From The August 2004 LE Magazine
By Kurt J. Samson
In 1983, the Life Extension Foundation introduced coenzyme Q10 (CoQ10) to the United States. Over the past 21 years, hundreds of studies have confirmed the safety and effectiveness of CoQ10 supplementation for health disorders ranging from neurological aging to heart disease.
Yet the US medical establishment and federal drug regulators have been hesitant to embrace these indings,
reserving opinion until more large-scale trials are completed. With several major studies under way, CoQ10 could be on the cusp of broader acceptance across a range of medical disciplines.
Ubiquinone, commonly referred to as coenzyme Q10, was originally so named because of its omnipresence in virtually every cell of the human body. According to Dr. Karl Folkers, a pioneer in the CoQ10 fermentation synthesis, CoQ10 should be properly renamed “vitamin Q,” and thus take its rightful place in the pantheon of essential nutrients.
Two main theories have been set forth as to how CoQ10 assists in achieving optimal health and regeneration from illness. First is its ability to increase the amount of energy available to those parts of the body whose cells most require it, including the heart, brain, kidneys, and skeletal muscles, among others. Second, many of the benefits derived from CoQ10 are thought to be a result of its potent antioxidant effects, as it scavenges dangerous free radical oxygen species that normally harm the body.
Dr. Folkers’ quest and legacy are being carried on by dozens of researchers whose efforts are continuing to bring information about CoQ10 to the forefront of academic medicine. A number of encouraging studies were published by respected medical and scientific journals in 2003 and early 2004. Life Extension surveyed the literature and herein presents some of the most significant highlights.
CoQ10 and Kidney Failure
In the Journal of Nutritional and Environmental Medicine, CoQ10 research pioneers Drs. Ram Singh and Adarsh Kumar reported the results of a very well-designed trial indicating CoQ10 might have a powerful role as adjunctive therapy in patients with end-stage kidney disease—in some cases even reducing or averting the need for dialysis. 
In a randomized, double-blind, placebo-controlled trial, the researchers found CoQ10 treatment decreased progression and reversed renal dysfunction in a majority of patients with end-stage disease, many of whom were able to discontinue dialysis over the course of the 12-week trial. The report followed up on a pilot study the scientists published in 2000 involving a smaller number of subjects.
End-stage kidney disease produces marked organ contraction and progressive dysfunction, with corresponding increases in levels of serum creatinine and blood urea nitrogen. Levels of toxic waste products accumulate in the blood because the kidneys cannot clear them from the body.
Dr. Singh and his colleagues documented significantly lower levels of serum creatinine and blood urea nitrogen in the CoQ10-treated patients, with increases in creatinine clearance and urine output regardless of patient dialysis or baseline status. More significantly, only half the number of CoQ10 patients required dialysis at the end of the study when compared to subjects receiving placebo.
The researchers also reported considerable increases in the antioxidant vitamins E and C and beta-carotene in treated subjects, while plasma levels of oxidative stress such as thiobarbituric acid reactive substances, diene conjugates, and malondialdehyde all fell dramatically.
Although one in five patients did not respond, the researchers concluded that CoQ10 supplementation improves renal function in end-stage patients regardless of dialysis status, and can delay or avert the need for dialysis. They suggested that higher doses than those used in their study (180 mg per day) might result in even greater improvement and response in others.
CoQ10 has been shown to be effective against chronic inflammation of the arteries and heart muscle tissue resulting in cardiac myopathy. In addition, studies by Japanese and Australian re-searchers, as well as by scientists in the US and elsewhere, have consistently shown the supplement’s effectiveness against congestive heart failure and in preventing secondary cardiac events after patients have suffered an initial heart attack.
In Molecular Cell Biology, Drs. Singh and Kumar published the results of another randomized, double-blind, placebo-controlled study showing CoQ10’s benefits in combating atherosclerosis, increasing survival, and reducing the risk of subsequent cardiac events in heart attack patients, including those taking lipid-lowering drugs. 
The scientists reported that among 73 patients receiving 120 mg per day of oral CoQ10 for one year after a first heart attack, the treated subjects suffered significantly fewer cardiac events than their untreated counterparts (24.6% vs. 45%). The CoQ10 group had a nearly 50% lower incidence of non-fatal heart attacks (13.7% vs. 25.3%) and significantly fewer deaths than the untreated patients.
