Friday, April 29, 2011

Anorexia and Season of Birth

Quick post tonight.  I have been at a conference all day (and will be there all day tomorrow), and I'm swimming in a bit of information overload.  However, a bunch of new ideas are now simmering for future posts.  I have some more Diet and Violence papers to blog about also, but first a little paper sent to me (of course) by Evolutionary Psychiatry's dear friend, That Paleo Guy, Season of birth and anorexia nervosa from the British Journal of Psychiatry.

(Retriever, I think this post will also address some of your questions from your excellent comment on my last post!).

Previous studies of anorexia and birth month were too small to be of much use.  You need a lot of cases to detect differences between patients and controls if season increases risk marginally.  In this study, the researchers combined the results from several different UK studies, and then used some fancy statistical techniques such as "harmonic and spectral analysis" as opposed to the traditional chi squared test to wring as much out of the data as they could.

All told, 1293 cases of anorexia nervosa were compared to births in the general population from 1950-1980.  The results:

Here is the pertinent graph (reproduced here with permission) and the source: linked at the British Journal of Psychiatry.

You will see there is a bit of a spike of anorexia cases for people born in the springtime, and a yearly nadir in October.

The discussion is short but sweet (and as the paper is free full text, I encourage you to take a look from the link in the first paragraph).

What these sorts of results show us is that early life and the neonatal period can plausibly be a time when suboptimal environments can eventually show up as disease later in life.  Apparently there was a finding recently that an interaction between a dopamine receptor gene and season of birth influences body weight regulation in women with bulimia (1).   But here is a problem with season-of-birth research - pregnancy is 9 months long, and obviously development occurs during all of that time, with vulnerable developmental windows of different sorts opening at different times all during the gestation.  The environmental factors that could affect a seasonal change include maternal nutrition, sunlight, vitamin D, stress, temperature, and infectious disease (you can probably think of a few more).

Here is a quote from the study pertinent to Retriever's question and encapsulates my thoughts as well:

Interestingly, vitamin D levels have been shown to be associated with psychiatric disorders.  Although the presence of low vitamin D levels in people with psychiatric illness may be the consequence of reverse causation, further support for a role of vitamin D comes from functional studies showing that it is also involved in neuroprotection and brain development.

So low vitamin D during development could plausibly cause problems - or maybe low vitamin D in mom is a sign of some sort of illness or problem, and that illness is the issue… if the first part is true, vitamin D supplementation will be protective.  Otherwise, who really knows?    Vitamin D has SO many roles in the body that pinning down the whys, wherefores, and causation chicken-egg issues can be super tricky.

It would be nice if some vitamin D levels were measured - in the Netherlands they keep samples of neonate blood and have measured vitamin D levels for schizophrenia research - I bet someone could do the same comparison with anorexia.  It would still just be an association, but at least we could say vitamin D was definitely involved somehow if such a study were done.

Well, better get some shut eye as I have to be up early for the train into the city.  Good night!

Thursday, April 28, 2011

Standing on the Sun Will Not Prevent Depression

Vitamin D. What a roller coaster. There's the Vitamin D Council telling you to aim for a level of 60-80 ng/ml, and then the Institutes of Medicine rather grumpily suggest 20 is sufficient with a monstrous report no one has time to read except Chris Masterjohn. Vitamin D Council says no risk of toxicity below 150 - Chris Kresser, Paul Jaminet, and Kurt Harris talk about lack of randomized controlled trials and suggest somewhere between 20-50 as a good range (depending on the expert and depending on your skin color), and there is risk of kidney stones, calcification, and premature aging at higher levels. As I am a (very) pale woman, and I have looked at a bit of the pregnancy and cancer literature, I tend to think, hey, pale pregnant women might do better a bit above 50, Caucasian women should aim for 40-50, and everyone else, 30-40 is probably a good range. But Kurt makes a good point in his podcast with Chris Kresser - the 25 (OH) Vitamin D3 level we al measure is still indirect. 1,25 OH Vitamin D is the active hormone, but its metabolism is tightly regulated and levels are rarely out of a narrow range no matter how deficient we are - so who knows what a low serum level of 25 (OH) Vitamin D3 actually means in local areas, such as the brain, or in scanning for cancer cells in other sequestered areas of the body.

I don't know if I really have much of a horse in this race, though, as the data for mental health is scanty, to say the least. But the theory is sound for vitamin D to play a prominent role in mental health, as it interacts with stress hormones and nerve growth and repair, and seems especially active in those areas of the brain associated with mood, appetite, and sleep (the hippocampus and hypothalamus).

Australian researchers have been valiantly paving the way in single megadoses in seniors for years now. In the Vital D Study, 2317 women over 70 living in the community were recruited from voting rolls (which is compulsory in Australia). Women were included in the study if they had a high risk of hip fracture or previous hip fracture, osteoporosis, or high risk of low vitamin D levels. For several years, they were given a single dose of 500,000 IU Vit D3 or placebo (in 10 easy to swallow capsules) once each year in the autumn or winter, and several measures were followed along the way.

One of the measures, more fractures, proved that standing on the sun once yearly is not a terrific way to prevent them. The active group getting the vitamin D had significantly more fractures and falls.

And then there is depression. It was a lot of people, so the typical short scales were used (the GHQ-12 questionnaire). I already blew the punch line in the title. The active group had no significant difference from the placebo group in the amount of depression or change of depression with the huge bolus of vitamin D3.

Let's look more closely. The average vitamin D level for all the women at the beginning of the study was about 50 nmol/L (1 ng/ml = about 2.5 nmol/l, so the more typical 25 OH vit D3 level measurement I'm used to seeing is 20 ng/ml.) For the most part, the women in the active arm had vitamin D levels 40% higher than the placebo arm, with a level of 120 nmol/l (48 ng/ml) after dosing, and 90 nmol/l (36 ng/ml) after 3 months.

And the discussion, which is (typically) the most interesting part. The association between vitamin D and mental health is inconsistent. Epidemiology shows a correlation between low levels of vitamin D and depression. In a small fibromyalgia study, mood and fibromyalgia symptoms were not related to vitamin D levels before or after supplementation, even in those with vitamin D deficiency. In another 6 month study of older women receiving 800 IU Vit D3 and 1000 mg calcium daily, depression scores did not improve compared to placebo. In another group of folks receiving 100,000 IU Vit D3 vs phototherapy for seasonal affective disorder, Vit D3 was a clear winner. In another study of obese individuals, 20,000-40,000 vit D3 per week for a year showed a beneficial effect on depressive symptoms, though those with a baseline level > 40 nmol/L (16 ng/ml) had no benefit.

How to pull it all together? Well, 1,25 OH Vitamin D, the active form, definitely has a role in the central nervous system in neurogeneration and repair. However, the CNS may have a separate conversion system from 25 OH Vit D3 than the rest of the body. Evidence from a study I blogged about earlier suggests maybe a u-shaped curve is applicable - neonates with the lowest and highest amounts of vitamin D had the highest risk of schizophrenia later in life.

It is probably safe to say that giving 70 year old women massive doses of vitamin D3 once a year is a bad idea - bones and mental state accounted for. "Clinical studies of vitamin D in clinical populations with documented insufficiency remain warranted." And, indeed, at no time in history would we ever have been exposed to 500,000 IU vitamin D3 in a single day.

