Archive for August, 2012

…thoughts on hiking, med school, and life…

The last couple of weeks have been a bit of a whirlwind.  First there was the Ancestral Health Symposium (more on that later- if I ever get my thoughts together), then there was the flurry of activity that marked the end of my Family Medicine Clerkship (topped off with a nice 2.5 hour exam), and before the dust settled I was off to the airport to make the most of every hour of the one-week vacation that my school grants third year medical students at the end of the Family Medicine Clerkship.  I spent that week touring Colorado with my long-time best friend.

I expect that everyone has heard the phrase “It’s the journey, not the destination”.  A quick internet search suggests that this gem comes from Ralph Waldo Emerson (1803-1882), though this is unsubstantiated by any reference… Sourced or not, it seems to be a sentiment that most people can get behind.  My recent mental meanderings- while hiking, while musing about med school, and while thinking about life- have me wondering otherwise.

I enjoy hiking.  As the demands of my degrees have changed I’ve had to take a step back from my equestrian endeavors and embrace other activities that can be picked up and put down a little more easily.  I’ve had a pretty good season for hiking thus far- hitting up a number of beautiful locations.  Some, like my recent trek up Matterhorn Peak in Colorado, were out and back trips, while others, like Falls Trail at Rickets Glenn in Pennsylvania, were scenic loops.  When it comes to hikes, these two adventures were very different.  Climbing the Matterhorn was, in all honesty, a grueling trudge through rather stark scenery to “bag” a 13er (a peak over 13,000 feet- Matterhorn is 13,590).  The Falls Trail at Rickets Glenn, on the other hand, is a non-stop feast for the eyes of waterfalls and lush greenery that takes you back where you started, with no single “goal” for the trip.  In the context of this post, one could easily argue that the former was all about the destination while the later was about the journey.

I said that the trek to the top of Matterhorn was a grueling trudge.  I’ll admit that I was rather ignorant of what I was getting myself into when I boldly posited that “We should climb Matterhorn.” Honestly, I made this statement based on the general location (in the San Juans near where we wanted to camp) and the name (named after the Swiss peak- which has a much higher death toll!).  I didn’t quite realize when we set out the magnitude of the mountain we were climbing, nor the type of country we would be traversing.  Unlike the lush countryside I am used to exploring back east, much of the hike up to the summit was above the tree line, in alpine tundra.  While the trip to the top was interspersed with pauses in which I appreciated the absolutely awe-inspiring views, it was a hike that in all honesty was rather dull.  The top, however, was anything but dull. Visually, the uninterrupted views of the Rocky Mountains extending for miles were breathtaking. Personally, the satisfaction of successfully climbing (I’m mildly averse to the term “bagging”) a large named mountain was immense (and I did it in Vibram Five Fingers- an additional triumph).  Was the journey worth these end satisfactions? Yes! But in this circumstance- the destination certainly trumped the journey.

View from Matterhorn

View from Matterhorn: A place to think…

Med school is also a journey.  Much like the climb up Matterhorn, parts of it are grueling and significant portions are unpleasant.  There are, however, moments of awe and wonder.

There are people that grew up knowing they wanted to be a doctor; I was not one of them.  In fact, I actively told people I would not be a doctor when I was asked the dreaded “What do you want to be when you grow up?” question.  Even as I completed college my inclination was always towards research and not clinical practice, and I committed to an MD/PhD program with the thoughts of using the clinical knowledge (and the professional clout of the MD) to pursue medical research.  Much like climbing Matterhorn- I really didn’t know what I was getting myself into when I signed on to attend med school.  The MD/PhD degree was a destination, something to be obtained without much thought to the journey.

Now that I am in med school, and I recognize the magnitude of the effort required to reach this goal, I wonder- if I knew what I was getting myself into when I embarked, would I have started?  While it is surely not the case for everyone, I entered med school with my mind on the destination, with almost complete ignorance of the journey that entailed.  It has been, and continues to be, one hell of a journey.  There are many aspects of this adventure: the people I have met (classmates, friends, professors, and patients), the events I have experienced, the emotions I have witnessed, the intimate details of their lives that patients have shared… These have made for an incredible experience, and are things I would never have experienced without the end destination of a degree in medicine.

Playing at Rickets Glenn

Playing at Rickets Glenn: Sometimes it’s about the journey, and sometimes the journey is more fun when you go off trail!

Destinations change.  Sometimes they are unreachable, sometimes they are not what you expect, and sometimes they are just a point on the way to a yet further destination.  They do, however, inspire journeys.  Journeys vary based on destination, and while life is not a destination, one might argue (and indeed I do) that the journey of life gets more interesting when you choose a destination.

