Neurodegeneration: Path to Prevention Part 1 – Introduction

NeurodegenerationThis series of posts has been in the works for a long time now, and is not even fully finished yet.  However, I wanted to get out the information that I have gathered so far.  This is a quite complex and involved topic and there is a ton of information out there.  Not only that, but most of that information is difficult to wrap your head around without an appropriate background education and knowledge.  Fairly recent events in my life have directed a lot of my thoughts to neurodegeneration and if/how it can be prevented through an ancestral approach to diet and lifestyle, so I decided why not write about it.  Funny thing is that since beginning to write this series of posts, Dr. Perlmutter went and published a great book on this exact topic “Grain Brain” and pretty much explained most of what I wanted to look into myself, plus a whole lot more :-(.  He does however promote a very low carbohydrate diet, and while this may be a very therapeutic type of diet for someone who is already metabolically deranged, or who has a neurodegenerative disease, it may not be ideal for an ancestral’ish healthy individual.  There are plenty of safe carbs in things like sweet potato, yams, and other tubers.

Regardless, this post will still fit well within the purpose of my blog: “to share my thoughts with like minded and open minded individuals and maybe help some people in the process”.  Also, Frontotemporal Lobar Degeneration (FTLD) has affected my family very recently, and the above noted book did not mention this type of neurodegenerative disease specifically.

Through research into FTLD I was also reminded about other neurodegenerative conditions that have or could possibly affect my immediate and extended family.  These include Alzheimer’s Disease, Type 2 Diabetes Mellitus related neurodegeneration, and Multiple Sclerosis.

Aside from this brief article by Chris Kresser, and these ones (1, 2, 3, 4, 5, 6, 7, 8, 9) specific to Huntington’s Disease, by Kevin Cann, I have not been able to locate a great deal on this topic specifically in the Paleo blogosphere, so I focused my search to peer reviewed science.

Neurodegeneration – Overview

I will end part 1 of this series with a general overview of neurodegeneration.  When reviewing this topic in general, what we find is that although the root causes are not yet fully understood for many neurodegenerative conditions, all of the above listed conditions seem to be tied specifically to inflammation, oxidative stress, metabolic derangement, autoimmunity, or all of the above combined.  Obviously, for you ancestral minded people out there, you are very aware of chronic inflammation/oxidative stress and its relation to many chronic modern diseases such as diabetes, arthritis, psoriasis, heart disease, stroke, MS, and other autoimmune diseases.  However, what you may not know is that systemic inflammation has now come to light as a player in Alzheimer’s disease, and more recently FTLD (1).  While systemic inflammation is seen in many cases of neurodegeneration, what is always seen is significant ongoing inflammation of the central nervous system, and cellular damage from oxidative stress (obviously the 2 are directly related).  What this means is that basically the immune system is primed, and inappropriately active in the brain, which is likely one of the main mechanisms that leads to the death of neurons.  Again, while the full picture still isn’t fully understood, specifically whether inflammation onset occurs before or after the condition prevents itself, it seems to make sense that given the chronic nature of these conditions, we are likely talking about underlying inflammatory and metabolic issues that have been taking place for some time.  There is also evidence that intestinal and blood brain barrier permeability is altered in some, if not all, of these conditions; again, it is the chicken and the egg scenario here regarding what comes first.  However, it is clear that these factors play a role in at least disease progression and quite possibly as a causative factor.

