Here Comes The Judge

What got me to actually sit down at the computer and start writing was a recent news report in my local newspaper (the Columbia Daily Tribune, Friday, October 21, 2011, page 5B; columbiatribune.com) that U.S. District Judge Consuelo Marshall issued a ruling that a false advertising lawsuit filed by the sugar industry against the CRA could go forward.  The CRA had argued that the lawsuit should be dismissed because HFCS is equivalent to sugar in the way it is metabolized and that the lawsuit was “an attempt to stifle a national conversation about the merits of HFCS versus sugar.”  In addition, the CRA lawyers argued that educational campaigns form the CRA shouldn’t be considered advertising.  The judge dismissed those claims stating that the CRA’s educational campaigns constitute commercial speech and that the industry group is not insulated from federal false advertising regulations just because its “educational” statements relate to a public health issue.  I almost forgot to mention that the CRA had asked the FDA’s permission to use the term “corn sugar” rather than HFCS in both advertising and product labeling.  As far as I know, the FDA has not ruled on the request.  So, what is this all about?

What is HFCS anyway?

To understand what HFCS is and isn’t, we need to discuss a little basic chemistry.  Don’t be afraid, it’s not complicated.  To most people, the word “sugar” means good old table sugar, a sweet-tasting white crystalline substance called sucrose and which is composed of a molecule of glucose and a molecule of fructose.  Another word for sugar is saccharide.  So,  sucrose is a disaccharide; glucose and fructose are six-carbon monosacharides.  Another important disaccharide is lactose (milk sugar), which is composed of a molecule of glucose and a molecule of galactose.  Saccharides are a class of carbohydrates, molecules that are composed of carbon, hydrogen, and oxygen.  Carbohydrates, along with proteins and fats are the basic body building blocks.  Sugars can be composed of many monosaccharide molecules linked together, called polysaccharides, which are important storage forms of sugars in both animals and plants.  Although all sugars (by definition) are sweet, there is a large difference in the sweetness of individual sugars: fructose is the sweetest sugar, almost twice as sweet as glucose.

Sucrose comes mainly from sugar cane (60%) and from sugar beets (40%).  Sugar cane was first found in Papua New Guinea and was domesticated about 10,000 years ago.  The discovery of beet sugar was not until about 250 years ago.  The history of sugar is a fascinating one which has been chronicled by N Deerr in The History of Sugar (volumes 1 and 2, London, Chapman and Hill Ltd., 1949 v-258/1950 v-259-636).  An excellent summary of the subject was written by M. Gracey, N Kretchmer, and E. Rossi (A glimpse into the history of sugar, in: Sugars in Nutrition, Ed. M. Gracey, N. Kretchmer, and E. Rossi.  Nestle Nutrition Workshop Series, Vol 25; Nestec Ltd., Vevey/Raven Press, Ltd., N.Y., 1991).  I can assure you that HFCS is no more controversial than sugar itself, which has been considered by many historians to be most responsible for slavery (both in the U.S. and globally).

Anyway, for a variety of reasons, beginning in the 1970′s, HFCS was introduced as an ingredient in many processed foods.  HFCS is made from corn syrup, a liquid composed mostly of glucose molecules.  It is commercially available from a number of manufacturers, but perhaps, the best known form of corn syrup is Karo Syrup (ACH Food Companies, Inc.).  Corn syrup is made first by milling corn into corn starch, and then adding an enzyme, alpha-amylase, which breaks the starch into oligosaccharides (small chains of glucose molecules).  The next step is adding another enzyme, glucoamylase (also know as gamma-amylase) which results in a syrup consisting of only glucose molecules.  To make HFCS, the corn syrup is converted into fructose by another enzyme, D-xylose.  The manufacturing process results in HFCS with 90% fructose (HFCS 90) or 42% fructose (HFCS 42).  HFCS 90 is used to make HCFS 55, which is used to sweeten sodas and various sport drinks.  HFCS 42 is used in many processed foods including some yogurts, frozen desserts, breakfast cereals, and baked goods, and has about the same composition as sucrose.

How much sucrose and HFCS do Americans actually consume?

