Health Articles

Sleeping pills linked to higher risk of cancer, death, study says

By Melissa Healy, Los Angeles Times/For the Booster Shots Blog

5:13 PM PST, February 28, 2012

advertisement

A new study suggests that the 6% to 10% of Americans who use prescription sleep medications such as zolpidem (Ambien), temazepam (Restoril), eszopiclone (Lunesta) and zaleplon (Sonata) are more likely to develop cancer, and far more likely to die prematurely, than those who take no sleep aids.

The increased rates kick in at really low levels too, the study says. For those prescribed as few as one to 18 sleeping pills in a year, deaths during the period of the new study were more than three and a half times greater than for those who got no such prescriptions, the study says. And for patients who took home the largest number of prescriptions for sleep aids--for more than 132 pills per year--the risk of death was five times greater than among those who appeared to take no sleep aids, according to the study.

Studies such as this one do not establish whether sleep drugs are a cause of the increased cancers and deaths or whether, perhaps, those who are at greater risk of dying or developing cancer are simply more likely to seek a prescription for sleep problems. To establish such cause-and-effect relationships, clinical trials, which would compare subjects taking sleep medications against those taking a sham drug, would be necessary, said study coauthor Dr. Daniel F. Kripke, a professor of psychiatry emeritus at UC San Diego now affiliated with the Scripps Clinic in La Jolla.

In addition, the "all-cause mortality" used in the study is a crude measure of a drug's risk, because the measure aggregates a wide range of seemingly unrelated health crises: automobile accidents, injuries, suicides, infectious diseases such as influenza, and chronic conditions, including asthma, diabetes and cancer.


The study, released this week by the British medical publication BMJ Open, found an increase in cancer incidence among those taking sleep medications that was modest but statistically significant. Compared with patients with no record of taking prescription sleeping pills, the study says, those who were the heaviest users of prescription sleep aids were 35% more likely to be diagnosed with cancer during the study period.

The use of sedative medications was a better predictor than a participant's current smoking habit of whether he or she would develop lymphoma or cancer of the lung, colon or prostate during the study period, according to the research.

Conducted by researchers from Scripps  and the Jackson Hole Center for Preventive Medicine in Jackson, Wy., the study tracked 10,531 patients given prescriptions for hypnotic sedatives for at least three months and for as long as four years. For comparison, researchers matched each patient prescribed with a sleep aid with at least two patients of similar age, gender and health status who had no record of having had sleep aids prescribed.

Zolpidem--sold as Ambien--was the most widely used prescription sleep medication used by study participants, followed by Restoril, the research says. But 4,117 of the participants got prescriptions for other sleep aids, including Lunesta, Sonata, benzodiazepines, barbituates and sedative antihistamines.

Given the millions of Americans for whom prescription sleep medication is a routine habit, the authors estimate that in 2010 alone, 320,000 to 507,000 deaths in the United States may have been associated with prescription sleep-aid use. Despite evidence that they may not add much to a night's sleep, Americans in 2010 filled some 66 million prescriptions for "hypnotics and sedatives," according to IMS Health, which tracks drug trends. That makes sleep aids the 20th most used class of prescription therapies.

Kripke  acknowledged he was "very shocked" by the higher cancer levels he found in this large population. "I suspect people who work for the manufacturers of these drugs might be shocked too."

Sanofi-Aventis, the maker of Ambien, said Tuesday in a statement that the BMJ Open study had limitations beyond those acknowledged by its authors. The company called the study's conclusions "highly questionable," and cited its average follow-up of 2.5 years as insufficient to detect whether cancers were new, and might be the result of sleep aids, or whether they had already taken hold at the time a patient got a prescription for sleep problems.

Kripke agreed that cause and effect had not been established but underscored that a litany of studies have stirred concern about the safety of sleep medications, including research that was submitted to the Food and Drug Administration when some of these drugs were approved.

Kripke said that beyond their common role in fatal medication overdoses, there's evidence that widely used sleep medications raise risks for many ills: "hangover" effects dull alertness and cognitive performance, which may lead to accidents and injuries; studies (including this one) have found that gastroesophageal regurgitation and peptic ulcers are more common among those taking sleep aids, which could drive up rates of infection and of cancer; other studies have linked sleep aids' use with  depression and sleep apnea, which in turn raise risks of suicide, diabetes and heart disease.

