Wednesday, October 17, 2012

Ketosis VI: Therapeutic Roles


We have covered most of the hardcore science that I wanted to review when looking at ketosis and ketogenesis.   We have covered most of the relevant biochemistry in terms of how are ketone bodies formed and how they are regulated.  That is all well and good, but I am sure many of you are just wondering how ketosis can benefit you, right?  Well, this article is meant to show you some of the benefits for ketosis. 

Ketogenic diets have been used as therapeutic diets for some conditions for over a century, and while it isn’t used as much anymore, it probably should be.  This article will mainly go over how it can help out those in a disease state; however, I think the mechanisms through which ketones act in the diseases show us some of the power of these energy molecules.  You many not have one of these diseases, but seeing how much they can help with certain conditions certainly makes you think twice about them.


Epilepsy

Severe epileptic seizures affect millions of people around the world every year, and despite the increasing number of anticonvulsant drugs on the market some patients still get seizures.  With modern pharmacology failing these people, what treatments are left for them?  Well, the ketogenic diet has been shown to reduce epileptic seizures by over 75% in many clinical studies since 1920 (1)! 

One of the mechanisms that a ketogenic diet helps with epilepsy is through its actions on GABA.  GABA is the major inhibitory neurotransmitter in our brain, and since epileptic seizures are characterized by large sudden increases in neuron firing, increasing GABA would be a great place to start looking for treatments.  It appears that ketone bodies may help facilitate the conversion of glutamate to GABA in our neurons (2).  While increasing GABA will help control seizures, decreasing glutamate will help just as much, because glutamate is the major excitatory neurotransmitter in our brains.

Another mechanism that ketone bodies might use is inhibiting VGLUT, which is a main glutamate transporter.  One study has shown that ketone bodies are a direct competitive inhibitor of VGLUT, however, they used large doses of ketone bodies in the study, so further research would be needed in a more physiologic setting (3).  

Other Neurological disorders

As we can see with epilepsy, and from the Brain Fuels article, ketone bodies have a potent effect on our brain and its biochemistry.  Ketone bodies have been found to help in a variety of other neurological disorders, and we don’t have to look to far to find papers telling us this benefit (4, 5, 6, 7).

Alzheimer’s is a disorder characterized by amyloid plaques and impaired glucose metabolism in the brain (8).  We know that ketones can help provide an energy substrate for our brains if glucose is not available, so that can be one way ketosis helps those with Alzheimer’s.  Also, one study found that a diet high in ketone producing MCTs caused a decrease in amyloid precursor protein and increased metabolic efficiency in dogs (9). Another long term study of mice showed an overall decrease in amyloid-beta from a high-fat diet (10).

As we saw in the brain fuels article, ketone bodies are an excellent source of energy for our brain, and are one of its most efficient fuels.  If I, or a loved one, had any sort of neurological disorder I would definitely try a ketogenic diet.  The data that they are helpful for the brain in particular is too overwhelming to not try it, even if it is a condition that hasn’t been studied with ketogenic diets much.

Hypertriglyceridemia

As we saw before, being in ketosis has the ability to lower triglycerides.  While we have already covered the biochemistry of this fact in earlier posts, I’d just like to share a couple of trials in which this effect happened in humans.

In one study, patients with severe hypertriglyceridemia were given a formula diet containing MCTs (11). And when I say severe, I mean SEVERE.  At the start of the trial these people had triglyceride levels averaging 1601 mg/dL! Now, while this isn’t a strict ketogenic diet, I think much of the benefits we will see from this diet are from ketogenesis, since the ability to easily form ketone bodies is the main difference between MCTs and other fats.  When given this formula the patients saw reductions in triglycerides from 1601 mg/dL all the way down to 554 mg/dL! While still extremely high, we can see the huge reduction in triglycerides.  Not only that, but this trial was only a week!  In a week they brought their triglycerides down over 1000mg/dL!  They also found significantly lower total cholesterol and fasting glucose levels.

In another trial, patients were again told to ingest 25-30g of either MCT or LCT oil (12).  While we can’t call these true ketogenic diets, I think that is the effect we are seeing.  They were told to maintain a normal activity level, and diet other than the added oil.  After 8 weeks the people in the MCT group had significant lowering of body weight, hip circumference, waist circumference, body fat, and triglycerides!  Wow, after 8 weeks of consuming only a modest amount of MCTs they were able to achieve great results in almost every marker for metabolic syndrome.

I think we can see a major benefit of ketosis from this section.  We can use ketosis as a way to try and normalize our metabolism, and kind of kick start it to start working again.  If we are metabolically deranged and can’t lose weight we need to fix our metabolism before we start to lose the weight.  Also, what is probably the best way to lose weight?  Starvation.  Through ketogenic diets we can stimulate that starvation response while still consuming food.  Not only that, but it normalizes our metabolism back to the way it should be running, because it needs to be as efficient as possible.  The next article will focus on practical ketosis recommendations, so I don’t want to go much further into it here, but I think this is powerful stuff.

Cancer

Cancerous tissue is unique, in that it supplies almost all of its energy from glucose.  It cannot use other forms of energy to supply its growth.  This was first observed by Ottto Warburg, and is thus termed the Warburg Effect (13).  If cancer tissue can only utilize glucose, then in theory a ketogenic diet should be an ideal treatment, since it provides little glucose, but will supply ketones that can be used by most of the other tissues of your body. Well, this is good in theory, however the data are much less ideal. 

I found some studies that supported that a low-carb, ketogenic diet could help with slowing cancer growth (14, 15, 16).  However, several other studies should little to no benefit of the ketogenic diet (17, 18).  I think a ketogenic diet is something to try in patients with cancer, as it the results show it works best as an addition to traditional treatment.  Also, I don’t really see any way that entering ketosis can “hurt” someone.

Summary

And there it is!  These are the conditions where I would definitely say a ketogenic diet has some proven science behind it being able to help.  If I had any sort of neurological disorder, hypertriglyceridemia, or cancer, I would definitely adopt a fairly strict ketogenic diet.  I think ketogenic diets also have a place in weight loss protocol for the obese, and can help to lower cholesterol levels. 

Like I was saying above I think one of the main benfits of ketosis is it helps to normalize our metabolism in a way.  It gets us back to letting our body run the show on which energy to use and when.  So I think ketosis has spot as an adjunct treatment for anything that has to do with metabolism, which is a huge array of diseases and disorders.  If anyone out there has had success on a ketogenic with a disease I didn’t mention, please leave your experiences in the comments!  Next time we will go over my practical recommendations for a ketogenic diet, and how to implement it into a normal lifestyle.

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