Kidneys and Ketones.

     When you shuffle thorough various low carb or nutrition blogs, you can't help but feel the splash of a new low carb diet study.  Especially when media generate headlines such as "Low carb, high fat diet could replace dialysis."  While it would have been prudent for MSNBC to clarify that this may end up only applying to mice, the results are still news worthy.  

     The work was conducted by researchers at the Mount Sinai School of Medicine in New York, NY. They investigated the effect of diet, specifically a ketogenic diet, on nephropathy in diabetic mouse models.  To many people, this may seem to be a paradoxical diet to study in diabetics - perhaps ketoacidosis comes to mind - but it looks to have potential.

Source:  OpenClipArt

     Nephropathy refers to damage of the kidneys and is a known complication of diabetes.  Prior to the advent of insulin therapy, type 1 diabetes (absence of insulin) caused a very short life expectancy.  However, as insulin allowed type 1 diabetics to live much longer lives, and as more and more people are becoming type 2 diabetics (insulin resistant), these individuals are living with long-term exposures to relatively high blood sugar.  Fortunately, the standard of care is to maintain blood glucose as near normal as possible, which has been shown to reduce - although not eliminate - complications of hyperglycemia.  These researchers had a hunch that there could me an additional strategy for reducing complications, and perhaps even reversing it.
     While working on other experiments, the researchers noted that ketones produced a molecular action that could benefit diabetic patients.  They also demonstrated that ketones directly reduce the oxidative damage induced by bathing neurons in a glucose solution.  Given that the ketogenic diet shifts cell metabolism away from glucose utilization and towards fat and ketone utilization,  they hypothesized that a ketogenic diet would protect against the hazardous effects of chronic hyperglycemia.
     The study used eight groups of animals:  four groups of normal "wildtype" mice, two groups of Akita mice (type 1 diabetes model), and two groups of leptin receptor knockout mice (type 2 diabetes model - see image).  All groups were placed on a control "chow" diet (high carb, low fat, moderate protein) until the diabetic models developed nephropathy; then two control groups and one group from each model were switched to a ketogenic diet (very high fat (87%), low carb and protein) until the end of the study.  The researchers then assessed blood markers, gene expression, and kidney histology for nephropathy.

Left is "wild type," right is db/db mouse.
Source:  ncbi.nlm.nih.gov

     The most impressive finding is that the elevated albumin-to-creatnine ratio (ACR - a marker for nephropathy) found in the chow-fed diabetic models was abolished in the ketogenic counterparts - a complete reversal of the marker (see figure below).

Source: PLoS ONE

     The ketogenic diet appears to blunt or completely reverse the oxidative or other stress mediated gene expression seen in the pathogenic mice.  These "functional" findings are the most impressive, but the study also showed a partial reversal of the histological damage in the kidneys; given more time, this could conceivably mean that a return to near or total anatomical normality may occur.  The idea that ketones greatly benefit diabetics may seem paradoxical, but it isn't so simple.
     When people talk about the Atkin's Diet - a ketogenic diet upon initiation - they invariably make the association to ketoacidosis in unchecked diabetes.  However, ketoacidosis is a consequence of systemic cellular starvation in the absence of insulin, which leads to an unregulated release of ketones into the blood that eventually turns the blood acidic.  Ketosis is a physiological elevation of ketones from fat metabolism in the absence of glucose and produces benign levels of ketones in the blood.  Despite the distinction, the connection between ketones and kidney protection is not obvious. 
     This study offers a proof of concept that some nutrition strategies can at least begin to reverse a disease process such as nephropathy.  While there is no question that this may not work in humans, or if anyone is sure that enough patients would maintain a ketogenic diet long enough to invoke an improvement, these finds are compelling.  Perhaps they will find other potential therapies using cream, eggs, and bacon.

Gary Taubes's article on sugar

Taubes has written another article that I wanted to share.  This one discusses sugar consumption - separately from carbohydrate consumption - and some real and potential consequences of it.  There is not enough evidence to conclude that sugar is as detrimental as some purport it to be; but it is categorically true that refined sugar (or naturally attained sucrose for that matter) is non-essential in the human diet.  In that respect, it's easy to draw some parallels with something like alcohol.

What do you think?  Is Sugar Toxic?

Some recent eats... before I post about aerobic exercise and diet.

Weekend breakfast with the girlfriend.  Veggie omelets topped guacamole, bacon, and strawberries on the side.

Weekend dinner with the friends.  BBQ beef ribs (pictured) with sweet potatoes and sautéed kale.  Hard not to enjoy such a colorful dinner.