Further, the researchers found plasma levels of vitamin E and protective high-density lipoprotein (HDL) were significantly higher in CoQ10 patients, and thiobar-bituric acid reactive substances, malondialdehyde, and diene con-jugates were lower than in the control group. According to Dr. Singh, it is important to note, with respect to concern over statin therapy and CoQ10 supplements, that half of the patients in each group were taking lovastatin.
Last year, Danish scientists at Copenhagen University Hospital’s Heart Center, led by noted re-searcher Dr. Svende Aage Mort-ensen, announced the launch of a large, two-year multinational trial to “establish the future role of CoQ10 as part of a maintenance therapy in patients with chronic heart failure.” 
The double-blind, multi-center trial will review morbidity and mortality data on patients with chronic heart failure taking supplemental CoQ10. In announcing the study design and endpoints in the journal Biofactors, which dedicated an issue to papers presented at the Third Conference of the International CoQ10 Association, Dr. Mortensen noted that double-blind, placebo-controlled trials have demonstrated the benefits of the bioenergetic antioxidant in more than 1,000 patients. Imp-roved exercise capacity, reduced hospitalizations, and significant improvements in various hemodynamic parameters have been the “overwhelming experience,” he writes, with only three of 13 studies showing neutral results.
“Thus, based on the available con-trolled data, CoQ10 is a promising, effective, and safe approach to chronic heart failure,” Dr. Mortensen concluded.
Dr. Mortensen also participated in a study examining serum concentrations of CoQ10 in 99 healthy male subjects taking daily 30-mg or 100-mg supplements for one month, compared with matched controls receiving placebo.
In this randomized, double-blind trial, he and Czech scientists at the Medical Faculty Hospital in Prague ascertained the median baseline serum level of CoQ10. Supplementation with 30 mg of CoQ10 resulted in an increase in the baseline concentration of CoQ10 of 44%, while an increase of 108% was noted in the group that received 100 mg of CoQ10. These changes were significantly higher in both groups of subjects supplemented with CoQ10 compared to the group that received placebo, regardless of baseline CoQ10 levels, age, or body weight.
Late last year, Japanese scientists at the University of Kyoto’s Graduate School of Medicine add-ed further evidence that CoQ10 protects the heart muscle against acute viral myocarditis, a life-threatening infection of the heart walls. 
Dr. Chiharu Kishimoto and colleagues infected mice with a strain of encephalomyocarditis virus in order to measure the degree of oxidative damage and DNA injury, using thioredoxin expression and 8-hydroxy-2’-deoxyguanosine in the myocardium to measure CoQ10’s benefits. The scientists found survival was about three times higher in treated mice, with significantly increased levels of CoQ10 in the heart muscles and a marked decrease in serum creatine kinase (a marker of heart muscle damage). Further, the up-regulation of myocardial thioredoxin indicating DNA damage was considerably lower in treated mice. The researchers concluded that pretreatment with CoQ10 (supplementation) can reduce the severity of viral myocarditis as well as oxidative stress and DNA damage in the myocardium.
CoQ10 deficiency in muscle cell mitochondria results in poor cellular respiration.
Oxidative mechanisms and endothelial cell inflammation are recognized as
important factors in coronary heart disease and atherosclerosis. Evidence
shows CoQ10 supplementation can improve the circulatory process and prevent
such irreversible and often fatal conditions as cardiomyopathy, congestive
heart failure, and rhabdolmyolysis (muscle wasting induced by statin drug
Since their introduction, HMG-CoA reductase drugs (statins) have
helped millions of people to lower their cholesterol levels. At
the same time, however, studies have shown that statin stalwarts
such as Lipitor® (atorvastatin), [6,7 ]Zocor® (simvastatin),  Pravacol® (pravastatin), [7,8] and Mevacor® (lovastatin) [8,9] can deplete natural levels of CoQ10 throughout the body.
Statins have surpassed hypertension medications in generating
revenues for pharmaceutical manufacturers, accounting for an estimated
$16 billion in revenues in 2003. These are powerful drugs, but
they also carry the risk of a dose-dependent decrease in the body’s
production of CoQ10. The FDA does not require statin manufacturers
to alert patients and physicians to this potential consequence,
even though many recent studies have demonstrated that CoQ10 deficits
in statin users can cause cognitive, muscular, cardiovascular,
and other problems. Conversely, CoQ10 supplementation can alleviate
these issues in many patients, researchers have found.
