Basic Science - Energy is Everything

Let's review.  Some 9 months ago, an excitable young psychiatrist of reasonable pedigree launched Evolutionary Psychiatry as a means to explore how the differences between our modern lives and diets compared to traditional/evolutionary experiences may influence the generation of mental illness.  To that end she peeled back the edges of several lines of inquiry - what mental illnesses are increasing rapidly, and what are the theorized reasons as to why?  What are the correlations between mental illness and the known diseases of civilization (heart disease and type II diabetes, primarily, though acne, IBS, and autoimmune diseases of all kinds fall in that rubric)? What dietary factors are drastically different between the nutrient-rich traditional fare and our post-modern industrial food, and what is known about how those dietary factors affect neurotransmitters and brain energetics?  So I read, and read, and read, and depend upon a small cadre of loyal compatriots and commenters with a similar nose for research and a similar goal, and together we have uncovered some interesting things, and nowhere in thousands of pages of reading have I uncovered something that would absolutely refute my original hypothesis.

Part of the story of Evolutionary Psychiatry is the story of its creator and how she [I] thinks.  And when I say I have no patience for philosophy, I mean it.  I've rarely made it past the "God cannot be both benevolent and omnipotent" chapter one of most philosophy books before they are consigned to the dustiest reaches of the bookshelf.  I am left-handed, so theoretically more able to bring in the right brain (though in all likelihood I am also predominantly left-brained like most of you).  I am a woman, therefore likely more balanced between dopamine and serotonin in my ponderings.  I think in collages.  In pictures.  In stories.  My influences are literature and music, the oral and written histories of our people.  For some, the structured rationality of philosophical thought creates links and certainty.  For me, that structure is an imposing irritant and a distraction from the elusive creative links.  I hope I make up in scope for what I lack in rigor.  I rely on folks like Denise and Ned to lose themselves in numbers.  I want the story behind the numbers.

In Evolutionary Psychiatry there are only a few truths that bob to the surface again and again.  Inflammation is the mediator of most evils.   Energy should be made efficiently or there will be a cost.  Fatty meat is good.  Starch is not a dirty word, but an excess sugar certainly is. Ketosis in moderation can be a powerful tool.  Plant protein should be regarded with suspicion as an inflammatory mediator.  Stress and sugar and poor sleep damage the brain.  We should probably consume a little more dirt and get a little more sunshine. 

But let's bring it back to energy.  Energy is everything, and the brain, for all its small size, a massive consumer of energy.  Energy for eukaryotic cells is primarily made in the mitochondria. 

Image from The Science Experts

There are a few "need to knows" about mitochondria.  Like most engines, they create waste.  However, it seems that what we want is plenty of mitochondria working at full efficiency.  If we have leftover or damaged mitochondria just hanging out, they seem to create destructive reactive oxygen species and general mischief (1).  Mischief such as dementia, premature aging, cancer, and probably autism. 

Things that make mitochondria happy and promote effiency and clean energy:

1) A high-fat diet and utilization of ketones
2) A ready supply of energy and mitochondrial cofactors such as the animal flesh-derived carnitine, creatine, and carnosine, and the cholesterol buddy buddy ubiquinone (CoEnzymeQ10), vitamin A, and the football crew of B vitamins are also utilized in the respiratory chain.
3) Protein and/or calorie restriction which promotes the activation of PPAR (that is peroxisome-proliferator acttivated receptors).  See, the mitochondria have two major types of garbage containment facilities, the lysosomes and the peroxisomes.  They are the waste clean-up crew, and they become more active in states of protein restriction and ketosis.  In addition, the old and inefficient mitochondria spewing more reactive oxygen species than they ought get properly decomissioned in states of protein restriction and ketosis.  This is one part of a positive clean-up process called "autophagy." 
4) Aerobic exercise seems to stimulate the creation of new, shiny, efficient mitochondria (2).

What sorts of things promote mitochondrial ineffiency and general dirty cell-killing cancer dementia promoting badness?

1) Hyperglycemia
2) Inactivity
3) Micronutrient deficiencies
4) Never dipping into ketosis

I'm guessing the mitochondrial research folks probably never heard of the paleolithic or primal style approach to diet and living.  But the common recommendations of that approach all converge to make mitochondria mighty happy.  Even the paleo conservatives with their fat phobia will be low carb and encourage intermittent fasting - which in combination should bring *some* ketones into the picture along with temporary protein restriction to promote autophagy.  Paleo/traditional foodists will be rather strident in getting plenty of micronutrients and will have the steaming plates of offal to prove it.  The special mitochondrial-loving amino acids found in meat will be, more than likely, adequately consumed by the meat-loving paleo eater.  In addition, activity is encouraged, lots of it, in realistic exertion and quantity.  The diet itself, being antinflammatory and muscle-sparing, is the perfect fuel to spur activity.

In contrast, the Standard American Diet du jour will promote inflammation ultimately resulting in hyperglycemia, weight gain, inflammation, fatigue, and sedentary living.  Micronutrient deficiencies will be the rule, unless one is exceedingly careful.  And one is told never to let 3 hours or more go by without eating lest the metabolism sputter to a halt (which I'm ashamed to admit I ever believed).  Restricting calories to the point of avoiding obesity only while eating 5-6 times a day is no picnic.  Welcome constant food with constant hunger and constant restriction.  One could hardly think of a more unnatural way to eat, or a better way to make for miserable free-radical spewing mitochondria.

Yes, more research papers, more basic science, a deeper look at a vast picture, and more of the same old answers.  If you haven't given IF a try, consider skipping breakfast every once in a while.  Or at least have some stretches of time where fat is the primary macronutrient you consume (but avoid those vegetable oils, of course).  You might be surprised how you feel - not weak, but focused, energetic, and driven.  All the better to devise a plan to bring back that large ruminant to the camp for a delicious supper.  Yum.

(Thanks once more to Jamie who sent me several of the papers and links.)

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