Saturday, December 31, 2011

Ring in the New Year

Whew.  A bit of a hiatus there.  I hadn't quite realized how much I had overextended myself until decamping to Texas for some serious sitting around.  There I had all sorts of unrealized ambitious plans to read and get caught up, visit some local Crossfits, answer some emails, etc.  I did very little at all besides the holiday stuff, a handful of morning runs, and reading some fiction.  Since the whole family was recovering from a steady onslaught of viral preschool nastiness that began before Thanksgiving, I sorely needed the rest.  A very mild but persistent case of walking pneumonia had settled in, so it was nice to take it easy and finally get well.

In the midst of the sitting around, I was able to visit two Austin "real food" restaurants, Hudson's on the Bend (where I had rattlesnake cakes - not gluten-free but very tasty, and Hudson's has several gluten-free options) and Foreign and Domestic (steak and pigs brains.  I have to say the brains at Animal were better, but the steak at F&D was fabulous, the yogurt with dill sauce sublime, and the atmosphere quintessential Austin).  I'm told the Noble Pig is also excellent (though it is a sandwich restaurant).

One of Lance Armstrong's yellow jerseys at Hudson's on the Bend
Pig brains and huckleberries
Yogurt with dill sauce
Perhaps the most ambitious thing I did all week was to go to the rail yard for the Austin Steam Train Association.  We were able to get a behind the scenes tour, and the kids were thrilled (kids love trains,  as do the adults at the Austin Steam Train Association).   

At this point I have numerous articles and a large stack of books waiting to be read.  I'm hoping that without my class, my schedule will be a bit more forgiving.  You never know what will turn up, however, and the backlog of emails and to-dos--formidable!

Friday, December 16, 2011

Time to Freak Out. Sensibly.

There is a reason I stick to relatively easily modifiable practices and how they might (possibly!) improve health and prevent disease.  I like fun exercise, real food, wool socks in the wintertime, and sunshine.  I don't like to think about the years of farm pesticide waste seeping into the groundwater, or the estrogenic compounds in plastic.  Plastic compounds are ubiquitous and incredibly convenient.  In all our packaged foods.  Sippy cups.  Tupperware.  IV bags and tubing.  Coating paper receipts.  In the lining of canned foods and soda.  The most famous is BPA (found primarily in receipts and number 7 plastic), but all sorts of plastic contain all sorts of weird compounds.

Image from Flickr Creative Commons
I like to live a relatively processed food and gluten free life - but philosophical ramblings about candy cigarettes aside, I don't dive across the table and grab the birthday cake out of my kid's hand at the party.  (I'm not generally tempted by the birthday cake myself, as it is generally of the grocery-store azol-dye soybean oil frosted variety.  There was an incredible ice cream cake at a recent party that I'll admit to stealing a few bites from).   There's a line between living a somewhat normal life and being completely obsessed and anxiety-ridden about food, and I certainly don't want the kids to be obsessed and anxiety-ridden about food.   Nor would I lie about my kids having celiac or peanut allergies - the last thing I want is a terrified preschool teacher calling me about the goldfish cracker my kid snatched from some other kid's lunch, and should she call an ambulance or what.  Nothing is totally off-limits within reason, though the healthy stuff has to be consumed first, before the leftover Halloween candy.  And yes, they do get gluten-free pretzels as a snack (they are cooked in palm oil).  And sometimes those sugar-bombs otherwise known as raisins.

So we muddle through, minimizing harm, and the way I approach plastics is to slowly transition away from them and avoid heating anything (or putting hot food) in them.  (I try not to think about those years and years of microwaved lean cuisines).  I get milk delivered from a local organic dairy in glass bottles.  Is that enough?  Some (many of you, perhaps) would say no.  But aluminum lunch containers are expensive (and have plastic lids that tend not to fit as closely as plastic on plastic), and many of the plastic ones I have are still serviceable and attractive.  Canned foods are also tricky - on a mostly "paleo" "real foods" "avoiding processed food" diet the major canned foods will be coconut milk and tomato products (maybe canned pumpkin?).  In general I made an effort to avoid these except for maybe once per week, figuring, again, the dose makes the poison, and tomato sauce makes anything more palatable for the kids (a variation of the old parenting trick of putting ketchup on everything.)

Ignorance is bliss, really.  At the end of November a research letter was published in JAMA- "Canned Soup Consumption and Urinary Bisphenol A: A Randomized Crossover Trial." In this little Harvard School of Public Health Study, student and staff volunteers consumed 12 ounces of either fresh (prepared without canned ingredients) or canned (Progresso brand) soup daily for lunch (they were vegetarian varieties of course - this is HSPH!).  For the first 5 day period, the soup was consumed daily.  After a 2-day washout, the treatment assignments were reversed.  Urine samples were taken on the 4th and 5th days of each phase.  Urinary BPA was found in 100% of Progresso consumers and 77% of fresh soup consumers, and following the 5 days of canned soup, urinary BPA was 1221% higher than the urinary BPA of the fresh soup consumers.

