Wednesday, September 30, 2015

Questioning the Nutritional Competency of Physicians

Considering the current lack of nutrition education in medical school curricula throughout the United States, it has become common in the lay public to question the dietary advice offered by physicians - assuming it's offered, at all. Can we trust what our doctors tell us about what we should eat?

In response to this question, I would be inclined to ask is you can really trust anyone's dietary advice, regardless of their education and credentials?

* * * * *

For many people, their doctor is the all-knowing encyclopedia of human form and function, an omniscient being, elevated to throne-like proportions; particularly in America, where status means everything. Physicians, through unparalleled grit and arduous training, sit at the pinnacle of the ladder of what we consider "success."

Don't know what's wrong with you? Go see the doctor. Inexplicable symptom your WebMD searches fail to diagnose? Time to see the doctor. Yet, on some level, we all know doctors are human like the rest of us. Their training, time- and labor-intensive as it is, doesn't enable some kind of super-human, photographic memory. One human being cannot be expected to remember everything they were ever taught.* (This is why, when they leave the room after the H&P, they often spend time consulting with other specialists or referencing their Merck Manual - or Dr. Google - about your case; if it happens to be an uncommon presentation.)

*Of course, no one prefers to think of doctors this way. In a sense, they are a little like commercial airplane pilots. Infallible is an unspoken requirement for the job. We disassociate humanity from these professionals, because our lives are literally in their hands. Who in their right mind is content to imagine their airplane pilot as an anxious drunk?

When it comes to prevention and wellness, from the standpoint of nutrition and exercise doctors have tended not to fare so well. From my experience, the task of discussing these options was generally delegated to other professionals, whether they be registered dietitians (RD), exercise physiologists (RCEP) or others. There's nothing wrong with sending patients out to have someone with more specialty training discuss their case with them, in greater detail. In fact, in some cases it's not only warranted, but you'd be doing your patients' a serious disservice not to. (It's important that all of us have an intimate understanding of our own limitations.) Depending on their level of expertise and the quality of their evidence-based practice, this might even be the best option. But, from what I've seen, it can take a lot just to get someone in for a check-up with their primary care provider. They're busy enough with school, work and families of their own. The point is, patients are people, and people are busy and frustrated, or generally stressed out with life. Getting them to go see a specialist practitioner, unless it's a life or death situation, may pose a challenge.

But most medical practices do not employ RDs, for example, or preventive health coaches of any kind; they're stuck in hospitals, rounding on intensive care patients with TPN - for good reason, of course. Not to mention, in today's healthcare economy, it can be a troubling extra expense for the primary care provider, who's already experiencing difficulty maintaining their overhead and getting by, with changes to the system that directly impact their ability to provide high-quality care.

Ideally, I would like for someone with extensive knowledge and expertise in nutrition (or exercise, depending on what we're considering), and the time to truly sit with someone and discuss their individual needs, to spend some quality time with patients, and create a personalized plan they can implement immediately and with sufficient ease; particularly considering medical providers don't usually have the time to get into the nitty gritty of what's involved, here, to be effective. Or, at least, one wouldn't think so. Unfortunately, ignoring the challenges that come with trying to implement something like this, and the compliance and patient adherence issues that would likely tag along with it, I am wrought with a bigger concern:

How can I trust the competency of the [average] nutrition professional, in a world where over 50% of our research findings are false,[1] in areas of biomedical science that are considered to comply with high-quality experimental science (e.g. Genetics and drug targets) -- compared to fields like nutrition, which, from my perspective, have not had such compliance, historically. Why should I put my faith, and, more importantly, my patients' health, in the hands of someone whose evidence base is predicated largely on nutritional epidemiology; precisely the kind of observational data that has done little more than confuse the world for the last 50 years, with sensationalism like the following (albeit slightly exaggerated):

Eggs are bad.
No, eggs are good!
Wait, wait, no... they're bad again.

