It Starts With Food and Two Years of Evolutionary Psychiatry

I first met Dallas and Melissa Hartwig at AHS11 at UCLA. They are formidable, friendly, bubbly, beautiful, and very tall. I first heard of them several months earlier from Jamie Scott, and then remembered a spat back and forth between Kurt Harris and someone named Dallas over dairy in the comments of Kurt's blog (then named PaNu). Shortly after that, I received a comment or email from Dallas writing he was adding me to the "resources" list of the Whole9 website ("if you care" he said, which I thought was funny.)

I poked around the website and decided to do a Whole30 leading into the inaugural Ancestral Health Symposium. I didn't achieve a "perfect" 30 days due to a vacation to Santa Fe, but I did have some very positive effects which I wrote about in this post. In the mean time, Dallas and Melissa had become part of a group of paleo journal club buddies who pass around interesting papers and whatnot, and they supplied me with a copy of their Whole30 Success Guide. Since then I've also ordered a couple of their T-shirts (one for my sister-in-law who is a big fan), and while they let me buy the gift, they always gave me my shirts with the admonishment that I was not to buy them (I have a feeling they are fond of me, and maybe one day I can leverage that so they can teach me to snowboard or something :-).  We met again at PaleoFx and bonded over our shared relative certainty that the consumption of starch (GASP) was not going to lead us to an early grave (don't even get me started on that one).

All this exposition is my way of giving you full disclosure. And it is a bit fun to walk down memory lane. I started this blog almost two years ago exactly, the readership blooming within a few months thanks to links from Nephropal, Mark Sisson, and Kurt Harris, and later Stephan Guyenet. In the intervening years, I've had the opportunity to meet or correspond (sometimes at great length) with most of the major ancestral health figures, and Dallas and Melissa are among my favorites. It is no secret that Kurt Harris is another great favorite, but I have to say that in his N=1 exchange with Dallas above, I tend to side with Dallas, though a bias comes from me and my family having some issues with dairy. Kurt's arguments (as always) are extremely solid and reasonable. It's also funny how much has changed these past two years, how much online drama we've endured, and how my internet friendships have expanded to include so many people from all over the world. I haven't looked at my oldest blog posts in quite a long time, and I wonder how much I will cringe at my certainty, my style, and ignorance displayed in those first months.

I'm not yet marinated enough in this evolutionary medicine adventure to write a book.  Dallas and Melissa, however, have been working with their paleo-style food and lifestyle both personally and professionally since about 2006 or so, experimenting with their first Whole30 in 2009. I've known they were working a book for quite a while, and was honored when they asked me to review one of their final drafts and perhaps write a quote for the jacket. I was very pleased with It Starts With Food and ended up at the top of the back cover.

I loved the practicality and writing style of the Whole30 Success Guide, so it was no surprise to me that It Starts With Food is an easy and solid read with good narrative drive that takes you right through. It is not the slog of some nutrition books, comparable to the fun read of The Primal Blueprint.

There are two things about this book, however, that take it beyond the previous Paleo bestsellers. One is the terrific attention to the psychology of change and how modern food affects the way we think and crave. Another is the attention to science and how Dallas and Melissa are careful not to overreach. I know they vetted the manuscript with a number of folks, including the Kracken, hoping not to make the mistakes of Paleo past (such as strict prescriptions for carbohydrate grams or saying that legumes will kill you via the power of phytates and lectins.) Their Rx is orthodox Paleo (plus a helping of healthy fat) but they have good solid reasons why every step of the way. Their idea, like Robb Wolf's (and borrowed and attributed to Robb Wolf) is a "perfect" elimination diet, from which you learn a lot about yourself and add back in other likely healthy foods to figure out the balance of your best nutrition with your life.

The psychology piece is incredibly important. It is not easy to do a Whole30, even if you don't have many emotional issues with food, or even if you have weight to lose or are fighting a live threatening condition such as an autoimmune disease to give you plenty of motivation. Mark Sisson breezes past the psychology with his 80/20 rule (not a bad rule for many, though I find I need more like 95/5 to stay lean and sharp), and Robb Wolf in The Paleo Solution had a tough love approach "buck up buttercup" or something to that effect, which I found a bit cringe-worthy (sorry, Robb).  His blog is never like that.

It Starts With Food gives us tough love with extensive handholding, which I know through plenty of clinical experience with addiction and eating disorders is the most effective non-pharmacologic and non-locking-people-up-for-a-spell way to get people through the first rocky part of a major life change.  In addition, with the science and unknowns fully acknowledged, I can recommend this book to my patients and relatives without caveats, which is why I said in my quote:  "Here is the nutrition book we've been waiting for."

