A recent report from the National Research Council and the Institute of Medicine made headlines when it pointed out how unhealthy Americans are compared with 16 other wealthy, developed nations: Australia, Canada, and all the nations of Europe. This report is nicely summarized in the Journal of the American Medical Association (JAMA February 27, 2013, vol. 309, pp 771-772) The following is a precis of this report. I might add that no cause was found for our lowest ranking in health and highest ranking in death rates.
Until age 75, we have the highest death rate, compared with those other countries, but if we reach age 75 then we have a higher life expectancy.
We have higher rates of disease and injury especially in motor vehicle accidents involving alcohol.
US infants are least likely to reach their first birthdays, compared to the other 16 countries.
We have lower birth weights, and mortality rates up to age 5 are also higher.
US teenagers die at a higher rate from motor vehicle crashes and homicides.
US teenagers also have the highest pregnancy rate and the highest prevalence of sexually transmitted diseases. They are also the least likely to practice safe sex.
We have the highest incidence of AIDS.
We also have the highest obesity rates and the highest rate of adult-onset diabetes, as well as the second highest rate of death from ischemic heart disease.
US patients are more likely to return to the emergency room and to be readmitted after hospital discharge.
We are less likely to smoke and drink, but we are more likely to abuse drugs and not fasten seat belts.
We have the highest child poverty rate.
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Even our wealthiest white citizens have a higher mortality than matched adults in other countries.
And no one reason or cause seems to explain our unhealthiness, especially since we pay more per capita on health care than do any of the other industrialized democracies.
Tuesday, February 26, 2013
Monday, February 18, 2013
Statins
Statins have been in the news lately, so I thought I might write a few words about them. Statins chemically mimic an enzyme in the liver (HMG-Co-A) that is used in the first step of making cholesterol, and when the liver tries to use the statin, then overall less cholesterol is produced, and your serum levels fall. The body makes most of its cholesterol between midnight and dawn, which is why the earliest statins, which had a short half-life, were prescribed to be taken at bedtime. But the later statins such as Lipitor and Crestor have a much longer half-life, so they may be taken at any time during the day, and food does not significantly affect their absorption.
There is absolutely no question, based on numerous clinical studies, that statins definitely provide secondary protection against a heart attack or a stroke. That is, if you have had a heart attack or a (non-hemorrhagic) stroke, taking a statin will lower your risk of having a second one. Whether or not you should also take aspirin should be decided by you and your doctor, and adding a regime of exercise provides an additional benefit above and beyond the benefit from taking the statin. All statins appear to give equivalent results.
The question of primary prevention is a little more complicated. There is no satisfactory study showing that a person with no risks for heart disease other than elevated cholesterol benefits from taking a statin. Many doctors will prescribe a statin for a patient with a risk factor for coronary artery disease or a stroke: smokers, diabetics, patients with ASCVD, and patients with significant narrowing of a carotid artery. There is evidence for decreased mortality when a patient with documented ASCVD takes a statin, even in the absence of a heart attack.
I have found the most troublesome side-effect to be leg cramps, which are sometimes severe enough to awaken patients at night. Often the leg pains can be helped by reducing the dose of the statin or switching to another brand. The statins can also raise liver enzymes, and some patients report difficulty with mental concentration. There is some weak data that statin use can slightly increase your risk of developing adult-onset diabetes, but it may also reduce your risk of getting cancer (see my earlier blog about this). The muscle cramps and occasional myositis may be related to the fact that all statins lower the level of Coenzyme Q-10.
Statins are one of the few drugs where the ingestion of grapefruit juice should probably be avoided. A chemical in grapefruit inhibits the P450 enzyme that degrades statins, so the use of grapefruits can raise the level of the statin in your blood and your liver.
Let me close by summarizing the results of the JUPITER study. This study showed that in patients who had an elevated CRP (a marker of inflammation) who also took a statin had a lower incidence of heart attacks, coronary artery surgery, and strokes. Strangely enough, there was no decrease in the indicence of deaths from coronary artery disease, but there were 20% fewer deaths from all causes, mainly cancer.
There are many, many clinical trials of statins in various medical conditions being conducted, and you can expect to see future stories about their benefits, side effects, or, occasionally, a null result. There was also a recent retrospective study showing that patients that lowered their LDL cholesterol through diet had an increased rate of cardiac events and deaths, so it may well be that the beneficial effect of statins is due more
to their anti-inflammatory effect than to their lowering cholesterol.
