2018年6月29日星期五
2018年5月29日星期二
A Heart Risk Factor Even Doctors Know Little About Lp(a)
A Heart Risk Factor Even Doctors Know Little About
To millions of Americans, Bob Harper was the picture of health, a celebrity fitness trainer who whipped people into shape each week on the hit TV show “The Biggest Loser.”
But last February, Mr. Harper, 52, suffered a massive heart attack at a New York City gym and went into cardiac arrest. He was saved by a bystander who administered CPR and a team of paramedics who rushed him to a hospital, where he spent two days in a coma.
When he awoke, Mr. Harper was baffled, as were his doctors. His annual medical checkups had indicated he was in excellent health. How could this have happened to someone seemingly so healthy?
The culprit, in turned out, was a fatty particle in the blood called lipoprotein(a). While doctors routinely test for other lipoproteins like HDL and LDL cholesterol, few test for lipoprotein(a), also known as lp(a), high levels of which triple the risk of having a heart attack or stroke at an early age.
For most people, lp(a) is nothing to worry about. Levels are strongly determined by genetics and the majority of people produce very little of it.
But up to one in five Americans, including Mr. Harper, have perilously high levels of it in their blood. Studies show that diet and exercise have almost no impact on lp(a), and cholesterol-lowering drugs only modestly lower it.
“People don’t know about it, physicians don’t know about it, and we have to get an education program out there, but that’s expensive,” said Dr. Henry N. Ginsberg, the Irving Professor of Medicine at Columbia University and a leading expert on lp(a). “I would say that somewhere between 15 to 20 percent of the population would clearly benefit from knowing that this is their problem.”
Lp(a) was discovered in 1963 by a Norwegian scientist, Kare Berg, who noticed that it was especially common among people with coronary heart disease. No one knows precisely what purpose lp(a) serves in the body, though some scientists speculate that it may have a beneficial role such as helping to repair injured cells or preventing infections by binding to pathogens in the blood.
But the downside of excessive lp(a) is clear: It accelerates the formation of plaque in the arteries, and it promotes blood clots.
“It’s sort of a double whammy,” said Dr. Donald Lloyd-Jones, a cardiologist at the Northwestern University Feinberg School of Medicine who helped write the American Heart Association’s cholesterol guidelines. “Biologically, lp(a) both gets into the artery wall and causes damage there more easily.”
Studies suggest that the threshold for high lp(a) begins around 30 milligrams per deciliter of blood. Heart disease risk jumps for those in the 80th percentile, with lp(a) levels above 60, and climbs sharply for the 5 percent of the population with lp(a) levels between 150 and 300, according to Dr. Ginsberg at Columbia. “Those people can be disasters in terms of cardiovascular risk,” he said.
Yet many people at high risk do not fit the typical profile of a person with heart disease. Sandra Revill Tremulis was a health-conscious medical device executive who moonlighted as an aerobics instructor, followed a strict diet, and maintained 16 percent body fat, equivalent to that of an elite athlete. Her LDL and total cholesterol levels were low, and at age 39, her Framingham risk score, which gauges heart disease risk, put her odds of having a heart attack in her 40s at just 1 percent.
But when she started experiencing extreme fatigue and struggled to finish her workouts, she went to an interventional cardiologist and asked for a thorough work-up — which revealed that she had a 95 percent blockage in one of her coronary arteries.
“I was imminent to have a widow-maker heart attack at age 39,” she said.
Further testing showed she had high lp(a), which she believes she inherited from her father, who died of a heart attack at age 50. Determined to raise awareness, Ms. Revill Tremulis started a nonprofit, the Lipoprotein(a) Foundation, and now travels the globe advocating for wider testing.
“Only a small percentage of physicians know about this,” she said. “The biggest challenge for patients is finding knowledgeable physicians who know about this and can help them.”
Dr. Lloyd-Jones at Northwestern said that testing for lp(a) should be considered for people with early-onset cardiovascular disease — which means younger than age 50 for men and age 60 for women — or a strong family history of it. Since high lp(a) is hereditary, those who have it often have a parent, sibling or grandparent who suffered a premature heart attack or stroke. When one person has it, it’s important to test other family members too.
“It’s what we call cascade screening, looking for affected first-degree relatives,” Dr. Lloyd-Jones said.
Once high lp(a) is identified, doctors try to mitigate its effects by controlling other risk factors. They aggressively lower patients’ LDL cholesterol, optimize their blood pressure and blood sugar, and strongly encourage healthy diet and exercise habits.
Two medications, niacin and a class of drugs known as PCSK9 inhibitors, have been shown to modestly reduce lp(a) levels. But niacin, a B vitamin, has many side effects, and PCSK9 inhibitors, which are not approved for lp(a) lowering, are not usually covered by insurance for that purpose and can cost as much as $14,000 a year.
At least one drug company, Akcea Therapeutics, a spinoff of Ionis Pharmaceuticals, is developing a drug specifically to combat lp(a), but the drug is still in mid-stage testing and it could be years before it reaches the market.
Since his heart attack, Mr. Harper of “The Biggest Loser” has embarked on a newfound mission to raise awareness about heart disease and to urge people to get tested for lp(a).
His days no longer revolve around intense and grueling workouts, he said. Instead he believes the key to being healthy is managing stress, getting proper sleep, eating a balanced diet and enjoying life because it could end at any moment, an approach he has outlined in his new book, “The Super Carb Diet.”
“Being healthy is not about what you can do in the gym,” Mr. Harper said. “It’s not about what you can do on the outside. It’s what’s going on in the inside. I really needed to find out what was going on with me, and that’s what this did. It woke me up.”
To millions of Americans, Bob Harper was the picture of health, a celebrity fitness trainer who whipped people into shape each week on the hit TV show “The Biggest Loser.”
But last February, Mr. Harper, 52, suffered a massive heart attack at a New York City gym and went into cardiac arrest. He was saved by a bystander who administered CPR and a team of paramedics who rushed him to a hospital, where he spent two days in a coma.
When he awoke, Mr. Harper was baffled, as were his doctors. His annual medical checkups had indicated he was in excellent health. How could this have happened to someone seemingly so healthy?
The culprit, in turned out, was a fatty particle in the blood called lipoprotein(a). While doctors routinely test for other lipoproteins like HDL and LDL cholesterol, few test for lipoprotein(a), also known as lp(a), high levels of which triple the risk of having a heart attack or stroke at an early age.
For most people, lp(a) is nothing to worry about. Levels are strongly determined by genetics and the majority of people produce very little of it.
But up to one in five Americans, including Mr. Harper, have perilously high levels of it in their blood. Studies show that diet and exercise have almost no impact on lp(a), and cholesterol-lowering drugs only modestly lower it.
“People don’t know about it, physicians don’t know about it, and we have to get an education program out there, but that’s expensive,” said Dr. Henry N. Ginsberg, the Irving Professor of Medicine at Columbia University and a leading expert on lp(a). “I would say that somewhere between 15 to 20 percent of the population would clearly benefit from knowing that this is their problem.”
Lp(a) was discovered in 1963 by a Norwegian scientist, Kare Berg, who noticed that it was especially common among people with coronary heart disease. No one knows precisely what purpose lp(a) serves in the body, though some scientists speculate that it may have a beneficial role such as helping to repair injured cells or preventing infections by binding to pathogens in the blood.
But the downside of excessive lp(a) is clear: It accelerates the formation of plaque in the arteries, and it promotes blood clots.
“It’s sort of a double whammy,” said Dr. Donald Lloyd-Jones, a cardiologist at the Northwestern University Feinberg School of Medicine who helped write the American Heart Association’s cholesterol guidelines. “Biologically, lp(a) both gets into the artery wall and causes damage there more easily.”
Studies suggest that the threshold for high lp(a) begins around 30 milligrams per deciliter of blood. Heart disease risk jumps for those in the 80th percentile, with lp(a) levels above 60, and climbs sharply for the 5 percent of the population with lp(a) levels between 150 and 300, according to Dr. Ginsberg at Columbia. “Those people can be disasters in terms of cardiovascular risk,” he said.