Red meat gives you cancer.
"Red meat gives you heart disease... through TMAO! We've found a mechanism."
"Oops, never mind. TMAO production is actually greater with fish consumption. We like fish."
"Systematic reviews reveal no connection of SFA to heart disease."

"Fiber is beneficial, ergo, we must eat all the fiber."
"Diverticulosis is a 'fiber deficiency disease'..."
"No, wait, no. There's no causal connection between fiber intake and diverticular disease."

Et cetera, ad infinitum.

Epidemiology, although imperative for detecting mass effects on a large-scale, with respect to infectious disease epidemics, is virtually worthless for giving us useful data with regard to what to eat, and which nutritional practices cause what physiological responses, apart from giving nutrition scientists more questions to attempt to find answers to. Then, of course, there's the additional concern I would have that the few controlled experiments in nutrition that are out there are under-powered to detect significant effects, riddled with statistical peculiarities, like the (massive) problem of multiplicity, and more. I don't mean to suggest this isn't also a problem within many or even most other areas of biomedical research. It certainly is. The point, however, is that I can't help but wonder how much I can actually trust the views of the typical nutritionist, when I can't trust their data. It has nothing to do with them, or their degree, but where their information is trickling down from.

With all that said, however, if the licensed nutrition professional (the RD, in this case) exists specifically to help educate and treat folks with nutritional deficiencies of some kind or another, or to help optimize someone's diet and individualize it for their personal needs, and the information that predicates their practice isn't very strong, what makes the physician think he or she is qualified or capable of providing expert nutritional advice to patients, when they have, at most, 20 hours of nutrition education throughout the entirety of their medical training[2] -- much of which probably told them that vitamins and minerals are useless, dieting doesn't work and medical nutrition therapy for prevention should join the ranks of complimentary and alternative "medicine" (CAM).**

**For the record, I think this is utter crap. It is my opinion that nutrition is perhaps the single most important and influential factor in maintaining ones health and preventing any undue lifestyle disease. I just also happen to hold the simultaneous belief that most of the data used to determine treatment paradigms in this field are currently poor, or analyzed and interpreted horrendously. I do believe, however, that there are more intelligent and practical determinations that can be made from the available data, depending on where one chooses to focus their attention. (Easier said than done, sometimes, I realize.)

On the one hand, I believe there are still medical schools that do not include nutrition in their curricula, at all. Not one single hour of lecture on the topic. That's abysmal, and pretty depressing, if you ask me. Then again, medical students amass an inordinate number of hours studying gastroenterology and the digestive system, medical physiology and biochemistry, the pathology and pathophysiology of every body system, and then some - which is an understatement, actually, if you ask me.

On the other hand, I suspect that all it would reasonably take for someone with this sort of unparalleled training in human physiology to teach themselves the requisite facts re: nutritional biology would be a bit of extrapolation from their organic and bio-chemistry and physiology training, and some intelligent re-affiliation with their biostatistics texts. (Considering most of the books used to teach physiology and pathology to dietetics students are watered down versions of medical physiology and classic tomes like Robbin's Pathologic Basis of Disease, which medical students learn from directly for years, I don't think it's too wild to suggest that these people are equally as capable of distilling the important points from the field of nutrition, if given sufficient attention and applying some critical thinking to the task.)**

**I do think it's an important consideration, however, to acknowledge that physicians are trained to think algorithmically. Knowing this, many physicians are bound to accept that the established paradigms and guidelines for nutrition (like the DGAC) are correct, until proven otherwise, and so, I suspect many of them just push the standard nutrition information: 6-11 servings of grains, 3-4 servings fresh fruits and vegetables, no processed junk, etc., a little like a robot, because "that's the [currently acceptable] answer," plugged into the [currently accepted] algorithms.

Frankly, almost no one questions whether physicians are capable or qualified to treat individuals with hypertension, for example, but how many total hours do you suspect medical schools actually spend lecturing on this specific subject? Consider the amount of material thrown at medical students over the course of the four years they spend in school; there's simply far too much of it for any one particular topic to take much more of their time than that. Not to mention, the majority of a physicians training actually occurs in their chosen specialty, during residency. So, attacking medical schools for their so-called "poor design," may not be the most efficient tactic to rectify this problem. Perhaps, if anything, the question ought to be: how can we incorporate more nutrition and preventive health education in primary care residencies?

