Schizophrenia and the Gut

If you are going to do something, go ahead and do it right.  Honestly, that's why I write the blog (in part). I wanted to know more about the interface between diet, lifestyle, inflammation, and the pathology of mental illness, and I couldn't find a trustworthy source.  It requires a lot of work and combing the literature, but at least it is interesting, and I learn a lot.

However, I have to say, much of the literature is pretty sad.  There are a bunch of quick & "easy" research projects requiring people, in general, to fill out some forms.  Occasionally medical records are chased down, and sometimes some physical markers are followed.  Then someone brings in the statistical wizard to generate the results, and the authors try to tie it all together with some references.  Occasionally there is a randomized trial, but the whole experiment has holes one could drive a truck through, so to speak, so one hardly knows what the information means. I'll take what I can get, and it's easy for me to be critical as I am not a researcher and I don't have to generate grants to keep my office real estate in the academic medical center.  But it is always nice to see a paper where they went that extra step.  They closed the loop, and with actual testing, not just extra math.

Black Keys--Gold on the Ceiling (right click to open in new tab)

The paper of the day is impressive for a variety of reasons:  Gastrointestinal inflammation and associated immune activation in schizophrenia (via the twitter feed of that zen dude Chris Kresser.)

And let's step back and think about the history of schizophrenia for a bit.  Nowadays in the era of specialized medicine, psychiatrists think BRAIN when it comes to "organic" issues and CHILDHOOD/LIFESTYLE/PERSONALITY when it comes to coping problems.  The pendulum has swung back and forth between the two (coping vs. brain pathology) in a crazy psychiatry war, more or less.  A better understanding of the functional metabolism of the brain is finally bridging the gap, but let me tell you, in a post 1960s academic medicine setting, no one except the radicals were tying the gut to schizophrenia.  It just wasn't on the radar.

And if you really think about it, once thorazine and the other dopamine blockers began marching out the doorways of Big Pharma, we had a nice and pretty brain-centered theory wherein the neurons began going haywire, producing psychosis.  Since drugs like cocaine and meth that increase dopamine can produce psychosis, and dopamine blockers reduce psychosis, everyone was happy.  And while a bunch of other neurotransmitters like glutamate and serotonin and acetylcholine and histamine appear to be tied in, it was still all the same variation of the same theory, and you know if we could just get the right combination of drugs to block the right neurotransmitters, maybe we could beat this thing.  The conception of a special, protected space beyond the "blood brain barrier" led to this lack of holistic thinking as well.

What we forgot is that schizophrenia has always been a whole-body disease, particularly involving the gut.  Celiac has a special link with schizophrenia, and adults with schizophrenia at autopsy often have extensive inflammatory changes in the GI tract.  These associations have gone back to the literature from the 1920s, prior to the development of the antipsychotics.  In the present day, it is nearly impossible to separate the effects of the illness itself from possible effects of antipsychotic medication.  Antipsychotics are known for slowing motility and probably affect the gut immune system by reducing the inflammatory response there, perhaps even reducing gut leakiness.  Curtis Dohan thought this last bit might actually be the primary therapeutic action of antipsychotics, rather than all that fancy dopamine blocking stuff in the brain.

(Do you know the doctors most likely to use the old fashioned antipsychotics and antidepressants, all of which have pretty impressive GI effects?  Psychiatrists, neurologists, and gastroenterologists.  Reglan and phernergan are dopamine blockers, chemically not all that different from antipsychotics like Haldol or Thorazine).

Think how radical that idea is.  Dopamine blockers ameliorate psychotic symptoms by reducing inflammation in the gut??  Okay, it's a cute theory, but except for Dohan and Dickerson, not a whole lot of good folks were doing work on it for many decades.

So this "Gastrointestinal inflammation and associated immune activation in schizophrenia" paper from Schizophrenia Research is rather like a bolt of lightning.  It was done at Sherppard Pratt/Johns Hopkins, for heaven's sake.

Here's the design.  Take a group of folks who developed schizophrenia within the past 24 months.  Then take a group of folks who have had schizophrenia for many years (average > 20 yrs).  Then compare to some normal controls recruited from the community.  These normal controls from the community were determined to be relatively free of psychiatric disease via a structured clinical interview (SCID), which is the gold standard.  (These little gold standard touches take some extra work and make me happy.  It can take an hour or more to administer a SCID.  I remember a Maes paper where he recruited the controls from employees in his lab.  Often folks who work in psych have an interest due to personal issues or close family members who have psychiatric problems, so the research field employees might make for biased controls.  I don't always comment on these issues with papers because there simply isn't time…)  The researchers then checked the subjects for serum antibodies to gluten, casein, T gondii, Saccharomyces cerevisiae, and some other bugs associated with schizophrenia or gut issues, and crunched the numbers.  (So we have an observational study, but with some nice data collection and a further twist I will get into later)  Antibodies to S. cerevisiae in the system (called ASCA) are used as a marker of intestinal inflammation (and can be used to help diagnose Crohn's disease, for example).

There are some gender-related twists and turns, but for the most part, they found that folks with new onset and longstanding schizophrenia had significantly elevated ASCA levels compared to controls.  High levels of ASCA correlated (for the most part) with anti-casein and anti-gluten antibodies, which would make sense.  If you have gut inflammation, then casein and gluten proteins could seep into the system, and your immune system starts to attack them.  Since gluten and casein could be neuroactive (and maybe neurotoxic), they could be another part of the pathology of schizophrenia (and autism, etc.).  ASCA levels did not significantly correlate with anti-gluten and anti-casein antibodies in the control group, which is interesting.

All right, but who cares.  All these folks with schizophrenia were recruited from Johns Hopkins, and pretty much all of them will be medicated.  The medication could be a part of some of these immune and inflammatory effects.  The researchers thought of this tangle, and they designed a second experiment with a second cohort comparing unmedicated recent onset schizophrenia patients in Germany with medicated recent onset schizophrenics from the same area.  Those recent onset unmedicated schizophrenics had about 1.5X the ASCA measures of the recent onset medicated schizophrenics from the same German cohort.

And, tying it all together with other associations between infections and schizophrenia, the new onset patients had significantly higher positive antibodies for T. gondii than the non-recent onset folks or the controls.

SO, we have found that folks with schizophrenia have a higher level of gut inflammation and antibodies to glutein and casein than conrols.  Could these vulnerabilities somehow begin in the brain?  Or does the issue start with the gut, immune activation, and systemic poisons (neuroactive food fragments and infections) hastening an inflammatory decline in the brain in the genetically vulnerable?  Do antipsychotics work by being anti-inflammatory in the gut, by decreasing dopamine activation in the brain, or both? (or neither?).

