Thursday, June 25, 2009


I expect I will receive more e-mails from this blog than from all the others together. Nutrition is fundamental, not only to life, but, as per Freud, the first stage of mental development. Our first sensation of love, warmth, and security was at our mother's breast. Because it has such a fundamental connection with our psyche, this is probably why we have more and different personal habits and religious taboos over food than any other aspect of our lives. We also have magical thinking about "good" foods and "bad" foods.

Mother's milk is heavy in sugar and fat, which is probably why we all love ice cream. (Separate thought:I prefer chocolate to vanilla, and I often wonder if people who prefer vanilla taste the chocolate in the same way that I do.) Fat is appreciated because it adds flavor and substance to food It also markedly slows stomach emptying, so we feel fuller for a longer period of time if the meal contains fat. Some of my patients equate "low fat" to "low taste" especially low-fat mayonnaise.

There are eight essential amino acids, which are called "essential" because every animal cell needs all eight to make proteins,and cannot synthesize them. Vegetables have at most seven of these amino acids, which is why a complete vegetable dish contains rice + beans, or corn + peas (aka the American Indians' succotash); that is, at least two vegetables.

There are also two or three essential fatty acids (depending on your definition), and again any animal cell contains all of them, which again is why you need at least two vegetables if no meat is eaten. This is probably why no one looks truly happy in a vegetarian restaurant, because they sense they are missing something (or subconsciously are aware of the fact that tofu lowers men's sperm count because soy is a phytoestrogen). On the other hand, everyone is all smiles in a steak restaurant.

Everyone should be aware that Vitamin B-12 is necessary for an animal cell to synthesize animal DNA, but not vegetable DNA. Vegetables contain no vitamin B-12 whatsoever. Therefore, if you eat neither meat nor fish nor eggs, you will eventually die from pernicious anemia. It as also a curious fact that no one is literally addicted to eating meat, or can achieve an altered mental state by eating meat (licking Colorado toads being a notable exception). All the addicting or mind-bending foods are vegetables, with their totally different chemistry: nicotine, alcohol, caffeine, opium, marijuana ,peyote, "magic" mushrooms, etc. In fact, if you kill an animal or fish at random and eat it, the odds are that it will agree with you. But if you eat a random vegetable or berry, there are good odds that it will make you ill or kill you (mushrooms, choke cherries, oleander, foxglove, mistletoe, rhubarb, yew, manicheel), not to mention the severe contact allergies from poison ivy, oak and sumac.

As for cholesterol, it is an essential component of the membrane of every animal cell, through which all nutrients pass. (Plant cells have a cell wall outside the cell membrane, which contains no cholesterol whatsoever.) So when we chemically lower cholesterol, we lower a constituent of the membrane of every cell of the body. This in turn alters trans-membrane potentials, ion fluxes, molecular transport, and sensitivity to neural stimulation. This may explain why some patients develop leg cramps (muscle cell irritability and sensitivity), or altered liver tests (? inflammation of the cell membrane and enzyme leakage), and sometimes just don't "feel right"(altered electric potentials in brain cells). If cholesterol is lowered by weight loss, the body responds as a whole, and therefore there are no such side effects. When Wise's Potato Chips tried to advertise their chips as "having absolutely no cholesterol", which is a literal scientific fact, the FTC pulled their add, claiming that patients would confuse "no cholesterol" with "no fat".

We don't even know how many meals we should eat daily: one, two, three,or six. We don't know the proper time of day to eat the largest meal, even though we know that all our minerals and hormones have a diurnal cycle (cortisol is highest in the AM, serum iron in the PM, etc.). We don't know if the fact semi-starved rats exceed their natural life span applies also to humans. We don't understand why, if a normal BMI is optimal for health, how is it that people with an elevated BMI survive heart attacks better.