Yet many people at high risk do not fit the typical profile of a person with heart disease. Sandra Revill Tremulis was a health-conscious medical device executive who moonlighted as an aerobics instructor, followed a strict diet, and maintained 16 percent body fat, equivalent to that of an elite athlete. Her LDL and total cholesterol levels were low, and at age 39, her Framingham risk score, which gauges heart disease risk, put her odds of having a heart attack in her 40s at just 1 percent.
But when she started experiencing extreme fatigue and struggled to finish her workouts, she went to an interventional cardiologist and asked for a thorough work-up — which revealed that she had a 95 percent blockage in one of her coronary arteries.
“I was imminent to have a widow-maker heart attack at age 39,” she said.
Further testing showed she had high lp(a), which she believes she inherited from her father, who died of a heart attack at age 50. Determined to raise awareness, Ms. Revill Tremulis started a nonprofit, the Lipoprotein(a) Foundation, and now travels the globe advocating for wider testing.
“Only a small percentage of physicians know about this,” she said. “The biggest challenge for patients is finding knowledgeable physicians who know about this and can help them.”
Dr. Lloyd-Jones at Northwestern said that testing for lp(a) should be considered for people with early-onset cardiovascular disease — which means younger than age 50 for men and age 60 for women — or a strong family history of it. Since high lp(a) is hereditary, those who have it often have a parent, sibling or grandparent who suffered a premature heart attack or stroke. When one person has it, it’s important to test other family members too.
“It’s what we call cascade screening, looking for affected first-degree relatives,” Dr. Lloyd-Jones said.
Once high lp(a) is identified, doctors try to mitigate its effects by controlling other risk factors. They aggressively lower patients’ LDL cholesterol, optimize their blood pressure and blood sugar, and strongly encourage healthy diet and exercise habits.
Two medications, niacin and a class of drugs known as PCSK9 inhibitors, have been shown to modestly reduce lp(a) levels. But niacin, a B vitamin, has many side effects, and PCSK9 inhibitors, which are not approved for lp(a) lowering, are not usually covered by insurance for that purpose and can cost as much as $14,000 a year.
At least one drug company, Akcea Therapeutics, a spinoff of Ionis Pharmaceuticals, is developing a drug specifically to combat lp(a), but the drug is still in mid-stage testing and it could be years before it reaches the market.
Since his heart attack, Mr. Harper of “The Biggest Loser” has embarked on a newfound mission to raise awareness about heart disease and to urge people to get tested for lp(a).
His days no longer revolve around intense and grueling workouts, he said. Instead he believes the key to being healthy is managing stress, getting proper sleep, eating a balanced diet and enjoying life because it could end at any moment, an approach he has outlined in his new book, “The Super Carb Diet.”
“Being healthy is not about what you can do in the gym,” Mr. Harper said. “It’s not about what you can do on the outside. It’s what’s going on in the inside. I really needed to find out what was going on with me, and that’s what this did. It woke me up.”
2017年8月24日星期四
Metabolic Theory of Cancer
Story at-a-glance
Oncologists in Turkey who aren’t under the same U.S. restrictions, are using a stacked ketogenic treatment protocol that is showing shocking remissions in many stage 4 cancer patients
By using metabolic support strategies such as ketogenic diet and fasting, a minimal dose of chemotherapy can be used, thereby eliminating many of the side effects and risks of treatment while actually improving outcomes
Stage 4 pancreatic cancer patients have a life expectancy of six months. Yet metabolically supported chemotherapy was able to induce complete remission even in patients with this advanced stage disease
Each and every day, more than 1,600 people prematurely die from cancer in the United States alone and 20,000 worldwide. While the situation can sometimes seem hopeless, there are effective ways to prevent becoming another statistic.
And, as you will soon learn, even late-stage cancer patients have cause for new hope these days.
In this interview, Travis Christofferson, author of "Tripping Over the Truth: How the Metabolic Theory of Cancer is Overturning One of Medicine's Most Entrenched Paradigms," and Dr. Abdul Kadir Slocum from the ChemoThermia Oncology Center in Turkey.
They present data from one of the first studies documenting the effectiveness of metabolic therapies and nutritional ketosis in the treatment of advanced stages of cancer.
"I'm very excited for this data to be presented," Christofferson says. "[Cancer] diagnosis has gone up from 1 in 4 to 1 in 3 and is heading toward 1 in 2 ... It's set to surpass heart disease as the No. 1 killer in the Western world by 2020 …
We've been treating this disease a long time. Nixon signed the Cancer Act in 1971 … Radiation and surgery have been around for over 100 years. Cytotoxic chemotherapy was developed right after World War II. [Yet] death rates from treatment have barely budged since the 1950s."
The War on Cancer Has Been Lost Many Times Over
In the mid-1970s, scientists believed they finally understood the molecular basis of cancer. The reigning hypothesis was that cancer was caused by sequential mutations to key oncogenes, which could then be precisely targeted using gene-based therapies. This ushered in the era of targeted therapy.
Alas, targeted cancer drugs have been a bitter disappointment. They barely moved the needle on cancer death rates. Globally, $91 billion was spent on oncology in 2013. In 2014, no cancer drug was approved costing less than $100,000 for a course treatment.
In 2015, eight drugs were approved that cost over $120,000 each for a course of treatment. As noted by Christofferson, this trajectory will eventually bankrupt the health care system. Adding insult to injury, these drugs have marginal efficacy at best.
Consider Tarceva, for example. This cancer drug was approved about 10 years ago. It has significant side effects, it's expensive, and boosts median survival for pancreatic cancer patients by a mere 10 DAYS!
"In the meantime, we have these non-patentable therapies sitting on the sidelines that could potentially be game changers for cancer, but they cannot get the billion-dollar backing to push through these huge trials to get the burden of proof to where the oncology community will actually incorporate them," Christofferson says.
"We have all these interesting metabolic therapies. We have repurposed drugs that we could use. The oppressive regulatory environment just needs to be loosened so we can surmount the burden of proof, Phase 1, Phase 2 data, if we have good objective response.
If they're safe — most of these drugs and therapies are extremely safe — that should be good enough.
In the epilogue in my book, I ask the question, 'What would it look like today if we had a less onerous regulatory environment like they did in the '70s, and good oncologists were allowed to … try some of these therapies in the clinic and see what happens?'
That's why I'm so happy we have Slocum here, because he's given us the first glimpse of what metabolic therapies will look like when they're incorporated into the clinic."
Turkish Oncologists Apply the Metabolic Theory of Cancer
Slocum, who is originally from the U.S. but grew up and completed his medical training in Istanbul, Turkey, is part of a four-member medical team at ChemoThermia Oncology Center.
The senior person of the team, professor Bulent Berkarda, was the first medical oncologist in Turkey. Educated in the U.S., Berkarda founded the first Department of Medical Oncology of Turkey at Istanbul University in 1974 and has now been practicing oncology for over 40 years.
Together with Berkarda, the other medical oncologist of the team, assistant professor Mehmet Salih İyikesici completed his education in the leading medical schools of Turkey.
"We started as a team back in 2010, asking the question, 'How can we help our patients in a better way? What can we add to our standard treatment protocols?," Slocum says. "In the last six years, we started applying the [metabolic] therapies and seeing how our patients respond.
Now, for the last two years or so, we're doing retrospective analyses of our patients, publishing our treatment outcomes and sharing the remarkable outcomes we were able to achieve by combining metabolic therapies with standard conventional protocols."
The treatment protocol at ChemoThermia Oncology Center includes:
Metabolically supported chemotherapy
Hyperthermia
Hyperbaric oxygen therapy
Glycolysis inhibitors, especially 2-deoxyglucose (2-DG) and dichloroacetate (DCA)
Ketogenic diet with phytopharmaceutical supplements
Metabolically Supported Chemotherapy
Metabolically-supported chemotherapy involves applying chemotherapy with a variety of interventions to support its effectiveness.