All pretty interesting questions.

Trans Fats and Aggression.. Also, Walter Willett.

Beatrice Golomb is one of my favorite researchers.  She is holding the line that statins might, just maybe, be rotten for the brain and cause cognitive difficulties.  And here she shows up as the primary author on a cool little observational study linking trans fats and aggression.

The weaknessess of the study:  observational, food frequency questionaires, not too many confounders accounted for (I'll get to that later).  The strengths:  decent sample size (>1000), long follow up, prospective (meaning following and measuring people from the beginning rather than restrospective, which means looking back and is pretty much the least reliable way to run a study).

I'm on kind of a Schubert kick.  Here is his Serenade.

The details of the study are a bit boring, but in short, a bunch of ordinary folks already lined up for a statin study (who weren't on any lipid lowering meds during this study) were co-opted to track trans fat intake.  Researchers use the same people for different studies all the time.   This study was done back before the USFDA required the amount of trans fat to be labled, so people could eat Hostess "Donettes" in blissful ignorance, and manufacturers had little incentive to get rid of the nasty stuff.

So, what did they find?  Well, amount of trans fat reported consumed in the beginning of the study FFQ correlated linearly with aggression scores measured years later.  The researchers accounted for aggression at baseline, sex, age, alcohol consumption, education, smoking, and exercise.  In fact, dietary trans fats were more predicitve of later aggressive behaviors than any of the other known confounders, and predicted aggression similarly in women and men.  Dietary trans fats were also associated with depression.

What is a plausible biochemical mechanism of trans fats causing crankiness?  Well, the neurons need plenty of omega 3 to keep the lights on, so to speak, and trans fats interfere with omega 3 metabolism.  In addition, trans fats on their own seem to cause inflammation, cell energetics problems, and oxidative stress.  Yuck.

I linked this Schubert piece a long time ago, but it is worth a revisit.  It was written when he was gravely ill and knew his death was imminent.  Despite his prodigious body of work he was barely into his 30s.

What don't I like about the findings of this study?  I've looked at a number of other studies about diet and aggression.  The most rigorous are the Diet and Violence studies done in prisoners, showing boosting micronutrient intake an several replicated randomized controlled trials significantly reduced violent acts.  There is also another throwaway observational study linking soda consumption to adolescent violence.

We all know that trans fats in the American diet circa 1999 were of the garbagey processed food variety.  Literal junk disguised as tasty treats, though synthetic vitamins might have been sprayed on the flour used as dictated by law.  Delicious!  So trans fats consumption is not only a marker of mere trans fat consumption, but also nutrient poor, calorie rich crapola that will decrease the amount of micronutrients one would take in.  At the same time, the energetics of the cells are compromised by the trans fats and the omega3 levels are torched.  One doesn't typically enjoy a meal of wild-caught pacific salmon and donettes, after all.

(Another very sticky point -- trans fat consumption correlated with the amount of linoleic acid taken in, yet Walter Willett has about a thousand powerpoint slides linking amount of omega 6 fatty acid consumption and good health.  How does he do it?)

I do find it very plausible that synthetic trans fatty acids are terrible for your brain and behavior.  And very plausible that processed foods cause problems too.  Here is what irks me about the government guidelines for food.  By adding the focus on total fat reduction, polyunsaturated fatty acids and whole grains, they steer folks away from nutrient-rich whole foods and towards convenience foods engineered to meet government guidelines, like lowfat whole grain goldfish crackers and electric green yogurt "food."  I actually think Walter Willett's purported breakfast of "kashi" (I'm sure he eats the real stuff, not the processed cereal), is probably, in general, a reasonable choice.  I think grains are relatively nutrient-poor compared to eggs and meat and dark green leafy veggies and the like.  I also think grains taste worse, though they can stretch out a meal and help with variety, and I am rather famous for my partiality to steak so I'm hopelessly biased.

I wish the government food plate looked more like this one.  I think we all agree trans fats are nasty, and this study is one more reason to look upon them with a wrinkled nose and suspicion.

Oh, man, when I posted this article I hadn't seen Willett's take on the red meat study yet!  Here's my personal take on the moustached epidemiology nutrition crusader, in case you haven't read it yet.  My opinion:  there will probably be a greater public health benefit from encouraging people to eat steak than to eat kashi (because who is really going to eat kashi?)…

Robb Wolf, James FitzGerald and the Ghosts of Crossfit Past

Lessons in life are often repeated, and we may not get it the first time around.  A high school reunion is coming up, and I've had the opportunity to chat with some old friends not in touch for 20 years.  And despite those decades they are still the same, still terrific people.  When I find such friends I do try to keep in touch nowadays, as it is so easy to link a facebook account.  But of course there is no substitute for seeing someone live and in person.  Biologically speaking we use all our senses when meeting up with someone, note chemokines, subtle changes in expression, a lively or reserved manner, the sparkle in one's eye… or the threat, as it is likely murder was a big contribution to mortality in the past.  These non-verbal signals are why in clinical psychiatry practice even a video therapy session will never quite replace the in person visit.

Schubert Impromptu No. 3 (right click to open in new tab)

At PaleoFx12 I had the great pleasure of meeting several fellow "paleo MDs."  After the final panel I went with two of them (we shall call them Catfish and Hollywood*) to BBQ and the wild Austin scene of SXSW on a Friday night.  When one meets another paleo blogger intensely interested in the science, as at AHS and PaleoFx, it is rather like crawling out of the desert into an oasis of likemindedness.  Meeting other paleo doctors is like crawling out and finding the Taj Mahal.  I hate to get all "poor me, I'm a physician," but the current suffocating paradigm of American medicine can be so deflating.  In psychiatry we are squeezed into this impossible space between the FDA, Medicare, the scientific literature or "evidence base", common sense, expectations, history, and ethics.  Sometimes there are no right answers, and clinical practice becomes the square root of a negative number.  So to meet other doctors who look at the evolutionary paradigm, and have succeeded in their personal lives implementing it and are thinking about implementing it for their patients is exhilarating.  They understand the legal and cultural ramifications of such a change.  In a very real sense, we are a brotherhood, and they are my kin.  Such meetings can be intense, but fulfiling.  We walked together past the Texas State Capital at midnight, knowing we would meet the next day for an after-conference training session at a local Crossfit (appropriately enough).