Statins sold in Canada are required to carry on their labels
a precautionary warning expressly stating that such CoQ10 depletion
can lead to impaired cardiac functioning in patients with congestive
heart failure. The US government requires no such warning, despite
an emerging generation of “super-statins” (rosuvastatin,
pitavastatin) that may further increase the risk and rate of CoQ10
depletion in patients taking the drugs. Schering-Plough recently
introduced Zetia®, a product that quadruples the dose of first-generation
statins. The FDA approved another powerful drug, Astra-Zeneca’s
Crestor®, in August 2003.
Writing in the November 2003 issue of Smart Money magazine, journalist
Eleanor Laise took Pfizer to task for failing to address patients
who have suffered memory loss, severe muscle pain, and other symptoms
of CoQ10 depletion after taking the company’s best-selling
statin Lipitor“. She noted that Pfizer has thus far balked
at acknowledging any association between statins, CoQ10 depletion,
and serious side effects. 
| Canadian health authorities require
that statins sold in Canada carry a precautionary warning
regarding CoQ10 depletion. Pfizer’s Lipitor® contains
The Effect on Ubiquinone
“Significant decreases in circulating ubiquinone
levels in patients treated with atorvastatin and other
statins have been observed. The clinical significance
of a potential long-term statin-induced deficiency of
ubiquinone has not been established. It has been reported
that a decrease in myocardial ubiquinone levels could
lead to impaired cardiac function in patients with borderline
congestive heart failure . . .”
While drug manufacturers and the FDA have yet to weigh in on
the issue, Merck, maker of the popular Zocor“, applied for
patents in 1989 and 1990 for CoQ10-simvastatin combination products.
The company’s 1989 patent application states that a combined
statin-CoQ10 product might be effective against not only cardiomyopathy,
but also elevated levels of the enzyme transaminase, which reflects
liver damage. The company has thus far declined to exercise these
patents, and the FDA and other major drug manufacturers have yet
to acknowledge the risk of CoQ10 depletion from statins.
According to a Pfizer official quoted in the Smart Money article,
the drug company has been unable to document “any specific
effect” on the heart muscle during clinical trials, a surprising
statement considering that several studies by respected medical
researchers at the time Lipitor“ was being tested warned
of the cardiovascular dangers of CoQ10 depletion.
“The depletion of the essential nutrient CoQ10 by the increasingly
popular cholesterol-lowering drugs HMG-CoA reductase inhibitors
(statins) has grown from a level of concern to one of alarm,” notes
Dr. Peter Langsjoen of East Texas University, in a comprehensive
review of animal and human studies of statins and CoQ10 depletion
published last year in the journal Biofactors.  “With ever
higher statin potencies and doses, and with a steadily shrinking
target LDL cholesterol, the prevalence and severity of CoQ10 deficiency
are increasing noticeably.”
Under revised target cholesterol guidelines issued by the National
Institutes of Health in 2001, as many as 36 million Americans are
now candidates for therapeutic statin intervention, up from 13
million under the old guidelines. Yet the issue of CoQ10 depletion
remains unresolved within the regulatory milieu that addresses
side effects and warning-label requirements.
“We are currently in the midst of a congestive heart failure
epidemic in the United States . . . As physicians it is our duty
to be absolutely certain that we are not inadvertently doing harm
to our patients by creating a widespread deficiency of a nutrient
critically important to heart function,” writes Dr. Langsjoen.
Dr. Langsjoen joined Dr. Mark Silver of the Heart Failure Institute
at Advocate Christ Medical Center in Oak Lawn, IL, in presenting
a study design for determining whether CoQ10 levels might be used
to measure myocardial diastolic function as an early marker of
ventricular dysfunction. 
They reasoned that statins in-hibit HMG-CoA reductase, the rate-limiting
step that inhibits cholesterol and CoQ10 synthesis in the liver.
Because CoQ10 plays an important role during oxidative phosphorylation
in the myocardial cell, evaluating CoQ10 action on ATP might be
used as an early-warning indicator of potential heart problems.
