Category Archives: Supplements and Vitamins

Treatment of Palpitations Due To Benign PVCs: Potassium, Magnesium and Lifestyle Adjustment

In a previous post, the skeptical cardiologist pontificated on the causes and evaluation of the most common cause of palpitations: premature ventricular contractions or PVCs.

The vast majority of these common extra beats turn out to be benign (meaning not causing death, heart attack or stroke), and most patients with sufficient reassurance of this benignity (often accompanied by significant caffeine reduction), do well. These people usually continue to notice the beats either randomly, or with stress, but they recognize exactly what is going on and are able to say to themselves “there go my benign PVCs again,” and aren’t worried or bothered.

A small percentage of patients that I diagnose with palpitations due to benign PVCs continue to have symptoms.

Part of my initial evaluation involves checking potassium, magnesium, kidney function, and thyroid levels.

Potassium Supplementation For PVCs

Low potassium levels (hypookalemia) have been clearly associated with an increase in ventricular ectopy. Patients who take diuretics like hydrochlorothiazide (HCTZ, often used for high blood pressure) or furosemide (Lasix, often used for leg swelling or heart failure), are at high risk for hypokalemia with potassium levels less than 3.5 meQ/L.

Hypokalemia can also develop if you are vomiting, having diarrhea, or sweating excessively. There are lots of other infrequent causes including excess licorice consumption. The body regulates potassium levels closely, due to its importance in the electrical activities involved in cardiac, muscular and neurological function.

The normal range of potassium (K) is considered to be 3.5 to 5 meq/L , however, I have found that PVCs are more frequent when the potassium is less than 4.

Most of my symptomatic PVC patients with potassium less than 4 find significant improvement with potassium supplementation.  I usually give them a prescription for potassium chloride (KCl) 10-20 meq daily to accomplish raising the level to >4.

An alternative to potassium supplements is ramping up how much
screen-shot-2017-03-02-at-6-18-48-pm screen-shot-2017-03-02-at-6-19-11-pmpotassium you consume in your diet. Most patients I talk to about low K immediately assume they should eat more bananas, but lots of fresh fruit and vegetables contain as much or more K than bananas.

The charts to the right show that a medium tomato contains as much K as a medium banana with a third of the calories. Avocados are a great source of K and contain lots of healthy fat. Yogurt (and I recommend full fat yogurt, of course) is a great source as well.

If you have  kidney disease you are much more likely to develop hyperkalemia, or high K, and you want to avoid these high K foods. Potassium infusions are used as part of a “lethal injection” in executions because extreme hyperkalemia causes the heart to stop beating. (In fact, Arkansas is hurrying to execute 8 men between April 17 and 27 utilizing KCl.  According to deathpenaltyinformation.org: “The hurried schedule appears to be an attempt to use the state’s current supply of eight doses of midazolam, which will expire at the end of April. Arkansas does not currently have a supply of potassium chloride, the killing drug specified in its execution protocol, but believes it can obtain supplies of that drug prior to the scheduled execution dates”)

Lifestyle, Stress  and PVCs

It’s probably time I revealed that I have PVCs. I feel them as a sense that something has shifted inside my chest briefly, like my breath has been interrupted, like my heart has hiccoughed. If I didn’t know about PVCs and hadn’t made the diagnosis very quickly by hooking myself up to an ECG monitor in my office, I know I would have become very anxious about it.

I know exactly what causes them: stress and anxiety. And this is the case for many patients. Stress activates our sympathetic nervous system, causing the release of hormones from the adrenal gland that prepare us for “fight or flight.” These hormones stimulate the heart to beat faster and harder and often trigger PVCs.

I rarely get PVCs these days, as the major source of stress in my personal life has gone away. This is also a typical story my patient’s relate: troubling palpitations seem to melt away when they retire or change to less stressful occupations, or as they recover from depression/anxiety/grief related to death of loved ones, divorce or illness.

You can’t always control external stresses, but several factors in your lifestyle are key to managing how those stresses activate your sympathetic nervous system and trigger troubling PVCs.

Dr. Mandrola lists as Steps 5-8 (Steps 1-4 are reassurance) for PVC treatment his “four legs of the table of health”:

: good food, good exercise, good sleep and good attitude. Cutting back on caffeine and alcohol, looking critically at the dose of exercise, going to bed on time, and smiling are all great strategies for PVCs.

Of these four table legs, I consider regular aerobic exercise the most important, and modifiable factor for PVC reduction.  Aerobic exercise improves mood and increases the parasympathetic (the calming component of the autonomic nervous system) activity, while lowering the output of the sympathetic nervous system.

The three factors that I find essential to handling the demanding and stressful job of being a cardiologist: restful sleep, regular, aerobic exercise and lots of love from my eternal fiancee (who also has occasional PVCs!)

watchos3-breathe-app-animation-wrap
Apple Watch trying to get me to breathe (something I ordinarily don’t do). According to Apple (my comments in parentheses) “Mindfulness is a state of active, open attention on the present. When you’re mindful, you observe your thoughts and feelings from a distance (my favorite way to think and feel) without judging them good or bad (even if I’m thinking about robbing a bank?). Instead of letting your life pass you by, mindfulness means living in the moment (a really boring moment) and awakening to experience (or lack thereof). (Apologies to SH :))

Beyond sleep and exercise there is a plethora of techniques that purport to help individuals deal with stress: yoga, meditation, and progressive muscular relaxation, among them.