I also love how Dallas and Melissa address the so-called radical nature of the fad "Paleo diet" (bizarrely downtrodden by the conventional nutritionists, dieticians, and doctors in so many mainstream publications compared to such champions of processed food as SlimFast and WeightWatchers).

 "It's really not that radical--unless you consider eating nutrient-dense, unprocessed food radical.  Which, in today's microwave-dinner-fast-food-low-fat era, might very well be the case."

This book is Dallas' side of the argument with Kurt Harris.  It says, look, there may be some people who are perfectly healthy eating dairy, but it is worth eliminating it from your diet for a spell to see how you do. Some people, like me, will find fat mass, complexion, and GI tract all the better for it.  Others will not. Some will do very well with a bit of black beans (I do) whereas others will find it disturbs the intestines. And, again, there is nothing radical about a 30 day prescription of elimination. The real question is, what do you do for the rest of your life, and the transition to beyond the Whole30. Dallas and Melissa have plenty of answers for that as well, as does everyone else�let the debates begin.

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Glutathione: We Loves It (NAC and Autism)

I love twitter.  And I'm nearing 10,000 tweets, which is probably diagnostic of something.  But twitter is a great way to find articles and studies and things of interest tweeted by others with similar interests.  And twitter is how I found this new study from Biological Psychiatry, A Randomized Controlled Pilot Trial of Oral N-Acetylcysteine in Children with Autism.  Everyone go follow Cognitie.  He's obviously intelligent and good-looking to boot, with lots of cool links and whatnot.

N-acetylcysteine is a supplement I've covered before, in Problems?  I Have a NAC for That.

(Phoenix:  Armistice.  Right click to open in new tab)

A healthy brain is all about balance.  One one side we have glutamate, which is the major excitatory neurotransmitter in the central nervous system.  Think of glutamate as a charioteer with a whip forcing the horses in your noggin to GO GO GO.  We're glad we have glutamate.  Without glutamate we'd be dead.  But the problem is, glutamate doesn't always know when to stop.  That's why we have GABA, the major inhibitory neurotransmitter in the central nervous system.  GABA is the groom who takes those horses out to pasture to munch on the green grass and rubs the horses down with a nice brush.  In the right balance, you have a winning horse.  With too much excitatory action you get a worn-out old nag.

In autistic spectrum disorders, there are a number of lines of evidence pointing to problems with the excitatory/inhibitory balance in the brain.  There seem to be increases in expression of RNA for genes in the glutamate pathway, and there are certain genes having to do with the glutamate system that increase the risk for having autism.  Glutamate is actually the precursor for GABA, and the enzyme that catalyzes the transformation from one to the other is glutamic acid decarboxylase.  Both reduced levels of this enzyme and increased levels of glutamate have been reported in areas of the brain and spinal fluid in some children with autism.

In addition, as I noted in a previous blog post, autism symptoms may be a result of redox imbalance.  That is, throughout the body, we have oxidants and antioxidants.  We oxidize things to burn them in order to make energy, but we are left with "reactive oxygen species" as part of the burning process.  Antioxidants go around and sop up the reactive oxygen species to prevent them from damaging and destabilizing proteins and fats and whatnot.  Reactive oxygen species run amok can damage neurons and cause major brain problems.

We're used to thinking of "antioxidants" as vitamins such as C and E.  However, the major antioxidants in the body are actually superoxide dismutase, catalase, and glutathione.  The glutathione is one of the ways where NAC comes in, because as a supplement it is the best way to replenish gluathione in the liver and the rest of the body.*

(Animal Kingdom: Strange Attractor )

In the brain, the cysteine from N-acetylcysteine activates a glutamate-cysteine antiporter (a type of transporter in and out of a cell that exchanges cysteine for glutamate).  Shoving glutamate into the extracellular space in the brain leads to downregulation of glutamate transmission in the central nervous system.  So if you have too much glutamate whipping the brain, NAC seems like a mighty useful supplement to take.  Therefore, if autism spectrum disorders (and other neurologic and psychiatric disorders) are a result of an excitatory:inhibitory imbalance, with overabundant excitation, NAC will bring the players more into balance.

At the same time, if autism spectrum disorders (and other neurologic and psychiatric disorders) are a result of redox imbalance, with reactive oxygen species terrorizing the delicate neurons, NAC will help the body make plenty of glutathione to help clean up those bad boys.