There is absolutely no question, based on numerous clinical studies, that statins definitely provide secondary protection against a heart attack or a stroke. That is, if you have had a heart attack or a (non-hemorrhagic) stroke, taking a statin will lower your risk of having a second one. Whether or not you should also take aspirin should be decided by you and your doctor, and adding a regime of exercise provides an additional benefit above and beyond the benefit from taking the statin. All statins appear to give equivalent results.
The question of primary prevention is a little more complicated. There is no satisfactory study showing that a person with no risks for heart disease other than elevated cholesterol benefits from taking a statin. Many doctors will prescribe a statin for a patient with a risk factor for coronary artery disease or a stroke: smokers, diabetics, patients with ASCVD, and patients with significant narrowing of a carotid artery. There is evidence for decreased mortality when a patient with documented ASCVD takes a statin, even in the absence of a heart attack.
I have found the most troublesome side-effect to be leg cramps, which are sometimes severe enough to awaken patients at night. Often the leg pains can be helped by reducing the dose of the statin or switching to another brand. The statins can also raise liver enzymes, and some patients report difficulty with mental concentration. There is some weak data that statin use can slightly increase your risk of developing adult-onset diabetes, but it may also reduce your risk of getting cancer (see my earlier blog about this). The muscle cramps and occasional myositis may be related to the fact that all statins lower the level of Coenzyme Q-10.
Statins are one of the few drugs where the ingestion of grapefruit juice should probably be avoided. A chemical in grapefruit inhibits the P450 enzyme that degrades statins, so the use of grapefruits can raise the level of the statin in your blood and your liver.
Let me close by summarizing the results of the JUPITER study. This study showed that in patients who had an elevated CRP (a marker of inflammation) who also took a statin had a lower incidence of heart attacks, coronary artery surgery, and strokes. Strangely enough, there was no decrease in the indicence of deaths from coronary artery disease, but there were 20% fewer deaths from all causes, mainly cancer.
There are many, many clinical trials of statins in various medical conditions being conducted, and you can expect to see future stories about their benefits, side effects, or, occasionally, a null result. There was also a recent retrospective study showing that patients that lowered their LDL cholesterol through diet had an increased rate of cardiac events and deaths, so it may well be that the beneficial effect of statins is due more
to their anti-inflammatory effect than to their lowering cholesterol.
Sunday, February 17, 2013
Stress and the Broken Heart
Gilbert and Sullivan were correct to have Ko-Ko sing in "The Mikado" that "a little tomtit" died of a broken heart. There is a broken heart syndrome well-known to cardiologists, who also refer to it as stress cardiomyopathy or takotsubo cardiomyopathy. Sudden stress, usually of an emotional nature, can cause sudden cardiac death, angina, and acute congestive heart failure. I will first discuss the effects of acute stress on the heart, and then the far-reaching effects of chronic stress on the heart and the circulatory system.
The broken-heart syndrome, which usually affects women, is thought to be due to the effects of an acute surge of adrenalin on the heart. Such an acute surge can cause reversible spasm of the coronary arteries, ballooning of the left ventricle, and a stunning of the cardiac muscle syncytium. The precise mechanism is not known, but the effect is real, and has been observed many times. Cardiac enzyme tests for a heart attack are normal, but an echocardiogram will show a ballooning and dysfunction of a portion of the left ventricle, thereby causing acute heart failure. Coronary artery catheterization shows no sign of blockage, and the EKG changes are not those shown by a heart attack. Such an attack which can be manifested by acute chest pain and shortness of breath can look like an anxiety attack, but a cardiac exam will typically show signs of heart failure. In some cases, cardiac arrhythmias can also occur. Recovery with proper treatment tends to be rapid, typically within one week. The interval between the emotional shock (often caused by the death of a spouse) and the cardiac event is variable, and any severe emotional shock can be the trigger. There is even one (apocryphal?) story of a woman having such an attack after winning the lottery.
Chronic stress caused by anxiety or depression or problems at home or at work can also cause deleterious chemical changes in the bloodstream, with eventual effects on the circulation of coronary as well as peripheral arteries, and a possible fatiguing of the cardiac muscle. We know that the stress caused by these mental conditions can cause elevated adrenalin and cortisol levels, as well as an elevated pulse rate and white blood count. This effect also raises blood pressure and makes the blood more liable to clot. There is a concomitant elevation of fatty acids, cholesterol and triglycerides. Whether or not chronic stress can lead to heart disease is not known, but, as indicated, chronic stress elevates all the chemicals in our bloodstream that we would prefer to be lower to protect against cardiac disease.