At the center, all oncology patients are put on a ketogenic diet, which creates metabolic stress on the cancer cells. Then, prior to administering the chemo, the patient will do a 14-hour fast, which further increases the metabolic stress on the cancer cells.
The patients will typically have a blood glucose level around 80 milligrams per deciliter (mg/dL) at this point. They then apply glycolysis inhibitors to inhibit the glycolysis pathway in the cancer cells, which creates a terrific amount of metabolic stress, as the cancer cells are already starved of glucose.
Insulin is then applied to lower the blood glucose levels to around 50 or 60 mg/dL, to cause mild hypoglycemia. At that point, chemotherapy is applied.
"[T]his increases the efficacy of chemotherapy in a tremendous way," Slocum says. "We've been applying this for the last seven years now. It's an improved version of insulin potentiation therapy (IPT). IPT is known for many years now, but it's not too widely applied.
Our version of chemotherapy is actually an improved and a much more effective version of IPT because it combines the metabolic theory with the IPT. Metabolically supported chemotherapy is just a different way to apply conventional protocols. We have seen that it increases the effectiveness of the standard chemotherapy regimes. This way, it gives us the option to apply lower doses, see much lower side effects, but much [better] outcomes."
As in the U.S., Turkish oncologists are bound by "standard of care" treatment protocols, which includes chemotherapy. As noted by Slocum, "according to the current regime worldwide … the patient, even in Turkey, must receive what's written in the guidelines. If you go against the guidelines and if the patient doesn't receive the standard of care, which is chemotherapy, then you're in trouble." They essentially get around this by just using the lowest dose possible that's written in guidelines.
The upshot of this metabolic approach is that a far lower dose of chemotherapy can be effectively used, thereby lowering the risk of side effects. In the days following chemotherapy, hyperthermia and hyperbaric oxygen therapy is applied, plus a daily infusion of glycolysis inhibitor therapies with high-dose vitamin C (50 grams) and dimethyl sulfoxide (DMSO).
Complete Response for Stage 3 Rectal Cancer
In the team's first publication in 2016, they reported complete response for stage 3 rectal cancer. The standard of care for rectal cancer and the only curative option has been surgery or chemo-radiotherapy followed by surgery. In this case, they used metabolically supported chemotherapy, radiotherapy and hyperthermia. No surgery was necessary.
"The reason we published that was to explain what metabolically supported chemotherapy is and show how effective it can be," Slocum says. "The patient we published was 81 years old back then.
Generally, in an 81-year-old patient you won't be able to apply standard chemotherapy regimens. She won't be able to tolerate it. By the means of the way we apply chemotherapy, this patient was able to receive chemotherapy at lower doses in a metabolically supported fashion, together with radiotherapy and hyperthermia."
In the video, Slocum shows the initial positron emission tomography-computed tomography (PET-CT) scan of this patient. The patient had a 5.5 centimeter large rectal tumor. Three months later, the tumor was in full remission.
"This publication mainly showed that chemotherapy, when applied in a metabolically supported fashion, can be applied to patients who normally can't receive treatment. Also, when it's applied with increased efficacy, responses that aren't normal, generally, which is a complete response in this stage of a disease, can be achieved by the means of metabolic support."
Case Series on Pancreatic Cancer
The second paper published last year was a case series of 33 patients with stage 3 and 4 pancreatic adenocarcinoma (pancreatic cancer) — one of the most aggressive and deadly cancers known. It was a retrospective analysis of patients treated at the clinic between 2011 and 2015. Eighty-one percent of these patients had stage 4 disease when the treatment began, and many of them also had large scale liver metastasis.
Generally, if a patient has stage 4 pancreatic adenocarcinoma, their life expectancy is about six months, at most 10 months. If they have large-scale liver metastasis, death typically occurs within weeks or months. Yet despite the majority being end-stage advanced patients, they responded remarkably well to the treatment.
Here, the standard conventional protocol using either gemcitabine-based chemotherapy or folfirinox was again applied in a metabolically supported fashion, together with hyperthermia, hyperbaric oxygen therapy, the ketogenic diet, supplements and glycolysis inhibitors.
When the paper was published in 2016, 54 percent of these patients were still alive, and most are still receiving follow-up treatments to this day. Following the conventional protocol, the expected median survival time for the gemcitabine-based protocol is 6.2 months. For the folfirinox regimen it's 11.1 months. Using a metabolically supported protocol, the median survival time shot up to 20 months — and 54 percent of the patients are still alive today.
"The one-year survival rate for gemcitabine-based protocol is 20 percent. For folfirinox, it's 48 percent. We've seen in our metabolically supported chemotherapy regimen, [survival rate] is 82.5 percent. This shows how effective metabolic support can change the outcomes of treatments and how effective these kinds of treatments can be," Slocum says.
"As all of us know, the scariest cancer diagnosis is pancreatic cancer. Currently in our regimens, we're seeing amazing outcomes. It's so exciting to see how small differences can change these patients' lives so much."
Case Series on Stage 4 Lung Cancer
Next, the team will be publishing a paper on stage 4 non-small cell lung cancer. Here, they applied a chemotherapy regimen using carboplatin and paclitaxel. Large-scale clinical trials show an expected survival time of six to 11 months. Moreover, stage 4 patients typically cannot tolerate conventional chemo regimens so no large-scale studies have focused on such late-stage patients.
Using the metabolically supported protocol, however, all of the 44 patients in the study were able to receive treatment, and the overall survival time is 43.4 months — that's more than 400 percent longer than the longest survival time mentioned in any standard chemotherapy regimen.
"This is a dramatic result, even though the patient group we had had more advanced disease and had poor performance status," Slocum notes. "[P]atients who normally were sent home to just wait for the end, to die, and also patients that won't be able to receive treatment … can respond [well] to treatment … The advantage of metabolic treatments is that they're generally not toxic at all. They support the general wellbeing of the patient while also treating the disease."
Survival Rates for Late Stage, Advanced Cancers Dramatically Improve With Metabolic Therapies
In the video, Dr. Slocum shows PET scans and reviews a number of different patient cases, showing the remarkable response of patients with advanced cancer of the rectum, pancreas, stomach, lung and breast.
This is, to the best of my knowledge, the first time all of this data has been publicly shared. It's really exciting to reveal to the world the shocking effectiveness of what Thomas Seyfried, Ph.D., has been speaking about for some time now. And, if you're stage 1 or 2, your cancer is going to be far easier to treat. The results for early stage cancers are likely to be beyond phenomenal.
"We hope that this kind of treatment will be the standard of care in the upcoming years. We are all trying to share what would work and how we're achieving these kinds of results," Slocum says. "Other clinics and other physicians will also hopefully start doing similar therapies."
Christofferson adds:
"[Thomas] Seyfried [Ph.D., a leading expert and researcher in the field of cancer metabolism and nutritional ketosis] and Slocum met in Tampa. They've started a collaboration ... Hopefully a year from now, when we talk about these shocking outcomes, they're even more shocking.
Just to summarize, [Slocum's] upcoming stage 4 lung cancer paper is incredible … A certain percentage of them aren't going to make it no matter what, but if they can get through this metabolic protocol, the median survival would increase 400 percent.
That's incredible. This stuff basically is free. It just took somebody motivated enough to do this. I mean 2-deoxyglucose (2-DG) is expensive, but ketogenic diet is free. It just takes work. I couldn't be happier that this data is coming to life."
Discipline Is Required When Your Life Is in Your Own Hands
It goes without saying that when using metabolic therapies, the patient carries a significant responsibility for their own outcome. The doctors are not going to cook your food, force you to take supplements or withhold food when it's time to fast. You have to be very diligent and disciplined in following the specified regimen. As noted by Slocum, when patients don't respond as well as expected, probing will usually reveal the problem — they didn't follow the diet, for example.