There's no single cause of austim, but NAC might be a way to kill several birds with one stone, as it were.  AND, in the brain the two pathways (excitatory:inhibitory and redox) come together, as glutathione can displace glutamate at its receptor.  Another win for NAC, it would seem.**

And, as noted in the excellent editorial in the same issue of Biological Psychiatry, Translating the Rosetta Stone of N-Acetylcysteine, these multiple effects may be why NAC has been shown to be efficacious in trials of so many psychiatric disorders.  In the first paper I linked above, a small pilot trial, symptoms of irritability in autism were much improved in 5 kids, minimally improved in 6 kids, no change in 2, and one child got worse (though after the trial and on no NAC the subject had the same symptoms which were eventually found to be due to constipation).  In the placebo group, two were much improved, five were minimally improved, five had no change, one was minimally worse, and one was much worse.  Postive trials for NAC have also been reported for certain symptoms of schizophrenia, bipolar depression, cocaine craving, smoking cessation, trichotillomania, and gambling. What is also fairly remarkable is a lack of negative studies (established agents for all of these conditions have many negative studies.)

We still don't know if NAC is entirely safe (I wrote some theoretical problems with long-term use in my original blog article), and dietary supplements that aren't pharmaceutical grade might not be as reliable in dose, active ingredient, etc. as prescription medication.  On the other hand, we know that prescription medicines aren't entirely safe, and in many cases, we know they have very considerable risks.
It would be nice to have some replication of these studies.  As it stands, however, NAC has more of an evidence-base for use trichotillomania than any standard pharmaceutical.

Out of all the supplements, the ones that impress me the most are NAC and magnesium.  NAC sure isn't "evolutionary psychiatry," but in this modern world of stress, poor sleep, and inflammatory food, beefing up the glutathione and taming the glutamate seems like a reasonable approach, particularly if you are having devastating symptoms (as in severe autistic disorders).

*Glutathione itself is poorly absorbed as a supplement, and is too large a molecule to be easily absorbed into the cells.  Cysteine is the rate-limiting component of the reactions taking glutamate + cysteine to eventually make glutathione.  Cysteine itself is not easily absorbed, but the acetylated form, N-acetylcysteine, is.  Therefore, if you take n-acetylcysteine, you supply both a necessary precursor for glutathione and a nifty way to mop up excess glutamate.  Win-win on that front.

**and another eek! for acetaminophen

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Do Sugar and/or Saturated Fat Make You Stupid?

Two more heavily publicized papers came out in the past week or so, just in time to be fodder for questions at my talk on Evolutionary Psychiatry and Alzheimer's Dementia in the upcoming week.

Have you ever heard the Adagio from Spartacus? Hang in there for a little bit. Around 1:09 you get the early rendition of one of the more romantic themes in classical music, repeated with greater power later in the ballet (2:47 and 7:04). The Russian composers really knew how to sock it to you with a good theme.

Can we say the same of rat researchers from UCLA?  Well, excepting our own good friend and AHS president Aaron Blaisdell, the jury is still out� These researchers pulled out some interesting things, though, in their little study on 24 rats.

"'Metabolic syndrome' in the brain: deficiency in omega-3 fatty acid exacerbates dysfunctions in insulin receptor signaling and cognition."

This paper combines everything awesome and evil all at once.  Rat study.  Fructose!  DHA.  Mazes.  The authors even begin the paper not with an abstract but with highlighted Key Points:  We provide novel evidence for the effects of metabolic dysfunctions on brain function using the rat model of metabolic syndrome induced by high fructose intake.  Etc.

So� we have some rats.  There are two diets and two drinks.  Group 1 gets regular rat chow with omega 3 and water to drink.  Group 2 gets regular rat chow with omega 3 and a 15% fructose drink instead of water.  Group 3 gets water and omega 3 deficient diets (and I doubt it is so easy to make a human in the wild quite so omega3 deficient as these rats), and group 4 gets the double whammy of an omega 3 deficient diet and the 15% fructose solution.  The diets go for 6 weeks, and in that time, we have a pretty remarkable change in the fructose-slurping rates.

The fructosed rats drink a lot more than the plain water-drinking rats, and even though they eat less food than the plain water rats, they take in more calories.  By the end of the 6 weeks, the fructosed rats have high glucose and insulin levels, and the triglyceride levels of poor group 4 (given fructose and omega 3 deficient diet) are over twice the levels of group 1 (omega 3 food + water).  The researchers found that the omega 3 in the diet seemed to protect the group 2 rats a little from the fructose, with less weight gain and less rat metabolic syndrome.

These rats had also been trained to go through a maze, and the fructose-poisoned omega 3 depleted rats did worse than any of the other groups in remembering how to get through the maze.  They lost the maze race, big time.  Again, the rats who had fructose and omega 3 had relatively preserved maze-solving abilities.