As for vitamins, a vitamin is a chemical which, if you do not ingest, you get ill and may die (scurvy, beri-beri, pernicious anemia, etc.), because your body needs it as a co-factor for essential enzymes, and cannot synthesize it.A,D,E, and K are fat-soluble vitamins, but C and all the B's will be excreted in your urine, if ingested in excess. Oddly enough, an excess of daily vitamin B-6 causes neurological symptoms, just as a deficiency of the same vitamin does. (cf article in NEJM, more than 10 years ago; research done at Albert Einstein Hospital)Since it is a pure chemical, your body cannot tell the difference between "natural" and synthesized vitamins. Since the FDA does not regulate or supervise vitamin manufacture, there is also absolutely no guarantee as to if a capsule labeled "400 U of Vitamin E" contains 0, 400, or 1200. And the idea that too much of a vitamin cannot hurt you never applies to fat-soluble vitamins, which are stored in your body. We have already seen studies of the coronary artery dangers of too much daily Vitamin E.

Finally, all the suggestions about "healthy" diets are based on retrospective and/or epidemiological studies, which all fail to remember that correlation does not mean causation. The only food intervention shown to lengthen life, mostly by preventing heart attacks, is alcohol. I have read studies with beer, scotch slivovitz, red wine, etc. It is the C2H5OH molecule that saves you. There was an article as far back in 1974 in JAMA, in which comparative autopsies showed that moderate male drinkers had larger diameter (i.e. wider and less clogged) coronary arteries than age and weight matched controls (non-smokers only). Every time a forward study (low fat, beta-carotene, selenium) has been done, the results have been nil, or even negative (especially with vitamin E).

The overall problem is that no prospective food study has ever been done with adult humans, so all are beliefs are just that; beliefs without a sound foundation in experimental fact.

Friday, June 19, 2009

Fatigue, Insomnia, Sleep Apnea, and Hypnotics

There are many beliefs about sleep, but not much verified knowledge. For instance, it is not true that one hour of sleep before midnight is worth two after.
It is true that a lot of fatigue is due to mental processes, rather than physical fatigue.
We are probably all underslept, since most adults have trouble getting "catch-up" sleep. When you were in high school or college, you could probably make up for the sleep deficit you incurred during the week by sleeping till noon or later on weekends. As we get older, we seem to lose this ability, while at the same time we awaken at night more frequently.
As a physician, I observe that my chronically underslept patients are more irritable, with degraded ego functions as well as more muscular pains and aches, and have some degree of depression. They also seem to function closer to baseline when doing well-known and repetitive tasks, but have trouble concentrating on crossword puzzles and the like. (Or as we used to say as interns, we could run a cardiac arrest with no sleep, but it was difficult to do an intake interview.)
Another danger of being underslept is falling asleep behind the wheel of your car, or making other errors. The government recognizes this by putting a limit on the number of consecutive hours a truck driver can drive, or a pilot can fly. The number of hours a medical intern can be on call at a hospital is also limited, but strangely enough a 60-year-old medical attending has no limits placed on his hours. In fact, if a patient called me at 10 at night and I told him/her that instead of getting my advice, because I had been awake for 16 hours ,they should go to the nearest emergency room where they could be seen by a well-rested doctor, they would be very upset.
Since lack of sleep is so corrosive and destructive, both mentally and physically, I see nothing wrong with the use of sleeping pills. I would prefer the use of sleeping pills to a patient falling asleep at the wheel of his/her car. Some patients are concerned about becoming dependent on sleeping pills, but I believe that many adults have "irritable sleep syndrome" and need some chemical help to get sufficient sleep.
Sleep apnea studies are in a curious position. They are reviewed by psychiatrists, neurologists, pulmonologists, and ENT doctors. The definition of sleep apnea is somewhat imprecise. (If you are not an overweight male who snores, the chance of your having sleep apnea is greatly lessened.) We all have apneas, generally defined as cessation of breathing for 10 or more seconds. The diagnosis is firmer if the oxygen saturation drops below 85% at the same time. There are also hypopneas, which are episodes of underbreathing without complete cessation. We have also known for a long time that everyone drops oxygen saturation during sleep, which is why we put nasal oxygen on all heart attack patients. Oxygen desaturation is a potent pulmonary artery vasoconstrictor, which overloads the right ventricle, which can tolerate volume overload better than pressure overload.
Since the number of apneas increases with age, the definition of sleep apnea depends in part on a patient's age. My two additional criticisms of all sleep apnea studies are:(1) no one asks the patient (usually a male) if he would be willing to wear a positive pressure sleep mask for the rest of his life, and (2) it would be more efficient to put a patient suspected of sleep apnea on a CPAP and then a BIPAP mask to see if they felt less tired, etc. the next day, but insurance and Medicare only pay for the mask if you first diagnose sleep apnea. In other words, unlike putting a patient on an antidepressant, CPAP cannot be used as a diagnostic/therapeutic treatment and test.
Before I send a chronically fatigued patient for a sleep apnea test, I try one month of Prozac or other SSRI, then one month on Effexor XR or Wellbutrin SR, and finally one month on Provigil, which is FDA approved for CNS stimulation of patients with sleep-shift disorder or chronic insomnia/fatigue, and seems to have no ischemic cardiac effects.