My personal clinical experience? A LOT (I'd say 1/2 to 2/3) of people who come to see me have horrible vitamin D levels. I live in the far north of the US, but it is not uncommon for levels of 12-14 ng/ml to show up on my initial tests, with the lowest I have seen being 4. I would have to say, sunshine and/or vitamin D supplementation (depending upon the season) has perked up my clinical population over a timeframe of, say, 6 months. At the same time we have implemented other interventions (nutrition, therapy, medication), so who knows what made the difference.

Is Vitamin D the end-all, be-all missing link to the question of crappy modern health and modern disease? No. Does it play a role? Most likely. But you can't overdose on vitamin D via sunshine, and you sure can via megasupplements. Vitamin D is a hormone that sticks around for a while, not something to muck around with willy-nilly. I supplemented this winter, as I was low. I'll make every effort to soak up the rays all summer. Will I supplement next winter? Probably not.

Tuesday, April 26, 2011

Diet and Violence

Paul Whiteley*, I believe, originally posted to the comments concerning some very interesting studies on diets and violence. Over the past 10 years, several groups of researchers have done some decent work in this area, and (for once in the nutritional-type literature) I can actually look at a randomized controlled trial of good size and design that was actually replicated.

The modern era of good studies begins with Oxford nutrition and criminology researcher, Bernard Gesch (1). Back in 2002, he published a (full free text) study entitled "Influence of supplementary vitamins, minerals, and essential fatty acids on the antisocial behavior of young adult prisoners." In this study, 231 (young, male, adult, prisoner) volunteers agreed to receive a daily vitamin, mineral, and essential fatty acid supplementation or placebo. The average length of the supplementation was about 142 days, and a number of measures were taken before and during the active phase, including psychological testing, reports of violent acts, and reports of disciplinary action. Prisoners were randomized in part based on baseline disciplinary status and their progress in the "prison regime."

Here are the active ingredients of the multimineral, multivitamin, one of which the prisoners in the active arm received daily:

The prisoners also received a fatty acid supplement with 1260 mg linoleic acid (I know - we'll talk about that later), 160 mg gamma linolenic acid, 80 mg EPA and 44 mg DHA. The placebo fatty acid pill was made from vegetable oil.

The results? The average number of "disciplinary incidents per 1000 person-days" dropped from 16 to 10.4 in the active group (p<0.001), which is a 35% reduction, whereas the placebo group only dropped by 6.7%. Especially violent incidents in the active group dropped by 37%, and in the placebo group only 10.1%. That's a pretty impressive finding, really. Currently, Gesch is working on a study of 1000 prisoners in 3 different UK prisons for a 3 year trial, including blood chemistry analysis to see what the baseline levels of micronutrients are in the prisoners, and also more cognitive testing, designed to answer some questions the earlier study couldn't answer. However, luckily for us (as the newer Gesch results have yet to be published), a Dutch research team led by Zaalberg repeated the experiment (more or less) in "Effects of Nutritional Supplementation on Aggression, Rule-Breaking, and Psychopathology Among Young Adult Prisoners." The researchers note that behavior issues have been linked to deficiencies in omega 3 fatty acids, and that low levels of magnesium and zinc are also associated with hyperactive behavior, impaired brain development, and cognitive dysfunction. Check out the quote from the study:

The mechanisms underlying potential associations between nutrition and behavior, however, are not yet clearly established. Although a clear comprehensive theory is lacking, several findings do offer some clues on the plausibility of dietary interventions. Epidemiological research, for instance, shows that major changes in dietary patterns over time have taken place, especially in industrialized world during the last century [Cordain et al., 2005; Crawford et al., 1999; Muskiet, 2005; Simopoulos, 1999]. These changes resulted in (micro)nutrient intakes that are significantly lower than in the ancient, Paleolithic diet. Indeed, some ecological studies show correlations between diet and behavioral outcomes [Christensen and Christensen, 1988; Hibbeln, 2001; Peet, 2004], including criminal behavior [Hibbeln, 2001]. A major limitation of epidemiological studies is, however, the impossibility of making causal inferences. For this reason, the findings mentioned above must be judged with caution and experimental confirmation is needed.

(I love these researchers already!) They did this trial specifically to see if they could replicate Gesch's work. Only they made some very likeable modifications in their supplement - specifically leaving out linoleic acid "because of its abundance in the Dutch diet", and using larger capsules that could include more bioavailable forms of minerals, so there was more magnesium (300mg of Mg citrate vs 30mg (of ?) in the Gesch trial). They also halved the amount of vitamin D (from 400 IU to 200 IU) in the supplement (but did not specify why). And no one supplemented with micro doses of lithium :-).

Here is how they changed the omega 3 compared to Gesch:

In all, 221 young male prisoners completed the study. Many dropped out, often due to transfer to another prison or being released. Of the completers, numbers of violent events in the active group dropped 34%, whereas incidents in the control group increased 14%. The overall number of incidents was lower (11 per 1000 person-days) in the Dutch prison compated to the UK one, but the percentage change was still significant. There were no significant differences in any of the cognitive, personality, and behavioral testing measures used, just the actual incidents. Which is interesting. Because you can't figure out, from this data, why the incidents decreased. If you could say - oh, look, impulsivity and attentional measures improved, then you could say that's why the behavior is better. But they didn't improve. Which means maybe the cognitive measures aren't very good, or the effect was too subtle to catch. Well, I know a prison warden cares more about decreasing reported numbers of violent incidents in a prison compared than decreasing the psychologic testing measures of impulsivity.

One problem with this second study is that at the beginning, 51% of the prisoners guessed wrong as to whether they were receiving active vs. placebo pill. By the end, only 25% guessed wrong, suggesting the blind was somehow partially broken (perhaps by smell of the pills?). Violent incidents were measured by the prison staff, it is unknown whether the prisoners told the staff if they suspected active or placebo pills. So keep that in mind when interpreting the results.

Here is the Dutch researcher's conclusion, and it will serve as mine as well:

To summarize, the prospect of influencing aggression and rule-breaking behavior with nutrients in moderate doses is important enough to warrant further research. This is particularly true as adequate supplementation may also have beneficial effects on mental health and cognitive functioning [Benton, 2001; Hibbeln, 2001; Richardson, 2004]. This study, however, did not confirm this association, except for some marginal trends in this direction. Yet, as the found decrease in the outcome measure—reported incidents and rule-breaking—is in line with the earlier British prison study of Gesch et al. [2002], we feel that further research on the association between dietary status and violent behavior is warranted

* I really enjoy Paul's blog, Questioning Answers, focused on research and thoughts about autistic disorders. He is far more sober in his interpretation of the science than I am myself - which is likely a far more accurate portrayal of the validity of the results.

Monday, April 25, 2011

A Summary of Endocannabinoids and Obesity

In my last post on endocannabinoids, I was trying to do a little too much with too little time, and I don't think the science came out too clearly.  Today I thought I would use the excellent Kim et al paper again for a quick summary of what is known about the effects of the endocannabinoids on obesity, both in the central nervous system (my usual bailiwick) and peripherally.  (Also, please check out Beth's post over at Weight Maven - she has diagrams too!)

Endocannabinoid AEA will activate the cannabis receptors in the brain and in the fat tissue and skeletal muscle.  The response is to increase food intake, possibly by increasing the appetite hormone ghrelin.  AEA is found at higher levels in obese individuals than lean individuals, and seems to promote fat storage. In the muscle, it decreases glucose uptake, which is one way to increase insulin resistance.

