Statin Related Muscle Pain and Coenzyme Q 10

Statins are used to lower cholesterol levels in an effort to reduce the risk of developing cardiovascular disease. They are used after a patient has exhausted lifestyle changes such as changing their diet to a low cholesterol diet, exercising regularly and losing weight without their cholesterol dropping to levels that are considered acceptable to reduce your risk of vascular events.

Patients starting on statins often complain of muscles aches, pains and slow recovery of muscle pain after exercising. In a few individuals the muscle pain, inflammation and damage becomes severe. One of the known, but little understood, negative side effects of statin medications are the lowering of your Coenzyme Q 10 level. CoQ10 works at the subcellular level in energy producing factories called mitochondria. Statin drugs, which inhibit the enzyme HMG-CoA Reductase lower cholesterol while also lowering CoQ10 levels by 16-54 % based on the study reporting these changes.

The November 16, 2018 edition of the Journal of the American Medical Association published a review article by David Rakel, MD and associates that suggested that supplementing your diet with CoQ 10 would reduce muscle aches and pains while on statin therapy. Twelve studies were reviewed and the use of CoQ10 was associated with less muscle pain, weakness, tiredness and cramps compared to placebo. The studies used daily doses of 100 to 600 mg with 200 mg being the most effective dosage. Finding the correct dosage is important because the product is expensive with forty 200 mg tablets selling for about $25.

Since CoQ10 is fat soluble, you are best purchasing formulations that are combined with fat in a gel to promote absorption. As with all supplements, which are considered foods not drugs , it is best if they are UPS Labs certified to insure the dosage in the product is the same as listed on the label and that it contains no unexpected impurities.

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More Good News for Coffee Drinkers

When I first started practicing, fresh out of my internal medicine residency and board certification, we were taught that consuming more than five cups of coffee per day increased your chances of developing pancreatic cancer. Thankfully that theory has been proven to be false.

Last week I reviewed a publication in a peer reviewed journal which showed that if you infused the equivalent of four cups of coffee into the energy producing heart cell mitochondria of older rodents, those mitochondria behaved like the mitochondria found in very young healthy rats. The authors of that article made the great leap of faith by suggesting that four cups of caffeinated coffee per day was heart healthy.

This week’s Journal of the American Medical Association Internal Medicine published a study which said if you drank eight cups of coffee per day your mortality from all causes diminished inversely. Their study included individuals who were found to be fast and slow metabolizers of caffeine. It additionally made no distinction between ground coffee, instant coffee or decaffeinated coffee.

The research study investigated 498,134 adults who participated in the UK Biobank study. The mean age of the group was 57 years with 54% women and 78% coffee drinkers. The study participants filled out questionnaires detailing how much coffee they drank and what kind. During a 10 year follow-up there were 14,225 deaths with 58% due to cancer and 20% due to cardiovascular disease. As coffee consumption increased, the risk of death from all causes decreased. While instant coffee and decaffeinated coffee showed this trend, ground coffee showed the strongest trend of lowering the mortality risk.

This is an observational study and, by design, observational studies do not prove cause and effect. It is comforting to know however that having an extra cup or two seems to be protective rather than harmful. At some point a blinded study with true controls will need to be done to prove their point. If the caffeine doesn’t keep you up or make you too jittery, and the coffee itself dehydrate you or give you frequent stools, then drink away if you enjoy coffee in large volume.

Fish, Fish Oils and Cardiovascular Disease

Years ago the scientific researcher responsible for the promotion of fish oils as an antioxidant and protector against vascular disease recommended we all eat two fleshy fish meals of cold water fish a week. He continued to endorse this dietary addition and included canned tuna fish and canned salmon in the types of fish that produced this positive effect.

Over the years I heard him lecture at a large annual medical conference held in Broward County and he fretted about the growth of the supplement industry encouraging taking fish oils rather than eating fish. He worried about the warnings against eating all fish to women of child bearing age because of the fear of heavy metal contamination and knew that the fish oils and omega 3 Fatty Acids played a developmental role in a growing fetus and child.