Apps touting methods for relaxation abound these days.  My new Apple Watch is constantly advising me to engage in a breathing exercise for a minute at a time. I don’t find any of these techniques helpful for me (I haven’t found a good way to shut my brain down without falling asleep), but they may work for you.

Magnesium, Snake Oil and PVCs

Patients will find that the internet is rife with stories of how this supplement or vitamin or herb dramatically cures PVCs.  You can be assured that a sales pitch accompanies these claims and that the snake oil being promoted has not been proven effective or safe. Because symptomatic PVCs like most benign, common and troubling conditions (lower back pain, fatigue, and nonspecific GI troubles come to mind),  are closely related to mood and wax and wain spontaneously; the placebo effect proves powerful. In such conditions, snake oil and charlatans thrive.

Magnesium is enthusiastically hyped on the internet for all manner of cardiovascular problems including PVCs. Even Dr. Mandrola, who I respect quite a lot as an EP doc who promotes lifestyle change and who is definitely not a quack, lists his step 10 for PVCs (apologetically) as follows:

  • Step 10 (a): Please don’t beat me up on this one. Some patients report benefit from magnesium supplementation. I have found it helpful in my case of atrial premature beats. Let me repeat, I am not promoting supplements. Healthy patients with benign arrhythmia might try taking magnesium, especially at night. Don’t take magnesium if you have kidney disease. And if you take too much, watch out for diarrhea.

Most of the internet’s top quacks, however, greedily market and glowingly swear by magnesium.  A Google search for magnesium cardiovascular disease yields 833,000 entries and the first page is a Who’s Who of quackery, including Dr Mercola (strong candidate for America’s greatest quack), Dr. Sinatra (see here, currently in the semifinals for America’s greatest quack cardiologist), NaturalNews and Life Extension (see here). This totally unsupported and dangerous blather from the Weston Price Foundation is often repeated and is typical:

(magnesium) Deficiency is related to atherosclerosis, hypertension, strokes and heart attacks. Deficiency symptoms include insomnia, muscle cramps, kidney stones, osteoporosis, fear, anxiety, and confusion. Low magnesium levels are found in more than 25 percent of people with diabetes. But magnesium shines brightest in cardiovascular health. It alone can fulfill the role of many common cardiac medications: magnesium inhibits blood clots (like aspirin), thins the blood (like Coumadin), blocks calcium uptake (like calcium channel-blocking durgs such as Procardia) and relaxes blood vessels (like ACE inhibitors such as Vasotec) (Pelton, 2001).

Magnesium levels are very important to monitor in hospitalized and critically ill patients, especially those receiving diuretics and medications that can effect cardiac electrical activity.

However, for individuals with normal diets and palpitations due to PVCs, there is scant evidence that it plays a significant role in cardiovascular health.

The MAGICA study looked at supplementation with both magnesium and potassium (in the active treatment group, daily oral dosing consisted of 2 mg of magnesium-dl-hydrogenaspartate (6 mmol magnesium) and 2 mg of potassium-dl-hydrogenaspartate (12 mmol potassium) daily. The dose was chosen to increase the recommended minimal daily dietary intake of magnesium (12 to 15 mmol) and potassium (20 to 30 mmol) by ∼50% in addition to usual diet ) in 307 patients with more than 720 PVCs per hour and normal baseline K and Mg levels.

The patients receiving magnesium/potassium supplements showed a decrease of 17% in frequency of PVCs but no improvement in symptoms.

A 2012 study in a Brazilian journal evaluated magnesium pidolate (MgP) in 60  patients with both PVCs and premature atrial contractions (PACs). The dose of MgP was 3.0 g/day for 30 days, equivalent to 260 mg of Mg elemental.

93% of patients receiving MgP experienced improved symptoms compared to only 13% of patients recieiving placebo. Both PVC and PAC frequency was reduced in those receiving MGP, whereas they increased by 50% in those receiving placebo.

This small study has never been reproduced, and the main results table makes little sense. It would not have been published in a reputable American cardiology journal and cannot be relied on to support magnesium for most patients with benign PVCs or PACs.

Drug or Ablation Treatment of PVCs: Usually Not Needed

A small percentage of my patients require treatment with beta-blockers which reduces the effects of the sympathetic nervous system on the heart. Very rarely, I will use anti-arrhythmic drugs. And every once in a while, very frequent PVCs resulting in cardiomyopathy require an ablation.

However, the vast majority of patients with benign PVCs, in my experience, feel drastically better with a simple non-pharmacological approach consisting of 4 factors:

  • Reassurance that the PVCS are benign
  • Caffeine (or other stimulant) reduction
  • Lifestyle adjustment with regular aerobic exercise
  • Increased potassium intake to keep K >4

Ectopically Yours

-ACP

 

 

 

How To Spot a Quack Health Site: Red Flag #1, Primary Goal Is Selling Supplements

During the process of compiling the Cardiology Quackery Hall of Shame, the skeptical cardiologist has recognized that the #1 red flag of quackery is the constant promotion of useless supplements.

