NEW YORK—High doses of Co-enzyme Q10 appear to slow the progression of early stage Parkinson’s disease, reported Clifford Shults, MD, at the annual meeting of the American Neurological Association.
Patients receiving CoQ10, 1,200 mg per day, for 16 months scored 44 percent better on standardized measures of Parkinson’s progression than those receiving a placebo, according to Dr. Shults, a neurologist at the University of California, San Diego and Veteran Affairs San Diego Healthcare System. The CoQ10-treated patients developed less disability overall, with the biggest effect seen in preventing decline in ability to carry on daily activities. This means that some of the patients taking the supplement maintained their independence for longer by retaining, for example, the ability to dress, shower, brush their teeth, and feed themselves.
The study, the first major placebo-controlled trial of CoQ10, was supported by a grant from the National Institutes of Health, Bethesda, Maryland, and the National Institute of Neurological Disorders and Stroke. In addition to its historical significance, the trial is also a landmark in that it is the first study to demonstrate clear neurologic benefits for a nutrient increasingly recognized for its positive cardiovascular effects. The data were published in the October 2002 issue of Neurology Archives.
The double blind study included 80 people with early signs of Parkinson’s disease (PD), randomly assigned to take 300 mg, 600 mg or 1,200 mg of CoQ10 or a placebo daily. The wafers, combining 300 IU of vitamin E with the co-enzyme or placebo, were taken with meals and at bedtime.
Progression of PD was measured by a battery of tests comprising the Unified Parkinson’s Disease Rating Scale (UPDRS). Mean total UPDRS scores were compared at enrollment in the study, and at 1, 4, 8, 12 and 16 months or until increased disability required conventional therapy with levodopa.
Slower Progression, Less Disability
The UPDRS assesses PD patients’ ability to function mentally, emotionally, and physically, and evaluates how they cope with daily tasks. A total score of 199 indicates the worst disability. Scores in each area are generally from zero to four, with zero corresponding to normal and four to helpless. The activities of daily living segment relates to speech, salivation, handwriting, cutting food, handling utensils, hygiene, walking, tremor and numbness.
A comparison of average UPDRS scores from start to finish of the study showed a significant difference (P = 0.04) only for those taking 1,200 mg CoQ10. This group experienced less worsening of symptoms, as indicated by a mean UPDRS rise of only 6.69 compared with 11.99 in the placebo group.
In practical terms, patients on 1,200 mg CoQ10 had less difficulty being understood, were able to walk without assistance, and to cut up most foods without help. “The groups receiving co-enzyme Q10 had less change and this was most striking in the group that received the highest dose. This was about a 44 percent reduction in the worsening. We saw a benefit on all three components of UPDRS but most prominently on the activities of daily living scale,” said Dr. Shults.
No Harm at High Doses
Dr. Shults said it was “premature” to make a broad recommendation that Parkinson’s patients routinely take high-dose CoQ10 until a larger study confirms these results.
On the other hand, there appears to be no harm in taking up to 1,200 mg daily. PD patients taking either 300 mg, 600 mg or 1,200 mg daily of the co-enzyme had no greater incidence of side effects such as headaches, stomach upset, or dizziness compared with those on placebo. “CoQ10 was remarkably well tolerated. No dose reductions were needed in either of the three groups,” said Dr. Shults. “The percentage of CoQ10 treated subjects reporting adverse event in the three groups was not significantly different from that in the placebo group. And there was no significant trend by dosage.”
Out of 84 lab parameters measured, the investigators found a marginally significant trend by CoQ10 dosage in increased serum carbon dioxide levels (P = 0.01), high mean corpuscular hemoglobin concentration (P = 0.08), elevated sodium (P = 0.06) and elevated uric acid (P = 0.08). But none of these changes were clinically significant. There were no significant differences among the treatment groups for body weight, blood pressure or heart rate. CoQ10 in excess of 300 mg daily can increase serum SGOT, an important liver enzyme. But Dr. Shults reported that he did not find this to be true in the study.
Levodopa Sparing Effect
PD affects about 1.5 million Americans, according to the National Parkinson Foundation. Although the cause is unknown, it is associated with a loss of dopaminergic neurons in the substantia nigra area of the brain. Since PD patients have less dopamine than people without the disease do, levodopa, a precursor of dopamine, is the most common conventional therapy.
Dr. Shults’ protocol permitted investigators to decide at each check-up whether a patient should be removed from the study and given levodopa. Although the mean time to levodopa treatment was not longer for patients taking CoQ10 compared to the placebo group, 11 out of 21 patients (52%) in the 1,200 mg group completed the study without levodopa, compared to only 5 of 18 (28%) in the placebo group.
“The group that received 1,200 mg a day tended to reach the need for levodopa more slowly, and there were fewer patients that needed levodopa in this group,” said Dr. Shults.