A friend on twitter, who happens to be a registered dietitian, studying for a Ph.D. in nutritional sciences, and who I have a great deal of respect for, recently posed this question, which I thought was interesting (and relevant):


Having already partially addressed the second question, I'd like to spend a moment reflecting on the first. "How are MDs expected to give diet advice in a 15 minute visit?"

As with most things in medicine and patient care, this question has a multifaceted answer, much of which I don't intend to get into. For instance, not every PCP only spends 15 minutes with a patient. But, let's say they did... I personally know many physicians (not all of whom are primary care docs) who successfully do this kind of thing, on a daily basis, which often seems to culminate in astonishingly positive results for their patients. These individuals include, but are not limited to:

               Dr. Rakesh Patel (family physician)
               Dr. Ted Naiman (family physician)
               Dr. Emily Deans (psychiatrist)
               Dr. Dea Roberts (preventive medicine physician)
               Dr. Jeff Stanley (internist)
               Dr. James Crownover (sports medicine physician)
               Dr. Jason Fung (nephrologist)
               Dr. Nicole Anderson (general practitioner)
               Dr. Victoria Prince (family physician)
               Dr. Anastasia Boulais (general practitioner)
               Dr. Colin Champ (radiation oncologist)

Then again, I also know a number of RDs and nutritionists who have succeeded in helping innumerable clients achieve equally positive results, yet, I imagine, spend substantially more time with each individual, coaching and educating them on nutrition. [Adele Hite, RD, MPH, Franziska Spritzler, RD, CDE, Amy Berger, MS, NTP, and many, many others...]

Perhaps the secret sauce is distilling the most important points into manageable chunks for people to implement, immediately, in consistent baby steps. Whatever it is, all of these professionals are making it happen, somehow. I don't think it is fair, at all, to suggest that physicians are incompetent in the area of nutrition and preventive health, it is merely that the vast majority of them either do not understand or appreciate this avenue of health science (generally, from my experience, because they've never bothered to look into it, or have other vested interests that occupy too much of their mental capacity -- once again, a single individual human being cannot know or do it all, and shouldn't be expected to.)

All things considered, I wouldn't be content to question the nutritional competency of the physician -- although most would still do well to examine the randomized-controlled clinical data that do exist, at present, and formulate their own educated opinions, as I believe I and many others have finally began to do. I would question the nutritional competency of anyone and everyone, irrespective of their purported expertise. In a world where one dietitian will tell you to eat the Blue Zone way, another will tell you to eat low-carb, high fat (LCHF), and a third will tell you to stop eating altogether; meanwhile, one doctor will tell you to go on a juice fast for three weeks, another will tell you to do a protein sparing modified fast, and yet a third will tell you that militant veganism is the road to optimal health, how can you afford not to question it all?

For what it's worth, I am not writing any of this with the intention of knocking my nutrition colleagues in any way, shape or form. I know a great deal of dietitians and nutritionists who are absolutely phenomenal, highly intelligent and very competent. Some of them are getting doctorates in nutrition and metabolism. Some are working in private practices of their own, changing lives every single day for the better. I commend them, and I have the utmost respect for each one of them. However, I find that the number of healthcare providers in the field of nutrition who have done the intellectual work necessary to truly weed out the important nuggets of information from the insanely convoluted world that is nutrition science and public health is absurdly low, and so my trust in the overall state of the profession has waned over the years.

We all know great physicians and awful physicians, fantastic nutritionists and horrible nutritionists. This goes for every career in health care; medicine, nursing, pharmacy, social work, physical therapy, etc.. Nobody is exempt. It's never about the degree, or the title one wears, but the individual who has earned it.


As always, "The greatest amount of scientific eminence is trumped by the smallest amount of scientific evidence."