Unfortunately, there is as yet little or no clinical data to show that lowering stress decreases the risk of developing a cardiac problem; even the type A hypothesis has not been well proven. And I doubt (but who knows?) that the effect of a daily glass of wine on lowering the risk of a heart attack is due to its relieving of stress. Since marijuana mellows most users, it will be interesting to examine the heart attack rates in Colorado and Washington State in 10 years, to see if there is any effect on the incidence of cardiac events that could be attributed to the chronic smoking of marijuana.
The broken-heart syndrome, which usually affects women, is thought to be due to the effects of an acute surge of adrenalin on the heart. Such an acute surge can cause reversible spasm of the coronary arteries, ballooning of the left ventricle, and a stunning of the cardiac muscle syncytium. The precise mechanism is not known, but the effect is real, and has been observed many times. Cardiac enzyme tests for a heart attack are normal, but an echocardiogram will show a ballooning and dysfunction of a portion of the left ventricle, thereby causing acute heart failure. Coronary artery catheterization shows no sign of blockage, and the EKG changes are not those shown by a heart attack. Such an attack which can be manifested by acute chest pain and shortness of breath can look like an anxiety attack, but a cardiac exam will typically show signs of heart failure. In some cases, cardiac arrhythmias can also occur. Recovery with proper treatment tends to be rapid, typically within one week. The interval between the emotional shock (often caused by the death of a spouse) and the cardiac event is variable, and any severe emotional shock can be the trigger. There is even one (apocryphal?) story of a woman having such an attack after winning the lottery.
Chronic stress caused by anxiety or depression or problems at home or at work can also cause deleterious chemical changes in the bloodstream, with eventual effects on the circulation of coronary as well as peripheral arteries, and a possible fatiguing of the cardiac muscle. We know that the stress caused by these mental conditions can cause elevated adrenalin and cortisol levels, as well as an elevated pulse rate and white blood count. This effect also raises blood pressure and makes the blood more liable to clot. There is a concomitant elevation of fatty acids, cholesterol and triglycerides. Whether or not chronic stress can lead to heart disease is not known, but, as indicated, chronic stress elevates all the chemicals in our bloodstream that we would prefer to be lower to protect against cardiac disease.
Unfortunately, there is as yet little or no clinical data to show that lowering stress decreases the risk of developing a cardiac problem; even the type A hypothesis has not been well proven. And I doubt (but who knows?) that the effect of a daily glass of wine on lowering the risk of a heart attack is due to its relieving of stress. Since marijuana mellows most users, it will be interesting to examine the heart attack rates in Colorado and Washington State in 10 years, to see if there is any effect on the incidence of cardiac events that could be attributed to the chronic smoking of marijuana.
Monday, January 21, 2013
Do Antioxidants Block Cancer Treatment?
This blog is based on a suppositional paper written by Dr. James Watson, of DNA fame, and published in Open Biology. He argues that the presence of antioxidants in cancer cells blocks anticancer treatments. The only clinical evidence of which I am aware that supports his thesis is the study of Finnish male smokers which showed that those who took antioxidant supplements had a higher incidence of lung cancer, and there also are several studies of cancer cells in vitro that seem to demonstrate a similar effect of antioxidants.
Dr. Watson's paper is long and highly technical, so I will summarize the key points here and try to interpret them for the reader who is not heavily involved in cancer research. I might just begin by remarking that no interventional diet study involving the addition of antioxidants to the daily diet (beta carotene, Vitamin E, selenium, Vitamin A, and Vitamin C) has been shown to prolong the human life span. I will also touch on the possible reason for the benefit of aspirin in cancer prevention and why tests are now being done to see if the diabetes drug metformin has anti-cancer properties.
Most agents used to kill organ (non bone-marrow) cancers, including Xrays and chemotherapy, work by generating ROS, or reactive oxygen species (such as OH-) which block key steps in the cell cycle and thereby hasten apoptosis, or cell self-destruction. The presence of ROS also generates a hypoxic environment in the cell, which drives a conversion of the cell from an epithelial to a mesenchymal type. But at the same time, in self-protection, the presence of ROS causes the cell to generate antioxidants, which render the cell resistant if not immune to both ionizing radiation and chemotherapy. In addition, mesenchymal cells are more prone to travel and metastasize. So the presence of ROS is both an accelerator and a brake.
The presence of the Myc gene activator can drive cancer cells forward, as can the presence of inflammatory cytokines such as interleukin-6. It is therefore theorized than the cancer-preventing property of daily aspirin (most convincingly demonstrated in colon cancer) derives from its anti-inflammatory and cytokine suppressing effect. And it has been shown that the turning off of Myc drives cancer cells towards apoptosis.