Such supplements typically:

-consist of “natural” ingredients

-are a proprietary blend of ingredients or a uniquely prepared single ingredient, and are only available through the quack

-have thousands of individuals who have had dramatic improvement on the supplement and enthusiastically record their testimonial to its power

-have no scientific support of efficacy or safety

-despite the lack of scientific data, the quack is able to list a series of seemingly valid supportive “studies”

-aren’t checked by the FDA

-apparently cure everything from heart disease to lassitude

I received an email today from a reader complimenting me on my post on the lack of science behind Dr. Esselstyn’s plant-based diet. The writer thought I would be interested in the work of a  Dr. Gundry.

I found on Dr. Gundry’s website an immediate and aggressive attempt to sell lots of supplements with features similar to what I describe above.

Dr. Gundry’s bio states “I left my former position at California’s Loma Linda University Medical Center, and founded The Center for Restorative Medicine. I have spent the last 14 years studying the human microbiome – and developing the principles of Holobiotics that have since changed the lives of countless men and women.”

Need I mention that “holobiotics” is (?are) not real.

Bonohibotically Yours,

-ACP

After writing this, I googled “red flag of quackery” images in the foolish hope that I might find a useable image. Lo and behold the image I featured in this post turned up courtesy of sci-ence.org. Here it is in all its glory, courtesy of Maki

2012-01-09-redflags2-682x1024

 

 

 

Snake Oil Du Jour: Turmeric

Part I of the skeptical cardiologist’s intermittent efforts at exposing the dark underbelly of the “superfood” snake oil parade deals with turmeric.

This key ingredienet of curry, has been seized upon by the useless and dangerous supplement/vitamin/nutraceutical industry recently and a patient asked me if he should take it.

A Google search yields overblown titles such as

-The amazing health benefits of turmeric  (MNN.com, a bogus website)

-6 Health benefits of Turmeric (Huffington Post, the health portion of which is full of hucksters)

-10 Proven Health Benefits of Turmeric and Curcumin (authoritynutrition.com, a bogus nutrition website)

-7 Powerful Turmeric Health Benefits and Side Effects (DrAxe.com, a bogus health website)

As I started researching turmeric I came across an outstanding summary of the topic on science-based medicine by Harriet Hall. I stopped the research and decided I would just put a link to that blog post on my site but never get around to it.

Today, however, another patient told me he was taking turmeric.

Consequently, I’m posting Harriet Hall’s article below in its entirety.

Turmeric: Tasty in Curry, Questionable as Medicine « Science-Based Medicine.

turmericA correspondent asked me to look into the science behind the health claims for turmeric. He had encountered medical professionals “trying to pass turmeric as some sort of magical herb to cure us from the ‘post-industrial chemical apocalypse.’” It is recommended by the usual promoters of CAM: Oz, Weil, Mercola, and the Health Ranger (who conveniently sells his own superior product, Turmeric Gold liquid extract for $17 an ounce).

Turmeric (Cucurma longa) is a plant in the ginger family that is native to southeast India. It is also known as curcumin. The rhizomes are ground into an orange-yellow powder that is used as a spice in Indian cuisine. It has traditionally been used in folk medicine for various indications; and it has now become popular in alternative medicine circles, where it is claimed to be effective in treating a broad spectrum of diseases including cancer, Alzheimer’s, arthritis, and diabetes. One website claims science has proven it to be as effective as 14 drugs, including statins like Lipitor, corticosteroids, antidepressants like Prozac, anti-inflammatories like aspirin and ibuprofen, the chemotherapy drug oxaliplatin, and the diabetes drug metformin. I wish those claims were true, because turmeric is far less expensive and probably much safer than prescription drugs. It clearly has some interesting properties, but the claims go far beyond the actual evidence.

The Natural Medicines Comprehensive Database has reviewed all the available scientific studies and has concluded that it is “Likely Safe,” “Possibly Effective” for dyspepsia and osteoarthritis, and “Insufficient Reliable Evidence” to rate effectiveness for other indications, such as Alzheimer’s, anterior uveitis, colorectal cancer, rheumatoid arthritis, and skin cancer.

Mechanism of action

The “14 drugs” website says turmeric is one of the most thoroughly researched plants ever, with 5,600 peer-reviewed studies, 175 distinct beneficial physiological effects, and 600 potential preventive and therapeutic applications. They provide a database of 1,585 hyperlinks to turmeric abstracts. Naturally I can’t read all of them, but a sampling indicates that they are almost entirely animal and in vitro studies. The NMCD has conveniently provided a list of the most pertinent studies.

The pertinent preclinical studies, in animal models and in vitro, indicate that curcumin has anti-inflammatory properties; can induce apoptosis in cancer cells and may inhibit angiogenesis; has antithrombotic effects; can decrease the amyloid plaque associated with Alzheimer’s; has some activity against bacteria, Leishmania, HIV; etc. These effects sound promising, but animal studies and in vitro studies may not be applicable to humans. As Rose Shapiro pointed out in her book Suckers, you can kill cancer cells in a Petri dish with a flame thrower or bleach. Preclinical studies must always be followed by clinical studies in humans before we can make any recommendations to patients.