Dinner this week.   Fried grass-fed hamburger with aged Gruyere and avocado (half of a giant one!).  I stocked up on quite a bit of Trader Joe's organic beef.  I appreciate that their organic variety is also grass-fed...rather than simply organic corn feed.

Veggies with a homemade dill ranch dressing.

Noting wrong with dinner and science (see books in the distance).  

The wine was left over from Sunday and I couldn't let it go to waste...

Civil Eats: Where do Americans get their calories?

I am busy this week crunching data for a potential research abstract, so I thought I would send in a blog substitute for today.  Check out this post by Civil Eats.

It has a really neat info-graphic that shows America's estimated per capita calorie consumption from various food groups between 1970 and 2008.  I find what we're eating to be more telling than how much.

The major limitation of this data is that it is derived from USDA food availability statistics and not from samples of what individuals actually consume.  While they have adjusted for grocery store waste, they have not adjusted for restaurant waste.  This could mean that all the oil leftover in deep-fryers is estimated into the consumption statistics.

Added sugar appears to have risen about 20%.  Meat, egg, and nut consumption has gone unchanged.  Grain consumption inflates in the 1980's (fear of fat trend?), and added fat inflates between 1990's and 2000's.  From this data, I find it hard to blame the consumption of animal products as a cause of our current dietary tribulation, so I'm maintaining that sugar and flour are the problems.  

Bison/Beef bone broth

Dinner this past week was accompanied by homemade bone broth.  It's my celebration of obscure grass-fed cuts of meat from the farmer's market.  I used bone-marrow bones and neck bones.  Cuts that are primarily bone are essentially scraps and are much cheaper than steak cuts.

First, I roasted the bones at 400 degrees Fahrenheit for about 20 minutes.

Meanwhile, I chopped up some celery, carrots, and onion.  I had some pre-chopped garlic on hand, so that cut a step (pun intended).

 

I removed the bones from the oven and made sure they had a nice roasted-brown color.  I had to be careful with the marrow bones as the fatty marrow can easily burn if left unchecked.  

I added the meat, vegetables, and 10 cups of water to my slow cooker.  I used parsley stems, a bay leaf, salt, and whole peppercorns for a bit of an accent.  I left the ceramic bowl in the fridge overnight, and simply put it in the slow cooker before leaving for the lab in the morning.

After cooking for ten hours, the broth was rich and the meat and vegetables were tender.  I strained the broth and ate the meat and vegetables.  And I definitely did not skim off the fat.  I paid a premium for what relatively little fat is left on the grass-fed meat!

A hot cup of broth is perfect for washing down roasted meat.  Just like an Inuit would!

Taube's article criticizing anti-obesity efforts

     Gary Taubes has authored an article about why he thinks current anti-obesity campaigns are doomed to fail, and mentions what the alternate strategy should be.  This article explains my fundamental opposition to calorie postings, which I've discussed in past blog posts (including the one 5 minutes ago!)

     If you have read his work before, you know what he has to say.  If you have not, then it is a good summary of his conclusions about the causes of obesity.

Follow up on calorie labeling in restaurants

     George Loewenstein, professor of Economic and Psycology at Carnegie Mellon University, authored an editorial in the American Journal of Clinical Nutrition entitled "Confronting reality: pitfalls of calorie posting" (AmJCN, apologies, but you can only read this article if you have a site-license via a library or university).
     According to the editorial, mandatory restaurant labeling is more about politics than good science.  The goal of the program is to reverse, or at least stop, the obesity epidemic by reducing calorie intake.  New York was the first city in the U.S. to implement this policy, and did so based on one study published in 2008. However, this study showed only modest benefit and, by design, was unable to determine causality.  This study could only generate a hypothesis.  Since then, more rigorous studies have shown a modest benefit, failed to show a benefit, and even caused some harm - people ordered more calories.
     A large proportion of people simply ignore the information.  However, some people might actually choose to order more calories.  Why?   Given a limited amount of money to spend, some people appear to order as many calories as they can in order to get a "better deal."  I would have to consult with my economist-in-training girlfriend to see if this is a sound explanation.  But perhaps it fails because the premise is wrong - obesity is not simply the result of oblivious gluttony (see next blog post).
     Regardless of the fundamental problem, namely that obesity is driven by the poor quality of the food and not merely the quantity, mandatory calorie postings in restaurants began with poor footing and they have not gained any since. The author remarks (with cynicism) that this policy may continue because it is better than the alternatives, such as taxing specific food items or reducing particular subsidies.  This industry-favoring approach is echoed in the campaign sponsored by the Hershey (yes, the chocolate) Center for Health & Nutrition in collaboration with the American Dietetic Association named Moderation Nation.  Hopefully the science will overcome the politics in this food fight.