After a number of baseline cardiovascular and metabolic measurements
are established for each subject, the researchers suggest, they
would receive oral atorvastatin (Lipitor®) of 20 mg per day
for three to six months, with baseline levels repeated after three
and six months of treatment. Patients demonstrating reduced measurement
of diastolic left ventricular function that worsened during the
three to six months of statin therapy would then receive 300 mg
per day for three months, with follow-up echocardiogram and blood
CoQ10 level measurements. The objective would be to see if CoQ10
supplementation could reverse statin-induced heart failure.
At the University of Texas at Austin’s Biochemical Institute,
researcher Dr. Flora Pettit discovered that CoQ10 may be helpful
in assessing susceptibility to statin toxicity and determining
which patients might benefit from CoQ10 supplementation.
She reported in the journal Drug Metabolism and Drug Interactions that even low levels of statins are toxic to human lymphocytes
in cell cultures, ading that the patient’s own plasma reversed
this toxicity in some instances.  Adding CoQ10 to plasma, however,
was more effective than plasma alone in reversing cell toxicity
in some of these patients, Pettit and colleagues found.
Coumadin and CoQ10
While some doctors have suggested that CoQ10 might interfere with the effects
of the popular blood-thinner warfarin (Coumadin“), a trial by Danish
researcher Jyette Engelsen and colleagues, published in the Danish medical
journal Ugeskrift for Laeger, found no association between CoQ10
supplementation (100 mg per day) and the clinical anti-coagulant effect observed
in a group of 24 patients on long-term warfarin treatment. 
Moreover, the study’s randomized, double-blind, placebo-controlled,
cross-over methodology presents a far more convincing argument
that the risk is minimal. Nevertheless, warfarin patients are advised
to consult their doctors and frequently monitor their blood test
results to assess clotting time (prothrombin time/INR), especially
in the first two weeks (something that is already done in most
cases, the scientists noted).
Muscular dystrophy patients receiving CoQ10 therapy showed significantly less
cytogeneic and DNA damage than their untreated counterparts, according to
a study by Dr. Lucia Migliore and colleagues at Pisa University in Italy.
They compared basal levels of nuclear DNA (nDNA) damage as measured by chromosomal
and DNA alterations in leukocytes in 13 patients. 
The subjects, ranging in age from 29 to 74 and presenting with
several forms of muscular dystrophy, were compared with a subgroup
of 10 patients who received a two-week course of ubidecarenone,
a CoQ10 analogue. Untreated muscular dystrophy patients showed
an increased level of chromosomal damage (frequency of micronucleated
lymphocytes) compared with equally matched individuals receiving
“Patients receiving ubidecare-none showed a statistically
significant reduction in the frequency of micronucleated cells
after therapy, while only a slight decrease was observed in the
levels of both primary DNA damage and oxidized bases,” the
scientists reported in the January 2004 issue of Mutagenesis.
Several interesting studies were reported on CoQ10’s effects against
certain cancers. Studying differences between malignant and non-malignant prostate
cancer cells, Dr. Jose L. Quiles and colleagues at the University of Granada,
Spain, found that malignant cells respond very differently to coenzyme Q10. 
CoQ10 supplementation significantly lowered cell growth of the
PC3 cancer line without affecting non-malignant cells. The authors
noted that if the findings are confirmed, they might present a “novel
and interesting” approach using coenzyme Q10 in cancer therapy.
CoQ10 may play a role in the health of sperm cells in fighting male infertility,
according to Dr. Antonio Mancini and colleagues at the Institute of Endocrinology
at Catholic University of the Sacred Heart in Rome, Italy. 
In an earlier study, they found CoQ10 was present in seminal
fluid and directly correlated to sperm motility in infertile men,
with the exception of those with varicocele, a dilation of the
pampiniform venous plexus associated with infertility.
A follow-up published in the journal Metabolism evaluated distribution
of CoQ10 in seminal fluid and plasma in 32 varicocele patients
and healthy male controls in an effort to determine whether any
metabolic abnormalities played a role in various seminal parameters
in varicocele patients.
The researchers reported a significantly higher proportion of
CoQ10 in the seminal fluid of varicocele subjects, with high cellular
CoQ10 levels correlated with low sperm concentration and motility,
suggesting that such patients may be more sensitive to peroxidative
damage and therefore reduced energy utilization that might then
translate into defective motility. Further, the findings might
indicate a possible molecular defect involved in the condition.