Essentially, if you have a life-threatening condition like stage 4 cancer, you need to be a bit obsessive compulsive and follow the regimen to the letter. You cannot veer from the protocol if you expect to achieve these kinds of results. You really need to remain in nutritional ketosis. That said, if you're merely seeking to optimize your health or slow down the aging process, cycling through "feast and famine" — opposed to continuously remaining in nutritional ketosis — appears to be a better approach.
Nutritional ketosis is a powerful intervention, as Slocum's team has shown. But if you do it continuously, it can actually be highly counterproductive. You need to have days where you eat more net carbs and more protein, especially with strength training, to prevent sarcopenia that is common in cancer.
This is because when cancer cells are deprived of glucose they have the ability to break down muscle tissue to extract glutamine. Interestingly, Seyfried is working with a glutamine inhibitor called DON to prevent this from happening, thereby making the therapy even more effective.
It is important to understand that the "metabolic magic" actually occurs during that refeeding phase when net carbs and protein are increased, which increases muscle growth. After a day or two, you then cycle back into nutritional ketosis. Typically, this is done once a week. To a degree, Slocum uses this technique on cancer patients as well, although they're only allowed to eat higher amounts of net carbs once every two or three weeks, on the day they receive chemo.
"As an example, patients come and they're on a ketogenic diet. When they come in for chemotherapy after a 14-hour fast, then [we] apply glycolysis inhibitors to increase metabolic stress even more and insulin to lower the glucose and then apply chemotherapy.
After applying chemotherapy, on the day of chemotherapy, they are able to eat whatever they want, especially because of the mild hypoglycemia caused by supplying insulin. The day of chemotherapy is when they get as much carbohydrates as they want … We also do intermittent fasting [for a minimum of 14 hours] every other week or so. It seems to be effective."
More Information
The ChemoThermia Oncology Center treats many international patients, including people from the U.S. and Canada. The center also has published protocols your oncologist could make use of, regardless of where you live.
"We hope there will be physicians open to applying similar regimens to ours," Slocum says. "But a lot of patients who aren't able to come to our clinic, they can [still] do it. They first have to go on a ketogenic diet, which is very effective. Together with that, they should go to their chemotherapy in a fasting state, as long as they can stand it — a minimum of 12 hours. We generally recommend a 14-hour fast. The longer … the better."
Ideally, a reduced amount of the chemotherapeutic agents would then be used. While the amount varies according to your diagnosis and condition, the center has included dose range recommendations in their publications. Typically, the lowest recommended dose is given, which will significantly reduce or avoid most of the complications associated with chemotherapy.
"I hope people out there can see how effective metabolic therapies can be and how they can enhance conventional treatment protocols also. I encourage clinicians out there to ask similar questions to us, to read the literature and start applying similar therapies to ours," Slocum says.
Christofferson adds:
"What I would like to say is [that] patients who are confused by the ketogenic diet often don't know the difference between protein and carbohydrate. That's where they often get tripped up, because they're not sure what a carbohydrate is. Companies are stepping into this fray, making prepackaged The ones I've seen are really well done by gourmet chefs and [use] real ingredients. That's another option. There's enough on patients' plates to begin with … That's going to take a lot of the guesswork out for patients, I think."
To learn more about nutritional ketosis and the metabolic theory of cancer, I highly recommend listening to the interview I did with Christofferson last year, and to read his book, "Tripping Over the Truth," which provides the background as to why and how this therapy works, and why the conventional approach to cancer is fatally flawed.
If you're beyond that point and really want to implement this kind of metabolic therapy, I highly recommend preordering a copy of new book, "Fat for Fuel," which gives you all the details on how to do that. Anyone that preorders it will have access to my recent 2017 lecture that I have given at several events. Normally these lectures are never posted online. Incidentally, Christofferson was one of the experts who helped edit my book and actually wrote a section on Dr. Rosedale's work. I'm grateful for all his assistance.
Besides the information in the book, you'll also find many collaborative supports, including a nine-hour-long free video series that we hope to launch in early May. Miriam Kalamian is also developing a certification course to go along with it through the American College of Nutrition, to have more qualified therapists out there.ketogenic meals for cancer patients that take out the guesswork.
This certification will teach any qualified clinician — primarily certified clinical nutritionists but also physicians — how to practically implement nutritional ketosis. Eventually, I expect there will be a virtual army of clinicians available to assist patients with this kind of protocol. Hopefully, at that point we'll finally start making a dent in cancer statistics.
Oncologists in Turkey who aren’t under the same U.S. restrictions, are using a stacked ketogenic treatment protocol that is showing shocking remissions in many stage 4 cancer patients
By using metabolic support strategies such as ketogenic diet and fasting, a minimal dose of chemotherapy can be used, thereby eliminating many of the side effects and risks of treatment while actually improving outcomes
Stage 4 pancreatic cancer patients have a life expectancy of six months. Yet metabolically supported chemotherapy was able to induce complete remission even in patients with this advanced stage disease
Each and every day, more than 1,600 people prematurely die from cancer in the United States alone and 20,000 worldwide. While the situation can sometimes seem hopeless, there are effective ways to prevent becoming another statistic.
And, as you will soon learn, even late-stage cancer patients have cause for new hope these days.
In this interview, Travis Christofferson, author of "Tripping Over the Truth: How the Metabolic Theory of Cancer is Overturning One of Medicine's Most Entrenched Paradigms," and Dr. Abdul Kadir Slocum from the ChemoThermia Oncology Center in Turkey.
They present data from one of the first studies documenting the effectiveness of metabolic therapies and nutritional ketosis in the treatment of advanced stages of cancer.
"I'm very excited for this data to be presented," Christofferson says. "[Cancer] diagnosis has gone up from 1 in 4 to 1 in 3 and is heading toward 1 in 2 ... It's set to surpass heart disease as the No. 1 killer in the Western world by 2020 …
We've been treating this disease a long time. Nixon signed the Cancer Act in 1971 … Radiation and surgery have been around for over 100 years. Cytotoxic chemotherapy was developed right after World War II. [Yet] death rates from treatment have barely budged since the 1950s."
The War on Cancer Has Been Lost Many Times Over
In the mid-1970s, scientists believed they finally understood the molecular basis of cancer. The reigning hypothesis was that cancer was caused by sequential mutations to key oncogenes, which could then be precisely targeted using gene-based therapies. This ushered in the era of targeted therapy.
Alas, targeted cancer drugs have been a bitter disappointment. They barely moved the needle on cancer death rates. Globally, $91 billion was spent on oncology in 2013. In 2014, no cancer drug was approved costing less than $100,000 for a course treatment.
In 2015, eight drugs were approved that cost over $120,000 each for a course of treatment. As noted by Christofferson, this trajectory will eventually bankrupt the health care system. Adding insult to injury, these drugs have marginal efficacy at best.
Consider Tarceva, for example. This cancer drug was approved about 10 years ago. It has significant side effects, it's expensive, and boosts median survival for pancreatic cancer patients by a mere 10 DAYS!
"In the meantime, we have these non-patentable therapies sitting on the sidelines that could potentially be game changers for cancer, but they cannot get the billion-dollar backing to push through these huge trials to get the burden of proof to where the oncology community will actually incorporate them," Christofferson says.
"We have all these interesting metabolic therapies. We have repurposed drugs that we could use. The oppressive regulatory environment just needs to be loosened so we can surmount the burden of proof, Phase 1, Phase 2 data, if we have good objective response.
If they're safe — most of these drugs and therapies are extremely safe — that should be good enough.
In the epilogue in my book, I ask the question, 'What would it look like today if we had a less onerous regulatory environment like they did in the '70s, and good oncologists were allowed to … try some of these therapies in the clinic and see what happens?'
That's why I'm so happy we have Slocum here, because he's given us the first glimpse of what metabolic therapies will look like when they're incorporated into the clinic."
Turkish Oncologists Apply the Metabolic Theory of Cancer
Slocum, who is originally from the U.S. but grew up and completed his medical training in Istanbul, Turkey, is part of a four-member medical team at ChemoThermia Oncology Center.