Now in mouse models of cancer, the anti-diabetic drug metformin preferentially killed mesenchymal stem cells, which cells are the most resistant to chemotherapy and the most prone to metastasize. The reason for this is probably its blocking of oxidative phosphorylation. There are currently a number of ongoing studies where metformin is being added to standard anticancer chemotherapies in humans to look for an enhanced killing effect.
To summarize Dr. Watson's thesis, and again I refer the interested reader to his paper, anticancer chemotherapy and Xrays generate ROS. The presence of ROS has a two-fold effect: it drives the cancer cell towards apoptosis, or cell death, and at the same time it induces antioxidants which render the cell resistant to further anticancer treatment as well as inducing a transformation to a mesenchymal stem cell. It is not known if the antioxidants themselves drive this change in addition to inducing resistance to treatment.
Based on this theory, and the limited data to date, it would seem prudent to avoid adding antioxidants to your diet which in theory would increase the antioxidant levels in every cell in your body by diffusion. Remember the study of Vitamin E, touted as an oxidant, which showed (in two different studies) that an increase in the intake of Vitamin E increased the rate of cardiac events and heart attacks.
Dr. Watson's paper is long and highly technical, so I will summarize the key points here and try to interpret them for the reader who is not heavily involved in cancer research. I might just begin by remarking that no interventional diet study involving the addition of antioxidants to the daily diet (beta carotene, Vitamin E, selenium, Vitamin A, and Vitamin C) has been shown to prolong the human life span. I will also touch on the possible reason for the benefit of aspirin in cancer prevention and why tests are now being done to see if the diabetes drug metformin has anti-cancer properties.
Most agents used to kill organ (non bone-marrow) cancers, including Xrays and chemotherapy, work by generating ROS, or reactive oxygen species (such as OH-) which block key steps in the cell cycle and thereby hasten apoptosis, or cell self-destruction. The presence of ROS also generates a hypoxic environment in the cell, which drives a conversion of the cell from an epithelial to a mesenchymal type. But at the same time, in self-protection, the presence of ROS causes the cell to generate antioxidants, which render the cell resistant if not immune to both ionizing radiation and chemotherapy. In addition, mesenchymal cells are more prone to travel and metastasize. So the presence of ROS is both an accelerator and a brake.
The presence of the Myc gene activator can drive cancer cells forward, as can the presence of inflammatory cytokines such as interleukin-6. It is therefore theorized than the cancer-preventing property of daily aspirin (most convincingly demonstrated in colon cancer) derives from its anti-inflammatory and cytokine suppressing effect. And it has been shown that the turning off of Myc drives cancer cells towards apoptosis.
Now in mouse models of cancer, the anti-diabetic drug metformin preferentially killed mesenchymal stem cells, which cells are the most resistant to chemotherapy and the most prone to metastasize. The reason for this is probably its blocking of oxidative phosphorylation. There are currently a number of ongoing studies where metformin is being added to standard anticancer chemotherapies in humans to look for an enhanced killing effect.
To summarize Dr. Watson's thesis, and again I refer the interested reader to his paper, anticancer chemotherapy and Xrays generate ROS. The presence of ROS has a two-fold effect: it drives the cancer cell towards apoptosis, or cell death, and at the same time it induces antioxidants which render the cell resistant to further anticancer treatment as well as inducing a transformation to a mesenchymal stem cell. It is not known if the antioxidants themselves drive this change in addition to inducing resistance to treatment.
Based on this theory, and the limited data to date, it would seem prudent to avoid adding antioxidants to your diet which in theory would increase the antioxidant levels in every cell in your body by diffusion. Remember the study of Vitamin E, touted as an oxidant, which showed (in two different studies) that an increase in the intake of Vitamin E increased the rate of cardiac events and heart attacks.
Thursday, January 3, 2013
BMI, Overweight, and Longevity
A recent article in the Journal of the American Medical Association (JAMA, 2013;309: 71-82) created quite a stir when it concluded that adults who were overweight but not obese had a 6% lower all-cause mortality rate. Nutritionists rushed to say that this did not mean that you should gain weight, although if the study had shown the reverse I am sure they would have unanimously recommended weight loss. This was not the first study to reach this conclusion, so I thought I should review it here, along with examining exactly what the BMI purports to measure since all obesity labels were based on the BMI (Basal Metabolic Index) results.
The BMI was first defined by Quetelet in the 1800's as a surrogate number for estimating the amount of body fat. It is defined as mass(kg)/height (m) x height, i.e. the mass divided by the square of one's height. Since your mass increases with your total body volume, it scales with the cube of your height, so it is immediately obvious that only dividing by the square of the height will overestimate the total body fat of taller individuals. Similarly, muscular athletes have very little total body fat, but since muscle has mass, the BMI will overestimate their total body fat as well. It is trivial to note that since most elderly patients have some degree of osteoporosis and therefore lighter bones, the BMI will mistakenly classify some of them as underweight.