As for how sleep medicine could be linked to cancer, that is harder to discern. A 2008 study by Kripke on rodents found hypnotics to have a carcinogenic effect, and suggested they can cause chromosomal damage. But human studies have been more mixed.

For those who rely on prescription sleep drugs to get to sleep and stay asleep, Kripke, a specialist in sleep disorders and their treatment, said that changes in "sleep hygiene" can make a difference, as can cognitive-behavioral therapy. But he added that many--especially older patients-- who lean on sleep aids should know that they may function perfectly well with a little less sleep, and that medications do not add large chunks of sleep-time to a night's rest anyway.

A NEW APPROACH TO METABOLIC SYNDROME
By: Michael P. Ciell, R.Ph.,

The Greatest Healthcare/Financial Crisis

Metabolic Syndrome (aka Syndrome X) with its four hallmark symptoms of obesity, hypertension, dyslipidemia and hyperglycemia is devastating our country as well as the whole of North America. In March of 2005 the National Institutes of Health and the New England Journal of Medicine published a paper stating that because of this epidemic the current generation is projected to have a shorter life expectancy then the previous one…for the first time in recorded history! Since that paper things have become much worse. Worse, despite the fact we have changed the USDA “Food Pyramid”, developed many new classes of pharmaceutical agents (especially ones for pre-diabetes and diabetes Type II), have taken soda machines out of schools, and even the First Lady’s top priority is the obesity epidemic. This syndrome, with all of its comorbidities (cardiovascular disease, stroke, many cancers, kidney failure, blindness, amputations ,etc.), accounts for the majority of healthcare dollars spent. If the tide is not turned, Metabolic Syndrome will bankrupt our country. This is a fact.

The Pathophysiology of Metabolic Syndrome
In 1987 the late Gerald Reaven, MD, Professor of Medicine at Stanford University’s College of Medicine, first demonstrated that the four hallmark symptoms shared a commonality: hyper-insulinemia coupled with insulin resistance. He coined the term “Syndrome X” to illustrate the point: the four legs of the “X” represent the symptoms (hypertension, central obesity, hyperglycemia and dyslipidemia) and the nexus of the “X” being the causal agents of too much insulin along with insulin resistance (the cells’ do not respond to normal physiologic amounts of insulin). This is the standard, accepted medical model of this disease.

The Failure of Current Treatments
We are being ravaged by this syndrome due to the simple fact that we have ignored the model! Instead of focusing our attention on the root cause we have decided to treat each of the symptoms as separate, unrelated diseases. Thus we have new dietary recommendations and “diets d’Jour”, as well as a plethora of exercise regimens prescribed for obesity and of course, the “diet pills”. There too are the myriad of prescription drugs to ‘control’ the other three symptoms. If our attention is on ‘controlling symptoms’ we have admitted, by default, that there is NOTHING WE CAN DO FOR THE CAUSATIVE FACTORS and we will just have to LEARN TO LIVE WITH OUR DISEASE (i.e. ‘it will always be with us, we’ll just control it’). This attitude of acceptance is bad enough and unaffordable in the long run, but that’s the least of it. If we understand the pathophysiology of this syndrome we readily can see why many of these treatments actually make the other symptoms much worse! Hyper-insulinemia means the patient’s pancreas is secreting an exaggerated amount of insulin in response to rises in blood glucose. This can easily be confirmed by doing a fasting insulin level OR the standard glucose challenge test and ordering insulin levels along with glucose levels at time zero, one hour and two hour intervals post challenge glucose administration.

Sadly, the vast majority of practitioners do not even think about such an important marker. So we dwell on just the glucose level or Hemoglobin A1c (merely symptoms ) and prescribe drugs such as the sulfonylureas (i.e. glyburide, glipizide, glimperide) which cause the pancreas to secrete EVEN MORE INSULIN or we actually give them INSULIN ITSELF in an aggressive attempt to control a symptom. If the model is correct then this therapy should make the syndrome worse……and it does! This is the fundamental reason why we have failed to stem the tide (or actually reverse) this seemingly insidious malady.