Decrees, accolades, credentials... none of these things matter. Science is concerned with evidence.



REFERENCES

[1] Ioannidis, J. P. (2005). Why most published research findings are false. Chance, 18(4), 40-47.
[2] Devries, S., Dalen, J. E., Eisenberg, D. M., Maizes, V., Ornish, D., Prasad, A., ... & Willett, W. (2014). A deficiency of nutrition education in medical training. Am J Med, 127(9), 804-806.

Wednesday, September 23, 2015

Believe What You Will

Belief is a funny thing, in that one need not reflect on a fact for a long time, in a deliberate attempt to determine its truth, in order to take it as being the truth. In essence, there is always a little faith tied to every belief. (Including within science, I might add - For an in depth analysis as to why I say this, I implore you to read this article by Stanford Philosophy: The Problem of Induction.)

With respect to scientific thinking, it is common for a belief to be predicated on Plato's epistemic rule for what constitutes knowledge. (i.e. Justified True Belief.)

Is your belief true, and are you justified in believing that this thing is, in fact, true?

According to Plato's dialogues, one cannot have knowledge of something unless they believe in this something, and if this something can be proved to be the case.* It is the word proved, in this context, that typically matters most to scientists and critical thinkers.

*This presupposition ignores the Gettier problem, in epistemology, which purports to disprove Plato's JTB concept of knowledge. However, interesting as it might be to go down that rabbit hole, I must insist that we temporarily accept this presupposition, for the sake of argument.

Proof requires evidence.

Evidence is - or, should be - the only thing that matters in science. The premise of empirical knowledge is that, once all the data is collected, analyzed and interpreted, beliefs will tend to shift in accordance with what the agreed upon result of this scientific synthesis seems to be, at least transiently.

The reality, however, is that, with particular regard to biological research, there is so much noise in the system, so much data to collect in different ways, so many hypotheses to refute as it were, that just about anything could have some credence. All one has to do is spin the data a certain way, give it a certain flare and a plausible underlying mechanism, and BAM!, we have a potential belief-winner.

If biology were more like analytical chemistry or experimental physics, it might be a different story. More solid evidence would be required to confirm mechanistic principles that underlie various conjectures. Experimental conditions set to confirm or disprove a cause and effect relationship would hopefully elucidate "the answer." And if, in 20, 50 or 800 years, someone has falsified the previous result with a more refined experiment and observation, the beliefs change accordingly.

A great example of such an event is the shift that took us from Newtonian (classical) mechanics to relativistic mechanics to describe so-called large scale, cosmological occurrences. It is understood to be the case in the physics community that Isaac Newton had it right with his laws of motion, but, when Albert Einstein came along and ruined all that perfect mathematical deliciousness with his theories of special and general relativity, an amazing shift occurred (over time) where people began to realize that he was, in fact, indisputably correct - with the implicit understanding, of course, that his theories were also subject to falsification, as are all other theories -- and their beliefs about Nature changed to reflect this paradigm shift.

The trouble is, biology -- although it rests on the laurels of physics and chemistry, from a purely reductionist perspective -- functions quite differently from its sister sciences, wherein, due to the innumerable and often immeasurable variability in the systems, it can be nearly impossible to discover "the answer." And, in fact, it may be the case that there is no such thing as the answer, at all; there may indeed be more than one answer, more than one mechanism that causes the exact same outcome or set of results.

Because of the aforementioned complexity in studying the life sciences, and the nature of biological phenomena to be convoluted and elusive, it is easy to suspect that we have an answer to a particular question, when, in fact, we might well be dead wrong. Or perhaps we're not so wrong, but just a little wrong. Or maybe we're on the right track, yet still no cigar. Or maybe we are right, but our ideas behind the mechanism are too simplistic....