Preliminary clinical research

There are preliminary pilot studies in humans suggesting that:

Clinical research on turmeric is being funded by the National Center for Complementary and Alternative Medicine (NCCAM), but the NCCAM website is not very encouraging. Under the section What the Science Says, it reads:

  • There is little reliable evidence to support the use of turmeric for any health condition because few clinical trials have been conducted.
  • Preliminary findings from animal and other laboratory studies suggest that a chemical found in turmeric—called curcumin—may have anti-inflammatory, anticancer, and antioxidant properties, but these findings have not been confirmed in people.
  • NCCAM-funded investigators have studied the active chemicals in turmeric and their effects—particularly anti-inflammatory effects—in human cells to better understand how turmeric might be used for health purposes. NCCAM is also funding basic research studies on the potential role of turmeric in preventing acute respiratory distress syndrome, liver cancer, and post-menopausal osteoporosis.

Side effects

Turmeric is generally considered safe, but high doses have caused indigestion, nausea, vomiting, reflux, diarrhea, liver problems, and worsening of gallbladder disease. The NMCD warns that it may interact with anticoagulants and antiplatelet drugs to increase the risk of bleeding, that it should be used with caution in patients with gallstones or gallbladder disease and in patients with gastroesophageal reflux disease, and that it should be discontinued at least 2 weeks before elective surgery. Purchasers of supplements are not given that information.

Conclusion

The “14 drugs” website recommends that everyone:

use certified organic (non-irradiated) turmeric in lower culinary doses on a daily basis so that heroic doses won’t be necessary later in life after a serious disease sets in.

There is no evidence to support any part of that recommendation. And the scientific evidence for turmeric is insufficient to incorporate it into medical practice. As with so many supplements, the hype has gone way beyond the actual evidence. There are some promising hints that it may be useful, but there are plenty of promising hints that lots of other things “may” be useful too. Since I have no rational basis for choosing one over another, I see no reason to jump on the turmeric bandwagon. On the other hand, I see no compelling reason to advise people not to use it, as long as they understand the state of the evidence well enough to provide informed consent and know that they are essentially guinea pigs in an uncontrolled experiment that makes no attempt to collect data. I will keep an open mind and stay tuned for further evidence in the form of well-designed clinical studies in humans.

So, the bottom line on turmeric, our “snake-oil du jour” is

-there is nothing to support its use for any health condition

-potential dangerous side effects

-interacts with legitimate prescription meds

-crucial ingredient in curry

My advice-DONT”T TAKE IT!

Gostephencurryily yours,

-ACP

Should You Take Prescription (“Pharmaceutical Grade”) Fish Oil?

Avid readers of the skeptical cardiologist know that he is not an advocate of fish oil supplements.

One of my first posts (1/2013) was devoted to taking down the mammoth OTC fish oil industry because recent scientific evidence was clearly showing no benefit for fish oil pills.

I concluded

", the bottom line on fish oil supplements is that  the most recent scientific evidence does not support any role for them  in preventing heart attack, stroke, or death. There are potential down sides to taking them, including contaminants and the impact on the marine ecosystem. I don’t take them and I advise my patients to avoid them (unless they have triglyceride levels over 500.)"

Despite a lack of evidence supporting taking them, the fish oil business continues to grow buttressed by multiple internet sites promoting various types of fish oil (and more recently krill oil)  for any and all ailments and a belief in the power of “omega-3 fatty acids”.

Fish Oil By Prescription: Superior to OTC?

IMG_5266A fish oil preparation, VASCEPA,  available only by prescription, was approved by the FDA in 2013.

Like the first prescription fish oil available in the US, Lovaza, VASCEPA is only approved by the FDA for treatment of very high triglycerides (>500 mg/dl).

This is a very small market compared to the millions of individuals taking fish oil thinking that  it is preventing heart disease.

The company that makes Vascepa (Amrin;$AMRN)would also like to have physicians prescribe it to their patients who have mildly or moderatelyelevated triglycerides between 200 and 500 which some estimate as up to 1/3 of the population.

The company has a study that shows that Vascepa lowers triglycerides in patients with such mildly to moderately elevated triglycerides but the FDA did not approve it for that indication.

Given the huge numbers of patients with trigs slightly above normal, before approving an expensive new drug, the FDA thought, it would be nice to know that the drug is actually helping prevent heart attacks and strokes or prolonging life.

After all, we don’t really care about high triglycerides unless they are causing problems and we don’t care about lowering them unless we can show we are reducing the frequency of those problems.

Data do not exist to say that lowering triglycerides in the mild to moderate range  by any drug lowers heart attack risk.

In the past if a company promoted their drug for off-label usage they could be fined by the FDA but Amrin went to court and obtained the right to promote Vascepa to physicians for triglycerides between 200 and 500.

Consequently, you may find your doctor prescribing this drug to you. If you do, I suggest you ask him if he recently had a free lunch or dinner provided by Amrin, has stock in the company (Vascepa is the sole drug made by Amrin and its stock price fluctuates wildly depending on sales and news about Vascepa) or gives talks for Amrin.

If he answers no to all of the above then, hopefully, your triglycerides are over 500.

Fun Facts About Vascepa (Yes It Melts Styrofoam!)

-Vascepa does not contain fish oil in a natural form.