I should also mention here that in 1998 the U.S. lowered its cutoff for the lower limit of overweight from a BMI of 27.8 to 25.0, in accordance with the WHO standards, thereby immediately reclassifying millions of Americans as overweight who the day before the change had "normal" weight. In addition, doctors in the US do not agree on the healthy lower limit of the BMI for adult women, and the WHO does not have the classification of "underweight". And the 0.5 to 1.0 inches in height that you lose with age increases your BMI without you actually gaining any weight.
The consensus in the US is that a BMI of 18.5 to 25 is normal weight, 25 to 30 is overweight, and greater than 30 is obese. Using these definitions, there have already been two published studies, one of diabetic patients and one of patients with ASCVD, and both demonstrated that overweight patients had a lower death rate than both normal weight and obese patients. No one has an explanation for these results, nor have I even seen theories that attempt to explain them. The JAMA study looked at 97 studies of all-cause mortality, encompassing 270,000 deaths and over 2,800,000 subjects, so it is fairly comprehensive.
We are left with the paradox that being overweight by BMI standards statistically increases your risk for high blood pressure, diabetes, ASCVD, stroke and some cancers, yet overall it is protective of mortality.
In a previous blog I listed the 11 countries in order of longevity. I will repeat the list here adding the mean BMI of each country. Except for Japan, #1 and with the lowest BMI, there is no clear pattern:
Japan---22, Switzerland---25, Australia---26, Italy 23.5, Israel---25, Iceland---26, Spain---24.5, France---23.5, Canada---25.5, Singapore---22, and New Zealand---26.6.
So once again we are left with "a beautiful theory ruined by an ugly fact" to quote a Nobel scientist. Perhaps we should re-normalize the BMI values and re-define normal weight. Or perhaps we should have a separate classification of "healthy BMI" and "unhealthy BMI". Or, more likely, there is a confounding fact of which we are unaware which would explain the results, but so far there are no candidates. It does make me feel better with my BMI of 27 because at 6'2" I doubt that I could get down to 185 pounds, even if I wanted to. I think we underestimate the genetic effects on us of our parents' diseases, especially parents of the same sex.
The BMI was first defined by Quetelet in the 1800's as a surrogate number for estimating the amount of body fat. It is defined as mass(kg)/height (m) x height, i.e. the mass divided by the square of one's height. Since your mass increases with your total body volume, it scales with the cube of your height, so it is immediately obvious that only dividing by the square of the height will overestimate the total body fat of taller individuals. Similarly, muscular athletes have very little total body fat, but since muscle has mass, the BMI will overestimate their total body fat as well. It is trivial to note that since most elderly patients have some degree of osteoporosis and therefore lighter bones, the BMI will mistakenly classify some of them as underweight.
I should also mention here that in 1998 the U.S. lowered its cutoff for the lower limit of overweight from a BMI of 27.8 to 25.0, in accordance with the WHO standards, thereby immediately reclassifying millions of Americans as overweight who the day before the change had "normal" weight. In addition, doctors in the US do not agree on the healthy lower limit of the BMI for adult women, and the WHO does not have the classification of "underweight". And the 0.5 to 1.0 inches in height that you lose with age increases your BMI without you actually gaining any weight.
The consensus in the US is that a BMI of 18.5 to 25 is normal weight, 25 to 30 is overweight, and greater than 30 is obese. Using these definitions, there have already been two published studies, one of diabetic patients and one of patients with ASCVD, and both demonstrated that overweight patients had a lower death rate than both normal weight and obese patients. No one has an explanation for these results, nor have I even seen theories that attempt to explain them. The JAMA study looked at 97 studies of all-cause mortality, encompassing 270,000 deaths and over 2,800,000 subjects, so it is fairly comprehensive.
We are left with the paradox that being overweight by BMI standards statistically increases your risk for high blood pressure, diabetes, ASCVD, stroke and some cancers, yet overall it is protective of mortality.
In a previous blog I listed the 11 countries in order of longevity. I will repeat the list here adding the mean BMI of each country. Except for Japan, #1 and with the lowest BMI, there is no clear pattern:
Japan---22, Switzerland---25, Australia---26, Italy 23.5, Israel---25, Iceland---26, Spain---24.5, France---23.5, Canada---25.5, Singapore---22, and New Zealand---26.6.