Ultimately, my point is simple: At the end of the day, everyone's hypotheses are valid - much more so, of course, if they are predicated on previously "proven" theories. More importantly, it is that science is an ever-changing, constantly adapting discipline, which requires supple minds to morph along with it. You cannot be a rigid thinker and call yourself a scientist. It is inappropriate for the discipline, and, if you are a biological researcher, it will (at least in my opinion) turn out to be the bane of your existence. You ought not conduct your life as a scientist by trying to angrily refute every conjecture thrown your way, regardless of your purported expertise or your credentials, even if you assume to "know" that they are incorrect. It is a fruitless endeavor.

The truth will out, in the end. As it did with Newton and Einstein, and then again with Bohr, Heisenberg and the advent of quantum mechanics, the data will eventually shine a light on the nature of reality, as we're meant to understand it, when the time comes. In the meantime, please do not assume I am suggesting you take the superficial view that these last few paragraphs appear to be saying, "every conjecture is okay, because it could be right, or it could be wrong, and you may just note know yet," or something like that. Rather, I'm saying, "Don't fret over every little thing, or take yourself (or others) too seriously."

"It is the mark of an educated mind to be able to entertain a thought without accepting it." - Aristotle

Thursday, September 17, 2015

A Life on Drugs: We've Lost Sight of What's Important

We are at a place in our healthcare economy where a vast majority of American adults are on more than one chronic medications, with what seems like no hope of ever coming off of any of them. Of the more common kinds, HMG-CoA reductase inhibitors (statins) are high on that list, as are anti-hypertensives, anti-depressants and anti-anxiolytics, and many others. Frankly, we are not really taught about taking people off of these drugs in health care, since, more often than not, this isn't something we imagine taking place. Rather, once someone is put on a medication, the likely course of action is that the disease process will continue to progressively worsen, not improve to a point where they no longer need the support of the drug.

Now, I would gladly be one of the first people to stand up and tout the benefits of a well-studied pharmaceutical drug that has a proven track-record of eradicating some disease or another, particularly with respect to things like infectious microorganisms. The fact is, we need medicine like this. If we didn't have access to certain kinds - e.g. vaccines, antibiotics, etc. - or, if they were never invented, droves of people would still be dying of smallpox.

That said, I can think of many examples of prescription drugs which have either not been proven sufficiently well, prior to their institution, or simply have so many adverse events that the purported benefits of taking the drug may not outweigh the side effects. The example I feel most comfortable giving here, with respect to the latter, is of statins. It is my fervent belief that lifestyle diseases cannot be cured or well-treated with pharmaceuticals, but that environmental and lifestyle changes must be implemented intelligently and consistently if one is to hope to truly overcome it. If poor diet, awful sleep habits and sedentary behavior is the cause of someone's disease, I find it doubtful that pharmacological inhibition of the mevalonate pathway, as is the case with HMG-CoA reductase inhibitors, for instance, will be of much help, rather than addressing the fundamental concerns mentioned previously. (Other scenarios, such as certain genetic conditions that predispose to severe hyperlipidemia, like heterozygous familial hypercholesterolemia, may be quite a different story - although, it's worth pointing out that the causes of death in persons suffering from heterozygous-FH are multifactorial and amount to more than just "they've got too much cholesterol in their blood."[1]

Millions of people in the United States are currently taking statin drugs. One of the more popular varieties is atorvastatin. It has been postulated many times that, should someone suffer from what's called hyperlipidemia, or coronary artery disease (CAD), taking a statin, such as Lipitor, may serve to prolong their lifespan. But, I have to wonder, if this is truly the case, by how much? In other words, would it be worth it? Do the pros of taking the medication outweigh whatever cons exist?

It turns out this was studied by Ferket, et al., in 2012, in asymptomatic individuals with established, non-fatal coronary artery disease.[2] Here's what the authors had to say on the matter:


Two important caveats come to mind, for me:

1.) Their model estimated... "x." That doesn't mean someone else's model, predicated on different criteria, couldn't be made to estimate "y."

2.) It's also important to note that the study population they are referring to are people with stable disease and non-fatal atherosclerosis. These numbers might look a little different, should they have examined folks with unstable atherosclerotic disease. Possibly. But, again, I would wonder by how much.