The senior person of the team, professor Bulent Berkarda, was the first medical oncologist in Turkey. Educated in the U.S., Berkarda founded the first Department of Medical Oncology of Turkey at Istanbul University in 1974 and has now been practicing oncology for over 40 years.
Together with Berkarda, the other medical oncologist of the team, assistant professor Mehmet Salih İyikesici completed his education in the leading medical schools of Turkey.
"We started as a team back in 2010, asking the question, 'How can we help our patients in a better way? What can we add to our standard treatment protocols?," Slocum says. "In the last six years, we started applying the [metabolic] therapies and seeing how our patients respond.
Now, for the last two years or so, we're doing retrospective analyses of our patients, publishing our treatment outcomes and sharing the remarkable outcomes we were able to achieve by combining metabolic therapies with standard conventional protocols."
The treatment protocol at ChemoThermia Oncology Center includes:
Metabolically supported chemotherapy
Hyperthermia
Hyperbaric oxygen therapy
Glycolysis inhibitors, especially 2-deoxyglucose (2-DG) and dichloroacetate (DCA)
Ketogenic diet with phytopharmaceutical supplements
Metabolically Supported Chemotherapy
Metabolically-supported chemotherapy involves applying chemotherapy with a variety of interventions to support its effectiveness.
At the center, all oncology patients are put on a ketogenic diet, which creates metabolic stress on the cancer cells. Then, prior to administering the chemo, the patient will do a 14-hour fast, which further increases the metabolic stress on the cancer cells.
The patients will typically have a blood glucose level around 80 milligrams per deciliter (mg/dL) at this point. They then apply glycolysis inhibitors to inhibit the glycolysis pathway in the cancer cells, which creates a terrific amount of metabolic stress, as the cancer cells are already starved of glucose.
Insulin is then applied to lower the blood glucose levels to around 50 or 60 mg/dL, to cause mild hypoglycemia. At that point, chemotherapy is applied.
"[T]his increases the efficacy of chemotherapy in a tremendous way," Slocum says. "We've been applying this for the last seven years now. It's an improved version of insulin potentiation therapy (IPT). IPT is known for many years now, but it's not too widely applied.
Our version of chemotherapy is actually an improved and a much more effective version of IPT because it combines the metabolic theory with the IPT. Metabolically supported chemotherapy is just a different way to apply conventional protocols. We have seen that it increases the effectiveness of the standard chemotherapy regimes. This way, it gives us the option to apply lower doses, see much lower side effects, but much [better] outcomes."
As in the U.S., Turkish oncologists are bound by "standard of care" treatment protocols, which includes chemotherapy. As noted by Slocum, "according to the current regime worldwide … the patient, even in Turkey, must receive what's written in the guidelines. If you go against the guidelines and if the patient doesn't receive the standard of care, which is chemotherapy, then you're in trouble." They essentially get around this by just using the lowest dose possible that's written in guidelines.
The upshot of this metabolic approach is that a far lower dose of chemotherapy can be effectively used, thereby lowering the risk of side effects. In the days following chemotherapy, hyperthermia and hyperbaric oxygen therapy is applied, plus a daily infusion of glycolysis inhibitor therapies with high-dose vitamin C (50 grams) and dimethyl sulfoxide (DMSO).
Complete Response for Stage 3 Rectal Cancer
In the team's first publication in 2016, they reported complete response for stage 3 rectal cancer. The standard of care for rectal cancer and the only curative option has been surgery or chemo-radiotherapy followed by surgery. In this case, they used metabolically supported chemotherapy, radiotherapy and hyperthermia. No surgery was necessary.
"The reason we published that was to explain what metabolically supported chemotherapy is and show how effective it can be," Slocum says. "The patient we published was 81 years old back then.
Generally, in an 81-year-old patient you won't be able to apply standard chemotherapy regimens. She won't be able to tolerate it. By the means of the way we apply chemotherapy, this patient was able to receive chemotherapy at lower doses in a metabolically supported fashion, together with radiotherapy and hyperthermia."
In the video, Slocum shows the initial positron emission tomography-computed tomography (PET-CT) scan of this patient. The patient had a 5.5 centimeter large rectal tumor. Three months later, the tumor was in full remission.
"This publication mainly showed that chemotherapy, when applied in a metabolically supported fashion, can be applied to patients who normally can't receive treatment. Also, when it's applied with increased efficacy, responses that aren't normal, generally, which is a complete response in this stage of a disease, can be achieved by the means of metabolic support."
Case Series on Pancreatic Cancer
The second paper published last year was a case series of 33 patients with stage 3 and 4 pancreatic adenocarcinoma (pancreatic cancer) — one of the most aggressive and deadly cancers known. It was a retrospective analysis of patients treated at the clinic between 2011 and 2015. Eighty-one percent of these patients had stage 4 disease when the treatment began, and many of them also had large scale liver metastasis.
Generally, if a patient has stage 4 pancreatic adenocarcinoma, their life expectancy is about six months, at most 10 months. If they have large-scale liver metastasis, death typically occurs within weeks or months. Yet despite the majority being end-stage advanced patients, they responded remarkably well to the treatment.
Here, the standard conventional protocol using either gemcitabine-based chemotherapy or folfirinox was again applied in a metabolically supported fashion, together with hyperthermia, hyperbaric oxygen therapy, the ketogenic diet, supplements and glycolysis inhibitors.
When the paper was published in 2016, 54 percent of these patients were still alive, and most are still receiving follow-up treatments to this day. Following the conventional protocol, the expected median survival time for the gemcitabine-based protocol is 6.2 months. For the folfirinox regimen it's 11.1 months. Using a metabolically supported protocol, the median survival time shot up to 20 months — and 54 percent of the patients are still alive today.
"The one-year survival rate for gemcitabine-based protocol is 20 percent. For folfirinox, it's 48 percent. We've seen in our metabolically supported chemotherapy regimen, [survival rate] is 82.5 percent. This shows how effective metabolic support can change the outcomes of treatments and how effective these kinds of treatments can be," Slocum says.
"As all of us know, the scariest cancer diagnosis is pancreatic cancer. Currently in our regimens, we're seeing amazing outcomes. It's so exciting to see how small differences can change these patients' lives so much."
Case Series on Stage 4 Lung Cancer
Next, the team will be publishing a paper on stage 4 non-small cell lung cancer. Here, they applied a chemotherapy regimen using carboplatin and paclitaxel. Large-scale clinical trials show an expected survival time of six to 11 months. Moreover, stage 4 patients typically cannot tolerate conventional chemo regimens so no large-scale studies have focused on such late-stage patients.
Using the metabolically supported protocol, however, all of the 44 patients in the study were able to receive treatment, and the overall survival time is 43.4 months — that's more than 400 percent longer than the longest survival time mentioned in any standard chemotherapy regimen.
"This is a dramatic result, even though the patient group we had had more advanced disease and had poor performance status," Slocum notes. "[P]atients who normally were sent home to just wait for the end, to die, and also patients that won't be able to receive treatment … can respond [well] to treatment … The advantage of metabolic treatments is that they're generally not toxic at all. They support the general wellbeing of the patient while also treating the disease."
Survival Rates for Late Stage, Advanced Cancers Dramatically Improve With Metabolic Therapies
In the video, Dr. Slocum shows PET scans and reviews a number of different patient cases, showing the remarkable response of patients with advanced cancer of the rectum, pancreas, stomach, lung and breast.
This is, to the best of my knowledge, the first time all of this data has been publicly shared. It's really exciting to reveal to the world the shocking effectiveness of what Thomas Seyfried, Ph.D., has been speaking about for some time now. And, if you're stage 1 or 2, your cancer is going to be far easier to treat. The results for early stage cancers are likely to be beyond phenomenal.
"We hope that this kind of treatment will be the standard of care in the upcoming years. We are all trying to share what would work and how we're achieving these kinds of results," Slocum says. "Other clinics and other physicians will also hopefully start doing similar therapies."