Choose a destination. It can be big or it can be small, but it should be something you choose. The journey of life seems much more interesting when you are chasing your own goal than when you are treading the path of someone else’s expectations. And don’t worry too much… you can always change your destination if a better one comes into view.

En route to Diamond Lake (Colorado): What you find on the way to your destination, and what you do with it, is all part of the fun.

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Road Trip!

I have more to write about lipids and liver (consider yourselves warned!), but I likely won’t have a post out on that subject for a little while.

During the last month I have been enjoying my Family Medicine Clerkship. I am very fortunate to be working with an excellent and enthusiastic physician, with whom I have had fantastic patient interactions both in the office and on house calls (Yes, house calls- who knew physicians still did those?!). Not only is this physician an enthusiastic practitioner and teacher, but she is also very supportive of my (not so main-stream) academic interests. This was evident in the office, where she was keen to push me towards patients whose medical conditions I was particularly interested in and where she encouraged me to talk about nutrition with many of the patients (Yes- evolutionarily appropriate nutrition- not some American Diabetic Association or “My Plate” nonsense”).  This physician was also keen that I pursue my academic interests outside of the clinic, so she has worked with me and my schedule so that I can attend the 2nd annual Ancestral Health Symposium in Boston at the end of this week.

This time last year I was in the throes of writing my thesis, and I was forced to watch the inaugural Ancestral Health Symposium from the sidelines (you can watch the videos from last years symposium here). I’m very excited to participate in person this year!  (If you’re unable to attend but want to be kept up to date, you can follow the twitter feed @Ancestry2012)

While I am looking forward to a number of the lectures on offer this year, I am equally excited about catching up with other people interested in Ancestral Health.  I’ve been fortunate to cultivate a number of friendships within this community over the last couple years, though because of distance I’ve only met a couple people in person.  While I’ve come to know some quite well through the powers of e-mail, Skype, and Twitter, there’s nothing quite like some face time with friends who share (arguably very nerdy) interests.

Anyway- this is a drawn out way of saying “Hey- I’m headed to Boston for AHS 2012. If you’ll be there and want to say ‘Hi’, please do!”.

Pic- for identification purposes!

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As my last post started to explore, different types of dietary fats have different effects on the progression of alcoholic liver disease. This post will further explore the protective effects of saturated fats in the liver.


For many, the phrase “heart healthy whole grains” rolls off the tongue just as easily as “artery clogging saturated fats”. Yet where is the evidence for these claims? In the past few decades saturated fats have been demonized, without significant evidence to suggest that natural saturated fats cause disease (outside of a few well touted epidemiological studies). Indeed, most of the hypothesis-driven science behind the demonization of saturated fats is flawed by the conflation of saturated fats with artificial trans fats (a la partially hydrogenated soybean oil).


In the face of a lack of any significant scientific evidence that clearly shows that unadulterated-saturated fats play a significant role in heart disease (and without a reasonable mechanism suggesting why they might), I think the fear-mongering “artery clogging” accusations against saturated fats should be dropped. On the contrary, there is significant evidence that saturated fats are actually a health promoting dietary agent- all be it in another (though incredibly important) organ.


Again (from my last post), here is a quick primer on lipids (skip it if you’re already a pro). For the purpose of this post, there are two important ways to classify fatty acids. The first is length. Here I will discuss both medium chain fatty acids (MCFA), which are 6-12 carbons long, and long chain fatty acids (LCFA), which are greater than 12 carbons in length (usually 14-22; most have 18). Secondly, fatty acids can have varying amounts of saturation (how many hydrogens are bound to the carbons). A fatty acid that has the maximal number of hydrogens is a saturated fatty acid (SAFA), while one lacking two of this full complement, has a single double bond and is called  monounsaturated (MUFA) while one lacking more (four, six, eight etc.) has more double bonds (two, three, four, etc.) and is called a polyunsaturated fatty acid (PUFA).


Next time you eat a good fatty (preferably grass-fed) steak, or relish something cooked in coconut or palm oil, I hope you will feel good about the benefits you are giving your liver, rather than some ill-placed guilt about what others say you are doing to your arteries. From now on, I hope you think of saturated fats as “liver saving (and also intestine preserving) lipids”. Here’s why:


In 1985, a multi-national study showed that increased SAFA consumption was inversely correlated with the development of liver cirrhosis, while PUFA consumption was positively correlated with cirrhosis [1].  You might think it is a bit rich that I blasted the epidemiological SAFA-heart disease connection and then embrace the SAFA-liver love connection, but the proof is in the pudding- or in this case the experiments that first recreated this phenomenon in the lab, and then offered evidence for a mechanism (or in this case many mechanisms) for the benefits of SAFA.