Sunday, June 7, 2009

Generic Drugs, Brand Names, and Tier I Drugs

Most people think that generic drugs always work, that all Tier I drugs of an HMO are pharmacologically equivalent,and that generic drugs are cheaper. Only the last statement is true, and the pharmacies also love generics because they have higher profit margins. (Brand name $80, charge to you $100, profit$20; generic $20, price to you $50, profit $30.) However, the generics do not always work as well as brand names, because there can be different "inert" compounds added to the parent drug to make the tablet. The FDA requires that the blood levels of the generic be the same as the brand name (+/- 10%), but only the brand name drug has been tested for clinical efficiency. There is no way of comparing tissue levels of the brand name drug to the generic, and this is especially important with drugs that act on the central nervous system (tranquilizers, sleeping pills, pain pills) after crossing the blood-brain barrier. Again, no generic is tested for clinical efficiency against the brand name drug.

The blood-brain barrier is nature's way of protecting the brain from noxious compounds that are dissolved in your blood. A drug has to cross the blood-brain barrier (through capillary walls) to reach the brain and achieve its effect. Whether a particular drug can do this is usually only determined by trial and error. For instance, penicillin readily crosses the blood-brain barrier, and is therefore extremely active in treating meningitis. Keflex, a cephalosporin, cannot cross the blood-brain barrier, and is therefore useless in treating meningitis, although it generally can treat any soft tissue infection or lung infection that penicillin does.
Within a particular class of drugs (e.g. beta-blockers) if a drug is lipophilic, this affects the ability of the brain to absorb the drug once it gets there. Marijuana is extremely lipophilic, so it is released very slowly from fatty tissue in the brain, and your urine can test positive for at least two weeks after inhaling it. There can also be subtle differences within a class of drugs: Coreg is the only beta-blocker shown to reduce microalbinuria in diabetic patients.

When it comes to other groups of drugs, there is wide human variation in responsiveness, since we are all biochemically different. Claritin and Zyrtec are over-the-counter (OTC) anti-histamines, and sometimes one will work on a patient's allergies, and sometimes the other, since they are chemically very different. Allegra is a prescription antihistamine, which works better in many patients, but unlike Medicare Part D, most HMO's ask me to certify that both OTC drugs did not work before they will pay for Allegra. The same problem arises is proton-pump inhibitors (PPI's) for acid reflux. The HMO's want me to try the patient on OTC Prilosec before paying for Prevacid, Aciphex or Nexium. Furthermore, if I want to prescribe Nexium at a double dose to suppress acid symptoms, which some patients need, I generally have to send them to a GI doctor to have the payment okayed. Remember, if you are forced to buy an OTC drug, your co-pay is 100%, and the cost to your HMO is $0.

The worst scenario is in CNS-acting drugs. In my experience, generic Ativan works less than 10% of the time, so if a patient does not respond to generic Ativan, I am not sure of the cause. I also have found that generic Prozac works less than 50% of the time, and there are treatment problems with generic Wellbutrin. If a patient responds well to the anti-depressant Lexapro, the HMO generally asks me to switch the patient to a generic form of Celexa, even though they are chemically totally different drugs. I have also found that the beta-blocker Nadolol is excellent prophylaxis against migraines, as is Inderal LA, but since only Inderal (which requires dosing 4 x a day) is available in a generic form, the LA Rx. is generally not paid for.

In your own case, I am certain that aspirin, Advil, and Alleve all work differently in you, even though they all are NSAID's (anti-inflammatories).

Viagra, Levitra, and Cialis all work to treat erectile dysfunction, but sometimes one drug will work, and sometimes another.

The main point is that drugs with the same physiological endpoint in the human body have different chemical structures, and they cannot all work equally well.