National Cholesterol Education Month is coming to a close. We’ve discussed what cholesterol is and how it is measured. We’ve talked about heart disease, dietary sources of cholesterol, and how diet, exercise, and weight loss can help to lower blood cholesterol levels.
This week we will discuss the specific use of cholesterol-lowering drugs in the treatment of multiple sclerosis. Several studies have been reported in the past decade, however producing contradictory results. There is no clear answer, yet, as to the benefit of using these statin drugs as disease-modifiers in MS.
If you need more help in lowering cholesterol beyond that of lifestyle changes, then your doctor may prescribe a cholesterol-regulating drug. The major types of choleterol-lowering drugs are: (excerpted from Your Guide to Lowering your Cholesterol with TLC (pdf)
* Statins"”lovastatin, pravastatin, simvastatin, fluvastatin, atorvastatin, and rosuvastatin. Statins stop an enzyme that controls the rate at which the body produces cholesterol. They lower LDL levels more than other types of drugs"”about 20-55 percent"”and also moderately lower triglycerides and raise HDL.
* Ezetimibe. This drug reduces the amount of cholesterol absorbed by the body. Ezetimibe can be combined with a statin to get more lowering of LDL. Ezetimibe lowers LDL by about 18-25 percent.
* Bile acid resins. These bind with cholesterol-containing bile acids in the intestines and are then eliminated from the body in the stool. They lower LDL cholesterol by about 15-30 percent.
* Nicotinic acid"”also called niacin. This is a water-soluble B vitamin that should be taken only under physician supervision. It improves all lipoproteins"”total cholesterol, LDL, triglycerides, and HDL"”when taken in doses well above the vitamin requirement. LDL levels are usually reduced by about 5-15 percent, and up to 25 percent in some patients.
* Fibrates. They mostly lower triglycerides and, to a lesser degree, raise HDL levels. Fibrates are less effective in lowering LDL levels.
Statins as Multiple Sclerosis Treatment
For the past decade, small preliminary studies have suggested that statins may be helpful as a disease-modifying treatment or add-on therapy for patients living with MS or those who have experienced a first neurological event. Early results were promising and suggest that MS patients who also take statins have less nerve damage over time. Researchers found that "statins inhibited the formation of lymphocytes and monocytes, immune-system cells which cause inflammation by attacking the body’s nerve cells" in people with MS.
In a small study in 2008, the MS patients treated with atorvastatin (Lipitor) seemed to get worse. Ten of the 17 patients who received either 40 mg or 80 mg of atorvastatin had either a relapse or a new lesion on MRI as compared to only 1 of 9 patients taking placebo who experienced a relapse or had active lesions on MRI. The authors concluded that atorvastatin (40 mg or 80 mg) taken with interferon beta-1a (Rebif) worsened the MS. This was disappointing news.
However MS patients in the ACTIVE trial (Atorvastatin Combined To Interferon to Verify the Efficacy) who took atorvastatin (20mg) in addition to Rebif (interferon beta-1a) had significantly fewer gadolinium-enhanced lesions after 24 months of treatment versus baseline and significantly fewer relapses. The MS patients who only received Rebif experienced a slightly elevated risk for a 1-point EDSS increase after 24 months. Researchers conclude that low-dose atorvastatin may be beneficial, as add-on therapy, in poor responders to high-dose interferon beta-1a alone.
Are you confused yet? I am.
A study announced earlier this year which looked at adding 40 mg simvastatin (Zocor) to Avonex showed that the total number of relapses in the simvastatin group were significantly lower than the placebo group. The final EDSS scores were lower in the simvastatin group, as were the number of gadolinium-enhanced and new T2 lesions, as compared to the placebo group. However, the difference in these trends was not statistically significant.
Yet another study suggests that drugs such as lovastatin or simvastatin may interfere with the remyelination process in patients with MS. Primary oligodendrocytes treated with lovastatin formed membrane sheets which were devoid of the major myelin proteins including myelin basic protein (MSP). Based on this and other results, the authors suggest careful monitoring of the effects of statins on myelination before they are used in demyelinating diseases.
This all leaves me wondering whether the simvastatin (40mg) I am taking to lower my LDL cholesterol levels may be helping my MS or hindering it. That’s a question which cannot be answered at this time. Fingers crossed that it is helping to lower my "bad" cholesterol at least. :)
The research studies have been too small to get good statistical data regarding the use of statin medications as add-on therapies or disease-modifiers in multiple sclerosis. Hopefully larger trials will be carried out in an attempt to answer relevant questions. In the meantime, we know that statins were well-tolerated and safe in patients who were on interferon therapies. That’s good news.
SOURCES: High Blood Cholesterol: What You Need To Know (pdf) by NHLBI
Lock, Christopher. "Are “statins” beneficial or harmful in multiple sclerosis?" Neurology 2008;71:e54-e56.
Another study was announced at ECTRIMS 2010 in which the patients who received simvastatin in combination with Avonex seemed to have more disease activity and progression. You can read a good summary at Medscape Medical News.