Christofferson adds:
"[Thomas] Seyfried [Ph.D., a leading expert and researcher in the field of cancer metabolism and nutritional ketosis] and Slocum met in Tampa. They've started a collaboration ... Hopefully a year from now, when we talk about these shocking outcomes, they're even more shocking.
Just to summarize, [Slocum's] upcoming stage 4 lung cancer paper is incredible … A certain percentage of them aren't going to make it no matter what, but if they can get through this metabolic protocol, the median survival would increase 400 percent.
That's incredible. This stuff basically is free. It just took somebody motivated enough to do this. I mean 2-deoxyglucose (2-DG) is expensive, but ketogenic diet is free. It just takes work. I couldn't be happier that this data is coming to life."
Discipline Is Required When Your Life Is in Your Own Hands
It goes without saying that when using metabolic therapies, the patient carries a significant responsibility for their own outcome. The doctors are not going to cook your food, force you to take supplements or withhold food when it's time to fast. You have to be very diligent and disciplined in following the specified regimen. As noted by Slocum, when patients don't respond as well as expected, probing will usually reveal the problem — they didn't follow the diet, for example.
Essentially, if you have a life-threatening condition like stage 4 cancer, you need to be a bit obsessive compulsive and follow the regimen to the letter. You cannot veer from the protocol if you expect to achieve these kinds of results. You really need to remain in nutritional ketosis. That said, if you're merely seeking to optimize your health or slow down the aging process, cycling through "feast and famine" — opposed to continuously remaining in nutritional ketosis — appears to be a better approach.
Nutritional ketosis is a powerful intervention, as Slocum's team has shown. But if you do it continuously, it can actually be highly counterproductive. You need to have days where you eat more net carbs and more protein, especially with strength training, to prevent sarcopenia that is common in cancer.
This is because when cancer cells are deprived of glucose they have the ability to break down muscle tissue to extract glutamine. Interestingly, Seyfried is working with a glutamine inhibitor called DON to prevent this from happening, thereby making the therapy even more effective.
It is important to understand that the "metabolic magic" actually occurs during that refeeding phase when net carbs and protein are increased, which increases muscle growth. After a day or two, you then cycle back into nutritional ketosis. Typically, this is done once a week. To a degree, Slocum uses this technique on cancer patients as well, although they're only allowed to eat higher amounts of net carbs once every two or three weeks, on the day they receive chemo.
"As an example, patients come and they're on a ketogenic diet. When they come in for chemotherapy after a 14-hour fast, then [we] apply glycolysis inhibitors to increase metabolic stress even more and insulin to lower the glucose and then apply chemotherapy.
After applying chemotherapy, on the day of chemotherapy, they are able to eat whatever they want, especially because of the mild hypoglycemia caused by supplying insulin. The day of chemotherapy is when they get as much carbohydrates as they want … We also do intermittent fasting [for a minimum of 14 hours] every other week or so. It seems to be effective."
More Information
The ChemoThermia Oncology Center treats many international patients, including people from the U.S. and Canada. The center also has published protocols your oncologist could make use of, regardless of where you live.
"We hope there will be physicians open to applying similar regimens to ours," Slocum says. "But a lot of patients who aren't able to come to our clinic, they can [still] do it. They first have to go on a ketogenic diet, which is very effective. Together with that, they should go to their chemotherapy in a fasting state, as long as they can stand it — a minimum of 12 hours. We generally recommend a 14-hour fast. The longer … the better."
Ideally, a reduced amount of the chemotherapeutic agents would then be used. While the amount varies according to your diagnosis and condition, the center has included dose range recommendations in their publications. Typically, the lowest recommended dose is given, which will significantly reduce or avoid most of the complications associated with chemotherapy.
"I hope people out there can see how effective metabolic therapies can be and how they can enhance conventional treatment protocols also. I encourage clinicians out there to ask similar questions to us, to read the literature and start applying similar therapies to ours," Slocum says.
Christofferson adds:
"What I would like to say is [that] patients who are confused by the ketogenic diet often don't know the difference between protein and carbohydrate. That's where they often get tripped up, because they're not sure what a carbohydrate is. Companies are stepping into this fray, making prepackaged The ones I've seen are really well done by gourmet chefs and [use] real ingredients. That's another option. There's enough on patients' plates to begin with … That's going to take a lot of the guesswork out for patients, I think."
To learn more about nutritional ketosis and the metabolic theory of cancer, I highly recommend listening to the interview I did with Christofferson last year, and to read his book, "Tripping Over the Truth," which provides the background as to why and how this therapy works, and why the conventional approach to cancer is fatally flawed.
If you're beyond that point and really want to implement this kind of metabolic therapy, I highly recommend preordering a copy of new book, "Fat for Fuel," which gives you all the details on how to do that. Anyone that preorders it will have access to my recent 2017 lecture that I have given at several events. Normally these lectures are never posted online. Incidentally, Christofferson was one of the experts who helped edit my book and actually wrote a section on Dr. Rosedale's work. I'm grateful for all his assistance.
Besides the information in the book, you'll also find many collaborative supports, including a nine-hour-long free video series that we hope to launch in early May. Miriam Kalamian is also developing a certification course to go along with it through the American College of Nutrition, to have more qualified therapists out there.ketogenic meals for cancer patients that take out the guesswork.
This certification will teach any qualified clinician — primarily certified clinical nutritionists but also physicians — how to practically implement nutritional ketosis. Eventually, I expect there will be a virtual army of clinicians available to assist patients with this kind of protocol. Hopefully, at that point we'll finally start making a dent in cancer statistics.
2017年6月20日星期二
Mevalonate Pathway - Statins
Acetyl and Mevalonate Pathway
1.) Cholesterol Inhibition
Not only is glial cell cholesterol synthesis in our brains vital for memory function and cognition, cholesterol also is the substrate for our most important hormones: aldosterone, cortisone, estrogen, progesterone and testosterone as well as the quasi-hormone, vitamin D (calcitriol). Cholesterol's vital role in membrane structure and function and lipid raft formation, makes it of critical importance in cell identification, cell communication and immunodefense.
Glial Cell Inhibition Potential Side Effects:
Amnesia
Forgetfulness
Confusion
Disorientation
Increased Senility
Hormone Lack Potential Side Effects:
Loss of Libido (sexual desire)
Erectile Dysfunction ( ED)
Osteoporosis
Hair Loss
2.) CoQ10 ( Ubiquinone ) Inhibition
Coenzyme Q10 (CoQ10) is important for structural integrity of cells, antioxidation and, as part of the mitochondria, the production of Adenosine Triphosphate (ATP) energy. Part of its extreme importance in anti-oxidation is because of its location within the mitochondria, protecting the delicate components of the itochondria from excess oxidative change and mutation.
Lack of Energy Potential Side Effects:
Chronic Fatigue Syndrome
Congestive Heart Failure
Fluid Retention
Shortness of Breath
Loss of Cell Wall Integrity Potential Side Effects:
Hepatitis
Pancreatitis
Myopathy (muscle pain and weakness, cramps)
Peripheral Neuropathy (numbness, tingling or burning sensations particularly in hands and feet)
Rhabdomyolysis (rapid breakdown of skeletal muscle tissue)
Excessive Oxidation Potential Side Effects:
Mitochondrial Damage
Permanent Neuropathy
Permanent Myopathy
Neurodegeneration
3.) Dolichol Inhibition
Dolichols are vital to the process of glycoprotein formation in the endoplasmic reticula of cells. In this capacity it is critical to the formation of the glycoproteins involved in neuropeptides, cell identification, cell messaging and immunodefense. Reduced bioavailability of dolichols can affect every cellular process in the body.
Neuropeptide Dysfunction Potential Side Effects:
Aggressiveness
Hostility
Irritability
Road Rage
Homicidal Behavior
Depression
Suicide
Altered Glycoprotein Synthesis Potential Side Effects:
Impairment of DNA error correction
Dysfunction of almost any cellular process
Altered cell identification
Altered cell messaging
Altered immunodefense
4.) Tau Protein Synthesis
When normal phosphorylation is interfered with by mevalonate blockade, our
cells increase the production of Tau protein. Tau is the protein substance of the neurofibrilatory tangles common to Alzheimers and other neurodegenerative diseases.