The researchers measured very specific elements in the rats' bodies and brains after the experiment.  Measures of energy metabolism were decreased in poor group 4, whereas omega 3 seemed to increase energy metabolism.  Other chemicals known to be important in the ability of the nerves to adapt and change according to different stimuli (called synaptic plasticity) were very decreased in the omega 3 deficient rats, and very much decreased in the fructose-poisoned omega 3 deficient rats.  Group 2 rats (+ omega 3, + fructose) had, again, some protection from the bad effects of the fructose.

And, not surprisingly, the omega 3 deficient rats had a decreased amount of DHA in the brain and an increased amount of omega 6 fats and their metabolites, like arachidonic acid.

Fructose in excess is well known to cause metabolic syndrome (hypertension, hypertriglyceridemia, and hyperinsulinemia are typical symptoms).  Did you know that metabolic syndrome affects the brain as well?  Of course you do. There are plenty of rat studies showing that downing vast quantities of coca-cola fructose is a pretty lousy idea, if one cares about one's liver or brain.  (I recommend this segment of the HBO Weight of the Nation series about the liver, and a good bit halfway through the next segment about sugar-sweetened drinks.)

So, we've now proven that fructose is bad (in the context of an excess calorie diet), and omega 3 is protective, and the main point is to not deprive your rats of omega 3.

Sugar can indeed make you dumb (in the context of an excess calorie diet).  Eating lab rat chow completely devoid of omega 3 can make you even dumber.  I don't recommend it.  But you can see how a modern processed food diet can mimic these changes.  Soda or juice or red bull or sweetened beverage of your choice and a lack of omega 3 does not a happy liver or brain make, and the changes occur quickly.

And now the second diet and dementia study of the week (involving actual humans! However, it is another observational study from the hospital where I'm academically attached).  Participants in the Women's Health Study (about 39,000 female health care professionals) filled out a food frequency questionnaire at baseline, and beginning five years later, an older sub cohort (about 6000 women over 65) underwent serial cognitive testing via telephone over the course of an additional four years. Data was gathered and statisticians went to work.

The women underwent cognitive testing three times, with the time between the 1st and 3rd test being an average of 4 years.  Women tended to do better the second time than the first time (having learned what the tests were going to be), but at the end of the four years, the scores dropped for most women from the second to the third test.  It declined the most for women who ate the most saturated fat, and actually test scores continued to improve for women who consumed the most monounsaturated fat.

There were no associations between total fat, trans fat, and polyunsaturated fat (which is mostly omega 6) and cognitive change.

By the time you pull out covarites you have a mell of a hess.  Saturated fat intake was associated with lower rates of high cholesterol, by the way (statinization??  This part of the study occurred from 1998-2002.  Statins came out in the late 80s and lipitor, the biggest-selling one I believe, was released in 1998. Though it is hard to tell if women on statins would have automatically been put into the "hypercholesterolemia" group or if just total cholesterol was used to make this group.  There are many frustrating things about the way the data is presented in this study).  MUFA (olive oil) consumption was also correlated with lower total cholesterol.  Women with known cardiovascular disease (history of a myocardial infarction, stroke, coronary artery bypass or stenting) were taken out of the data and the trend remained similar.  More total fat intake was associated with lower exercise, smoking, and higher BMI.  Previous epidemiology studies all linked saturated fat intake to poorer cognitive function over time.  The main difference in this study is that these health care professionals had much lower total trans fat intakes than the average American.  Trans fats have been previously associated with poorer cognitive function in other epidemiological studies, and trans fat consumption tracks with saturated fat consumption.

The paper is a little too brief and too heavy on statistical mumbo-jumbo to bother much with coming up with any mechanisms.  It does recommend a Mediterranean diet at the end, and immediately classifies PUFAs and MUFAs as "good fats" and saturated fats and trans fats as "bad fats" in the discussion.

I think when it comes down to it, we will find that these women who were chowing down on the saturated fats in the 1990s are going to be women who were less likely to take care of their health in other ways.  The olive oil fans were also more educated (even then olive oil was starting to be popular) and likely to take the best care of themselves.  I'm not surprised to see these correlations.  I still can't figure out how saturated fat all on its own can cause cognitive decline, mechanistically.  I find it very interesting that the highest saturated fat eaters had lower levels of hypercholesterolemia in this large group, and the paper makes no attempt whatsoever to explain this finding.  Hmmmm.

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Mom's Wheat Sensitivity and Offspring's Schizophrenia Risk

In the midst of all the chaos this week came a very interesting diet/mental illness risk paper.  Particularly good because it comes from the premier psychiatry journal (that we in the biz call the "Green Journal" because the cover is� well�anyway): The American Journal of Psychiatry (and looks like the full text is available for free) --- Maternal antibodies to dietary antigens and risk of nonaffective psychosis in offspring.