Although there marking material states “VASCEPA is obtained naturally from wild deep-water Pacific Ocean fish” the active ingredient is an ethyl ester form of eicosapentoic acid (EPA) which has been industrially processed and distilled and separated out from the other main omega-3 fatty acid in fish oil (DHA or docosohexanoieic acid).

Natural fish oil contains a balance of EPA and DHA combined with triacylglycerols (TAGS).

-Vascepa Does Eat Through Styrofoam.

IMG_5272
Using a fork to poke hole in the Vascepa capsule

I came across reports of this phenomenon while researching Vascepa: it is commonly cited by fish oil marketers who are using the natural form of fish oil. 

I tested this for myself and watched as my little styrofoam cup bottom was eaten away.

IMG_5282
After pouring the oil into the cup, a bubbling began and in about 10-15 minutes the entire bottom of the cup disintegrated, forming a gooey mess on the paper below.

I’m not sure what the significance of this is as many concentrated organic oils (like lemon oil apparently) will do the same thing but it does seem to be a marker for the chemically processed, synthetic ethyl esters of EPA or EPA plus DHA.

 

Most Patients Should Avoid Prescription Fish Oil Unless/Until Studies Show a Benefit

Fish oil in its natural form which is within the actual fish surrounded by a host of nutrients, vitamins, mineral, antioxidants  and chemicals we don’t fully understand is the best fish oil to consume.

I’m willing to bet that if I put a raw piece of salmon in that cup it would not eat through it (I feel another experiment coming up!).

Synethestically Yours

-ACP

 

 

 

Red Yeast Rice: Let’s Lower Our Cholesterol With Unknown Amounts of a Statin Drug

Red Yeast Rice sits atop the "Heart Healthy" shelves at Whole Foods, surrounded by other useless "natural" supplements like ubiquinol (Coenzyme Q-10) and reservatrol.
Red Yeast Rice sits atop the “Heart Healthy” shelves at Whole Foods, surrounded by other useless “natural” supplements like ubiquinol (Coenzyme Q-10) and reservatrol.

Over the years I’ve had a number of patients tell me that they prefer to take over the counter (OTC) dietary supplements containing “natural” cholesterol lowering ingredients rather than the statin drug I have prescribed.

Red yeast rice (RYR)  is a common ingredient in these supplements and is promoted widely and enthusiastically across the internet and in supplement or natural food stores for the purpose of lowering cholesterol and heart disease risk.

RYR  has been used for centuries in China for coloring, food and medicine. It is made by fermenting red rice with a specific  type of yeast (Monascus purpureus).

Red yeast rice contains chemicals that are similar to prescription statin medications. One of these, called monacolin K, is chemically identical to  the statin drug lovastatin (brand name Mevacor).

The History Of Statin Drug Development

The history of the discovery and isolation of lovastatin, the first FDA approved statin, is worthy of a digression here as I think it illustrates the process of discovery, isolation and characterization of a chemical that becomes a safe and effective treatment.

Akin Endo,whose research over decades was crucial to discovering statins, writes that he was inspired by Alexander Fleming, who discovered penicillin in the blue-green mold belonging to the genus Penicillium in 1928.

He writes; “Although no metabolites that inhibited any enzymes involved in cholesterol synthesis had been isolated previously, I speculated that fungi like molds and mushrooms would produce antibiotics that inhibited HMG-CoA reductase. Inhibition of HMG-CoA reductase would thus be lethal to these microbes.”

Endo began analyzing thousands of molds and fungi for biologically active chemicals that would inhibit HMG-CoA reductase.

In 1971, after studying 3800 different strains of fungi he found a promising candidate: citrinin. Unfortunately,

“Citrinin strongly inhibited HMGCoA reductase and, furthermore, lowered serum cholesterol levels in rats. However, the research was suspended because of its toxicity to the kidneys. ”

End spent another 10 years isolating another promising HMG-CoA reductase inhibitor, “compactin, ” from mold and studying it in rats and other animals. Compactin demonstrated marked cholesterol lowering properties in dogs and monkeys and in the few humans who received it but the pharmaceutical company he worked for shut down the project after it appeared that in doses 200 x what were considered appropriate, it increased lymphoma risk in dogs.

The large pharmaceutical company, Merck, got wind of Endo’s studies with compactin, studied his data and realized the potential of similar but safer HMG-CoA reductase inhibitors.  Drugs which inhibited HMG-coA reductase were now being termed statins.

Merck set out to find its own statins and in February 1979 isolated a statin very similar to compactin in chemical structure, called mevinolin, from the fungus Aspergillus terreus.

Endo, working separately and also in February 1979, isolated another statin (named monacolin K) from cultures of Monascus ruber.(RYR).In  the fall of the same year, it was confirmed that monacolin K and mevinolin were the same compound (later both changed to lovastatin).

The drug showed dramatic activity in lowering LDL cholesterol, with very few side effects. This led Merck to begin large-scale clinical trials of lovastatin in patients at high risk and long-term toxicity studies in dogs in 1984. The drug dramatically reduced cholesterol levels and was well tolerated. No tumors were detected. In 1987, Merck gained FDA approval  and lovastatin became the first commercial statin.

Since then, six other statin drugs, some of which are synthesized in the laboratory rather than isolated from mold, have been approved for human therapy. These drugs have prevented thousands of heart attacks and contributed to the dramatic drop in cardiovascular deaths seen in developed countries over the last 30 years.

