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.”
2016年11月4日星期五
The facts about flaxseed and hypertension
A Winnipeg scientist and his team have shown that the humble flax seed has the power to dramatically reduce high blood pressure - a development that could help cut the incidence of cardiovascular disease by as much as 50 per cent.
BY JOEL SCHLESINGER
Winnipeg Health Region
Wave, January / February 2013
Dr. Grant Pierce is not a fish person.
"I just don't like the taste," he says simply.
The Winnipeg scientist's dislike of fish may seem like a trivial detail, especially when raised in the context of his research into the health benefits of certain types of foods.
But it is, nonetheless, one of the reasons why Pierce decided to embark on a major research project more than 10 years ago that now promises to change much about how we treat high blood pressure and cardiovascular disease in Canada and around the world.
At the time, Pierce, Executive Director of Research at St. Boniface Hospital, was helping to launch the newly minted Canadian Centre for Agri-Food Research in Health and Medicine (CCARM). The research facility, a partnership between St. Boniface Hospital, the University of Manitoba and Agriculture and Agri-Food Canada, is dedicated to exploring the health benefits of foods, particularly those grown on the Prairies.
As Pierce, a physiology professor in the Faculty of Medicine at the University of Manitoba, reviewed his options, he started to focus on flax seed, and with good reason.
New research at the time suggested that significant health benefits could be derived from omega 3 fatty acids found in fish. Studies indicated that, among other things, omega 3 fats could boost brain development and promote heart health.
Flax also contains omega 3 fatty acid, but it differs from the kind found in fish. Omega 3 fatty acids eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) are found in fish, while a third omega 3 called alpha-linolenic acid (ALA) is found in flax.
At the time, it was thought that the omega 3 fatty acids found in fish were more beneficial than the kind found in flax. As a result, the health spotlight shone on omega 3-laden fish, while the humble flax seed remained in the shadows - a healthy food to be sure, but not necessarily as beneficial as some others.
Pierce decided to test that theory.
"When it came to looking at flax seed, I was persuaded by the effect of fish and the omega 3 fatty acids they contain and their effect on cardiovascular health," says Pierce.
"You hear all the time that the omega 3s found in fish are very good for brain development and a variety of things," he says. "Well, if you follow this thinking logically, that means vegetarians haven't had good brain development as they grew up. I don't go for that. They must have had their omega 3 fatty acids from another source, and I bet you they fared just as well."
Pierce figured he probably wasn't the only one who didn't care for fish, and concluded that there might be some interest in researching alternative food sources to fish-based omega 3s. And since flax is grown in abundance in Manitoba, the plant seemed like the perfect choice for the first long-term study at CCARM.
"If the fatty acid in flax is structurally different than fish, then potentially it's biologically different," says Pierce. "In other words, it may have a different biological effect. It may be worse. It may be better. And we wanted to examine that."
Now, more than 10 years later, following a series of studies and clinical tests involving 110 people, Pierce believes flax is ready to step out from the shadows and claim its rightful place as one of nature's true super foods. That's because he and his team have recently completed a clinical trial demonstrating that flax, depending on how it is consumed, has the potential to significantly reduce blood pressure, thereby possibly decreasing the incidence of stroke by as much as 50 per cent and heart attack by about 30 per cent. The findings mean, in effect, that the tiny brown seeds derived from the pale blue flowering plant grown across Manitoba could be as powerful as any blood pressure medication on the market today.
The health implications flowing from the research are huge. Hypertension (high blood pressure) is a leading cause of cardiovascular illness, including stroke and heart disease. In Canada, cardiovascular disease is one of the leading causes of death, accounting for an estimated 29 per cent of all deaths, or about 70,000 people each year, according to the Heart and Stroke Foundation of Canada. In Manitoba, a report produced by Manitoba Health says about 235,683 people in this province had hypertension in 2010/11. That represents about 27.2 per cent of the population 20 years of age or older, compared to 21.7 per cent in 2000/01. The report also says about 1,514 people in Manitoba suffered a stroke in 2009/10, while 2,420 had a heart attack.
In addition to shedding light on possible new approaches to treating and preventing disease, the research also underscores the importance of the work being done at CCARM, located at the St. Boniface Hospital Research Centre.
Pierce helped launch CCARM in 1999 with a view to filling a gap in the medical research world. As he explains, drug companies spend billions of dollars annually on the research and development of new drugs, but comparatively little is spent on researching the health benefits of particular foods or how they might be used. The reason is that drug companies can't patent the information that might come from researching the health benefits of a particular food, consequently there is no incentive to spend money researching its value. Even the health food and supplement industry - a multi-billion dollar business - spends relatively little to actually research the claims often made for their products.
That's where CCARM comes into play. Researchers at the centre are dedicated to researching nutraceuticals or functional foods that may have some health-related benefits. A functional food is something like muffins that contain a dose of bran. A nutraceutical is an extract like ginseng or Echinacea extract.
Pierce says the goal is simple: "Either we prove that these foods or nutrients are of benefit to our health, or we prove that they aren't. If the marketing claims hailing their benefits turn out to be unsupported by good scientific data, people can stop wasting their money on products that they thought were good for them."
From the outset, the vision at the centre has been ambitious, focusing on long-term, complex studies that can be costly. As a result, it is important to look for locally-grown foods that are potentially healthy and marketable - two factors that can help attract potential investors.
The research into flax is a good example of how that relationship works. The study's primary goal was to determine whether flax had significant health benefits, and involved dozens of willing participants and a host of medical researchers and clinicians at the University of Manitoba and St. Boniface Hospital. But it also drew on the expertise and support of the Canadian International Grain Institute, the Food Development Centre in Portage la Prairie, Canada Bread and the federal and provincial governments, who were interested in the economic implications of discovering the health benefits of a locally-grown crop.
From the outset, Pierce knew that his research would likely confirm that flax did indeed have a number of health benefits. One area he wanted to investigate was whether it would help reduce cholesterol.
High cholesterol contributes to the buildup of plaque in the arteries, which restricts the flow of blood and can cause heart attacks.
"Omega 3 fatty acids are anti-inflammatory and we now know that inflammation is an important component of heart disease, creating blockages in your arteries and altering how your arteries work," he says.
The first step in the multi-year research project involved basic lab work - looking at cells in a petri dish under a microscope. Once the basic tests were completed, the team began animal testing. Lab animals were fed a high-cholesterol diet. While the control group animals received regular food, others had milled flax seed added to their diet. The animal studies yielded impressive results, showing flax had the potential to significantly reduce the cholesterol-filled blockages in arteries. Further animal studies also demonstrated that flax prevents cholesterol buildup from a diet high in trans-fats.
The research team found other benefits. When researchers induced conditions in flax-fed animals that resembled heart disease, their hearts were found to have added resistance to developing an irregular heartbeat.
"One of the major complications in a heart attack is that the heart will go into something called an arrhythmia, or an irregular heartbeat, and ultimately, if it's severe enough, that's what kills many patients," says Pierce. "Flax prevented some of the most dangerous arrhythmias."
In addition, researchers also discovered that flax made the animals' smooth muscle lining in their arteries relax more than the control group. This relaxing effect on arteries could potentially reduce the incidence of adverse cardiovascular events - such as heart attacks or strokes, which occur when blood flow is substantially reduced to parts of the brain. The findings were significant enough to prompt more research involving clinical trials in humans with heart disease.
"Because of those three effects we found in the animals, we got pretty excited," Pierce says. "The animal work was so positive, we knew it was time to move on to human studies to see if it's beneficial to us."
Those studies started four years ago. Even though the first phase of the clinical study involved only a year of monitoring patients, Pierce says a lot of groundwork had to be done first. His team needed to carefully design an experiment that would show as conclusively as possible that flax does or does not benefit human health.
Pierce hypothesized that previous studies that had shown minimal cardiovascular health benefits from flax had more to do with the design of the studies than with the plant itself. So he and his team carefully built their study from the ground up, with financial support from the Canola Council of Canada, Flax 2015, the Flax Council of Canada, the Agri-Food Research Development Initiative, St. Boniface Hospital Foundation and a variety of other companies and organizations.
Before working with patients suffering from heart disease - a group that could dramatically show the most potential benefit - the team ran a number of mini-trials on healthy individuals to answer a number of questions, which arose earlier in the research.
"That's why the animal work is done, and prior to going into the clinical trials, you work on healthy people first. There were some basic questions that needed to be answered prior to setting up a major trial in a diseased population," says Pierce.
One of the most important of these questions was how much flax would a patient need to ingest in order to achieve optimal results? But before they could find an answer to this problem, they had to figure out the best way for the patients to ingest flax. Was it better to eat flax as whole seed, as a milled product or as an oil?