"Nonaffective psychosis" are psychotic disorders not related to major depressive disorder or bipolar disorder (both of which can cause psychotic symptoms during severe episodes).  The most common primary nonaffective psychosis will be schizophrenia, though there are a few other rarer disorders, such as delusional disorder.

Lest we forget who the enemy is, it is inflammation.  Yes, our immune system, in the context of our modern lifestyle is often like an group of soldiers armed to the teeth with too much to do on one hand (all these modern epidemics of infections) and too little on the other (wherefore art thou, old friends?).  Lest we forget, without inflammation, we will die.  Our immune system is necessary, just like an army from time to time.

To put the screws on schizophrenia risk, let's say now, with relative surety, that there is no single cause.  Schizophrenia isn't even a single disorder, but rather a variety of disorders with similar enough symptoms to be lumped together by that most imperfect of documents, the DSMIV.  But, a few things come up over and over when we look at the suspicious characters, and these things all go back to the immune system (inflammation), genetic risk, and those contributions to the pathology of schizophrenia (ultimately brain damage of a particular kind, a neurodegenerative disease).

Risk factors for developing schizophrenia that I've heard over the years:

Family history
Urban
Advanced paternal age (and to a lesser extent, advanced maternal age)
Infections (particularly toxo and herpes)
Birth in the winter months (could be associated with infections or�)
...Low vitamin D at birth
Complications during pregnancy or birth
Cannabis use, particularly at a young age

(before I forget, it's a beautiful day� Punching in a dream by Naked and Famous)

So we get the usual hodgepodge of genetic risk (family history) plus environmental stress (particularly severe stressors that occur when the brain is forming) = increased risk of developing the disease(es).  Ultimately at a certain stage of development (typically late adolescence for men and about 10 years later for women), brain cells begin to die, signals misfire, and we end up with the typical symptoms.

It makes perfect sense that if we have a sensitivity to something in our diet, inflammation will increase, and that risk for all sorts of autoimmune conditions and other chronic diseases will increase.  And, as we already know, there is an association between schizophrenia and celiac disease, and schizophrenia and weird wheat antibodies.

So now, the new paper in the Green Journal.  It's one of those cool studies that are only possible in Scandanavian countries where you pay 70% of your income in taxes and the government keeps tab on all your health information from birth to death.  In this case, the neonatal blood samples of a whole population of folks were collected (everyone in born Sweden since 1975) and a sample of folks later diagnosed with schizophrenia and matched healthy controls were analyzed.  IgG antibodies (immune response) to gliadin (from wheat) and casein (from milk) were measured.  Newborns have immature immune systems and do not make IgG antibodies.  These antibodies must have been made by the mother and passed through the placenta in the late stages of pregnancy to the baby.

Don't all run out and get expensive IgG tests to see if you are "sensitive" to foods.  I've never seen anything compelling to show me these tests were a reliable indicator of allergies.  Wheat is so commonly eaten that almost anyone with an inflamed or "leaky" gut will have IgG antibodies floating around� however, in this study, it was the 10% of folks who had the highest IgG signal to gliadin whose offspring had increased risk of schizophrenia.  IgG antibodies to casein were not linked to any increased risk.  If only the 5% of babies with the very highest levels of IgG antibodies to gliadin were consider, the odds ratio of developing schizophrenia later in life jumps to 2.5.  Don't get me wrong, the absolute risk will still be pretty low, but any time an odds ratio jumps to >2 one should prick up one's ears as it is an interesting finding.  These findings were not attenuated by adjusting for confounders.

In general, a highly positive IgG test to gliadin means you have a risk of having celiac disease (though it is not one of the standard tests, which are typically measures of types of HLA genes, anti tissue transglutaminiase, and IgA to gliadin).  Did the moms with the highest IgG in this study have untreated celiac disease, and thus a fully flowered autoimmune disease with all the inflammation on board, affecting mom as well as fetus?  Sure, except full blown untreated maternal celiac disease is typically associated with malnutrition and small birth weight, whereas in this study there was no correlation between high anti-gliadin IgG and low birth weight.  In addition, while 90% of folks with celiac will have the HLA-DQA*0501 and DQB*0201 alleles, these alelles are not increased among folks with schziphrenia. 


All told, once again we have a link between wheat and schizophrenia, one not explained by celiac disease alone.  More unveiling of the connection needs to be done.