Having prefaced with those two statements, I think this was an incredibly interesting study. All the more fascinating, because they seemed to have found a maximum lifespan increase in primary CVD prevention patients of roughly 0.7 years.

Let's assume that this result holds for a moment. Listed below are just a few of the well-documented adverse events associated with statin therapy, in the primary biomedical literature:

               - Short-term memory loss and cognitive impairment[3]
               - Worsened insulin resistance, or newly developed type 2 diabetes mellitus[4-5]
               - Severe muscle disease, including myositis and rhabdomyolysis[6-7]
               - Mitochondrial dysfunction[8]
               - Significant vascular calcification and arteriosclerosis[9]
               - Atherosclerosis and heart failure[10]

So, you tell me (because it may just be a thing of personal preference or philosophy); would it be worth it for you, to have just one more year of life, but to potentially suffer any one of a number of significant side effects in the process, or even develop other serious and debilitating diseases?

Moving along....

Years ago, there was yet another cholesterol-related drug in the clinical trial phases of testing, but was, it turned out, a miserable failure, because it was killing people.[11] Torcetrapib, a cholesteryl-ester transfer protein (CETP) inhibitor, was actually completely halted during the testing process, the clinical trials stopped in their tracks, because the deaths were piling up with a frequency that the FDA was uncomfortable with.

This led Tall and colleagues, among other researchers throughout the world, to question whether or not the cause of these deaths was the molecule in the drug, or the mechanism, itself.

In my opinion, all one must do to reach a conclusion here is to look at the aforementioned adverse events, when we inhibit cholesterol synthesis or mess with the mevalonate pathway, and it should be clear to us all: the problem seems to be with the evolutionarily conserved mechanisms we are messing with, not necessarily the molecules.

Now, in 2015, Big Pharma has its eye on another "big win" for preventing cardiovascular disease - still regarding cholesterol, mind you. Another mechanistic inhibitor, pharmacological PCSK9-inhibition. Where statins target synthesis, CETP-inhibitors attempt to block the transfer of cholesterol and triacylglycerols from lipoproteins to cells, PCSK9-inhibitors work to prevent certain strains of the enzyme proprotein convertase subtilisin/kexin type 9 (PCSK9), from downregulating or destroying LDL-receptors in the liver, which is the primary disposal site of excess LDL-particles from the blood.

What will the results of these experiments be, I wonder? It could be that this turns out to be a miracle drug for someone with advanced hyperlipoproteinemia. But, what, for example, do you suppose might happen to an otherwise healthy person when their overly eager health care provider prescribes the PCSK9-inhibitor as a first line of defense, in the primary prevention setting, not realizing that very low cholesterol is also quite dangerous. Hypocholesterolemia is associated with cognitive deficits, increased risks of cancer, and, most notably, a three-fold higher risk of hemorrhagic stroke. There is a reason that every single eukaryotic cell in the entire body synthesizes and requires cholesterol to some degree to exist healthfully.

Just today, I saw on Twitter a post from Nature Medicine regarding the membrane protein Nogo-B, which has recently been shown to have inhibitory effects on sphingolipid biosynthesis in murine models. How long do you suspect it will be before they've concocted a pharmaceutical drug designed to inhibit human sphingolipid biosynthesis, because of this new information? Whether that may turn out to be beneficial or harmful, I couldn't say. But that's not the point.

My point is that we've lost sight of what is most important in health care: quality of life. (In favor of "quantity of life.") In an attempt to halt one aspect of the progression of one disease, we have forsaken functional, positive health, well-being and quality of life, in the hopes for longevity, in the form of "delaying death."

This is not health. This is not what health care should be about. We can and should do better.