During this part of the research, they discovered that patients eating whole seeds showed no increase in omega 3 fatty acids in their blood. But significant levels of omega 3 did show up in the blood tests of participants ingesting flax oil or the milled product.
With that problem solved, Pierce and his team moved onto a trial to determine how much flax seed someone would have to consume in order to derive a benefit.
Eventually, they determined that 30 grams of milled flax provided a dose of ALA that would likely provide heart-healthy benefits. But uncertainty persisted because flax seed omega 3 oils (ALA) have a different molecular structure than the (DHA and EPA) omega 3s found in fish.
In a nutshell, the ALA found in flax has a shorter molecular structure. This type of beneficial fat is also found in walnuts, hemp seed, kiwis, canola and soybean, but flax contains the highest concentrations.
"The only difference amongst different omega-3 fatty acids we found was the way they're absorbed," explains Pierce. "If I gave you a pill that contains fish oil and a pill that contains flax oil, the EPA and DHA seemed to be absorbed a little bit better, so you have to take a little bit more of the flax oil to get the ALA levels in your bloodstream to a level equivalent to the fish oils."
Yet, arguably, the most important research work, contingent to the success of the larger clinical research puzzle, was developing food products that would contain enough flax to be beneficial while still being palatable.
And that is not an easy thing to do, according to Dr. Michel Aliani, Director of the Weston Sensory and Food Research Centre in the Department of Human Nutritional Sciences at the University of Manitoba, and a member of the CCARM research team.
Flax on its own is not exactly tasty. The seed is bitter and quite granular, potentially making any product containing it bland, dry and largely unappealing. "We knew more or less that the food would be healthy, but the challenge is whether people can eat it on a daily basis," says Aliani.
That's where Canada Bread and the Food Development Centre in Portage la Prairie stepped in. They developed food products using flax donated by Pizzey's Milling and Glanbia Nutritionals. From buns, bagels, biscuits and muffins to pasta and snack bars, they developed a variety of baked goods and other products that would appeal to clinical trial participants' tastes.
"Developing foods that contain the required amount of flax has been a major challenge in and of itself, let alone making them tasty," he says. "We had to have 30 grams of flax seed in one muffin or bagel, and that's huge (equal to three heaping tablespoons of flax) because it amounts to about one-fifth to one-sixth of the entire muffin or bagel," he says. "The study participants had to eat one of these per day and this was a very long study."
Researchers had to figure out how to include that much flax into a recipe without compromising the integrity of the food product. Would a muffin or bagel with that much flax even hold together?
"Even today," Aliani says, "recipes for future studies are constantly being honed, yet what they have discovered so far is that certain ingredients make flax more palatable. Raisins and cinnamon, for instance, combine to mask flax's bitterness."
With years of painstaking background work complete, it was time to move on to the heart of the research - clinical trials with patients who had cardiovascular disease. "We knew from the animal work that flax seems to reduce atherosclerosis, arrhythmia and help relax arteries," Pierce says. "So we wanted a population of patients with those types of problems."
They found a good match in the patients under the care of Dr. Randy Guzman, Director of the I.H. Asper Clinical Research Institute and Vascular Research at St. Boniface Hospital and an associate professor of surgery in the Faculty of Medicine at the University of Manitoba. His patients suffered from peripheral arterial disease, a condition that clogs arteries and blocks blood flow. "These are patients with arterial problems outside of the chest - or cardiac area - and instead, they often have problems in their lower extremities," says Guzman. "The same plaques that block up the arteries that feed blood to the heart can block up other arteries, like in the legs."
About 80 per cent of the patients were on medication for high cholesterol while 75 per cent took medication for high blood pressure. Because these patients are considered to be very ill, even though they're under medical care and making efforts to improve their health, Pierce says they were ideal candidates for the clinical phase of the study. "They have a high incidence of heart attacks and strokes. They have a lot of arrhythmias, and they have all the characteristics that made us think, 'Hey, this is exactly the group that flax seed may help'."
Although the study set out to measure cholesterol levels, with the hypothesis that flax would reduce blood cholesterol over the course of a year, Pierce says they discovered an unexpected and pleasant surprise. Patients' blood pressure fell.
"Approximately 75 per cent of the patients who came into our trial were hypertensive," Pierce says, adding their average blood pressure was 158 millimetres mercury (mmHg) systolic over a diastolic of about 81 mmHg. "These patients were already on anti-hypertensive drugs and still their blood pressure was poorly controlled, partly because they had so many things going on with them that the physician can't keep up in treating all of the problems."
After a month into the trial, their blood pressure decreased and continued to fall until the six-month mark when it stabilized. By the end of the study, the average study participant's blood pressure decreased 15 millimetres mercury (mmHg) systolic and seven mmHg diastolic.
At first, Pierce wasn't sure what to make of the results. "I'm not a blood pressure researcher, so, to be honest, when we got the results, I said, 'Hmm, okay, I guess these are good. Let's consult with some hypertension experts,'" he says. "Their response was, 'Your results are fantastic.' So we went into the blood pressure literature and that's when we realized, 'Wow! We have a major effect here'."
Guzman concurs with the results. "It's a significant finding and the magnitude is substantial," he says. "The exact mechanisms as to how high blood pressure can cause heart attacks or strokes is complicated," says Guzman. "But the bottom line is if you can reduce blood pressure in patients, you can also decrease their risk of having a stroke or heart attack."
Pierce attributes the reduction in blood pressure to three main ingredients in flax:
Omega 3 fatty acids: These are known to reduce inflammation, and a buildup of plaques in the artery walls is suspected to be a by-product of an immune system response to high-fat diets, stress and other factors that lead to arterial inflammation.
Fibre: Flax is high in soluble fibre, which absorbs bad fats from the body, reducing cholesterol levels and blood pressure.
Lignans: These are potent antioxidants, more potent than Vitamin E.
Pierce believes it was these three ingredients working together that created the synergistic effect that reduced the study participants' blood pressure during the trial.
"You have to remember, one millimetre difference is a huge impact on heart attacks and stroke," he says. That's a result even better than those found from consuming fish. "Fish can reduce blood pressure in hypertensive patients by about four millimetres mercury systolic, so it's nowhere near the level for flax." Furthermore, flax may be more beneficial than fish because it contains less cholesterol than fish.
In addition to a drop in blood pressure, the participants also experienced a cholesterol reduction of about 10 per cent, but Pierce says those findings are currently being written up for publication in a medical journal later this year.
But Pierce says it's the blood pressure findings that are the most compelling at this stage. No other food or supplement comes close. "There's no comparison. Flax seed is better than any other dietary intervention ever shown," he says. That includes the DASH diet (Dietary Approaches to Stop Hypertension), the Mediterranean-style diet prescribed to patients with high blood pressure. "And it's at least as good as many of the drugs that are on the market today," he says.
For Pierce, the findings are exciting.
"I would hazard to say this is the most significant finding our lab has produced, and I doubt that I will ever find anything better," he says. "If this has an influence on reducing heart attacks and stroke by as much as the research suggests, I don't think it gets much better than that."
Still, the research is only getting started. "Our paper on flax and hypertension is currently being revised for publication in the best heart journal in the world," he says "and we continue to learn more about how it works from animal trials."
Aliani says like any good science, Pierce's research has opened up many new avenues of investigation. "In scientific research, if you have a question, and answer it - case closed - that's not really good science," says Aliani, who is now working on a study investigating flax's benefits for Type 2 diabetes patients. "In good science, the answer to one question should open a lot of others, and that's the case here."
Indeed, questions abound for Pierce. A lot of research is still left to do.
"For example, these patients were on hypertensive medication so, really, I don't know whether flax reduces blood pressure in these patients on its own, or did it boost the effects of the drugs?" he says. "In our next trial, that's what we want to look at - take patients who are not on drugs yet and see if we can reduce the number of them who end up taking drugs, or eliminate the need for them to go on anti-hypertension drugs altogether."
"The good part is that past work shows flax does not reduce blood pressure in people who are not hypertensive. Our study confirms that." In other words, people with normal blood pressure won't lower their blood pressure where they may be at risk of passing out.
Eventually, Pierce would like to examine whether flax can help prevent high blood pressure. "Technically, as a scientist, I cannot say it (flax) will prevent the development of high blood pressure because you'd need another study to determine if that's the case," he says. "That's a super study, one we'd love to do - it won't be the next study we do - but honestly, that's where I believe the real gold is; that's where I believe the real beneficial effects are to be found. If it does prevent or delay disease, then it is a realistic approach for reducing health-care costs in Manitoba and Canada."
BY JOEL SCHLESINGER
Winnipeg Health Region
Wave, January / February 2013
Dr. Grant Pierce is not a fish person.
"I just don't like the taste," he says simply.
The Winnipeg scientist's dislike of fish may seem like a trivial detail, especially when raised in the context of his research into the health benefits of certain types of foods.