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One Hundred Years of Solitude

I hate the impracticality of magical realism.  It seems like hubris to swallow the laws of time and physics in poetry but expect a reader to care about the story.  And yet sometimes there is a phrase or paragraph of such power, such wisdom, that you feel gut-punched.  Your breath is gone.  For that reason a book like One Hundred Years of Solitude should be read.  Here is how it begins:

Many years later, as he faced the firing squad, Colonel Aureliano Buendia was to remember that distant afternoon when his father took him to discover ice.  At that time Macondo was a village of twenty adobe houses, built on the bank of a river of clear water that ran along a bed of polished stones, which were white and enormous, like prehistoric eggs.  The world was so recent that many things lacked names, and in order to indicate them it was necessary to point.

In the village (and later dazzling city of mirrors) Macondo, one can seemingly invent the world according to one's own perceptions.  It's a dizzying history, fragmented and timeless.  Ultimately, hubris and lack of self reflection lead to the downfall of the Buendia family and of Macondo.

This weekend, something terrible happened to Dr. Jack Kruse.  No innocent person should be summarily escorted off a cruise ship and dumped at Galveston harbor by Carnival security and the FBI.  I wouldn't wish such a thing on anyone.  In fact, six months ago I myself was questioned by Homeland Security, and for a while it seemed certain my computer was going to be confiscated by the feds, though the computer and myself were about 2000 miles away when the actual crime took place.  I was a bit shaken up; ultimately there was no way I could possibly end up in trouble, facing the accusation of the federal authorities was an awful experience.

Why am I writing about the Low Carb Cruise event?  Well, less than 24 hours after it happened, in a series of tweets and emails and blog posts and facebook posts (some of which are noted on Evelyn's blog), I had learned that *my* name was being circulated as a possible "perpetrator," though Evelyn's has been featured far more prominently and a woman from NY (who could only be Evelyn) was mentioned in a local news story by Kruse himself.  There was ugly finger-pointing.  "Perpetrators" were being threatened with 15-20 years federal prison time, civil suits, and other nastiness.

I did follow the parody twitter feed (whose tweet about explosives and legionnaire's disease and an "epic bio-hack" was apparently and very unfortunately misinterpreted by Carnival security, though it was obviously a reference to Jack's use of dynamite at his Paleo-Fx talk and his alleged self-injection with MRSA).  I even retweeted the feed several times.  I thought it was funny, and sometimes the quotes referenced me, for example one about how dangerous bananas can be.  I had guesses about who the owner of the feed might be, but did not know.  Nor do I have any clue who called (or emailed?  The reports differ...) Carnival and apparently pointed security in the direction of Jack Kruse.  That person is truly malicious.

How could a relatively mild-tempered psychiatrist who was minding her own business on a Sunday without much of a thought about neurosurgeons, cruises, or microbiology suddenly have her friends email her with forwards of alarming and threatening messages?

I opened the door.  I went to Free the Animal not too terribly long ago and engaged Richard Nikoley on his own turf.  I made it clear in no uncertain terms that I felt that injecting oneself with MRSA prior to surgery was a stupid and unethical thing to do.  Nor do I consider such a statement to be that far out on any limb, or to be that controversial.  I'm guessing that if you lined up 10 (non-biohacking neurosurgeon) surgeons and asked them about the incident, 10 out of 10 would say they thought the incident was made up or that the perpetrator was off his rocker.  Ultimately I felt that rendering my opinion on the subject was the right thing to do, as silence in the blogosphere is too often associated with approval or assent.

Thereafter things got uglier than usual over at Richard's blog.  He publically thrashed Melissa McEwen,  and I decided I was sick of the whole scene.  I thought I would stick to science and forgo any ranting for a while, and I unfollowed FTA on twitter and on this blog, just as I had previously unfollowed Kruse's twitter and facebook feeds.

A rather peaceful few weeks ensued.  But I opened the door.  And as much as one can seal it and try to block out any cracks of light, sometimes the door will burst open.  It's not the worst thing.  A psychiatrist should not shy away from aggression.  Aggression has to be met.  Actions do have consequences, and when something bad or unpleasant happens, the first thing one should do is reflect upon how one might change the situation, or whether one could have done something differently.  What a terrible situation, to be so polarizing and to have engaged in such behavior that someone would actively seek to have you removed from a cruise ship and searched and questioned by homeland security, for example.  So angry about what happened, which was indeed a terrible thing, no question, that you bring news cameras to your home and proceed to threaten and bluster even random commenters on David Csonka's website (linked above) who vaguely criticize, and list the telephone number on a public blog of the FBI agent who is investigating the case!  No thought of how other innocent people might be irresponsibly blamed or troubled, as it seems Jack was irresponsibly treated by the cruise ship security.