The first significant piece of support for SAFA consumption came in 1989, when it was shown in a rat model that animals fed an alcohol-containing diet with 25% of the calories from tallow (beef fat, which by their analysis is 78.9% SAFA, 20% MUFA, and 1% PUFA) developed none of the features of alcoholic liver disease, while those fed an alcohol-containing diet with 25% of the calories from corn oil (which by their analysis is 19.6% SAFA, 23.6% MUFA, and 56.9% PUFA) developed severe fatty liver disease [2].


More recent studies have somewhat complicated the picture by feeding a saturated fatty-acid diet that combines beef tallow with MCT (medium chain triglycerides- the triglyceride version of MCFAs). This creates a diet that is more highly saturated than a diet reliant on pure-tallow, but it complicates the picture as MCFA are significantly different from LCFA in how they are absorbed and metabolized. MCFA also lead to different cellular responses (such as altered gene transcription and protein translation). Nonetheless, these diets are useful for those further exploring the role of dietary SAFA in health and disease.


These more recent studies continue to show the protective effects of SAFA, as well as offer evidence for the mechanisms by which SAFA are protective.


Before we explore the mechanisms, here is a bit more evidence that SAFAs are ‘liver saving’.



A 2004 paper by Ronis et al confirmed that increased SAFA content in the diet decreased the pathology of fatty liver disease in rats, including decreased steatosis (fat accumulation), decreased inflammation, and decreased necrosis.  Increasing dietary SAFA also protected against increased serum ALT (alanine transaminase), an enzymatic marker of liver damage that is seen with alcohol consumption [3].  These findings were confirmed in a 2012 paper studying alcohol-fed mice. Furthermore, these researchers showed that SAFA consumption protected against an alcohol-induced increase in liver triglycerides [4].  Impressively, dietary SAFA (this time as MCT or palm-oil) can even reverse inflammatory and fibrotic changes in rat livers in the face of continued alcohol consumption [5].


But how does this all happen?


Before I can explain how SAFA protect against alcoholic liver disease, it is important to understand the pathogenesis of ALD. Alas, as I briefly discussed in my last post, there are a number of mechanisms by which disease occurs, and the relative importance of each mechanism varies based on factors such as the style of consumption (binge or chronic) and confounding dietary and environmental factors (and in animals models, the mechanism of dosing). SAFA is protective against a number of mechanisms of disease progression- I’ll expound on those that are currently known.


In my opinion, the most interesting (and perhaps most important) aspect of this story starts outside the liver, in the intestines.


In a perfect (healthy) world, the cells of the intestine are held together by a number of proteins that together make sure that what’s inside the intestines stays in the lumen of the intestine, with nutrients and minerals making their way into the blood by passing through the cells instead of around them. Unfortunately, this is not a perfect world, and many factors have been shown to cause a dysfunction of the proteins gluing the cells together, leading to the infamous “leaky gut”. (I feel it is only fair to admit that when I first heard about “leaky gut” my response was “hah- yeah right”. Needless to say, mountains of peer-reviewed evidence have made me believe this is a very real phenomenon).


Intestinal permeability can be assessed in a number of ways.  One way is to administer a pair of molecular probes (there are a number of types, but usually a monosaccharide and a disaccharide), one which is normally absorbed across the intestinal lining and one that is not. In a healthy gut, you would only see the urinary excretion of the absorbable probe, while in a leaky gut you would see both [6]. Alternatively, you can look in the blood for compounds such as lipopolysaccharide (LPS-a product of the bacteria that live in the intestine) in the blood. (Personally, I would love to see some test for intestinal permeation become a diagnostic test available to clinicians.)


Increased levels of LPS have been found in patients with different stages of alcoholic disease, and are also seen in animal models of alcoholic liver disease.  Increased levels of this compound have been associated with an increased inflammatory reaction that leads to disease progression.  Experimental models that combine alcohol consumption and PUFA show a marked increase in plasma LPS, while diets high in SAFA do not.



But why? (Warning- things get increasingly “sciencey” at this point. For those less interested in the nitty-gritty, please skip forward to my conclusions)


Cells from the small intestine of mice maintained on a diet high in SAFA, in comparison to those maintained on a diet high in PUFA, have significantly higher levels of mRNA coding for a number of the proteins that are important for intestinal integrity such as Tight Junction Protein ZO-1, Intestine Claudin 1, and Intestine Occludin.  Furthermore, alcohol consumption further decreases the mRNA levels of most of these genes in animals fed a high-PUFA containing diet, while alcohol has no effect on levels in SAFA-fed animals.  Changes in mRNA level do not necessarily mean changes in protein levels, however the same study showed an increase in intestinal permeability in mice fed PUFA and ethanol in comparison to control when measured by an ex-vivo fluorescent assay. This shows that PUFA alone can disturb the expression of proteins that maintain gut integrity, and that alcohol further diminishes integrity. In combination with a SAFA diet, however, alcohol does not affect intestinal permeability [4].