The other major human endocannabinoid, 2-AG, also increases food intake, and is also found at higher levels in obese individuals.  The amount of 2-AG you have circulating in your body is positively correlated with how much body fat you have, and inversely related to insulin sensitivity.  It also decreases glucose uptake in the muscle.

CCK is a hormone secreted from the intestines when we eat.  Normally it sends a signal to the brain telling us that yes, indeed, we have eaten, and we can back off with the hunger signals already.  AEA and 2-AG at higher levels seem to interfere with this whole signaling process - and, once again, higher levels of AEA and 2-AG are found in obese individuals.

Leptin is a hormone that acts in the hypothalamus of the brain.  When it is working normally, leptin sends a signal that we have fed and we need to not be hungry anymore.  However, obese individuals often have high leptin levels, suggesting that the brains of obese individuals have become resistant to leptin's effects.  Leptin-resistant mice have increased levels of endocannabinoids swimming around in their plump mouse bodies.  In mice born without the ability to make leptin, treatment with leptin will very quickly lower endocannabinoid levels.  So obviously there is cross-talk and regulation that somehow becomes broken in the case of obesity.

SO - omega 6 fatty acids become endocannabinoids, which are associated with increase fat tissue, decreased insulin sensitivity, and leptin resistance.  Oops!  (But keep in mind we only have the "associated with" there, not the smoking gun.  It's just… such a pretty theory, I can't help but squee a little.)

Kim et al. are very pro-omega 3 fatty acid, suggesting that it will help reduce obesity, reduce endocannabinoid signaling, and increase insulin sensitivity.  They do use the work of William Lands to suggest that "an increase of dietary omega 3 PUFA was more efficient in decreasing eicosanoid formation from omega-6 derivatives than decreasing omega-6 PUFA in the diet."  (Eicosanoids are the bioactive molecules, such as prostaglandins, endocannabinoids, and thromboxane, that are made from omega 3 and omega 6 fatty acids.)

I just downloaded and took a gander at the Lands paper referenced, and the whole time the good Dr. Lands talks about how the current 7% of US and Denmark diets of omega 6 PUFA is too high, and increasing the total ratio of omega 3 to omega 6 PUFA is the reasonable way to go  - it seems that in systems that are deficient in omega-3, we will hungrily gobble up the omega 3, so that is perhaps what Kim et al means by "an increase of… omega 3… was more efficient… that decreasing… omega 6 PUFAs in the diet."  But who knows what they were thinking.

Very interesting quote from the Lands article about fish, however:

"A fatal hypersensitivity to environmental stimuli ("fainting shock" syndrome) is exhibited by rainbow trout that are fed diets containing n-6 fatty acids without sufficient counterbalancing amounts of n-3 fatty acids ( 10)."

Fainting shock syndrome!  Wow.  If you are a rainbow trout, do not eat corn oil.  Enough said.

Thursday, April 21, 2011

An Introduction: More on Endocannabinoids *cough* With a Focus on Obesity Regulation

I'm very tempted to link a Pink Floyd song here. But, truth be told, that was a little before my time. Instead we'll do some more Metric (right click in new tab - yes, it is from the movie Eclipse, which I haven't seen. Glittery vampires aren't really my thing. But the song is rather dreamy - and I had to change the original link for one with an ad as the original was removed.  Sorry 'bout that).

I took the day off today - try to do that every four months or so, but last year was mostly unable to due to growing a new business. However, I won't be missed too much for a couple of days now, and I was finally able to clean up my room after a little too long. (Working mom, two kids, not much time - and usually I spend what moments I have reading and blogging!) In amongst the stack of papers was my last lipid profile, (yes, I am going to pull a Gary Taubes here) done back in 2009, pre-paleo, when I was on what I call a "Michael Pollan" style diet. Lots of whole grains, fruits, lean meat, fish, and vegetables, avoiding vegetable oil, not too deathly afraid of butter, but most breakfasts were oatmeal + frozen fruit + skim milk nuked in the microwave. Very different from today's breakfasts of eggs or nothing. Anyway, as I was breastfeeding at the time, the nurse did not have me fast for this test (tell a breastfeeding woman to fast on a high carb diet and she will probably take off your head and eat it). It was drawn around 1:35 pm for a disability insurance physical, so probably 60 minutes after my last meal. I had trouble losing the excess baby weight before primal/paleo and weighed 25-30 pounds more then than I do now:

glucose: 91
triglycerides: 100
total cholesterol: 183
LDL: 106
HDL: 57
Chol/HDL ratio: 3.2

It's not all that terribly interesting. I imagine total cholesterol and HDL are higher now, and who knows what my fasting glucose and triglycerides were. I should add that the only one I know of in my extended family who died of heart disease was my paternal grandfather, who succumbed to a heart attack at 89 after 30 years of poorly controlled type II diabetes. That said, I think the labs do show that a high carb diet won't necessarily throw your glucose or even triglycerides "through the roof" after a meal.

Endocannabinoids are ubiquitous in the central nervous system. Pharmaceutical companies are pretty excited about them, for if they get the formula right somehow, there is the potential to throw expensive patented medicines at "food intake disorders, chronic pain, emesis, insomnia, glaucoma, motor disorders, stroke, and severe psychiatric conditions such as depression, autism, and schizophrenia." (1)

What is an endocannabinoid, to start? Well, it is a locally acting neurotransmitter. It is made nearby to where it is used, making it unlike a hormone (or the cannabis plant active component THC), which often has effects from far away. The major endocannabinoids (eCB) in the nervous system are derivatives of arachidonic acid, itself a derivative of the omega 6 linoleic acid. eCBs are a molecular key. Don't think it escaped my attention that the omega-3 derived receptor molecules could serve as a regulation system at the endocannabinoid receptor lock, as I discussed in a previous post. That tends to be how these things work. O6 is on a see-saw with O3, and the evolutionary body and brain never saw a massive imbalance of the two known as the Western Diet coming.

Because eCBs are locally acting, one has to consider their effects locally. As a psychiatrist, one of my major interests in the prefrontal cortex (PFC). That is basically the outer rind of your brain right in front. Have a thin prefrontal cortex? You are much more likely to have impulsive behaviors and get caught doing silly things and end up in jail. A thick prefrontal cortex? You probably think too much, don't take risks at all, and would make a great living in academia. A medium prefrontal cortex? Absent a conscience, you would be master criminal, never to be caught (that might be the glass half empty view of things). Otherwise, you might end up like me, with a conservative medical practice and a renegade blog.

So, at least in mice (and I don't have reason to think human prefrontal cortexes vary much except in size and complexity), eCBs are very important in regulation of all sorts of molecular systems in the prefrontal cortex. Y'all might remember that excitatory neurotransmitter, glutamate - well, turns out that eCBs will inhibit it. And, as I discussed in the previous post, they tend to turn down the volume on excessive or repetitive stimulus in the PFC via a process known as long term depression. Though that sounds bad, long term depression is good. It's your brain's way of modulating signals. Sort of like how hopefully you can tune out the jackhammer going all day across the street while at work.

In other areas of the brain, endocannabinoids regulate key positions, such as appetite and addiction. The major endocannabinoid receptor in the central nervous system, CB1, seems to have a part in emotion processing, pain perception, and motivation for food intake (2). The CB1 receptor inverse agonist (an agonist activates a receptor, an antagonist typically merely blocks a receptor from being activated, while an inverse agonist sort of reverse-activates a receptor, just so you know), rimonabant, seemed like a hopeful drug to help with weight loss, smoking cessation, and other drug dependence. Plans for investigation of this drug included uses in cardiovascular disease, shock, liver disease, gastrointestinal disease, and arthritis.

