Three patients who suffered from potentially deadly heart failurewere remarkably freed from their symptoms after their condition was found to have spontaneously reversed, found a new study that reported on the unprecedented cases.
Vishwam Sankaran
·2-min read
Deadly ‘irreversible’ heart condition reversed for first time in major breakthrough
Three patients who suffered from potentially deadly heart failure were remarkably freed from their symptoms after their condition was found to have spontaneously reversed, found a new study that reported on the unprecedented cases.
Transthyretin cardiac amyloidosis, the deadly condition, is caused by the build-up of sticky, toxic proteins in the heart. Until now, it was thought to be irreversible as half the patients suffering from the condition died within four years of diagnosis.
But the new study, published recently in the journal The New England Journal of Medicine, reported the cases of three men, aged 68, 76 and 82, who were diagnosed with the condition but later recovered.
Researchers, including those from University College London (UCL), confirmed the symptom reversal using heart scans that showed the build-up of amyloid proteins had cleared.
“We have seen for the first time that the heart can get better with this disease. That has not been known until now and it raises the bar for what might be possible with new treatments,” said study lead author Marianna Fontana from UCL.
Researchers also found evidence that the three men had antibodies that specifically targeted the amyloid proteins – an immune response that was not found in other patients whose condition progressed as normal.
“Whether these antibodies caused the patients’ recovery is not conclusively proven. However, our data indicates that this is highly likely and there is potential for such antibodies to be recreated in a lab and used as a therapy,” said UCL’s Julian Gillmore, another study author.
The condition is known to be caused by deposits composed of a blood protein called transthyretin, and can be either hereditary or non-hereditary.
While current treatments aim to relieve the symptoms of heart failure such as fatigue, swelling in the legs or abdomen and shortness of breath, they do not tackle the amyloid, scientists said.
With advancements in imaging techniques over the decades, clinicians have been able to diagnose substantially more people with the disease.
In the latest study, researchers looked through records of 1,663 patients diagnosed with the deadly condition after one man, aged 68, reported his symptoms improving.
Two more cases were identified after which all three men’s recoveries were confirmed via blood tests and imaging techniques like echocardiography.
Then a heart muscle tissue analysis of one of the patients revealed a strange inflammatory response surrounding the amyloid protein deposits in the heart – a response that was not seen in biopsies from patients in whom the condition had not reversed.
On further analysis, researchers found antibodies in the three patients that bound specifically to the heart protein deposits.
Scientists believe these proteins could be harnessed to build therapies that can suppress the toxic, sticky protein’s production.
“This work not only represents a major breakthrough in our understanding of cardiac amyloidosis, but crucially opens up new possibilities for more effective treatment options,” said Jon Spiers, chief executive of the Royal Free Charity.
PUBLISHED: 11:36 BST, 31 July 2018 | UPDATED: 11:44 BST, 31 July 2018
A common blood pressure drug has been recalled worldwide and production has stopped after it was found to contain a cancer-causing chemical.
The drug Valsartan, made in a factory in China, was recalled in 22 countries including the UK and the US earlier in July, but the warning is now worldwide.
Investigators found a chemical used in rocket fuel, called N-Nitrosodimethylamine, had contaminated the drug's production at Zhejiang Huahai, a Chinese supplier which ships the medicine worldwide.
N-Nitrosodimethylamine is thought to be carcinogenic, meaning it could cause cancer in humans, so production of the pills has stopped.
China's National Health and Family Planning Commission said yesterday that the drug must not be used for diagnosis or treatment, and the pills have already been banned in the UK and US.
Experts say the contamination could date back as far as 2012, when the company changed its manufacturing process.
+1
British pharmacists were today warned a change in how valsartan is manufactured has caused a dangerous impurity in several medications
The US Food and Drug Administration banned Valsartan on July 17, two weeks after the UK recalled the drug, which has been widely prescribed across the world for 15 years.
America's decision to follow suit came on the heels of a warning from European regulators earlier that day that the drug's dangers may have been present in batches as far back as 2012.
Valsartan was originally developed by Novartis and the Swiss company marketed it as Diovan, but it is now off patent and is used in a number of generic medicines supplied by various companies.