The training session was an OPT presentation by James FitzGerald.  Apparently he has the honor of being kicked out of Crossfit just like Robb Wolf.  And to me this situation (ghost-like at paleoFx as the last time Robb and James were in Austin was for the infamous Black Box Summit where they were summarily dismissed from the official Crossfit fold) is absolutely remarkable.

Have you ever met Robb Wolf?  He is an incredible presence.  Intense, organized, smart, driven, good-looking, and by all accounts devoted and kind.  Any reasonable business would love to have him as the poster boy of the Good Example.  James FitzGerald was a similarly impressive specimen.  It is hard to define him without using swear words (as he ended about every third sentence with one or another), but  it is clear from his presentation that he thinks in 17 directions at once, he cares intensely about athletes and training, and he has the wisdom to break it down and know what is going wrong to you can set it right.  Though much of the presentation went over my head as a non-trainer, I was captivated by James' ideas and break-down of the essential problems facing an athlete in an intense moment.  Is it blood flow, psychologic barriers, lungs, training, diet… whatever it is ask the athlete his or her experience after the WOD and he or she will tell you.  James has been in the research game from the beginning, and he noted with excitment that we could throw out the numbers from endurance athletes and straight -up weight training, as the differences with Crossfit-style training showed whole new numbers, and whole new possibilities of human capability.  

How could Crossfit HQ dismiss James and Robb for the crimes of suggesting paleo nutrition, the idea of on-ramp beginners training rather than ubiquitous "scaling"  and *gasp* periodization?    

The answer is in my wheelhouse.  Personality.  James and Robb with their brilliance and drive were a threat to the powers that be.  At that moment HQ were more comfortable jettisoning the bright stars than accepting new ideas.  As wildly off base as such a business decision could be, it makes sense in light of an understanding of a personality in charge confronted with the young challengers.

In the paleosphere we have the same challenge.  There are flamboyant and brittle personalities who insist they are correct, and new information coming online all the time.  What does the newbie hold onto?  With opposing and strongly-argued viewpoints, what do we believe?

Forget the paleo myths.  Forget the personalities.  Are you eating (for the most part) real food (excepting autoimmune disease).  Are you exercising?  How is your sleep?  What are you feeling?  What are the pitfalls?  What is your family doing?

Fix those issues and answer those questions first.  Know where you are, and then look for more guidance.  We are working on a network of doctors who might help.  I hope cults of personality won't get in the way, but don't let it confuse you.  What makes sense, from every angle?  Never suspend disbelief.

* so named because a woman at a restaurant mistook him for a Hollywood star.  And while he was certianly ruggedly handsome and in good shape, I felt the incident serrved as an example of how a good lifestyle and exercise regimen could beautify someone  to more mythical status...

Context and the Stages of Change

Sitting here at the DFW airport waiting for my connection home seems like a good opportunity to put up a second post inspired by my experience at PaleoFx12, Theory to Practice Conference.  The previous post covers the first couple of days.  The final conference day proper began with my putting on my watch upside-down in the dark, so I arrived half an hour early, just in time to be asked to go on a morning panel unexpectedly.   The panel was for general Q&A and it devolved into a “safe starches” debate where Kruse, Gegaudas, and Rosedale warned of the dangers of glucose (glucose = DEATH) whereas Paul Jaminet and  Lane Seibring noted that insulin is not a dirty word, and Dallas Hartwig found that in his experience as a nutritional and training consultant (I would say to generally healthy folks, as opposed to Rosedale), the quality of the food seemed to matter more than the macronutrient class.  My major contribution was the admission that I had, indeed, consumed a banana that very morning, and that I was quite comfortable with that decision.

I’m sick of the whole debate, personally, as I take a sky-high view that excess energy from sat fat and glucose  is stored long term as palmitate (carb or fat) and excess energy in the form of glucose or too many free fatty acids floating around seems to cause damage and inflammation. And while there are a number of important details I am glossing over (but have looked at in excruciating detail, yeah, I know de novo lipogenesis and glycation and etc.), I don’t think either fat or carb as a macronutrient class per se causes one to overconsume.  Low carb and ketogenic diets can be fantastic tools.  Others do better and sleep better at even a high carb, low fat level, and I don’t think they are dooming themselves to an early grave.  (And the ketogenic folks still have to get over the hump of the low fasting insulin and the low glucose levels of the Kitavans or pretty much anyone who eats a low fat diet but has no problems with insulin resistance and obesity - Rosedale doesn’t know if the Kitava measurements were accurate but I encouraged him to email Dr. Lindeberg to ask about the methods.)  

On the other hand, I’m not convinced that we have an absolutely essential need for dietary glucose (for mucous formation or to protect the thyroid from damage), and I don’t think natural saturated fats are bad for you.  On balance I would hedge my bets in favor of including a bit of starch as that seems to be the most common ancestral precedent, and tubers and starchy fruits have some electrolytes and whatnot that are not always as robust in a meat+veggie+fat diet.  In general I think a macronutrient focus is confusing and spends too much energy looking in the wrong direction.  Think of all those billions of wasted money on poorly designed nutrition studies.  On a more specific level there are many conditions and personal needs that would weigh in favor of more fat for some and more carbs for others.  You know, context.  

Phew.  I hope that is the last time I have to write or say anything about that issue.  Hah.

After that panel I had little patience for the medical talks and spent much of the day networking or attending the training/fitness panels.  One of my general interests is training and athleticism and it was nice to see that side of the health industry.  While food and training methods were obviously highlighted, there was a lot of focus on the psychological aspects, reminding me that a trainer’s job is not so very different than a psychiatrist’s (though a trainer has a better chance of making his or her clients better-looking).

I was pleased to make more ancestral health doctor connections and further the dialogue with some old and new friends over the course of the day, and I did get an opportunity to speak with Chris Kresser (a careful and brilliant guy.)  Oh, and I met Andy Deas!  He was off to the hinterlands after I spoke with him so hope his trip turns out okay.

Finally, my panel came up, a discussion mediated by Dean Dwyer about the psychology of change.  I was excited about being on this panel, as it became clear over the course of the conference that some of my fellow doctors and the trainers and nutritionists (and layfolk on their own journeys through change) were in need of some guideposts.  Facilitating healthy change is the bread and butter of a psychiatry practice (in the guise of little pills sometimes), and there is a large body of literature on the subject.

I think all of us thrilled with the success we have had with an ancestral health influenced diet and lifestyle are happy to extol the benefits to the rooftops, buying copies of The Paleo Solution or the Primal Blueprint for all of our friends and relatives (or patients or clients).  We may have been hurt or confused when those same folks ignored us and continued to complain about the same issues or problems we thought might be helped by a little diet and lifestyle tweak (hint, the grains or vast amounts of soda just might be contributing to your tummy pains).  An understanding of the stages of change model can help us to direct our interventions and energies in a more productive manner than just proposing a big change and then being hurt-feelinged when our fantastic ideas are rejected.