But it is, nonetheless, one of the reasons why Pierce decided to embark on a major research project more than 10 years ago that now promises to change much about how we treat high blood pressure and cardiovascular disease in Canada and around the world.
At the time, Pierce, Executive Director of Research at St. Boniface Hospital, was helping to launch the newly minted Canadian Centre for Agri-Food Research in Health and Medicine (CCARM). The research facility, a partnership between St. Boniface Hospital, the University of Manitoba and Agriculture and Agri-Food Canada, is dedicated to exploring the health benefits of foods, particularly those grown on the Prairies.
As Pierce, a physiology professor in the Faculty of Medicine at the University of Manitoba, reviewed his options, he started to focus on flax seed, and with good reason.
New research at the time suggested that significant health benefits could be derived from omega 3 fatty acids found in fish. Studies indicated that, among other things, omega 3 fats could boost brain development and promote heart health.
Flax also contains omega 3 fatty acid, but it differs from the kind found in fish. Omega 3 fatty acids eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) are found in fish, while a third omega 3 called alpha-linolenic acid (ALA) is found in flax.
At the time, it was thought that the omega 3 fatty acids found in fish were more beneficial than the kind found in flax. As a result, the health spotlight shone on omega 3-laden fish, while the humble flax seed remained in the shadows - a healthy food to be sure, but not necessarily as beneficial as some others.
Pierce decided to test that theory.
"When it came to looking at flax seed, I was persuaded by the effect of fish and the omega 3 fatty acids they contain and their effect on cardiovascular health," says Pierce.
"You hear all the time that the omega 3s found in fish are very good for brain development and a variety of things," he says. "Well, if you follow this thinking logically, that means vegetarians haven't had good brain development as they grew up. I don't go for that. They must have had their omega 3 fatty acids from another source, and I bet you they fared just as well."
Pierce figured he probably wasn't the only one who didn't care for fish, and concluded that there might be some interest in researching alternative food sources to fish-based omega 3s. And since flax is grown in abundance in Manitoba, the plant seemed like the perfect choice for the first long-term study at CCARM.
"If the fatty acid in flax is structurally different than fish, then potentially it's biologically different," says Pierce. "In other words, it may have a different biological effect. It may be worse. It may be better. And we wanted to examine that."
Now, more than 10 years later, following a series of studies and clinical tests involving 110 people, Pierce believes flax is ready to step out from the shadows and claim its rightful place as one of nature's true super foods. That's because he and his team have recently completed a clinical trial demonstrating that flax, depending on how it is consumed, has the potential to significantly reduce blood pressure, thereby possibly decreasing the incidence of stroke by as much as 50 per cent and heart attack by about 30 per cent. The findings mean, in effect, that the tiny brown seeds derived from the pale blue flowering plant grown across Manitoba could be as powerful as any blood pressure medication on the market today.
The health implications flowing from the research are huge. Hypertension (high blood pressure) is a leading cause of cardiovascular illness, including stroke and heart disease. In Canada, cardiovascular disease is one of the leading causes of death, accounting for an estimated 29 per cent of all deaths, or about 70,000 people each year, according to the Heart and Stroke Foundation of Canada. In Manitoba, a report produced by Manitoba Health says about 235,683 people in this province had hypertension in 2010/11. That represents about 27.2 per cent of the population 20 years of age or older, compared to 21.7 per cent in 2000/01. The report also says about 1,514 people in Manitoba suffered a stroke in 2009/10, while 2,420 had a heart attack.
In addition to shedding light on possible new approaches to treating and preventing disease, the research also underscores the importance of the work being done at CCARM, located at the St. Boniface Hospital Research Centre.
Pierce helped launch CCARM in 1999 with a view to filling a gap in the medical research world. As he explains, drug companies spend billions of dollars annually on the research and development of new drugs, but comparatively little is spent on researching the health benefits of particular foods or how they might be used. The reason is that drug companies can't patent the information that might come from researching the health benefits of a particular food, consequently there is no incentive to spend money researching its value. Even the health food and supplement industry - a multi-billion dollar business - spends relatively little to actually research the claims often made for their products.
That's where CCARM comes into play. Researchers at the centre are dedicated to researching nutraceuticals or functional foods that may have some health-related benefits. A functional food is something like muffins that contain a dose of bran. A nutraceutical is an extract like ginseng or Echinacea extract.
Pierce says the goal is simple: "Either we prove that these foods or nutrients are of benefit to our health, or we prove that they aren't. If the marketing claims hailing their benefits turn out to be unsupported by good scientific data, people can stop wasting their money on products that they thought were good for them."
From the outset, the vision at the centre has been ambitious, focusing on long-term, complex studies that can be costly. As a result, it is important to look for locally-grown foods that are potentially healthy and marketable - two factors that can help attract potential investors.
The research into flax is a good example of how that relationship works. The study's primary goal was to determine whether flax had significant health benefits, and involved dozens of willing participants and a host of medical researchers and clinicians at the University of Manitoba and St. Boniface Hospital. But it also drew on the expertise and support of the Canadian International Grain Institute, the Food Development Centre in Portage la Prairie, Canada Bread and the federal and provincial governments, who were interested in the economic implications of discovering the health benefits of a locally-grown crop.
From the outset, Pierce knew that his research would likely confirm that flax did indeed have a number of health benefits. One area he wanted to investigate was whether it would help reduce cholesterol.
High cholesterol contributes to the buildup of plaque in the arteries, which restricts the flow of blood and can cause heart attacks.
"Omega 3 fatty acids are anti-inflammatory and we now know that inflammation is an important component of heart disease, creating blockages in your arteries and altering how your arteries work," he says.
The first step in the multi-year research project involved basic lab work - looking at cells in a petri dish under a microscope. Once the basic tests were completed, the team began animal testing. Lab animals were fed a high-cholesterol diet. While the control group animals received regular food, others had milled flax seed added to their diet. The animal studies yielded impressive results, showing flax had the potential to significantly reduce the cholesterol-filled blockages in arteries. Further animal studies also demonstrated that flax prevents cholesterol buildup from a diet high in trans-fats.
The research team found other benefits. When researchers induced conditions in flax-fed animals that resembled heart disease, their hearts were found to have added resistance to developing an irregular heartbeat.
"One of the major complications in a heart attack is that the heart will go into something called an arrhythmia, or an irregular heartbeat, and ultimately, if it's severe enough, that's what kills many patients," says Pierce. "Flax prevented some of the most dangerous arrhythmias."
In addition, researchers also discovered that flax made the animals' smooth muscle lining in their arteries relax more than the control group. This relaxing effect on arteries could potentially reduce the incidence of adverse cardiovascular events - such as heart attacks or strokes, which occur when blood flow is substantially reduced to parts of the brain. The findings were significant enough to prompt more research involving clinical trials in humans with heart disease.
"Because of those three effects we found in the animals, we got pretty excited," Pierce says. "The animal work was so positive, we knew it was time to move on to human studies to see if it's beneficial to us."
Those studies started four years ago. Even though the first phase of the clinical study involved only a year of monitoring patients, Pierce says a lot of groundwork had to be done first. His team needed to carefully design an experiment that would show as conclusively as possible that flax does or does not benefit human health.
Pierce hypothesized that previous studies that had shown minimal cardiovascular health benefits from flax had more to do with the design of the studies than with the plant itself. So he and his team carefully built their study from the ground up, with financial support from the Canola Council of Canada, Flax 2015, the Flax Council of Canada, the Agri-Food Research Development Initiative, St. Boniface Hospital Foundation and a variety of other companies and organizations.
Before working with patients suffering from heart disease - a group that could dramatically show the most potential benefit - the team ran a number of mini-trials on healthy individuals to answer a number of questions, which arose earlier in the research.
"That's why the animal work is done, and prior to going into the clinical trials, you work on healthy people first. There were some basic questions that needed to be answered prior to setting up a major trial in a diseased population," says Pierce.
One of the most important of these questions was how much flax would a patient need to ingest in order to achieve optimal results? But before they could find an answer to this problem, they had to figure out the best way for the patients to ingest flax. Was it better to eat flax as whole seed, as a milled product or as an oil?
During this part of the research, they discovered that patients eating whole seeds showed no increase in omega 3 fatty acids in their blood. But significant levels of omega 3 did show up in the blood tests of participants ingesting flax oil or the milled product.
With that problem solved, Pierce and his team moved onto a trial to determine how much flax seed someone would have to consume in order to derive a benefit.
Eventually, they determined that 30 grams of milled flax provided a dose of ALA that would likely provide heart-healthy benefits. But uncertainty persisted because flax seed omega 3 oils (ALA) have a different molecular structure than the (DHA and EPA) omega 3s found in fish.