Improved gut integrity is no doubt a key aspect of the protective effects of SAFA. Increased gut integrity leads to decreased inflammatory compounds in the blood, which in turn means there will be decreased inflammatory interactions in the liver.  Indeed, in comparison to animals fed alcohol and PUFA, animals fed alcohol with a SAFA diet had significantly lower levels of the inflammatory cytokine TNF-a and the marker of macrophage infiltration MCP-1 [4].  Decreased inflammation, both systemically and in the liver, is undoubtedly a key element of the protective effects of dietary SAFA.


This post is already becoming dangerously long, so without going into too much detail, it is worth mentioning that there are other mechanisms by which SAFA appear to protect against alcoholic liver disease. Increased SAFA appear to increase liver membrane resistance to oxidative stress, and also reduces fatty acid synthesis while increasing fatty acid oxidation [3]. Also, a diet high in SAFA is associated with reduced lipid peroxidation, which in turn decreases a number of elements of inflammatory cascades [5]. Finally- and this is something I will expand on in a future post- MCFAs (which are also SAFA) have a number of unique protective elements.


I realize that this post has gotten rather lengthy and has brought up a number of complex mechanisms likely well beyond the level of interest of most of my readers…


If all else fails- please consider this:


The “evidence” that saturated fats are detrimental to cardiac health is largely based on epidemiological and experimental studies that combined saturated fats with truly-problematic artificial trans-fats. Despite the permeation of the phrase “artery clogging saturated fats”, I have yet to see the evidence nor be convinced of a proposed mechanism by which saturated fats could lead to decreased coronary health.




There is significant evidence, founded in epidemiological observations, confirmed in the lab, and explored in great detail that shows that saturated fats are protective for the liver. While I have focused here on the protective effects when SAFA are combined with alcohol, they offer protection to the liver under other circumstances, such as when combined with the particularly liver-toxic pain-killer Acetaminophen [7].


Next time you eat a steak, chow down on coconut oil, or perhaps most importantly turn up your nose at all things associated with “vegetable oils” (cottonseed? soybean? Those are “vegetables”?), know that your liver appreciates your efforts!



1.            Nanji, A.A. and S.W. French, Dietary factors and alcoholic cirrhosis. Alcohol Clin Exp Res, 1986. 10(3): p. 271-3.

2.            Nanji, A.A., C.L. Mendenhall, and S.W. French, Beef fat prevents alcoholic liver disease in the rat. Alcohol Clin Exp Res, 1989. 13(1): p. 15-9.

3.            Ronis, M.J., S. Korourian, M. Zipperman, R. Hakkak, and T.M. Badger, Dietary saturated fat reduces alcoholic hepatotoxicity in rats by altering fatty acid metabolism and membrane composition. J Nutr, 2004. 134(4): p. 904-12.

4.            Kirpich, I.A., W. Feng, Y. Wang, Y. Liu, D.F. Barker, S.S. Barve, and C.J. McClain, The type of dietary fat modulates intestinal tight junction integrity, gut permeability, and hepatic toll-like receptor expression in a mouse model of alcoholic liver disease. Alcohol Clin Exp Res, 2012. 36(5): p. 835-46.

5.            Nanji, A.A., K. Jokelainen, G.L. Tipoe, A. Rahemtulla, and A.J. Dannenberg, Dietary saturated fatty acids reverse inflammatory and fibrotic changes in rat liver despite continued ethanol administration. J Pharmacol Exp Ther, 2001. 299(2): p. 638-44.

6.            DeMeo, M.T., E.A. Mutlu, A. Keshavarzian, and M.C. Tobin, Intestinal permeation and gastrointestinal disease. J Clin Gastroenterol, 2002. 34(4): p. 385-96.

7.            Hwang, J., Y.H. Chang, J.H. Park, S.Y. Kim, H. Chung, E. Shim, and H.J. Hwang, Dietary saturated and monounsaturated fats protect against acute acetaminophen hepatotoxicity by altering fatty acid composition of liver microsomal membrane in rats. Lipids Health Dis, 2011. 10: p. 184.

What is “Fatty Liver”? Well here’s a slide from my research showing a slice of liver from a control-fed rat on the left and an alcohol-fed rat on the right. Arrows mark macrovesicular lipid accumulations (other models can show much more impressive lipid accumulations).

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