In addition to tackling high blood pressure, it is also prescribed to treat heart failure.
The main manufacturer in China is Zhejiang Huahai, which was founded in 1989 and listed on the Shanghai stock exchange in 2003, was one of the first Chinese companies to get drugs approved in the US market.
Company also makes ingredients for HIV and depression drugs
That same firm makes active ingredients for a number of different medicines to treat heart problems, depression, allergies and HIV, according to its website.
Overall, more than two-thirds of all active drug ingredients originate in China and India, industry experts estimate, with China accounting for the lion's share.
The revelation that the problem with Valsartan likely dates back to changes in manufacturing processes at Zhejiang Huahai Pharmaceutical six years ago suggests many patients could potentially have been exposed to cancer risk.
The European Medicines Agency (EMA), which first raised the alarm over the Chinese supplied Valsartan on July 5, said it was working to establish how long and at what levels patients might have been exposed to the impurity known as NDMA.
Chemical thought to cause cancer in humans
NDMA, or N-nitrosodimethylamine, is classified as a probable human carcinogen. Based on results from laboratory tests, it may cause cancer with long-term use.
'It is still too early to provide information on the longer term risk NDMA may have posed for patients.
'EMA has made this aspect of the review a priority and will update the public as soon as new information becomes available,' the agency said.
EU authorities recalled medicines containing Valsartan from Zhejiang Huahai, and the EMA said such medicines should no longer be available in pharmacies.
The U.S. Food and Drug Administration also took action to recall affected valsartan-containing medicines.
Zhejiang Huahai has already acknowledged that there was an impurity in some of its Valsartan, which it said had sales of $50 million in 2017.
The EMA said NDMA was an unexpected impurity that was not detected by routine tests carried out by Zhejiang Huahai, adding that the manufacturing changes introduced in 2012 were believed to have produced NDMA as a by-product.
EU and US depend on Asia for drugs - but don't pay enough attention to safety
The case shows the reliance of consumers around the world on medicines containing active pharmaceutical ingredients made in China.
Regulators have been stepping up oversight of foreign factories in recent years to try and ensure the quality of drugs made in China and India, which is another major supplier to global drug markets.
But it remains a work in progress, as highlighted by the EMA's Executive Director Guido Rasi, who wrote recently in the agency's annual report:
'We need to think globally and work strategically with partners from around the world to make best use of our inspection capacity, so that patients can rely on the quality, safety and efficacy of all medicines, no matter where they have been manufactured.'
WHAT ARE THE VALSARTAN CONTAINING DRUGS THAT ARE AFFECTED?
Coenzyme Q10 and ubiquinol are two vitally important supplements that many are still unaware of. Risa Schulman, Ph.D., is a biologist and functional food expert who has spent the last two decades researching these and other supplements.
Story at-a-glance
Coenzyme Q10 (CoQ10) is used for energy production by every cell in your body. It also helps protect against cellular damage from free radicals
CoQ10 is especially important if you take a statin drug as statins deplete your body of CoQ10, thereby speeding up progression of heart disease
Ubiquinol is the reduced form of CoQ10. This is the form your body naturally uses, and research shows ubiquinol is superior for your health in a number of ways, primarily due to its superior bioavailability
26 June 2016
By Dr. Mercola
Coenzyme Q10 and ubiquinol are two vitally important supplements that many are still unaware of. Risa Schulman, Ph.D., is a biologist and functional food expert who has spent the last two decades researching these and other supplements.
"I kind of pulled together my love of human physiology, plant physiology and the environment into a lifelong career, looking at how compounds in plants and various natural products can help us to keep our bodies working optimally," she says.
"My mission is to dig into the science and separate the wheat from the chaff ... and then to get the word out to the public as to what the health benefits are, how they can be used, and what things are useful."
Coenzyme Q10 Versus Ubiquinol
Ubiquinol is the reduced version of coenzyme Q10 (CoQ10, aka ubiquinone). They're actually the same molecule, but when CoQ10 is reduced it takes on two electrons, which turns it into what we call ubiquinol.