And, as we mentioned in the last eCB post, even when rimonabant was used in psychiatrically healthy patients, the treated patients tended to struggle with mood symptoms, anxiety, and suicidal and aggressive tendencies. As my 2 year old would say, "Oopsie daisy!" On rimonabant, these anxious and suicidal symptoms occured 28% of the time, compared with 14% of those taking a placebo.

What is interesting to me is that psychiatrists traditionally viewed the opiate system as being more associated with reward and pleasure than the cannabinoid system. And yet a strong opiate blocker, naltrexone, can be used for a period of months in people with no seeming side effects. I've prescribed it a number of times, and no one developed anxiety or suicidal tendencies - quite the opposite, in fact. People noticed a decrease in cravings and overall discomfort. Not that naltrexone is an evolutionary answer - it is just interesting, compared to rimonabant (which I must admit, I've never prescribed.) And, indeed, the eCB system interacts only indirectly with the dopamine/opiate system. I find that quite remarkable.

But let's move on to something of interest to a more general audience - endocannabinoids and obesity, and we will refer to a neat paper Endocannabinoid signaling and energy metabolism: A target for dietary intervention (by Kim et al.)

I'm going to do a rare switch from alternative rock and classical at this point and recommend Dvorak's Serenade in E Major.

CB1 is found in the brain, but also in in muscle, the GI tract, and fat tissue. In obesity research, the focus is often turned on the hypothalamus, the brain's center of appetite and sleep and hormonal regulation. And, indeed, when we experience food deprivation, our eCBs go to work, making us hungry and interacting with some other rather famous hormones => orexin, leptin, and insulin. The endocannabinoid system in the muscles and gastrointestinal tract and fat tissue seems to communicate with the brain, directing overall energy intake in relation to expenditure. Loss of leptin and insulin regulation of the endocannabinoid system is suspected to be part of the cause of obesity and type II diabetes.

Omega 3 fatty acids are known to be satiating (3) (except, frankly, in sushi, which always makes me more hungry. Why is that?) Researchers have speculated (as I do now) that the increase in omega 3 PUFAs in the receptors leads to changes in the receptor affinity for the omega 6-derived eCBs. Interestingly, in the Kim paper, he notes omega 3 intake is associated with lower endocannabinoid levels (AEA and 2-AG) as less arachidonic acid (the eCB precursor) is incorporated into the cell membranes. The researchers go so far as to suggest that increasing the dietary ratio of omega 3 PUFAs would be a "practical approach for changing the fatty acid composition of cellular membrane phospholipids to alter membrane signaling to serve as a promising tactic to decrease the synthesis of endogenous ligands for cannabinoid receptors and minimize ECS activation."

In cows, dietary modulations of arachidonic acid and DHA (even studies using krill oil, which I would suggest is outside a cow's evolutionary experience) have been shown to change the levels of endocannabinoids in the central nervous system - AA increases eCBs, DHA seems to decrease them. This change occurs rapidly - within 2 weeks. The researchers move on to humans, discussing studies of omega 3 intake among obese and diabetic women and men, whose inflammatory markers, hunger, and body weight decreased within a few days of eating more omega 3s. Leptin is also thought to be increased by the omega 3 fatty acids (at least in rats).

There are a number of other hormonal systems involved with obesity, including regulation of the eCB system and ghrelin and CCK. In short, "the EC system works with the endocrine system and neural networks associated with the hypothalamus and the gastrointestinal tract to regulate the energy balance of the individual."

I could go on for a while, and I will have more posts on endocannabinoids and psychosis and neuroplasticity and neurotoxicity. But here we have a local neurotransmitter regulated system of addiction, pain, and appetite dependent (perhaps) upon dietary regulation of omega 3 and omega 6 fatty acids. You see why scientists suspect a multigenerational effect of the excess omega 6 in brain development and the earlier onset of fat gain and diabetes this last generation.

Scary, really. I avoided omega 6 (as much as I knew how) through both pregnancies, and then breastfed, eschewing formula (except for a small amount when the youngest was 11 months old) - both were weaned to whole cow's milk in addition to regular food around a year. My kids are very tall (99-110% of normal height for age) and average about 70% of normal weight for age. The charts are based on averages of singleton births in the US in the year 2000 or so, well into the reign of omega 6 PUFAs. I don't know how much of the kids' stats are due to genetics or food or what, but I'll leave it like my stats from my Michael Pollan diet - an interesting data point.

There is more to come with the endocannabinoids. I promise.

Wednesday, April 20, 2011

Odds and Ends and the Donate Button

I've gone on a little endocannabinoid paper feast so I should have some more entries about that up soon.  Very interesting stuff, very complicated and interrelated with everything, and a zillion papers from the last several months, so cutting edge too.  The sort of system you don't want to screw up if you can help it.

In the mean time, you might have noticed my "Donate" button added to the right there.  I held off adding one for a while but it seemed like the right time now that there are a couple of options to give people.  If you feel this website is of value to you, feel free to donate - if you don't want to donate but still want to support the site financially, click though my blog at Psychology Today.  I've already received a few donations and they are much appreciated!  The textbooks do add up - I don't anticipate these websites or endeavors to break even in the near future (if ever),  but every little bit helps it to be less of a financial drain on the family.  That said, the intellectual value to me from doing the work for the site and the participation and back and forth of ideas in the comments is really invaluable.

Thanks so much!   

Monday, April 18, 2011

Omega 3s, Mice, and Receptors for Funny Cigarettes

Jamie (who has a fabulous post up now about Survival of the Fittest) sent me a link to a new paper this morning.  Or possibly last night.  The mound of papers is starting to slide, and sometimes I lose track.  In any case the paper is from Nature Neuroscience, and that always makes me flinch a bit, because Nature Neuroscience is rather advanced.  In most papers, every other word is an abbreviation for some sort of obscure brain chemical or neurologic process, which makes for a lot of blinking and re-reading.  Fortunately, for the same reason, most Nature Neuroscience papers are very short.

Nutritional omega-3 deficiency abolishes endocannabinoid-mediated neuronal functions.

Endocannabinoids!  I know!  Those are our innate chemicals that stimulate the endocannabinoid receptors, which happen to also be stimulated by the merry-making chemical known as THC in marijuana.  I am not, personally, a marijuana fan, having seen too many psychotic young people brought in by parents after a summer of six bowls a day, and also seeing a few too many older folks who could barely put a sentence together after four decades or more of heavy use.    And of course the innumerable people with lack of motivation, weight gain, and rebound anxiety "but I just smoke one or two puffs a day, doctor."  And I'm sorry, you really aren't as interesting as you think you are when you are high.  It's just cold hard fact.  It is especially uninteresting in the emergency room at 3am.  Trust me.

But, as with anything in nature, we have our little endocannabinoids (anandamide and 2-arachidonoylglyceral (2-AG)) that stimulate our endocannabinoid receptors which serve a very useful purpose in the brain.  In fact, there was a great hub-bub a few years back about a potential new weight loss drug, rimonabant.  This drug blocked the cannabis receptors, leading to weight loss.  (Actually, leptin will short-circuit the binding of endocannabinoids in the hypothalamus, also decreasing appetite and resulting in weight loss (1)) I believe rimonabant was approved in Europe and may be in use there.  However, it was never FDA approved in the US due to some unfortunate side effects such as anxiety, depression, insomnia, mood swings, and even aggression (2).  The longer you were on rimonabant, the worse the side effects became.  In fact, a doctor in Texas had his license suspended after prescribing himself rimonabant for weight loss, and then becoming erratic and aggressive at his place of work.