In a nutshell, the ALA found in flax has a shorter molecular structure. This type of beneficial fat is also found in walnuts, hemp seed, kiwis, canola and soybean, but flax contains the highest concentrations.
"The only difference amongst different omega-3 fatty acids we found was the way they're absorbed," explains Pierce. "If I gave you a pill that contains fish oil and a pill that contains flax oil, the EPA and DHA seemed to be absorbed a little bit better, so you have to take a little bit more of the flax oil to get the ALA levels in your bloodstream to a level equivalent to the fish oils."
Yet, arguably, the most important research work, contingent to the success of the larger clinical research puzzle, was developing food products that would contain enough flax to be beneficial while still being palatable.
And that is not an easy thing to do, according to Dr. Michel Aliani, Director of the Weston Sensory and Food Research Centre in the Department of Human Nutritional Sciences at the University of Manitoba, and a member of the CCARM research team.
Flax on its own is not exactly tasty. The seed is bitter and quite granular, potentially making any product containing it bland, dry and largely unappealing. "We knew more or less that the food would be healthy, but the challenge is whether people can eat it on a daily basis," says Aliani.
That's where Canada Bread and the Food Development Centre in Portage la Prairie stepped in. They developed food products using flax donated by Pizzey's Milling and Glanbia Nutritionals. From buns, bagels, biscuits and muffins to pasta and snack bars, they developed a variety of baked goods and other products that would appeal to clinical trial participants' tastes.
"Developing foods that contain the required amount of flax has been a major challenge in and of itself, let alone making them tasty," he says. "We had to have 30 grams of flax seed in one muffin or bagel, and that's huge (equal to three heaping tablespoons of flax) because it amounts to about one-fifth to one-sixth of the entire muffin or bagel," he says. "The study participants had to eat one of these per day and this was a very long study."
Researchers had to figure out how to include that much flax into a recipe without compromising the integrity of the food product. Would a muffin or bagel with that much flax even hold together?
"Even today," Aliani says, "recipes for future studies are constantly being honed, yet what they have discovered so far is that certain ingredients make flax more palatable. Raisins and cinnamon, for instance, combine to mask flax's bitterness."
With years of painstaking background work complete, it was time to move on to the heart of the research - clinical trials with patients who had cardiovascular disease. "We knew from the animal work that flax seems to reduce atherosclerosis, arrhythmia and help relax arteries," Pierce says. "So we wanted a population of patients with those types of problems."
They found a good match in the patients under the care of Dr. Randy Guzman, Director of the I.H. Asper Clinical Research Institute and Vascular Research at St. Boniface Hospital and an associate professor of surgery in the Faculty of Medicine at the University of Manitoba. His patients suffered from peripheral arterial disease, a condition that clogs arteries and blocks blood flow. "These are patients with arterial problems outside of the chest - or cardiac area - and instead, they often have problems in their lower extremities," says Guzman. "The same plaques that block up the arteries that feed blood to the heart can block up other arteries, like in the legs."
About 80 per cent of the patients were on medication for high cholesterol while 75 per cent took medication for high blood pressure. Because these patients are considered to be very ill, even though they're under medical care and making efforts to improve their health, Pierce says they were ideal candidates for the clinical phase of the study. "They have a high incidence of heart attacks and strokes. They have a lot of arrhythmias, and they have all the characteristics that made us think, 'Hey, this is exactly the group that flax seed may help'."
Although the study set out to measure cholesterol levels, with the hypothesis that flax would reduce blood cholesterol over the course of a year, Pierce says they discovered an unexpected and pleasant surprise. Patients' blood pressure fell.
"Approximately 75 per cent of the patients who came into our trial were hypertensive," Pierce says, adding their average blood pressure was 158 millimetres mercury (mmHg) systolic over a diastolic of about 81 mmHg. "These patients were already on anti-hypertensive drugs and still their blood pressure was poorly controlled, partly because they had so many things going on with them that the physician can't keep up in treating all of the problems."
After a month into the trial, their blood pressure decreased and continued to fall until the six-month mark when it stabilized. By the end of the study, the average study participant's blood pressure decreased 15 millimetres mercury (mmHg) systolic and seven mmHg diastolic.
At first, Pierce wasn't sure what to make of the results. "I'm not a blood pressure researcher, so, to be honest, when we got the results, I said, 'Hmm, okay, I guess these are good. Let's consult with some hypertension experts,'" he says. "Their response was, 'Your results are fantastic.' So we went into the blood pressure literature and that's when we realized, 'Wow! We have a major effect here'."
Guzman concurs with the results. "It's a significant finding and the magnitude is substantial," he says. "The exact mechanisms as to how high blood pressure can cause heart attacks or strokes is complicated," says Guzman. "But the bottom line is if you can reduce blood pressure in patients, you can also decrease their risk of having a stroke or heart attack."
Pierce attributes the reduction in blood pressure to three main ingredients in flax:
Omega 3 fatty acids: These are known to reduce inflammation, and a buildup of plaques in the artery walls is suspected to be a by-product of an immune system response to high-fat diets, stress and other factors that lead to arterial inflammation.
Fibre: Flax is high in soluble fibre, which absorbs bad fats from the body, reducing cholesterol levels and blood pressure.
Lignans: These are potent antioxidants, more potent than Vitamin E.
Pierce believes it was these three ingredients working together that created the synergistic effect that reduced the study participants' blood pressure during the trial.
"You have to remember, one millimetre difference is a huge impact on heart attacks and stroke," he says. That's a result even better than those found from consuming fish. "Fish can reduce blood pressure in hypertensive patients by about four millimetres mercury systolic, so it's nowhere near the level for flax." Furthermore, flax may be more beneficial than fish because it contains less cholesterol than fish.
In addition to a drop in blood pressure, the participants also experienced a cholesterol reduction of about 10 per cent, but Pierce says those findings are currently being written up for publication in a medical journal later this year.
But Pierce says it's the blood pressure findings that are the most compelling at this stage. No other food or supplement comes close. "There's no comparison. Flax seed is better than any other dietary intervention ever shown," he says. That includes the DASH diet (Dietary Approaches to Stop Hypertension), the Mediterranean-style diet prescribed to patients with high blood pressure. "And it's at least as good as many of the drugs that are on the market today," he says.
For Pierce, the findings are exciting.
"I would hazard to say this is the most significant finding our lab has produced, and I doubt that I will ever find anything better," he says. "If this has an influence on reducing heart attacks and stroke by as much as the research suggests, I don't think it gets much better than that."
Still, the research is only getting started. "Our paper on flax and hypertension is currently being revised for publication in the best heart journal in the world," he says "and we continue to learn more about how it works from animal trials."
Aliani says like any good science, Pierce's research has opened up many new avenues of investigation. "In scientific research, if you have a question, and answer it - case closed - that's not really good science," says Aliani, who is now working on a study investigating flax's benefits for Type 2 diabetes patients. "In good science, the answer to one question should open a lot of others, and that's the case here."
Indeed, questions abound for Pierce. A lot of research is still left to do.
"For example, these patients were on hypertensive medication so, really, I don't know whether flax reduces blood pressure in these patients on its own, or did it boost the effects of the drugs?" he says. "In our next trial, that's what we want to look at - take patients who are not on drugs yet and see if we can reduce the number of them who end up taking drugs, or eliminate the need for them to go on anti-hypertension drugs altogether."
"The good part is that past work shows flax does not reduce blood pressure in people who are not hypertensive. Our study confirms that." In other words, people with normal blood pressure won't lower their blood pressure where they may be at risk of passing out.
Eventually, Pierce would like to examine whether flax can help prevent high blood pressure. "Technically, as a scientist, I cannot say it (flax) will prevent the development of high blood pressure because you'd need another study to determine if that's the case," he says. "That's a super study, one we'd love to do - it won't be the next study we do - but honestly, that's where I believe the real gold is; that's where I believe the real beneficial effects are to be found. If it does prevent or delay disease, then it is a realistic approach for reducing health-care costs in Manitoba and Canada."