There are five basic stages in a big lifestyle change, such as giving up an addiction or changing one’s diet.  The first stage is called “Precontemplation” (and in addiction circles is sometimes referred to as denial).  In Precontemplation you aren’t really thinking about changing your diet, drinking habits, or lifestyle habits.  Many of the folks who see me for the first time are in this stage, as are many of your friends and family.  Since Precontemplation can often be characterized by denial, saying “hey, you should really stop eating wheat to see if your stomach pains and skin problems get better” will often be met by responses such as, “well, I love bread.” Or “but I always eat whole grains, they are healthy” or “My brother only eats bread and he doesn’t have any stomach or skin issues.”  When someone is in a Precontemplation phase, a recommendation for dramatic change will often be met by arguing the other side.  The best strategy is not to urge someone immediately towards Action (the fourth stage of change) but rather towards the next stage, which is Contemplation.

To move someone from Precontemplation to Contemplation, the best approach is a personal one.  You might ask if the person thought his or her symptoms had anything to do with diet, or poor sleep, or smoking (or whatever the major lifestyle problem is).  It’s important to support the person in understanding their current dilemma.  If they say, “yeah, maybe I shouldn’t eat so many donuts” you might say, “oh, yes, I know how donuts smell so good.  It can definitely be hard to give them up.  But you know, they don’t taste as good sometimes when you haven’t had one in a while.  Too sweet, if you can believe it.”  Sometimes folks stay in the Precontemplation time for a while, until their own understanding and circumstances cause them to move forward.  By serving as a supportive example and continuing to highlight possible issues or problems that might be caused by the bad habits (“I noticed you always have bronchitis in the winter.  Do you think it is due to the smoking?”), you can continue to nudge the person towards Contemplation.  In short, the personalized nudging just seems to work better and more often (and, over time, with less frustration) than: “You’ve got to stop smoking.  It will kill you.  Here, check out this smoking cessation website.”

The next stage, Contemplation, is where the fun starts.  This is the person who will welcome support going forward to the next stage, Preparation.  The Contemplator is still ambivalent, but not in denial.  This person may welcome more stories of anecdotes about successful life transformations and links to various resources.

The next stage is Preparation.  These are the folks who are calling the gym to ask about prices and class times, or newbies stumbling onto Mark’s Daily Apple.  Support and encouragement and resources are key here.  And, as always, a personalized supportive intervention focused on particular stumbling blocks is key.  “You mentioned it must be hard to go out to a restaurant when you aren’t eating dairy or grains.  Go to the Whole30 website because they have a ton of ideas about what to do…” (etc.)

Stage four is Action.  Exciting times.  These folks are often active on the forums and experiencing major changes.  Again, support is important here.  

Finally there is the last stage, Maintenance.  Maintenance can be tricky.  The early bloom of “wow, this is so awesome” has come off, and the grind of continuing lifestyle change (oh man, I really really want a donut, or I just want to sleep in and not go to the gym today) can go from one or two “slip-ups” to just not continuing (one day off the gym becomes a week or a month).   Robb Wolf noted in his talk that he had figured out a number of people dropped out of the gym after day 38, so he recommending instituting some protocols, such as a reduced cost or free personal training session or a supportive check-in email that would come into play around that time.  In addition, obviously, life is very different after a massive lifestyle change.  You don’t have that percocet to comfort you during the day anymore (which can sometimes feel overwhelming even though you are no longer spending $200 a day on your habit and your friends and family have started to trust you again), or maybe you are uncomfortable with the attention you get after losing 100 pounds.  You might feel distant from friends or family who don’t embrace the same change and might even (explicitly or unconsciously) prod you to go back to the old habits you fought hard to drop.  Maintenance can easily go to Stage 6 which in addiction is called Relapse.   In many respects, Maintenance requires more support than the previous stages, and the problems aren’t as obvious.  “You’ve lost 100 pounds and you look amazing” may feel uncomfortable to someone who has spent years being self-conscious about his or her body and is dealing with excess skin issues.  And Maintenance may look a little different and less magical than the final product you imagined at the Preparation stage.  I will never be a Sports Illustrated swimsuit model, for example, no matter how many Whole30s and Met-cons I do.    

So the underlying theme here is support, and the type of support needed differs as one progresses through the stages of change.  Providing the wrong type of support at the wrong time can be alienating and off-putting, and push someone the wrong direction, no matter how well-meaning you are.  And spending one’s energy providing the wrong support is very frustrating and can lead to ruptures of relationships.

Hopefully this post is helpful to anyone who hasn’t heard of this model and is struggling.  There’s one more PaleoFx post to come, when I get another moment!

PaleoFx Austin: Theory to Practice

Back in December (I believe) Michelle Norris was kind enough to invite me to the PaleoFx conference.  Since I'm from Austin originally and it was scheduled for March (which tends to be a particularly miserable last month of winter in the Northeast), I said sure and bought a plane ticket.  I wasn't quite sure what the phrase "theory to practice" would mean as a conference theme.  I'm scheduled to be on the Psychology of Change panel tomorrow evening, but in the mean time I'm soaking up the conference milieu.

Michelle and Keith Norris along with Kevin Cottrell have done an amazing organization job in the short half year since the conference was originally conceived.  The venue in the north end of the UT football stadium is fanstastic, with fabulous views of the Austin skyline and a large staff of volunteers to keep everything running smoothly.

View from the venue

Old stomping grounds

 I've seen most of my old friends from AHS11 (Dallas and Melissa Hartwig, Paul Jaminet, Clifton Harski, Diana Rogers, Basil G., and David and Karen Pendergrass) along with many new ones, such as @Fitbomb and @Nomnompaleo (who posted a pic of me in one of those elusive obligatory pictures with Robb Wolf! Scroll down a bit.  I'm in a red shirt and not looking at the camera.  Take my word for it.)  Their upcoming ipad cooking app looks incredible, by the way.

