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.


   

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.

   

   

Sunday, December 23, 2012

Aspirin

     There have been many articles written about the uses and benefits of aspirin, and I thought I would review them here. Without clouding the discussion, it is important to understand the distinction between primary and secondary benefits from taking a drug. If the drug has a primary benefit, then it prevents the disease or condition from occurring, and everyone might benefit from taking it. If the drug has a secondary benefit, then it is given to patients who already have had an attack of the disease, to prevent a second attack. It is always easier to demonstrate the existence or non-existence of a secondary effect, because the greatest risk factor for an attack of any disease (especially a heart attack) is having had a previous attack of the disease. One example of primary benefit would be in taking medicine as malaria prophylaxis when traveling to a malarious region of the world. Another example would be yellow fever vaccine. One example of a secondary benefit is giving all survivors of a heart attack a daily dose of a statin, which decreases the chance  of having a second heart attack.

     Aspirin, abbreviated ASA, is acetylsalicylic acid. Hippocrates knew that the bark of the willow plant could reduce fever, reduce pain, and reduce inflammation. The active ingredient was salicylic acid, which is an extreme irritant to the stomach. Most people are unaware that not only do we ingest salicylic acid in our diets, but that our bodies synthesize it from benzoic acid.  In 1897 a German chemist working for Bayer, (Felix Hoffman) was able to synthesize ASA by acetylizing salicylic acid, thereby making it much less injurious to the mucosal lining of the human stomach. Although he was not the first to create ASA in the lab, Bayer successfully patented ASA and initially made it available only through a doctor's prescription. Interestingly enough, about the same time Bayer chemists synthesized heroin which is diacetyl morphine, and it was sold  over-the-counter as a non-addictive(!) form of morphine.

     The precise mechanism of the action of aspirin in inhibiting the formation of prostaglandins  (by inhibiting the action of cyclo-oxygenase enzymes) and thromboxanes  is unimportant for the purposes of our discussion, except to note that the inhibition is irreversible and the effects of a single dose of aspirin on the bleeding time can last for 10 days, unlike the other Non-Steroidal Anti-Inflammatory Drugs (NSAID's) such as Advil whose effect is reversible. Since aspirin binds irreversibly to platelets, patients about to undergo surgery are advised to avoid all aspirin and aspirin-containing products for 10 days before surgery, since that is the length of time for which an extension of the bleeding time due to aspirin can be measured. The aspirin achieves this effect through its binding to platelets, which normally can clump together to form a clot and stop bleeding, and platelets bound to aspirin do not clump together.

     Let me list a few known facts. Aspirin is 99% cleared by metabolism in the liver, but if too large a dose is taken the hepatic clearance mechanism is saturated, renal clearance is needed, and the clearance kinetics shift from first order to zero order.  Thus the half-life of a 325 mg pill is 3 hrs, but a 2000 mg dose has a half-life of 9 hours.
In the United states, the basic strength of an adult ASA tablet is 325 mg, and that of a children's tablet 81mg. In Europe the strengths are 300mg and 75 mg respectively, but it makes no apparent clinical difference. Adding caffeine to an aspirin pill increases its pain-reducing strength, hence the popularity of APC's or Excedrin migraine compounds (aspirin, phenaciten or Tylenol, and caffeine). ASA in an effervescent solution is absorbed faster, hence the popularity of Alka-Seltzer. The bleeding effect of aspirin on the stomach can be reduced by taking ASA along with 500 mg of Vitamin C, or 500 mg of SAMe, or 350 mg of deglycyrrhizinated licorice. Many  people who take aspirin on a daily basis develop an iron-deficiency anemia from microscopic bleeding somewhere in the GI tract, and buffering the aspirin seems to make no difference. But buffered ASA is absorbed more slowly, and some recent studies suggest that this is the cause of apparent "aspirin resistance". I should mention here that aspirin given intravenously causes absolutely no GI irritation.