So what on earth is going on with those endocannabinoid receptors, and what does that have to do with omega 3s and mice?  Back to the paper, which I have obviously been avoiding for a couple of paragraphs now.  These researchers had two groups of mice, one born after a pregnancy of omega 3 supplementation (for some reason, the researchers used ALA, but I honestly have no clue as to the conversion to DHA in mice) and then continued on supplementation.  The other group was fed a diet rich in peanut oil (mostly linoleic acid - omega 6) without omega 3s.  Then the researchers used some very sophisticated machinery and lots of abbreviations to prove that "dietary PUFAs influence eCB-mediated synaptic plasticity… in PFC slices prepared from mice that had received an n-3 diet, tetanic stimulation induced a robust eCB-LTD of excitatory synapses onto layer V/VI pyramidal neurons in the PrPFC."

Roughly translated, our brain has off switches if we get too much stimulation in one area.  For example, have a buddy poke you in the forehead between your eyes repeatedly.  At first you won't be able to stop blinking when the finger comes close, but after a while, you can keep your eyes open.  This is a process called stimulus "extinguishment." There is a lot of evidence that problems such as psychosis and even depression develop because certain signals just keep going and going and going and getting through, without extinguishing.   In the brain, a signal that goes on too strong for too long will result in a process called "long term depression" (LTD).  Simply stated, a repeated signal ad nauseum or a signal that is too much will result in the synapse being modulated to reduce the signal strength.  This process is an important part of "synaptic plasticity."  And it turns out this process is modulated in the mouse prefrontal cortex by the endocannabinoid system.  And in mice raised on a lifelong diet deficient of omega 3 fatty acids, the long term depression did not occur in the prefrontal cortex.  This means the omega 3 deficient mice had decreased neuronal plasticity.  Their brains were, essentially, more brittle, less flexible in responding to different stimuli.

The researchers used excessive abbreviations to prove that it was the endocannabinoid systems affected in the mouse, not a myriad of other systems, including our old frenemy the NMDA receptor.

There is an interesting wrinkle.  PUFAs happen to be the precursors to our own natural funny cigarette compounds, anandamide and 2-AG.  It is possible that a high level of PUFAs result in an excess of natural funny cigarette compounds (OMG, that soybean oil ranch dressing was like, so totally amazing man) which then saturate and perhaps desensitize our endocannabinoid receptors.  In this mouse paper groups of lifetime n-3 deficient and n-3 replete mice had equal circulating levels of natural endocannabinoids in their little mouse brains.  In other papers, there were differences, suggesting that there may be compensatory mechanisms for endocannabinoid levels.

So, what are the effects of omega 3 deficiency on mouse behavior again?  They are more depressed, are less motivated and explore their environments less.  They scratch more, indicating anxiety.  They also avoid open spaces and like to remain close to walls, also thought to be a sign of mouse anxiety.  The researchers then gave the sad and nervous mice of control and omega 3 deficient groups some cannabinoid agonists (not puff the magic dragon, but another one hilariously called WIN), and the mice perked up and started hanging out in the middle of open space again, and presumably began planning trips to the minimart for twinkies and bugles.  The omega 3 deficient mice were less responsive to WIN than the regular mice, consistent with the theory that cannabis receptor functioning was a bit shorted out in the deficient mice.

There is a lot to like about this paper.  It doesn't answer all questions, to be sure, but it brings up plausible links between industrial diets, depression, anxiety, and even possible connections to hypothalamic dysfunction, leptin, and obesity.  It plugs some missing links in the overall picture of mood and appetite regulation.  Word.

Updated "Your Brain on Ketones" for Psychology Today

Here it is, my most popular post at the new site with a new introduction for those not familiar with the concept of physiologic ketosis: 

Your Brain on Ketones

Friday, April 15, 2011

Binge Eating and the Sugar Fat Showdown

As so often happens when one takes a closer look at references from one paper or another, one will find a paper far superior to the first. The glass half empty view is one of regret for wasting all that time on the inferior paper. The glass half full - hey, now I have more material for another post. Only I have a stack of about 20 papers in the queue, and these industrious researchers are coming out with more all the time, so material isn't really a problem, even after 170 blog entries.

Let's go for some peppy-ish music today. "What You Know" by Two Door Cinema Club. (right click in new tab)

The great thing about this superior paper is that it is free full text, and well worth taking a look for yourself. Avena et al, Sugar and Fat Bingeing Have Notable Differences in Addictive-like Behavior. It was published in a Journal of Nutrition Symposium, "Food Addiction: Fact or Fiction," and they wrote a convincing work. One caveat - this paper is primarily a review of rat studies. The brand new paper I blogged about last week where they stuck humans in the MRI is one of the first in humans showing neural correlates of addiction with the chocolate milkshakes. So there is definitely more work to be done before we stick a fork in it and declare that we have all the answers. That said, let's visit our rat studies.

People and rats tend to binge on "highly palatable energy-rich food." Binge episodes in research (and in my clinical experience) usually involve episodes of "bread or pasta, followed in frequency by sweets, fatty foods, or salty snacks" (the salty snacks are typically chips or popcorn, so for the most part grains + salt + vegetable oil). Those who prefer to binge on sweet food tend to binge more frequently.

By bingeing, I don't mean hanging out on the couch and eating half a bag of Doritos while watching old episodes of Top Chef. Binge eating in humans has a specific definition - a larger amount of food than normal within a 2 hour period, associated with at least three of the following: 1) eating until uncomfortably full, 2) eating large amounts of food when not hungry, 3) eating more rapidly than normal, 4) eating alone due to embarrassment about the amount of food consumed, 5) feeling disgusted, depressed, or guilty about the amount of food consumed, and 6) distress or anxiety regarding binge eating. Obviously rats don't fill out questionnaires about how they feel about eating, so I'm assuming the rat definition isn't quite so strict (and I would call this issue a problem with animal models of binge eating). I don't know if rats feel guilty about over-consuming.

The human definition is important to remember, because most obese people are not binge eaters. However, binge eaters are far more likely to be obese, and about 1/3 of people in medical treatment for obesity struggle with binge eating. Binge eating is an extreme of the overall issue with obesity in the West - somehow food consumption gets unhooked from the energy in and out regulatory cycles that kept us relatively lean for 10,000 generations - with emotional baggage and addiction to boot.

Back to rats! Many laboratories have done studies with sugar solutions, and they find (in general) that rats will binge on sugar if they are given intermittent access to it, or if they are given sugar after a period of fasting. Typically the sugar solutions are similar to the sugar concentration of soft drinks. Rats who have sugar and their regular diet available all the time tend to eat as much sugar as the restricted rats do, but they don't binge on it. And, importantly, the sugar bingeing rats and the sugar + regular food freely available rats don't tend to get fat. They eat sugar and compensate by eating less rat food.

Contrary to the notion that we don't "binge on fat alone," rats certainly do. Corwin et al. have demonstrated several times that rats who have ready access to their rat food will binge on shortening when it is available for only 2 hours each day. (I myself have never experienced an overwhelming urge to down a bucket of Crisco, come to think of it, and one of the papers notes "humans rarely if ever binge on pure fat.") Proving that at least some diet and obesity researchers have functioning brains and sticktoitiveness, Corwin more or less repeated the experiment with trans-fat free shortening 10 years later, and rats will binge on the new improved Crisco or the old, more deadly version. But, just like the sugar-eating rats, the rats tend to compensate for the extra Crisco binge, at least in these 6 week experiments, by eating less of their regular rat chow.