I then attended lectures, in particular one sponsored by the Cleveland Clinic, during which they promoted Krill oil as the chosen form of fish oil supplements because it remained liquid and viscous at body temperature of 98.6 while others solidified. I listened to this debate only to hear the father of the science speak again and this time advocate that one or two fleshy fish meals a month was adequate to obtain the protective effect of Omega 3 Fatty acids. He felt that the supplements did not actually provide a protective effect as eating real fish did. Since I love to eat fresh fish I had no problem with this message but others are not comfortable buying and preparing fish at home or eating it at a restaurant. Supplements to them were the answer.

Steve Kopecky, M.D. examined the question in an article published in JAMA Cardiology this week. He looked at 77,917 high risk individuals already diagnosed with coronary artery disease and vascular disease who were taking supplements to prevent a second event. His study concluded that taking these omega 3 supplements had no effect on the prevention of recurrent cardiovascular events. The study did not discuss primary prevention for those who have not yet had a vascular illness or event.

Once again it seems that eating fish in moderation, like most anything, is the best choice. I will continue to eat my fresh fish meals one or two times per week, not necessarily for the health benefit but because I enjoy eating fresh fish.

I advise those worried about preventing primary or secondary heart and vascular disease to find a form of fish they can enjoy if they want this benefit. If you really wish to reduce your risk of a cardiovascular event; I suggest you stop smoking, control your blood pressure and lipid profile, stay active and eat those fresh fish meals.

Primary Care Docs Outperform Hospitalists …

A study published recently in JAMA Internal Medicine looked at 650,651 Medicare patients hospitalized in 2013. It showed that when patients were cared for by their own outpatient physician they had a slightly better outcome than when the patients were attended to by full-time hospital based specialists who had not previously known them.

As an internal medicine physician who maintains hospital privileges, as well as caring for patients in an office setting, this study supports the type of medicine I have been trying to practice for the last 38 years. However, I am not naïve enough to believe it entirely.

In recent months similar studies have touted the benefit of female physicians over their male counterparts, younger physicians over older physicians and even foreign trained physicians over those trained in the USA. Based on these studies, one might conclude you should be treated by a young female outpatient physician who trained in a foreign country. While the JAMA study shows the success of the outpatient primary care physician, those in hospitalist medicine could similarly produce their own studies showing the benefit of using a hospital based physician or hospitalist.

I do believe having a familiar physician, you know and trust, adds a major level of comfort when you are ill. Having that physician consult within his or her referral network of physicians who know how that doctor expects the communication between doctors, and care to occur, is an additional benefit.

The fact that your personal physician knows what you look like in health gives them a distinct advantage in recognizing when you are ill. They know you and all about you and that helps. It especially helps patients with complex medical issues who require more time and thought. Being able to review the old records and previous specialty consultations which you were a part of seems to impart an advantage that someone just joining the care team does not yet possess.

This study does not say that outpatient primary care docs are better than hospitalists. It only points out that in a senior citizen population in 2013, patients cared for by their own primary care doctor had a better 30 day survival after a hospital stay.

Increased Dementia Risk in Senior Citizens Due to Proton Pump Inhibitors (PPIs)

Brittany Haenisch, PhD of the German Center for Neurodegenerative Diseases in Bonn, has reported in JAMA Neurology, a study from health insurance data suggesting that taking Proton Pump Inhibitors (PPIs) such as Aciphex (omeprazole), Protonix (pantoprazole), Nexium (esomeprazole), and Prevacid (lansoprazole), was associated with a markedly increased risk of developing dementia. The correlation was stronger in men than women with a slightly increased risk for those taking Nexium.

The study, conducted from 2004 through 2011, looked at 73,679 people age 75 years or older and who were free of dementia at “baseline”.  It revealed 29,510 patients (40%) developed dementia and, of these, almost 3,000 (average age of 84) were taking a PPI medication. The authors concluded that avoiding PPIs may prevent dementia.

All of these medicines are now freely sold over the counter not requiring a prescription. Their use has dramatically increased. There is belief from animal studies that PPIs cross the blood brain barrier and effect the production of amyloid and tau protein associated with dementia. In humans, B12 levels can be lowered effecting cognitive ability. None of this data shows a clear cause and effect relationship so we cannot say PPIs hasten the onset or cause dementia. Newer well designed controlled and blinded studies will be needed for this purpose.

In the interim, I will ask my patients to reduce or avoid these medications. We can treat heartburn and indigestion with products such as antacids, weight loss, eating smaller portions and staying upright after those meals, loosening your belt at the waist and avoiding those foods that reduce lower esophageal sphincter muscle pressure leading to reflux.