The Concept of Homeostasis
If insulin just mediated glucose uptake by our cells and did nothing else, we probably would not have this problem. However this is not the case and when the amount of insulin remains consistently elevated it does other things…..and these things are NOT good. Before discussing the effects of hyper-insulinemia, a review of the fundamental concept of homeostasis should be addressed.

The body is an organism that strives to maintain a constant internal environment in the face of constantly changing, often hostile, external factors. Blood pressure, blood glucose, body temperature, acid / base balance, etc. must remain within a relatively narrow range in order to survive. It does so by means of the action/reaction principle, or mechanisms that exert opposite effects so that a balance may be
achieved. Examples are: vasodilation / vasoconstriction, oxidation / reduction, anabolism/catabolism, assimilation / elimination, etc. These systems are exquisitely regulated primarily by the nervous system and the endocrine (hormonal) system. So if the environmental temperature is 125 degrees, our internal temperature remains at 98.6 degrees. Likewise if the temperature drops to 20 degrees, certain mechanisms are in place to make certain our internal temperature remains a constant 98.6. Glucose homeostasis is essential for life as certain cells in the body can only use glucose as an energy source (certain brain cells, the adrenal medulla, red blood cells, etc.). Whether in times of feast or famine, blood glucose must remain in a certain range and insulin and glucagon are the master hormones that control this process (forget about ghrelin, leptin, incretins and all these ‘new mini-hormones’ that are in the literature today…these are subservient to the two masters). The body needs BOTH of these “master hormones” to maintain balance ( as they have exactly opposite physiological functions….if you know what insulin does, then you automatically know what glucagon does…the exact opposite!) and if an imbalance occurs, dysfunction or “disease” will arise.

The Physiological Effects of Insulin
Insulin’s primary function is mediating glucose uptake to muscle cells, and in this way, helps regulate blood glucose homeostasis. However insulin binds to many other receptors in the body and affects MANY other physiological parameters. And here’s the “rub”. If insulin receptors on the muscle cells become resistant to insulin’s effect (and do not uptake glucose in an effective manner) the pancreas will produce more to ensure glucose uptake will occur. But if we increase insulin levels, what happens to OTHER receptors that are not “resistant” yet and modulate other bodily functions? This scenario becomes way more complicated, in that, these receptors become ‘insulin resistant’ at different times. So a ‘typical Syndrome Xer’ presents to the physician with some central obesity, slightly elevated blood pressure, slightly elevated blood glucose and a less than stellar lipid panel. He is told to lose some weight by eating more fruits and vegetables, cut down on fats and cholesterol (have oatmeal instead of bacon and eggs) and do some light exercise. This is standard, first line therapy of lifestyle changes and sounds very reasonable. This compliant patient makes these changes and returns in two months, shocked and disappointed that his symptoms have become worse! Now he is given a low dose ACE inhibitor coupled with a diuretic for his hypertension and placed on metformin and glyburide to help control hyperglycemia. The glyburide tells the pancreas to secrete even more insulin and he gains more weight. Insulin also “ramps up” the enzyme HMG-Co A reductase which basically tells the body to produce even more cholesterol.

Excess insulin also drives the kidneys to retain sodium and waste magnesium,
which is an essential element for insulin receptor sensitivity. Hypertension and insulin resistance worsen. Usually at this point (if not done sooner) a statin is added along with niacin and another oral hypoglycemic and we ‘start the march’ to insulin therapy. This is why many of these patients will find themselves on six to nine prescription drugs and this is the current “Standard of Care” for this syndrome.

Let Your Food Be Your Medicine
Let us now suppose that the above patient visited a Chiropractic physician first. This particular physician is skilled in the use of a ‘muscle sparing’ protein diet, not a hyper protein diet ala Atkins. This diet is also low in fat, particularly saturated fat and is very carbohydrate restrictive (providing about 40 grams of carbohydrates daily mainly from fibrous vegetables). The physician explains the “medical model” of Syndrome X and relates how the overproduction of insulin can contribute to all his symptoms.