2016年9月24日星期六
中国重大突破 癌细胞用这种方法弄死了
他和研究团队一起发现了“饿死”癌细胞的新疗法，并发表在国际生物和医学领域权威杂志elife上，得到了国际著名肿瘤学者的肯定。
“癌细胞也需要‘吃’东西才能生存，剥夺它的食物，癌细胞就会死亡。”浙江大学肿瘤研究所教授胡汛说，就是循着这个看似简单的原理，他和研究团队一起发现了“饿死”癌细胞的新疗法，并发表在国际生物和医学领域权威杂志elife上，得到了国际著名肿瘤学者的肯定。
经过多年基础研究，胡汛发现葡萄糖是癌细胞必需“吃”的东西，照理看剥夺葡萄糖癌细胞就会死亡。但实际上葡萄糖供应不足时，肿瘤没有饿死还不断生长。
胡汛教授道出了其中奥秘：肿瘤中有大量的乳酸，乳酸解离成乳酸阴离子和氢离子，成为癌细胞的两位“帮手”，让其自身能够根据“食物”的多少决定“消耗”多少。
两位“帮手”协同作用，使得癌细胞在葡萄糖含量很少时，非常节约地利用葡萄糖；在没有葡萄糖的情况下进入“休眠”状态；当有葡萄糖供应时即刻恢复生长状态。
因此，若想有效“饿死”癌细胞，不仅要剥夺葡萄糖，还需同时破坏乳酸阴离子和氢离子的协同作用。在葡萄糖饥饿或缺乏的前提下，只要去除这两个因子中的任何一个，癌细胞就会快速死亡。
研究人员用碱如碳酸氢钠（小苏打）来去除肿瘤内的氢离子，就可破坏乳酸根和氢离子的协同作用，从而快速有效地杀死处于葡萄糖饥饿或缺乏的肿瘤细胞。
将基础科研成果快速转化成肿瘤临床治疗，让更多患者受益是关键。
2012年起，拥有30年临床经验的浙江大学医学院附属第二医院放射介入科医生晁明和胡汛团队一拍即合，投入到对原发性肝细胞肝癌新型疗法研究中，并将这种方法命名为“靶向肿瘤内乳酸阴离子和氢离子的动脉插管化疗栓塞术”，简称“TILA-TACE”。
临床上，晁明给出解释：“常规动脉插管化疗栓塞术（cTACE）切断了肿瘤的‘食物通道’，然后我们再用碳酸氢钠去除肿瘤内的氢离子，相当于不仅不给肿瘤‘吃饭’，还让它去健身房快速消耗，迅速‘饿死’。”
令人欣喜地是，他们进行的临床研究结果显示：用cTACE治疗了37例病人，18例有效；用TILA-TACE治疗了40例病人，40例有效。
而且在这个临床研究中用TILA-TACE治疗的肝癌都是难治型肝癌。
而国际上综合报道，cTACE治疗的平均客观有效率位35%。35%到100%，这样巨大的对比，不仅让国际同行在接受这篇文章时，非常慎重，就连两位教授也一直是带着怀疑在进行这项研究。
“目前初步统计，病人的中位生存期，已超过三年半；后续还需要大样本的随机对照研究，如果证实有效，对肝癌治疗来说，确实是一个飞跃。”两位专家表示。
“癌细胞也需要‘吃’东西才能生存，剥夺它的食物，癌细胞就会死亡。”浙江大学肿瘤研究所教授胡汛说，就是循着这个看似简单的原理，他和研究团队一起发现了“饿死”癌细胞的新疗法，并发表在国际生物和医学领域权威杂志elife上，得到了国际著名肿瘤学者的肯定。
经过多年基础研究，胡汛发现葡萄糖是癌细胞必需“吃”的东西，照理看剥夺葡萄糖癌细胞就会死亡。但实际上葡萄糖供应不足时，肿瘤没有饿死还不断生长。
胡汛教授道出了其中奥秘：肿瘤中有大量的乳酸，乳酸解离成乳酸阴离子和氢离子，成为癌细胞的两位“帮手”，让其自身能够根据“食物”的多少决定“消耗”多少。
两位“帮手”协同作用，使得癌细胞在葡萄糖含量很少时，非常节约地利用葡萄糖；在没有葡萄糖的情况下进入“休眠”状态；当有葡萄糖供应时即刻恢复生长状态。
因此，若想有效“饿死”癌细胞，不仅要剥夺葡萄糖，还需同时破坏乳酸阴离子和氢离子的协同作用。在葡萄糖饥饿或缺乏的前提下，只要去除这两个因子中的任何一个，癌细胞就会快速死亡。
研究人员用碱如碳酸氢钠（小苏打）来去除肿瘤内的氢离子，就可破坏乳酸根和氢离子的协同作用，从而快速有效地杀死处于葡萄糖饥饿或缺乏的肿瘤细胞。
将基础科研成果快速转化成肿瘤临床治疗，让更多患者受益是关键。
2012年起，拥有30年临床经验的浙江大学医学院附属第二医院放射介入科医生晁明和胡汛团队一拍即合，投入到对原发性肝细胞肝癌新型疗法研究中，并将这种方法命名为“靶向肿瘤内乳酸阴离子和氢离子的动脉插管化疗栓塞术”，简称“TILA-TACE”。
临床上，晁明给出解释：“常规动脉插管化疗栓塞术（cTACE）切断了肿瘤的‘食物通道’，然后我们再用碳酸氢钠去除肿瘤内的氢离子，相当于不仅不给肿瘤‘吃饭’，还让它去健身房快速消耗，迅速‘饿死’。”
令人欣喜地是，他们进行的临床研究结果显示：用cTACE治疗了37例病人，18例有效；用TILA-TACE治疗了40例病人，40例有效。
而且在这个临床研究中用TILA-TACE治疗的肝癌都是难治型肝癌。
而国际上综合报道，cTACE治疗的平均客观有效率位35%。35%到100%，这样巨大的对比，不仅让国际同行在接受这篇文章时，非常慎重，就连两位教授也一直是带着怀疑在进行这项研究。
“目前初步统计，病人的中位生存期，已超过三年半；后续还需要大样本的随机对照研究，如果证实有效，对肝癌治疗来说，确实是一个飞跃。”两位专家表示。
2016年7月2日星期六
禁食饥饿疗法
禁食或者说饥饿疗法，属于食疗范畴，在中医被称为辟谷疗法。如广州有个习惯，小儿发热时，老人会让孩子禁食，这样可以不用药物治疗，饿两顿饭就好了；还有患急性胃肠炎的病人，也是不吃饭为好，配合药物治疗有利病情康复。轻度疾病的可单独应用禁食即饥饿疗法，往往能奏效。至于外科手术后的禁食，那是在情理之中的，更容易理解。人们为了治病健身而主动在短期内辟谷，使肌体在饥饿状态下靠自身机能治愈某些疾病或强身健体，这就是辟谷疗法。
许多人认为自然辟谷不就是饿肚子，不吃饭，其实自然辟谷与绝食（饥饿疗法）表面上殊途同归，都是不吃饭，但是却有着本质的区别，因为在辟谷期间，通常都要配合一定方法，通过吸气，意念调控，心理能量的一系列方法来调理身体，治疗疾病，健身强体。
自然辟谷与饥饿不同
绝食都能激发潜能，但程度深浅不一；自然辟谷或绝食期，当人体处于某一生理极限的时候，生理系统应急性反应，竭力维持生命活动的正常运行，必将不惜一切，拿出老本---原气（潜能），供生命活动的需要，灵性激活，潜能激发。但自然辟谷通过一定方法或者有一定修为，或慧根颇佳；潜能开发，元气固秘，不依赖于食源，而是通过方法采吸自然能量来维持人体所需要的能量，也可以通过调动潜能配合自身能量合成物质供生命活动需要。这样可坚持一月、二月，一年、二年，甚至更长时间。饥饿疗法虽能开发潜能，但元气不固，营气涣散，合成物质的能力很薇弱，体能主要来自身体的物质分解，一般不能超过七天左右。时间太长，势必造成严重的营养不良，甚至加重病情。
行气者不一定要辟谷，但辟谷者必须要兼练行气之功，故“辟谷服气”每则相提并论。具体方法可参见自健养生的系列服气方法，特别强调的一点是应该强化吞津纳气，吸气，入静法。吞津、采气、静养应相辅相成，如此通过这一系列方法不会造成对身体的伤害。
自然辟谷有能量作为基础
苏联从事体育生命科学研究的，作了这样一组长跑实验：有一组是按照正常运动员的标准补给，因为消耗大，吃的也比较多；另一组运动量同样大，但补给不按标准，而且仅给予极少量，接近辟谷形式。但苏联人不懂辟谷，而称之为减食。几天跑下来，吃东西少的这一组，精力充沛，体质基本如前；大吃大喝那组体重反而下降。苏联人从生理解剖进行探讨，发现人体胃里有一种固氮菌。这种东西把人体从空中摄入胃中的氮气固定下来，制成氨基酸蛋白质，以供人体需要。而这个理论恰恰与古代中国养生实践相吻合。