In your body, this conversion occurs thousands of times every second inside your mitochondria — the "engine" of each cell in which energy is produced
"The reason it does this flipping back and forth between these two forms of the molecule is that this is part of the process that helps us to change our food into energy," Schulman explains.
"This is very important to healthy functioning, and obviously important for all muscles, in particular your heart muscle, which works hardest of all the muscles."
In addition to converting food into energy, ubiquinol also has a number of additional functions. For starters, ubiquinol is a lipid-soluble (fat-soluble) antioxidant, meaning it works in the lipid portions of your body, such as your cell membranes. It's one of the very few antioxidants that are fat-soluble.
"Vitamin E is one of the other ones that is very well known. But ubiquinol is actually more powerful than vitamin E, because vitamin E cannot completely lodge itself inside the membrane where all the oxidative activity is happening whereas ubiquinol can."
The second thing that sets ubiquinol apart from other antioxidants is that it can regenerate itself. Vitamin E, for example, cannot. In fact, vitamin E is regenerated by ubiquinol. Ubiquinol is also the only fat-soluble antioxidant that's actually generated within your body and doesn't have to be ingested from your food.
Why Ubiquinol Is a Better Choice for Many
Ubiquinol production ramps up from early childhood up until your mid- to late 20s. By the time you hit the age of 30, it begins to decline. Young people are able to use CoQ10 supplements quite well, but older people do better with ubiquinol as it's more readily absorbed.
According to Schulman, some people cannot convert CoQ10 to ubiquinol at all in their bodies, and they definitely need to use ubiquinol or they won't get any of the benefits.
"If someone takes a CoQ10 supplement, the body very quickly will convert it to ubiquinol, because that's the preferred form. It will transport that CoQ10 through the blood, as ubiquinol, into the tissues and eventually into the mitochondria,"she explains.
“But there are some people who lack the enzyme that helps to convert the CoQ10 to ubiquinol. That could be partly due to aging, but it’s also genetic. There’s something called a single nucleotide polymorphism SNP).
There's a particular SNP that's called NQO1. When a person has either one or two copies of this SNP, their ability to convert CoQ10 is either slightly or severely compromised.
What that means, practically, is that if this person takes a CoQ10 supplement ... their body can't convert it in a way that makes it usable. Those people in particular can benefit very much from taking ubiquinol, instead of ubiquinone."
Research has shown that Hispanic and Chinese populations are especially prone to having this single nucleotide polymorphism. There are also genetic tests you can get that can identify whether you have it.
How to Regenerate CoQ10 Naturally
Interestingly, recent research shows you can improve your body's conversion of CoQ10 to ubiquinol by eating lots of green leafy vegetables, which are loaded with chlorophyll, in combination with sun exposure.
Once chlorophyll is consumed it gets transported into your blood. Then when you expose significant amounts of skin to sunshine, that chlorophyll absorbs the solar radiation and facilitates the conversion of CoQ10 to ubiquinol.
You can also improve absorption of CoQ10 by taking it with a small amount of healthy fat, such as some olive oil, coconut oil, or avocado.
Ubiquinol Combats Free Radicals in Your Mitochondria
About 90 percent or more of the reactive oxygen species (ROS) in your body are produced in your mitochondria. Using the analogy of the mitochondria as an engine, the combustion (metabolism) that takes place in there creates exhaust fumes — damaging byproducts.
One of the functions of ubiquinol is to mop up those byproducts. When ubiquinol is lacking, the byproducts remain and begin damaging the cell. Ubiquinol is particularly beneficial for your heart health, a marker for which is C-reactive protein. When C-reactive protein is elevated it suggests you have a heightened risk for heart disease, as it's a marker for inflammation.
Two other markers for inflammation are gamma-glutamyl transferase (GGT), which is an early marker of heart failure, and NT-proBNP. There's an association between the levels of these two markers and ubiquinol as well. When ubiquinol is supplemented, both these markers go down and genes associated with them are downregulated.
The Case for a Healthy High-Fat Diet
Over the past 15 years, scientists have begun to recognize that ROS are not 100 percent bad. They're also important signaling molecules. If you indiscriminately suppress them you can actually run into complications with the Law of Unintended Consequences. In my view, a wise strategy is to simply feed your body a cleaner fuel to suppress excess ROS generation.