Females also demonstrate a reproductive protective benefit. During
preeclampsia, a life-threatening disorder affecting about 7% of
late-stage pregnancies, women suffer edema, hypertension, and proteinuria.
Serum levels of CoQ10 are severely decreased in preeclampsia patients,
reported Dr. Enrique Teran, a scientist at the University of Ecuador
in Quito. 
In a study published in the journal Free Radical and Biological
Medicine, Dr. Teran and his colleagues measured concentrations
of CoQ10 in a group of 18 healthy pregnant women, 12 subjects with
preeclampsia, and 22 women who were not pregnant or hypertensive.
In the normal pregnant women, CoQ10 levels were significantly higher
than in nonpregnant women or those with preeclampsia. The mean
level of CoQ10 was 1.08 in healthy pregnant women, 0.86 in non-pregnant
women, and 0.70 in women with preeclampsia.
A study conducted by research-ers at Columbia University College of Physicians and Surgeons in New York found CoQ10 deficiency in the brains of 17 patients with cerebellar ataxia and/or atrophy, suggesting an ataxic syndrome responsive to therapy with the supplement.  The scientists examined the distribution of CoQ10 in different brain regions in animals and in one human subject before and after administering CoQ10 supplements. In experimental rats, the lowest levels of CoQ10 were found in the cerebellum, but the relative proportion was similar in the blood, organs, and tissue.
CoQ10 and the Brain
In the human subject, daily supplementation with CoQ10 increased levels in the blood and liver, but CoQ10 levels in the brain remained low in four brain regions.
Nonetheless, the findings suggest “selective vulnerability” in the cerebellum to CoQ10 depletion and its protective mechanisms, according to Drs. Ali Naini and Salvatore DiMauro.
In the journal Ophthalmologica, Dr. Janos Feher, a researcher at the University of Rome, Italy, reported that CoQ10 may improve retinal function in patients with age-related macular degeneration by improving the performance of mitochondria in the retinal pigment epithelium. 
Dr. Feher and associates treated 14 patients diagnosed with early age-related macular degeneration using a preparation that included CoQ10, acetyl-L-carnitine, polyunsaturated fatty acids, and vitamin E. A matched control group received vitamin E alone. A number of tests were then performed at 3, 6, 9, 12, and 24 months.
In patients receiving the CoQ10 mixture, all functions were slightly improved after three months and remained level throughout the two-year study period, while degeneration and visual function among participants in the control group continued to slowly decline.
In a study of Parkinson’s disease patients, 360 mg a day of CoQ10 was administered for only four weeks, producing a mild symptomatic improvement compared to placebo. More important, an established clinical test to measure Parkinson’s symptom function showed significantly better improvement of performance in the CoQ10-supplemented patients compared with the placebo group. 
This new study helped to corroborate a report last year that Parkinson’s patients consuming 1200 mg a day of CoQ10 showed a 44% reduction in the decline of motor skills, movement, and mental function compared to the placebo group. Those receiving this high-dose CoQ10 also demonstrated an improved ability to perform daily living tasks. This 16-month study was remarkable in that CoQ10 slowed the progression of the disease, something that Parkinson’s drugs do not do. 
As the many studies outlined in this article show, biomedical researchers are discovering that CoQ10 shows promising effects against disorders as far-ranging as kidney failure, heart disease, muscular dystrophy, and macular degeneration. Despite the ever-growing number of clinical trials attempting to unlock CoQ10’s disease-preventing capabilities, widespread acceptance of CoQ10 by mainstream medical practitioners and federal health regulators continues to lag far behind the research findings. As larger and more varied studies of CoQ10 are undertaken and the results disseminated, the day when this critical nutrient gains the attention it deserves appears to be drawing ever nearer.
1. 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):13-22.
2. Singh RB, Neki NS, Kartikey K, et al. Effect of coenzyme Q10 on risk of atherosclerosis in patients with recent myocardial infarction. Mol Cell Biochem. 2003 Apr;246(1-2):75-82.
3. Mortensen SA. Overview on coenzyme Q10 as adjunctive therapy in chronic heart fail ure. Rationale design and end-points of Q- symbiol” – multinational trial. Biofactors. 2003;18(1-4):79-89.