You may find it hard to believe, but since 1970, U.S. consumption of HFCS has risen from zero to about 40 lbs/yr/person.  At the same time, consumption of sucrose has decreased from about 70 lbs per person to about 40 lbs per person.  Net (total) sugar consumption has risen from about 80 lbs/yr to about 100-120 lbs/yr.  Thus, virtually all of the increase in total sugar consumption is the result of increased consumption of HFCS in its various forms.  But, the ratio of fructose to glucose intake has remained about the same over time

Why is HFCS so widely-used?

The development of HFCS was to a great extent the result of political and economic circumstrances.  Cane sugar quotas in the U.S. have kept the price of can sugar high while corn subsidies have made growing corn relatively inexpensive.  The bottom line is that it is cheaper to make HFCS than to process cane sugar.  It is also important to note that HFCS has some desirable qualities; It mixes well with foods and keeps foods moist.

How is HFCS metabolized?

Remember that HFCS and sucrose are composed of glucose and fructose molecules.  It is the fructose that most experts have focused on as a possible health culprit, beyond the fact that sugar in the form of glucose, sucrose or fructose add calories to the diet- about 4 calories/gram consumed.  Metabolism of glucose is relatively simple.  Glucose can be used by all cells in the body for energy, it can be stored in the form of glycogen (long chains of glucose molecules, much like starch, and used as a building block for polysaccharides.  Fructose, on the other hand, is taken up mainly by the liver and can be converted into glucose, glycogen, triglycerides  and some fatty acids.  It is the role of fructose in fat metabolism that has generated the most controversy.  There are considerable data in both animal and humans that consumption of large amounts of fructose raise triglyceride levels and increase insulin levels, promoting insulin resistance.  Does fructose promote cardiovascular disease?  Does fructose promote the development of diabetes mellitus? Does high fructose intake stress the liver?  These are just some of the questions that have been raised about dietary consumption of fructose, and by extension, consumption of HFCS.

Is HFCS metabolized differently than sucrose derived from cane and beet sugars?

There is considerable controversy whether HFCS has unique properties such that it is metabolized differently than sucrose derived from cane or beet sugar.  In my opinion, there are no credible data to show that HFCS and sucrose are metabolized differently or that the fructose in HFCS is any different than frucose in sucrose or fructose in fruits, honey, maple sugar, agave syrup or brown rice.

So, what’s the problem?

In my opinion, the problem is that we in the U.S., consume far more calories than we need and many of those calories come from foods containing various sugars, including HFCS.  The latest data show that Americans currently consume, on average,  about 130 lbs of sugar a year which works out to be almost 40 teaspoons of sugar every day.  It’s extraordinary.  We have twin epidemics of obesity and diabetes mellitus and plenty of cardiovascular disease to go around.  We don’t need to single out a single food or food additive (i.e., HFCS) as the reason for our many ills; there is plenty of blame to go around, including our fondness for inactivity.  But, it is clear that if we curb our sugar intake, we will benefit.  I am neither defending or condemning the use of HFCS in foods.  I seriously doubt that if tomorrow, the use of HFCS in foods and drinks were banned, it would have any impact on the prevalence of obesity, diabetes or heart disease.  We  will still eat too much (including an extraordinary amount of the various sugars) and exercise too little.

If you find this subject interesting, I urge you to read an article by Mary Franz (“High-fructose corn syrup: what’s the fuss about?,” published in Diabetes Self-Management, May/June 2011, pages 33-37) and an article by Gary Taubes (“Is sugar toxic?,” published in the New York times Magazine, April 17, 2011).  The Taubes article discusses the highly controversial views of Robet Lustig, a physician from the University of California San Francisco.  Don’t miss the Lustig video on You-Tube which is a lecture he gave in 2009 entitled “Sugar: the bitter truth.”  I’m not saying whether I agree or disagree with Lustig’s views, but………..

Finally, what about calling HFCS corn sugar?  In my opinion, it’s clearly false advertising.  Why don’t the corn growers just call HFCS something like “sugar derived from corn?”  Or, maybe, just continue to call it HFCS?