So once again we are left with "a beautiful theory ruined by an ugly fact" to quote a Nobel scientist. Perhaps we should re-normalize the BMI values and re-define normal weight. Or perhaps we should have a separate classification of "healthy BMI" and "unhealthy BMI". Or, more likely, there is a confounding fact of which we are unaware which would explain the results, but so far there are no candidates. It does make me feel better with my BMI of 27 because at 6'2" I doubt that I could get down to 185 pounds, even if I wanted to. I think we underestimate the genetic effects on us of our parents' diseases, especially parents of the same sex.
Friday, December 28, 2012
How to Lose Weight
There has been a recent upsurge in articles advising people how to lose weight "successfully", i.e. to lose weight and keep it off. There are discussions and theories about fructose in the diet, about insulin resistance, about the relative merits of the Ornish and Atkins diet, about stomach-banding operations, about the role of exercise and heredity, etc. But we still know far too little about how the body processes ingested calories of all kinds---fats, proteins, and carbohydrates.
What we do know is that the body has the enzymes necessary to interconvert carbohydrates and fats, protein and fats, and carbohydrates and protein, with the exception of the eight essential amino acids and the three necessary fats. We will assume an adequate intake of these latter two as well as sufficient daily vitamin intake, be it contained in the food eaten or taken as a daily supplement. And let us recognize that eating is like breathing, in that there is an involuntary autonomic drive, which can be overridden by voluntary means.
Not to be obvious, but we always have examples of people who are grossly overweight and dangerously underweight, viz. sumo wrestlers and anorectic patients (and I am not here going to discuss the distorted body images that are involved).
Let us first consider the marvelous caloric balancing act that the body does daily and therefore yearly without any conscious guidance. It is generally agreed that ingestion of approximately 3500 calories can be converted to one pound of flesh, and oxidation of one pound of flesh releases 3500 calories (remember that part of the food we eat daily is oxidized just to generate the heat needed to keep our body temperature fixed and comfortable). We also know that exercise generates heat, so that the body shivers when it is cold as a way of raising its temperature. Now there are about 350 days in a year, and if we divide 3500 calories by 350 days we see that the body must ingest fewer than 10 extra calories a day or burn it off in some manner if we don't want to gain weight. No one knows how the brain instructs the body to do this marvelous act, and yet most of us have weights that are fairly constant year to year, which means that the brain is micromanaging our caloric intake and expenditure in a way that we could not possibly do consciously. Could any of us eat the same amount of calories plus or minus 10 calories on a daily basis? I think not, no matter how committed we were. Remember that in a 2000 calorie daily diet, 10 calories is 0.5% of the daily allotment, and even if we had the will, we do not have the skill to measure the total daily calories we eat to an accuracy of 0.5%.
So how does one go about losing weight? The body has a fixed daily energy expenditure to keep your core temperature at 98.7 or whatever your normal temperature is. Then there is an additional energy expenditure, also gained by oxidizing food or flesh, for the motion of your muscles, both involuntary (e.g. heart and diaphragm) and voluntary, as in your skeletal muscles. That's it. So if we ingest more calories than are needed to be oxidized to supply our daily energy requirements we will gain weight, and if we ingest less, we will lose weight. In other words, there are two types of foods: too much and too little. (And once we solve the weight problem we can proceed further as to food pyramids and the like.)
At this point, I will give a small nod to the nutritionists, and add that the two most useless types of calories come in the form of white potatoes and white bread. Both have a high glycemic index, potato more than bread, and therefore stress your insulin-glucose system. No one on a diet should eat either of them, IMHO. The question of whether or not you should eat chocolate before your main meal so as to decrease your appetite and therefore eat less remains unanswered.
Now for the hard part: actual weight loss. There are myriads of suggestions out there including drinking water before meals, leaving the table before you feel full, eating smaller portions, drinking more caffeinated beverages, eating more fiber, taking diet pills, exercising more, etc. But the advice begs the question of actually losing weight. Besides feeling your clothes become looser, the only way to know if you have lost weight is to step on a scale. And I mean an old-fashioned scale, not a digital one which can have errors.
Weigh yourself today and then re-weigh yourself tomorrow, or in two days, or at least in seven days. If you have gained weight then eat less, and keep on eating less between successive weighings until you start to lose weight. Then just continue. So long as you eat fewer calories than your body burns, you will lose weight. It all comes down to a fuel-energy balance, which is why your car weighs more when you fill it up with gas and then steadily loses weight as you burn the gas in the tank and it is used up. If you find as most people do that exercise both makes you feel better from the endorphins it generates and helps you to lose weight by suppressing your appetite and burning off calories, then do it.If it helps you to make a daily food/calorie list, then do it. If it helps you to omit lunch (I never have lunch when I am at home) then do so.