Neuro-Degenerative Diseases Include:
Parkinson's Disease
Alzheimer's Disease
Amyotrophic Lateral Sclerosis (ALS)
Primary Lateral Sclerosis (PLS)
Multiple Sclerosis (MS)
Multiple System Atrophy (MSA)
Frontal Lobe Dementia
5.) Selenoprotein
Only recently discovered were selenoproteins and the effect of statin blockade of the mevalonate pathway on their role in human physiology. Deficiency of selenoproteins has been proven to result in various types of myopathies formerly seen only in areas known to be deficient in this trace element. Additionally cognitive dysfunction is known to be associated with selenium lack.
6.) Nuclear Factor - kappa B (NF-kB)
The benefit of statin drugs in cardiovascular disease control is in their ability to inhibit this vital transcriptase. The entire anti-inflammatory and immunomodulatory effect of statins is mediated by statin inhibition of nuclear factor-kappa B. Improvement in atherosclerosis results from the inhibition of the key inflammatory elements: smooth muscle migration. lymphocyte adhesion, macrophage attraction and platelet activation associated with inhibition of NFkB.
The immunodefense system is also keyed to NF-kB, explaining the changing patterns of certain infections and cancers. The rise in cancers of all kinds secondary to statin use is of major concern.
2017年5月27日星期六
First Duchenne MD Patient to Be Approved for Adult Stem Cell Treatments in US Turns 30
Ryan Benton, the first patient to be approved in the United States for allogenic adult stem cell transplantation as a Duchenne muscular dystrophy (DMD) treatment, turned 30 this year — largely exceeding his original life expectancy.
DMD is a genetic disease that affects 1 out of every 3,600 male infants, leading to progressive muscle degradation. The average life expectancy for people with this disease is about 25 years. Benton, of Wichita, Kansas, was diagnosed with DMD at age 3, and doctors predicted he would live only into his late teens to early 20s.
At age 22, his health began to seriously deteriorate. At the time, research indicated that adult stem cell therapy might reverse DMD progression, so Benton met with Neil H. Riordan, PhD, the founder of the Stem Cell Institute in Panama City, Panama, and Medistem Panama.
Although he knew that there was no guarantee, Benton decided in 2009 to receive the stem cell treatment provided by Dr. Riordan’s team of physicians at the Stem Cell Institute. However, due to the laws that restricted adult stem cell therapy in the U.S., he had to travel to Panama. Shortly after the first treatment, he started feeling stronger and experienced no adverse side effects. He ended up making a total of seven trips to Panama for treatments, and after five years was granted approval by the Food and Drug Administration (FDA) for stem cell therapy inside the United States.
But the FDA’s approval was limited to his treatment exclusively, and only allowed for twice yearly treatment for a maximum of three years. Although the treatments improved lung capacity and muscle mass, increasing the ability to breathe and physical strength, the cells started to lose their effectiveness three to four months after each treatment.
In January 2016, the FDA granted approval for Benton to undergo an additional treatment per year, allowing for a more effective reversion of the disease’s progression. Additionally, the regulatory agency approved the therapy for another patient, a 6-year-old boy also showing benefits from previous treatments in Panama. The boy has already received his first treatment in the U.S., potentially paving the way for future patients.
DMD is a genetic disease that affects 1 out of every 3,600 male infants, leading to progressive muscle degradation. The average life expectancy for people with this disease is about 25 years. Benton, of Wichita, Kansas, was diagnosed with DMD at age 3, and doctors predicted he would live only into his late teens to early 20s.
At age 22, his health began to seriously deteriorate. At the time, research indicated that adult stem cell therapy might reverse DMD progression, so Benton met with Neil H. Riordan, PhD, the founder of the Stem Cell Institute in Panama City, Panama, and Medistem Panama.
Although he knew that there was no guarantee, Benton decided in 2009 to receive the stem cell treatment provided by Dr. Riordan’s team of physicians at the Stem Cell Institute. However, due to the laws that restricted adult stem cell therapy in the U.S., he had to travel to Panama. Shortly after the first treatment, he started feeling stronger and experienced no adverse side effects. He ended up making a total of seven trips to Panama for treatments, and after five years was granted approval by the Food and Drug Administration (FDA) for stem cell therapy inside the United States.
But the FDA’s approval was limited to his treatment exclusively, and only allowed for twice yearly treatment for a maximum of three years. Although the treatments improved lung capacity and muscle mass, increasing the ability to breathe and physical strength, the cells started to lose their effectiveness three to four months after each treatment.
In January 2016, the FDA granted approval for Benton to undergo an additional treatment per year, allowing for a more effective reversion of the disease’s progression. Additionally, the regulatory agency approved the therapy for another patient, a 6-year-old boy also showing benefits from previous treatments in Panama. The boy has already received his first treatment in the U.S., potentially paving the way for future patients.
2017年3月29日星期三
Severe Eczema Drug Is Approved by F.D.A.; Price Tag Is $37,000 a Year
The Food and Drug Administration on Tuesday approved a drug to treat people with a serious form of eczema, a potential breakthrough for people who have suffered for years without relief. But it will not come cheap.
The drug, to be called Dupixent, will carry a list price of $37,000 a year, a hefty price tag for patients who are increasingly being asked to pay a larger share of the drugs they take. Still, its price is a bit lower than many other commonly used biologic drugs, such as Humira and Enbrel, that treat other skin diseases.
In an effort to head off another public battle over the soaring cost of some prescriptions, the drug makers Regeneron Pharmaceuticals and Sanofi took the unusual step of directly negotiating with insurers over the price and other details ahead of time. What consumers pay for drugs has come under heightened scrutiny in the last few years, most recently by President Trump, who has promised several times to take drug companies to task over their costly products.
“Things have really deteriorated in our industry,” said Dr. Leonard S. Schleifer, the chief executive of Regeneron. “There’s so much concern over drug pricing that there’s an enormous amount of finger-pointing that is going on that’s counterproductive. It isn’t necessarily incentivizing the right behavior.”
The best-selling products Humira and Enbrel, which treat the skin disease psoriasis and other conditions, carry annual list prices of about $50,000.
Although many patients with insurance will not be asked to pay the full $37,000, consumers have been more exposed to rising prices in recent years because insurers often require them to pay a percentage of a drug’s list price — sometimes up to half — or pay the full price until their deductible is met.
They also often must demonstrate that other, cheaper drugs did not work before an insurer will cover more expensive drugs. Regeneron has said it also negotiated a more streamlined approval process, although patients will still have to try other drugs first. It also said it had a patient assistance program to help people who have troubling paying.
Regeneron and Sanofi held much of the bargaining power in negotiating Dupixent’s price because it has been shown to work well and has no real competition, said Dr. Steve Miller, the chief medical officer at Express Scripts, the nation’s largest pharmacy benefit manager, which often negotiates with drug makers on behalf of clients like insurers and large employers.
With breakthrough treatments, “companies can really go to the high end of that demand for reimbursement,” Dr. Miller said, “and all we have is the bully pulpit to complain about it.”
In trying to reach an agreement before approval, Dr. Miller said, “this is how the system is supposed to work.”
Christine Cramer, a spokeswoman for CVS Health, another leading pharmacy benefit manager, said, “While we believe our advocacy on behalf of our clients did ultimately influence Regeneron’s initial pricing strategy, the drug will be expensive.”
But Peter Maybarduk, director of the Access to Medicines program at Public Citizen, a consumer group, noted that negotiations still took place out of the public eye and within the context of a system that is inherently unfair. “It’s the arrangement that corporations found beneficial in a system that provides monopolies and rewards secrecy, and we should ask for considerably more as the standard,” he said.