There will be some with conditions such as Barret’s Esophagus, which is precancerous, and recent bleeding ulcers which require the use of PPIs for eight or more weeks and then switch to Tums, Rolaids, Gaviscon or Carafate. Some patients will need the PPIs for symptom relief beyond eight weeks and they will need to make a tough decision between symptom relief and increased dementia risk while the researchers search for the answer.

High Disability and Death Rates in Bleeds Associated with New Oral Anticoagulants

In the trailer for the movie Jaws 2 they show a swimmer in the ocean with a deep voice saying, “Just when you thought it was safe to go back into the water…” followed by the classic music associated with a shark attack and a big fin approaching the unsuspecting swimmer. I feel much the same way upon reading a Medpage Today online journal review of an article in JAMA Neurology published on December 14, 2015. Jan C. Purrucker, MD and colleagues looked at 61 consecutive patients with non-trauma related cerebral hemorrhages due to the newer oral anticoagulants Pradaxa, Xarelto and Eliquis. Overall there was a death rate of 28% at three months and “two out of 3 survivors had an unfavorable outcome.”

In October of 2015 the FDA approved the use of the antibody fragment idarucizumab (Praxbind) to reverse anticoagulation in patients bleeding from the administration of the oral anticoagulant Pradaxa. There are currently no medications to reverse the bleeding from the drugs Xarelto or Eliquis but we are promised that new products are in development. The article goes on to discuss how physicians have been forced to improvise when patients on these medications show up bleeding. They have tried fresh frozen plasma, 3-factor, 4-factor and activated prothrombin complex concentrates prothrombin complex concentrates, recombinant factor VIIa and cryoprecipitate alone or in combination with marginal success at best.

Despite there being no antidote to these blood thinners, the massive direct to consumer advertising continues on television prime time and magazines as if the products are no more dangerous than an antacid for heartburn. Coumadin or warfarin is the prototype anticoagulant working by inhibiting vitamin K dependent clotting factors. Its effects are reversible with administration of Vitamin K and clotting factors if bleeding occurs. Coumadin requires periodic blood tests (INR) to check on its efficacy and there is a long list of medications and foods that need to be avoided or adjusted while taking it. It is less convenient but safer in the sense that its effects can be reversed with medication.

The newer oral anticoagulants were championed by several studies that suggested that they were more effective in preventing embolic strokes in patients with the heart rhythm atrial fibrillation. Many experts in the field felt that those conclusions were flawed because the Coumadin group was not tightly regulated to keep their INR in a therapeutic non-clotting range thus unfairly biasing the results in favor of the newer agents.

There is no question that the newer agents are more convenient than warfarin treatment, but until there are readily available antidotes, complications seem to be more difficult to limit and control.

Viagra, Cialis and Levitra Use and Malignant Melanoma

Risk v1Jiali Han, Ph.D of the Indiana University School of Public Health in Indianapolis reported in JAMA that use of Viagra or sildenafil was associated with an 84% greater risk of malignant melanoma. Their preliminary data obtained from the Health Professionals Follow-up Study (HPFS) looked at 51,529 men aged 40 – 75 years old and all health professionals. Beginning in 1986 these individuals filled out a detailed health questionnaire every other year. The researchers reached their conclusions after reviewing the 2,000 HPFS survey and excluding all participants with a history of melanoma, squamous cell cancer or basal cell skin cancer prior to calendar year 2000. They were left with 25,848 men who had a mean baseline age of 64.8 years. 5.3 % of these men (1370) reported use of sildenafil (Viagra). From 2000 until 2010 142 melanomas were reported in that group.

The authors theorize that Viagra and the other drugs promote tumor growth by inadvertently inhibiting our immune system’s ability to suppress tumor growth messages at the genetic and molecular level. They emphasize that this is a preliminary study that does not prove cause and effect but does generate enough concern to warrant the creation of a study to answer the question” Our data provide epidemiological evidence on possible skin adverse effects of PDE5A inhibitors and support continued investigation of this relationship.” There was no mention of frequency of use or dosage and development of melanoma.

The authors were clear that if the relationship does in fact hold true, it extends to all the drugs in this class. Considering the billions of dollars in pharmaceutical profit involved it is hard to imagine that the question will not be addressed in a well-planned and funded study.