Ryr And Cholesterol Lowering

This brings us back to RYR and its ability to lower cholesterol. Small studies using a version of RYR that contained lovastatin have demonstrated a reduction in cholesterol compared to placebo.

However, because many red yeast rice supplements contained lovastatin (also called monacolin)In May 1998, the FDA ruled that Cholestin (the RYR product used in the studies showing cholesterol lowering benefit) was not a dietary supplement but an unapproved drug.

As a result,  Pharmanex removed RYR from Cholestin. Since that ruling, the FDA has written warning letters to several other dietary supplement manufacturers to remove drug claims or eliminate red yeast rice with high lovastatin levels from their products, including Heart and Cholesterol (Mason Vitamins, Miami Lakes, Florida)  Cholestrix (Sunburst Biorganics, Baldwin, New York), Red Yeast Rice and Red Yeast Rice/Policosanol Complex , and Red Yeast Rice (Nature’s Way Products Inc, )

A study in 2010, found levels of monacolins varying one-hundred fold in 12 RYR preparations available commercially (total monacolins (0.31-11.15 mg/capsule), monacolin K (lovastatin) (0.10-10.09 mg/capsule), and monacolin KA (0.00-2.30 mg/capsule).

Even more worrisome was that four products had elevated levels of citrinin. You remember citrinin, don’t you? That is the chemical that Endo initially identified as a candidate for cholesterol lowering drug but rejected because it was causing kidney failure in his rats.

Because of limited government oversight and variable manufacturing processes, one can also expect that the same manufacturer will have marked variation of monacolin content and citrinin from batch to batch or bottle to bottle.

Problems With Alternative Medicine In General

These problems with RYR supplements are typical of all supplements.As the the authors wrote

“Our results highlight an important issue with red yeast rice and many other alternative medicines: the lack of standardization of active constituents. Standardization of ingredients is difficult for several reasons: (1) There are variable growth and/or culture conditions and differences in harvesting and processing among manufacturers; (2) medicinal agents from natural sources are complex substances with many chemical constituents, many of which have unclear roles in their pharmacologic activity; and (3) different manufacturers may standardize products to amounts of 1 or 2 chemicals thought to be active ingredients, while other constituents are not standardized and may also have biologic and pharmacologic activity.”

One has to ask, given this background, why would a patient choose to take a “natural” OTC supplement containing an unknown amount of both a). Effective cholesterol lowering chemicals and b)potentially toxic extraneous chemicals over the precisely formulated, carefully regulated, fully studied, pure statin drug available by prescription.

It’s especially baffling to me when one considers that lovastatin comes from RYR. Thus it would have to be considered “natural.”

Akira Endo spent decades carefully identifying the effective and safe chemical portion of RYR. It is now available as a generic costing pennies per pill.

We know exactly how many milligrams you are consuming. We know what benefits to expect and what side effects can occur based on studies in hundreds of thousands of patients who have taken a similar dosage.

You are much better off taking the prescribed statin drug than RYR.

Skeptically yours,

ACP

Calcium Supplements: Would You Rather Have a Hip Fracture or a Heart Attack?

ct_calcium
Does taking extra calcium pills contribute to the deposition of calcium into the coronary arteries that we see in CT scans like this?

Since I’ve been utilizing coronary calcium CT scans to detect early atherosclerotic plaque (see here) in my patients, I have frequently been asked about the relationship between calcium supplements and heart attack risk.

For example, Mrs. Jones has just found out that she has a very high calcium score and that it reflects the amount of atherosclerotic plaque lining and potentially clogging the coronary arteries to her heart. She has also been taking calcium and Vitamin D supplements recommended to her to prevent bone thinning and fractures in the future.

Did all that extra calcium she was consuming end up depositing in her coronary arteries, thus increasing her risk of heart disease?

This is a complex and not fully settled issue, however, there is enough evidence to suggest that we be cautious about calcium supplements.

A recent meta-analysis (Bolland MJ, Avenell A, Baron JA, Grey A, MacLennan GS, Gamble GD, et al. Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis. BMJ 2010;341:c3691) of cardiovascular events in randomized, placebo controlled trials of calcium supplements (without vitamin D co-administration) showed that calcium supplements significantly increased the risk of myocardial infarction by 31% in five trials involving 8151 participants.

A recent meta-analysis of trials involving calcium and Vitamin D supplements found a similar increased risk of cardiovascular disease in the subjects randomized to taking calcium and Vitamin D.

These authors concluded

“in our analysis, treating 1000 patients with calcium or calcium and vitamin D for five years would cause an additional six myocardial infarctions or strokes (number needed to harm of 178) and prevent only three fractures (number needed to treat of 302”

How Might Calcium Supplements Increase Cardiovascular Risks?

Calcium supplements acutely and chronically  increase serum calcium concentration. Higher calcium levels are associated with more carotid artery plaque, aortic calcification, and  a higher incidence of heart attack and death.

Just like atherosclerosis, the process of calcium deposition into the arteries is very complex. Higher calcium levels could alter certain regulators of the process, such as fetuin A, pyrophosphate and bone morphogenic protein-7 or bind to calcium receptors on vascular smooth muscle cells lining the arteries

Higher calcium levels may also promote clot formation.