�in that flash of lucidity he became aware that he was unable to bear in his soul the crushing weight of so much past�he admired the persistence of the spiderwebs on the dead rose bushes, the perseverance of the rye grass, the patience of the air in the radiant February dawn.  And then he saw the child.  It was a dry and bloated bag of skin that all the ants in the world were dragging toward their holes along the stone path in the garden�The first of the line is tied to a tree and the last is being eaten by the ants.

Truth sometimes is strange and awful.  Self-reflection can be painful, but helps us to grow.  If we do not see it in time, the world we thought we had vanishes, a mirage.  No matter how loud or threatening or how aggressive we are, ultimately we return to the earth, and we are only the measure of what people remember.

Dr. Kruse will always have his followers, his believers.  They will jump with him off the shore and into the icy waters, and pay the fees for what I consider to be very dubious writings, and all the best of luck to them.

I prefer more solid and boring ground: eat healthy, exercise, sleep, relax, don't invite too much drama upon oneself... though my morbid curiousity is a definite failing.  Another weakness to reflect upon, no doubt.  There are many.

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Some New Observational Studies and Alzheimer's Dementia

I'm gearing up for a talk later this month for the Massachusetts Psychiatric Society Geriatric Interest Group, which means I'm trying to keep abreast of all the latest diet and dementia studies.  A couple new big ones came out, both from groups with which we are familiar.  The first is from the Nurse's Health Study which purports that eating berries can protect us from cognitive decline via the magical power of flavinoids.  The second paper is from the same group who linked consumption of organ meats with dementia in northern Manhattan in one of those dreaded dietary pattern studies.

They have similar designs.  Follow a large group of people without dementia at baseline for a number of years, tracking demographic and dietary information along the way. Track new diagnoses of dementia or test people with basic cognitive screens on a regular basis.  In addition, the members of the Washington Heights/Hamilton Heights Columbia Aging Project (WHICAP) had plasma beta amyloid peptide measured.  It is thought that blood levels of beta amyloid correlate with brain levels, and other studies have shown that higher beta amyloid in the plasma correlates with the onset of dementia.

In the WHICAP crew, those who had higher intake of omega 3 fatty acids had lower levels of plasma beta amyloid, even after adjusting for confounders.  This finding would make biologic sense, as omega 3 fatty acids in lipid rafts help cleave amyloid precursor protein (APP) into harmless bits, whereas arachidonic acid in the same place allows for APP to be made into beta amyloid, the component of those plaques that build up in the brain.  However, the dietary sources of omega 3 PUFAs are listed as "salad dressing, fish, poultry, margarine, and nuts," which, excepting the fish, are generally terrific dietary sources of omega 6 PUFA, not omega 3.  To get an idea of the confounders, "Participants with higher plasma levels of [beta amyloid] peptide were older and less educated and had lower intakes of omega 3 PUFA, omega 6 PUFA, and MUFA�" and "Participants with higher omega 3 PUFA, higher omega 6 PUFA, or higher MUFA intakes had a higher education, were more likely to be white or black and less likely to be Hispanic."

The researchers tried to adjust for subtype of omega 3 PUFA (bless their hearts, considering they were working from food frequency questionnaires) and "none of the subtypes of omega 3 PUFA was significantly associated with the level of beta amyloid, suggesting that overall intake of omega 3 PUFAs might play a more important role."  (Or maybe it all just suggests that people who eat "healthy" in general eat fairly healthy who are also better educated and wealthier have a lower risk of dementia and less inflammation on board, as plasma beta amyloid is linked with inflammation and oxidative stress.)

In rodents models, a bit of omega 3 in the chow can reduce plasma beta amyloid by a whopping 70% in a matter of weeks compared to "low DHA control chow" and plaque burden in the brain is "reduced by 40.3%."  In human experiments (only one of which measured plasma beta amyloid and have been small), there hasn't been much benefit to adding omega 3s in folks with dementia, though those with mild cognitve impairment might be helped.  I'm guessing that it is difficult for a human to be quite as depleted of omega 3 and topped off with omega 6 as much as those lab rats with their shudder-worthy processed rat chow.

In the Nurses Health Study, blueberries and strawberries take center stage.  Nurses who admit to eating buckets of them (chock full of the antioxidant anthocyanidin) had better cognitive scores as the study went forward over the decades.  And while according to Walter Willett the confounders are easily accounted for, you may not be surprised to know that the berry eating nurses were wealthier, more likely to exercise, more likely to eat fish, and more likely to eat more calories period.

But, in the interest of some discussion, yes, bioflavinoids are very sexy.  In the Nurses Health Study, the riches sources were strawberries and blueberries, but tea, oranges, and apples are also common sources.  The anthocyanidins in the berries, in particular, are known to be able to cross the blood brain barrier and work in the hippocampus, a central brain area of learning and memory.  Not only are they antioxidants, but might also directly deactivate cellular inflammatory mechanisms.