To continue the analogy of your mitochondria being an engine, to prevent pollution you want to use a cleaner-burning fuel. Glucose is an inherently "dirty" fuel that generates lots of ROS, whereas healthy dietary fats, including saturated fats, burn much cleaner and more efficiently.
In fact, burning carbohydrates is associated with a 30 to 40 percent increased production of ROS compared to burning fat. It makes a lot of sense that if you produce fewer ROS to begin with, then you don't have to be as careful about supplying your body with antioxidants. (Personally, I have some concern over indiscriminate use of antioxidants, but not necessarily ubiquinol.)
“Counter to how we’ve all been trained to think in the last years, regarding the free radical theory of aging, you don’t want to suppress it all the time,” Schulman says. “In fact, free radicals actually play a very critical positive role in the body because they turn on various very important functions.
Nitric oxide, for example, has free radical properties. It's a critical signaling molecule and is also critical for the health of your arteries. I haven't read anything in the literature regarding whether there's a discriminating or non-discriminating suppression of reactive oxygen species by ubiquinol in the mitochondria.
But my understanding of the biochemistry and the bioenergetics that are happening there leads me to believe that it's more of a random process."
Another strategy you could use to reduce the production of excess ROS involves the timing of your last meal of the day. Many make the mistake of eating a large meal before they go to bed.
By supplying your body fuel at a time when very little is needed leads to the generation of excess ROS that then must be countered with antioxidants. Avoiding food for at least three hours or more before bedtime can take the load off your body by preventing excess ROS production in the first place.
Finally, making sure you are not overloaded with iron is another powerful strategy. Believe me, iron overload is every bit as dangerous as vitamin D deficiency. If you are an adult male or non-menstruating woman then you are at high risk.
Please make sure you get your ferritin level checked and confirm that the level is below 80 nanograms (ng)/milliliters (ml), preferably between 40 and 60 ng/ml. If it is higher than that then it is imperative that you regularly donate your blood or have therapeutic phlebotomies to get it in that range.
Statin Users Are in Dire Need of CoQ10
At least 1 in 4 American adults over the age of 40 are currently taking a statin drug to lower their cholesterol. Soon that number is expected to reach 1 in 3. Statins work by inhibiting the enzyme HMG-CoA reductase, which is one of the facilitators of your body's production of cholesterol. But statins also impair production of CoQ10, and the resulting depletion can have very severe consequences.
"This is a very important topic," Schulman says. "Many who take statins have the side effects of muscle pain, fatigue and memory loss — to such a point that compliance becomes an issue; people don't want to be on statins anymore. It's been documented and recognized medically that these are real effects and that they're due to the statins. What's actually happening? The way a statin works is that it blocks your body's production of cholesterol.
We're always thinking about cholesterol from the diet ... Most people don't realize that cholesterol in the body comes from two places: from the diet and from your internal production of cholesterol. Cholesterol is quite important to your body, because cholesterol is one of the major components of cell membranes. It's also the precursor for all the sex hormones. It's not all bad. It's just bad when there's too much and that depends on what kind as well."
Besides shutting down your body's ability to produce ubiquinol, statin drugs also shut down the conversion of vitamin K1 to vitamin K2, which is critically important in many body functions, including heart health.
Impairing these three pathways — the production of cholesterol and CoQ10, and the vitamin K1 to K2 conversion — has adverse effects on the production of energy and on cardiovascular health, and here's why: when you reduce your ubiquinol levels, the conversion of your food to energy becomes less efficient, which leads to lower energy, fatigue and muscle pains.
And the longer you're on a statin drug, the more ubiquinol-starved your body becomes and the more severe the side effects become. Recently published papers have also detailed the cardiovascular repercussions of statins. As it turns out, they actually end up causing many of the disease endpoints the drugs promised to prevent. But that's not all!
Statins Severely Compromise Your Metabolism
As mentioned, one of the most rational strategies to reduce ROS production is to burn clean fuel. Ultimately, that results from eating a diet high in healthy high-quality fats. When fat is metabolized, ketones are created — a fat-soluble molecule that is readily burned in the mitochondria without causing the production of excess ROS.