The Diethylstilbesterol (DES) story

DES is a synthetic nonsteroidal estrogen that was developed in the late 1930s.  It was widely used as a supplement to cattle feed (to fatten them up) and in humans as estrogen replacement therapy and for treatment of prostate and breast cancers.  In the late 1940s, one study showed that DES could prevent miscarriage if given early in pregnancy.  Other studies had shown no benefit, yet DES was widely used for quite a long time despite very convincing data that accumulated showing no benefit with respect to miscarriages.  Eventually, doctors got the message and use of DES faded away.  Then, in 1971, the NEJM published results from a very scary study performed by Herbst et al., showing an association between DES use during pregnancy and development of a rare vaginal cancer (clear-cell adenocarcinoma) many years later in female offspring of these mothers.  I still remember when the news hit.  I was a pediatric resident physician and doing my pediatric endocrinology rotation.  Even back then I was reading the NEJM regularly (I have been a regular subscriber since 1965).  I remember the many discussions we all had about the data.  As it turned out, by the early 1990s, 431 cases of the rare cancer had been identified in young women exposed to DES in utero.  The median age of cancer diagnosis was 19 years.  We now know that the mechanism for the development of the cancer was probably drug-induced abnormal development of the Mullerian ducts (these ducts develop into the uterus, fallopian tubes,  and a bit of the vagina).  It was all a nightmare for the mothers, the young women, and the physicians involved in their care.

What did we learn from the DES catastrophe?

I am not certain what the collective “we” learned from the DES story.  I do know what I learned- that all medical treatments, be they procedures or medications, have risks and benefits.  Many times we know what the potential benefits are for a given treatment, but do not know what the risks might be.  Thus, it is always important to consider and to weight unknown risks vs. the potential benefits.  This is no easy task but it needs to be done and physicians who do not do this, do a disservice to their patients.  The potential benefit of a given treatment must be compelling enough to counter the unknown risks of the therapy, whatever the therapy might be.  We (here I mean the collective “we”), keep learning this lesson over and over.  Just this week, I read an article (and two accompanying editorials) in the NEJM entitled ” Stenting versus aggressive medical therapy  for intracranial arterial stenosis.”  In summary, the study showed that stenting was associated with many more deaths than the medical therapy.  As it turned out, the stenting procedure was approved by the FDA in 2005 after a small non-randomized study showed benefit from the stenting vs. medical therapy.  Now the “experts” are moaning and groaning about the fact that FDA approval for the stenting procedure was probably inappropriate given the very limited data and that a large randomized trial should have been performed, which as it turns out was the substance of the current NEJM article.  Then there is the story about the “metal-on-metal” hip replacement devices that is turning out to be another medical therapy catastrophe (see “Medical Devices-balancing regulation and innovation, ” written by Curfman GD and Redberg RF in this week’s NEJM).  I could go on and on.  We as caregivers all need to go back and review the DES story and understand why we need to learn as much as possible about risks and benefits of any given therapy/device before we “jump in.”  Obviously, if a patient faces certain death and a new therapy comes along, it would not be appropriate to “sit on one’s hands.”  But, few new medical treatments meet that urgency standard.  Pressures from device manufacturers and pharmaceutical companies and the researchers who either developed or tested the treatments, should not trump the need for careful unbiased assessment of the risks and benefits of the proposed treatment.

What should people in the U.S. do to prevent/minimize risks for the development of thyroid cancer ?

Last week, the Pediatric Endocrine Society (formerly named in honor of Lawson Wilkins) published a letter summarizing the risk of exposure to radioiodine from Japan.  The letter was written by Andrew Bauer, a pediatric endocrinologist at Walter Reed Army Medical Center in Washington, D.C.    Dr. Bauer reviewed the situation and offered advice regarding the use of potassium iodine (KI) to high risk populations in the U.S. (i.e., young children and pregnant women).  Oral KI is highly effective in preventing radioiodine from being taken up by the thyroid, thereby effectively eliminating the risk of developing thyroid cancer from the exposure.  Dr. Bauer made clear in his letter, that at present, there is no reason to consider KI prophylaxis anywhere in the U.S.  I think it would be worthwhile for both pediatric endocrinologists and primary care doctors to read Dr. Bauer’s letter, but I haven’t yet figured out how to provide a link to the letter, unless you are a member of the Pediatric Endocrine Society, but I will try to do so.  Meanwhile, a number of other professional societies have published statements on-line (e.g., Radiation Risks to Health: a joint statement from the American Association of Clinical Endocrinologists, the American Thyroid Association, The Endocrine Society, and the Society of Nuclear Medicine, March 18, 2011).  So far all the experts are saying we should stay cool and avoid the temptation to stock up on KI.