Correcting hyperinsulinemia is very straightforward: all carbohydrates (with the exception of fiber) will eventually be turned into glucose….sometimes quickly, sometimes slowly. As the glucose is absorbed the pancreas begins to secrete insulin (in this case, too much insulin). By restricting the carbohydrates the production of insulin is immediately reduced. The patient is interested but confides that he can be hypoglycemic at times and is afraid of such a restrictive protocol. The physician relates that hypoglycemia is usually the consequence of an overproduction of insulin, not a lack of carbohydrates. He further explains the body has “three tanks of energy” from which to draw. Glycogen (or our stored glucose), muscle, which can be broken down via gluconeogenesis to supply glucose and fat (triglycerides) which can be turned into glucose (from the glycerol) and ketonic bodies which most of the cells In the body can use for fuel. But the body draws on these compartments in a very specific order. It will always use the glycogen first and only when ‘that tank’ is empty, will it then begin to simultaneously burn muscle and fat.

The physician tells the patient if he keeps “putting fuel in the glycogen tank”, he will never be able to access his fat reserves, thus the restriction of carbohydrates. He also says that we never want to lose muscle, thus the inclusion of the adequate amount of protein to replenish what is lost to gluconeogenesis. During the first three days of this protocol the patient may feel a little tired or weak (as the body depletes its glycogen) but once this is gone and the body ‘switches over to muscle and fat’, he will have plenty of energy and hypoglycemic episodes will be a thing of the past. His patient is interested but asks: “ketonic bodies”, does that mean ketosis…I thought that was bad?” Again the physician explains that ketoacidosis is bad and that is why a Type I diabetic would never be placed on this program. In this case ketosis just means ‘living off your reserves’ and is the reason human beings were able to survive times of famines. His concerns allayed, the patient begins the program.

Six weeks later the elated patient returns to his Chiropractor. He is thirty pounds lighter and says that his medical doctor told him his blood work was fantastic! In layman’s terms the physician tells him: “Well you have actually reset your pancreas, it no longer is pumping out too much insulin and now you can start to put fruits, grains and dairy back into your diet”. After this patient’s glycogen reserves were depleted and carbohydrates continued to be restricted, the body had to ensure proper blood glucose levels were maintained. Under these conditions the pancreas produces more glucagon (which raises blood sugar) and much less insulin (whose primary function is to lower blood sugar).

But there is more to glucagon than this primary function. Glucagon stimulates two adipocyte (fat cell) enzymes (HSL and ATGL) and inhibits a third (Lipoprotein lipase). The result is the release of trigylcerides from the fat cell (to be used a fuel) as opposed to insulin’s effect which is to store fat. Glucagon enhances the entry of free fatty acids across the mitochondrial membranes so they can be used as fuel (insulin inhibits this). Glucagon also greatly inhibits the action of HMG-CoA reductase (along with all the other enzymes necessary for cholesterol synthesis) and forces cells to pull cholesterol from the blood stream via ‘ramping-up’ LDL receptors (1983 Nobel Prize in Medicine). This is why this patient’s lipid panel came back stellar. Finally in the kidneys the retention of sodium (caused by excess insulin) has now been corrected and his hypertension has resolved. The pathophysiology of Syndrome X is predictable. The reversal of this syndrome is also predictable and repeatable! As a matter of fact this exact method is being employed by over 700 chiropractic practices in the United States and Canada as well as many medical practices. Tens of thousands of patients have experienced same benefits described here.

Lack of Sleep Means Lack of Weight Loss

Posted By Dr. Axe On November 3, 2011 

^[1]Sleep is one of the most undervalued essential practices in modern society.  In 1910, an average night’s sleep was 9 hours. By 1975, it was down to 7.5 hours. From 2000 to 2002, polls found that it had fallen to 6.9 hours. Today, many people average just 5-6 hours of sleep per night.

At the same time, obesity rates have doubled! Sleep and the neuroendocrine system are intricately entwined. Chronic lack of sleep is thought to be linked to diabetes, hypertension, obesity and memory loss. Lack of sleep increases blood pressure ^[2] and the risk of heart disease.