Ketones are produced in the liver, and the enzyme that produces ketones is the same that produces cholesterol, namely HMG-CoA reductase. So when you're taking a statin drug, you also severely diminish your liver's ability to make ketones, thereby compromising your ability to benefit from a clean fuel (fat). In short, your metabolism becomes severely compromised.
Even if you're taking vitamin K2 and ubiquinol, you still have to address the fact that you cannot make ketones, because you cannot take a ketone supplement. Ultimately, this has cardiovascular consequences as well, because your heart is the most mitochondrial-dense tissue in your body. If you deprive your cardiac tissue of fuel, by definition you impair your cardiovascular health.
Ubiquinol Benefits Heart Failure Patients
Heart failure is nearly at epidemic levels. There's a specific physiological condition called diastolic dysfunction where your ventricle hardens. As a result, your heart cannot properly refill with blood during diastole. This can eventually progress to heart failure. Unfortunately, many who have this condition don't even know it. There are markers that can be used to screen for it though, including NT-proBNP and GGT.
"There are a couple of papers out there now that talk about actual physician experience with patients with heart failure. They had some of these patients on CoQ10, and then they ended up switching to ubiquinol because of the better absorption. But the bottom line is that they saw a reversal in the New York Heart Association class.
That's the New York Heart Association's way of rating the severity of the disease. They see reductions in the severity of the disease. They see improvement in the ejection fraction, which is a measure of how well the heart is working in patients ... This is one of the other fantastic benefits of ubiquinol and something that both doctors and patients should know about,"Schulman says.
I personally think all heart failure patients should be on ubiquinol. To me, failure to do so is medical negligence. When it comes to heart health, a more general benefit is that ubiquinol also acts as an antioxidant in your blood, where it prevents the oxidation of LDL cholesterol, thereby helping prevent atherosclerosis. This is another important heart health function of ubiquinol.
Suggested Dosing Recommendations
Dosing requirements will vary depending on your individual situation and needs, but some general guidelines can still be made. As a general rule, the sicker you are, the more you need. According to Schulman, the highest amount she's seen used in a research setting was 600 milligrams (mg) per day, and that was for severely ill people.
If you're just starting out with ubiquinol, start with 200 to 300 mg per day. Within three weeks, your plasma levels will typically plateau to its optimum level. After that, you can go down to a 100 mg/day maintenance dose. This dose is typically sufficient for healthy people. If you have an active lifestyle, exercise a lot, or are under a lot of stress due to your job or "life" in general, you may want to increase your dose to 200 to 300 mg/day.
Remember, if you're on a statin drug you MUST take at least 100 to 200 mg of ubiquinol or CoQ10 per day, or more. To address heart failure and/or other significant heart problems you may need around 350 mg per day or more. Ideally, you'll want to work with your physician to ascertain your ideal dose. Your doctor can do a blood test to measure your CoQ10 levels, which would tell you whether your dose is high enough to keep you within a healthy range.
CoQ10 (or ubiquinol) is also appropriate for those with other chronic diseases besides heart problems, such as diabetes, amyotrophic lateral sclerosis (ALS), chronic fatigue and autism for example. Ideally, you'll want to split the dose up to two or three times a day, rather than taking it all at once, as this will result in higher blood levels.
Other dosing guidelines, as presented by Dr. Stephen Sinatra (a board-certified cardiologist, and a prominent expert in the field of natural cardiology) include:
Hypertension, 200 mg/day
World class athletes who need extra ATP turnover, 300 to 600 mg/day
Heart transplant or severe congestive heart failure (CHF), 300 to 600 mg/day in divided doses
Arrhythmia, 200 mg/day
Typical athletes, 100 to 300 mg/day
Mitral valve prolapse, a combination of 400 mg magnesium and 100 to 200 mg of ubiquinol
(CNN)The odds of surviving a heart attack are better than ever in the United States thanks to improvements in therapies.
But that means about 2.5 million Americans live with heart failure that blocks blood vessels and reduces blood supply to the body.
By Carina Storrs, Special to CNN
Updated 1710 GMT (0010 HKT) April 4, 2016
A new study provides an early indication that cell therapy using cells from bone marrow could one day help treat heart failure.