The conference began with a talk by Jack Kruse, a neurosurgeon who with his typical messiahnistic style told us about a patient who had decided against futile cancer treatment, choosing instead to enjoy the last months of her life.  Since a surgeon's job is typically to solve problems, cut things out, fix things, etc., her request did not go well with his boss.  She seemed to connect to him as a young resident and willed him a gift of fine wine and letters after her death.  Though he didn't really absorb the full impact she had on his life at that point, he found at a later date, in conjunction with an epiphany about his own medical issues, that her example helped him to live in the moment and devote his practice to the way he feels medicine should be done, rather than standard clinical conventional medicine.  Kruse's talk was far more focused and cogent than what I can make of his blog posts.  There was a rather strange moment where he lit a stick of dynamite (I'm assuming a faux explosive as it's likely he took a plane to get here…).  I was standing between Mark Sisson and Paul Jaminet so I figured I could duck behind them if things got out of hand… Kruse's talk did properly solidify the theme of theory to practice.  The ideas and stress here is more about what we do as clinicians, gym owners, trainers, and nutritionists than the scientific nitty gritty as to why.

Afterwards the presenters were invited to a special dinner in North Austin.  I drove with Paul Jaminet in the car and we talked about his upcoming plans, Shou-Ching's research, and his work with Aaron Blaisdell to help with publishing an Ancestral Health academic journal, all very exciting stuff.  We passed the restaurant and turned around in the shopping center where I went to buy shoes as a little kid, and I have to admit it is a bit strange to have the paleo world overlap with my old stomping grounds of north Austin and the University of Texas.  Almost as strange as having so many people I don't know recognize me!

This morning the conference proper really began with CJ Hunt presenting on his documentary "In Search of the Perfect Human Diet" and Robb Wolf.  Robb as always is an engaging speaker and his energy and ideas and enthusiasm for bringing people together along with a dedication to doing things right never cease to amaze me.

I had been asked to connect with a few high-powered behavioral/brain researchers and also some other paleo-minded physicians prior to the conference.  It is plus of the somewhat slower pace (lengthy Q&A sessions, breaks between speakers and an hour lunch, provided) of PaleoFx compared to AHS11 that I was able to spend some quality time to talk with these fabulous people about actual practice of research, and especially of the nuts and bolts of the clinical practice of medicine.  The fellow physicians are an amazing, enthusiastic bunch who practice what they preach.  I was also able to meet Chris Kresser in person and talk some shop.  I can't help but think these connections will enable us to bring the actual practice of ancestral health forward inch by inch, and this meeting opportunty is the lasting gift of the PaleoFx organizers.

It's also striking that in person the similarities of message and ideas (eat wholesome food, manage stress, exercise but not like a maniac, and sleep for heaven's sake) far outweigh some of the differences of substance and style among the "paleo" blogs.  One panel group "The Future of Paleo" discussed this issue explicitly, and Robb Wolf made the point that incivility in disagreement may well blow up paleo, when the simplicity of the basic message (Archevore's initial rules + stress management, exercise, and proper sleep) will go 90% of the way to tuning up the health of most people.  Robb's and Mark Sisson's approach of focusing on the health benefits and success stories along with spending their energy on debunking conventional wisdom has proven to be effective and non-devisive.  On the other hand, with so many different flavors of what constitutes a paleo practitioner these days there are bound to be disagreements and some outright weird advice.

Mark Sisson spoke about his upcoming 90 day journal project he will be publishing to help people figure out how to implement the Primal Blueprint as it fits and works with his/her lifestyle and needs.  Mark is a healthy, vigorous walking billboard for his program, and he talked about some different ways to approach the diet depending on your goals.

I left before the Rosedale talk so I could spend some quiet time with the family and catch up on my sleep.  More tomorrow and some pictures (or the next day, when I get a chance at the computer again…)

Angelo Coppola and Jimmy Moore

Melissa and Dallas

Fitbomb and Nomnom!

Depression: A Genetic Faustian Bargain with Infection?

In the past week or so there has been a deluge of papers relevant to the sphere of this blog.  And it is March, as in "beware the Ides of."  Any psychiatrist readers (northern hemisphere and likely accentuated at the higher latitudes) will know exactly what I mean.  As the sunlight returns the agitation and anxiety and insomnia are awakened.  The phone at clinic is ringing off the hook.  (Well, it is always ringing off the hook, but now more so than usual).  More importantly there is life, and family, and not nearly enough time in the day or week or universe.

Next week I'll be flying to Austin, so this song seems apropos: Los Lonely Boys--Heaven (right click to open in new tab).

In the mean time I can at least attend to a few of the papers and maybe crank out a new Psychology Today blog post or two…so I will start with a paper available full text online (from a Nature offshoot, Molecular Psychiatry) with the provocative theory of PATHOS-D.  It is really an amazing paper.  Go over and take a peek.  Absorb the diagrams.  It's a little dry, but way better than most of the nutrition literature.

Here is the theory.  Depression*, as we know, is associated with certain types of inflammation in the brain.  There are certain red immune system flags we see with the syndrome of depression quite frequently, most specifically increases in the cytokines TNF-alpha, IL-6, and C-reactive protein.    These chemicals found in the blood and spinal fluid tell us a brigade of our immune system is on high alert, kicking a** and taking names, so to speak.  Problem is, when there are no invading a**es left to kick (or the invaders are too clever and elude our defenses), our brains get the full onslaught and neurons die and then you can't concentrate, and you avoid social activities, and you cry a lot, and eventually your primary care doctor gives up on your therapist and celexa and sends you to see someone like me.

And we certainly know that genes in combination with stress will predispose us to depression.  But some folks are bulletproof.  They won't get depressed in the most dire of circumstances.  Other people seem to be far more vulnerable.  All it takes is a bit of a mismatch between temperament of parent and child and we have major psychopathology.  A predisposition to depression is hereditary, therefore it must be encoded in our genes.  But what genes?  The PATHOS-D authors would suggest that the genes that predispose us to depression also protect us from infection.

Infection?  All of us humans in the brave new modern world have endured 10,000 years of agriculture, which brought with it dense population and massive infectious disease. Tuberculosis, for example, is said to have killed most humans who have ever lived.  The same genes that might give us a genetic advantage against infectious pathogens may lead to vulnerability to depression.

Inflammation, like an army, is a double-edged sword.  People with trigger-happy immune systems are more likely to survive many infections (though a tricky beast like the 1919 flu killed the young adults with the most robust immune systems via massive pulmonary immune reactions and septic shock).  Since infections in the developing world tend to preferentially kill young children, there is strong selection pressure for genes that will save you when you are young, even if those genes have a cost later in life.  The selection pressure would have to be strong, as a clinical depression has obvious survival downsides, for both the person affected and his or her offspring.  Depression tends to be chronically recurring and also will strike folks in 20s and 30s, unlike, say, Alzheimer's or most cardiovascular disease, thus selection pressure against depression alleles would likely be significant…unless those same alleles protected against something even more deadly that often strikes even younger, like infectious disease.