A recent study by the University of Chicago found that cutting sleep from 8 hours to 4 hours a night for less than one week produced physiological changes that resembled the effects of advanced aging and early diabetes.

Those changes happened in less than one week!

The study’s participants took 40% longer to regulate their blood-sugar levels after eating and their ability to secrete insulin and respond to it decreased by 30%.

Lack of sleep affects the secretion of thyroid-stimulating hormone and increased levels of the “stress hormone,” cortisol.

The study found that recovery occurred and above-average functioning occurred when the subjects slept more than 8 hours a night.

So how does sleep affect weight?

Sleep affects the release of hormones by the hypothalamic-pituitary axes (HPA) and the autonomic nervous system (ANS). Sleep triggers or inhibits the production or release of various hormones.

Growth hormone is affected by sleep. You can work out for hours, but if you don’t get enough sleep your body is not going to turn fat into muscle.

Lack of sleep raises the level of cortisol which triggers the fight-or-flight response. During stress, our body shuts down normal maintenance. It activates fat storage and releases lots of sugar (for instant energy) into the bloodstream. It depletes the body of nutrients and triggers cravings for simple carbohydrates and sugar. Chronic stress promotes insulin resistance.

Leptin and ghrelin are two very important appetite-controlling hormones that are linked to sleep. Leptin suppresses appetite and ghrelin increases it. When people are subjected to sleep loss, leptin levels fall and ghrelin levels rise. Even when they received plenty of nutrition, people that didn’t get adequate sleep were compelled to eat more. Because leptin levels were low, their brains just didn’t get the message that they were satiated—instead they just kept getting the message: “Hungry! Eat!” When deprived of sleep, study participant’s desire for high-carbohydrate and calorie-dense foods increased by 45%.

A joint study conducted by Stanford University and the University of Wisconsin measured leptin and ghrelin levels, body fat and sleep amounts in 1000 people. They found that those who slept less than 8 hours a night had low leptin levels, high ghrelin levels and higher levels of body fat. The participants that slept the fewest hours a night weighed the most.

Another study, presented at the 2006 American Thoracic Society International Conference, came up with some confounding information. 70,000 middle-aged women were studied for 16 years.

The study found that:

• Women who sleep 5 hours or less weigh more than those that sleep 7 hours.
• Women who sleep 5 hours per night are 32% more likely to experience weight gain of 33 pounds or more and 15% more likely to become obese than those that sleep 7 hours.
• Women that sleep 6 hours a night are 12% more likely to gain 33 pounds or more and 6% more likely to become obese than those that sleep 7 hours.

What was confounding in this particular study is the fact that the women that slept less did not eat more.

“Prior studies have shown that after just a few days of sleep restriction, the hormones that control appetite cause people to become hungrier, so we thought that women who slept less might eat more,” says the study’s leader, Sanjay Patel. “But, in fact, they ate less. That suggests that appetite and diet are not accounting for the weight gain in women who sleep less.”

So even though leptin and ghrelin levels might affect appetite, it is more likely that the hormones that affect the metabolism of glucose and insulin-response are behind weight gain during sleep deprivation.

Dr. Axe's Action Steps

1. Wake up and go to bed at the same time everyday. Ideally, you should be in bed around 10:00-11:00pm.
2. Limit alcohol and caffeine intake.
3. Don’t eat late at night.
4. Take evening baths.
5. Exercise regularly, but not before bedtime.
6. Don’t watch TV or use the Internet before bed.
7. Keep the room as dark as possible.
8. Don’t read or work in bed at any time of the day.
9. Write a to-do list at night so you’re not mentally going over one as you try to sleep.
10. Keep the room as dark as possible.
11. Don’t watch TV or use the Internet before bed.
12. Exercise regularly, but not before bedtime.
13. Take evening baths.
14. Don’t eat late at night.
15. Limit alcohol and caffeine intake.
16. Wake up and go to bed at the same time everyday. Ideally, you should be in bed around 10:00-11:00pm.
17. Don’t read or work in bed at any time of the day.
18. Write a to-do list at night so you’re not mentally going over one as you try to sleep.