4. Kishimoto C, Tomioka N, Nakayama Y, Miyamoto M. Antioxidant effects of coenzyme Q10 on experimental myocarditis in mice. J Cardiovasc Pharmacol. 2003 Nov;42(5):588-92.
5. Rosenfeldt F, Hilton D, Pepe S, Krum H. Systematic review of effect of coenzyme Q10 in physical exercise, hypertension and heart failure. Biofactors. 2003;18(1-4):91-100.
6. Langsjoen PH, Langsjoen AM. The clinical use of HMG CoA-reductase inhibitors and the associated depletion of coenzyme Q10. A review of animal and human publications. Biofactors. 2003;18(1-4):101-11.
7. Passi S, Stancato A, Aleo E, Dmitrieva A, Littarru GP. Statins lower plasma and lymphocyte ugiquinol/ubiquinone without affecting other antioxidants and PUFA. Biofactors. 2003;18(1-4):113-24.
8. Mortensen SA, Leth A, Agner E, Rohde M. Dose-related decrease of serum coenzyme Q10 during treatment with HMG-CoA reductase inhibitors. Mol Aspects Med. 1997;18(suppl):S137-S144.
9. Folkers K, Langsjoen P, Willis R, et al. Lovastatin decreases coenzyme Q levels in humans. Proc Natl Acad Sci USA. 1990 Nov;87(22):8931-4.
10. Laise, E.
The Lipitor Dilemma
Smart Money. November, 2003.
11. Silver MA, Langsjoen PH, Szabo S, Patil H, Zelinger A. Statin cardiomyopathy? A potential role for Co-Enzyme Q10 therapy for statin-induced changes in diastolic LV performance: description of a clinical proto- col. Biofactors. 2003;18(1-4):125-7.
12. Pettit FH, Harper RF, Vilaythong J, Chu T, Shive W. Reversal of statin toxicity to human lymphocytes in tissue culture. Drug Metabol Drug Interact. 2003; 19(3):151-60.
13. Engelsen J, Neilsen JD, Hansen KF. Effect of coenzyme Q10 and ginkgo biloba on war- farin dosage in patients on long-term war- farin treatment. A randomized, double-blind, placebo-controlled cross-over trial. Ugeskr Laeger. 2003 Apr 28;165(18):1868-71.
14. Migliore L, Molinu S, Naccarati A, Mancuso M, Rocchi A, Sicilano G. Evaluation of cyto-genetic and DNA damage in mitochondrial disease patients: effects of coenzyme Q10 therapy. Mutagenesis. 2004 Jan;19(1):43-9.
15. Quiles JL, Farquharson AJ, Ramirez-Tortosa MC, et al. Coenzyme Q10 differentially moderates phospholipid hydroperoxide glu- tathionate peroxidase gene expression and free radicals production in malignant and non-malignant prostate cancer. Biofactors. 2003;18(1-4):265-70.
16. Mancini A, Milardi D, Conte G, et al. Coenzyme Q10: another biochemical alteration linked to infertility in varicocele patients? Metabolism. 2003 Apr;52(4):402-6.
17. Teran E, Racines-Orbe, Vivero S, Escudero C, Molina G, Calle A. Preeclampsia is associated with a decrease in plasma coenzyme Q10 levels. Free Radic Biol Med. 2003 Dec 1;35(11):1453-6.
18. Naini A, Lewis VJ, Hirano M, Dimauro S. Primary coenzyme Q10 deficiency and the brain. Biofactors. 2003;18(1-4):145-52.
19. Feher J, Papale A, Mannino G, Gualdi L, Balacco Gabrielli C. Mitotropic compounds for the treatment of age-related macular degeneration. The metabolic approach and a pilot study. Ophthalmol. 2003 Sept- Oct:217(5):351-7.
20. Muller T, Buttner T, Gholipour AF, Kuhn W. Coenzyme Q10 supplementation provides mild symptomatic benefit in patients with Parkinson’s disease. Neurosci Lett. 2003 May 8;341(3):201-4.
21. Shults CW, Oakes D, Kieburtz K, et al. Effects of coenzyme Q10 in early Parkinson disease: evidence of slowing of the function al decline. Arch Neurol. 2002 Oct;59(10):1541-50
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