(Second song - Crystal Vases by The Last Royals)

Another group of rat researchers, leaving no stone unturned, compared intermittently available Crisco (in 2008 I don't know if this was trans-fat Crisco as Corwin's paper in 2007 noted they had trouble getting a hold of trans fat Crisco at the time for their comparison group) to rats given a high fat diet (I couldn't find the exact composition of their high fat diet, but every rat diet I could find at Dyets Inc., where the researchers obtained their rat food, uses soybean oil and corn oil for the fat) every third day for 8 weeks. Both groups would binge on the fat (for one group, pure crisco, for the other, high fat food mix), both groups gained fat (though didn't necessarily gain weight over all). Only the hydrogenated shortening exposed group had changes in leptin levels (their leptin levels increased, which is common with obesity) - this suggests that, at least in rats, hydrogenated vegetable oil has the potential to be more endocrine-disruptive than plain old vegetable oil, but both groups gained body fat, so who knows.

These same researchers also had groups of rats who got the high fat diet every day, a control diet every day, or Crisco every day, and none of the groups (intermittent, constant exposure, control, or not) had any differences in the amount of calories consumed. Only the intermittently exposed rats had bingeing behavior. All of the high fat or Crisco rats (intermittently exposed or not) gained body fat.

Now what we've been waiting for - the sweet-fat mixes. The combination of sweet and fat activates a cornucopia of taste receptors and neuropeptide signaling systems. Sweet-fat combos (some researchers use cookies, in the Avena paper, they used Research Diets #12451 (with sucrose, soybean oil, and I'm guessing industrial lard)), with intermittent access result in bingeing rats again, with the rats consuming 54% of their daily calories during the 2 hour sweet-fat food available window. These rats tend to eat less of their regular rodent chow to compensate, but compared to control groups without sweet-fat access, they actually eat more calories overall. This is the first model that results in rats gaining body weight with bingeing behavior.

SO - in rats, at least, sugar alone causes binges when intermittently available. Vegetable fat and high-vegetabe fat diets will do the same (causing body fat increase without overall weight gain), and the sweet-fat mix (though finally using lard, it is in combination with soybean oil, and industrial lard undoubtedly has a higher omega 6 content than pasture pig lard, which I think is around 12% PUFA) causes bingeing AND weight gain.

A few more interesting things from the Avena paper: Rats given daily intermittent access to sugar will binge in the first hour of sugar access, and when the rats are given a high dose of naloxone (an injectable opiate blocker used in humans for overdoses - you end up with someone who is breathing again but in abrupt opiate withdrawal, so alive, but extremely unhappy and uncomfortable), they exhibit symptoms of opiate withdrawal. Similar signs of rat opiate withdrawal emerge spontaneously in sugar-bingeing rats who are put on a 24 hour fast, no naloxone necessary. And sugar-bingeing rats given a regular diet for 2 weeks will then eat 24% more sugar than ever before after the two weeks without. Sugar-addicted rats who have their fix taken away will also be more anxious, aggressive and will have lower body temperature (a sign of rat stress).

Similar findings (using naloxone again) were seen in rats fed an ad libitum "cafeteria-style" diet with a variety of foods such as cheese, cookies, and chocolate chips. And rats exposed to corn oil will show an increase in dopamine (the feel good chemical) release, and this release will also happen when exposed to just the taste of the oil. Avena's group tried to replicate these findings with a variety of sweet-fat or high fat combinations of rodent chow, but didn't observe the naloxone withdrawal effect, which is interesting.

And, another DING DING moment - Avena's group had found the withdrawal and unhappiness in sugar-bingeing rats after a 24 hour fast. They tried the same thing with rats fed a high fat diet (I'm sure the typical horrid industrial rodent chow), and observed that the rats were not anxious or have indications of distress after 24 hours without food. The researchers felt this was due to sugar stimulating opiate systems, and fat likely not doing so. I also wonder if high-fat rodents were more able to burn ketones so didn't experience uncomfortable fluctuations of energy as a high-carb (again, typically the industrial sugar, corn starch, casein, lactose, soybean oil blah blah blah combination) rat will tend to without eating.

The take-home message? Rats will binge on sugar and vegetable fat, but it is the sugar-fat combination that is the most detrimental to rat body-fat %. It seems that the sugar packs the most addictive punch, while the increase vegetable fat (particularly Crisco, whether trans-fat free or not) in combination with the rest of the industrial diet perhaps causes more metabolic harm.

Does this information apply to humans? Well, there are some differences (i.e. lack of human crisco-diving behavior) and many similarities. And gluten grains seem to be missing in these animal studies, while humans with binge-eating behaviors binge most commonly on bread and pasta.

You know what I think already. Eat real food, avoid the industrial stuff (particularly the vegetable oils), and to really play it safe, avoid the gluten grains too. I don't go too far out of my way to avoid too much sugar, personally - avoiding processed food in general does the trick. I eat fruit if I feel like it (usually bananas or berries, but grapes or apples or oranges are also typical), and usually it ends up being one serving a day. And when I cook recipes with sugar (which isn't all that often), I do cut sugar to 1/2 or 1/4 what the recipe calls for, and I tend to use raw honey or some other specialty ingredient - more because it is expensive and precious and more fun to eat, and easier to savor. I've had my current little bear of raw honey for 6 months. If you are worried about too much fructose, use rice syrup. I don't sweat a little ketchup or tomato paste or balsamic vinegar - it's never that much. Food should be an amazing celebration of nature, not a technological marvel (unless you are enjoying a high-end meal at a molecular gastronomy restaurant). Real food can be enjoyed and celebrated, and it is life-giving and nourishing, never the enemy.

I also have a new post on Psychology Today - Depression Crashed Your Party

Tuesday, April 12, 2011

Other Posts Everywhere

I have another longer look at sugar, vegetable oils, binge eating, addiction, and the brain coming up (chased down some of the references from the papers I mentioned on Saturday, and they do not disappoint), but for today I have a guest post on Mark's Daily Apple, and another Psychology Today post… enjoy!

Your Brain and The Primal Blueprint

Sad Monkeys

And welcome Mark's Daily Apple visitors!  If you think my blog looks interesting, you can start with this post:

Evolutionary Psychiatry, the Key Posts

And if you are looking for something more specific, take a gander at the site Map (has most posts listed by condition (ex. depression or autism,  or nutrient)).

Have fun!

Saturday, April 9, 2011

A Small Post On The Neurobiology of Binge Eating Disorders

Indulge me for a moment. Here is one of my favorite pieces of music: Chopin's Etude No. 3 in E major. (right click to open in new window). The best youtube quote about it: "Too beautiful to be an etude."

One more indulgence. A quote from A Room with a View by E.M. Forster. For springtime.

From her feet the ground sloped sharply into view, and violets ran down in rivulets and streams and cataracts, irrigating the hillside with blue, eddying round the tree stems, collecting into pools in the hollows, covering the grass with spots of azure foam. But never again were they in such profusion; this terrace was the well-head, the primal source whence beauty gushed out to water the earth.
Standing at its brink, like a swimmer who prepares, was the good man. But he was not the good man that she had expected, and he was alone.