The other day I got into a discussion with a primary care physician (PCP) about a hypothetical patient.  We had been discussing a case history for an upcoming medical student examination.  The patient was a 40 year old female with a medical history suggesting hypothyroidism.  The physical examination revealed an enlarged thyroid gland.  The question was as follows: what thyroid function studies should be ordered?

The Answer

The PCP said that he would order total thyroxine (TT4), free thyroxine FT4), and thyroid-stimulating hormone (TSH).  I was a bit surprised by his answer and asked if he didn’t also want to order thyroid peroxidase (TPO) antibodies?  He replied something to the effect that in the “real world” docs don’t mess with that kind of stuff.  I became even more surprised and then asked him whether he thought it was important to know what one was treating.  He got a bit hostile and replied that if the TSH were high and the FT4 and TT4 levels low, he would have a diagnosis, primary hypothyroidism.  He explained that the cost of the TPO antibodies (about $50-$80) depending on the laboratory) was not worth the benefit.  My response was “hmmmm.”

What did I really think?

I did not agree with the PCP’s approach to the hypothetical patient but I did not go ballistic since there was some merit to his argument.  On the other hand, it is my opinion that testing for TPO antibodies in the patient described above is worth the modest extra expense.  First of all, as a general principle it is important to know what one is treating.  While primary hypothyroidism is a diagnosis, there are many different causes for the condition and the approach to treatment might well be dictated by the specific etiology.  In those parts of the world where iodine deficiency is not endemic, the most common reason by far for primary hypothyroidism is chronic lymphocytic thyroiditis (CLT) or Hashimoto’s thyroiditis as it is commonly called.  This is an autoimmune disorder which is highly prevalent in females, particularly those over 40 years of age.  As I have discussed in previous entries, the physical examination often offers clues to the diagnosis; in my experience, careful examination of the thyroid gland will reveal a small lymph node on the left, just above the thyroid isthmus.  This node is called a delphian node and its presence means the patient has either CLT or autoimmune hyperthyroidism or Graves disease.  I can’t remember if I have ever had a patient with a delphian node who did not have positive thyroid antibodies.

Anyway, the differential diagnosis of primary hypothyroidism includes CLT, goitrogens (mostly iodine-containing products), familial inborn errors of metabolism (genetic abnormalities of the various steps to synthesis of thyroid hormones or their degradation), gland dysplasia (e.g., hemithyroids), and other rather uncommon entities.  I find thyroid antibodies most helpful when the TSH and FT4 come back normal (I can’t think of any reason to order TT4 but that’s a topic for another time).  The question becomes why is the gland enlarged (here we are assuming that the physician is skilled at telling when a thyroid gland is enlarged rather than there just being a prominent fat ring around the neck)?  It is still likely that the patient has CLT or possibly a so-called simple colloid goiter an entity I don’t understand; I don’t even know if the disorder exists even though almost all textbooks that cover thyroid disorders list it in the differential diagnosis of goiters (a goiter is just another way of describing an enlarged thyroid gland).  If the patient has CLT and enlargement of the thyroid, many endocrinologists will recommend treatment with replacement doses of L-thyroxine to “put the gland at rest.”  There are some data suggesting that such treatment can prevent progressive destruction of the gland which can occur; a number of studies have shown that TPO antibodies are cytotoxic even though most of the inflammation in CLT is lymphocyte-mediated.

So, it’s not so simple deciding what laboratory tests to order or not to order.   I will return to my original argument that whenever possible it’s good to know what specific disorder is being treated with medications, or  maybe, even if the treatment is just observation.  But I can sort of see the PCP’s point of view, sort of.