Dupixent treats severe to moderate atopic dermatitis, a common form of eczema that goes beyond the occasional bouts of itchy, dry skin that many people get. For people with serious forms of the disease, other treatments often do little to calm their skin, leading to sleeplessness, depression and social anxiety. Regeneron said Tuesday that an estimated 300,000 people in the United States could qualify for its drug.
“I always say that atopic dermatitis doesn’t kill you, it just ruins your life,” said Dr. Elaine Siegfried, a professor of pediatrics and dermatology at the St. Louis University School of Medicine. She was not involved in the clinical trials that led to approval, but she said she was likely to enroll patients in pediatric studies that are getting underway. Dupixent, she said, appears to work well, with few serious side effects. “It is groundbreaking,” she said.
Debbie Byrnes, a sixth-grade teacher from San Antonio who participated in the clinical trial, had suffered for years with severe eczema that often covered her face. “That was the really difficult thing for me — I could never hide it,” she said. “I would have days when I went into school, and the kids would look at me and say, ‘What happened to you?’ ”
Ms. Byrnes said she began noticing a difference about five days after her first dose and has now been using the drug for two years. Her skin is now almost completely clear, and occasional flare-ups are quickly brought under control. “If you saw me,” she said, “you wouldn’t know that I ever had atopic dermatitis.”
Before a drug is approved, pharmaceutical companies usually keep the price a secret and do not directly negotiate with insurers until the product is approved by the F.D.A., in part because of concerns that doing so could violate agency rules. But in January, the agency said that drug companies were allowed to discuss price and other issues with insurers in advance.
Even if Dupixent’s $37,000 list price is below those of established drugs like Humira, Regeneron and Sanofi will very likely get to keep more than AbbVie, which makes Humira. That is because the net price of Dupixent, Dr. Schleifer said, will still be over $30,000. Although the rebates that drug makers negotiate with insurers are not public, Richard T. Evans, an analyst for SSR Health, a stock analysis company, has estimated that AbbVie would get to keep less than that, or about $27,500 a year for each patient who uses Humira.
He said a similar drug, nemolizumab, is also being tested for people with moderate to severe eczema and could hit the market in a few years. “Right now they have the benefit of being alone,” Mr. Evans said. “But going forward, I think there will be a lot of price competition.”
In reaching tentative agreements ahead of time, Regeneron and Sanofi appear to have been trying to avoid the pushback they encountered in 2015, when their expensive drug to treat high cholesterol, Praluent, was approved. Although Praluent and a similar drug, known as PCSK9 inhibitors, have been found to be beneficial to patients who don’t respond to other treatments, insurers have limited access and sales have not lived up to expectations.
“We all got that wrong,” Dr. Schleifer said. “But if we can make all of it work so that everybody’s feeling good, then we’ve really changed the paradigm.”
The drug, to be called Dupixent, will carry a list price of $37,000 a year, a hefty price tag for patients who are increasingly being asked to pay a larger share of the drugs they take. Still, its price is a bit lower than many other commonly used biologic drugs, such as Humira and Enbrel, that treat other skin diseases.
In an effort to head off another public battle over the soaring cost of some prescriptions, the drug makers Regeneron Pharmaceuticals and Sanofi took the unusual step of directly negotiating with insurers over the price and other details ahead of time. What consumers pay for drugs has come under heightened scrutiny in the last few years, most recently by President Trump, who has promised several times to take drug companies to task over their costly products.
“Things have really deteriorated in our industry,” said Dr. Leonard S. Schleifer, the chief executive of Regeneron. “There’s so much concern over drug pricing that there’s an enormous amount of finger-pointing that is going on that’s counterproductive. It isn’t necessarily incentivizing the right behavior.”
The best-selling products Humira and Enbrel, which treat the skin disease psoriasis and other conditions, carry annual list prices of about $50,000.
Although many patients with insurance will not be asked to pay the full $37,000, consumers have been more exposed to rising prices in recent years because insurers often require them to pay a percentage of a drug’s list price — sometimes up to half — or pay the full price until their deductible is met.
They also often must demonstrate that other, cheaper drugs did not work before an insurer will cover more expensive drugs. Regeneron has said it also negotiated a more streamlined approval process, although patients will still have to try other drugs first. It also said it had a patient assistance program to help people who have troubling paying.
Regeneron and Sanofi held much of the bargaining power in negotiating Dupixent’s price because it has been shown to work well and has no real competition, said Dr. Steve Miller, the chief medical officer at Express Scripts, the nation’s largest pharmacy benefit manager, which often negotiates with drug makers on behalf of clients like insurers and large employers.
With breakthrough treatments, “companies can really go to the high end of that demand for reimbursement,” Dr. Miller said, “and all we have is the bully pulpit to complain about it.”
In trying to reach an agreement before approval, Dr. Miller said, “this is how the system is supposed to work.”
Christine Cramer, a spokeswoman for CVS Health, another leading pharmacy benefit manager, said, “While we believe our advocacy on behalf of our clients did ultimately influence Regeneron’s initial pricing strategy, the drug will be expensive.”
But Peter Maybarduk, director of the Access to Medicines program at Public Citizen, a consumer group, noted that negotiations still took place out of the public eye and within the context of a system that is inherently unfair. “It’s the arrangement that corporations found beneficial in a system that provides monopolies and rewards secrecy, and we should ask for considerably more as the standard,” he said.
Dupixent treats severe to moderate atopic dermatitis, a common form of eczema that goes beyond the occasional bouts of itchy, dry skin that many people get. For people with serious forms of the disease, other treatments often do little to calm their skin, leading to sleeplessness, depression and social anxiety. Regeneron said Tuesday that an estimated 300,000 people in the United States could qualify for its drug.
“I always say that atopic dermatitis doesn’t kill you, it just ruins your life,” said Dr. Elaine Siegfried, a professor of pediatrics and dermatology at the St. Louis University School of Medicine. She was not involved in the clinical trials that led to approval, but she said she was likely to enroll patients in pediatric studies that are getting underway. Dupixent, she said, appears to work well, with few serious side effects. “It is groundbreaking,” she said.
Debbie Byrnes, a sixth-grade teacher from San Antonio who participated in the clinical trial, had suffered for years with severe eczema that often covered her face. “That was the really difficult thing for me — I could never hide it,” she said. “I would have days when I went into school, and the kids would look at me and say, ‘What happened to you?’ ”
Ms. Byrnes said she began noticing a difference about five days after her first dose and has now been using the drug for two years. Her skin is now almost completely clear, and occasional flare-ups are quickly brought under control. “If you saw me,” she said, “you wouldn’t know that I ever had atopic dermatitis.”
Before a drug is approved, pharmaceutical companies usually keep the price a secret and do not directly negotiate with insurers until the product is approved by the F.D.A., in part because of concerns that doing so could violate agency rules. But in January, the agency said that drug companies were allowed to discuss price and other issues with insurers in advance.
Even if Dupixent’s $37,000 list price is below those of established drugs like Humira, Regeneron and Sanofi will very likely get to keep more than AbbVie, which makes Humira. That is because the net price of Dupixent, Dr. Schleifer said, will still be over $30,000. Although the rebates that drug makers negotiate with insurers are not public, Richard T. Evans, an analyst for SSR Health, a stock analysis company, has estimated that AbbVie would get to keep less than that, or about $27,500 a year for each patient who uses Humira.
He said a similar drug, nemolizumab, is also being tested for people with moderate to severe eczema and could hit the market in a few years. “Right now they have the benefit of being alone,” Mr. Evans said. “But going forward, I think there will be a lot of price competition.”
In reaching tentative agreements ahead of time, Regeneron and Sanofi appear to have been trying to avoid the pushback they encountered in 2015, when their expensive drug to treat high cholesterol, Praluent, was approved. Although Praluent and a similar drug, known as PCSK9 inhibitors, have been found to be beneficial to patients who don’t respond to other treatments, insurers have limited access and sales have not lived up to expectations.
“We all got that wrong,” Dr. Schleifer said. “But if we can make all of it work so that everybody’s feeling good, then we’ve really changed the paradigm.”
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