Everyone has a different pattern for weight loss, just as everyone has a different need for sleep. We are all wired differently, but the iron laws of physiology (physics as applied to the body) tell us that fuel is either oxidized or stored, and the amount of fuel ingested is the ultimate determinant. And yes, people do have different fundamental metabolic rates, so that a diet that works for one person may not work for another.
And no one knows why everyone likes ice cream: I personally think that it is because it is similar in taste to frozen mother's milk: sugar and fat.
What we do know is that the body has the enzymes necessary to interconvert carbohydrates and fats, protein and fats, and carbohydrates and protein, with the exception of the eight essential amino acids and the three necessary fats. We will assume an adequate intake of these latter two as well as sufficient daily vitamin intake, be it contained in the food eaten or taken as a daily supplement. And let us recognize that eating is like breathing, in that there is an involuntary autonomic drive, which can be overridden by voluntary means.
Not to be obvious, but we always have examples of people who are grossly overweight and dangerously underweight, viz. sumo wrestlers and anorectic patients (and I am not here going to discuss the distorted body images that are involved).
Let us first consider the marvelous caloric balancing act that the body does daily and therefore yearly without any conscious guidance. It is generally agreed that ingestion of approximately 3500 calories can be converted to one pound of flesh, and oxidation of one pound of flesh releases 3500 calories (remember that part of the food we eat daily is oxidized just to generate the heat needed to keep our body temperature fixed and comfortable). We also know that exercise generates heat, so that the body shivers when it is cold as a way of raising its temperature. Now there are about 350 days in a year, and if we divide 3500 calories by 350 days we see that the body must ingest fewer than 10 extra calories a day or burn it off in some manner if we don't want to gain weight. No one knows how the brain instructs the body to do this marvelous act, and yet most of us have weights that are fairly constant year to year, which means that the brain is micromanaging our caloric intake and expenditure in a way that we could not possibly do consciously. Could any of us eat the same amount of calories plus or minus 10 calories on a daily basis? I think not, no matter how committed we were. Remember that in a 2000 calorie daily diet, 10 calories is 0.5% of the daily allotment, and even if we had the will, we do not have the skill to measure the total daily calories we eat to an accuracy of 0.5%.
So how does one go about losing weight? The body has a fixed daily energy expenditure to keep your core temperature at 98.7 or whatever your normal temperature is. Then there is an additional energy expenditure, also gained by oxidizing food or flesh, for the motion of your muscles, both involuntary (e.g. heart and diaphragm) and voluntary, as in your skeletal muscles. That's it. So if we ingest more calories than are needed to be oxidized to supply our daily energy requirements we will gain weight, and if we ingest less, we will lose weight. In other words, there are two types of foods: too much and too little. (And once we solve the weight problem we can proceed further as to food pyramids and the like.)
At this point, I will give a small nod to the nutritionists, and add that the two most useless types of calories come in the form of white potatoes and white bread. Both have a high glycemic index, potato more than bread, and therefore stress your insulin-glucose system. No one on a diet should eat either of them, IMHO. The question of whether or not you should eat chocolate before your main meal so as to decrease your appetite and therefore eat less remains unanswered.
Now for the hard part: actual weight loss. There are myriads of suggestions out there including drinking water before meals, leaving the table before you feel full, eating smaller portions, drinking more caffeinated beverages, eating more fiber, taking diet pills, exercising more, etc. But the advice begs the question of actually losing weight. Besides feeling your clothes become looser, the only way to know if you have lost weight is to step on a scale. And I mean an old-fashioned scale, not a digital one which can have errors.
Weigh yourself today and then re-weigh yourself tomorrow, or in two days, or at least in seven days. If you have gained weight then eat less, and keep on eating less between successive weighings until you start to lose weight. Then just continue. So long as you eat fewer calories than your body burns, you will lose weight. It all comes down to a fuel-energy balance, which is why your car weighs more when you fill it up with gas and then steadily loses weight as you burn the gas in the tank and it is used up. If you find as most people do that exercise both makes you feel better from the endorphins it generates and helps you to lose weight by suppressing your appetite and burning off calories, then do it.If it helps you to make a daily food/calorie list, then do it. If it helps you to omit lunch (I never have lunch when I am at home) then do so.
Everyone has a different pattern for weight loss, just as everyone has a different need for sleep. We are all wired differently, but the iron laws of physiology (physics as applied to the body) tell us that fuel is either oxidized or stored, and the amount of fuel ingested is the ultimate determinant. And yes, people do have different fundamental metabolic rates, so that a diet that works for one person may not work for another.