Researchers gave 60 patients with heart failure an injection of the therapy in the heart and compared their rates of death and heart problems to those of 66 similar patients who received a placebo injection of saltwater in the heart.
The researchers found that, during the year following the treatment, the patients who received the cell therapy had a 37% lower rate of death and hospitalization for heart failure-related problems, such as fluid buildup in the body or shortness of breath, compared with the placebo group. In the cell therapy group, 3.4% of the patients died and 51.7% were hospitalized for heart problems, whereas 13.7% of the placebo group died and 82.4% were hospitalized.
"This would be considered a huge success because this much of a reduction has not been shown with any other (cell) therapy," said Dr. Amit N. Patel, director of the clinical regenerative medicine program in the University of Utah Department of Surgery.
The therapy is working probably because it either "slows down or reverses the rate of progression of disease," said Patel, who led the clinical study, which was published on Monday in the journal The Lancetand presented at the annual scientific meeting of the American College of Cardiology. Rather than increasing the number of muscle cells or blood vessels in the heart, the therapy is probably making the muscle cells work better, he added.
The company that developed the cell therapy technology, called Vericel Corp., funded and was involved in the study, although Patel said he had the final say about what was included in the article.
Here's how the therapy, which is called Ixmyelocel-T, is carried out: The researchers remove about three tablespoons of bone marrow from the hip bone while the patient is lightly sedated. The cells in the bone marrow then grow in an instrument called a bioreactor for two weeks, producing a "soup" of cells containing certain types of stem cells and immune cells that can help remodel tissue and reduce inflammation, Patel said. Finally the researchers use special catheters to identify the weakest parts of the heart and inject the soup into these areas.
In the year after the injection, 20.3% of the patients in the cell therapy group experienced an adverse event such as infection or stroke, compared with 41.8% of the placebo group. "It was surprising that the (placebo) patients did significantly worse," Patel said. This could have been because they underwent the same invasive procedures as the treatment group, but did not receive the same potentially beneficial cell therapy, which could have anti-inflammatory effects that decreased adverse events, he said.
"The study is very exciting because for the first time it showed a physical impact on clinical events, and in this case that was mortality and rehospitalization for heart failure," said Dr. Thomas J. Povsic, an interventional cardiologist and associate professor of the Duke Clinical Research Institute. Povsic was not involved in the study, but wrote an editorial about the study for the same issue of The Lancet.
Nevertheless, this therapy will need to be tested on more patients, Povsic said. "Although the study in The Lancet is very encouraging, it's still a relatively small study by cardiovascular standards. In heart disease we typically study hundreds to thousands of patients," he said.
The researchers and Vericel are hoping to start a larger phase 3 clinical trial of Ixmyelocel-T that includes more heart failure patients. The new study was a phase 2 trial, and these trials generally focus on establishing the effectiveness and safety of a new therapy.
There are currently several phase 2 and 3 trials underway testing cell therapies for the treatment of various types of heart disease. So far, studies have either not addressed the therapy's effect on clinical outcomes, or failed to observe an improvement in heart disease.
Earlier cell therapies used all the cells in the bone marrow instead of selecting for certain types of cells, and thus might have been diluting their beneficial effects, Povsic said. "We are moving more and more away from first generation cell therapy," said Povsic, who is involved in two ongoing trials looking at the effect of selected cells from bone marrow in patients with heart failure or angina, a type of heart disease that reduces blood supply to the heart.
No cell therapies have been approved worldwide for heart failure patients. There are also no approved cell therapies for other types of heart disease in the United States, but several therapies are available in Asia, including a stem cell-based treatment for people who have had a heart attack.
The therapy in the new study would be appropriate for patients who have heart failure and are getting worse, despite taking medicines such as beta blockers and ACE inhibitors, Patel said. Nearly all the patients in the study were on one of these drugs. However, the therapy would not be appropriate for patients whose heart failure is so bad that they are often hospitalized for heart complications, Patel said. These patients would be candidates for a heart transplant or left ventricular assist device.
"There's a growing population of (heart failure) patients that are on medicines and who continue to have significant symptoms," Povsic said.
