To: Drs Ostrow, Kulick, Gleyzer                                                           

September 26, 2005

Coenzyme Q10

Three weeks ago I presented the query: Given an essentially well patient on a statin drug, would you recommend Coenzyme Q10, how much and why?

  • Dr. G gives 50 mg CoQ10. He does not get serum levels.
  • Dr. J does not recommend unless patient is symptomatic.
  • Dr. K titrates from 100 to 200 mg for all statin users. Doesn’t think serum levels are really established and would be unreliable.
  • Dr. O refers out for management but would recommend 100 to 300 mg, is curious about levels and suggests checking Dr. Sinatra’s newsletter.

Literature review:

The paper that is the most relevant is by Mortensen1, and was published in 1997. 45 “healthy” hypercholesterolemics were placed on escalating doses of pravachol or lovastatin, increasing every six weeks for 18 weeks. Lipid and CoQ10 levels were obtained every six weeks. Both drugs significantly lowered cholesterols. Both statin treatments significantly decreased serum CoQ10 levels to approximately 70% of the baseline level in a dose dependant fashion. Levels dropped from 1.27 mmol/ml to 1.02 on pravastatin 40 mg/day, and from 1.18 mmol/ml to .84 on lovastatin 80 mg/day. So, what is clinically significant?

First, lets look at published CoenzymeQ10 levels in different patient groups.

        Blood levels
 mcg/ml
STUDY  CONDITION  # CASES  DOSE  BEFORE  AFTER 
Langsjoen2
nonhypertrophic  143  100 mg  0.85  2.0
  Cardiomyopathy,         
  NYHA classes III&IV      
Baggio3
CHF, safety   2.664  50-100     
Sinatra4
Maximal levels         
  2x norm for healthy        
  4-7x norm for sick      
Weber5
healthy young  22  90 mg  07umo1/L  1.7 
Mortensen1  well hypercholesterolemics      1.02, 1.27   
Teran23 well normal women  22    0.86   
  Well Pregnant  18    1.08   
  Preeclampsia  12    0.70   
Kamikawa6
stable angina  12  150 mg  0.95  2.2 
Langsjoen7
cardiovascular Dz  424  75-600 mg    >2.1 
Fujimoto 8
 COPD  21  90 mg  0.56   
  Pulmonary Fibrosis  9  90 mg  0.45   
Lockwood9
Breast cancer  case 1  390 mg  0.83  3.64   
    case 2  390 mg  0.62  3.77 
Folkers10
Musc. Dystrophy  12  100 mg  0.5-.84   


If for the sake of argument we take a normal wellness range to be from 0.95 to 1.35 mcg/ml, the ranges for groups with various medical conditions is not that much lower. More importantly, measurable clinical benefit is obtained by raising levels, often to higher than the normal level. A large number of different types of conditions seem to respond to oral supplementation. The only downside seems to be the financial cost. To fully address the question of whether “healthy” hypercholesterolemics on statin drugs will benefit by concomitant CoQ10 we would need to know the Number Needed to Treat (NNT) to show benefit, and this is not available. Industry based newsletters report rates of rhabdomyolysis from 0.44 per 10,000 to 1 in 10 for patients using now banned cerivastatin and a fibrate.11 To my knowledge, we do not know whether coenzymeQ10 is derived from mitochondrial DNA, and we certainly  do not know whether particular individuals may have organism or organ specific deficiency in coenzyme Q10 production that make them more susceptible to relative coenzymeQ10 deficiency.

 

We now have confirmation that coenzyme Q10 markedly improves statin–induced myopathic pain from a randomized double–blind controlled trial with 41 patients.12 Dr Kelly has found that in her experience the incidence of myopathic pain in this statin using group is more like 25% than 5%.   As a Chronic Pain center, we may see a larger number of persons with unexplained myalgias, and those who are on a statin drug may have self selected to come to our practice. It therefore seems prudent to recommend coenzyme Q10 to all patients on statin drugs, at least for a trial to see if their symptoms improve. For those with a variety of systemic diseases, it should be an early consideration.

Expected results:

  1. ↓ LDL, ↑ HDL, ↓ Lp(a)13
  2. ↓ blood pressure14  15 16
  3. Improved NYHA CHF class2 17
  4. ↑ ejection fraction, decreased angina18
  5. ↓ insulin resistance19
  6. Improved renal function20
  7. ↑ PaO2, decreased heart rate in COPD8
  8. ↑ T4/T8 ratios, ↑ IgG levels21

Effective doses range from 90 mg to 390 mg, and published studies in Parkinson patients have gone as high as 1200 mg. My own clinical experience is that there is a significant subset of patients that will report an off-on effect that typically occurs while titrating up from 100 to 400 mg per dose. Some patients report doses later in the day may make it hard to sleep. Studies from Denmark suggest that a simple soya bean oil suspension of coenzymeQ10 has the highest bioavailability.22 Patients with IBS and absorbtion difficulties may need special consideration, and would benefit most by serum coenzymeQ10 levels if clinical results are ambiguous.

  • Quest Diagnostics perform serum CoQ10 levels.
  • Order number: K80025, 3 ml frozen serum in  SST tube.

When Julian Whitaker MD, petitioned the FDA to force manufacturers of statin drugs to include a recommendation for coenzyme Q10 supplementation on their labels in October of 2002, some may have seen it as grandstanding. If Peter Langsjoen MD is correct, that we are at the onset of a pandemic of statin cardiomyopathies, then look for a reintroduction of the Merck statin/CoQ10 patented product, or a more selective cholesterol formation inhibitor. One solution that drug companies are probably now exploring, would be to find a drug that selectively blocks squalene synthetase, as below.