The brain is named in beautiful words, intimidating words, but beautiful nonetheless. We'll start with the animal models of binge eating (1), which seem to have something in common with the human experience. Animals seem more likely to binge in cases of prior food restriction (and the bingeing can continue for long periods after restriction is over), and in periods of anxiety.

Daily binge eating on a "palatable sugar solution or fat diet" will repeatedly release the feel-good chemical dopamine from its home, the nucleus accumbens. Sugar-bingeing rats will have increased dopamine1 receptor binding in the nucleus accumbens, and decreased dopamine2 receptor binding in the dorsal striatum. This pattern is very similar to changes observed with drug dependency. There are also changes in opiate receptor expression in binge eating rats, and if you inject opiate into the nucleus accumbens, it will stimulate binge eating.

Some facts about binge eating in humans - the definition is that someone will eat an "objectively large amount of food" accompanied by feelings of loss of control. 30% of obese individuals attending weight control programs have the disorder. Obese binge eaters will eat significantly more calories than obese nonbinge eaters in order to feel full, or even when asked to eat normally.

In a study on humans, Wang et al discovered that food stimulus significantly increased dopamine signals in binge eaters in the basal areas of the brain, whereas non binge-eaters did not show the same increase.
Previous studies had shown that exposure to "palatable food stimuli" was associated with an increase in striatal dopamine release, and this release was correlated with ratings of "meal pleasantness" following consumption of favorite food. As with the other studies of folks with eating disorders, low dopamine levels (associated with an increase in receptors, to compensate) has been shown to be present in binge eaters.

People with binge eating disorder tend to overeat compulsively and have some impulsivity (also seen in substance abusers), and food is a potent reinforcer of the behavior, and fasting can enhance the rewarding effects (thus my little caveat about IFing and eating disorders).

Here's the evolutionary psychiatry money quote from the Wang article: "Some ingredients in palatable food such as sugar and corn oil can result in impulsive ingestion in patterns reminiscent of those seen with drug intake in addiction." DING DING DING DING.

And the sweet taste of sugar, without the nutritional component, can also induce release of dopamine (um… diet coke addiction, anyone?).

So I don't think I venture far out on a limb to suggest that eating disorders are addictive, or that certain types of extremely palatable food (sugar and corn oil, and in my clinical experience, for some people, wheat) are addictive. Abstinence with support is the tried and true method to help addictions. Hard, though, to get the appropriate sort of universal support when your government (and therefore any trained nutritionist or dietician or doctor of the conventional stamp) is telling you to eat corn oil and grains and carbs to lose weight and to be healthy in general.

Oh! Totally forgot to link yesterday in this blog - a new Psychology Today post is up. Click for me if you please!

Friday, April 8, 2011

Eating Disorders, Obesity and Addiction

I've been meaning to do more on eating disorders for a while, but I find the research frustrating.  As do eating disorder researchers - see, within eating disorders even more than in some other areas, the diagnoses proscribed by the DSMIV don't really fit the symptoms most people have.  There are three "official" categories - anorexia nervosa (AN) (restricting eating, underweight, obsessed with body image), bulimia nervosa (BN) (bingeing and purging via vomiting, excessive exercise, or laxatives, typically normal weight or fluctuating weights, body image issues), and eating disorder not otherwise specified (EDNOS)(anyone who seems to have an eating disorder that doesn't quite meet the other criteria).  Most people with eating disorders fall into the last category, simply because many people with primary anorexia also binge and purge in some way, and bulimics will often have periods of restriction.  Even worse, there is an entire category of eating disorders that has no "official" diagnosis, the binge eating disorders (BED) (bingeing without restricting or purging, patients are often overweight but some are normal weight), and it is actually more common than anorexia. (These numbers are approximate as many folks with eating disorders don't seek treatment, but the estimates are that 0.5% of the adult Western population has AN, 1% has BN, and 3% have BED.  There are no estimates for EDNOS.)

When you review the literature for "evidence-based" treatments, there really are none for EDNOS (1), simply because research has focused on AN and BN.  In anorexia, there are a few firm things to recommend - if severely underweight, refeed under supervision, and other treatments don't work particularly well until the starvation is to some extent reversed.  For young people, family therapy is recommended.  In bulimia, there is a particular type of cognitive behavioral therapy that is specific for the disorder and has good evidence base.  

Eating disorders are among the most deadly of psychiatric disorders in the short term (anorexia is probably fatal in 5-10% of cases, though this number is dropping as acute treatment is getting better, whereas BN and EDNOS have a mortality rate of about 3.5%, and people with all the disorders, including BED, have a higher risk of suicide) - but the good news is at 10 year follow-up, between 70-80% of people with the disorders no longer have symptoms.

What is particularly frustrating about eating disorder literature is that no one has a real clue (backed by solid evidence) as to what causes them.  There are some genetic links, some common psychologic features and environmental risk factors, and it is likely that people with low amounts of serotonin and dopamine in certain areas of the brain are more vulnerable to developing eating disorders.  

My own suspicion (speculative, but sensible) is that the combination of societal pressures to be thin and our modern industrial diet's terrible track record of putting on fat lead to very common restricting behaviors, which basically makes everyone a member of a little Minnesota Starvation Experiment, only we are not locked down, so we continuously restrict, worry about exercise, then begin to obsess about food and have anxiety and depressive side effects, then we (quite sensibly) cave in to the evolutionary imperative to eat, regain the weight,  etc. etc.  A particular subset of people, often young women who perhaps face the most societal pressure, will develop extreme behaviors and become eating disordered.  Thus my conjecture is that the industrial food is the problem, and wholesome unprocessed food (get rid of the excess sugar, excess linoleic acid, and gluten grains) a large part of the solution.   My stance is actually as unproven as it is controversial - as many people with eating disorders restrict varieties of food, during recovery it is common practice to teach people to eat "everything in moderation" (though focusing on healthy, nourishing food, of course), so to suggest restricting whole categories of food again without a solid evidence base could be seen as feeding into the disorder.

But there is an issue with "everything in moderation," I think, putting aside the entire "paleolithic" nutritional paradigm and the neolithic agents of disease causing obesity in the first place. And that is that eating disorders are addictive (2).   While some folks with addiction can actually, eventually, moderate their intake of the addictive substance, most people do better, at least for a while, with complete abstinence.  Obviously one cannot completely abstain from food - but if we suspect the neolithic agents as building an addictive cycle neurochemically in the brain (and this is definitely speculation, but an educated guess, I would say), then it would seem that getting rid of them in the diet would be of obvious help.  Once the situation is stabilized, and a more natural and realistic relationship with food and body and diet are adopted, then it would make sense to adopt more moderation to make life easier and less food-obsessed.  But everyone is different - some people get very despondent with the idea that anything is off-limits.  Treating eating disorders like every psychiatric condition requires some common sense, flexibility, and innovation.

Let's get back to my addiction angle for a minute, and, while I'm going to spend some time in a second post focusing on the neurobiology of binge eating, today I'm going to drop "eating disorders" and look at a new paper called Neural Correlates of Food Addiction.  This study is actually about food and obesity in general.