我们古人，尤其是道家，很多人都经历了服气辟谷这样一个养生阶段，他们不但不象绝食的人昏昏迷迷的，反而生命力更旺盛，而且还能延年益寿。中国的实践和国外的科学研究，证实人体具有直接从宇宙中吸收营养，补充自己的能力。这一观念确定之后，再也不会担忧辟谷不吃饭会饿坏自己，就可以在很自然、很轻松的状态下度过你的辟谷期。从宇宙中摄取能源的渠道不全是通过鼻和口，古人将把全身的穴位都打开后，穴位从宇宙中直接摄取能源，摄取的成分有多少，量有多大，全凭心意用功夫，道家佛家的秘中之密就是意密。在服气辟谷期间，该怎么想，这是最关键的问题。怎么想呢？比如说你要采宇宙间的能源，你就不要光想说采宇宙的真气，那这个范围就小了。你就想光、电、声、能、气，全被你采来，凡是人体需要的养分、能源、凡是你需的，你都往里送。只要按照一定的方法就完全能够成功。
自然辟谷源于道家，通过一些方法积聚能量，再慢慢调理能量于体内，再修丹，练精化气，证得无漏，进入炼气化神阶段，自动出现的‘气满不思食’的现象。唐末钟离权钟“玉龙捧圣，大药过关……自然息住脉停，真炁充满而不思食……”真正的辟谷，没有饥饿感，而且食则胃不适；饥饿疗法是在主观或客观条件下，少食或不食的方法。绝食期没有强烈的饥饿感和食欲，食则胃舒神爽。
通常我们通过静坐，观想宇宙能量，或者其它方式来积聚能量；还有通过采气，吞纳自然之气来培补人体能量。具体修炼方法，在 面授时我们会系统进行心传口授。
饥饿疗法的起源
辟谷治病并不稀奇，当今世界不少国家以此方法治疗疾病。如在日本有“断食寮”，在美国、欧洲和原苏联有“断食疗养院”我国古代就有并流传至今的“辟谷”之说，实际上就是饥饿疗法。我国现存最早的辟谷资料是长沙马王堆出土文物《却谷食气》它与《阴阳十一脉灸经》和《导引图》写在同一幅帘书上。是我国目前所能见到的最早专门论述辟谷的文献之一。“辟”字在古代同“避”因此所谓辟谷就是避开五谷杂粮而不食。司马迁编写的《史记》里也记载着“汉高祖”的军师，张良晚年辟谷一事。可见辟谷养生在我国是历史悠久的。辟谷在世界宗教里也颇为流行，许多宗教和教名为“明心见性”“体悟真理”而进行辟谷。例如释迦牟尼、耶酥和穆默德都有辟谷数天，以悟道的记载，印度的瑜伽功，并有辟谷断食之说。
饥饿疗法的发展
目前世界各国对于辟谷疗法治病已有了系统而深入的探讨，如：英国的卡林顿医学博士著《活力，断食与营养的关系》；美国的洽凯博士著《完全的健康》；马克欧义博士著《断食与健康》；日本小岛八郎著《断食疗法》；以及我国台湾省段木干教授著《断食》等书均陆续问世。从应用方面来看，许多国家设有断食治疗的医院，如柏林的一家断食医院有三百多张床位；前苏联国莫斯科精神病院设禁食部；日本现在有三千多家断食寮；我国台湾省有长青断食中心。又如美国的克拉斯综合病院，澳洲的雪梨健康中心以及由名医薛尔顿，华克尔两位博士主持的美国德洲疗养所等，也都是以辟谷治病而名扬世界的。
古代中医学理论的启示
（一）阴阳与经络学说
阴阳学说认为：人体阴阳之间相对的协调平衡是健康的标志，而“阴阳失调”则是体内阴阳气血，脏腑经络失调的总称，是一切疾病发生发展的根本原因。各种致病因素作用于肌体，破坏了人体阴阳的相对平衡，造成阴盛阳衰或阳衰阴盛就会导致疾病的发生，在论述疾病的预防和发展病因时都十分强调人体正气，认为正气旺盛，邪气就不易侵入，疾病也不会发生，《素问遗篇，刺法论》提出“正气存内，邪不可干”说明增强体质，蓄养正气是抵抗外来邪气侵袭，防御疾病发生的一个重要环节。这里说的“正气”可归属为阳，而“邪气”可归属于阴。又如中医学在论述疾病的治疗原则时，不仅提到调整阴阳而且谈及扶正祛邪与治标治本的问题。如果按阴阳学说来归类，也可以把扶正和治本的“正”与“本”归属为阳；而怯邪和治本中的“邪”与“标”归属于阴。所以我们认为中医学关于疾病预防和治疗原则，均可用“调整阴阳”来概括。即人体健康是阴阳平衡的结果，人体生病是阴阳失调的结果，据此而论治疗疾病就必须从调整阴阳入手。因此说纠正阴阳的偏盛或偏衰是非常必要的、在医疗实践中发现：无论任何治疗手段虽各有特色，但他们又有统一的共性就是“刺激”肌体而治疗疾病，但通过“刺激”并不是直接治疗的，而“刺激”的结果却是一致的，它激活了人体的经络系统，促进经气沿经络正常循行，而只有经气正常，才能充分发挥“自身调控”作用，使阴阳失衡的肌体重新恢复正常平衡状态，所患的疾病也就得到痊愈。这也就是辟谷疗法的最大奇特性。
通过此法强身治病，自古就有先例，也是我国古代一种独特的养身保健方法。现在世界上有不少国家也用此法治病保健，虽然人们对饥饿治病的机理还不十分清楚，但从临床观察发现，辟谷对人体疗效比用药、针灸、推拿等疗效还非常显著。
（二）辟谷疗法的特点
疗效显著，适应广：如神精系统、呼吸系统、运动系统、内分秘系统及心脑血管系统的多种病症都有较好的疗效，收到了疗程短、见效快，比传统的疗法特别显著。除对于常见病外，还对一些疑难杂病有着难以完全解释的特殊疗效。
没有副作用，安全性强，辟谷疗法是不使用药物，故没有用药所带来的毒副作用，可又节省药费开支。所以此疗法比较安全可靠，不会发生医疗事故。
即能治病防病，又能减肥美体，特别是肥胖者更为突出。
(三)辟谷在动物实验中的结果
台湾省家禽试验所对864只产蛋能力退化的纯种来享鸡，做10天停供饲料而供水的实验，当恢复供料、供水40天后发现老母鸡中的75%再度产蛋，说明辟谷对生命的返老还童的作用。美国营养学教授马凯博士作的马凯模范实验，证实，老鼠每周禁食两天，不易生病，且寿命延长一倍。加洲大学“老化”研究中心，华福特教授，在历经30年的动物实验之后，现在自己也坚持每周禁食2天，用以健身。相信人类将来并可通过辟谷疗法治病健身。
辟谷过程中的生理变化和反应
我们吃下的食物，在消化道被吸收之后，其营养成份被肠壁吸收而入血液，这些营养成份在体内大致有三种作用：一是作为“建筑材料”被用于新细胞的构建；二是作为“能源物质”被用于躯体、脏气、运动和各种新陈代谢活动；三是作为调节物质被用于各种生理反应或维持渗透压。但是肌体吸收的营养物质，往往超过身体所需的份量，这些多余的营养成份就是通过化学转化作用，贮藏于体内，一旦辟谷这些贮存的营养成份就被肌体所动用，再次通过化学转化作用，从贮藏部位“析出”而进入血液运至所需部位被重新利用。
（一）体重的变化
在辟谷的第一天至第五天时体重减轻最为明显，一天平均会减轻1至2千克，从第五天前后，每天减轻0.5至1千克。以后几乎都以一定的递减方式在减轻体重（有时也例外）。由于肌体对辟谷的逐步适应，使肌体的消耗趋于最小限度，当体重减少到原来体重的40%时，还不至于造成死亡。但也不会有生命危险，到这种程度，大约需要40天左右，我本人两次辟谷都已超过39天，而且感觉非常好。
（二）内脏器官的变化
从脏器的体积来讲，随着断食天数的增加，肌肉减少较多。肺、骨骼神经等器官的结构不易减少。肾上腺和甲状腺反而增大，辟谷的前3天胃液照常分秘，故有饥饿感是辟谷最难的时期。3天至1周以后胃因长期没有食物，胃液分秘便会减少，饥饿感并降低。
（三）生理机能的变化
辟谷期间高血压患者的血压会显著下降，而低血压患者反而会上升。正常血压者一般也略有降低。脉搏和呼吸频率没有太大变化，但视觉、听觉、触觉会变得更敏锐，记忆力和联想力也会增强。白细胞总数量在此时第1周内没有改变，第7天后开始增加，到第11天起急速增多，日增1.57倍以上，说明辟谷能提高肌体免疫力。
（四）舌苔的变化