Bone Fracture versus Heart Attack

The informed doctor would have to tell Mrs. Jones that her calcium supplements may have contributed to her advanced coronary calcium and raised her risk of heart attack and stroke.

As with all medications, she and her doctor are going to have to discuss the relative risks and benefits.

If she has great concerns about fractures and has very low bone mineral bone density (osteoporosis) along with no family history of premature heart disease then the calcium supplementation may be appropriate.

Conversely, if she has high risk factors for coronary heart disease and/or a strong family history of premature coronary heart disease and only slightly low bone mineral density, avoiding the calcium supplements would be appropriate.

Preventing Fractures and Heart Attacks

It’s best to get calcium from the foods we eat rather than a sudden concentrated load of a supplement. Full fat dairy products like yogurt and cheese are heart healthy (see here and here) and they are an excellent source of calcium.

Weight-bearing exercise (such as running/jogging/hiking) and strength-building exercise (lifting weights, resistance machines, etc.) are also important for strengthening bones.

Thus, eating full fat dairy and aerobic exercise will help prevent both a fracture and a heart attack.

The Ultimate Reason to Stop Taking Worthless Dietary Supplements: They Don’t Even Contain What They Claim to Contain

The skeptical cardiologist has written multiple rants about the worthlessness of taking dietary supplements, herbs, vitamins and minerals.

Today the New York Times is reporting a “cease and desist” letter the New York State  Attorney General has sent to GNC, Target, Walgreens and Walmart regarding their sale of “adulterated and/or mislabeled dietary herbal supplements.”

It turns out that 5 out of 6  of these supplements when tested by analytic DNA technology  were “either unrecognizable or a substance other than what they claimed to be.”

If the lack of evidence supporting efficacy and safety of these herbal supplements wasn’t sufficient to stop you from buying these products, perhaps the fact that the bottles you purchase don’t contain what they are supposed to contain will.

Hopefully, this will begin the downfall  of the multibillion dollar worthless and unregulated dietary supplement industry.

Still More Reasons Not to Take Worthless Vitamins and MultiVitamins

As I have pointed out in a previous post, there is no reason to take multivitamins or any individual vitamin or supplement to prevent cardiovascular disease.

The U.S. Preventive Services Task Force (USPSTF) has just  updated its 2003 recommendation on vitamin supplementation to prevent cardiovascular disease and cancer and published this analysis in the April 15, 2014  Annals of Internal Medicine issue.

Their recommendations agree with mine and those of the American Heart Association, the American Cancer Society and the Academy of Nutrition and Dietetics.

After analyzing all available studies they found insufficient evidence to support

  • the use of multivitamins to prevent cardiovascular disease or cancer
  • the use of single or paired nutrients (except β-carotene or vitamin E) for the prevention of cardiovascular disease or cancer (including Vitamins A, C, D, E, folic acid, selenium and beta-carotene)

About half the country is taking these worthless vitamins, supplements and multivitamins and spending 28 billion dollars per year on them.

This money would be much better spent on gym memberships or  on the purchase of real, unprocessed food which contains all the vitamins and nutrients you need.

 

 

Time to Stop Taking Worthless Vitamins and Minerals

As I pointed out in an earlier blog , individual vitamins and multivitamins have been proven over and over to have no benefit for heart disease.
A recent series of articles in the Annals of Internal Medicine summarized in this accompanying editorial, confirms this and further shows that multivitamins have no benefit on preventing cognitive decline with aging.
The U.S. Preventive Services Task Force reviewed all studies on multivitamins, single and paired vitamins and concluded that there was no benefit of taking these on overall mortality, cardiovascular mortality or cancer.
Hopefully this series of articles will start the decline of the multibillion dollar Vitamins and Supplement industry in the U.S.
For my patients, I recommend a healthy diet that includes, fruits, vegetables, and fish which will provide all the micronutrients and vitamins they need. There is no evidence that you can substitute taking industry-processed micronutrients or fish-oil and expect the benefits to be the same

Omega-3 fatty acids, and heart disease: Do fish oil supplements prevent heart attacks or death from heart disease

In recent years, a steady stream of experts, including the ubiquitous Dr. Oz, Screen shot 2013-01-26 at 9.47.51 AMhave advised every one to take fish oil supplements to protect their heart health

In fact, there is little to no evidence that fish oil supplements or fish oil enhanced foods should be consumed for any health purpose.
Omega-3 fatty acids (also known as  ω−3 or n−3) are polyunsaturated fatty acids (PUFA) that can be derived from marine or plant oils. They are considered essential fatty acids in humans, vital for normal metabolism but not synthesized by the human body.

The long chain omega-3 fatty acids eicosapentanoic acid (EPA) and docosahexanoic acid (DHA)  are felt to be the most beneficial. The best food source of DHA and EPA is cold water fatty fish and shellfish. The fish highest in these fatty acids are salmon, sardines, mackerel, herring and tuna.

Alpha-linolenic acid (ALA) is an omega-3 fatty acid which is predominantly found in plant oils (flaxseed, canola, and soybean oils) and walnuts. It can, to a limited extent, be converted in human bodies  to EPA and DHA, thus can be considered a precursor.