"The increase in urinary BPA concentrations following canned soup consumption is likely a transient peak of uncertain duration.  The effect of such intermittent elevations in urinary BPA concentration is unknown.  The absolute urinary BPA concentrations observed following canned soup consumption are among the most extreme reported in a nonoccupational setting."

I have to admit I'd canned (heh heh) Progresso and other pre-prepared soups from my eating list a long time ago due to the biochemistry-happy omega-6 fest in the list of ingredients… as expected from any processed food maker trying to scratch a profit by using the least expensive commodity items.  I try to use marinara sauce from a glass jar whenever possible (we'll ignore the plastic seal around the top), and I'm looking for good convenient alternatives to canned coconut milk… but the pantry still has some canned items, to be sure.  And certainly the cardboard box variety of foods has plastic in the lining as well, right?  I make more and more of my own bone broth, but sometimes you just need a bit of stock on hand.  Am I being hopelessly neurotic and silly worrying about plastics, BPA, and canned items (and handling receipts as little as possible)?

Well, 2011 has not been a friendly year for BPA.  A month before the research letter in JAMA alarmed the Progresso soup executives, another scary article was published in Pediatrics: Impact of Early-Life Bisphenol A Exposure and Executive Function in Children (free full text!).  A prospective observational study, so the typical caveats apply.

Urine was collected from pregnant women at 16 and 26 weeks, and at birth) and later from the resultant babies at 1, 2, and 3 years of age.  The results?  Well, BPA was detected in >97% of the gestational and child urine samples.  With adjustment for confounders, each 10-fold increase in gestational BPA concentrations was associated with more anxious and depressed behavior on standardized scales, along with poorer emotional control.  This was true more of girl babies than of boys.  The urinary levels in the children themselves didn't make much difference in behavior, and there was no difference between girls and boys.

There was another scary article about exposure of infants to breastfeeding moms replete with BPA that I can't find now, and this cute article from January in JAMA about nematodes and BPA.  I avoid gluten (for the most part) due to some skin effects and general creepiness, and I don't see why I should feel differently about estrogenic compounds leaching from plastics.

But no, I don't leap across the table and grab the Capri Sun out of my kid's hand at the birthday party either.  Nor will I add a machete to my list of standard kitchen tools so that I can make coconut milk from scratch.   I drink from a plastic-free water container at the gym and the next set of lunchbox containers will be metal… but life has to be lived.  And at least I can worry about these things affecting my children, rather than tuberculosis, mines, or revolution.

Saturday, December 10, 2011

Evolution and Anorexia Nervosa

There was a bit of a dust-up in the paleo and low carb blogosphere about some comments Gary Taubes apparently made about anorexia and insulin in an interview.  He noted that insulin was used as a therapy for anorexia, thus suggesting that (perhaps) anorexia, like obesity, is a disorder of fat metabolism. My suspicion is that Gary was using those studies as an example of how insulin could cause weight gain.   On the other hand, one doesn't need exogenous insulin to refeed anorexics  - the time-tested method is to keep those far gone enough to have medically dangerous symptoms (unstable blood pressure, dropping electrolytes, or super slow heart rate) under lock and key and get calories in whatever way possible (including via a tube inserted into the stomach.)

One of my attendings in at Children's Hospital characterized anorexia as "a desperate disease."  Often purging and starvation are combined (though this combination would be more correctly called "eating disorder not otherwise specified" or "anorexia nervosa, bingeing-purging subtype" than strict anorexia nervosa), and there were many cases of young teenagers hiding vomit and stool in places in their rooms to conceal purging and to get laxatives (not surprisingly, constipation is a symptom of anorexia).

Cowboy Junkies - Bea's Song (one of the better songs ever written - right click to open in new tab)

My evolutionary psychiatry interest has always been in how psychiatric disorders have changed over the past 100 years of rapidly changing lifestyle and diet.  Anorexia nervosa is one of those illnesses that was exceedingly rare until 50 years ago, then escalated rapidly, then leveled off so far as prevalence, though those who are affected encompass more children and more men now than ever before.  My educated guess is that only a small percentage of us are capable of starving ourselves outright without being under lock and key, and that vulnerable population shows symptoms earlier and earlier in life as societal pressures and the obesogenic environment increases.