He and his colleagues have been studying CoQ10 in the context of PD for over a decade; they hypothesized that it could be a factor in protecting dopamine-producing neurons from the degeneration seen in diseases such as PD. CoQ10 is integral to mitochondrial adenosine triphosphate and energy production. PD patients have lower levels of CoQ10 and mitochondrial activity than do those without the disease (Shults CW et al. Ann Neurol 1997; 42:261–264).
Taking CoQ10 orally clearly increases plasma concentrations (Shults CW et al. Neurology 1998; 50:793–795). Mice fed CoQ10 also have increased amounts of the co-enzyme in the brain, indicating the orally ingested co-enzyme can reach the brain (Matthews RT et al. Proc Natl Acad Sci 1998; 95:8892–8897). In a separate study, mice given CoQ10 with food suffered less dopamine loss when treated with a chemical known to damage dopamine-producing neurons, compared with mice not given the co-enzyme (Flint Beal M et al. Brain Research 1998; 783:109–114).
In the present study, plasma levels of CoQ10 and mitochondrial activity increased significantly in the 1,200 mg group. The researchers noted that the plasma and presumably brain levels of CoQ10 might be the factor that determines the effectiveness of the treatment (Shults CW et al. Neurology Archives 2002; 59:1541–1550).
PD patients interested in taking CoQ10 need to be aware of differences in brands and possible drug interactions. As with most vitamins and supplements available from health food stores not all brands of CoQ10 exhibit the same purity, concentration of coenzyme, or isomeric form of CoQ10. Some brands of CoQ10 have been tested by Consumer Lab.com and are posted on their website: http://www.consumerlab.com.
Be Aware of Propylene Glycol
One concern for anyone taking 1,200 mg of CoQ10 daily is that they could be absorbing unsafe amounts of propylene glycol. Approximately 25 percent of retail CoQ10 products contain propylene glycol, according to Cheryl Myers, director of product development for Vitaline, the company that provided the product for Dr. Shults’ study.
Propylene glycol is a non-active excipient compound added to improve the absorption of CoQ10. The Food and Drug Administration classifies propylene glycol as “generally recognized as safe” as an additive in food, and it is not always listed on product labels. The maximum safe amount of propylene glycol according to the 1994 Handbook of Pharmaceutical Excipients (American Pharmaceutical Association/Royal Pharmaceutical Society of Great Britain), is 1,000 mg per day.
“In some products we looked at there was the same amount of propylene glycol as CoQ10,” said Ms. Myers, noting that taking twelve 100 mg capsules of the co-enzyme daily could push propylene glycol ingestion past the safe limit by twenty percent. The Vitaline CoQ10 used in this study does not contain propylene glycol according to Ms. Myers. It can be purchased directly from Vitaline by calling 1-800-287-5972.
Trans versus Cis
Another issue for PD patients is that the more expensive trans isomer of CoQ10, as used in this study, is produced by a fermentation process, whereas the cheaper cis form is made through chemical reaction in a laboratory. The trans form resembles the endogenous co-enzyme more closely than the cis form, Ms. Myers told Holistic Primary Care. The problem is that product labels do not always indicate whether a bottle contains the cis or trans form. “People would have to ask the company which form it is before they purchase it.”
CoQ10 is manufactured in the body and can be obtained in small amounts from foods such as unsaturated oils, fish, meat and nuts. However the amounts used in this study would be impossible to obtain from food. Eating one pound of sardines, two pounds of beef or one and a half pounds of peanuts only provides 30 mg of CoQ10 according to Kathrynne Holden, MS, RD, who responds to questions on the National Parkinson Foundation website http://www.parkinson.org/index.htm.
To date, there have been no specific studies testing whether CoQ10 interferes with conventional PD treatments like levodopa or selegiline. Patients in Dr. Shults’ study were not taking any other PD medications. Vitaline’s Ms. Myers stressed that the company is, “unaware of any interactions with prescription medications with the possible exception of warfarin or coumadin. There are mixed reviews on that. Some say that because CoQ10 is so similar to Vitamin K—they look very much alike chemically—it may interfere with the effect of coumadin.” People using warfarin should not take CoQ10 without discussing it with their physicians.
Some medications, including some diabetes drugs, cholesterol lowering statins, and the dietary supplement Cholestin, may interfere with endogenous production of CoQ10. Many doctors now routinely prescribe CoQ10, particularly for patients taking statins, according to Ms. Holmes, of the National Parkinson’s Foundation.
While the data from this trial are definitely promising, the proper role of CoQ10 in the management of PD remains to be determined. Researchers are planning a Phase III trial to test whether CoQ10 slows the progression of Parkinson’s disease at doses of 1,200 mg and possibly higher for longer periods, but the study has not yet been funded.
Dr. Shults can be contacted via email at: cshults@ucsd.edu.