There is some evidence that consuming fish on a regular basis is associated with lower risk of coronary heart disease and stroke. Therefore, I can agree with current AHA and USDA guidelines which recommend consumption of fatty fish at least twice a week and I advise this for my patients.

Predominantly on the basis of one very positive study performed in Italy in 1999 (the GISSI study, which gave EPA/DHA to heart attack survivors), most cardiologists, the AHA, and the supplement industry had concluded by 2005 that fish oil reduced mortality and cardiac morbidity. The best evidence then was that the fish oil supplement was helpful after a heart attack (so-called secondary prevention). However, there was a very powerful urge to extrapolate this recommendation to patients without heart disease (so-called primary prevention).

Such expanded recommendations were reflected in the media. For example, Forbes proclaimed

“One Supplement That Works:

A lot of nutritional supplements are quack medicines. Not fish oil”

By 2009 sales of OTC fish oil supplements had risen 18% in one year to 739 million and Americans were buying 1.8 billion worth of foods (such as margarine and peanut butter) fortified with extra omega-3s. By  2011, Americans were spending 1.1 billion on supplements.

GlaxoSmithKline developed and patented a high-concentration fish oil (Lovaza) that gained an indication for treating high triglycerides which had global sales of 1 billion dollars in 2008. Supported by heavy advertising and promotion to physicians (through dinner lectures, lunches and other promotions), this expensive version of fish oil is widely prescribed by physicians for reasons other than the very high triglyceride elevations it has an indication for.

Forbes wrote

“In the history of nutritional supplements there’s something striking about omega-3: the fact that it works. Much of the $25 billion a year that Americans spend on supplements is money down the drain”

While the second part of that sentence is true (the vast majority of supplements/nutraceuticals/minerals that Americans take in a search for longevity or arthritis relief are worthless) the first part is not true.

The subsequent  hype for the benefits of fish oil supplements, especially in the world of nutritional supplement has been outrageous and inaccurate.

A typical product description reads as follows.

“We believe this is the highest quality Omega-3 available.
This highly concentrated Pharmaceutical Grade Omega-3 Fish Oil delivers 800mg of EPA and 600mg of DHA.
The important benefits of Omega-3 have been proven in thousands of independent studies by universities, governments, and health organizations. Because of such research, people around the world are now taking fish oil for reasons ranging from brain development, mild depression and heart function to arthritis and our immune systems.
It causes NO fishy or un-pleasant after taste.
This Omega 3 has been verified by a 3rd party to be Mercury Free.”

If one reads further down the page, however, the most important sentence is the following (and this is true for all supplements_






These statements have not been evaluated by the FDA. This product is not intended to diagnose, treat, cure or prevent any disease

So , the fish oil pushers  make a series of totally unsubstantiated claims about the benefits followed by the statement that it is not intended to benefit any one in any way.

The most recent systematic review and meta-analysis of omega-3 fatty acid supplementation and the risk of major cardiovascular events (published Sept. 2012,) concluded:

“overall, omega-3 PUFA supplementation was not associated with a lower risk of all-cause mortality, cardiac death, sudden death, myocardial infarction,  or stroke based on relative and abolute measures of association”

Studies performed in the last 5 years of omega-3 PUFA supplementation do not support a role for them in reducing heart disease, either in high risk individuals without documented heart disease or those who have already had heart attacks.

Most of my patients continue to take fish oil supplements because they think that there may be a benefit without any down side. However, there are a number of potential down sides that should be considered.
1. There is no government regulation or measurement of the contaminants in fish oil supplements.
According to Consumer Reports

“Most tested pills are claimed to be “purified” or “free” of PCBs, mercury, or other contaminants, claims that have no specific regulatory definition, the Food and Drug Administration says. The agency has taken no enforcement action against any omega-3 maker over PCBs or other contaminants, an FDA spokeswoman said, because it has seen no public-health risk”

2. A major source of the fish oil in fish oil supplements, menhaden, is being over fished. Menhaden are a sardine-like forage fish that range in huge schools from Canada to Florida and into the Gulf. As filter feeders, they form an important base of the marine food chain. They have historically been harvested for food and later, for use as fertilizer and more recently for use in aquaculture and in omega-3 supplements. This fish, which has been called “the most important fish in the sea,” feeds on phytoplankton and is essential for a healthy marine ecosystem. The Atlantic States Marine Fisheries Commission (ASMFC) recently approved a 20% decrease in fish catch for the Atlantic Coast menhaden bait and reduction fisheries, The numbers of these fish have declined by 90% in the last 4 decades. Without doing extensive research on your particular fish oil supplement you can’t be sure you aren’t contributing to  this problem.

So, the bottom line on fish oil supplements is that  the most recent scientific evidence does not support any role for them  in preventing heart attack, stroke, or death. There are potential down sides to taking them, including contaminants and the impact on the marine ecosystem. I don’t take them and I advise my patients to avoid them (unless they have triglyceride levels over 500.)

Americans want a “magic-bullet” type pill to take to ward off aging and the diseases associated with it. There isn’t one. Instead of buying pills and foods manipulated and processed by the food industry which promise better health, I advise following Michael Pollan’s simple advice

“Eat food. Mostly plants. Not too much”