And no one knows why everyone likes ice cream: I personally think that it is because it is similar in taste to frozen mother's milk: sugar and fat.
Tuesday, December 25, 2012
Tylenol/Acetaminophen/Paracetamol
Shortly after I posted my blog on aspirin, several readers asked for similar information on Tylenol. Tylenol is the trade name for acetaminophen. Paracetamol is the chemical name throughout Europe. Phenacitin used to be marketed for the same purposes, since it is metabolized to acetaminophen in the body, but several studies suggested that phenacitin was carcinogenic, while paracetamol was not. The abbreviation for paracetamol is APAP.
APAP is used for pain relief and to reduce fever, and its potency for both purposes is equivalent to aspirin. At high doses (1,000 mg) there is some evidence of an anti-inflammatory effect, but it is never marketed as such. Unlike aspirin, APAP as a fever reducer is safe for children of all ages, provided the dosage limits are observed. Traditionally the dose of APAP for adults has been 2x325=650 mg or 2x500=1,000mg per dose. The suggested maximum dose used to be 4,000 mg/day. However, one very good article in NEJM showed that cirrhotics could suffer increased liver damage at total doses above 3,600 mg/day, and since APAP toxicity is the leading cause of acute liver failure in the world, the suggested maximum has been lowered to 3,000 mg/day by the FDA. The FDA can only suggest this maximum dose, and is not permitted to mandate it.
APAP starts to work to relieve pain within 10 minutes of ingestion. It is metabolized by the liver, and its half-life varies between one and four hours. The liver's act of metabolizing it depletes the liver's store of glutathione, and this in turn makes APAP potentially toxic to the liver, an effect which is worsened by the simultaneous ingestion of alcohol. APAP is metabolized by three different chemical processes in the liver; the one mediated by cytochrome P450 (a name familiar to doctors and pharmacists) produces the toxic metabolite.
APAP will relieve the pain of osteoarthritis, but unlike aspirin and other NSAIDs does not affect the inflammation of the joint. Although APAP does not attach to platelets and is not a blood thinner or anti-coagulant, sustained daily use may increase the chance of gastric bleeding. The underlying process is poorly understood because we still do not know the full mechanism of action of APAP, although several suggestions have been advanced. One is that its pain-relieving action involves cannabinoid receptors in the brain(!). As a side note, APAP can relieve pain in dogs, but is toxic to cats through the formation of methemoglobin which inhibits the oxygen-carrying ability of the blood.
And it is a tribute to the power of advertising that so many customers still will pay extra for the brand name Tylenol rather than the generic acetaminophen.
APAP is used for pain relief and to reduce fever, and its potency for both purposes is equivalent to aspirin. At high doses (1,000 mg) there is some evidence of an anti-inflammatory effect, but it is never marketed as such. Unlike aspirin, APAP as a fever reducer is safe for children of all ages, provided the dosage limits are observed. Traditionally the dose of APAP for adults has been 2x325=650 mg or 2x500=1,000mg per dose. The suggested maximum dose used to be 4,000 mg/day. However, one very good article in NEJM showed that cirrhotics could suffer increased liver damage at total doses above 3,600 mg/day, and since APAP toxicity is the leading cause of acute liver failure in the world, the suggested maximum has been lowered to 3,000 mg/day by the FDA. The FDA can only suggest this maximum dose, and is not permitted to mandate it.
APAP starts to work to relieve pain within 10 minutes of ingestion. It is metabolized by the liver, and its half-life varies between one and four hours. The liver's act of metabolizing it depletes the liver's store of glutathione, and this in turn makes APAP potentially toxic to the liver, an effect which is worsened by the simultaneous ingestion of alcohol. APAP is metabolized by three different chemical processes in the liver; the one mediated by cytochrome P450 (a name familiar to doctors and pharmacists) produces the toxic metabolite.
APAP will relieve the pain of osteoarthritis, but unlike aspirin and other NSAIDs does not affect the inflammation of the joint. Although APAP does not attach to platelets and is not a blood thinner or anti-coagulant, sustained daily use may increase the chance of gastric bleeding. The underlying process is poorly understood because we still do not know the full mechanism of action of APAP, although several suggestions have been advanced. One is that its pain-relieving action involves cannabinoid receptors in the brain(!). As a side note, APAP can relieve pain in dogs, but is toxic to cats through the formation of methemoglobin which inhibits the oxygen-carrying ability of the blood.
And it is a tribute to the power of advertising that so many customers still will pay extra for the brand name Tylenol rather than the generic acetaminophen.
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