In short, I concur that fish and berries are good for you.  However, these studies were not designed to prove that by any means, but rather to point out some interesting population trends as related to dementia and cognitive decline.  Consider them pointed out.

I'm a bit sick of these sorts of studies, to be honest.

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Depression, Antidepressants, and the Endocrine System

It's all connected.  I know it, you know it.  Hormones and mood and the brain and inflammation� precisely how and precisely what to do about it?  Well, that is surely the sticking point.

Santigold: LES Artistes (right click to open in new tab)

I'm working from a paper today (as always) but it is not the world's greatest paper (1).  A small study hardly worth mentioning, but the discussion and conclusions have some interest.  So put your mind in an open frame but don't believe too much what you are reading.

Depression.  Not just a state of mind, really.  Can I tell you how common it is for someone to come in to see me, having just experienced a major loss (job or death in the family) and tell me: "My antidepressant isn't working.  I'm really sad."

I don't know why it is we are blessed and cursed with emotions.  There's some good explanation about how hominids survived via groupings and attachment and all that.  We are left with the baggage, as it were.  We love.  We hate.  We murder, and we grieve.  Sometimes if you sit outside and let the humid air in through your nose and watch the leaves flicker in the wind you can forget all that for a moment, and just exist, where dying is tomorrow, or yesterday, and not important.  Outside of the moment we are left with hopes, ambitions, failures, and loss.

My 9th grade biology teacher, Mr. Turner (who abandonned the profession to become a forest ranger) said to us once:  "Evolution is a fact.  Deal with it."

We have a hormonal system to deal with trauma of all kinds.  Emotional, physicical, present, past.  The lack of differentiation is the problem, frankly.  But it is what it is.  And folks suffering from  major depressive episode frequently have activation of the hypothalamic-pituitary-adrenal axis along with an increase in insulin resistance and increased accumulation of visceral fat.  Things go to hell in a handbasket pretty quickly.  There are elevations in inflammatory cytokines, not just in the brain, but all over the body.

In the traditional medical model, we add antidepressants to the mix.  I know there is no such thing as a serotonin or norepinephrine deficiency but bear with me.   Long ago, the tricyclics, which can indeed improve depression symptoms but result in an increase in body weight and possible worsening of diabetes.  The newer agents of SSRIs (prozac and the like) are actually associated with an improvement in glycemic control.

(Classical music, some of the best ever: Beethoven: Symphony No 7, II)  Classical not your drug of choice?  Sleigh Bells, Comeback Kid, ads up front.  Sorry about that.)

Weirdly, the old fashioned antidepressants who cause weight gain and dry mouth are known to decrease cortisol, whereas the new ones with fewer weight gain side effect have no immediate effects on the HPA axis.  (The wizened psychiatrists who sit in the front row of grand rounds always bemoan the lack of use of the old fashioned antidepressants in favor of the SSRIs.  But no one wants to be fat and dry-mouthed, not to mention the death in overdose so possible with the tricyclics).

Wht could be going on?  Cortisol from stress centrally increasing craving for high-caloric, palatable food� and increasing the secretion of resistin, an adipokine that causes decreased insulin sensitivity and an increase in fat storage and diabetes? In rats that is probably true.  In humans?  Not so clear.

Resistin is typiclly released in rats due to inflammatory and obesigenic influences.  But what about adiponectin, the supposedly antiinflammatory and anti-obesity hormone release in humans in response to stress or excess sugar� In humans, adiponectin is higher in women than in men, and are reduced in obesity and insulin resistance.

In the small study in the paper I've linked, free cortisol levels (STRESS) were strongly associated with levles of resisin in depressed patients.  In follow up, those who were on medicine and had decreased symptoms also had decreased levels of resistin.  There were no changes in hormone levels for those who did not improve on antidepressant treatment.  BMI was correlated with resistin also.

What do we learn?  Depression = increased cortisol secretion = increased resisitin = increased obesity.  Direct or indirect mechanisms may be unknown.  In mice, increased resistin increases fasting glucose in insulin resistance.  This may be true in depressed humans and may explain the link between depression and diabetes.  We don't know for sure.

Adiponectin concentrations didn't change during the six weeks of measurements of these depressed patients on or off antidepressants.  Only resistin measurements were statistically significant.

The endocrine system is always a bit of an investment in reading, and it doesn't always deliver.  That's why we read the Hunger Games Trilogy instead of books about the thyroid.  I get it.  Peeta v. Gale is more interesting than resistin and adiponectin.  That's not hard to understand.  We're human, after all.  We love, we hate.  We let go, we give in.

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