     There are studies showing that taking a daily aspirin (check with your doctor for the suggested dose) can lower the risk of a second heart attack, a stroke following a TIA, a cardiac embolus if you have atrial fibrillation, and cancer of the colon; the first two are examples of secondary prevention, and the last two of primary prevention. It is extremely dangerous to give aspirin to febrile children up to the age of 16  because ASA in a febrile child can trigger a sometimes fatal condition known as Reye's syndrome, which is swelling of the brain compounded by liver failure. A few people develop an acute allergic reaction to aspirin with angioedema. Aspirin exposed to water decomposes back into acetic acid (vinegar) and salicylic acid, hence the vinegary smell when you open a large bottle of aspirin that you  have had for some time.

     There are many drug interactions with ASA; for instance Diamox (acetazolamide) enhances the likelihood of salicylate poisoning, and alcohol increases the risk of gastric bleeding, as does taking Advil or any other NSAID along with aspirin. Because aspirin is  bound to protein in the blood, it can displace other drugs that are bound to protein, thereby raising their plasma concentration to dangerous levels. Some of these drugs are tolbutamide, methotrexate, Dilantin, valproic acid, and probenecid. Taking ASA can  raise the blood level of uric acid. Very rarely through a kidney-based mechanism, aspirin can cause elevated potassium in your blood; this is especially true for diabetics (hyporenin hypoaldosteronism).Aspirin can also inhibit the renal clearance of penicillin G if either drug is given in very high dose. And paradoxically, very high doses of aspirin can cause fever rather than alleviate it.  So whenever you get a prescription for any drug, it would be wise to ask your doctor about possible interactions with ASA.

     And please never forget that unless your doctor gives you permission, never take aspirin with any drug that can cause bleeding, such as Advil, Alleve, Coumadin, Xarelto, and, sometimes, alcohol.

 

   

Wednesday, December 12, 2012

Rabies, Daytime Raccoons, and Bats

     There has been a significant increase in animal rabies in New Jersey this year, so it is prudent and also required by law to have your pet dogs and cats receive an annual rabies vaccine. When they do so, they get a color coded (all red, or all blue,etc. ) and shaped (fire hydrant, disk, sword) medallion for their collar so that at a glance you can determine if an unleashed pet who bit your child has been vaccinated against rabies this year. Rabies travels up from the site of the bite along the nerves to infect the brain, and then moves into the salivary glands of the animal. Raccoons are nocturnal animals by nature and instinct, so if you see a raccoon during the day, it is safest to assume that it is crazed from  rabies, and to call the local animal control office. Do not approach it or let your children or pets come near to it. A rabid raccoon may also become aggressive and charge at you, so it is safest to gather everyone into the house. The raccoon also may  bite other animals (skunks, horses, cows,  squirrels, and foxes and make them rabid as well.
     Bats are natural harborers of the rabies virus, which is a  harmless commensal for the bat. Therefore assume that ALL bats are rabid, and if one flies into your bedroom get out at once and call your doctor. They have small, sharp, needle-like teeth and you may not feel the bite.  If they fly around your campfire, get away from the campfire. And please don't make homes on poles  for bats in the hopes that they will keep your neighborhood free of mosquitoes  because they may  also bite and infect any raccoons, foxes and coyotes  in the neighborhood, as well as you and your loved ones. They also like to nest during the day under closed sun umbrellas by your pool.  (The recent epidemic of bat deaths due to the white-nosed fungus has nothing to do with their carrying rabies, and the most common place to encounter bats is in caves.)
     Three humans in the past 10 years have survived rabies attacks after the virus reached their brain, but they required prolonged stays in an ICU, and their survival was distinctly unusual.

Monday, December 10, 2012

Walking on Eggshells, Usually in the Presence of a SO with a Borderline Personality Disorder

     The information contained herein is taken from a site, http://bpd411.org, operated by the Turtle Island Center for Family Services. It deals with the trials, tribulations and stresses inflicted by BPD's on those around them, especially those who have a close emotional tie with them. It is not uncommon for BP's to exhibit strong narcissistic qualities, but this blog discusses the poor unfortunates who have to deal with them.
Patients with a Borderline Personality Disorder are literally incapable of seeing things from the other person's point of view and generally insist that any stresses in the relationship come from the actions of the other person, who is then forced to "walk on eggshells" to avoid provoking an outburst of emotional or physical aggressiveness. This becomes an impossible situation because any slight or mild criticism or disobedience is seen by the BP as an ego attack that has to be met with full fury.