REFERENCES

[1] Sijbrands, E. J., Westendorp, R. G., Lombardi, M. P., Havekes, L. M., Frants, R. R., Kastelein, J. J., & Smelt, A. H. (2000). Additional risk factors influence excess mortality in heterozygous familial hypercholesterolaemia. Atherosclerosis, 149(2), 421-425.
[2] Ferket, B. S., van Kempen, B. J., Heeringa, J., Spronk, S., Fleischmann, K. E., Nijhuis, R. L., ... & Hunink, M. M. (2012). Personalized prediction of lifetime benefits with statin therapy for asymptomatic individuals: a modeling study.
[3] Galatti, L., Polimeni, G., Salvo, F., Romani, M., Sessa, A., & Spina, E. (2006). Short‐Term Memory Loss Associated with Rosuvastatin. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, 26(8), 1190-1192.
[4] OHMURA, C., WATADA, H., HIROSE, T., TANAKA, Y., & KAWAMORI, R. (2005). Acute onset and worsening of diabetes concurrent with administration of statins. Endocrine journal, 52(3), 369-372.
[5] Koh, K. K., Quon, M. J., Han, S. H., Lee, Y., Kim, S. J., & Shin, E. K. (2010). Atorvastatin causes insulin resistance and increases ambient glycemia in hypercholesterolemic patients. Journal of the American College of Cardiology, 55(12), 1209-1216.
[6] McClure, D. L., Valuck, R. J., Glanz, M., & Hokanson, J. E. (2007). Systematic review and meta‐analysis of clinically relevant adverse events from HMG CoA reductase inhibitor trials worldwide from 1982 to present. Pharmacoepidemiology and drug safety, 16(2), 132-143.
[7] Manoukian, A. A., Bhagavan, N. V., Hayashi, T., Nestor, T. A., Rios, C., & Scottolini, A. G. (1990). Rhabdomyolysis secondary to lovastatin therapy. Clinical chemistry, 36(12), 2145-2147.
[8] Statin adverse effects: a review of the literature and evidence for a mitochondrial mechanism. Am J Cardiovasc Drugs. 2008; 8(6): 373-418. doi: 10.2165/0129784-200808060-00004.
[9] Auscher, S., Heinsen, L., Nieman, K., Vinther, K. H., Løgstrup, B., Møller, J. E., ... & Egstrup, K. (2015). Effects of intensive lipid-lowering therapy on coronary plaques composition in patients with acute myocardial infarction: assessment with serial coronary CT angiography. Atherosclerosis, 241(2), 579-587.
[10] Okuyama, H., Langsjoen, P. H., Hamazaki, T., Ogushi, Y., Hama, R., Kobayashi, T., & Uchino, H. (2015). Statins stimulate atherosclerosis and heart failure: pharmacological mechanisms. Expert review of clinical pharmacology, 8(2), 189-199.
[11] Tall, A. R., Yvan-Charvet, L., & Wang, N. (2007). The Failure of Torcetrapib Was it the Molecule or the Mechanism?. Arteriosclerosis, thrombosis, and vascular biology, 27(2), 257-260.

Wednesday, September 16, 2015

A Calorie is a Calorie... Right?

I will offer my best attempt at explaining this concept, while keeping the impending rant relatively brief.

How many times have you seen both of these phrases, at one time or another?:

1. "A Calorie is a Calorie." (Thus insinuating that the composition of our food doesn't matter.)
2. "A Calorie is not a Calorie." (Thus implying that the quality and composition of the food we eat is the only thing that matters.)

In order to satisfactorily answer the question whether a Calorie is a Calorie, we must first define our terms.

A calorie is a unit of thermochemical energy, equal to approximately 4.184 joules. Roughly speaking, it is the amount of heat released from a substance when that substance is oxidized, or burned. Classically: a calorie is the "amount of energy needed to raise the temperature of 1 g of water by 1 degree Celsius, at a pressure of 1 atm."

Important to note here is that a calorie and a Calorie are not mathematically equivalent. Calorie, with a capital C, is actually 1,000 gram calories, or 1 kilocalorie (kilogram calories; 4,184 J). It's confusing at first, I know, but you'll get it.