辟谷期间，口腔内粘着性增多，照镜子看舌面长了黄白色的舌苔，甚至有些出现黑色舌苔，10天以内很少清洁，若继续辟谷，舌苔会清洁，表示身心、净化可继续辟谷，效果非常理想，已达到排毒标准。
（五）排便与排尿的变化
辟谷期间大便次数一般在开始后的最初1-4天内排一次便，这种大便叫“宿便”，它的颜色一般是黑绿色，黑色或茶褐色，呈泥巴状（也有少数例外）且均有恶臭气味与正常大便差异较大。宿便的排除只见于辟谷期间，宿便一经排出体外，顿觉全身舒爽轻松愉快。在饮水不多情况下尿量会逐渐减少，颜色变浓，排尿次数并减少，如饮水正常，尿量、色，也正常，排尿次数与辟谷前无甚差异。
（六）辟谷的疗法的反应
1、出现失眠现象：在此期间多数人精神反而是振奋的，睡眠时间缩短而出现失眠现象，但不疲劳。但是失眠者在此期间睡眠时间却相对增加很多。
2、出现呕吐或腹泻症状：据观察以消化系统疾病患者出现此症状的较多。
3、出现发热、头痛症状：很少有此症状，个别也有打喷噎，流鼻涕等类似感冒的症状。
4、出现情绪反应：情绪抑郁患者，在辟谷过程中可能会出现发怒，烦躁不安，豪啕大哭等情绪反应。据观察出现此反应者，以中年女性较多，但很少见。
5、皮肤出现丘疹或瘀斑：个别有此现象，临床发现，一个身体健康没病的人参加辟谷一般没有反应，而患有疾病的人在此期间会出现反应，并且辟谷反应很明显，治病效果也就越好。似乎辟谷反应就是愈病的前兆，由于这些反应与辟谷者所患疾病有关，故把这些反应叫排毒排病反应。
6、辟谷期间，口腔内粘着性增多，照镜子看舌面长了黄白色的舌苔，甚至有些出现黑色舌苔，10天以内很少清洁，若继续辟谷，舌苔会清洁，表示身心、净化可继续辟谷，效果非常理想，已达到排毒标准。
辟谷过程中的代谢变化
它是一种人为的主动性的限制进食，属于治疗性饥饿与恶性肿瘤，昏迷或严重肠胃炎症等疾患，所致的病理性饥饿决对不同，但辟谷均可导致肌体内部发生一系列代谢改变。这些变化一般都是在激素的影响下，各组织细胞从依赖食物提供葡萄糖，逐步适应了靠自身储存的脂肪，作为主要能量来源的过程。
辟谷肌体的主要能量来源是储存于体内的蛋白质和脂肪，其中脂肪约占能量来源的85-90%，早期肌体主要靠糖异生和周围组织以脂酸和酮体为燃料，节省葡萄糖的利用，使血糖水平维持恒定，保证脑组织正常活动的需要，辟谷晚期又以脂酸氧化供能为主，而节省酮体的利用，脑则以酮体代替葡萄糖作为主要能源。减少蛋白质的消耗。但饥饿发展到最后，待储脂肪耗尽时又需大量蛋白质长期的净负氮平衡体内蛋白质丢失1/3至1/2时，则可不避免地导致死亡。在整个饥饿适应中，血胰岛素/高血糖素始终具有最重要的调节作用。
辟谷治病健身的生理生化机制
（一）清洁消化道，提高消化吸收能力
大家经常听到“宿便”这一术语，它实际上是指长期停滞淤积于肠内的内容物，包括食物残渣，肠道细菌及发酵食物残渣，所产生的分泌物等。它会滋生大量微生物及有毒有害物质，其结果引起肌体中毒症状。这种病情便是医学上所谓的“食物自身慢性中毒”也是致病之源，要想彻底清除宿便，唯有施行辟谷，做几次“大扫除”才能彻底清“仓”有很好的疗效，在辟谷的同时，消化道壁上的衰老或机能不健全的细胞，则会脱落而随宿便，排出消化道壁上的脂肪成份，并会分解。当进食后消化道壁上机能，旺盛的细胞相对增多，肠胃机能进一步增强，使整个消化系统的肌能状态得以改善，工作效率进一步提高，不仅能避免“食物”本身慢性中毒，而且由此而发的疾病也会自然痊愈，身体会日趋强壮。
（二）分解消耗多余的脂肪减肥降脂
辟谷可使肌体多余脂肪分解，作为能源物质供给辟谷状态下的肌体利用，较长时间的辟谷，会使肌体消耗大量的脂肪，具有明显的减肥降脂效果，由于辟谷刺激，使肌体的调解机能进一步加强，代谢活动得到改善，脂肪的合成代谢与分解代谢，趋于动态平衡，最终动态平衡，最终彻底根除肥胖症，所以采用辟谷疗法减肥降脂，是最好的良方。
（三）疏通和软化血管，避免栓塞和硬化
辟谷后，由于营养物质的匮乏而使肌体的物质合成代谢受抑，物质的分解代谢相对加快，促进物质分解的酶类的分解作用相对加强，在脂肪动员的同时，血管腔内的血栓也会被溶解而使血流畅通，沉积于动脉内膜的脂质（胆固醇）也会分解“析出”，使动脉管辟得到软化，故辟谷疗法能有效地疏通和软化血管，避免血栓塞和硬化所导致的心脑血管疾病。
（四）清除体内有害物质，净化内环境
经常运转的机器，需经常擦洗减少摩擦，才能延长机器寿命，人体需要经常不断地排除积蓄的有害物质，才能保持肌体细胞的活动，如何排除体内有害物质：一是通过正常人体的排泄作用，二是通过辟谷，它可靠肌体通过“内耗”自净作用和排泄作用，从而达到治病健身的目的，也是对细胞的一种强刺激，它可刺激细胞恢复正常代谢，从而提高细胞的活力，辟谷后肌体先消耗的是弱化、病变、衰老的组织细胞附着物等。辟谷能引起肌体的这种废物利用，医学上称为“自身融解”可以说是：辟谷疗法是不使用刀子的内脏手术，且比外科医生作得更自然、更精细、更有效，丝毫无损健康而可去除百病的特异方法。辟谷可刺激“内脏系统”一方面源源不断地向内环境补充细胞代谢所需的营养物质和氧气，同时又持续不断地由内环境向外环境排出细胞所产生的各种代谢废物及二氧化碳气体等，这即实现了细胞与外界环境之间的物质交换，也维持了内环境理化性质的相对稳定，为细胞提供了适宜的生活环境，故辟谷具有净化内环境的作用，所以能够治病，健身，延年益寿。
（五）激活免疫系统，提高肌体免疫力
辟谷作为一种良性刺激，对免疫器官同样起作用，它所造成的营养物质缺乏，会刺激构成免疫器官的细胞，使其代谢活跃。而进食、断食、再进食这种刺激方式会导致构成免疫器官的组织细胞的更新，辟谷造成肌体“内耗”使内环境内，抑制免疫的有害物质分解，并排出体外，从而解除免疫抑制，提高免疫系统的免疫功能。另一方面特别是在辟谷结束后，由于食物的不断补充，而使合成代谢“原材料”充足，合成新蛋白质速率相对加快，结果使肌体老化的组织蛋白质，得到更新和组织机能的改善，从而使肌体的整体机能得到很好的加强，“返老还童”也就在于此。
（六）增加肌体自身调节机能，使器官系统的功能协调一致
临床实践证明，辟谷3-5天之后，其神经系统的兴奋性明显提高，这是表明辟谷对神经系统具有一定的刺激作用，但从最终效果来看，这种刺激对神经系统并无伤害性，而是一种能增强神经调节机能的良性刺激。所以可使肌体调控神经，进行自我调整，使调节机能更灵活，更完善，更精确，以保证肌体各部分协调统一。
2016年6月28日星期二
9合1 HPV疫苗 覆蓋能導致9成子宮頸癌的HPV型號
根據2012年的數據，子宮頸癌每年全球有50萬宗新症。子宮頸癌雖然過去一直是頭號女性殺手，但往往需要多年才會發展成形，所以及早檢查及預防至為重要。子宮頸細胞檢驗可以及早發現病變，並加以治療，子宮頸癌因而是其中少數可以及早檢驗並醫治的癌症之一。
子宮頸癌是由HPV（人類乳頭瘤病毒）引起，亦是香港女性常見的癌症，婦產科專科醫生譚家輝指出於2013年已有503宗新症，年輕女性亦有機會患上此病。由於每名曾有性行為的女士也有機會染上HPV，而治療方法有機會需要切除子宮，對患者做成身心創傷，故此病不容忽視。
最有效的預防子宮頸癌的方法是注射HPV預防疫苗及定期作柏氏抹片檢查，現時最新推出的9合1疫苗，可以覆蓋能導致9成子宮頸癌的HPV型號，再配合定時的婦科檢查，可大大減低患上子宮頸癌及相關癌前病變的機會。
單一伴侶 亦有機會患上