     The victim in this situation has  to maintain an exceptionally high and excessive level of vigilance over both actions and words, as well as extreme caution in some situations and thus we are dealing with a relationship that is both tense and dysfunctional for the tiptoer. The SO of the BPD feels that if (s)he is  careful enough  then (s)he  will avoid provoking that craziness and rage of which the BP is capable of unleashing at the least perceived provocation. The SO feels that there must be some way (s)he can get it "right" so that the relationship  can be OK again. The SO is generally told by the BP over and over that any problems are all the SO's fault, and any negative issues in the relationship derive from the SO's behavior. And any self-blaming attitude the SO might have in always vigorously emphasized and reinforced by the BP. And the BP always holds him/herself blameless, and maintains that only the SO needs self-work and therapy.

     Vigilance can be a useful frame of mind when one is exposed to real danger (think Hurricane Sandy or jaywalking or being the goalie in soccer or hockey). But if you are forced to  maintain a hyper-vigilant state for too long a period of time, and are unable to take needed rest breaks for your psyche, then the perpetual stress will start to wear you down. Paying perpetual vigilance to everything around you leaves you no time to experience any joy or pleasure in your own life, and your own needs for nurturing and true companionship are incapable of being met. Just think of the spouses of alcoholics who end up going to Alanon because their spouses never quit drinking.

     We all occasionally walk on eggshells at various times in our life to preserve peace in the family, but that is quite different from being "on" 24/7. When you are always walking on eggshells, you have no time for self-development, receive no positive reinforcement, and your own emotions can be narrowed down. You may limit your choices severely in order to avoid "provoking" an outburst. You might even stop laughing, being playful and telling jokes about funny things in life because your entire vista with this person  is grey and black. Your own emotional needs of course are never attended to, so you never feel fulfilled. It is more like walking through a minefield, looking at your BP for any signs of disapproval or incipient hostility and criticism. You may even be fearful that in one of these temper outbursts real physical harm will come to you or the BP or someone else.

     You are entitled to peace in your own life. Your triggering his/her rage does not mean that you always make mistakes. Slowly your sense of self-worth becomes corroded and destroyed, and you lose the ability to think clearly for yourself. You start to wonder where your old self has gone, the happy, joyous, carefree self. Walking on eggshells also involves your excusing his behavior towards you because of his childhood trauma, or poor upbringing, etc, none of which you were responsible for. (S)he may also shrink and restrict your social circle, using various excuses. You may become totally subservient in an attempt to ward off further outbursts of rage. And finally you are usually forbidden to talk about this to your family and friends, or to seek out a therapist, because that would be seen by the BP  as a betrayal of the relationship.

     It is important  to understand that the raging is not controllable by you. It is not a response to what you do but to something inside the BP. You did not create his/her state of mind, you are not responsible for the outbursts of anger and rage from the BP, and you certainly can't cure him/her. His/her actions will continue towards you so long as you are there to receive them. And please, please, please never compromise your own safety. "The Devil made me do it" is not a valid excuse for emotional and physical abuse, and certainly has no place in a loving relationship, and in the long run you will be both frustrated and drained.

Mad Cow Disease

     The first case of mad cow disease (MCD) in six years was found in a dairy cow in California this past April. The cow showed no signs of infection with MCD (more properly called Bovine Spongiform Encephalopathy, or BSE). It had no weakness, altered gait, or decrease in milk production. This past year the U.S. Department of Agriculture tested 40,000 cows for BSE, down from the 380,000 they tested after  the MCD epidemic was noticed in England and attributed to eating meat or spinal cord tissues from infected cows. The disease in humans is progressive, 100% fatal, and has a lead time between infection and detection  in humans of years or decades. The curious fact to me is that one cow farmer (dairy or meat, I forget which) wanted to test ALL his cows for the disease, and the USDA refused him permission. I can think of no non-political reason for their denial, since he was willing to spend his own money on the testing so he could assure his customers that his animal products were disease-free. BTW I still continue to eat meat.