A quote from my previous blog post linked above (the medical literature references can be found there):

All eating disorders remain relatively rare [though in total they are more common than schizophrenia and bipolar I disorder]. Anorexia afflicts about 0.5% of women and 0.1% of men. Bulimia around 1-3% of women (also 0.1% of men), and binge eating disorder 3.3% of women and 0.8% of men. Anorexia nervosa remains the most deadly of all psychiatric disorders, with a 5-10% death rate within 10 years of developing the symptoms, and an 18-20% death rate within 20 years. Anorexia is endemic in the fashion industry, to the point where models are now being airbrushed to add curves. Another model, Isabelle Caro, died at age 28 of anorexia, and Ana Reston of Brazil died at age 20, still modeling with a BMI of less than 14.
Photo of Isabelle Caro from Wikipedia
The current state of the art treatment of anorexia begins with refeeding, mostly because we know that semi-starvation itself causes obsessions, depression, and fixation on food.   In the hospital, patients work closely with dietitians, trying to learn how to eat a healthy amount and to establish a better relationship with food.  While medicines that promote weight gain are prescribed, antidepressants and other agents are fairly useless in a starvation situation.

You can imagine the typical well-meaning dietician designed diets for these sick young people.  It's the food pyramid with way too many grains, too little fat, and a focus on "healthy" rather than good old fashioned farm fresh food.  And while I don't really have any objections a food pyramid Mediterranean-style whole foods diet (autoimmune issues with grains notwithstanding), I know that what happens in real life is not skipping breakfast, a light lunch, and a late supper of mussels, olive oil, roasted peppers, tapenade and homemade sourdough bread, but rather three meals and two snacks a day, a version of Weight Watchers™ with Skinny Cow ice cream sandwiches, whole grain Rice o Roni, cans of beans, omega-6 laden commercial salad dressing, boneless skinless chicken breasts,  and "lite" yogurt.

The problem with so many meals a day is that one has to think about food constantly.  I don't think that is the best way to recover from an eating disorder, though one would have to be careful with fasting as well.  I believe intermittent fasting is a valuable practice, a way to lower food reward and to ultimately establish a good relationship with food - I don't have to have it right now, but later would probably be fine too - however, fasting can trigger binges in those who are vulnerable.  It is not verboten in those of normal or excess weight, but should be undertaken with care and support.  In my mind, the healthiest diet is one that you don't have to think about all that much - poached eggs, a beef stew with some liver chunks you cook once and eat all week long.  Cold potatoes and butter.  Forgetting to eat every now and again.

M83  Midnight City (right click to open in new tab)

I believe Jamie sent me this recent paper, Role of the evolutionarily conserved starvation response in anorexia nervosa.  It is a fascinating piece, with an in-depth consideration of biology, evolution, and insulin.

The authors speculate that "AN [anorexia nervosa] may be caused by defects in the evolutionarily conserved response to food and nutrient shortage associated with reduced calorie intake."

Some more facts about eating disorders - in 10-20% of patients, the disorder is short-lived.  In 20-30% it is chronic and unremitting.  The most seriously affected are at greatest risk for hypothyroidism, loss of bone density, electrolyte disturbances, low blood cell counts, amenorrhea, suicide, and death.

In anorexia, the physiology of starvation is paramount.  Both brain and peripheral metabolism responses come into play, orchestrated by the brain and the endocrine system (I don't think obesity is far different - I see no reason that obesity would be regulated by fat tissue or the liver when the brain and endocrine system are doing their thing).

The goal of the starvation response is to conserve energy, delay growth, preserve ATP (by increasing efficiency of energy metabolism) and to minimize oxidative damage.  In starvation, changes in the hypothalamus of the brainstem result in a fall in blood insulin levels and a suppression of other anorexogenic factors.  Once ketosis occurs with the depletion of glycogen stores, there is an increase in output from the sympathetic nervous system and stimulation of food-seeking behaviors.  These multiple pathways explain why fasting can be healthy, but also stressful.

One of the major biochemical pathways activated is the IGF-1/FOXO response (an insulin growth factor 1 pathway).  So the authors of this paper postulate something a bit similar to Gary Taubes - anorexia arises when there is defective regulation in the starvation pathway, similar to how insulin deficiency (due to insulin resistance) is a factor in diabetes.  Meaning there is a lot going on with respect to home life, environment, stress, and temperament in eating disorders, but only a select few have the genetic capability to deliberately starve themselves is response to the environment, and those few may have differences in the IGF-1/FOXO pathway.  The researchers were able to find some yeast, fruit flies, worms, and mice with defects in that pathway who tend to restrict food and develop more slowly (or, alternatively, eat more and spontaneously gain weight), and who have genetic differences in the IGF-1/FOXO pathway.

Evidence for genetic vulnerability to anorexia includes the fact that eating disorders are highly heritable. (Uruguayan model Luisel Ramos and her sister both died from anorexia in recent years).   When doing genome-wide linkage analysis of families with eating disorders, many components of the starvation response pathway are located in highly suspect genetic areas.  In practical terms, the increased impetus on thinness and subsequent dieting brings out the reinforcing starvation response as a result of the genetic vulnerability.  A single episode of excessive caloric restriction seems to bring out long-term changes in the neurotransmitter production mediated by FOXO.