Cool theory, but where is the evidence?

Well, just as in schizophrenia, geneticists have tried to brute force hack the human genome in order to find a "depression gene."  And just like in schizophrenia, they haven't had a lot of success.  The answer (again, similar to schizophrenia and probably a lot of other diseases that don't fall into a simple single-gene model) will likely lie in looking at a group of genes for particular functions (say, immune function, or brain communication) and finding many different problems in those pathways in those who are genetically predisposed to depression.   In all the genome searching, a couple of genes have come up consistently involved with depression in certain predisposed families.  Both of them happen to be involved with cytokine signaling/immune function.  That would be a heck of a coincidence.

One allele, -308A, has found to be associated with increased risk of depression along with decreased risk of tuberculosis infection, parvovirus B19, hepatitis B, and a lower risk of death when hospitalized while critically ill.

What about other genes that have been found to be associated with depression risk but weren't found on large population genome-wide association studies?  We've discussed many of these genes and pathways in the history of this blog. MTHFR 677T is a version of methylenetetrahydrofolate reductase with reduced activity.  That means the folate we eat in our diets will have a harder time being transformed into the folate that is active in the brain (methylfolate).  Since folate is necessary to make things such as neuroransmitters and DNA, a brain without folate is in a sad state.  Low MTHFR is associated with increases in homocysteine and overall inflammatory tone.  Since low folate is also associated with devastating birth defects, one would think there would be pretty strong selection pressure against this gene, but it is actually fairly common in the population.  Why?  Well, the inefficient version of MTHFR is found to be protective against cytomegalovirus infection, sexually transmitted disease, and hepatitis B.  In places where there is sufficient folate in the food, MTHFR inefficiencies may not be devastating and could mean protection against infections that cause other devastating birth defects and disease.  In sub-Saharan Africa there is low folate availability, and the MTHFR 677T allele is nearly absent there.

ApoE is another molecule we've discussed at some length.  It is a signaling molecule located on the surface of lipoproteins (which carry around fats and cholesterol and vitamins, like LDL).  ApoE4 is the original, ancestral allele, and those who carry it have a higher risk for both Alzheimer's disease and depression.  E4 is associated with increased inflammation in general.  E2 is a protective version and means decreased risk of major depressive disorder and Alzheimer's compared to E4.  The E4 allele may be protective against childhood diarrheal illnesses, while those with E2 seem to be more vulnerable to tuberculosis and malaria.

The most studied (and debated) alleles associated with depression are so-called short and long form of the 5HTTLPR.  This gene is a promotor region that tells the cell to make a serotonin transporter.  Those with the short allele (particularly with two short alleles) seem to have a much higher risk of developing major depression when exposed to early childhood trauma, whereas the long form of the gene is protective.  However, the short gene isn't all bad.  Those who have it seem to have a lower risk of dying from sudden infant death syndrome, and the gene is associated with higher circulating cytokines in response to stress, which could protect you if the stress is from being wounded or an infection.  In populations where the short gene is more common, there also tends to be more exposure to epidemic infections, suggesting selection pressure for the short gene.

Finally, there is some thought put into the clinical syndrome of depression and how it might protect you and your offspring if you do have an acute infection.  It is well known that inflammatory mediators (such as IL-6 or interferon) induce depression symptoms on their own.  If you have come down with an infectious disease, being depressed would keep you isolated and conserve energy, reduce appetite (maybe to induce ketosis to improve viral and bacterial immunity?)

I think the strength of an evolutionary/ancestral paradigm for studying disease helps to provide a sensible framework, like the PATHOS-D theory.  Clinically, it helps us to focus on the immune system and inflammation, and how that may have been altered by modern diet, stress, lack of parasites and pseudocommensals, changed sleep, infectious burden, and physical activity.   Forget the random crapshoot of mere brute force epidemiology.  There are too many confounders, and it will lead us in the wrong direction as often as not.  

*here we are using the clinical definition of depression.  Not just a sad mood for reason, such as grief.  Usually we are talking about a sad mood with inability to enjoy things we used to enjoy, poor concentration, poor or unrestorative sleep, appetite change (classically poor appetite), guilt, self-doubt, and even suicidal thoughts.  

Reviews of Escape the Diet Trap, Eat Like a Dinosaur, and Well Fed

One of the perks of having a relatively well-read blog (here and on Psychology Today) is getting free copies of recent books that come out.  Some of them are from the Psychology Today bloggers, others from the paleosphere.  I also purchase Evolutionary Psychiatry-related books, mostly textbooks, and nowadays I can use my blog income and donations to do so, so I've about broken even with my endeavors.  The hard part comes with getting time to read these books.  It's a lot easier to make time for a 5-6 page paper or even a handful of them than to sit down and give a book the attention it deserves.  Even harder to write a detailed review.  Synopses were always my achilles heel when it came to selling my writing in the past.

First off, Escape the Diet Trap.  Dr. John Briffa is a physician in private practice in London, seen here cleaning the floor with a statin apologist on television.   Dr. Briffa was kind enough to send me a copy of his book, and he mentions my blog under the "resources" section, and he signed it for me.  

In general there is a lot to like about this book, and it begins with a nice understandable rebuttal of the diet-heart hypothesis with an evolutionary medicine-reasoned slant.  The recommended diet is low-carb paleo with lots of behavioral tips and techniques.  In addition, he recommends walking, high intensity intervals, and strength training (even giving a little routine) matched to one's basic fitness level.  It's a very reasonable, researched work that does not make any outlandish claims, and is bound to work for most people, particularly at the beginning of their fat-loss journeys.  There are easy charts that tell you what to eat and sample menus, along with testimonials.  He also introduces the concept of intermittent fasting, which is a neat diet trick and very effective for some.

The book is definitely geared toward the insulin resistant and does plug the carbohydrate-insulin hypothesis for fat gain, which is my only quibble with it.  However, I think low carb is a great starting point for most people who aren't athletes or bodybuilders who have some weight to lose, for other reasons than the carbohydrate-insulin hypothesis.  Going low carb (and adding the paleo restrictions) will automatically eliminate a lot of foods that are low in nutrients and high in calories.  It will also keep one out of trouble with snack foods, engineered foods (as in everything you can buy to eat at a gas station), and restaurant foods.   It will get you used to cooking and used to eating a bit more healthy fat.  I don't think super low carb is great for everyone, particularly athletes or anyone doing a lot of glycolytic work, and I don't think low carb is the end all be all, the only way to longevity, or the only optimal human diet.  I don't think glucose is poison and I'm not afraid of insulin myself.   Dr. Briffa mentions that athletes will do better with more carbs, and says "part of the problem, though, is that many of us eat like marathon runners but spend practically all our time sitting on our bums." (p. 236)  Most recreational exercisers will do fine on a moderately low carb diet, and I have no quibble with this fact.