Neurodegeneration – Systemic or Neuroinflammation 

You may now be curious as to where the interplay lies with systemic/peripheral (outside of the central nervous system) inflammation and neuroinflammation.  In the past, it was thought that these systems were totally separate and could not influence one another as the blood brain barrier was not considered very permeable (basically not much could get through).  However, this theory has proven to be false and much more complicated than originally thought.  There is a great deal of evidence out there now enlightening the fact that systemic inflammation (in many different forms) can most definitely lead to neuroinflammation.  Here is a link to a review article explaining this association (2).  Here is another study providing very detailed descriptions of how systemic inflammation may be able to cross the blood brain barrier, or otherwise influence neuroinflammation (3)

Neurodegeneration – Genetics

While these conditions are also tied in some part to genetics (ie. inheritance), as it is with many chronic conditions, the presence of inherited genes will only increase the risk of developing this condition, not guarantee that an individual will develop it.  As with most chronic conditions, the cause lies somewhere within the interplay of genetics, environment, and their relation to gene expression (i.e. epigenetics).  Genotype vs Phenotype: meaning that just because we have a certain gene coding for any given process in the body (genotype), it does not mean that the specific gene is actually turned on, for lack of a better term, and expressing itself.  In the end, what matters is whether any given gene is actually turned on and expressing itself leading to physiological/physical expression (phenotype).  Also, even if a gene is turned on, our environment/lifestyle may be sufficient enough to protect us from the disease causing effects of the active gene putting us at risk.

As a quick example, if you read my post on meditation, you will note that I provide a pretty good example of controlling gene expression.  It goes a little something like this:

We all have specific genes that allow us to produce an inflammatory response in our body for healing and/or some event that our body perceives as stressful or threatening (negative thoughts are included here).  However; meditation has been shown to reduce our bodies expression of genes leading to inflammatory responses – reference included in above link.

Obviously this shows that simple environmental factors have a large part to play in how our genes are expressed.  Guess what – diet is a huge part of our environment!

One more point to throw in the mix is that single nucleotide polymorphisms, which are basically genes that differ across the human population but occur at a frequency high enough that they are not considered mutations, can impact the expression of other genes, or have protective effects against the expression of mutated genes.  An example of this is actually seen in one type of FTLD caused by MAPT gene mutations.  A specific single nucleotide polymorphism has been shown to protect against disease expression in individuals with a MAPT mutation (4, 5)

A final takeaway here is that the cause of neurodegenerative diseases, although many of them being tied strongly to genetics and familial history, are multifactorial and environmental factors most definitely play a role in disease contraction, even in those who have a genetic predisposition or risk factor.

This concludes my first post on neurodegeneration.  In neurodegeneration part 2 I will discuss FTLD specifically, and how it relates to inflammation/oxidative stress, autoimmunity, and metabolic derangement.  Ultimately, I hope to provide a solid argument as to why an ancestral lifestyle is the path to prevention/protection since it allows for proper regulation of inflammation, oxidative stress, metabolism, gene expression, and the immune system; thus, giving our bodies the absolute best chance to function as they were meant to.  If you are not familiar with how an ancestral/paleo lifestyle is beneficial and promotes maximum health, please visit my resources page and read the books and blogs noted.  I don’t think it is necessary to recreate the wheel on explaining the basics and benefits of ancestral/paleo living on the above noted aspects of health; however, in this series I may include some basic links to helpful information on paleo/ancestral living in general.  If you are mainly interested in this type of lifestyle and brain health, one of your first stops on my reference list should definitely be “Grain Brain”.  Although, as noted above, there is significant debate about whether a very low carb ancestral diet (as recommended in grain brain) is necessary for people who don’t have an active neurodegeneration.  Either way, it is still a fantastic book full of great information.

Sincerely,

The Barefoot Golfer·

           

References:

1.) http://www.ncbi.nlm.nih.gov/pubmed/?term=loss+of+function+mutations+in+the+progranulin+gene+are+related+to+pro-inflammatory

2.) http://www.ncbi.nlm.nih.gov/pubmed/24144733

3.) http://www.ncbi.nlm.nih.gov/pubmed/?term=the+blood+brain+barrier+in+neurodegenerative+disease%3A+a+rhetorical+perspective

4.) http://www.ncbi.nlm.nih.gov/pubmed/23742080

5.) http://www.ncbi.nlm.nih.gov/pubmed/21178100

 

6 Comments

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