譚醫生指出，子宮頸癌主要分四期，最早期的病徵不明顯，部份是從柏氏抹片檢查得知，比較明顯的病徵是陰道不正常出血，經期之間或性行為之後出血。較易患有子宮頸癌的人士，大多是較年輕開始有性生活、食煙、多名性伴侶及多次生育。但原來很多患者也沒有上述的高危因素，譚醫生表示︰「曾有位32歲的未婚女士，有固定的伴侶及未曾懷孕，不煙不酒，因異常陰道出血而求醫，才發現患上子宮頸癌。」
治療康復 變成不育
譚醫生補充，大部份的患者需要切去子宮，甚至切走部份陰道和子宮頸兩旁組織，導致失去生育能力。上述病人痊癒後變成不育，做成了沉重的心理傷害。相反，最早期的患者，可能只須切除部份子宮頸組織，仍能保留生育能力，但康復後懷孕仍會增加早產風險。
HPV病毒 引起病患
子宮頸癌的主因是由HPV引起，HPV有超過100種類別，當中並非每種也會導致子宮頸癌，譚醫生指出，常見的6及11類型主要會引發「椰菜花」（生殖器官濕疣），不會引起癌症或嚴重癌前病變，屬低危類別。而人類乳突狀病毒（HPV，或稱人類乳頭狀瘤病毒）為一類病毒，涵蓋 100 多種病毒，包括影響生殖器的 40 多種，其中至少13種可致癌，當中以16及18類型「最惡」，有近7成的子宮頸癌的個案都是由此兩類HPV引起。另外兩成的個案普遍從31、33、45、52及58類HPV引起，當中52與58在亞洲人的出現率較高。
最新疫苗 防禦更佳
要防範子宮頸癌，最佳方法是注射HPV預防疫苗及定期作柏氏抹片檢查，而現時已有HPV預防疫苗，可預防6、11、16及18類型HPV，覆蓋7成子宮頸癌，據現有數據指出其有效期超過10年。最新推出的9合1疫苗，除保留上述4個HPV的預防功效外，更加入防禦上述另外5種引起子宮頸癌的HPV，包括31、 33、45、52及58類型。9成子宮頸癌是由這9種HPV引起。此外，9合1疫苗就連對嚴重癌前病變期的覆蓋率，亦由5成提升至8成。譚醫生說︰「如發現病人子宮頸出現嚴重的癌前期，可能需局部切除組織，預防變成癌症，對病人造成身心的傷害，故加強這方面的預防，有助減輕病人的精神負擔。」
9歲起 可注射
最佳的注射HPV預防疫苗的時間，是在接觸HPV之前、即首次性行為前，建議9歲起已可注射，新疫苗可覆蓋能導致9成子宮頸癌的HPV型號。當然，已有性行為的人士亦可注射，只是保護率不及從未接觸HPV的女性高。譚醫生說︰「HPV預防疫苗需注射三針，如果打了4合1HPV預防疫苗，亦可考慮再打最新的疫苗，以加強保護。」他補充，接種後最常見的不適主要出現於注射部位和頭痛，而曾對HPV疫苗敏感者不應接種。重要的是就算已注射HPV預防疫苗的女性，亦應定時進行柏氏抹片檢查，以保萬全。
子宮頸癌是由HPV（人類乳頭瘤病毒）引起，亦是香港女性常見的癌症，婦產科專科醫生譚家輝指出於2013年已有503宗新症，年輕女性亦有機會患上此病。由於每名曾有性行為的女士也有機會染上HPV，而治療方法有機會需要切除子宮，對患者做成身心創傷，故此病不容忽視。
最有效的預防子宮頸癌的方法是注射HPV預防疫苗及定期作柏氏抹片檢查，現時最新推出的9合1疫苗，可以覆蓋能導致9成子宮頸癌的HPV型號，再配合定時的婦科檢查，可大大減低患上子宮頸癌及相關癌前病變的機會。
單一伴侶 亦有機會患上
譚醫生指出，子宮頸癌主要分四期，最早期的病徵不明顯，部份是從柏氏抹片檢查得知，比較明顯的病徵是陰道不正常出血，經期之間或性行為之後出血。較易患有子宮頸癌的人士，大多是較年輕開始有性生活、食煙、多名性伴侶及多次生育。但原來很多患者也沒有上述的高危因素，譚醫生表示︰「曾有位32歲的未婚女士，有固定的伴侶及未曾懷孕，不煙不酒，因異常陰道出血而求醫，才發現患上子宮頸癌。」
治療康復 變成不育
譚醫生補充，大部份的患者需要切去子宮，甚至切走部份陰道和子宮頸兩旁組織，導致失去生育能力。上述病人痊癒後變成不育，做成了沉重的心理傷害。相反，最早期的患者，可能只須切除部份子宮頸組織，仍能保留生育能力，但康復後懷孕仍會增加早產風險。
HPV病毒 引起病患
子宮頸癌的主因是由HPV引起，HPV有超過100種類別，當中並非每種也會導致子宮頸癌，譚醫生指出，常見的6及11類型主要會引發「椰菜花」（生殖器官濕疣），不會引起癌症或嚴重癌前病變，屬低危類別。而人類乳突狀病毒（HPV，或稱人類乳頭狀瘤病毒）為一類病毒，涵蓋 100 多種病毒，包括影響生殖器的 40 多種，其中至少13種可致癌，當中以16及18類型「最惡」，有近7成的子宮頸癌的個案都是由此兩類HPV引起。另外兩成的個案普遍從31、33、45、52及58類HPV引起，當中52與58在亞洲人的出現率較高。
最新疫苗 防禦更佳
要防範子宮頸癌，最佳方法是注射HPV預防疫苗及定期作柏氏抹片檢查，而現時已有HPV預防疫苗，可預防6、11、16及18類型HPV，覆蓋7成子宮頸癌，據現有數據指出其有效期超過10年。最新推出的9合1疫苗，除保留上述4個HPV的預防功效外，更加入防禦上述另外5種引起子宮頸癌的HPV，包括31、 33、45、52及58類型。9成子宮頸癌是由這9種HPV引起。此外，9合1疫苗就連對嚴重癌前病變期的覆蓋率，亦由5成提升至8成。譚醫生說︰「如發現病人子宮頸出現嚴重的癌前期，可能需局部切除組織，預防變成癌症，對病人造成身心的傷害，故加強這方面的預防，有助減輕病人的精神負擔。」
9歲起 可注射
最佳的注射HPV預防疫苗的時間，是在接觸HPV之前、即首次性行為前，建議9歲起已可注射，新疫苗可覆蓋能導致9成子宮頸癌的HPV型號。當然，已有性行為的人士亦可注射，只是保護率不及從未接觸HPV的女性高。譚醫生說︰「HPV預防疫苗需注射三針，如果打了4合1HPV預防疫苗，亦可考慮再打最新的疫苗，以加強保護。」他補充，接種後最常見的不適主要出現於注射部位和頭痛，而曾對HPV疫苗敏感者不應接種。重要的是就算已注射HPV預防疫苗的女性，亦應定時進行柏氏抹片檢查，以保萬全。
2016年6月27日星期一
男女体脂率数据对照
男女数据的对照：
男子的体脂率 体型特点
4%~6% 臀大肌出现横纹(健美运动员最理想的竞技状态)。
7%~9% 背肌显露，腹肌、腹外斜肌分块更加明显(健美运动员竞技状态)。
10%~12% 理 全身各部位脂肪不松弛，腹肌分块明显。
13%~15% 想 全身各部位脂肪基本不松弛，腹肌开始显露，分块不明显。
16%~18% 型 全身各部位脂肪就腰腹部较松弛，腹肌不显露。
19%~21% 腹肌不显露，腰围通常是81~85厘米。
22%~24% 腹肌不显露，腰围通常是86~90厘米。
25%~27% 腹肌不显露，腰围通常是91~95厘米。
28%~30% 腹肌不显露，腰围通常是96~100厘米。
31%以上 腹肌不显露，腰围通常是101厘米以上。
女子的体脂率 体型特点
8%~10% 极少数女运动员达到的竞技状态(会引起闭经、月经紊乱和乳房缩小)
11%~13% 背肌显露，腹外斜肌分块更加明显(女子健美运动员竞技状态)
14%~16% 背肌显露，腹肌分块更加明显。
17%~19% 理 全身各部位脂肪不松弛，腹肌分块明显。
20%~22% 想 全身各部位脂肪不松弛，腹肌开始显露，分块不明显。
23%~25% 型 全身各部位脂肪基本不松弛，腹肌不显露。
26%~28% 全身各部位脂肪就腰腹部明显松弛，腹肌不显露。
29%~31% 腹肌不显露，腰围通常是81~85厘米。
32%~34% 腹肌不显露，腰围通常是86~90厘米。
35%~37% 腹肌不显露，腰围通常是91~95厘米。
38%~40% 腹肌不显露，腰围通常是96~100厘米。
41%以上 腹肌不显露，腰围通常是101厘米以上
订阅：
博文 (Atom)