The thing that bothers me is this: by saying "a Calorie is not a Calorie," what you are effectively suggesting is that 4.184 J does not equal 4.184 J. Uh... Yes it is and yes it does. It's math, and the thing about mathematical proofs is: they can be proven. But let's ignore the philosophy and science of mathematics, for the time being. I understand what you are really trying to say. You're trying to say that "Counting calories is ineffective." So, why why not just say that? Let us all choose to be more precise in our thinking, and in the way we convey those thoughts to the world.

Make no mistake about it. A Calorie is a Calorie is a Calorie, because, 4.184 J is 4.184 J is 4.184 J.

That said, just because 1 Calorie = 1 Calorie, chemically and mathematically, that does not necessarily mean that oxaloacetate is phosphoenolpyruvate is acetyl-CoA is alpha-ketogluterate, or that protein is carbohydrate is fat. Or, for that matter, that glucose is fructose is cellulose is ribose. Or, really, any other combination of similar nutrition-related sets you can conceive of. Do you see where this is going? That's because these compounds are actually different "things" with different biochemical and physiological actions. Different molecules, different substrates, different structures, composed of different things, or even just different amounts of different "stuff." Point being, just as 8 of something is always the same as any other 8 of the same something, a Calorie is and will always be a calorie.

Duh.

But by conceding the truth of that cliched statement, I've told you nothing useful about metabolic processes. At least not with regard to their various causes and effects. Appealing to an energy flux, with respect to physiology and metabolism, speaks only to the large-scale (macro-level) results of thousands of chemical interactions happening within the system, yet it says nothing about those (micro-level) biochemical interactions.

What frustrates me about the opposing idea, that "a Calorie is a Calorie," at least as it is currently argued in the nutrition sphere, is that this notion implies that the 1st law of thermodynamics (the conservation of mass and energy) and "Calories in, Calories out" are exactly equivalent scientific hypotheses. In fact, they are not -- at least not from a pragmatic perspective, and I'll tell you why.

Calories in, calories out (CICO) could only be identical to Energy Conservation if all of the incoming energy and all of the outgoing energy (and every biochemical or biophysical transformation in the middle) could be measured and accounted for. As far as I am aware, this is currently impossible. Calories in, as measured by the average person, is often hundreds of Calories off the mark; and even our best methods of measurement in this area are not precise enough to account for all the physiological activity that takes place after said energy has been consumed. (After all, we don't just care about what's incoming, we care about what our cells are doing with this energy, and this is incredibly complex. To my knowledge, this is not something we are able to measure with any amount of precision.) On the other end of the spectrum, Calories out is equally, if not much more, challenging to measure.

You know that little monitor on your elliptical which tells you how many calories you're supposedly burning, during your workout? It's wrong; and not just some of the time, it's always wrong. So wrong, you'd be astonished. You might as well put a piece of black electrical tape over it and forget it's even there, that's how useless it is.

In most cases, energy expenditure is so multivariate, complicated, dynamic and difficult to measure with sufficient accuracy and precision, that it's a wonder anyone can conflate CICO with energy conservation - even if the underlying conception isn't entirely incorrect.

You shouldn't come away from this post going: this author thinks all Calories are equivalent, so eat whatever you'd like. Don't misinterpret. I'm saying all calories of the same amount are equivalent amounts of energy -- however, the substrates from which they came may not be. The latter is not only more important, but far more interesting, in my opinion, as this is where the intricate biology takes place, and is one of the things that separates us from physical machines.

Human beings are not bomb calorimeters.

(As an aside: we do not "burn calories" -- our cells burn chemical substrates and release the thermochemical energy in their chemical bonds as heat. Which substrates are oxidized, at what rates, in which pathways, etc., all of this matters far more in describing the "whys" of metabolic interactions than any appeal to an energy flux ever could.)**

**To the many internet nutrition gurus who have come to believe that the human body - or, indeed Life (i.e. cells), in general - does not obey and cannot be described by the laws of thermodynamics, I suggest you do some reading in statistical mechanics and non-equilibrium thermodynamics, because the statement: "We are open systems, therefore, thermodynamics doesn't apply" is misleading and incorrect.