The recent flow of literature confirms that muscle soreness and or rhabdomyolitis may occur spontaneously or be amplified by exercise in persons on statin drugs. Stronger, liophilic statins (Crestor, Simvastatin) are more suspect than earlier, weaker ones (Mevacor, Pravastatin). This can be confirmed by 1) low coenzyme Q10 levels,  disappearance of symptoms with stopping statin or reducing statin potency, and by a trial of Coenzyme Q10 (or ubiquinol) at 200-400 mg morning and afternoons.

1 Mortensen SA, Leth A, Anger E, Rhode M, Dose-related decrease of serum Coenzyme Q10 during treatment with HMG-CoA reductase inhibitors, Molec Apects Med, Vol 18 (suppl) p137-44, 1997.

2 Langsjoen PH, Langsjoen PH, Folkers K, Asix-year clinical study of therapy of cardiomyopathy with coenzyme Q10, Int J Tissue React, 1990: 12(3):169-72.

3 Baggio E, Gandin R Placher AC, etal, Italian multicenter study on safety and efficacy of coenzyme Q10, Mol Aspects Med, 1994;15:S287-94.

4 Siantra Stephen A, Sinatra heaqlth report, June 2002;V8#6.

5 Weber C, Jakobsen TS, Mortensen SA, Paulsen G, Holmer G, Antioxidant effect of dietary coenzyme Q10 in human blood plasma, Internat J Vit Nutr Res.,1994;V64:p311-15.

6 Kamikawa T Kobayashi A, Yamashita T, Hayashi H, Yamazaki N, Effects of coenzyme Q10 on exercise tolerance in chronic stable angina pectoris, Am J Cardiol, 1985,56:247-51.

7 Langsjoen H, Langsjoen P, Langsjoen P Willis R, Folkers K, Usefulness of Coenzyme Q10 in clinical cardiology: a long term study, Mol Aspects Med(England), 1994;15 Suppl:p165-75.

8 Fujimoto S, Kurihara N, Hirata K,Takeda T, Effects of CoenzymeQ10 administration on pulmonary function and exercise performance in patients with chronic lung diseases, Clin Investig (Germany) 1993;V71(8 suppl):pS162-6.

9 Lockwood K, Moesgaard S, Yamamoto T, Folkers K, Progress on therapy of breast cancer with vitamin Q10 and regression of metastases, Biochem Biophys Res Commun (US),Jul 6,1995;212(1):p 172-7.

10 Folkers K, Simonsen R, Two successful double-blind trials with Coenzyme Q10 on muscular dystrophies and neurogenic dystrophies, Eiochim Biophys Acta (Netherlands), May 24 1995;1271(1):p 281-6.

11 Elliot William T, statins and the incidence of rhabdomyolysis, Pharmacology Watch, Febr 2005.

12 Kelly Patricia, annual meeting of Am Coll of Cardiol, as reported in Family Practice News, June 1 2005.

13 Singh RB, Niaz MA, Serum concentration of lipoprotein(a) decreases in treatment with hydrosoluable Q10 in patients with coronary artery disease, Int J CDardiol,1999;68(1):23-9.

14 Langsjoen P, Langsjoen P, Willis R, Folkers K, Treatment of essential hypertension with Coenzyme Q10, Mol Aspects Med (England)1994;15 suppl: p 265-72.

15 Digiesi V, Cantini F, Brodbeck B, Effect of CoenzymeQ10 on essential arterial hypertension, Curr Ther Res,1990;47:841-5.

16 Burke BE, Neuenschwander R, Olsen RD, Randomized, double–blind, placebo controlled trial of CoenzymeQ10 in isolated systolic hypertension, South Med J, 2001;94(11): p 1112-17.

17 Langsjoen PH, Folkers K, Lyson K, Muratsu K, Lyson T, Effective and safe therapy with coenzyme Q10 for cardiomyopathy, Klin Wochenschr (Germany,West) Jul1 1988;66(13):p583-90.

18 Langsjoen PH, Folker K, Lyson K, Muratsu K, Lyson T, Pronounced increase of survival of patients with cardiomyopathy when treated with coenzymeQ10 and conventional therapy, Int J Tissue React (Switzerland).1990;12(3): p163-8.

19 Singh RB, etal, Effect of hydrosoluable coenzyme Q10 on blood pressure and insulin resistance in hypertensive patients with coronary artery disease, J Hum Hypertens, 1999;13(3): p203-8.

20 Singh RB, Kumar A, Randomized, double-blind, placebo controlled trial of coenzyme Q10 in patients with end-stage renal failure, J Nutr Environ Med, 2003;13(1): p13-22.

21 Folkers K, Hanioka T, Xia LJ, McRee J Jr, Langsjoen P, Coenzyme Q10 increases T4/T8 ratios of lymphocytes in ordinary subjects and relevance to patients having AIDS related complex, Biochem Biophys Res Commun (United States), Apr 30 1991;176(2): p786-91.

22 Weis M, Mortnesen SA, Rassing MR, Moller-Sonnergaard J, Poulsen G, Rasmussen, Bioavailability of four CenzmeQ10 formulations in healthy volunteers, Mol Aspects Med (England), 1994;15 suppl: p273-80.

23 Teran E, Racines-Orbe, ViveroS, Escudero C, MolinaG, Calle A, Preeclampsia is associated with a decrease in plasma coenzyme Q10 levels, Free Radic Biol Med., 2003 Dec 1;35(11):1453-6.