The bottom line in America - 1/3 of adults are obese.  Obesity-related disease is the second-leading cause of preventable death, and most obesity treatments are unsuccessful, with patients regaining all the lost weight within 5 years.  Food and addictive drug use both result in the release of dopamine in the mesolimbic regions of the brain (at least in animal studies), so one gets a sense of "reward" and happiness from eating.  Obese versus lean individuals show greater activation in the addictive behavior centers of the brain in anticipation of receiving "palatable" foods (obesity and food researchers here typically mean sugar and fat and salt - my still-unproven conjecture is that the massive excess of linoleic acid, fructose, and the easy, cheap availability of fatty-grain chips and the like and sweetened grain desserts are the issue, and while a gorgeous bone marrow dressing on a salad and a delicious steak would also light up the reward areas of the brain, it is part of the natural order of things to shut the reward cycle off if our bodies reach a certain level of fat stored on hand.)  And, interestingly, one finds this to be the case in obese individuals and people addicted to drugs - obese people anticipate food intensely, but when the actual food comes, they have less enjoyment (in general, the reward brain areas light up less) than someone who is lean.  The same is true for drug addiction - the brain seems to like the anticipation much more than the actual event.

In the study, 48 young (human) women with an average BMI of 28 were selected from women enrolled in a program "developed to help people maintain a healthy weight on a long term basis."  Those with history of eating disorders, head injury, or current smoking, illicit drug use, or psychiatric diagnosis were excluded.  Each participant was measured and weighed and took some tests assessing their level of food addiction (the research standard is a 25 item Yale Food Addiction Scale.)  The test among these young women had a normal distribution.

Then the participants were put into an MRI for a baseline measurement after fasting 4-6 hours (no caffeine either).  Then the women were exposed to pictures of a chocolate milkshake or a picture of a glass of water for a few seconds.  Thereafter they received one of two "deliveries" - half a milliliter of chocolate milkshake* or a calorie-free tasteless solution meant to mimic saliva.  All of this was randomized - some women got a picture of water then saliva, some milkshake picture then saliva, some water picture then milkshake, etc.   And 40% of the time, no "taste delivery" was made to give the researchers an idea of what a scan would look like without the paired stimulus.  The taste delivery occurred via some sort of tubing system within the MRI scanner itself, which is kind of a neat trick.

Results!  The women (lean or obese) with a high level of food addiction on the scale test showed more activation of brain centers associated with addiction and reward in anticipation with the milkshake picture, and less activation with the actual milkshake.   This is pretty solid human evidence that there are certain people who are truly addicted to chocolate milkshakes.

Interesting tidbits from this study - the addiction scores were not associated with BMI of the participants (average age of 20.8).  However, those with high scores on the addiction scale test were far more likely to have periods of binge eating, emotional eating, and "problematic eating attitudes."   The researchers felt that the young age of the sample might mean that the lean women with a high food addiction score would have increased risk of obesity, as older obese adults tend to have higher food addiction ratings.  I suppose time will tell.

The main problem with the study is that the researchers did not measure hunger in the participants.  Though they all fasted about the same amount of time, some may have been hungrier than others, and hungrier people have greater food reward signals in the brain.  The other limitation I see is the selection in the first place - rather than selecting random young women from a college campus, for example, they chose those enrolled in a healthy eating seminar.  

Well.   What did we learn, really?  "Highly palatable" food can be addictive to certain susceptible individuals.  Usually things are highly palatable because they are somehow good for us.  I have the feeling that in an environment without the neolithic agents of disease, the food reward system would work as planned, just like the sex reward and the exercise reward.  Jack up the system with weird chemicals in excess of anything we ever experienced in evolution - like heroin, tobacco, or ho-hos, and some people will develop a problem.
* Obesity researcher milkshake recipe:  4 scoops Haagen-Dazs vanilla ice cream, 1.5 cups of 2% milk, and 2 tbs of Hershey's chocolate syrup.  Personally I would recommend using some variety of artesian or homemade reduced sugar chocolate ice cream and whole milk without the syrup ;-)  Also whipped cream and chocolate shavings on top.

Saturday, April 2, 2011

Spring Fever

Updated Zombieland for Psychology Today - go over there and take a look, will you?  I know I should have waited for the week day, but I have Zombieland II to do also, and when I do get a relative moment of peace around here, I do like to take advantage.

We even had a chance to go outside, where my daughter's little plastic boat was found unhappily waiting for the snow to melt.  A turkey loped through the yard this morning, and you can see his or her track in the upper left.  We have a large family of wild turkeys in the neighborhood.

Friday, April 1, 2011

That O6/O3 Ratio, Still Important

Oof.  I'm tired.  Oldest child has a spiky fever of unknown origin (FUO in the medical speak) and youngest child is nearly two and tiring by default.  I get these rather silly emails from babysomethingorother telling me about her 23 month old expected developmental stages.  This week's was about her learning to throw things.  Well, she's been throwing things with gusto for quite a while, babysomethingorother.  She also fingerpaints in yogurt on the refrigerator if I allow it.  I guess she's advanced.  Must be the pasture butter and salmon.  They are both sleeping now and thus, a post.

Well.  The lovely Victoria sent me this new paper last week.  If you can't be bothered to click, basically it is a PUFA and dementia and depression paper.  Dementia is bad, depression is bad.  Those with an early form of dementia called mild cognitive impairment who are also depressed are more likely to progress to severe dementia.  Is there a common biologic mechanism?  (Me: YES OF COURSE.  It's called inflammation.  Also, crappy brain energetics.  Researchers:  Let's take a calm and compelling look at the evidence, particularly as regards to the omega 3 and omega 6 fatty acids and the resultant suspected increase in vulnerability to inflammation.  Me: Sigh.  Yes, let's.)

Okay - so if you look at PUFA O3:O6 in the red blood cell plasma membranes, which is felt to be a marker of the bodily PUFA ratio in general, in general (but not always), studies have shown that a lower Omega 3 DHA is associated with depression (in young and old populations) and worsening dementia.  In this study, red blood cell PUFA status was compared between healthy controls and older people with mild cognitive impairment and also with depressive symptoms.

The methods section is tedious but important but we'll skip in my article to the results.  79 volunteers, 50 with mild cognitive impairment and 29 healthy controls.  Anyone on an omega 3 supplement was excluded (3 people total - in Australia something like 50% of the pregnant moms were excluded from the omega 3 study because they were already on supplements.  I guess the older crowd is not so proactive. )

It's complicated, but basically higher levels of n-6 PUFAs were associated with poorer cognitive performance, as well as lower levels of n-3 DHA and EPA.  Similar results were found for "self-reported mental health."  Also "Bodily Pain."  Many of these were linear relationships - basically the more inflammatory omega 6 you have glopping around in your bod, the more you are likely to be depressed, cognitively impaired, and in Bodily Pain.  The researchers go so far as to recommend that older adults have their RBC O3:O6 ratio measured to establish a risk profile for mild cognitive impairment or depression.

I would say - this is an actionable ratio, folks!  Can the corn chips and industrial salad dressings!  There is some evidence that the omega 6 metabolism pathway is overactive in depressed folks with early dementia.  All the more reason not to feed the O6 machine.  In the brain, we are supposed to have a crapload of DHA.  If we don't have enough DHA, it is replaced with a different looking and different functioning omega -derived AA.

Last year my beloved Texas Longhorns football team played for the national championship.  Our tried and true senior quarterback was taken out early in the game in a freak accident, to be replaced by an untried greenhorn.  We lost.  Our freshman replacement quarterback was well-intentioned but in the wrong place at the wrong time.  He just wasn't the same.

"Previous research has shown associations between better mental and physical health and a more varied diet in older age."  I'm not exactly sure what that means.  I think it means eat some fish already.