)

  • The widespread use of statins to lower cholesterol has been shown to cause a significant depletion of CoQ10. With higher statin usage and doses, CoQ10 deficiency is becoming more prevalent and severe, especially in elderly patients and those with heart failure. CoQ10 supplementation may be beneficial for preventing or reversing deficiency without affecting the efficacy of statins. (Langsjoen 2003)(Littarru 2007)
  • One study showed that CoQ10 supplementation improved statin‐associated muscle symptoms, including muscle pain, weakness, cramps, and tiredness, regardless of the CoQ10 dosage (100–600 mg per day) or the duration of supplementation (30 days to three months). (Qu 2018)
  • Ubiquinol has been shown to have up to 2–3 times higher bioavailability than ubiquinone. (Evans 2009)(Kurowska 2003) This suggests that lower doses of ubiquinol may be used to achieve the same effect as higher doses of ubiquinone.
CoQ10 in the Fullscript catalog

Beta-carotene

30 mg per day (Institute of Medicine 2000)

  • In a randomized controlled trial of men with hypercholesterolemia, simvastatin therapy decreased serum beta-carotene levels by 19.5%. (Jula 2002) 
  • Another study demonstrated that during the first 12 weeks of statin therapy, low-density lipoprotein (LDL) antioxidant capacity and serum concentrations of beta-carotene decreased by 20%. (Vasankari 2013)
  • Supplementation of 30 mg per day or more of beta-carotene for long periods of time may be associated with carotenodermia, but this effect is more cosmetic than adverse and is considered harmless and readily reversible. (Böhm 2020)
Beta-carotene in the Fullscript catalog

Vitamin E

100–400 IU per day (Pruthi 2001)

  • During the first 12 weeks of statin therapy, LDL antioxidant capacity and serum concentrations of alpha-tocopherol decreased by 16%. (Vasankari 2004)
  • In the same study, after 52 weeks, serum gamma-tocopherol levels in the simvastatin group returned to baseline, but LDL antioxidant capacity and serum alpha-tocopherol levels remained reduced. (Vasankari 2004)
Vitamin E in the Fullscript catalog

Disclaimer

The Fullscript Medical Advisory Team has developed or collected these protocols from practitioners and supplier partners to help health care practitioners make decisions when building treatment plans. By adding this protocol to your Fullscript template library, you understand and accept that the recommendations in the protocol are for initial guidance and may not be appropriate for every patient.

View protocol on Fullscript
References
  1. Böhm, V., Lietz, G., Olmedilla-Alonso, B., Phelan, D., Reboul, E., Bánati, D., Borel, P., Corte-Real, J., De Lera, Á. R., Desmarchelier, C., Dulinska-Litewka, J., Landrier, J., Milisav, I., Nolan, J., Porrini, M., Riso, P., Roob, J. M., Valanou, E., Wawrzyniak, A., . . . Bohn, T. (2020). From carotenoid intake to carotenoid blood and tissue concentrations – implications for dietary intake recommendations. Nutrition Reviews, 79(5), 544–573. https://doi.org/10.1093/nutrit/nuaa008
  2. Caso, G., Kelly, P., McNurlan, M. A., & Lawson, W. E. (2007). Effect of coenzyme Q10 on myopathic symptoms in patients treated with statins. the American Journal of Cardiology, 99(10), 1409–1412. https://doi.org/10.1016/j.amjcard.2006.12.063
  3. Evans, M., Baisley, J., Barss, S., & Guthrie, N. (2009). A randomized, double-blind trial on the bioavailability of two CoQ10 formulations. Journal of Functional Foods, 1(1), 65–73. https://doi.org/10.1016/j.jff.2008.09.010
  4. Institute of Medicine (US) Panel on Dietary Antioxidants and Related Compounds. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington (DC): National Academies Press (US); 2000. 8, β-Carotene and Other Carotenoids. Available from: https://www.ncbi.nlm.nih.gov/books/NBK225469/
  5. Jula, A., Marniemi, J., Huupponen, R., Virtanen, A., Rastas, M., & Rönnemaa, T. (2002). Effects of diet and simvastatin on serum lipids, insulin, and antioxidants in hypercholesterolemic men. JAMA, 287(5), 598. https://doi.org/10.1001/jama.287.5.598
  6. Kurowska, E. M., Dresser, G., Deutsch, L., Bassoo, E., & Freeman, D. J. (2003). Relative bioavailability and antioxidant potential of two coenzyme Q10 preparations. Annals of Nutrition & Metabolism, 47(1), 16–21. https://doi.org/10.1159/000068910
  7. Langsjoen, P. H., & Langsjoen, A. M. (2003). The clinical use of HMG CoA‐reductase inhibitors and the associated depletion of coenzyme Q10. A review of animal and human publications. BioFactors, 18(1–4), 101–111. https://doi.org/10.1002/biof.5520180212
  8. Langsjoen, P. H., & Langsjoen, A. M. (2013). Comparison study of plasma coenzyme Q10 levels in healthy subjects supplemented with ubiquinol versus ubiquinone. Clinical Pharmacology in Drug Development, 3(1), 13–17. https://doi.org/10.1002/cpdd.73
  9. Littarru, G. P., & Langsjoen, P. (2007). Coenzyme Q10 and statins: Biochemical and clinical implications. Mitochondrion, 7, S168–S174. https://doi.org/10.1016/j.mito.2007.03.002
  10. Pruthi, S., Allison, T. G., & Hensrud, D. D. (2001). Vitamin E supplementation in the prevention of coronary heart disease. Mayo Clinic Proceedings, 76(11), 1131–1136. https://doi.org/10.4065/76.11.1131
  11. Qu, H., Guo, M., Chai, H., Wang, W., Gao, Z., & Shi, D. (2018). Effects of coenzyme Q10 on Statin‐Induced myopathy: An Updated Meta‐Analysis of Randomized Controlled Trials. Journal of the American Heart Association. Cardiovascular and Cerebrovascular Disease, 7(19). https://doi.org/10.1161/jaha.118.009835
  12. Šabovič, M. (2014). Coenzyme Q10 supplementation Decreases Statin-Related Mild-to-Moderate muscle symptoms: a randomized clinical study. Medical Science Monitor, 20, 2183–2188. https://doi.org/10.12659/msm.890777
  13. Vasankari, T., Ahotupa, M., Viikari, J., Nuotio, I., Strandberg, T., Vanhanen, H., Gylling, H., Miettinen, T., & Tikkanen, M. J. (2004). Effect of 12‐month statin therapy on antioxidant potential of LDL and serum antioxidant vitamin concentrations. Annals of Medicine (Helsinki)/Annals of Medicine, 36(8), 618–622. https://doi.org/10.1080/07853890410018844