Bus drivers vs. conductors

Dr. Morris was a British epidemiologist who hypothesized in the 1940’s that one could prove that exercise was heart-healthy by studying  bus drivers and conductors on London double-decker buses.  Drivers spend 90% of their workday sitting down while conductors walked up and down the bus stairs about a million times each day (actually about 600 stairs per day).  In a paper published in 1953, Dr. Morris showed that heart attack rates were dramatically lower in the conductors.  Follow-up studies showed that although the conductors, on average weighed less than the drivers, the rates were not closely related to weight or body type, including waist size.  He later studied postal workers, clerks and telephone operators vs. those who delivered the mail by walking or by bicycling.   The delivers had much lower risks of heart attack.  The strongest proof for the relationship between physical activity and risk for heart attack came from studies Dr. Morris conducted in the 1960s.  He looked at heart attack risks in a large group of men with sedentary government jobs in relation to their degree of aerobic activities outside work.  He found that those who performed vigorous exercise on a regular basis had a 50% risk reduction for heart attack.  The importance of Dr. Morris’s studies cannot be overemphasized.  In my opinion, most of what we now know about exercise and cardiovascular health was the direct result of his ground-breaking work.

The limitations of epidemiologic studies

Not to diminish the importance of Dr. Morris’s work, I need to remind you that epidemiologic studies cannot prove cause and effect but only show relationships.  For example, maybe bus drivers, postal clerks, and office workers are under more stress than bus conductors and postal delivery personnel?  And maybe people who have sedentary government jobs and who don’t exercise regularly just have different personality types (e.g., ‘type A” vs  whatever) than those who do exercise regularly and that is the reason for the study findings?  Anyway, it’s a pretty good bet that it’s the exercise per see that lowers the heart attack risk.  By the way, it may just be a fluke but Dr. Morris exercised regularly his whole life and lived to 99 and ½ and didn’t die of heart disease.

Why don’t we have enough primary care providers?

One reason for the shortage of primary care physicians is that few physicians want to go into primary care: in 2007 only 17% of medical graduates said they intended to go into primary care.  I would be very surprised if the percentage is any higher now.  It seems that every medical student I see in my clinics intends to go into either dermatology or radiology.  Why is that?  It’s simple- $$$$$ + lifestyle.  Specialists generally make much more money than primary care providers and most (not all) have easier jobs (I am a specialist and I am not afraid to say it- I hope my specialist friends who work really hard don’t read this).  The immediate question is how to pay primary care providers more.  The debate is framed nicely by Mr. Pear in his article.  Specialists agree that primary care providers need to be paid more but the specialists don’t want that pay increase to come from their incomes.  I’m sure it’s already an ugly debate and I predict it will get much uglier before the dust settles.

The bottom line

We desperately need many, many more primary care physicians, nurses, and whatever.  It will take time- years and years to achieve the desired levels.  We need to get started.  It will cost some money but it will be worth it.  With respect to the debate about shifting payments from specialists to primary care providers, I will offer no opinions except that I predict someday soon, primary care providers will be serving as “gatekeepers” for speciality care services.  Assuming I am correct, specialists would be wise to remember that their livelihoods will to a great extent depend on referrals from primary care providers.  Of course, another way to look at the issue is that the major cost reductions we need to achieve in our health care system, are less related to direct payments to physicians but rather for the unreasonably costly services physicians generate (e.g., procedures, medications).  We would probably do better not to delude ourselves into thinking that speciality physician salaries are an important part of the astonishingly high U.S. health care costs relative to other civilized places around the world.

I was a bit nervous about the fact that we had initiated treatment with the gluten-free diet before the patient saw the gastroenterologist- gi docs traditionally like to do small intestine biopsies to confirm the diagnosis of celiac disease before recommending a gluten-free diet. In this instance, the gi doc felt that the biopsy would not be useful as the patient was already on a gluten-free diet but that the response to treatment clearly confirmed the diagnosis (remember that the blood tests were strongly positive for celiac disease). So, the gi doc and I are still friends (at least I think so).

I have been assured by my webmaster that he and colleagues are working to “clean up” the problem (I think this problem has affected thousands of sites) as quickly as possible. I recommend that you go directly to the website rather than being lazy and just punching in a Google search for “endodoc” until the problem has been resolved. Sorry for any inconvenience this may have caused you.

Finally, I apologize for not having a new entry for a while now- I was out of town doing this and that. I promise to get back in the groove quickly.