Thus caloric restriction and weight loss predispose to additional episodes of dieting, especially in susceptible individuals wih defective regulation of their starvation response, or with perseverative bias in behavior, reflected in obsessive thoughts and compulsivity.

How do these general ideas affect treatment?  Family therapy, distress tolerance, and cognitive behavioral therapy around distorted body image is a cornerstone of therapy for eating disorders, along with the refeeding.

Should we use insulin to treat anorexia?  Well, the reactive hypoglycemia and other risks are problematic.  A more sophisticated approach is to use IGF-1 itself - it can increase appetite and reverse bone loss seen in anorexia.  Long term treatment tends to result in hyperplasia of the lymphatic tissue, tumor promotion, and excess accumulation of body fat.  

Better that we never begin dieting in the first place.  Skipping the processed foods and ensuring there are plenty of healthy fat and nutrients for the brain and muscles seems like the optimal and common sensical approach in that regard.  I'm not sure what to do about the fashion industry...

Saturday, December 3, 2011

Beyond the Chemical Imbalance Part 2

Love the new song from the new album by the Black Keys:  Lonely Boy (from El Camino)   I know this guy's video will get slashed soon enough, but for now… enjoy!  The Black Keys said Lonely Boy is a departure from their typical style, as it is up-tempo.  I wish they would do more like this one!

Are you peppy yet?  You ought to be, because we are going to dive back in to this paper (sent to me by Jamie some weeks ago):  Beyond the serotonin hypothesis: Mitochondria, inflammation, and neurodegeneration in major depression and affective spectrum disorders.

There's all this talk about pathogenesis, chickens, and eggs.  Well, I know where it ends.  We chase the trail back to the beginnings (is it abuse?  temperament? soda?  ho-hos?  winter? rancid vegetable oil?  bad reality TV?  the jury is still out).

But here is where it ends.  Ground zero.  Ratty neurons, smoking mitochondria, and brain damage.  Inflammation.

Inflammation is the term for the complex biological response of tissues to harmful stimuli, such as pathogens, damages cells, or irritants.  Inflammation is a protective attempt by the organism to remove the injurious stimuli as well as initiate the healing process for the tissue.
I knew there was a reason I liked this paper so much.  Two sentences of real wisdom.   The paper continues on to talk about cell death, mitochondria, and the cell "executioners" called capases.  They are cysteine proteases that bring it when a cell needs offing.  These are the cellular equivalent of the Necro-whatevers from Chronicles of Riddick.   Overproduction of reactive oxygen species by shoddy, inefficiently-acting mitochondria is a central feature of neuron cell death.   The tricky wicket is that mitochondrial dysfunction and cell death leads to more inflammation, dysfunction, and cell death.

The presence of an inflammatory response in major depression… is evidenced by, amongst other things, increased plasma levels of pro-inflammatory cytokines and acute phase reactants, oxidative damage to red blood cell membranes and serum phospholipids, and lowered serum zinc.
Pro-inflammatory cytokines can induce depression in 70% of people treated with such agents.  Elevations of cytokines have been reported in depression, anxiety, fibromyalgia, migraines, IBS, chronic fatigue syndrome, diabetes, autoimmune arthritis… of course, says any doctor.  The so-called "mitochondrial cocktail" can improve mitochondrial function after a few months and includes the following:  CoQ10, riboflavin, and at least one additional antioxidant (vit C, E, or alpha lipoic acid), and l-carnitine or creatine.

Older school psychopharmacologists will try the following:

Tricyclic antidepressants - they act as classical mitochondrial decouplers by hindering ATP synthesis and enhance ATPase activity.  They tend to change how mitochondria function in a neuroprotective way.

SSRIs: some seem to be toxic to mitochondria at large doses, but protective at lower doses.  In animal models, all antidepressants attenuate inflammation-induced brain cytokine production and prevent the development of depression induced by high dose interferon.  In fact, antidepressants seem to have this effect regardless of mechanism (SSRI, tricyclic, lithium) - which is a major argument against the monoamine theory of depression.

Lithium: seems to enhance mitochondrial function in humans and rats.  Long-term is even better than short-term.  Lithium is the favored medicine of the gray-haired psychopharmacologist.  Between the neuroprotective effects and the anti-suicide benefit, you might expect people to encourage lithium to be in the water

Shock therapy:  Yes, it is still around.  Frankly, there is no faster treatment for depression and it works in refractory cases, thus is often a lifesaver.  It has terrible side effects, there's no denying it.  And it seems to increase the mitochondrial efficiency in rats.

Up to 50% of patients with major depression are unresponsive to medications… here is a poem from old Egyptian papyrus (from the anchor paper)

Disease has sneaked into me.  I feel my limbs heavy.  I no longer know my own body.  Should the master physician come to me… My heart is not revived by his medicines.