Dr. Briffa stresses that his recommendations are not a "diet" (in fact the front cover says "this is not a diet book" in addition to the title of "Escape the Diet Trap"), and I like that focus as a lifestyle change, as the evidence is clear that you really can't ever return to your previous way of eating if it got you fat in the first place.  (I would think that is obvious, but $80 a day juice cleanses and cabbage diets are always plugged in the mass media, for sure).  He also stresses that we shouldn't consciously restrict calories (again, diets that force you to starve yourself by merely cutting calories will always fail, long term).  Portion control (using, for example, the palm of your hand as a measure for protein needs in a meal, as I've seen recommended ) and intermittent fasting are ways of backing into calorie counting without going nuts, and I'm always surprised (when I'm not cheating at all) how much volume of real food it actually takes to keep me running at full steam.

My only disagreement with the book, really, is his inclusion of white potatoes (and presumably other starchy tubers, such as cassava) in the "foods to avoid" list and the restrictions on fruit if we are considering this book a diet for the rest of one's life.  It's pretty clear that unless you cross the line of 50 grams of fructose daily (Staffan Lindeberg kept quoting the figure of 5 pineapples, which seems like nearly a physically impossible amount of sweet fruit for a non-fruitarian), your liver is well able to handle the amount in most fruit.  Going nutty with the dried fruit and fruit juice is a different story.  I think folks who have sugar-related emotional eating might to better getting rid of fruit for a time, or maybe forever, but for most it is a healthy part of the diet.  And while I object to restaurant french fries and potato chips, I simply don't see anything wrong with eating cooked potatoes (or other starchy root vegetables) as a general rule, and I think for those worried about the sustainability of the paleo diet with such a huge world population, the inclusion of potatoes will go a long way to feeding a lot of people with limited resources.

In short, I would recommend this book to anyone wanting to lose weight (especially those with a lot of weight to lose) or as a gentle introduction to a paleo-style diet (or ideally both!).  Like most paleo books, people will need a bit of education after the fact to get them away from the idea of low carb as the only option. 

Second up is the brand spanking new Eat Like a Dinosaur from the Paleo Parents.  Between them, Matt and Stacy have lost over 200 pounds and cured their children of many behavioral, skin, and hypersensitivity issues by switching to a paleo-style diet.  They sent me two copies of their book, and I am going to give one to a colleague with three small children.  

Eat Like a Dinosaur is a dairy-free, grain-free cookbook with a bit about the family, followed by a cute little children's story to help the kids understand the new way of eating, and then about a zillion recipes geared for families and a major influence on getting the kids involved with obtaining food, cooking, eating, which is great.  The recipes are mostly low carb, and use low carb flour substitutes such as almond and coconut flour.  Sweet potatoes are included, along with some desserts and sweets (using natural sugars such as maple syrup, honey, and palm sugar).

I think this book is a fabulous resource for families who have strict dietary needs, such as kids with celiac or hypersensitivities.  There are more than 150 recipes and lots of tips and tricks for snacks, making school lunches, and how to make meals fun for everyone.  The pictures aren't fantastic and there are a few typos, but those are small complaints.  I'm also wary of any recipe with coconut flour as a major ingredient (having made some horrible pancakes and muffins with it) and would probably modify some to include organic white rice flour myself, but as I rarely bake, I don't know that I will be experimenting with these anytime soon.  I know the kids would love some of the cupcake options, the icing, the smoothies, the fruit and nut bars, and other tasty treats.  There are also many, many recipes incorporating organ meats, dark green leafy vegetables, brussels sprouts, and other "adult" foods. All the low carb staple substitutes are there as well, including cauliflower rice, mashed cauliflower, almond flour pie crust, low carb cookies, etc.

My husband and I have more of a European philosophy that children should eat pretty much what adults are eating, and we really shouldn't go out of our way too much to make special foods so they will eat them.  I don't have a lot of time to make cutesy food (and I don't have four different kinds of low carb gluten-free flour on hand), but then my kids aren't really all that picky.  They care more about the plate than the food, though given the opportunity they will of course complain about most everything healthy and beg for goldfish crackers or ice cream.  However, given the popularity of books like Deceptively Delicious, there must be a lot of families out there who are desperate to find ways to surreptitiously stuff their kids with vegetables and real food.  Now I have a hard time believing that Jessica Seinfeld herself purees vegetables for an hour or two every weekend for her children, I know some parents do.  Eat Like a Dinosaur has lots of simple ways to make good food cute (like putting tuna salad in a carved out cucumber boat), and if I had the time, necessity, or motivation, I would likely utilize them.  I'm likely to dive into this book for recipes for chicken nuggets, and cakes and cookies for birthday parties, pot-lucks, and family get togethers.

Given the unmitigated garbage that is marketed and fed to kids on a daily basis (I challenge any real food-loving or paleo parent to go to any snack time in any school and not be a bit horrified by the petroleum food dye blue low fat yogurt and ubiquitous fruit juice boxes and rainbow goldfish that pass as healthy food these days) and the frankly bizzare public health message that stresses a low fat, low meat diet and high amounts of grains for kids who have such a need for lots of very nutrient-dense brain and growth foods, I certainly applaud very wholesome real food and healthy fat message of Eat Like a Dinosaur.  

I think growing, energetic kids do fine (or even better) with plenty of starchy carbs (and I do give my kids organic white rice, usually cooked in homemade stock with grassfed butter, dulse flakes,  or coconut milk and a cinnamon stick) in part to hide some of the fat in their lunch (schools are obligated to encourage you to feed low-fat, which is of course ridiculous).  My kids seem to do fine with dairy, also, and they get full fat organic milk and yogurt.  I might try to wean the older one (who is 4&1/2) off so much milk, but she seems to be doing that naturally as she ages.

In short, Eat Like a Dinosaur is perfect for kids and families who want to be strict paleo (with a ton of  baking and substitution options) and is great for getting kids who have allergies on board with the restrictions of a paleo diet.

