Thursday, April 28, 2011

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.
     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.

1 comment:

  1. Very great article about nutrition. I will keep in touch with your interesting blog!