The last book on my list is one I bought myself (though I bought it in part because the gorgeous Melissa and Dallas Hartwig gave me their Whole30 Success Guide last summer, which I thought was terrific).  Melissa Joulwan of The Clothes Make the Girl has written by far my favorite paleo cookbook, Well Fed (paleo recipes for people who love to eat).  Most of the recipes are Whole30 compliant, and every one I have tried is very tasty.  I love Well Fed because there is a big section on shopping, supplies, and making "hot plates" for ideas for eating good (mostly simple) food all the time with minimal prep (for "real food").  There are also plenty of recipes for those nights when you want to spend some time making a special meal.  So far I've made the chocolate chili, the moroccan meatballs, the meatza, and the "best" chicken and they were all terrific.  Honestly it is the best practical cookbook for eating clean (though Mark Sisson's Primal Blueprint Quick and Easy Meals is a close second).  You aren't going to find as many sweet crowd pleasers for adult parties, but Paleo Comfort Foods has those.  

I love the Whole30 and Well Fed because I think they start where Escape the Diet Trap leaves off, with super dialed in nutrition to give you a clean starting point to see what foods you tolerate and which ones you don't.  For the most part they also meet my personal food philosophy, which is mostly simple and easy with portion control, and some special dishes.  I "cheat" more than they recommend (with chocolate, some gluten and processed foods, white potatoes, white rice, and alcohol), but when I have the Whole30 dialed in, I get lean, lean, lean.  As long as I avoid dairy, I can cheat with some impunity and I don't tend to gain, but I didn't figure that out until after I did the Whole30.  I do like the idea of purely nutrient-rich food and sugar avoidance as a starting point to clear the decks.  However, personally I don't see anything terribly wrong with a bit of white potato or white rice, particularly if you beef up the nutrition of the rice in the cooking.  (Unpolished, unfortified white rice killed the Japanese in droves with beri-beri back in the day, so no one can argue it is a super food, and if it is grown in the US it has some arsenic).

Speaking of my personal nutrition and exercise philosophy, for exercise I do Crossfit, which is somewhat controversial but works very well for me.  I have a lot of experience with weightlifting (even took a class in college), and the head trainer at my box is very experienced training beginners and athletes and has a healthy philosophy, avoiding the "sexy met-con" for the most part in exchange for lots of basic strength training and "short and sweet" WODs.  "Let's keep the cortisol under control."  He doesn't restrict the sumo deadlift high-pull which worries my friends Jamie Scott and Dallas Hartwig.  And I do have a fritzy shoulder (pre-dating Crossfit by about 18 years) so I do consciously (for the most part) take care not to push it too hard.  I think Crossfit is a great option for the experienced exerciser who has limited time and likes the motivation of an involved and enthusiastic community.  My six am box-mates will send me a facebook message if I'm not there when expected, I get a lot of personalized attention on technique and the like, and you can't really say the same thing about a normal globo-gym if you don't pay for a personal trainer.  I wouldn't go to just any Crossfit with just any trainer, however, without some experience and wisdom about your own limits. 

In the future I will do a few more book reviews.  I'll do an Evolutionary Psychology triple-header and other reviews of How to Be Sick and Harnessed.  In the mean time there are a bunch of new nutrition and mental health papers to look at, and some other larger topics to explore.  I'm also heading into another season of talks, conventions, and podcasts, so the timing for these endeavors is rather unpredictable.

Brain Aging and Omega 3

Framingham, Massachusetts, founded in 1700, is a manufacturing area somewhat to the north of where I live.  Most folks interested in the medical sciences have heard of Framingham because it houses the subjects of one of the longest-running and famous studies of all time, the Framingham Heart Study.  Begun in 1948, scientists have followed several generations of residents assessing diet, heart health, and other markers of disease.

In this new paper, the second Framingham study generation (average age 67) was observed for a relationship between red blood cell omega 3 (specifically DHA) levels, scores on cognitive testing, and MRIs.  It's a snapshot, just some interesting info, but let's see what we find.

Many studies measure levels of omega 3 in the body.  Plasma levels (from the blood) reflect dietary intake over a few days.  Red blood cells live about 120 days, so RBC membranes have omega 3 levels that correlate to dietary intake over the same amount of time.  These levels also correlate with fatty acid concentrations in other tissues, like the heart.  

First off, the MRIs.  The images were studied to look for measures of brain aging, such as lower brain volume, hippocampal volume, and white matter hyperintensity volume.   Gray matter is the cell bodies, white matter is the wiring (more or less), and "white matter hyperintensity" can indicate scarring or other damage.  The Framingham participants in the lowest quartile of RBC DHA amount had the oldest-looking brains, with lower total volumes and more white matter hyperintensity.  Once you got past the lowest quartile, however, there was no further relationship between the DHA levels and these brain findings.  So it appears there is a threshold where you need enough omega 3, and beyond that more omega 3 is not helpful (if we assume causation, that lower dietary omega 3 will cause problems and higher is protective).

The cognitive testing was fairly basic, but given over 1500 participants in the study, that is not surprising.  Delayed verbal memory, visuospatial memory, similarities testing, and a trails test were done.  In general these tests can give a rough picture of how good your memory, reasoning, attention, and executive functioning are.  RBC DHA levels were continuously and positively associated with 3 of the 4 tests (only verbal memory had no association).  

We know from other observational studies that regular fish consumption is (for the most part) associated with a lower risk of cardiovascular disease and dementia.  It seems that the ability to make DHA and EPA from the shorter ALA decreases as we age, so the older we are, the more important it is to get long chain omega 3s in the diet.  As I have reviewed in past blog posts, controlled trials supplementing with DHA, EPA, or both seem to have no effect in advanced dementia, but do seem to have a positive effect in mild cognitive impairment (a very early form of dementia that can progress further) and very mild Alzheimer's dementia.

Alzheimer's dementia and vascular dementia (dementia caused by the cumulative damage of strokes) are the most common forms of dementia, and having sufficient long chain omega 3s could protect us from both.  DHA and EPA seem to lower blood pressure, vascular inflammation, and reduce blood clotting.  These long chain omega 3s are also vital constituents of the "lipid rafts" and therefore cell membrane function.  As I've reviewed in the past, good levels of DHA in the brain seem to reduce neuroinflammation and the creation of amyloid beta plaques (associated with Alzheimer's).

Since long chain omega 3 fatty acids duke it out with the omega 6s for a spot on the plasma membrane of cells, it seems plausible that you don't need to eat fish three times a week if you keep your omega 6 intake low.  If you listen to this guy, your omega 6 intake will be high.  If you avoid processed foods, peanut and seed oils, and large quantities of most nuts and poultry and conventional eggs and lard… well, omega 6 will be less.  Your brain can tell the difference!